CA1340991C

CA1340991C - A-unsaturated amines, their production and use

Info

Publication number: CA1340991C
Application number: CA000573430A
Authority: CA
Inventors: Isao Minamida; Koichi Iwanaga; Tetsuo Okauchi
Original assignee: Takeda Chemical Industries Ltd
Current assignee: Sumitomo Chemical Co Ltd
Priority date: 1987-08-01
Filing date: 1988-07-29
Publication date: 2000-05-16
Anticipated expiration: 2017-05-16
Also published as: EP0509559A2; DE3886467D1; CN1093083A; EP0302389A2; IL100688A; CN1083432C; EP0509559A3; JP2551392B2; IL100688A0; EP0509559B1; JPH0749424B2; JPH05345774A; KR0122856B1; CN1091737A; CN1027447C; JPH05345761A; IL87250A0; EP0529680A2; EP0302389A3; DE10399003I2

Abstract

.alpha.-Unsaturated amines of the formula:

(see formula I) wherein X1 and X2 are such that one is an electron-attracting group with the other being a hydrogen atom or an electron-attracting group; R1 is a group attached through a nitrogen atom; R2 is a hydrogen atom or a group attached through a carbon, nitrogen or oxygen atom; n is an integer equal to 0, 1 or 2; A is a heterocyclic group or a cyclic hydrocarbon group, and salts thereof and their agrochemical use as insecticidal and/or miticidal agents are described.

Description

1 340 gg ~
a-Unsaturated Amines, Their Production and Use This invention relates to agrochemically useful a-unsaturated amines having insecticidal/miticidal activity, their production and use.
Among a.-unsaturated amines, such compounds as (i) cimetidine (described for example in Journal of Medicinal Chemistry 24, 9:13, 1981),(ii) ranitidine (described for example in Agents Actions 11, 160, 1981) and (iii) famotidine (described for example in Journal of Medicinal Chemistry 27, 849, 1984)are known as histamine H2 receptor antagonists.

NfiCH3 i ) NC-N=C--NfiCHZCH2SCH2 N

i CH3 (ii ) OZN-CH=C-NfiCfi2CHZSCHZ CHIN
CH~
HZ <NHZ
--N = C
N NHZ
C~~i) fizNS02-N=C-CfIzCHzSCH2 ~_ 0 As agricultural insecticide/miticides, organo-phosphorus or carbamate pesticides which are highly toxic to warm-blooded animals have heretofore been 1.5 employed. However, there has been an emergence of noxious insects, particularly of the order "Hemiptera", which are resistant to these pesticides, and there has been a long-standing need for the development of a pesticide effective against these resistant pests.
Getting im;~etus from the aforementioned histamine H2 receptor antagonists, the present inventors synthesized various a-unsaturated amines and investigated their activitie:5. As a result, we discovered surprising-ly that compounds of the invention which have no 1 340 gg 1 alkylene group or only a short alkylene group in the side chain have agriculturally useful insecticidal/miticidal activity.
Based on the above f=finding, the present inventors conducted further research and have come up with the present invention.
The invention is, thus, concerned with:
(1) novel a-urLSaturated amines of the formula:
R~ R
X jC - C-:','V-CnH2n -A° LIB
wherein X1 and X2 are such that one is an electron-attracting group with the other being a hydrogen atom or an electron-attracting group; R1 is a group attached through a nitrogen atom; R2 is a hydro~~en atom or a group attached through a carbon, nitrogen or oxygen atom; n is an integer equal to 0, 1 or 2; A is a heterocyclic group; with the proviso that:
(a) when R2 is a hydrogen atom, then R1 is a group of the formula: 'R3a -N\
Ra. a [in which R3a is hydrogen, C1_4 alkyl, C~_9 aralkyl or C1_4 alkanoyl and R'~a is hydrogen, 21_4 alkyl, C1_4 alkoxy-C1_4 alkyl, (di-C1_~~ alkylamino)-C1_4 alkyl, tri-C1-4 alkylsilyl-C1_4 alk~rl, C2_4 alkenyl or pyridyl- or thiazolyl-C1_2 alkyl wherein t;he pyridyl or thiazolyl moiety may be substituted by halogen or R3a and R'~a taken together with the N

adjacent nitrogen atom constitute pyrrolidino] and A is pyrazinyl or thiazolyl, each of which may be substituted with halogen, C1_4 alkyl, C1_4 alkylthio, or C1_4 alkoxy or A~ is pyridyl substituted with halogen, Cl_4 alkyl, Cl_4 alkylthio or C1_4 alkoxy, (b) when one of X1 and X2 is nitro and the other is hydrogen, R2 is hydrogen and R3a is hydrogen, then R4a is hydrogen, (di-C1_4 alkylamino)-C1_4 alkyl, tri-C1_4 alkylsilyl-C1_4 alkyl or pyridyl- or thiazolyl-C1_2 alkyl wherein the pyridyl or thiazolyl moiety may be substituted by halogen, and (c) when one of X1 and X2 is nitro and the other is hydrogen, R2 is hydrogen and R4a is hydrogen, then R3a is hydrogen, C~_9 aralkyl or C1_4 alkanoyl, or a salt thereof anal (2) insecticidal/pesticidal compositions containing an a-unsaturated amine of the formula:
Rl R~
X ~C = C-N-CnH2n -A ~ I ~
X
wherein X1 and X2 are such that one is an electron-attracting group with the other being a hydrogen atom or an electron-attracting group; R1 is a. group attached through a nitrogen atom; R2 is a hydrogen atom or a group attached through a carbon, nitrogen or oxygen atom; n is an integer equal to 0, 1 1 340 gg'_ 4a or 2; A is heterocyclic group or c cyclic hydrocarbon group, with the proviso that when R1 is (3-N-pyrrolidinoethylamino and R2 is a hydrogen atom, then A is a group of the formula:
~lal or ~ wherein Hal Hal is a halogen atom (e. g. C1, Br, F, etc.), or a salt thereof, and their production.
Referring to the above formulas [I°] and [I] , one of X1 and X2 is an electron-attracting group with the other being a hydrogen atom or an electron-attracting group. The electron-attracting group X1, X2 includes, among others, cyano, vitro, C1_4alkoxy-carbonyl (e. g. methoxycarbonyl, ethoxycarbonyl, etc.), carboxyl, C6-l0aryl.oxy-carbonyl (e. g. phenoxycarbonyl etc.), heterocycleoxycarbanyl wherein the heterocycle moiety is N

1340991 ' as mentioned below (e. g. pyridyloxycarbonyl, thienyloxycarbonyl, etc.), C1_4alkylsulfonyl which may be substituted with halogen (e. g. methylsulfonyl, trifluoromethyl.sulfonyl, ethylsulfonyl, etc.), aminosulfonyl, di-Cl_4alkoxyph.osphoryl (e.g. diethoxyphosphoryl, etc. ) , Cl_4acy1 which may be substituted with halogen (e.g. a Cl_4alkylcarbonyl such as acetyl, trichloroacetyl, trifluoroacetyl, etc.), C1_4alkylsulfon.ylthiocarbamoyl (e. g. methylsulfonylthio-carbamoyl, etc.), cai:bamoyl and so on. One of X1 and X2 may be a halogen atom such as fluorine, chlorine, bromine or iodine, and X1 anc~ X2 may join together with the adjacent carbon atom to form ~CO-O CH 3 a ring such as, for example, C Preferred V
CO-O CH3.

examples of the group C= are 02NCH=.
X
Referring i:.o the above formulas [ I ° ] and [ I ] , R1 may be a group attached through a carbon, oxygen or sulfur atom, but a group attached through a nitrogen atom is preferred.
Thus, for examp:Le, a group of the formula -N can be used. In the above formula, R3 is for ~R4 example a hydrogen atom, an alkyl group (for example, ~ 340 99 ~

a C1_6 alkyl group such a.s methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, n-hexyl,, etc. ) , an C6_lo aryl group (for example, phenyl, etc.), an C~_9 aralkyl group e.g. phenylalkyl (such as benzyl, etc.), a heterocyclic group as mentioned below (for example, pyridyl, etc.),, a C1_4 acyl group (for example, formyl, acetyl, propionyl, etc.),a C6_lo arylcarbonyl (for example, benzoyl, etc.), an alkoxycarbonyl group (for exapmle, C1-4 alkoxycarbonyl grc>ups such as methoxycarbonyl, ethoxycarbonyl, etc. ) , a C6_~o aryloxy-carbonyl group (for example, phenoxycarbonyl, E:tc.), a heterocycleoxycarbonyl group wherein the heterocycle moiety is as mentioned below (for example, furyloxycarbonyl, etc.), a C6-to arylsulfonyl group (for example, phenylsulfonyl, etc.), an alkylsulfonyl group (for example, C1_4 alkylsulfonyl groups such as methylsulfonyl, etc.), a dialkoxyphosphoryl group (for example, di-C1_4 alkoxyphosphoryl groups such as diethoxyphosphoryl, etc.), an alkoxy group (for example, C1_4 alkoxy groups such as methoxy, ethoxy, etc.), a hydroxy group, an amino group, a dialkylamino group (for example, di-C1_4 alkylamino group, such as dimethylamino, diethylamino, etc.), an acylamino group (for example, C1_4 alkanoylamino groups such as formylamino, acetylamino, propionylamino, etc.), an alkoxycarbonylamino group (for example, C1_4 alkoxy-carbonylamino groups such as methoxycarbonylamino, etc), an alkylsulfonylamino group (for example, C1_4 alkylsulfonylamino groups such as methylsulfonylamin.o, etc.), a di-alkoxyphosphorylamino group (for example, di-C'1_4 alkoxyphosphorylamino groups such as diethoxyphosphorylamino, etc.), an C~_9 aralkyloxy group (for example, benzyloxy, etc.), an alkaxycarbonylalkyl group (for example, Cl_4 alkoxy-carbonyl-C1_4 alkyl groups such as methoxycarbonylmethyl, etc.) or the like. R4 is for example a hydrogen atom, or an all~:yl (for example, C1_4 alkyl groups such as methyl, ethyl, etc.), cycloalkyl (for example, C3_6 cycloalkyl groups such as cyclohexyl, etc.), alkenyl (for example, CZ_4 1 , __ 134p gg 1 alkynyl groups such as ethynyl, etc.) group which may optionally be sub:~tituted by 1 to 3 substituents (e. g.
hydroxyl, C1_4 alkoxy such as methoxy, halogen such as fluorine, di-C1_4 alkylamino such as dimethylamino, C1_4 alkylthio such as ~~ i-propylthio and n-propylthio, C1_3 alkanoylamino such as acetylamino, C1_9alkylsulfonylamino such as methylsulfonylamino, tri-C1_9 alkylsilyl such as trimethylsilyl, pyridyl or thiazolyl which may optiona=Lly be substitute=d with a halogen atom, etc.).
Furthermore, R3 and R4 may, taken together with the adjacent 1C nitrogen atom, constitute a 5- or 6-membered cyclic amino group such as N N~ N-CH3 N 0 N and so on.

- s - 'I 3 4 0 9 9 'I
The group attached through a nitrogen atom, represented by :R1, includes an amino group which may optionally be substituted (for example by any of the alkyl, aryl, aralkyl, heterocyclic, acyl, alkoxycarbonyl, aryloxycarbonyl, heterocycleoxycarbonyl, arylsulfonyl, alkylsulfonyl, dialkoxyphosphoryl, cycloalkyl, alkenyl, cycloalkenyl and alkynyl groups mentioned in the above definition of R3 and R4) such as di-substituted amino groups, e.g. di-C1-6 alkylamino, N-C1-6 alkyl-N-formyl-amino, etc., mono-substituted amino groups, e.g.
mono-C1-6 alkylamino etc., and unsubstituted amino, a hydrazino group which may optionally be substituted (for example by any of the alkyl, acyl, alkoxycarbonyl, alkylsulfonyl, dialkoxyphosphoryl and other groups mentioned in the. above definition of R3) or a hydroxyamino group which may optionally be substituted (for example by any of the a:Lkyl, aralkyl and other groups mentioned in the above description of R3).
R2 is a hydrogen atom or a group attached through a carbon, nitrogen or oxygen atom. The group attached through a carbon atom, R2, includes, among others, C1_4 acyl (for example, formyl, acetyl, propionyl, etc.), alkyl (for example, C1_4 alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, 2:~ etc.), alkenyl (for example, C2_4 alkenyl groups such as vinyl, allyl, etc.), cycloalkyl (for example, C3_6 cycloalkyl groups such as cyclopentyl, cyclohexyl, etc.), C6-10 aryl (for example, phenyl, etc.), C~_g aralkyl -9- 1 3 4 0 9 9 1 _ (e. g. phenylalkyl (such as benzyl), etc.) and heterocyclic as mentioned below which is bonded at a carbon atom thereof (for example, 3- or 4-pyridyl, etc.). These groups may each be substituted by 1 to 3 substituents (for example, C1-4 alk.ylthio groups such as methylthio, ethylthio, etc., C1-4 alkoxy groups such as methoxy, ethoxy, etc., mono- or di-C1_4 alkylamino groups such as methylamino, dimethylamino, etc., C1_4 alkoxy-carbonyl groups such as methoxycarbonyl, ethoxycarbonyl, etc., C1-4 alkylsulfonyl groups such as methylsulfonyl, ethylsulfonyl, etc., halogen atoms such as fluorine, chlorine, bromine iodine, etc., Cl-4acy1 groups including alkanoyls such as acetyl, etc., benzoyl, phenylsulfonyl, pyridyl and so on).
The group attached through a nitrogen atom, R2, includes, gong others, the groups mentioned in the definition of R1. The group attached through an oxygen atom, R2, include, among others, al:koxy (for example, C1-4 alkoxy groups such as methoxy, ethoxy, etc.), cycloalkoxy (for example, C3-6 cy~~loalkoxy groups such as cyclohexyloxy etc.), alkenyloxy (for example, C2-4 alkenyloxy groups such as vinyloxy, allyloxy, ete.), cycloalkeny)_oxy (for example, C3-6 cy~~loalkenyl_oxy groups such as cyclohexenyl-oxy etc.), alkynyloxy (for example, ethynyloxy etc.), C6-10 aryloxy (for example, phenoxy, etc.), heterocycleoxy wherein the hete:rocycle moiety is as mentioned below -1°- 1340991_ (for example, thienyloxy etc.) and hydroxyl. These groups may each have 1 to 3 substituents (for example, halogen such as fluorine, chlorine, bromine, phenyl and so on). R2 is preferably a group attached through a carbon, nitrogen or oxygen group, such as formyl, an alkyl group (particularly C1-4 alkyl groups such as methyl, ethyl, etc.) which may optionally be substituted (for example by the C1-4 alkylthio, C1-4 alkoxy, mono- or di-C1-4 alkylamino, C1-4 alkoxycarbonyl, C1-4 alkylsulfonyl, acetyl, benzoyl, phenylsulfonyl, pyridyl, etc.), an amino _group which may optionally be substituted (for example,those mentioned in the definition of R1) and a hydroxyl group which may optionally be substituted for example by the above-mentioned C1-4 alkyl, C3_6 cycloalkyl, C2-4 alkenyl, C3-6 cYcloalkenyl, C2-4 alkynyl, Cr-10 aryl and heterocyclic groups (particularly C~-4 alkoxy groups such as methoxy and so on). The symbol n means 0, 1 or 2. Therefore, -CnH2n- in the formulas [I°]
and [I] represents a :single bond, -CH2-, -CH2CH2-, or -C:H-, although the single bond or -CH2- is preferred. The symbols A° and A mean a heterocyclic group as mentioned below (such as 3-pyridyl, 6-chloro-3-pyridyl, 6-methoxy-3-pyridyl, 6-methyl-3-pyridyl, 3-quinolyl, etc.), preferably one which may optionally be substituted ~340991 with one to three of the choices (i), (iv), (Viii), (XVii), (XLVi), (XLViii) and so on as mentioned below, or a cyclic hydrocarbon group as mentioned below (such as cyclopropyl, cyclohe~;yl, phenyl, p-chlorophenyl and so on)~
preferably one which may optionally be substituted with one or two of the choice (XVii) as mentioned below. The heterocyclic group of: A° or A is more preferably a pyridyl or thiazolyl group which may optionally be substituted, such as 3-pyridyl, 6-~chloro-3-pyridyl,6-bromo-3-pyridyl, 2-chloro-5-thiazolyl and so on. The cyclic hydrocarbon group A is more preferably a halophenyl group such as p-chlorophenyl and so on.
As the alkyl, c:ycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, aralkyl, heterocyclic and cyclic hydro-:15 carbon groups in the definitions of X1, X2, Rl, R2, R3, R4, A° and :~1, the following groups, among others, may be employed and each of these groups may have 1 to 5 substituents such as (i) through (Lii) which appear hereinafter .
:20 The alkyl croup preferably contains l to 20 carbon atoms and is more preferably a group of 1 to 8 carbon atoms. This all~yl group may be straight-chain or branched. Specific examples of the alkyl group include methyl, ethyl, 1?ropyl, isopropyl, butyl, isobutyl, 25 sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, 1 340 gg ~
nonyl, 2-ethylhexyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, octadecyl, nonadecyl, eicosyl and so on.
The cycloalkyl group is preferably a group of 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and so on.
The alkenyl group is preferably a group of 2 to 6 carbon atoms. Specific exannples of such alkenyl group include vinyl, allyi, isopropenyl, nnetha11y1, 1,1-dimethylallyl, 2-butenyl, 3-butenyl, 2-pentenyl., 4-pentenyl, 5-hexenyl and so on.
The cycloalkenyl. group is preferably a group of 3 to 6 carbon atoms, such as 1-cyclopropenyl, 2-cyclo-propenyl, 1-cyclobute;nyl, 2-cyclobutenyl, 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 1,3-cyclohexadien-1-yl, 1,4-cyclohexadien-1-yl, 1,3-cyclopentadien-1-y1~2,4-cyclopentadien-1-yl amd so on.
The alkynyl group is preferably a group of 2 to 6 carbon atoms, such as ethynyl, propargyl, 2-butyn-1-yl, 3-butyn-1-yl, 3-butyn.-2-yl, 1-pentyn-3-yl, 3-pentyn-1-yl, 4-pentyn-2-yl, 3-hexyn-1-yl and so on.
The aryl group miay for example be phenyl or naphthyl.
The aralkyl group may for example be benzyl, phenethyl, naphthylmeahyl or the like.

The heterocyclic: group includes, among others, 5-to 8-membered rings each containing 1 to 5 hetero atoms such as oxygen, sulfur and nitrogen or fused rings derived therefrom, such as 2- or 3- thienyl, 2- or 3- furyl, 2- or 3- pyrrolyl, 2-~, 3- or 4- pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5- thiazolyl, 3-, 4- or 5- pyrazolyl, 2-, 4- or 5- imidazol.yl, 3-, 4- or 5- isoxazolyl, 3-, 4-or 5- isothiazolyl, 3- or 5- (1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-t.riazolyl, 1,2,4-triazolyl, 1H- or 2H
tetrazolyl, N-oxido- 2-, 3- or 4- pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5- pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, N-oxido-3- or 4-pyridazinyl, .L5 benzofuryl, benzothia.zolyl, benzoxazolyl, triazinyl, oxotriazinyl, tetrazo~lo[1,5-b]pyridazinyl, triazolo[4,5-b]pyrida.zinyl, oxoimidazinyl, dioxotriazinyl, pyrro~lidinyl, giperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, morpholinyl, 1,4-thiazinyl, 1,3-thiazinyl, pipera.zinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolin.yl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthy-ridinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl, phenoxazinyl and so on.
The cyclic hydrocarbon group includes, among others, C3-6 cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc., C3-6 cyclo-alkenyl groups such as 1-cyclopropenyl, 2-cyclobutenyl, 1-cyclohexenyl, 2-cyclohexenyl, 1,3-cyclohexadien-1-yl, etc., and C6-10 aryl groups such as phenyl, naphthyl ~. 5 and so on .
(i) C1_4 Alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, etc.
are used.
(ii) C3-6 Cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. are used.
. (iii) C6-10 Aryl groups such as phenyl, naphthyl, etc.
are used.
(iv) C1-4 Alkoxy groups such as methoxy, ethoxy, propoxy, isopro:poxy, butoxy, tert-butoxy, etc. are used.

- is -(v) C3-6 Cycloalkyloxy groups such as cyclopropyloxy, cyclopentyloxy, cyclo~hexyloxy, etc. are used.
(vi) C6-10 Aryloxy groups such as phenoxy, naphthyloxy, etc. are used.
(vii) C~-12 Aralkylo~xy groups such as benzyloxy, 2-phenethyloxy, 1-phenethyloxy, etc. are used.
(viii)Cl-4 Alkylthio groups such as methylthio, ethylthio, propylthio, butylthio, etc. are used.
(ix) C3-6 Cycloalkylthio groups such as cyclopropyl-1.0 thio, cyclopentylthio, cyclohexylthio, etc. are used.
(x) C6-10 Arylthio groups such as phenylthio, naphthylthio, etc. are used.
(xi) C~-12 Aralkylthio groups such as benzylthio, 2-phenethylthio, 1-phenethylthio, etc. are used.
1.5 (xii) Mono-C1-4 alkylamino groups such as methylamino, ethylamino, pro;pylamino, isopropylamino, butylamino, isobutylamino, tert-b~utylamino, etc. are used.
(xiii)Di-C1-4 alkylamino groups such as dimethylamino, diethylamino, dipropylamino, dibutylamino, N-methyl-N-~'.0 ethylamino, N-methyl-N-propylamino, N-methyl-N-butyl-amino, etc. are used.
(xiv) C3-6 Cycloalkylamino groups such as cyclopropyl-amino, cyclopentylamino, cyclohexylamino, etc. are used.
%'-5 (xv) C6-10 Arylamin.o groups such as anilino etc. are used.
1 34p g9' (xvi) C~-12 Aralkylamino groups such as benzylamino, 2-phenethylamino, 1-p~henethylamino, etc. are used.
(xvii)Halogen atoms such as fluorine, chlorine, bromine and iodine are used.
(xviii)C1-4 Alkoxycarbonyl groups such as methoxy-carbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxy-carboyl, butoxycarbonyl, tert-butoxycarbonyl, isobutoxycarbonyl, etc. are used.
1'~ (xix) 06_10 Aryloxycarbonyl groups such as phenoxy-carbonyl etc. are used.
(xx) C3-6 Cycloalkyloxycarbonyl groups such as cyclopropyloxycarbonyl, cyclopentyloxycarbonyl, cyclo-hexyloxycarbonyl, etc. are used.
15 (xxi) C~-12 Aralkyloxycarbonyl groups such as benzyloxy-carbonyl, 1-phenethyloxycarbonyl, 2-phenethyloxycarbonyl, etc. are used.
(xxii)C1-5 Alkanoyl groups such as formyl, acetyl, propionyl, butyryl, pivaloyl, etc. are used.
20 (xxiii)C1-1J Alkanoyloxy groups such as formyloxy, acetoxy, butyryloxy, pivaloyloxy, pentanoyloxy, hexanoyloxy, heptanoyloxy, octanoyloxy, nonanoyloxy, decanoyloxy, undecanoyloxy, dodecanoyloxy, tridecanoyloxy, tetradecanoyl-oxy, pentadecanoyloxy, etc. are used.
25 (xxiv)Carbamoyl groups which may optionally be substituted, ... - 17 -1 34p gg 1 such as carbamoyl, N-methylcarbamoyl, N,N-dimethyl-carbamoyl, N-ei_hylcarbamoyl, N,N-diethylcarbamoyl, N-phenylcarbamoyl, pyrrolidinocarbamoyl, piperidino-carbamoyl, pipE~razinocarbamoyl, morpholinocarbamoyl, N-benzylcarbamoyl, etc. are used.
(xxv) Substituted carbamoyloxy groups such as N-methyl-carbamoyloxy, N,N-dimethylcarbamoyloxy, N-ethylcarbamoyl-oxy, N-benzylcarbamoyloxy, N,N-dibenzylcarbamoyloxy, N-phenylcarbamoyloxy, etc. are used.
(xxvi)C1-4 All~:anoyl;~mino groups such as formylamino, acetamido, propionam:ide, butyramido, etc. are used.
(xxvii)C6-10 Arylca:rbonylamino groups such as bent-amido etc. are used.
(xxviii)C1-4 p,lkoxycarbonylamino groups such as methoxycarbonyl.amino,, ethoxycarbonylamino, butoxycarbonyl-amino, tert-but.oxycarbonylamino, etc. are used.
(xxix)C~-12 Aralkyloxycarbonylamino groups such as benzyloxycarbon.ylamino, 4-methoxybenzyloxycarbonylamino, 4-nitrobenzylox:ycarbonylamino, 4-chlorobenzyloxycarbonyl-amino, etc. are used..
(xxx) Substituted sulfonylamino groups such as methane-sulfonylamino, ethanEaulfonylamino, butanesulfonylamino, benzensulfonylamino, toluenesulfonylamino, naphthalene-sulfonylamino, trifluoromethanesulfonylamino, 2-chloro-ethanesulfonylamino, 2,2,2-trifluoromethanesulfonylamino, - 1 340 99 ~
etc. are used.
(xxxi)Heterocyclic groups nuclearly containing 1 to 5 hetero atoms of N, O and/or S, such as pyrrolidinyl, pyrrolyl, pyrazolyl, imidazolyl, furyl, thienyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, piperidi-nyl, pyridyl, piperazinyl, pyrimidinyl, pyranyl, tetrahydropyranyl, tetrahydrofuryl, indolyl, quinolyl, 1,3,4-oxadiazolyl, th.ieno[2,3-d]pyridyl, 1,2,3-thiadiazol-yl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1~~ 1,3,4-triazolyl, tetrazolyl, 4,5-dihydro-1,3-dioxazolyl, tetrazolo[1,5-b]pyridazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, etc. are used.
(xxxii)Heterocyclethio, heterocycleoxy, heterocycleamino, and heterocycle~~arbonylamino groups and groups derived therefrom by attachment of any of heterocyclic groups (xrxi) to the S, O, N atom or the carbonylamino group are used.
(xxxiii)Di-C1-4 alkylphosphinothioylamino groups such as dimethylphos;phinothioylamino, diethylphosphinothioyl-2'~ amino, etc. are used.
(xxxiv)Alkoxyimino groups such as methoxyimino, ethoxyimino, 2-fluoroethoxyimino, carboxymethoxyimino, 1-carboxy-1-methylethoxyimino, 2,2,2-trichloroethoxy-carbonylmethoxyimino, 1-(2,2,2-trichloroethoxycarbonyl)-25 1-methylethoxyimino, (2-aminothiazol-4-yl)methoxyimino, (1H-imidazol-4-yl)methoxyimino, etc. are used.
(xxxv)C1-4 Alkylsulfonyloxy groups such as methane-sulfonyloxy, ethanesu.lfonyloxy, butanesulfonyloxy, etc.
are used.
(xxxvi)C6-10 Arylsulfonyloxy groups such as benzene-sulfonyloxy, toluenesulfonyloxy, etc. are used.
(xxxvii) Di-C6-.10 arylphosphinothioylamino groups such as diphenylphosphi.nothioylamino, etc. are used.
(xxxviii)Thioca.rbamoylthio groups which may optionally be substituted, such as thiocarbamoylthio, N-methylthio-carbamoylthio, 1V,N-di.methylthiocarbamoylthio, N-ethyl-thiocarbamoylth:io, N-benzylthiocarbamoylthio, N,N-dibenzylthiocarbamoylthio, N-phenylthiocarbamoylthio, etc. are used.
(x~ix)Silylox~ groups such as trimethylsilyloxy, t-butyldimethylailyloxy, t-butyldiphenylsilyloxy, dimethylphenyls:ilylaxy, etc. are used.
(xL) Silyl groups such as trimethylsilyl, t-butyldi-methylsilyl, t-butyldiphenylsilyl, dimethylphenylsilyl, 2;0 etc. are used.
(xLi) C1-4 Alkylsulfinyl groups such as methylsulfinyl, ethylsulfinyl, propylsulfinyl, butylsulfinyl, etc. are used.
(xLii)C6-10 Arylsulfinyl groups such as phenylsulfinyl, naphthylsulfinyl, etc. are used.
(xLiii)C1-4 A1'.kylsulfonyl groups such as methanesulfonyl, ethanesulfonyl, butanesulfonyl, etc. are used.

2°- 1340991 .
(xLiv)C6_10 Arylsulf~onyl groups such as benzenesulfonyl, toluenesulfonyl, etc. are used.
(xLv) C1-4 Alkoxycarbonyloxy groups such as methoxy-carbonyloxy, ethoxyca.rbonyloxy, tert-butoxycarbonyloxy, etc. are used.
(xLvi)Halo-C1-4 alkyl groups such as trifluoromethyl, 1,1,2,2-tetrafluoroethyl, difluoromethyl, monofluoromethyl, trichloromethyl, dich.loromethyl, monochloromethyl, etc.
are used.
(xLvii)Halo-C1-4 alkoxy, halo-C1-4 alkylthio, halo-C1-4 alkylsulfinyl a:nd halo-C1-4 alkylsulfonyl groups as well as groups derived therefrom by attachement of any of halo-C1-4 alkyl groups (xLvi) to the O, S, sulfinyl and sulfonyl moieties thereof are used.
~-5 (xLviii)Cyano, nitro, hydroxy, carboxyl, sulfo and phosphono group's are used.
(xLix)C1-4 Alkyloxysulfonyl groups such as methoxysulfonyl, ethoxysulfonyl, butoxysulfonyl, etc. are used.
(L) C6-10 Aryloxysulfonyl groups such as phenoxysulfonyl r tolyloxysulfonyl, etc. are used.
(Li) C~-12 Aralkyloxysulfonyl groups such as benzyloxy-sulfonyl, 2-phenethyloxysulfonyl, 1-phenethyloxysulfonyl, etc. are used.
(Lii) Di-C1-4-alkyloxyphosphoryl groups such as ~5 dimethoxyphosphoryl, diethoxyphosphoryl, dibutoxyphosphoryl, etc. are used.

Preferred examples of the unsaturated amines of formulas [I°] and LI] or salts thereof include:
The a.-unsaturated amines of the formula:
R,a RZa I I a OzN-CH=C-N-CH2-Aa [I
wherein Rla is a mono-Cl-6 alkylamino group, an N-Cl-6 alkyl-N-formylamino group or an amino group; R2ais an Cl-4 alkyl group or a.n Cl-4 alkoxy group; Aa is a 1'7 chloropyridyl group, or salts thereof;
the a-unsaturated amines of the formula:
R vb 02N-CH=C-NH-Cliz-Aa [
1'~ wherein Rlb is a mono-C1-6 alkylamino grou or an P
N-Cl-6 alkyl-N-formylamino group; Aa has the meaning defined hereinbefore,, or salts thereof;
the a.-unsaturated amines of the formula:
R ~c RZb 2t) I I . b [I~]
OZN-CH=C-N-CHZ-A
wherein Rlc is a di-Cl-6 alkylamino group; R2b is a hydrogen atom, a formyl group or an Cl-4 alkyl group;
b A is a pyridyl group or a chloropyridyl group, or salts thereof; and the a.-unsaturate:d amines of the formula R' R2 X\>C=C-N-A° [Idl X'~
wherein the symbols have the meanings defined herein-before , or salts thez-eof .
Referring to they above formulas [Ia], [Ib] and [Ic], the mono-C1-6 a.lkylamino group represented by Rla or Rlb includes, among others, monomethylamino, 1.0 monoethylamino, mono-n-propylamino, mono-i-propylamino, mono-n-butylamino, mono-i-butylamino, mono-n-hexylamino, etc. and preferably mono--C1-4-alkyl amino groups such as mono-methylamino, monoethylamino and so on. The N-Cl-6 alkyl-N-formyi-amino group represented by Rla or Rlb includes, among 1.5 others, N-methyl-N-fo~rmylamino, N-ethyl-N-formylamino, N-n-propyl-N-formylam~ino, N-i-propyl-N-formylamino, N-n-butyl-N-for:mylamino, N-n-hexyl-N-formylamino, etc.
and preferably N-C1-4 alkyl-N-formylamino groups such as N-methyl-N-formylamino, N-ethyl-N-formylamino and so on. The di-C1-6 alkylamino group represented by Rlc includes, among others, dimethylamino, N-ethyl-N-methylamino, diethylamino, di-n-propylamino, di-i-propyl-amino, di-n-butylamino, di-i-butylamino, di-n-pentylamino, di-i-pentylamino, di-~n-hexylami.no, etc. and preferably ~5 di-C1_4 alkylamino groups such as dimethylamino, N-ethyl-N-methylaminc> and diethylamino.

The C1-4 alkyl group represented by RZa or RZc includes, among others, the alkyl groups mentioned in the defini-tion of R2 abovE~ and :preferably methyl, ethyl and so on. The Cl-4 a:Lkoxy group represented by R2a includes, among others, the alkoxy groups mentioned in the definition of R'~ above and preferably methoxy, ethoxy and so on. The chloropyridyl group represented by Aa or Ab includes, among others, 2-chloro-3-pyridyl, 4-chloro-3-pyri<iyl, 5-chloro-3-pyridyl, 6-chloro-3-pyridyl, 1« 3-chloro-4-pyridyl, etc. and preferably 6-chloro-3-pyridyl and so on. The pyridyl group represented by Ab includes 3-pyridyl, 4-py:ridyl, etc. and preferably 3-pyridyl.

1 340 gg ~
Typical a-unsaturated amines of formulas [I°) and [I] or salts thereof include .
The a-unsaturated amines of the formula .
R3a R4a ~~ R2c ~2N~ I I
/C = 'y - N - CnH2n - Ac [ Ie l X2a wherein X2a is a hydrogen atom, C1_4 alkoxycarbonyl or C1_4 alkylsulfozylthiocarbamoyl; R2c is a hydrogen atom, C1-3 acyl, C1_4 alkyl, mono- or di- C1_4 alkoxy-C1_4 alkyl, C~_g aralkyl, mono- or di- C1_4 alkylamino or C1_4 alkoxy;
Ac is 3- or 4- pyridyl, pyrazinyl or 4- or 5- thiazolyl which may optionally be substituted with halogen, C1_4 alkyl or C1_4 a:Lkoxy; and R3a, R4a and n are as defined above, or salts thereof;
the a-unsaturated amines of the formula .
p2N\ ~i ld R2c C = (~ - N - CnH2n-Ad [Ifl X2a~
wherein X2a is <~ hydrogen atom, C1_4 alkoxycarbonyl or C1_4 alkylsulfonylthiocarbamoyl; Rld is amino, mono-or di- C1_4 alkvlamino, N- C1_4 alkyl - N- C1_3 acylamino, C~_g aralk;ylamino, halogenothiazolyl- C1_2 alkylamino or C:~_4 al:koxy -C1_2 alkylamino;
R2c is a hydrogE:n atom, C1_3 acyl, C1_4 alkyl, mono- or di- C1_4 alkoxy-- C1_4 alkyl, C~_g aralkyl, mono- or di--25- 1 340 99 ~
C1_4 alkylamino or C1_4 alkoxy;
n is an integer- equal to 0, 1 or 2; and Ad is 3- or 4-pyridyl, pyrazinyl o:r 5-thiazolyl which may optionally be substituted wit=h halogen, C1_4 alkyl or C1_4 alkoxy, or salts thereof;
the a-unaaturai~ed amines of the formula .
02N\ Rle ~i 2d /C =- C - LEI - CH2 - Ae [Ig]
X2b wherein X2b is a hydrogen atom or C1_2alkylsulfonylthio-carbamoyl; R1-a is amino, mono- or di-C1_2alkylamino or N-C1_2alkyl-N-formylamino; R2d is a hydrogen atom, C1_2alkyl or C1._3acy7L; and Ae is a group of the formula .
~ Hal or ~~ wherein Hal is a ~Hal halogen atom, or salts thereof;
the a-unsaturated amines of the formula .
p2N Rlf FZ2d \
'C = C - ~j - CH2 - Ae [Ih]
X2c wherein X2c is a hydrogen atom or methylsulfonylthio-carbamoyl; Rlf is amino, methylamino, dimethylamino or N-methyl-N-form.ylamino ; R2d is a hydrogen atom, formyl or C1_2alkyl ; and Pie is a group of the formula .

-26- 1 340 99 ~
~ Hal or I~ wherein Hal is Hal a halogen atom, or salts thereof ; and the a-unsaturated amines of the formula .
F;le R2E:
02NCH = C'. - N -- CH2 --~~- Hal [ Il ]
wherein Rle is amino,, mono- or di-C1_2alkylamino or N-C1_2alkyl-N-formylamino ; R2e is C1_2alkyl or formyl ;
and Hal is a halogen atom, or salts thereof.
In the above formulas [Ie] to [Ii], the groups representE:d by X2a, X2b and X2c, the groups representE~d by Rld, Rle and Rlf, the groups represented by R2c, R2d and R2 e, and the groups representE~d by Ac, Ad and Ae are as mentioned abovefor X2, R1, R2, A° and A, respectively.
The compound [7.]or its salt can be produced by the analogous known procE~sses and further by the following processes, for instance.
Process 1) x'v /S-RS y-N-CnHZn-A
C=C
~S- R,6 CIIJ

X \C=C-N-'~nHZn-A R~ ~ C I ]
Xs /
C 1~ J
or R
CVJ ~ X 'C-~-S-R5 C~ CI J
Z ~

1 34p gg 1 wherein X1, X2, R1, R2, n and A have the meanings defined hereinb~~fore; R5 is an C1-4 alkyl group such as methyl, ethyl, etc. or an C~_garalkyl group such as benzyl etc.; Y is a hydrogen atom or an alkali metal such as sodium, potassi.m, etc.
Process 2) R = C'i~ ] N H R 3 R' HN-CnH2n-,~ R3--NCS~ S=C -~_CnH2n_A
C~Jy-ct l0 N133 RZ X' CX7 5 z~CH ~
R5s -~-N-CnHEn_A X
C IX
NIiR' Rp x' I
>C=C -N-CnHzn-A
xz C I -1) or CVQ'] NHR' R' R'-NCS I I
CIIIJY=H -~ s=C-N_CnHzn-A
CVO' J
NR' R2 R I R5S-C--N-CnHZn_A C----C IX' NtiR' R' X' >C=C -N-CnH2n-A
XZ
C I _ 2) _28_ or ~Y~ ] R1 R1-H A-CnHzn-NCS l R5i S= C- NH- CnHZn _ A --CV]Y-fi CV(Q"]
R~ R~
R'S-C=N-Cr~fizn-A ~ X C=C-NH-CnHzn-A
XZ
CIX" ] . . C I - 3]
wherein X1, X2, R1, R2, R3, R4, R5, n and A have the meanings defined hereinbef ore , Process 3) Hal ~ ) C III ]
OzN-CH=C~Hal or OzN-CHz~a C I ]
ii ) CV ]
C XI ] C xl< ]
or C XI ] .~~r . C Xll ) i i ) C III ] ~ C I ~~
wherein Hal is the meanings defined hereinbefore.
Process 4) X1 Rz X /CH - CON - Cn H zn - A halogenating agent , C X III ]
X t Ha:l. R z XZjC=~__N-CnHzn-A CV] ~ CI ]
C X Iv ]
X ~ h.alogenat-, X i R i or X=,CH- COR _ing agent ~C= ~-Hal [~ [ I ]
[X V ] j Xx~ [X VI]

- 134099' ' wherein X1, X2, R1, R2, Hal, n and A have the meanings defined hereinbefore.
Process 5) X~ R~ R= CXY~7 A-CnHZn-Had C I 7 Xz,C=(,-NH -CX V~]
wherein X1, X2, R1, R2, Hal, n and A have the meanings defined hereinbefore.
Process 6) X3 R~ R i) Hydrolysis c R600C~C C-N-CnHzn-A ii)Decarboxylation CXI:K7 X3 R' Rs jC=C-N-CnH;,n-A
fi C I -- 4 wherein R1, R2, n, A and R5 have the meanings defined hereinbefore; X3 is an electron-attracting group.
Process 7) XyC-C_ R Xy R~ H
Xp/ N-Cru[2n-A or X2/C=C_N_CnH2n-A
2o C I -57 C I -67 Alkylation, acylation, alkoxycarbonylation, sulfonylation or phosphorylat:ion [I]
wherein X1, X2, R1, R2, n and A have the meanings defined hereinb~~fore; R6 is a group attached through a nitrogen atom containing at least one hydrogen atom.
In the processes 1) to 7), the compounds [III], [IV]

[v] , [vI] , [Ix.l , [Ix' ] , [Ix"] , [x] , [xm] , [xvI] , [xvll] , [XVIII], [XIX],, [I-5], [I-6] and so on may be used in a form of a salt (e.g. one as mentioned below in a salt of the compound [ J: ] ) .
In accordance with the aforementioned Process l), a compound of general formula [II] is reacted with an amino compound of general formula [III] or a salt thereof to give a compound of general formula [IV]
which is then reacted with an amino compound of general formula [V] or ,~ salt thereof, or a compound of general formula [II] is reacted with a compound of general formula [V] to give a compound of general formula [VI]
which is then reacted with a compound of general formula [III], to thereby give a compound [I]. In practicing the :Process 1), the reactions of [II]~[IV], [IV]~[I], [II]'~[VI) and [VI]~[I] may respectively be conducted in an appropriate solvent. There is no limitation on such a solvent provided that it does not interact with the reactant, reagent or reaction product to give byproducts but a solvent capable of dissolving both the reactant and reagent is preferred. As examples of such solvent, there may be mentioned alcohols such as methanol, etlZanol, propanol, butanol, etc., aromatic hydrocarbons such as benzene, toluene, xylene, etc., ethers such as diethyl ether, dipropyl ether, dibutyl ether, tetrahyd:rofuran, dioxane, etc., nitriles such as acetonitrile, p:ropionitrile, etc., acid amides such as dimethylformamide, dimethylacetamide, etc., sulfoxides such as dimethyl fulfoxide~etc., sulfones such as sulfolane~

- 1340991 .
etc., and phosphoram:Ldes such as hexamethylphosphoramide etc., as well as various mixtures thereof and mixtures thereof with water. While each of the above reactions is generally conducted at atmospheric pressure, it is possible to conduct the reaction under reduced pressure as taught by Japanese Unexamined Patent Application KOKAI-62-138478 (1987) to remove the byproduct low-boiling thiol and thereby suppress the secondary reaction. When a low-boiling solvent is used, the reaction is preferably conducted at su:pratmospheric pressure. For the aforesaid respective reactions, the reaction temperature may range from 30 to 150°C and preferably from 50 to 150°~~. The reaction time is generally 5 minutes to 48 hours, depending on the reaction temperature, reactant, reagent and solvent. The proportions of :reagents [III] and [V] in the reactions [II)~[IV] and ('II]~[VI] may each be 1 to 1.2 molar equivalents relative to [II]. The use of [III] and (V]
in further excess is preferably avoided to prevent by-production o:f the diamino compound. As the reaction [II) > [IV]and [:II] >[VI] in a concentrated reaction mixture may occasionally give the by-product, the diamino compound, it is desirable to avoid the reactions in such condition. The proportions of reagents (V]and [III]in the reactions [IV]~[I]and (VI]-~[I] are generally 1 to 1.5 molar equivalents and, unlike in the reactions [II]->(IV] and (II]~
[VI], the use of [Vj or [III] in greater excess may not occasionally induce byproduct formation. A base may be permitted to be concomitantly present for the purpose of promoting the reaction or suppressing secondary reactions. As the base for such purposes, there may be used organic bases such as triethylamine, N-methylmorpholine, pyridine, 1,8-diazabicyclo[5,4,0]-7-undecene, 1,5-azabicyclo[4,3,0]non-5-ene, etc. and inorganic bases such as potassium carbonate, potassium hydrogen carbonate, sodium carbonate, sodium hydrogen carbonate, lithium carbonate, lithium hydrogen carbonate and so on. Where an alkali metal salt of reagent [III] or [V] is used, the sodium salt, lithium salt, potassium salt, etc. can be employed. The compound [IV] or [VI] may be isolated and purified by conventional procedures such as concentration, concentration under reduced pressure, pH adjustment, redistribution, solvent extraction, distillation, crystallization, recrystallization, chromatography, etc. and subjected to the next reaction. Alternatively the reaction mixture containing [IV] or [VI] may be such be directly used as the starting reactant for the next reaction.
The starting compound of general formula [II] for Process 1) can be synthesized by the procedures described in Chem. Ber. 1170, 591 (1967), Acta. Chem. Scand. 22, 1107 (1968), Synthesis 1986, 967, Chem. Ber. 95, 2861 :Z5 (1962), Tetraheron 30, 2413 (1974), Synthesis 1984, 797 and other literature or by procedures analogous thereto.

1 340 99 ~
The compound [III] cam be synthesized by the procedures described in Organic Functional Group Preparations, Academic Press, Vol 1., Chapter 13 (1968) and Vol 3, Chapter 10 (1972) and. other literature or by procedures analogous thereto, anal the compound (V] can be syn-thesized by the procedures described in Survey of Organic Syntheses, Wiley-Interscience (1970), Chapter 8 and other literature or by procedures analogous thereto.
The aforementioned Process 2) comprises (1) reacting an amino compound of general formula [III]
(Y=H) or an alkali metal salt (e. g. Na or K salt) with an isothiocyani~~ ester of general formula [VII] to give a thiourea of general formula [VIII], then reacting said thiourea [VIII] with. the compound of the formula : R5I (e. g. methyl iodide, etc.)to give an isothiourea of general formula [IX], and reacting [IXj with an active methylene compound of general formula [X], (2) reacting an amino compound of general formula [III] (Y=H) or an alkali metal salt thereof with an isothiocyanic ester [VII'], then reacting the resulting thiourea (VIII'] with the compound of the formula : R5I (e. g.
methyl iodide, etc.) to give an isothiourea [IX'] and reacting [IX'j with an active methylene compound [X], or (3) reacting an amino compound of general formula [V](Y==H) or an alkali metal salt thereof with an isothiocyanic acid ester [VII"j, reacting the resulting thiourea [VIII"] with the compound of the formula . R5I (e. g.
methyl iodide, etc), a.nd reacting the resulting isothiourea [IX"]
with an active methyl.ene compound, to thereby give the desired compound [I].
Referring to Process 2), the reactions [III]Y=H~
[VIII], [III]Y=Hj[VIII'] and [V]Y=H~[VIII"] and the reactions [VIII][IX], [VIII']~[IX'] and [VIII"]j[IX"]
can each be conducted. by the known procedures described in the literature or by procedures analogous thereto.
As said literature, there may be mentioned Chemical Society of Japan (ed.): Shin Jikken Kagaku Koza (New Series of Experimental Chemistry), Vo. 14, III, Maruzen (1978), Chapters 7 anal 21; Organic Functional Group Preparations, Vol. 2, Academic Press'(1971), Chapters 6 and 7, ditto The Second Edition (1986), and so on.
Each of the reactions [III]Y=H3[VIII], [III]Y=H~
[VIII'], and [V]Y-H'~[VIII"] can be conducted in an appropriate solvent. There is no limitation on such a solvent provided that it does not interact with the reactant or the reagent but it is preferable to select a solvent capable of dissolving both the reactant and reagent. As examples of such solvent, there may be mentioned aromatic hydrocarbons such as benzene, toluene, xylene, etc.; aliphatic hydrocarbons such as pentane, hexane, heptane, petroleum ether, ligroine, petroleum benzene, etc.; ethers such as diethyl ether, - 1 34p g9 ~
w dipropyl ether, dibut.yl ether, tetrahydrofuran, dioxane, etc.; acid amides such as dimethylformamide, dimethyl-acetamide, etc.; sulfoxides such as dimethyl sulfoxide etc.; sulfones such as sulfolane etc.; phosphoramides such as hexamethylphosphoramide etc.; and halogenated hydrocarbons such as chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, etc. as well as various mixtures thereof. The reaction temperature is about -30° to 200°C and preferably 0 to 150°C. The reaction time varies with such conditions as reaction temperature, reactant, reagent, reaction system concent-ration and solvent, but generally in the range of 1 minute to 24 hours.
The proportions of compounds [VII], [VII'] and [VII"] required for the respective reactions may range from 0.5 to 2 molar equivalents, preferably 0.8 to 1.2 molar equivalents, relative to [III]Y-H, [III]Y=H and [V]Y-H. The compounds [VIII], [VIII'] and [VIII"] thus obtained can each be subjected to the next reaction either without :isolation or after isolation from the reaction mixture by the known procedure.
Each of the reactions [VIII]~[IX], [VIII']~[IX') and [VIII"]~[IX"] may also be conducted in a solvent.
In addition to 'the solvents mentioned for the reactions [III]Y-H~[VIII], [III]Y=H~[VIII'] and [V]Y=H~[VIII"], 1340991_ such other solvents a.s alcohols, e.g. methanol, ethanol, propanol, butanol, et.c.; ketones, e.g. acetone, methyl ethyl ketone, etc.; a.nd esters, e.g. methyl acetate, ethyl acetate, butyl acetate, methyl formate, ethyl formate, ethyl propionate, etc. can also be employed.
The reagent methyl iodide may be utilized as the solvent. For the purpose of promoting the reaction and minimizing the formation of byproducts, a base may be permitted to be present in the reaction system or permitted to act on the reaction system before or after the reaction and there are cases in which such practice contributes to improved results. As the base that can be used for the above purpose, there may be mentioned sodium hydride, sodium metal, alcoholates such as sodium ethoxide, sodium methoxide, potassium tert-butoxide, etc., organic bases such as triethylamine, diisopropylethylamine, pyridine, N,N-dimethylaniline, etc. and inorganic bases such as potassium carbonate and so on. The proportion of the base is preferably 0.8 to 1.2 molar equivalents relative to [VIII], [VIII'] or [VII:I"]. In the absence of a base in the reaction system, [IX], [IX'] or [IX"] is formed as the hydroiodide so 'that this hydroiodide must be neutralized to obtain [IX], [IX'] or [IX"]. The base for this purpose is preferably a water-soluble inorganic base 134p gg 1 such as sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide and so on. The reaction temperature is 0 to 100°C and preferably 20 to 80°C. The reaction time is generally 0.1 to 24 hours.
The proportion of methyl iodide required for the reaction is not less than 1 molar equivalent relative to [VIII], [VIII'] or [VIII"] and may be used in a larger amount as the solvent. The [IX], [IX'] or [IX"]
thus produced may be isolated by the conventional procedure before submission to the next reaction or the reaction product mixture may be directly used as the starting material in the next reaction.
Each of the reactions [IX]j[I-1], [IX']~[I-2] and [IX"]~[I-3] can be conducted in accordance with the procedures described in Tetrahedron 37, 1453 (1981) Indian Journal of Chemistry 15B, 297 (1977) and other literature. The reaction may be conducted using the active methylen~~ compound [X] in excess as a solvent or may be carried out in a different solvent. As the solvent just mentioned above, there may be used aromatic hydrocarbons su~~h as benzene, toluene, xylene, etc., aprotic polar solvents such as dimethylformamide, dimethylacetamide, dimethyl sulfoxide, sulfolane, hexamethylphosphoramide, etc., and ethers such as 134pgg 1 tetrahydrofuran, diox:ane and so on. Particularly where an aprotic polar solvent is used and the reaction is conducted under reduced pressure with the byproduct methylmercaptan being' dispelled out of the reaction system, the formation. of byproducts can be suppressed and the reaction yield improved. The reaction may also be conducted in the presence of a catalyst. As such catalyst, there may be employed zinc chloride, zinc bromide, zinc iodide, cupric chloride and so on. The reaction temperature is 30 to 200°C, preferably 50-150°C.
The reaction time is generally 0.1 to 48 hours. The proportion of a~~tive methylene compound [X] necessary for the reaction is 1 to 5 molar equivalents relative to [IX], [IX'] or [IX"]. Where [X] is a low-boiling compound, it can be used in a solvent amount.
The starting compounds [VII], [VII'] and [VII"]
can be synthesized by the procedures described in Organic Functional Group Preparations, Vol. 1, Academic Press (1968), Chapter 12 and other literature or by procedures analogous thereto, and the compound [X] can be synthesized by procedures described in Formation of C-C Bonds, Vol. 1, Georg Thieme Publishers, Stuttgart (1973) and other literature.
The aforementioned Process 3) comprises reacting a compound [XI] or [XII] with an amino compound of 1340991 , general formula [III] or a salt thereof (e. g. the salt of an alkali metal such as Na or K) and reacting the resulting product further with an amino compound of general formula [V] or a salt (alkali metal salt) thereof or, alternatively, reacting a compound [XI] or [XII] with an amino compound of general formula [V] or a salt thereof and then reacting the resulting product with an amino compound of general formula [III] or a salt thereof to give the desired compound [I].
The reactions in Process 3) can be conducted in the same manner as those in Process 1) and the reaction conditions described for Process 1) can be utilized.
However, since compounds [XI] and [XII] are generally more reactive than compound [II], the reactions are preferably conducted under somewhat milder conditions as compared with Process 1).
The compounds [X.I] and [XII] can be prepared by procedures described in Chemical Abstracts 44, lOllf, Journal of Organic Chemistry 25, 1312 (1960) and other literature or by procedures analogous thereto.
The aforementioned Process 4) comprises reacting an acid amide of general formula (XIII] or an acid amide of general formula (XV] with a halogenating agent to give a halide of general formula [XIV] or [XVI]
and reacting the halide with an amino compound of - ? 340 99 ~
general formula [V] o~r a salt thereof or an amino compound of general formula [III] or a salt thereof to give the desired compound [I].
The reaction of [XIII]~[XIV] and that of [XV]~[XVI]
are preferably ~~onducted in a solvent. As such solvent, there may be mentioned halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroeth,ane, etc., ethers such as diethyl ether, tetrahydrofuran, dioxane, etc., nitriles such as acetonitrile, p:ropionitrile, etc. and so on. This reaction is pre:Eerably carried out under anhydrous conditions. The halogenating agent may for example be phosphorus pent<~chloride, hosphorus oxychloride, phosphorus triclzloride, thionyl chloride, oxalyl chloride or the like. The proportion of the halogenating agent is 1 to 10 molar equivalents, preferably 1 to 5 molar equivalents, re:Lative to [XIII] or [XV]. Preferably a base is permittcsd to 'be present in the reaction system in order to trap the 'byproduct hydrogen chloride, and as such base, there may be used various organic bases such as pyridine, triethylamine, diisopropylethylamine, N-methylmorphol:ine, N,N-dimethylaniline, N,N-diethylamine and so on. The reaction temperature is -80° to 100°C
and preferably ~-50° to 50°C. The reaction time is generally 0.1 to 24 hours, depending on the reactant, - 1 34p 99 ~
base, solvent, reaction concentration and reaction temperature. The products [XIV] and [XVI] can be isolated and purified by the aforementioned known procedures before submission to the next reaction or the reaction product mixture may be directly used in the next reaction.
The reaction of [XIV]~[I] and that of [XVI]~[I]
can each be conducted. in a solvent similar to those mentioned for the reactions of [XIII]~[XIV] and [XV]~
[XVI], preferably under anhydrous conditions. The proportion of [V] or a salt thereof and that of [III]
or a salt.thereof are 1 to 10 molar equivalents, preferably 1 to 5 molar equivalents, relative to [XIV]
and [XVI], respectively. For the purpose of trapping the byproduct hydrogen chloride, [V] or a salt thereof or [III] or a salt thereof can be used in excess but for economy, a different base is preferably permitted to be present. A such base, there may be used any of the bases mentioned for the reactions of [XIII)~[XIV]
and [XV]~[XVI]. The reaction temperature is -80°C to 100°C and preferably -50°C to 50°C. The reaction time is generally 0.1 to 24 hours. The starting compounds [XIIIJ and [XV] can be synthesized by the procedures described in Formation of C-C Bonds, Vol. 1, Georg Thieme Publishers, Stuttgart (1973) and Chemical -42- 134Q 99 1 .
Society of Japa:n(ed.): 'Shin Jikken Kagaku Koza' (New Series of Experimental Chemistry), Vol. 14, II, Maruzen (1977), Chapters 5 and 7 and other literature or by procedures analogous thereto.
The aforementioned Process 5) comprises reacting a compound of general formula [XVII] with a halide of general formula [XVII:I] to give the desired compound [I].
The reaction according to Process 5) is preferably conducted in an appropriate solvent. As such solvent, there may be employed. acid amides such as dimethylform-amide, dimethylacetamiide, etc., sulfoxides such as dimethyl sulfoxide etc., sulfones such as sulfolane etc., phosphoramides such as hexamethylphosphoramide etc., ethers such as tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diethylene glycol dimethyl ether, etc., and so on. Mixtures of such solvents may likewise be employed. This reaction is preferably conducted in the presence of a base. As such base, there may be mentioned sodiwn hydride, potassium hydride, lithium hydride, calciwn hydride, n-butyllithium, lithium diisopropylamide, sodium amide and so on. It is preferable that the compound [XVII] be converted to the salt of said base before it is subjected to the reaction.
The proportion of the base is preferably 1 to 1.5 molar equivalents relative to [XVII]. This reaction is preferably conducted under anhydrous conditions and may be carried out in an atmosphere of nitrogen gas or argon gas. The proportion of [XVIII] is 1 to 2 molar equivalents, preferably 1 to 1.5 molar equivalents, relative to [XVII]. The reaction temperature is -70°C
to 150°C and preferably -50°C to 100°C. The reaction time is generally 0.1. to 48 hours.
The compound [XV'II] can be easily prepared, for example by using a compound of general formula R2NH2 7.0 wherein R2 has the meaning defined hereinbefore, instead of compound [III] in said Processes 1 through 4). The compound [XV'III] can be synthesized by the process described in Organic Functional Group Prepara-tions, Vol. 1, Academic Press (1968), Chapter 6 and J.5 other literature or b~y procedures analogous thereto.
The aforementioned Process 6) comprises subjecting a compound of general formula [XIX], which falls within the category of compound [I], to hydrolysis reaction and, then, to d~ecarboxylation reaction to give a 20 compound of general formula [I-4] which falls within the category of compound [I].
The above ;hydrolysis reaction can be conducted under the conditions of hydrolysis of esters which are known in the art .
2:5 Thus, in a solvent (inclusive of a solvent mixture) 1 34Q gg ~
such as water, alcohc>ls (e. g. methanol, ethanol, propanol, butanol, di.ethylene glycol, 2-methoxyethanol, etc.), ketones (e. g. acetone etc.), ethers (e. g.
tetrahydrofuran, dio~:ane, dimethoxyethane, etc.), amides (e. g. dimethyl.formamide, dimethylacetamide, hexamethylphosphorami.de, etc.), sulfoxides (e. g.
dimethyl sulfoxide et.c . ) , sulfones ( a . g. sulfolane etc.) and carboxylic acids (e. g. formic acid, acetic acid, etc.), the hydrolysis reaction can be conducted .LO using an acid (for example, mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, etc., organic acids such as p-toluenesulfonic acid etc., strongly acidic ion exchange resins, and so on) or a base (for example, sodium hydroxide, potassium .L5 hydroxide, potassism carbonate, sodium hydrogen carbonate, barium hydroxide, calcium hydroxide, sodium methoxide, ammonia and so on), although the use of a base is preferred. The proportion of the base is about 1 to 10 molar equivalents, preferably about 1.2 to 4 molar 20 equivalents, relative to [XIX). The reaction temperature is about -20°C to 200°C, preferably about -5°C to 120°C, and the reaction time is about 0.1 to 48 hours, preferably about 0.1 to 24 hours.
The decarboxylation reaction proceeds simultaneously 25 with said hydrolysis reaction in many cases and usually no special procedure is required. If necessary, this reaction may be carried out by heating in the hydrolysis solvent. The reaction temperature is generally about 0 to 200°C, preferably 30 to 150°C, and the reaction time is 0.1 to 48 hours and preferably 0.1 to 24 hours.
The aforementioned Process 7) comprises subjecting a compound of general formula [I-5] or a compound of general formula [I-6] to alkylation, acylation, alkoxy-carbonylation, sulfon.ylation or phosphorylation to give 1. 0 a compound [ I ] .
For alkylation, the amino group in [I-5] or [I-6]
is alkylated with an alkylating agent such as an alkyl chloride, alkyl bromide, alkyl iodide, dialkyl sulfate or the like. T:he proportion of the alkylating agent is 1.5 about 1 to 3 equivalents relative to the starting compound in many instances. This alkylation reaction may be conducted under the same conditions as those described for Process 5 ) .
The acylat:ion, sulfonylation, phosphorylation and 20 alkoxycarbonyla~tion reaction can each be conducted by procedures known per se or by procedures analogous thereto.
The acylat:ing agent for said acylation reaction may for example be an acyl halide or acid anhydride containing a group of R1 or R2. The sulfonylating 25 agent for said :~ulfon~ylation reaction may for example be a sulfonyl halide or sulfonic anhydride containing a group of R1 or R2. The alkoxycarbonylating agent for .said alkoxycarbonylat.ion reaction may for example an alkoxycarbonyl halide: or carbonate containing a group of R or R . The preferred halogens in the above-mentioned halide reagents are bromine and chlorine.
The proportion of each such reagent is at least one molar equivalent, preferably about 1 to 5 molar equi-valents, relative to the starting compound. Where an acid anhydride is used as the acylating agent in the above acylation reaction, it can be employed in excess.
These reactions are carried out in a solvent capable of dissolving the compound [I-5) or [I-6) and the respective reagents and as preferred examples of such solvent, there may be mentioned dichloromethane, chloroform, dichloroethane, tetrahydrofuran, dioxane, N,N-dimethyl-formamide, N,N-dimethylacetamide, dimethyl sulfoxide, hexamethylphosplaorotriamide, pyridine and so on. The reaction temperature is about -50°C to 150°C and the 2'0 reaction time is about 0.1 to 48 hours. The reaction may be hastened and the secondary reactions suppressed to improve the yield when the reaction is conducted in the concomitant presence of an amine such as triethyl-amine, dimethyl~~ninopyridine, pyridine, N,N-dimethylani-2.5 line, N,N-diethylaniline, etc., sodium hydride, potassium hydride, sodium amide, n-butyllithium, lithium diisoproi~ylamide: or the like.
The object compound (I] or salt thereof thus produced can be isolated and purified by conventional procedures such as concentration, concentration under reduced pressure, distillation, fractional distillation, pH adjustment, redistribution, solvent extraction, crystallization, recr~~stallization, chromatography and so on.
1CI Where the compound [I] is obtained as the free compound, it can be converted to an agro-chemica.ily.acceptable salt and where a salt is obtained, it can be converted to the free compound [I], using the conventional procedure in either case. Where the compound [I]
1~; contains acidic group=~ such as carboxyl, sulfo and/or phosphono groups in its positions X1, X2, R1, R2 and/or A, it may form a salt with a base. As the base used for this purpose, there ma.y be mentioned inorganic bases 20 such as sodium, potassium, lithium, calcium, magnesium, ammonia, etc. and organic bases such as pyridine, collidine, triethylamine, triethanolamine and so on.
Where the compound [I] contains basic groups such as amino, substituted amino and/or other groups in its - 1340991 .
positions X1, X~, R1, R2 and/or A, it can form an acid addition salt. As examples of such acid addition salts, there ma~T be mentioned hydrochloride, hydro-bromide, hydroiodide, nitrate, sulfate, phosphate, acetate, benzoai=e, maleate, fumarate, succinate, tartarate, citrate, oxalate, glyoxalate, aspartate, methanesulfonatc~, methanedisulfonate, 1, 2-ethanedi-sulfonate, benzenesulfonate and so on.
The compound [I] may form an inner salt, which also falls within the scope of the invention.
The compound [I] and its stereoisomer and tautomer (for example, where the compound [I] is a compound of the formula NH RZ
c I
Xz;;C=C-N-CnHzn-A [I' ]
wherein the symbols have the meanings defined herein-before , its tautomer of the formula L. 0 R 3 I
N F; Z
II i Xs jCH-C-N--CnH2n-A [I ]
wherein the symbols have the meanings defined herein-before, also falls into the category of compound 1 340 99 1 , [I]) can be used., either independently or in the form of a mixture, as. an insecticidal/miti(acari)cidal agent.
The compound [I] and its salt according to the invention are effective in the control of household pests and animal or p7.ant parasitizing insects and mites, and exhibit strong pesticidal effects as a contact poison when applied directly to the host animals and plants. The most salient feature of the 1Q compound, however, is that it displays potent pesticidal effects even after it has been absorbed into plants via the root, leaf, stem or the like and come into contact with the pests as the pests suck or gnaw on the plants.
This property is advantageous in the control of suck-l~i ing/biting insets and ticks. Furthermore, the compound of the invention is of low toxicity to plants and fish, thus having safe and useful characteristics as an agricultural pesticide.
The compound [I] and its salts and compositions 2(1 containing the same are particularly effective in the control of the following kinds of pests: pests of the order Hemiptera ouch as Eurydcma rugos~zm, Scotinophara lurida, Riptortu;s clavatus, Stephanitis nashi, Laodelphax stiatollus, Nilawarvata lu ens, Nephotettix cincticeps, Unaspis yanonens.is, AEhis glycines, Lipaphis erysimi, Brevicoryne brassicae, Aphis gossypii, Sogattela furcifera, Nezara viridula, Trialeurodes vaporariorum, Myzus persicae, Pseudococcus comstocki, Aphis romi, Nezara spp.~Cimex lectularius, Psylla spp., etc.; pests of the order Lepidoptera such as Spodoptera litura, Plutella xy:Lostella, Pieris ra ae crucivora, Chilo suppressalis, Plusia nigrisigna, Halicoverpa assulta, Leucania separata, Mamestra brassicae, Adoxophyes oran~a, Notarcha derogata, Cnaphalocrocis J.0 medinalis, Phth~~rimaea operculella, etc.; pests of the order Cleoptera such as Epilachna viqintioctopunctata, Aulacophora fem~~ralis, Phyllotreta striotata, Oulema oryzae, Echinocnemus sguameus, etc.; pests of the order Diptera such as Musca domestics, Culex pipiens pallens, 7.5 Tabanus trigonu;s, Hylemia antiqua, Hylemia platura etc.; pests of 'the order Orthoptera such as Locusts migratoria, Gry:llotalpa africana, etc., cockroaches such as Blattel:la g-ermanica, Periplaneta fuliginosa, etc.; spider mimes such as Tetranychus urticae, c.0 Panonychus citr:i, Tetranychus kanzawai, Tetranychus cinnabarinus , Pansn~tchus ulmi , Aculo s pelekassi , etc . , and nematodes such as Aphelenchoides besseyi and so on.
For application of the compound [I] or salt of the invention as an insectide/miti(acari)cide, it can be formulated into any possible and desired application form for agrochemicals. Thus, by dissolving or dispers-ing one or more species of compound [I] and salt thereof in an appropriate liquid carrier or vehicle or admixing them with or causing them adsorbed on an appropriate solid carrier, an emulsifiable concentrate, oil preparation, wettable powders, dusts, granules, tablets, aerosol, ointment or the like can be manu-factured. If necessary, such compositions may be further supplemented with emulsifiers, suspending agents, spreader-stickers, penetrating agents, wetting agents, thickeners, stabilizers and so on, and any of such preparations can be manufactured by the per se known procedures.
1.5 The concentration of the active ingredient (compound [I] or salt thereof) in such an insecticidal/miti(acari)cidal composition of 'the :invention depends on the intended application. Generally speaking, the proper concentration is about 10 to 90 weight percent for emulsifiable concentrate and wettable powders, about 0.1 to 10 weight percent for oils and dusts and about 1 to ;?0 weight percent for granules, for instance. However, the concentration may be adjusted according to the: intended application. In the case of ~~5 an emulsifiable concentrate or a wettable powder, it is diluted with wat=er or the like to a suitable concentration (for example, 100 to 100,000-fold dilution) before spraying.
The liquid carrier (solvent) includes, among others, water, alcohols (e. g. methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, ethylene glycol, etc.), ketones (e. g. acetone, methyl ethyl ketone, etc.), ethers (e. g. dioxane, tetrahydrofuran, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether, etc.), aliphatic hydrocarbons (e. g. kerosin, kerosene, 7.p fuel oil, machine o:il, etc.), aromatic hydrocarbons (e. g. benzene, toluene, xylene, solvent naphtha, methylnaphthalene, etc.), halogenated hydrocarbons (e. g. methylene chloride, chloroform, carbon tetra-chloride, etc.), acid amides (e. g. dimethylformamide, 7.5 dimethylacetamide, etc.), esters (e. g. ethyl acetate, butyl acetate, fatty acid glycerin esters, etc.), nitriles (e.g. ~acetonitrile, propionitrile, etc.) and so on. One of 'these solvents or a mixture of two or more of them ca:n be used as the carrier.
a!0 The solid ~~arrier (diluent-volume builder) includes, among others, vegetable powders (e. g. soybean flour, tobacco flour, wheat flour, sawdust, etc.), mineral powders (e. g. clays such as kaolin, bentonite, acid clay, etc., tales such as talc, pyrophillite, etc.
~!5 and silicates such as diatomaceous earth, mica powder, etc.), alumina, sulfur powder, activated carbon and so on. These powders can be used singly or as a mixture.
The ointment base that can be employed include, among others, any or a mixture of polyethylene glycol, pectin, higher fatty acid polyhydric alcohol esters such as monostearic acid glycerin ester etc., cellulose derivatives such as methylcellulose etc., sodium alginate, bentonite, higher alcohols, polyhydric alcohols such as glycerin, vaseline, white petrolatum, liquid paraffin, lard, vegetable oils, lanolin, anhydrous 1.0 lanolin, hydrogenated oils, resins, etc., or mixtures thereof with the any of the following surfactants.
Surfactants which can be optionally used as said emulsifier, spreader/sticker, penetrating agent, dispersing agent, etc. include soaps and nonionic or 1.5 anionic surfactants such as polyoxyethylene alkyl aryl ethers (e. g. Noigen, E.A. 142, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.,JAPAN;
Nonal~, Toho Chemical, JAPAN), alkylsulfates (e. g. Emal 10~, Emal 40~, ~;nanufactured by Kao Corporation, JAPAN), 2 0 alkylsulfonates ( a . g. Neogen° , Neogen ~; manufactured by Daiichi Kogyo Se:iyaku Co., Ltd.; Neopellex~, manufactured by Kao Corporation), polyethylene glycol ethers (e.g. No:nipol 85~, Nonipol 100~, Nonipol 160~, manufactured by Sanyo Chemical Industries, Ltd., JAPAN) and ~5 -s4- 1 34p 99 ~ .
polyhydric alcohol esters (e.g. Tween 20~, Tween 80~, manufactured by Kao Corporation).
The compound of the invention can be used in combination with other insecticides (pyrethroid insecticides, organophosphoru~; insecticides, carbamate insecticides, natural insecticides, etc.), miticides (acaricides), nematocides, herbicides, plant hormones, plant growth regulators, fungicides (copper fungicides, organo-chlorine fungicides, organosulfur fungicides, phenolic li) fungicides, etc.), synergists, attractants, repellents, pigments, fertilizers and so on.
The resulting insecticidel/miticide according to the invention is of low toxicity and safe and is an excellent agrochemical. Z'he insecticidal/miticidal agent of the invention can be used in the same manner as the con-ventional insecticides and miticides and produces effects surpassing those of the latter. For example, the insecticidal/miticidal agent of this invention can be applied for control of pests by such procedures as 20 nursery bed treatment, stem/foliage spray or dusting, direct application to pests, paddy water treatment, soil treatment and so on. The dosage can be selected from a broad range according to the timing, site and method of application. Generally speaking, the preferred 2!i dosage of the active ingredient (compound [I] or a salt 1 340 gg ~
thereof) per hectare is 0.3 g to 3,000 g and, for still better results, 50 g to 1,000 g. Where the in-secticidal/miticidal agent of the invention is provided as a wettable powder, it can be used as diluted so that the final concentration of the active ingredient will be in the range of 0.1 to 1,000 ppm, preferably 10 to 500 ppm.
The compound [:I) of the invention has excellent 7.0 insecticidal/miticidal activity which is well demonstrated by the following test examples.
Test Example 1 Effect against :brown planthoppers (Nilaparvata lugens) An emulsif.iable concentrate of the compound of the J.5 invention, prepared in the same manner as Example 112 below, was diluted with water to a concentration of 500 ppm and sprayed over the stems and leaves of rice seedlings in th~a 2-:Leaf stage at the rate of 10 ml per paper pot. Water was put in test tubes and the treated ~!0 rice seedlings were placed therein. Then, 10 brown planthopper larvae were released in each tube, which was then capped with an aluminum cap. The test tubes were maintained in an incubator at 25°C and the dead insects were counted 7 days after release. The ~'.5 mortality was calculated using the following formula.

56 934099 ) Number of dead insects Mortality (o) - x 100 Number of insects released The results are shown in Table 1.
Table 1 Effect against brown planthoppers Compound of the invention o Mortality after (Compound No.) 7 days l.07 100 7.528 100 :?041 100 :?552 100 1 34p gg ~ , Compound of the invention % Mortality after (Compound No.) 7 days) g5 100 109 ~00 t340 gg 1 Compound of the invention ~ Mortality after (Compound No.) ~ ~laYs 113 loo mixture ( 7 : 3 ) o ~= 114 and 115 10 0 116 loo 11.7 loo 11.8 100 mixture (90:10) of 7_19 and 120 100 mixture (40:60) of 7_19 and 120 100 mixture (70:30) of 7_23 and 124 100 12.5 100 12.8 100 It is apparent :From Table 1 that the compound [I]
of the invention has excellent pesticidal activity against brown pl~~nthoppers.
The following reference and working examples are further illustrative of the invention but should by no means be construed a,s limiting the scope of the invention.
In the procedures of column chromatography described in the reference and working examples, elution was carried out under monitoring by thin layer chromatography (TLC). For TLC observation, Merck Kieselgel 60 F254 (Art. 5715) was used as the TLC plate, the column chromatographic eluent as the developing solvent, and the W detector as the means of detection. As the silica gel for column packing, Merck Kieselgel 60 (70-230 mesh, Art. '7734) was used. The NMR data represent 1H-NMR spectra determined using tetra-methylsilane as either an internal or an external standard and, unless otherwise indicated, a Varian EM390 (90 MHz) spectrometer. The NMR data carrying the indication of 400 MHz were generated using a JEOL
GX-400 (400 MHz) spectrometer. All the b data are in ppm. Where a solvent mixture was used as the developer or eluent, the ratio of respective solvents is given in parentheses.
The abbreviations used in the reference and working examples have the following meanings.
Me: methyl; nPr: n-propyl, iPr: isopropyl, Et:
ethyl, Ac: acetyl, s: singlet, br: broad, d: doublet, t: triplet, q: ~~uartet, m: multiplet, dd: doublet doublet, tt: tr.iplet triplet, dt: doublet triplet, td:
triplet doublet, ddd: doublet doublet doublet, S+S: two singlets, J: coupling constant, Hz: hertz, CDCR,3:
chloroform-d, D20: deuterium oxide, DMSO-d6:
dimethyl-d6'sulfoxide, ~: weight ~,m.p. . melting point.

~340991 .
F:eference Example 1 N-Methyl-N-3-pyridylmethylamine To 25 ml of a 20$ aqueous solution of NaOH stirred under cooling with ice-water, a 40°s aqueous solution of methylamine (1?~.6 g, 0.175 mole) was added dropwise over 5 minutes, followed by further dropwise addition of an aqueous scolut.ion (10 ml) of 8.2 g (0.05 mole) of 3-pyridylmethyl. chloride hydrochloride over 10 minutes.
The mixture wa:c further stirred at room temperature for 2 hours and, then, extracted with CH2C12 (100 ml x 3). The extract was dried aver MgS04 and distilled to remove the solvent. The residue was subjected to vacuum distillation to give 2.6 g of the title compound as a yellow oil.
b.p.. 66°C:/2 mmHg NMR (CDC1_!) &: 1.48 (s, NH), 2.45 (s, NMe), 3.76 ( s , C:H 2N ) FCeference Example 2 N-(6-Chloi-o-3-~pyridylmethyl)phthalimide In 20 ml of Et:OH, 9.4 g (6.4 x 10 2 mole) of phthalimide anct 4 . f. g of KOH were stirred for 30 minutes, followed by addition of 100 ml of DMF
(dimethylformamide) and 5.2 g (2.5 x 10 2 mole) of 6-chloro-3-pyridylmethyl chloride. The mixture was stirred at 60°C: for 1 hour. The EtOH and DMF were distilled off under reduced pressure and the residue was chromatogra.phed on a silica gel column and eluted with CH2C12. 'Ihe above procedure gave 6.7 g of the title compound as colorless needles.
m.p.. 142-143°C
NMR (CDC13) s: 4.85 (s, 2 H), 7.28 (d, J=8.9 Hz, 1 H), 7.6-8.0 (m, 5 H), 8.51 (d, J=2.8 Hz, 1 H) Reference Example 3 6-Chloro-3-pyridylmethylamine 7.0 Hydrazine hydrate (1.7 ml) was added to a refluxing solution of 6.5 g (2.4 x 10 2 mole) of N-(6-chloro-3-pyridylmethyl)phthalimide in 100 ml of EtOH, and the mixture was further refluxed for 1 hour. After addition of 20 ml of water, the ethanol was distilled off under reduced pressure.
7.5 Concentrated hydrochloric acid (25 ml) was added to the residue and the mixture was refluxed for 1 hour. After cooling, the reaction mixture was neutralized with NaOH
and the aqueous layer was saturated with NaCl and extracted with Et20. The extract was dried over Na2S04 ~!0 and the solvent was distilled off to give 2.4 g of the title compound as a yellow oil.
NMR (CDC13) 8: 1.4-2.0 (br, 2 H), 3.89 (s, 2 H), 7.27 (d, ,1=8.9 Hz, 1 H), 7.67 (dd, J=8.9 &
2.7 Hz, 1 H), 8.32 (d, J=2.7 Hz, 1 H) a! 5 1 34p gg 1 Reference Example 4 1-Methylthio-1-piperidino-2-nitroethylene In 20 ml of EtOH was dissolved 1.7 g (0.01 mole) of 1,1-bis(methylthio)-2-nitroethylene under heating and 0.9 g (0.01 mole) of piperidine dissolved in 10 ml of EtOH was added d:ropwise in 3 portions at 30-minutes intervals under reflux. After 2 hours of reflux, the solvent was distilled off and the residue was chroma-tographed on a silica gel column and eluted with AcOEt-toluene (2:3). The above procedure yielded 0.8 g of the title compound as yellow prisms.
m.p.: 65-67°C
NMR (CDC13) b: 2.45 (s), 6.6.8 (s) IR (Nujol): 1650, 1530, 1380 cm 1 Reference Example 5 1,1-bis(Methylthio)-2-nitroethylene was reacted with various amines in the same manner as Reference Example 4 to give the following compounds.
(1) 1-Methylamino-1-methylthio-2-nitroethylene (yellow ~;0 scales ) m.p.: 111-112°C
NMR (CDC13) b: 2.45 (s), 3.15 (d), 6.62 (s), 10.5 11, r c 1 IR (Nujol): 3200, 1575, 1345 cm 1 (2) 1-(2,2-Dim~~thy:L-1-hydrazino)-1-methylthio-2-nitro-ethylene (pale yellow prisms) m.p.: 139-140°C

NMR (CDC13) b: 2.26 (s), 2.65 (s), 6.40 (s), 10.46 (br s) IR (Nujol): 3130, 1535, 1340 cm 1 Reference Example 6 N-(6-Chloro-3-pyridylmethyl)-N-methylamine (1) In 30 ml of toluene, 0.8 g (5.7 x 10 3 moles) of 6-chloropyridine-3-aldehyde and 10 g of Na2S04 were mixed and while the mixtures was stirred, a 40% aqueous solution of methylamine (1.4 g, 1.1 x 10 2 mole) was added dropwise over 30 minutes, followed by addition of g of MgS04. The mixture was allowed to stand at room temperature overnight, after which it was filtered.
:L5 The filtrate was concentrated to give 0.6 g (yield 68%) of N-(6-chloro-3-py:ridylmethylidene)methylamine as crystals.
NMR (CDC13) &: 3.52 (d, 3 H), 7.35 (d, J=8.8 Hz, 1 H), 8.04 (dd, J=8.8 & 2.7 Hz, 1 H), :'-0 8.2-8.4 (m, 1 H), 8.59 (d, J=2.7 Hz, 1 H) (2) In 10 ml of MeOH was dissolved 0.6 g (3.8 x 10 3 moles) of the N-(6-chloro-3-pyridylmethylidene)methyl-amine obtained in (:L) and under stirring at 0°C, 0.07 g (1.9 x 10 3 mole) of sodium borohydride was added in :'5 small portions. After 30 minutes, MeOH was distilled off and the residue was diluted with 5 ml of water and extracted with ~~cOEt. (10 ml x 3). The extract was dried over MgSO~~ and concentrated to give 0.43 g (yield 710) of the title compound as a yellow oil.
NMR (CDC13) S: 1.90 (s, 1 H), 2.44 (s, 3 H), 3.74 (s, 2 H), 7.28 (d, J=8.2 Hz, 1 H). 7.67 (dd, J=8.2 & 2.8 Hz, 1 H), 8.31 (d,J=2.8 Hz, 1 H) Reference Example 7 Pyridine-3--aldehyde or quinoline-3-aldehyde was reacted with various; amines or 1,1-dimethylhydrazine in the same manner as Reference Example 6 (1) to give the following compounds.
(1) N-(3-PyridS~lmethylidene)ethylamine (pale yellow oil) ivluti (CDC13,) 8 . 1.30 (t) , 3.66 (q) , ts.31 (s) (2) N-(3-Pyrid~~lmethylidene)-2-dimethoxyethylamine (yellow oi:1) NMR (CDC13) &: 3.43 (s), 3.83 (d), 4.71 (t), 8.35 (s) (3) N-(3-Pyrid~,~lmethylidene)-2-methoxyethylamine (pale yellow oil) NMR (CDC13) b: 3.39 (s), 3.76 (m), 8.36 (s) (4) N-(3-Quino:lylme~thylidene)methylamine (yellow oil) NMR (CDC13) &: 3.53 & 3.54 (each s, =NMe), 7.1-8.5 (m, 61a, quinoline-H6), 9.28 & 9.30 (each s, CH=N) 134p gg 1 IR (neat): 1690, 1645, 1615, 1490, 785, 750 cm 1 (5) 1,1-Dimethyl-2-(3-pyridylmethylidene)hydrazine (colorless oil) b.p.: 110°C/2 mmHg NMR (CDC13) b: 3.00 (s, NMe2), 7.15 (s, CH=N) IR (neat): 1580, 1550, 1465, 1415, 1040, 710 cm 1 (6) N-(3-Pyridylmethylidene)-n-propylamine (pale yellow oil) NMR (CDC13) 8: 0.95 (t), 1.75 (m), 3.62 (t), 7.33 (dd), 8.12 (dt), 8.31 (s, CH=N), 8.62 (dd), 8.86 (d) (7) N-(3-Pyridylmethylidene)-n-butylami:ne (pale yellow oil) NMR (CDC13) s: 0.94 (t), 1.20-1.90 (m), 3.65 (t), 7.33 (dd), 8.12 (dt), 8.31 (s, CH=N), 8.62 (dd), 8.86 (d) (8) N-(3-Pyridylmethylidene)benzylamine (pale yellow oil) NMR (CDC13) &: 4.84 (s, CH2), 7.33 (s, C6H5), 7.33 (dd), 8.15 (dt), 8.40 (br s, CH=N), 8.65 (dd), 8.88 (d) Reference Example 8 The compounds of Reference Example 7 (1)-(4) and (6)-(8) were respectively reacted in the same manner as Reference Example 6 (2) to give the following compounds.

(1) N-Ethyl-N-(3-pyridylmethyl)amine (pale yellow oil) b.p.. 60°C%0.7 mmHg NMR (CDC13) &: 1.13 (t), 1.45 (br s), 3.70 (q), 3.82 (s) (2) N-(2-Dimethoxyethyl)-N-(3-pyridylmethyl)amine (yellow oil.) NMR (CDC13) b: 1.73 (br s), 2.75 (d), 3.36 (s), 3.82 (br s), 4.46 (t) (3) N-(2-Methox:yethyl)-N-(3-pyridylmethyl)amine (colorless oil) b.p.: 90°C/0.7 mmHg NMR (CDC13) b: 1.86 (br s), 2.82 (t), 3.36 (s), 3.53 (t), 3.83 (s) (4) N-Methyl-N-(3-quinolylmethyl)amine (yellow oil) NMR (CDC13) &: 2.24 (s, NMe), 3.09 (br, NH), 3.86 (s, NCH2), 7.3-8.2 (m, 5 H, quinoline-H5), 8.83 (d, J=2 Hz, 1 H, quinoline-H1) (5) N-(n-Propyl)-N-(3-pyridylmethyl)amine (yellow oil) b.p.. 85°C/1.5 mmHg NMR (CDC13) 6: 0.90 (t), 1.30-1.76 (m), 1.64 (br s, NH), 2.60 (t), 3.80 (s), 7.23 (dd), 7.67 (dt), 8.43-8.63 (m) (6) N-(n-Butyl)-N-(3-pyridylmethyl)amine (pale yellow oil) b.p.. 83°C/1 mmHg NMR (CDC13) 6: 0.78-1.06 (m), 1.1-1.75 (m), 1.45 (br s, NH), 2.63 (t), 3.80 (s), 7.24 (dd), 7.69 (dt), 8.46-9.63 (m, 2 H) (7) N-Benzyl-N-(3-pyridylmethyl)amine (colorless oil) b.p.: 125°C/0.5 mmHg NMR (CDC13) &: 1..83 (br s, NH), 3.77 (s, 4 H), 7.26 (dd), 7.32 (br s, C6H5), 7.66 (dt), 8.43-8.60 (m, 2 H) Reference Example 9 1,1-Dimethyl-2-(3-pyridylmethyl)hydrazine In 100 ml of d:ry ethyl ether was suspended 4.6 g of lithium aluminum hydride and with stirring in a nitrogen gas stream, a solution of 12.0 g of 1,1-dimethyl-2-(3-pyridylmethylidene)hydrazine in 50 ml of dry ethyl ether was added dropwise. The mixture was refluxed for 5 'hours and, then, cooled (5°C) and with stirring, 5 ml of water, 5 ml of 20o aqueous sodium hydroxide and 15 ml of water were added dropwise in succession. The insoluble matter was filtered off, the filtrate was concentrated, and the residue was purified by silica gel c~alumn chromatography (eluent: chloroform-ethanol=10:1). The resulting oil was distilled under reduced pressure to give 2.5 g of the title compound as a yellow oil.
b.p: 100-115°C,~1 mmHg NMR (CDC13) &: 2.47 (s, NMe2), 2.81 (br s, NH), a34ogg~
3.93 (s, CH2N) Reference Exam le 10 2,6-Dichloro-3-pyridylmethylamine (1) In 40 ml of DMF was suspended 3.9 g (0.021 mole) of potassium phthalimide followed by addition of 3.9 g (0.02 mole) of 2,6-dichloro-3-pyridylmethyl chloride and the mixture was stirred at 60-70°C for 2 hours.
The DMF was distilled off under reduced pressure and the residue was diluted with 50 ml of water and extracted with CHC13 (50 ml x 3). The extract was dried over MgS04 and concentrated and the resulting precipitate was collected by filtration, washed with ether and dried to give 3.8 g of N-2,6-dichloro-3-pyridylmethyl)phthalimide as white prisms.
m.p.: 189-190°C
NMR (CDC13) t5: 4.95 (s, 2 H), 7.22 (d, J=8.5 Hz), 7.6':~ (d, J=8.5 Hz), 7.66-8.0 (m, 4 H) (2) In a mixture of 50 ml EtOH and 20 ml DMF was dissolved 3.1 g (0.01 mole) of N-(2,6-dichloro-3-pyridyl-methyl)phthal:imide under heating, followed by addition of 0.75 g (0.015 mole) of H2NNH2~H20 under reflux. After 1 hour of ref:Luxing, EtOH and DMF were distilled off.
To the residue: wei:e added 10 ml of concentrated hydro-chloric acid and 5 ml of water, and the mixture was refluxed for :30 minutes. The resulting crystals were filtered off and the filtrate was neutralized with NaHC03 and a:~trac:ted with CH2C12 ( 30 ml x 3 ) . The extract was dried over MgS04 and the solvent was distilled ofj= to give 1.45 g of the title compound as a yellow oil.
NMR (CD(;13) 8: 1.55 (s, 2H), 3.96 (s, 2H), 7.27 (d,. J=8.5 Hz), 7.82 (d, J=8.5 Hz) Reference Example 11 N-(2,6-I)ichl.oro-3-pyridylmethyl)-N-methylamine In 50 m7. of acetonitrile was dissolved 7.8 g (0.1 mole) of 40% aqueous methylamine and with stirring and ice-cooling, a s~~lution of 3.9 g (0.02 mole) of 2,6-dichloro-3-p~~ridylmethyl chloride in 10 ml of aceto-nitrile was added dropwis~ over 5 minutes. After completion of: the dropwise addition, the mixture was stirred at room t.emperautre for 2 hours and, then, concentrated. The residue was extracted with ether (30 ml x 3 ) and dried over MgS04. Finally, the solvent was distilled. off to give 3.2 g of the title compound as a pale yellow oil.
NMR ECDC'.13) b: 1.46 (s, NH), 2.46 (s, 3 H), 3.82 (s, 2 H), 7.26 (d, J=8.5 Hz), 7.75 (d, J=8.5 Hz) Reference Example 12 1-[N-(2,6-Dichloro-3-pyridylmethyl)-N-methyl]amino-_,o_ 134099 ~
1-methylthio-2-nitroethylene The reaction according to Reference Example 4 was repeated except that N-(2,6-dichloro-3-pyridylmethyl)-N-methylamine was used in lieu of piperidine. The procedure gave the title compound as yellow prisms.
m.p.: 111-112°C
NMR (CDC13) s: 2.46 (s, 3 H), 3.12 (s, 3 H), 4.84 (s, 2 H), 6.79 (s, 1 H), 7.35 (d, J=8.5 Hz), 7.66 (d, ~J=8.5 Hz) Reference Example 13 1,1-bis(Methylthio)-2-nitroethylene was reacted ,. with various amines in the same manner as Reference Example 4 to give the following compounds.
(1) 1-Dimethylamino-1-methylthio-2-nitroethylene (yellow oil) NMR (CDC13) ~: 2.46 (s, 3 H), 3.21 (s, 6 H), 6.69 (s, 1 H) (2) 1-(N-Ethyl-N-methyl)amino-1-methylthio-2-nitro-ethylene (:yellow oil) NMR (CDC13) &: 1.27 (t, J=6.5 Hz, 3 H), 2.48 (s, 3 H), 3.13 (s, 3 H), 3. 64 (q, J=6.5 Hz, 2 H), 6.73 Qs, 1 H) (3) 1-(4-Chlorobenzyl)amino-1-methylthio-2-nitro-ethylene (pale yellow crystals) m.p. . 121-:L23 °(:

-'l 1 340 99 ~
NMR (CDC13) &: 2.43 (s, Me), 4.60 (d, J=6 Hz, CH2), 6.59 (s, =CHN02), 7.23 & 7.36 (each d, J=9 Hz, each 2 H, benzene-H4), 10.71 (br, NH) Reference Exam le 14 N-Methyl-N-[2-(3-pyridyl)ethyl]amine (1) In 100 ml of CHC13 was dissolved 6.39 g (0.052 mole) of 2-(3-pyr:idyl)ethanol followed by dropwise addition of 15.6 ml of thionyl chloride with stirring at room temperature. Then, the mixture was stirred for 1.5 hours, after which the solvent was distilled off.
After addition of ether, crystals were recovered by filtration and dried. The procedure gave 9.13 g of 2-(3-pyridyl)ethy:L chloride hydrochloride as white crystals.
m.p.. 15'7-158°C
NMR (DMSO-d6)8: 3.33 (t, J=7 Hz, CH2C1), 4.02 (t, J=7 Hz, CH2-pyridine), 8.10 (dd, J=6 & 8 Hz), 8.6~~ (m) , 8.90 (d, J=6 Hz), 9.00 (d, J=2 Hz), 11.!i (br) (2) To 32.6 <~ of 40o aqueous methylamine solution was added 7.48 g ;0.062 mole) of 2-(3-pyridyl)ethyl chloride hydrochloride in small portions with stirring. The mixture was transfered to a stainless steel reaction column and heated at an external temperature of 80°C
for 4 hours. After cooling, 3.36 g of NaOH was added with ice-cooling and stirring and the mixture was saturated with sodium chloride and extracted with CH2C12. The extract was dried over MgSO4 and the CH2C12 was distilled off to give 6.32 g of the title compound in crude form as a yellow oil.
NMR (CDC13) S: 1.58 (s, NH), 2.44 (s, NMe), 2.82 (m, CH2CH2), 7.21 (dd, J=5 & 8 Hz, 1 H), 7.55 (m, 1 H), 8.47 (m, 2 H) :Reference Example 15 Pyridine-4-aldehyde and pyridine-2-aldehyde were respectively reacted with methylamine in the same manner as Reference EXample'6 (1) to give the following compounds.
(1) N-(4-Pyridylmethylidene)methylamine (yellow oil) NMR (CDC13) ~5: 3.52 (d, J=2 Hz, MeN), 7.53 (m, 2 H, :pyridyl-H2), 8.20 (m, CH=N), 8.65 (m, 2 H, pyr idyl-H2 ) IR (neat): 1645, 1590, 1410, 995, 810 cm 1 (2) N-(2-Pyr.idylrnethylidene)methylamine (yellow oil) NMR (CDC13) t5: 3.54 (d, J=2 Hz, MeN), 7.30 (m, 1 H, ~ayridine-H1), 7.71 (m, 1 H, pyridine-H1), 7.9'7 (m,, 1H, pyridine-H1), 8.40 (m, CH=N), 8.3:1 (d,, J=5 Hz, 1 H, pyridine-H1) IR (neat): 1Ei50, 1585, 1645, 1430, 990, 770 cm 1 Reference Example 16 The compounds of Reference Example 15 (1) and (2) were respecti~~ely reacted in the same manner as Refer-ence Example 6 (2) to give the following compounds.
(1) N-Methyl-N-(4-pyridylmethyl)amine (yellow brown oil) NMR (CDC13) b: 1.86 (br s, NH), 2.44 (s, Me), 3.76 (s, CH2), 7.30 (m, 2 H, pyridine-H2), 8.53 (m, 2 H, pyridine-H2) IR Eneat): 3260, 1600, 1440, 1410, 790 cm 1 :l0 (2) N-Methyl-N-(2-pyridylmethyl)amine (orange-colored oil) NMR (CDC13) b: 2.48 (s, Me), 3.87 (s, CH2), 7.0-7.4 (m, 2 H, pyridine-H2), 7.64 (t, J=8 Hz, 1 H, pyridine-H1), 8.56 (d, J=4 Hz, ~-5 pyridine-H1 ) IR (neat): 1590, 1570, 1470, 1430, 755 cm 1 Reference Example 17 N-(6-Chloro-3-pyridylmethyl)-N-ethylamine Using 6-chloro~-3-pyridylmethyl chloride and 700 ~'.0 aqueous ethylamine ;solution, the reaction according to Reference Example 1:L was carried out to give the title compound as a brown oil.
NMR (CDC13) b: 1.11 (t, J=7 Hz, CH2CH3), 1.43 (s, NH), 2.68 (q, J=7 Hz, CH2CH3), 3.79 (s, CH2-pyrid:ine), 7.28 (d, J=8 Hz, 1 H), 7.71 (dd, J=2 & 8 Hz, 1 H), $.33 (d, J=2 Hz, 1 H) IR (neat): 1595, 1565, 1460 (sh), 1450, 1380, 1100 cm Reference Example 18 O-Methyl-N-(3-pyridylmethyl)hydroxylamine In 200 ml of acetonitrile was suspended 6.6 g (0.04 mole) of 3-pyridylmethyl chloride hydrochloride, followed by addition of 10 g (0.12 mole) of O-methyl-hydroxylamine hydrochloride and 16.2 g (0.16 mole) of 1.0 triethylamine. The mixture was stirred at 50°C for 15 hours. The insoluble matter was filtered off and the filtrate was concentrated. The residue was subjected to silica gel column chromatography, using EtOH-CHC13 (1:10) as an eluent. The procedure gave 1.0 g of the 1.5 title compound as a yellow oil.
NMR (CDC12) &: 3.47 (s, 3 H), 4.05 (s, 2 H), 5.73 (br, ~TH), 7.27 (dd, J=8 & 5 Hz, 1 H), 7.73 (dt, J=8 ~ 2 Hz, 1 H), 8.50-8.70 (m, 2 H) IR (neat): 3200, 1580, 1425, 710 cm 1 Reference Example 19 (2-Methoxy)ethyl isothiocyanate In 70 ml o:f water was dissolved 4.6 g (0.11 mole) of NaOH. Then, 6.4 ml (0.11 mole) of carbon disulfide was added with 'vigorous stirring and 8.0 g (0.11 mole) of 2-methoxyethvylam_Lne was added gradually in droplets.

The mixture was stirred at 70°C for 2 hours, after which 8.2 ml (0.11 :mole) of methyl chloroformate was added dropwise at room temperature. The mixture was stirred at 50°C for 1 hour. The oil separated from the aqueous layer was extracted with ether and dried over MgS04. The ether was distilled off and the residue was distilled under reduced pressure to give 7.6 g of the title compound as a colorless oil.
b.p: 77-8D°C/22 mmHg 7.0 NMR (CDC13) b: 3.41 (s, 3 H), 3.4-3.8 (m, 4 H) IR (neat): 2080, 1720, 1340 cm 1 Reference Example 20 6-Chloro-3-pyr:idylmethyl chloride and 6-chloro-3-pyridylmethyl chloride hydrochloride J.5 (1) In 70 ml of MeOH was suspended 12.0 g (0.086 mole) of 6-hydroxynic~otinic acid followed by addition of 4 ml of concentrated H2S04. The mixtrue was refluxed for 10 hours. After c~~oling, MeOH was distilled off and the residue was adjusted to pH about 8 with a saturated 2.0 aqueous solution of sodium hydrogen carbonate . The precipitate was collected i~y filtration, rinsed (twice) with water and dried to give 10.5 g of methyl 6-hydroxynicotinate as pale yellow ~~rystals. This product was in the pyridone structvure .
25 NMR (DMSO-d6) t5: 3.77 (s, 3 H), 6.38 (d, J=10 Hz, 1 H), 7.8a (dd, J=10 & 3 Hz, 1 H), s.a5 (d, J=3 Hz, 1 H), 11 (br) (2) In 100 ml of acetonitrile was dissolved 4.0 g (0.026 mole) of methyl 6-hydroxynicotinate followed by addition of 0.9 ml of triethylamine. The mixture was refluxed and 3.7 ml of phosphorus oxychloride was added dropwise with stirring over a period of 15 minutes.
The mixture was further ref luxed for 3 hours. After cooling, the acetonitrile was distilled off and the 7.0 residue was diluted with 20 ml of water and adjusted to pH about 8 with a saturated aqueous solution of sodium hydrogen carbonate. The resulting crystals are collected by filtration, rinsed with water and dried to give 3.6 g of methyl 6-chloronicotinate as pale yellow needles.
7.5 m.p.. 87-88°C
MNR (CDC13) 8: 3.97 (s, 3 H), 7.44 (d, J=8 Hz, 1 H), 8.27 (dd, J=8 & 2 Hz, 1 H). 9.02 (d, J=2 Hz, 1 H) IR (Nujol): 17:15, 1585, 1440, 1290, 1280, 1125 cm-1 (3) To a mixture of 3.0 g (0.0175 mole) of methyl 6-chloronicotinate, 2.0 g of sodium borohydride and 60 ml of THF on reflu:x, 8.0 ml of MeOH was added with stirr-ing over a peri~~d of 1 hour . After completion of the ~'S dropwise additi~~n, the mixture was further refltixed for 30 minutes and when cold, the solvent was distilled off. The residue was diluted with 30 ml of water, saturated with NaCl and extracted with CH2C12 (20 ml x 3). The CH2C12 layer was dried over MgS04 and the CH2C12 was distilled off to give 2.3 g of 6-chloro-3-pyridylmethanol as a yellow oil. When left standing at room temperature, this product was thoroughly crystal-lined.
NMR (CDC13) b: 2.89 (br, 1 H), 4.69 (s, 2H), 7.28 J.0 (d, J=9 Hz, 1 H), 7.69 (dd, J=9 & 3 Hz, 1 H), 8.28 (d, ,7=3 Hz, 1 H) (4) In 500 ml of CHC13 was dissolved 47.3 g (0.33 mole) of 6-chloro-3~-pyridylmethanol followed by drop-wise addition of 99.3 ml of thionyl chloride with J.5 stirring at room temperature. After completion of the dropwise addition, the mixture was further stirred for 1.5 hours and, then, allowed to stand overnight. The CHC13 was distilled off under reduced pressure, whereby crystals and oil were obtained as a residue. The a!0 residue was diluted with ether, collected by filtration and dried to give 4!i.2 g of 6-chloro-3-pyridylmethyl c:hlor:ide hydrochloride as white crystals.
NMR (DMSO-d6) ~5: 4.82 (s, 2 H), 7.51 (d, J=8 Hz, 1 H), 7.97 (dd, J=8 & 2 Hz, 1 H), 8.50 (d, J=2 a!5 Hz, 1 H) _78_ The mother liquor remaining after separation of the above crop of crystals was concentrated and the insoluble residue was dissolved in EtOH, diluted with toluene and concentrated. The above procedure was carried out for a total of 3 times to recover 9.04 g of crude 6-chloro-3-py:ridylmethyl chloride as an oil.
(5) In 50 ml of water was suspended 15.0 g (0.076 mole) of 6-chloro-3-pyridylmethyl chloride hydrochloride and the suspension was adjusted to pH about 8 with a '.0 saturated aqueous solution of sodium hydrogen carbonate.
The resulting mixture was extracted with ether (100 ml x 3) and dried over MgS04. The ether was then distilled off under reduced pressure to give a crystalline residue. After addition of hexane, the crystals were _.5 recovered by filtration, washed with hexane and dried to give 11.0 g ~~f 6~-chloro-3-pyridylmethyl chloride as white prisms.
m.p.: 39-4~a°C
NMR (CDC13) b: 4.56 (s, 2 H), 7.35 (d, J=8 Hz, 1 :'-0 H), 7.73 (dd, J=8 & 2 Hz, 1 H), 8.40 (d, J=2 Hz, 1 H) IR (Nujol): 1585, 1445, 1280, 1135, 1105, 820, 740 cm Reference Example 21 %5 N-Methyl-N~-(2-pyrazinyl)methylamine (1) In 300 ml of CC14 was dissolved 9.4 g (0.1 mole) 1 340 gg 1 _ of 2-methylpyrazine followed by addition of 13.4 g of N-chlorosuccinirnide and 0.5 g of benzoyl peroxide. The mixture was ref:Luxec~ for 24 hours. After cooling, the insoluble matter was filtered off and the filtrate was concentrated to givE: 11.0 g of 2-chloromethylpyrazine as oil.
NMR (CDC13;1 &: 4.73 (s, 2 H), 8.36-8.70 (m, 2 H), 8. 80 i; s, 1. H) (2) The reaction according to Reference Example 11 was ~.0 carried out using 2-chloromethylpyrazine in lieu of 2,6-dichloro-3-pyridylmethyl chloride to give the title compound as oil"
NMR (CDCl3;i S: 2.50 (s, 3 H), 2.63 (br, 1 H), 3.93 (s, 2 H), 8.45-8.60 (m, 2 H), 8.63 (s, 1 H) J.5 Reference Example 22 1-[N-(6-Chloro-:f-pyridylmethyl)-N-n-propyl]amino-1-methylthio-2-nit:roet:hylene (1) In 15 ml of. acetonitrile was dissolved 6.05 g (0.0373 mole) of: 6-chloro-3-pyridylmethyl chloride, and under cooling with i.ce-water and stirring, the solution was added dropwi.se t:o a solution of 10.97 g of n-propylamine in 50 ml. of acetonitrile. After completion of the dropwise addition, the mixture was stirred at ~'S room temperature' for 1 hour and at an external tempera-ture of 50°C fo:r an additional 1 hour. The acetonitrile was distilled o:ff and the residue was diluted with aqueous sodium hydrogen carbonate solution and extracted with CH2C12 (100 ml x 3). The extract was dried over MgS04 and distilled to remove CH2C12, whereby 6.94 g of N-(6-chloro-3-pyridylmethyl)-N-n-propylamine was obtained as a yE~llow-brown oil.
NMR (CDC13) 8: 0.90 (t, J=7 Hz, CH2CH3), 1.32 (s, NH), :L.52 (sextet, J=7 Hz, CH2CH3), 2.59 (t, 1~~ J=7 Hz, NCH2CH2), 3.79 (s, CH2-pyridine), 7.29 ~(d, ~r=8 Hz, 1 H), ?.71 (dd, J=8 & 2 Hz, 1 H) , 8. 35 .Zd, J=2 Hz, 1 H) (2) In 100 ml of EtOH was dissolved 4.47 g of 1,1-bis(methylthio)~-2-nitroethylene under heating at the 1'~ reflux temperature. Then, with stirring and refluxing, a solution of 3..50 cr (0.0190 mole) of N-(6-chloro-3-pyridylmethyl)-Zd-n-propylamine in 15 ml of EtOH was added dropwise and the mixture was further refluxed for 12.5 hours. The' reaction mixture was allowed to stand 20 at room temperat=ure overnight and the resulting crystals were filtered off. The filtrate was concentrated an~i they residue was subjected to silica gel (250 g) column chromatography using EtOH-CHC13 (1:20) as an eluent. The procedure gave 2.98 g of the 2'~ title compound ~~s a yellow viscous oil.

NMR (CDC13) b: 0.90 (t, J=7 Hz, CH2CH3), 1.68 (sextE~t, J=7 Hz, CH2CH3), 2.46 (s, MeS), 3.42 (t, J==7 Hz, NCH2CH2), 4.70 (s, CH2-pyridine), 6.80 I;s, =ClHN02), 7.36 (d, J=8 Hz, 1 H), 7.61 (dd, ~T=8 & 2 Hz, 1 H), 8.29 (d, J=2 Hz, 1 H) Reference Example 23 1-[N-(6-Ch7_oro-3-pyridylmethyl)-N-i-propyl]amino-1-methylthio-2-nitroethylene The reactions according to (1) and (2) of 1.0 Reference Example 22 were carried out using i-propylamine in 1_ieu of n-propylamine to give the following compounds ai:. the respective steps.
(1) N-(6-Chlorc>-3-pyridylmethyl)-N-i-propylamine (oil) NMR (CDC13) s: 1..07 (d, J=6 Hz, Me2CH), 1.21 (br s, NH), 2.84 (septet, J=6 Hz, CHMe2), 3.77 (s, CH~~), 7.28 (d, J=8 Hz, 1 H), 7.71 (dd, J'=8 & .? Hz, 1 H), 8.35 (d, J=2 Hz, 1 H) (2) Title compound (miscous oil) NMR (CDC13) b: 1..35 (d, J=7 Hz, CHMe2), 2.38 (s, MeS), 4.64 (s, CH2), 6.57 (s, =CHN02) Reference Example 24 2-Chloro-5-methyl_aminopyridine To 5.0 g (0.039 mole) of 5-amino-2-chloropyridine was added 40 ml of ethyl orthoformate and the mixture was refluxed for 5 hours. The reaction mixture was _82_ 1340991 _ concentrated under reduced pressure and the residue was dissolved in 50 ml of EtOH. After addition of 1.8 g of sodium borohydride, t:he mixture was stirred at 70-80°C
for 3 hours. The reaction mixture was concentrated and after addition of 50 ml of iced water and 5 ml of concentrated hydrochloric acid, the mixture was adjusted to pH 7-8 with NaHC03 and extracted with AcOEt ( 50 ml x 3 ) . The AcO~Et layers were pooled, washed with water and dried over IKgS04. The AcOEt was distilled off and _~.0 hexane was added to the crystalline residue. The crystals are collected by filtration, washed with hexane and dried to give 5.1 g of the'title compound as white crystals.
m.p.. 70°C
7.5 NMR (CDC13) 8: 2.85 (br d, J=4.5 Hz, 3 H), 3.3-4.3 (m, 1 H), 6.87 (dd, J=8.0 & 3.0 Hz, 1 H), 7.11 (d, J=8.7 Hz, 1 H), 7.78 (d, J=3.3 Hz, 1 H) Reference Example 25 20 N-(2,6-DimE~thyl-4-pyridylmethyl)-N-methyla.mine (1) In 77 ml oi: CHC13 was dissolved 7.00 g (0.0511 mole) of (2,6-dimethyl-4-pyridyl)methanol and with stirring at roorn temperature, 15.3 ml of thionyl chloride was added dropwise. After completion of the 25 dropwise addition, the mixture was stirred for 3 hours _s3_ 1 3 40 9 9 1 and concentrated. The residue was diluted with aqueous sodium hydrogen carbonate solution and extracted with AcOEt (100 ml x 3). The extract was dried over MgS04 and distilled to remove AcOEt. The procedure gave 6.37 g of (2,6-dimethyl-4-~pyridyl)methyl chloride as oil.
NMR (CDC13) S: 2..53 (s, Me x 2), 4.45 (s, CH2), 6.98 (s, pyridine-H2) (2) The reaction according to Reference Example 11 was carried out using (2,6-dimethyl-4-pyridyl)methyl 7.0 chloride in lieu of 2,6-dichloro-3-pyridylmethyl chloride to give the title compound as oil.
NMR (CDC13) . 2.44 (s, NMe), 2.50 (s, pyridine-Me x 2), 3.68 (s, CH2), 6.94 (s, pyridine-H2) Reference Example 26 7.5 N-(2-Chloro-3-pyridylmethyl)-N-methylamine (1) To 10.24g(0.065 mole) of 2-chloronicotinic acid were added 20 m:l of 1,2-dichloroethane and 9.5 ml of thionyl chloride and the mixture was refluxed for 1 hour. The reaction mixture was concentrated to give a!0 11.9 g of 2-chloronicotinyl chloride as an orange-colored oil. WlZen left standing at room temperature, this product so:Lidified thoroughly.
NMR (CDC13) 8: 7.54 (dd, J=8 & 5 Hz, 1 H), 8.48 (dd, ;1=8 & 1 Hz, 1 H), 8.65 (dd, J=5 & 1 Hz, 25 1 H) (2) In 100 ml of cold water was dissolved 8.98 g of sodium borohydride and with ice-cooling and stirring, 11.7 g (0.0665 mole) of 2-chloronicotinyl chloride was added in small portions. The mixture was further stirred at the same temperature for 30 minutes and, then, extracted with Et20 (100 ml x 3). The extract was dried over ;MgS04 and distilled to remove Et20. The procedure gave 8.75 g of (2-chloro-3-pyridyl)methanol as a pale yellow oil. When left standing at room temperature, this product solidified thoroughly.
NMR (CDC13) &: 4.53 (br, OH), 4.77 (s, CH2), 7.30 (m, 1 H), 7.97 (m, 1 H), 8.25 (m, 1 H) (3) The reaction according to Reference Example 25 (1) was carried out using (2-chloro-3-pyridyl)methanol in lieu of (2,6-dimethyl-4-pyridyl)methanol to give (2-chloro-3-pyridy:l)methyl chloride as a yellow oil.
NMR (CDC13) 8: 4.71 (s, CH2), 7.31 (dd, J=8 & 5 Hz, 1 H), 7.88 (dd, J=8 & 2 Hz, 1 H), 8.33 ~( dd, J=5 & 2 Hz , 1 H ) c.0 (4) The reaction according to Reference Example 11 was carried out using (2-chloro-3-pyridyl)methyl chloride in lieu of 2,6-<iichloro-3-pyridylmethyl chloride to give the title c:ompou:nd as a yellow oil.
NMR (CDC13) b: 1.95 (s, NH), 2.47 (s, Me), 3.84 ~5 (s, CH2), 7.26 (dd, J=8 & 5 Hz, 1 H), 7.80 _g5- 1 3 40 99 1 (dd, J=8 & 2 Hz, 1 H), 8.30 (dd, J=5 & 2 Hz, 1 H) Ref e~rence Example 27 2-P4erhyl-5-methylaminopyridine oxalate To 5.0 g (0.04 mole) of 5-amino-2-methylpyridine was added 40 ml of ethyl orthoformate and the mixture was refluxed for 1 hour. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in 50 ml of EtOH, followed by addition of 2.1 g of sodium borohydri.de. The mixture was refluxed with stirring for 2.5 hour's. The reaction mixture was concentrated and 50 ml of ice-water and 8 ml of concent-rated hydrochloric acid were added to the residue. The mixture was adjusted to pH 7 with~NaHCO.~ and extracted ~~aith AcOEt (50 :ml, 30 ml x 2). The AcOEt layers were combined, washed with. aqueous sodium chloride solution and dried over :MgSOq. The AcOEt was distilled off and the residue was diluted with Et~O and the insoluble matter was filtered off. To the filtrate was added a solution of oxalic acid in EtOH (ca. l00) and the L. O
resulting crystals were collected by filtration, washed with EtOH and dried. The procedure gave 4.3 g of the title compound .as pale yellow crystals.
rr~.p.: 118.5-119.5°C
~FMR (DMSO-d~) 8: 2.43 (3 H, s), 2.73 (3 H, s), 2: 5 7.1-7.5 (2 H, m), 7.8-8.0 (1 H, m), 8.2-9.0 (n) -$6- 1 3 4 0 9 9 1 RefE:rence Example 28 1~1-(5-Bromo-3-pyridylmethyl)-N-methylamine The steps (1), (2), (3) and (4) of Reference Example 26 were repeated except that 5-bromonicotinic acid was used in lieu of 2-chloronicotinic acid to obtain the following compounds in the respective steps.
(1) 5-Bromonicotinyl. chloride (white crystals) N14IR (CDC13) 8: 8..54 (m, 1 H), 8.99 (d, J=1 Hz, 1 N), 9.25 (d., J=1 Hz, 1 H) (2i (5-Bromo-3-pyrid.yl)methanol (crude orange-colored oil) NMR (CDC13) &: 4.39 (br s, OH), 4.73 (s, CH2), 7.90 (m, 1 H), 8.47 (d, J=1 Hz, 1 H), 8.55 ;d, J=2 Hz, 1 H) (3) (5-Bromo-3-pyridyl)methyl chloride (crude oil) rTMR (CDC13) b: 4.57 (s, CH2), 7.92 (m, 1 H), 8.56 (d, J=1 Hz, 1 H), 8.65 (d, J=1 Hz, 1 H) ;4) Title compound (crude oil) NMR (~2DC13) b: 2.44 (s, Me), 3.76 (s, CH2), 7.89 (m, 1 H), 8.48 (d, J=1 Hz, 1 H), 8.57 (d, J~=1 Hz, 1 H) Reference Example 29 N-(2-Methy:lthio-3-pyridylmethyl)-N-methylamine The steps (1), (2), (3) and (4) of Reference Example 26 were repeated except that 2-methylthionico-_87_ tinic acid was used in lieu of 2-chloronicotinic acid to obtain the following compounds in the respective steps.
(1) 2-Methylthioni.cotinyl chloride (white - pale yellow crystals) NMR (CDC13) &: 2.56 (s, MeS), 7.17 (dd, J=5 & 8 Hz, 1 H), 8.52 (dd, J=8 & 2 Hz, 1 H), 8.67 (dd, J=5 & 2 Hz, 1 H) (2) (2-Methylthio-3-pyridyl)methanol (pale yellow oil, crystallized thoroughly on standing) 2dMR (CDC13) b: 2.56 (s, MeS), 3.46 (br s, OH), 4.62 (s, CH2), 6.99 (dd, J=5 & 8 Hz, 1 H), 7.62 (dd, J=8 & 1 Hz, 1 H), 8.33 (dd, J=5 & 8 H2, 1 H) (3) (2-Methylthio-3-pyridyl)methyl chloride (pale :fellow oil) NMR (CDC13) 8: 2.61 (s, MeS), 4.60 (s, CH2), 6.9'a (dd, J=5 & 8 Hz, 1 H), 7.58 (dd, J=8 & 2 Hz, 1 H), 8.43 (dd, J=5 & 2 Hz, 1 H) (4) Title compound (yellow oil) NMR (CDC'13) 6: 1.50 (s, NH), 2.44 (s, MeN), 2.57 (s, MeS), 3.73 (s, CH2), 6.97 (dd, J=5 & 8 Hz, 1 H), 7.51 (dd, J=8 & 1 Hz, 1 H), 8.37 (dd, J=5 & 1 Hz, 1 H) Reference Example 30 _g$_ 1340991 N-Methyl-N-(4-~thiazolyl)methylamine (') The .reaction procedure of Reference Example 21 (1) was repeated except. that 4-methylthiazole was used in lieu of 2-methylpyrazine to give crude 4-chloromethyl-t.hiazole as oil.
L~1MR (CDC13) 8: 4.72 (s, CH2C1), 7.37 (m, 1 H), 8.78 (d, J=2 Hz, 1 H) 2) T~!~e reaction procedure of Reference Example 11 was repeated except that crude 4-chloromethylthiazole was used in lieu of 2,6-dichloro-3-pyridylmethyl chloride and the reaction wa.s conducted at room temperature for 1 luour and further at 50 °C for 2 hours . The. procedure gave the title compound as a crude oil.
NMR (CDC13) 6: 2.43 (s, MeN), 3.89 (s, CH2), 7.1'7 (m, 1 H), 8.74 (d, J=2 Hz, 1 H) Reference Example 31 2-Chloro-5-ethylaminopyridine .A nixture of 10 g (0.078 mole) of 5-amino-2-chloro-~~yridine and 50 ml of ethyl orthoacetate was refluxed for 2 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ~~0 ml of dry '.fHF. Then, the solution was added dropwise to a suspension of 7.0 g of lithium '~orohydride in 100 ;ml of dry THF over a period of 15 minutes with constant stirring. After completion of 134Q99 1~
dropwise addition, the mixture was refluxed with stirring for 27 hours. After cooling, the solvent was distilled off . To tree residue were added 100 ml of ice-water and 35 ml c>f concentrated hydrochloric acid and the mixture was heated at 67°C for a while. After cooling, the reaction mixture was adjusted to pH 7 with NaHC03 and extracted with AcOEt (50 ml x 3). The AcOEt layers were combined, washed with aqueous sodium chloride solution and, dried over MgS04. The AcOEt was distilled off and the: residual crystals were collected by filtration, washed. with hexane and dried. The procedure gave 9.2 g of the title compound as pale yellowish green crystals. .
m.p.. 65-66°C
NMR (CDC13) s: 1.25 (3 H, t, J=7.4 Hz), 2.9-3.4 (2 H, m), 3.4-4.1 (1 H, m, NH), 6.86 (1 H, dd, J=9.0 & 3.0 Hz), 7.09 (1 H, d, J=7.8 Hz), 7.77 (1 H, d, J=2.7 Hz) Reference Example 32 2-Chloro-5-n-propylaminopyridine (1) To 6.4 g (0.05 mole) of 5-amino-2-chloropyridine was added 25 g of triethyl orthopropionate and the mixture was refluxed for 3 hours. Then, at an external temperature of '70°C, the reaction mixture was concent-rated under reduced pressure using a vacuum pump. The procedure gave 10.5 g of N-(6-chloro-3-pyridyl)-O-ethylpropionimidate as a yellow oil.
NMR (CDC1.,) 8: 1.07 (t, J=8 Hz, 3 H), 1.33 (t, J=7 Hz, 3 H), 2.16 (q, J=8 Hz, 2 H), 4.22 (q, J=7 Hz, 2 H), 7.06 (dd, J=8 & 3 Hz, 1 H), 7.25 (d, J=8 Hz, 1 H), 7.87 (d, J=3 Hz, 1 H) (2) To a 70o solution of sodium dihydro-bis(2-methoxy-ethoxy)aluminat~~ in toluene was added 100 ml of toluene and a solution of 8.5 g (0.04 mole) of N-(6-chloro-3-pyridyl)-O-ethylpropionimidate in 20 ml of toluene was added dropwise over 5 minutes with stirring at room temperature. T'.he mixture was further stirred at room temperature for 1 hour and at 50°C for 2 hours, after which 50 ml of water was added dropwise over 5 minutes under ice-cooling. The mixture was stirred at 50°C for 15 minutes. The toluene layer was separated, dried over MgSO4 and concentrated and the residue was ,subjected to silica gel column chromatography using hexane-acetone (2:1) as the eluent. The procedure gave 2'.0 5.9 g of the title compound as a yellow oil.
NMR (CDC13) b: 0.99 (t, J=7 Hz, 3 H), 1.65 (m, 2 H), 3.07 (dt, J=7 & 6 Hz, 2 H), 3.83 (br, 1 H), 6.86 (dd, J=8 & 3 Hz, 1 H), 7.10 (d, J=8 Hz, 1 H), 7.77 (d, J=3 Hz, 1 H) 2;5 Reference Example 33 2-Chloro-5-n-but.ylaminopyridine The steps (1) and (2) of Reference Example 32 were repeated except that trimethyl orthobutyrate was used in lieu of triethyl orthopropionate to obtain the :Following compounds i.n the respective steps.
(1) N-(6-Chloro-3-pyridyl)-O-methyl butyrimidate (yellow oil) NIA (CDC13) S: 0.85 (t, J=7 Hz, 3 H), 1.33-1.80 (m, 2 H), 2.16 (t, J=7 Hz, 2 H), 3.80 (s, 3 1.0 ~-i) , 7. 06 (d.d, J=8 & 3 Hz, 1 H) , 7. 27 (d, J=8 Hz, 1 H), 7.88 (d, J=3 Hz, 1 H) (2) Title. compound (yellow crystals) m.p.: 46-48°C
NtrIR (CDC13) &: 0.93 (t, J=7 Hz, 3 H), 1.16-1.83 1.5 (m, 4 H), 3.08 (dt, J=7 & 6 Hz, 2 H), 3.78 (br, 1 H), 6.84 (dd, J=8 & 3 Hz, 1 H), 7.08 (d, J'=8 Hz, 1 H), 7.75 (d, J=3 Hz, 1 H) &.eference Example 34 3-Methylamino-5-trifluoromethylpyridine The reaction procedure of Reference Example 24 was repeated except that 3-amino-5-trifluoromethylpyridine Yaas used in lieu of 5-amino-2-chloropyridine to obtain the title compound as white crystals.
m.p.: 69-70°C
~5 NMR (CDC3): 2.89 (3 H, d, J=5.1 Hz), 3.8-4.5 (1 H, _92_ 1340991 m, NH), 6.9~-7.1 (1 H, m), 8.1-8.3 (2 H, m) Reference Example 35 N-Methyl-N-(6-methyl-3-pyridylmethyl)amine (1) The reaction procedure of Reference Example 20 (3) was repeated except that methyl 6-methylnicotinate was used in lieu of methyl 6-chloronicotinate to give crude 6-methyl-3-pyridylmet.hanol as a yellow oil.
:~VMR (CDC13) &: 2.49 (s, Me), 4.66 (s, CH2), 4.93 (br, C~H), 7.14 (d, J=8 Hz, 1 H), 7.63 7.0 (dd, J=8 & 2 Hz, 1 H), 8.36 (d, J=2 Hz, 1 H) (2) The reaction procedure of Reference Example 25 (1) was repeated except that crude 6-methyl-3-pyridyl-methanol was used in lieu of (2,6-dimethyl-4-pyridyl)-methanol to give crude (6-methyl-3-pyridyl)methyl l.5 chloride as oil.
tJMR (CDClz) b: 2.54 (s, Me), 4.55 (s, CH2), 7.16 (d, J=8 Hz, 1 H), 7.62 (dd, J=8 & 2 Hz, 1 H), 8.49 (dd, J=2 Hz, 1 H) (3) A mixture of 16.6 g of 40% aqueous MeNH2 solution ~'.0 and 52 ml of CH3CN wa.s cooled with ice and 6.08 g (0.043 mole in terms of pure: product) of crude (6-methyl-3-pyridyl)-methyl chloride was added dropwise with constant stirring. After comF~letion of dropwise addition, the mixture was stirred a.t room temperature for 1.5 hours, :'-5 at the end of which time the solvent was distilled off.

- 1 340 99 ~
The solid residue wa~~ extracted with CH2C12 and the CH?C12 layer was dried over MgS04. The CH2C12 was distilled off and the: residue was diluted with 70 ml of Et20 and filtered to remove the insoluble matter.
Finally the filtrate was concentrated to recover 4.60 g of the title compound. as a crude oil.
NMR (CDC13) b: 2.43 (s, MeN), 2.53 (s, pyridine-Me), 3.71 (s, CH:2), 7.13 (d, J=8 Hz, 1 H), 7.57 (dd, J=8 & 2 Hz, 1 H), 8.40 (d, J=2 Hz, 1 H) Reference Example 36 N-(6-Fluoro-3-pyridylmethyl)-N-methylamine (1) A mixture of 7.2 g (0.0648 mole) of 2-fluoro-5-methylpyridine, 12.0 g of N-bromosuccinimide, 0.5 g of benzoyl peroxide and 200 ml of CC14 was refluxed for 2 ~zours. After cooling, the precipitate was filtered off and the filtrate was washed with water and dried.
Finally, the CC14 was distilled off to recover 12.68 g of crude (6-fluoro-3-pyridyl)methyl bromide as a pale yellow oil.
NMR (CDC13) b: 4.47 (2 H, s, CH2), 6.96 (1 H, dd, J=8.4 & 2.7 Hz), 7.86 (1 H, ddd, J=8.4, 2.4 &
8.4 Hz), 8.29 (1 H, d, J=2.4 Hz) (2) To a mixture of 2.5 g of 40o aqueous methylamine solution and 30 ml of CH3CN was added dropwise 3.0 g of crude (6-fluoro-3-pyridyl)methyl bromide with constant - ~1 340 99 1 stirring. The mixture was allowed to stand at room temperature overnight: and concentrated under reduced pressure. The residue was extracted with AcOEt and the extract was dried over MgS04 and concentrated. The procedure gave 1.35 g~ of the title compound as a crude orange-colored oil.
NMR (CDC13) 6: 2.53 (3 H, s, Me), 3.94 (2 H, s, CH2) 5.40 (1 H, s, NH) Reference Example 37 J.0 N-(6-Bromo-3-pyridylmethyl)-N-methylamine (1) The reaction procedure of Reference Example 36 (1) was repeated except that 2-bromo-5-methylpyridine was used in lieu of 2-flu.oro-5-methylpyridine to recover crude (6-bromo-3-pyridyl)methyl bromide as a yellow 7.5 oil.
NMR (CDC13) &: 4.42 (2 H, s), 7.48 (1 H, d, J=8.4 Hz), 7.61 (1 H, dd, J=8.4 & 2.7 Hz), 8.40 (1 H, d, J=2.7 Hz) (2) To a mixture of 12.3 g of 40% aqueous methylamine ~!0 solution and 40 ml of CH3CN was added 8.0 g of crude (6-bromo-3-pyridyl)methyl bromide with stirring. The :.nixture was further stirred at room temperature for 30 minutes. The reaction mixture thus obtained was concentrated and the residue was diluted with toluene a!5 and subjected to azeotropic distillation to remove the water. Then, the soluble fraction was extracted with Et~O. The Et20 layer was dried over MgS04 and concent-rated to recover 4.4 g of the title compound as a yellow oil.
NMR (CDC13) s: 2..48 (3 H, s), 2.73 (1 H, s), 3.80 (2 H, s), T.45 (1 H, d, J=8.4 Hz), 7.63 (1 H, dd, J=8.4 &. 2.7 Hz), 8.36 (1 H, d, J=2.7 Hz) Reference Example 38 N-(6-Bromo-3-pyridylmethyl)-N-ethylamine 1.0 The reaction procedure of Reference Example 37 (2) Haas repeated except that 70% aqueous ethylamine solution was used in lieu of 40o aqueous methylamine solution to recover the title compound as a crude oil.
NMR (CDC1.~) s: 1.11 (3 H, t, J=8.1 Hz), 2.16 (1 H, 1.5 br s), 2.68 (2 H, q, J=8.1 Hz), 3.78 (2 H, ;s), 7.45 (1 H, d, J=8.4 Hz), 7.58 (1 H, dd, =8.4 & 2.7 Hz), 8.33 (1 H, d, J=2.7 Hz) Reference Example 39 N-(2-Chloro-5-thiazolylmethyl)-N-methylamine The reaction procedure of Reference Example 11 was repeated except that crude 2-chloro-5-chloromethyl-thiazole was used in lieu of 2,6-dichloro-3-pyridyl-methyl chloride and that CH2C12 was used as the extract-ant. The procedure gave the title compound as a crude a5 oil.

- 1 34p 99 ~
NMR (CDC13) 8: 2.45 (s, MeN), 3.89 (s, CH2), 7.37 (s, thiazol.e-H) Reference Example 40 N-(2-Chloro-5-thiazolylmethyl)-N-ethylamine The reaction procedure of Reference Example 17 was repeated except that crude 2-chloro-5-chloromethylthia-zole was used in lieu of 6-chloro-3-pyridylmethyl chloride and that CH~,C12 was used as the extractant.
The procedure gave the title compound as a crude oil.
NMR (CDC1.3) S: 1..10 (t, J=7 Hz, CH2CH3), 2.69 (q, J=7 Hz, CH2,,CH3), 3.93 (s, CH2N), 7.36 (s, thiazole-H) Referencd Example 41 2-Chloro-5-thiazolylmethylamine (1) The reaction procedure of Reference Example 10 (1) was repeated except that crude 2-chloro-5-chloromethyl-thiazole was used in lieu of 2,6-dichloro-3-pyridyl-methyl chloride to give N-(2-chloro-5-thiazolylmethyl)-phthalimide as pale yellow crystals.
m.p.: 108-109°C
tJMR (CDC13) &: 4.97 (2 H, s), 7.60 (1 H, s), 7.6-8.1 (m, 4 H) (2) The reaction procedure of Reference Example 3 was repeated except that N-(2-chloro-5-thiazolylmethyl)-c.5 ~ohthalimide was used in lieu of N-(6-chloro-3-pyridyl-X3'4499 ~
methyl)phthalimide to give the title compound as a yellow oil.
NMR (CDC1,3) b: 1.68 (2 H, br s), 4.04 (2 H, s), 7.38 (1 H, s) Reference Example 42 2-Methoxy-5-methylaminopyridine The reaction procedure of Reference Example 24 was :repeated except that 5-amino-2-methoxypyridine was used in lieu of 5-amino-2-chloropyridine to give the title compound as a yellow oil.
NMR (CDC13) 8: 2.81 (3 H, s), 3.1-3.8 (1 H, m), 3.87 (3 H, s), 6.64 (1 H, d, J=9.0 Hz), 6.98 (1 H, dd, J=8.7 & 3.2 Hz), 7.59 (1 H, d, J=2.4 Hz) -97a- 1 3 4 g g p 1 Reference Example 43 6-Bromo-3-pyridylmethylamine (1) The reaction procedure of Reference Example 10 (1) was repeated except that crude 6-bromo-3-pyridylmethyl bromide was used in lieu of 2,6-dichloro-3-pyridylmethyl chloride, to give N-(6-bromo-3-pyridylmethyl)phthalimide as white crystals.
m.p.. 130-131°C
NMR (CDC13)d: 4.;83(s,2H), 7.44 (d,J=8Hz,lH), 7.6-8.0 (m,SH), 8.49 (d,J=:2Hz,lH) (2) The reaction procedure of Reference Example 3 was repeated except that N-(6-bromo-3-pyridylmethyl)phthalimide was used in lieu of N-(6-chloro-3-pyridylmethyl)phthalimide, to give the title compound as pale yellow crystals.
m.p.. 57-58°C
NMR (CDC13)8: 1.46 (br s,2H), 3.86 (s,2H), 7.42 (d, J=8Hz,lH), 7.58 (dd,J=8&2Hz,lH), 8.32 (d,J=2Hz,133) Reference Example 44 N-(6-Chloro-3-pyridylmethyl)-N-(2,2,2-trifluoroethyl)amine In 15 ml of water was dissolved 12.55 g of 2,2,2-trifluoroethylamine hydrochloride, followed by addition of 68 ml of CH3CN, .and further 9.35 g of Et3N and then 3.00 g (0.0185 mole) of 6-chloro-3-pyridylmethyl chloride under cooling with ice-water and stirring. The mixture was stirred at room temperature for one hour, at 50°C for one hour and at 70°C for 90 hours. The CH3CN was distilled off, and the residue was foll~~wed by addition of NaHC03 and then extracted with CH2C12 (100 ml x 3). The extract was dried over MgS04 -97b-and distilled to remove CH2C12. To the residue was added 100 ml of Et20 and the resulting unsoluble matter was filtered off. The filtrate was concentrated to give 3.85 g of the title compound as yellow oil.
NMR (CDC13)d: 1.81 (br,NH), 3.21 (q,J=9Hz,CF3CH2), 3.92 (s, pyridine-CH2), 7.30 (d,J=8Hz,lH), 7.71 (dd, J=8&2Hz,lH), 8.32 (d,J=2Hz,lH) Example 1 1-Methyl_thio-:L-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 1-1) and 1,1-bis(3-pyridylmethyl)-amino-2-nitroethylene (Compound 1-2) In 100 ml of F~tOH was dissolved 5.0 g (0.03 mole) of 1,1-bis(methylthio)-2-nitroethylene with heating and, then, a solution of 3.2 g (0.03 mole) of 3-pyridylmethylamine in 30 ml of EtOH was added dropwise in 3 installments at intervals of 20-30 minutes while refluxing. The mixture was further refluxed for 2 hours and the EtOH was distilled off. The residue was subjected to silica gel column chromatography using CHC13-MeOH (5:1) as an el.uent. The procedure gave 4.0 g and 0.5 g of the title Compound (1-1 and 1-2), respectively, each as a white powder.
Compound 1-1 m.p.. 129-130°C
Compound 1-2 m.p.. 141-143°C
NMR (DM~O-d6) 8: 4.55 (d), 6.52 (s), 10.26 (br s) IR (Nujol*) : .4150, 1575, 1390 cm-1 Example 2 1-Methylthio-1.-(N-methyl.-N-3-pyridylmethyl)amino-2-~ 34~ 99 1 nitroethylene (Compound 2) The procedure of Example 1 was repeated except that N-methyl-N-pyridLylmethylamine was used in lieu of 3-pyridylmethylamine to give the title compound as a pale yellow viscous oil.
NMR (CDC13) b: 2.50 (s), 3.06 (s), 4.81 (s), 6.81 (s) Example 3 1-Methylamino-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 3) In 50 ml of EtOH was dissolved 2.3 g (0.01 mole) of 1-methylthio-1-(3-pyridylmethyl)amino-2-nitroethylene with heating and, then, a solution of 1.2 g (0.015 mole) of 40% aqueous methylamine in 10 ml of EtOH was 7.5 added dropwise over a period of 30 minutes while refluxing. The mixture was further refluxed for 2 hours, after which it was concentrated. The crystals were collected by filtration and recrystallized from acetonitrile to give 1.6 g of the title compound as :! 0 white prisms .
m.p.: 159-160°C
NMR (DMSO-<i6) b: 2.86 (br s), 4.49 (d), 6.46 (s) Example 4 1-Methylth:Lo-1-(3-pyridylmethyl)amino-2-nitro .'S ethylene was reacted with various amines (or ammonium) -ioo- ?34099 ~
in the same manner as. Example 3 and the reaction product was purified by recrystallization or silica gel column chromatography to give the following compounds 4 - 22.
(1) 1-Ethylamino-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 4) m.p.: 161-162°C
(2) 1-iso-propylamin.o-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 5) m.p.: 148-150°C
NMR (CDC13) b: 4.46 (d), 6.52 (s), 7.28 (br s), 10.1 (br s) (3) 1-n-Butyla~nino-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 6) m.p.: 110-.112°C
(4) 1-Allylamino-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 7) m.p.: 114-:115°C
(5) 1-n-Pentyl<amino-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 8) m.p.: 97-98°C
(6) 1-Anilino-:L-(3-pyridylmethyl)amino-2-nitroethylene (Compound 9) m.p.: 217-218°C
2.5 (7) 1-Amino-1-(3-pyridylmethyl)amino-2-nitroethylene - ioL -(Compound 10) m.p.. 177-178°C (decompn.) (8) 1-(2-n-Propylthi.aethyl)amino-1-(3-pyridylmethyl)-amino-2-nitroethylene ECompound 11) (white prisms) m.p.: 93-94°C
NMR (CDC13) 6: 4.48 (d), 6.23 (br s), 6.63 (s), 10.5 (br s) (9) 1-(2-Dimet:hylaminoethyl)amino-1-(3-pyridylmethyl)-amino-2-nitroet:hylene (Compound 12)(white prisms) 7.0 m.p.: 110-111°C
NMR (CDC13) s: 2.02 (s), 4.30 (m), 6.60 (s), 10.3 (br s) (10) 1-(2-Hydroxyethyl)amino-1-(3-pyridylmethyl)amino-2-nitroethylene (Compound 13) 7.5 m.p. 161-163°C

(11) 1-(2-Methoxyethyl)amino-1-(3-pyridylmethyl)amino-2-nitroethylene (Compound 14) m.p.: 108-:L09°C

(12) 1-(2,2-Dimethoxyethyl)amino-1-(3-pyridylmethyl)-20 amino-2-nitroethylene (Compound 15) (white prisms) m.p.: 96-98°C
NMR (CDC13) &: 6.55 (s), 6.85 (br s), 10.3 (br s) (13) 1-(3-Pyri<iylmethyl)amino-1-(2,2,2-trifluoroethyl)-amino-2-nitroethylene (Compound 16) ~5 m.p.. 164-:L65°C

NMR (DMSO-d6) b: 4.09 (m), 6.58 (s) (14) 1-(3-Pyridylmet.hyl)amino-1-(trimethylsilylmethyl)-amino-2-nitroethylene~ (Compound 17) m.p.: 156-157°C
NMR (CDC13) &: 0.10 (s), 2.67 (d), 4.32 (d), 6.37 (s), 7.12 (br s), 10.1 (br s) (15) 1-Hydrazino-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 18) m.p.. 176-177°C (decompn.) 1.0 (16) 1-Dimethylamino-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 19) m.p.: 68-70°C
NMR (CDC13) s: 2.93 (s), 4.48 (d), 6.52 (s), 9.77 (br s) ~.5 (17) 1-(3-Pyridylmethyl)amino-1-pyrrolidino-2-nitro-ethylene (Compound 20) (pale yellow powder) m.p.: 103-:105°C
NMR (CDC13) &: 4.61 (d), 6.63 (s), 10.42 (br s) (18) 1-(4-Methylpiperazino}-1-(3-pyridylmethyl)amino-20 2-nitroethylene (Compound 21) NMR (CDC13) &: 2.32 (s), 2.46 (t), 3.25 (t), 4.53 (d), 6.50 (s), 9.73 (br s) (19) 1-(Morpho:Lino)-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 22) 5 m.p.. 102-:L03°C

-io3- '9340 99 1 Example 5 1-Piperidino-1-(3-pyridylmethyl)amino-2-nitro-ethylene (Compound 23) In 20 ml of EtOH was dissolved 0.8 g (0.004 mole) of 1-methylthio-1-piperidino-2-nitroethylene followed by addition of 0.4 g (0.004 mole) of 3-pyridiylmethyl-amine. The mixture was refluxed for 2 hours. The ethanol was distilled off and the residue was purified by silica gel column chromatography to give 0.3 g of :L0 the title compound as. a pale yellow powder.
m.p.: 106-108°C
Example 6 1-(2,2-Dimethyl-1-hydrazino)-1-(3-pyridylmethyl)-amino-2-nitroethylene (Compound 24) l5 The procedure of Example 5 was repeated using 1-(2,2-dimethyl-1-hydrazino)-1-methylthio-2-nitroethylene to give the title compound as white prisms.
m.p.: 158-159°C
NMR (CDC13) 8: 2.63 (s), 4.36 (d), 6.45 (s), 6.85 20 (br s), 10.36 (br s) Example 7 1-Amino-1-(N-methyl-N-3-pyridylmethyl)amino-2-nitro-ethylene (Compound 25) In 50 ml o:E MeOH was dissolved 7.2 g (0.03 mole) 25 of 1-methylthio-1-(N-methyl-N-3-pyridylmethyl)amino-2--io4- ~~34099'~ _ nitroethylene followed by addition of 10 ml of 25s aqueous ammonia. The mixture was refluxed for 2 hours, after which the solvent was distilled off. The residue was subjected to silica gel column chromatography using CHC13-MeOH (5:1) as an eluent to give 1.5 g of the title compound as white prisms.
m.p.: 158-1'~9°C
NMR (DMSO-d6) b: 3.06 (s), 4.66 (s), 6.63 (s), 8.93 (br s) Example 8 1-Methylam:ino-1-(N-methyl-N-3-pyridylmethyl)amino-2-nitroethylene (Compound 26) (1) In 30 ml o:E toluene was dissolved 2.5 g (0.02 mole) of N-methyl-N-3-pyridylmethylamir~e followed by addition of 1.5 g (0.02 mole) of methyl isothiocyanate and the mixture was stirred at room temperature over-night. Finally, the solvent was distilled off to give 3.8 g of N-methyl-N'-:methyl-N'-3-pyridylmethylthiourea as a yellow viscous oil. This oily product was purified by silica gel column chromatography using HeOH-CHC13 (1:10) as an eluent to give crystals.
m.p. . 86-87°C
NMR (CDC13) 8: 3.06 (s), 3.17 (d), 5.22 (s), 6.16 (br s), 7.28 (dd. J=8 & 5 H2, 1H), 7.74 (m. 1H), c.5 8.54 (m. 2H) (2) In 30 ml of MeOH was dissolved 3.8 g (0.02 mole) of the N-methyl--N'-methyl-N'-3-pyridylmethylthiourea obtained in (1) followed by addition of 2.8 g (0.02 mole) of methyl iodide. The mixture was refluxed for 4 -io5- '1340 99 1 hours. The solvent was distilled off and the residue was diluted with 10 ml of a saturated aqueous solution of sodium hydrogen carbonate and extracted with AcOEt (50 ml x 3). The extract was dried over MgS04 and the solvent was distilled. off to give 1.0 g of crude S-methyl-N-methyl-N'-methyl-N'-(3-pyridylmethyl)iso-thiourea as a yellow oil.
NMR (CDC13) &: 2.33 (s), 2.83 (s), 3.26 (s), 4.56 (s), 7.25(dd, J=8 & 5 Hz, 1H), 7.60(m, 1H), 8.55(m, 2H) 1.0 (3) To 1.0 g (0.048 mole) of the S-methyl-N-methyl-N'-methyl-N'-(3-py:ridylmethyl)isothiourea obtained in (2) was added 5 ml of, nitromethane and the mixture was stirred at 90°C for 15 hours. The nitromethane was distilled off and the residue was subjected to silica gel column chromatography using CHC13-MeOH (5:1) as an eluent to give 0.3 g of the title compound as a yellow viscous oil. Tlzis product was cooled (to 5°C) and the resulting crystals were washed with ethyl acetate and dried. The meli_ing point of this product was 86-87°C.
2:0 NMR (CDC13.) 8: 2.83 (s), 3.07 (d), 4.43 (s), 6.53 (s), 7.35 (dd, J~8 & 5 Hz, 1H), 7.61(m, 1H), 8.60(m, 1H), 9.73 (br s) Example 9 1-(6-Chloro-3-py:ridylmethyl)amino-1-methylthio-2-nitroethylene (Compou;nd 27) To 100 ml of EtOIH were added 2.4 g (1.5 x 10 2 -LO6- 134099'1.
mole) of 1,1-bis(methylthio)-2-nitroethylene and 1.4 g (9.8 x 10 3 mole) of 6-chloro-3-pyridylmethylamine and the mixture was refluxed for 2 hours. The EtOH was distilled off a:nd the residue was subjected to silica gel column chromatography using CH2C12 as an eluent.
The procedure gave 1.2 g of the title compound as a pale yellow solid.
NMR (DMSO-c36) 8: 2.48 (s, 3 H), 4.71 (d, J=6.7 Hz, 2 H), 6.66 (br s, 1 H), 7.50 (d, J=8.8 Hz, 1 H), 7.84 (dd, J=8.8 & 2.8 Hz, 1 H), 8.41 (d, J=2.8 Hz, 1 H), 10.0-11.0 (br, 1 H) Example 10 1-(6-Chloro-3-pyridylmethyl)amino-1-methylamino-2-nitroethylene (Compound 28) In 100 ml of EtO:H was dissolved 1.2 g (4.6 x 10 3 mole) of 1-(6-chloro-3-pyridylmethyl)amino-1-methylthio-2-nii_roeth~ylene and on reflux, a solution of 0.84 g of 40% aqueous methylamine in 30 ml EtOH was added dropwise over 1 hour. After cooling, the ;20 reaction mixturE~ was ~~oncentrated under reduced pressure to about 50 ml and the resulting crystals were collected by filtration and dried to give 0.6 g of the title compound as pale yellow needles.
m.p. : 181-1_83 °C
:?5 NMR (DMSO-d6) s: 2.6-3.1 (m, 3 H), 4.47 (d, J=6.3 1340991_-_ Hz, 2 H), Ei.45 (s, 1 H), 7.48 (d, J=8.8 Hz, 1 H), 7.81 (cLd, J=8.8 & 2.7 Hz), 8.39 (d, J=2.7 Hz, 1H), 9.5-10.4 (br, 1 H) Example 11 1-[N-(6-Chloro-3-pyridylmethyl)-N-methyl]amino-1-methylamino-2-nitroet.hylene (Compound 29) (1) Using N-(6-chloro-3-pyridylmethyl)-N-methylamine, the procedure of Example 8 (1) was repeated to give N-(6-chloro-3-pyridylmethyl)-N-methyl-N'-methylthiourea as crystals.
m.p.: 109-110°C
NMR (CDC13) s: 3.06 (s, 3 H), 3.16 (d, J=4.8 Hz, 3 H), 5.22 (s, 2H), 5.8-6.3 (br, 1 H), 7.30 (d, J=8.6 Hz, 1H), 7.76 (dd, J=8.6 & 2.7 Hz, 1H), 8.30 (d, J=2.7 Hz, 1 H) (2) Using the 1V-(6-chloro-3-pyridylmethyl)-N-methyl-N'-methylthiourea otained in (1), the procedure of Example 8 (2) was repeated to give S-methyl-N-(6-chloro-3-pyridylmethyl)-N-methyl-N'-methylisothiourea as oil.
NMR (CDC13) S: 2.36 (s, 3 H), 2.94 (s, 3 H), 3.27 (s, 3 H), 4.63 (s, 2 H), 7.30 (d, J=8.6 Hz, 1 H), 7.62 (dd, J=$.6 & 2.7 Hz, 1 H), 8.31 (d, J=2.7 Hz, 1 H) (3) Using the :3-methyl-N-(6-chloro-3-pyridylmethyl)-N-methyl-N'-methylisothiourea obtained in (2), the procedure of Example 8 (3) was repeated to give the title compound as crystals.
m.p.: 103-104°C
NMR (CDC13) 8: 2.80 (s, 3 H), 3.07 (d, J=4.8 Hz, 3 H), 4.38 (s, 2 H), 6.51 (s, 1 H), 7.37 (d, J=8.6 Hz, 1 H), 7.58 (dd, J=8.6 & 2.7 Hz, 1H), 8.31 (d, J=2.7 Hz, 1 H), 9.5-9.9 (br, 1 H) 7.0 Example 12 1-Methoxy-1-(3-pyridylmethyl)amino-2-nitroethylene (Compound 30) In one liter of MeOH was dissolved 16.5 g (0.1 mole) of 1,1-bi,s(methylthio)-2-nitroethylene with 7.5 heating and on :reflux, a solution of 11.0 g (0.1 mole) of 3-pyridylmet:hylamine in 200 ml of MeOH was added dropwise in 4 installments at 1-hour intervals. The mixture was further refluxed for 3 hours and the MeOH
was distilled o:Ef. The residue was purified by silica :?0 gel column chromatography to give the title compound as white prisms. :In this procedure, the compound 1-1 described in Example 1 was also produced as a byproduct.
m.p.: 129-130°C
?5 NMR (CDC13) 6: 3.86 (s, OMe), 4.60 (d, CH2N), 6.68 (s, =CHN02), 10.15 (br, NH) -l09- 1340991 ' Example 13 1-[N-Ethyl-N-(3-pyridylmethyl)]amino-1-methylamino-2-nitroethylene (Compound 31) (1) In 50 ml of ethyl ether was dissolved 2.4 g of N-ethyl-N-(3-pyridylmethyl)amine followed by addition of 1.3 g of methyl isothiocyanate. The mixture was stirred at room temperature (25°C) for 1 hour. The resulting precipitate was collected by filtration, washed with a small amount of ethyl ether and dried to give 3.7 g of N-methyl-N'-ethyl-N'-(3-pyridylmethyl)thio-urea as white prisms.
m.p.: 122-:123°C
NMR (CDC13) b: 1.16 (t; CH2CH3), 3.16 (d, MeN), 3.55 (q, CH2CH3), 5.12 (s, ~ ~ CH2N), 5.95 (br s, NH) N
(2) In 30 ml o:E dry tetrahydrofuran was dissolved 3.1 g of the N-methyl-N'-ethyl-N'-(3-pyridylmethyl)thiourea obtained in (1) followed by addition of 0.6 g of 60%
sodium hydride. The :mixture was stirred at room temperature (25°C) for 1 hour. Then, 2.1 g of methyl iodide was added dropwise and the mixture was further stirred for 3 hours. The reaction mixture was concent-rated and the residue was diluted with 50 ml of a saturated solution of sodium chloride and extracted 3 ~'S times with 50 m:1 portions of ethyl acetate. The - mo -extracts were pooled and dried over MgS04. The solvent was then distilled off to give 3.1 g of crude S-methyl-N-methyl-N'-ethyl-N'-(3-pyridylmethyl)isothiourea as a yellow oil.
NMR (CDC13) 6: 1.06 (t, CH2CH3), 2.30 (s, MeS), 3.23 (s, MeN), 3.35 (q, CH2CH3), 4.53 (s, ~~-CH2) (3) To 2.2 g of the S-methyl-N-methyl-N'-ethyl-N'-(3-:~0 pyridylmethyl)isothiourea obtained in (2) was added 10 ml of nitromethane and the mixture was refluxed for 16 hours. The reaction mixture was concentrated and the residue was subjected to silica gel column chromato-graphy using methanol-chloroform (1:5) as an eluent to :l5 give 1.4 g of t:he title compound as a yellow viscous oil.
NMR (CDC13) S: 1.20 (t, CH2C_H3), 3.08 (d, MeN), 3.18 (q, CH2CH3), 4.46 (s,~~-CH2), 6.53 N
20 (s, =CHNO~), 9.86(br s, NH) Example 14 1-[N-(2-Dimethoxyethyl)-N-(3-pyridylmethyl)]amino-1-methylamino-2-nitroethylene (Compound 32) Using N-(2~-dimethoxyethyl)-N-(3-pyridylmethyl)amine 25 in lieu of N-ethyl-N-(3-pyridylmethyl)amine, the steps 134099 1 ' (1), (2) and (3) of Example 13 were carried out to give the following compounds at the respective steps.
(1) N-Methyl-N'-(2-d.imethoxyethyl)-N'-(3-pyridylmethyl)-thiourea (pale yellow viscous oil) NMR (CDC13) b: 3.13 (d, MeN), 3.37 (s, Me0), 3.53 (d, NCH2CH), 4.30 (t, CH2CH), 5.22 (s, CH2), 7.02 (br s, NH) (2) S-Methyl-N-methyl-N'-(2-dimethoxyethyl)-N'-(3-pyri-J_0 dylmethyl)isothiourea (yellow oil) NMR (CDC13) 8: 2.26 (s, MeS), 3.24 (s, MeN), 3.35 (s, Me0), 3.46 (d, CH2CH), 4.48 (t, CH.2CH), 4.69 (s,C~~CH2) N
J.5 (3) Title compound (yellow viscous oil) NMR (CDC13) b: 1.20 (t, CH2CH3), 3.08 (d, MeN), 3.18 (q, CH,2CH3), 4.46 (s, ~ ~CH2), 6.53 ~/N
(s, =~~HN02), 9.86 (br s, NH) :? 0 Example 15 1-Ethylami:no-1-[N-methyl-N-(3-pyridylmethy)]amino-2-nitroethylene (compound 33) The steps (1), (2) and (3) of Example 13 were repeated except that N-methyl-N-(3-pyridylmethyl)amine :?5 and ethyl isothiocyan.ate were used in lieu of N-ethyl-N-(3-pyridylmethyl)amine and methyl isothiocyanate, respec-tively, to give the following compounds in the respective steps.
(1) N-ethyl-N'-methyl-N'-(3-pyridylmethyl)thiourea m.p.:110-111°C
NMR (CDC13) 6:1.23 (3 H, t, J=7.5 Hz), 3.05 (3 H, s), 3.5-3.9 (2 H, m), 5.20 (2 H, s), 5.8-6.2 (1 H, br), 7.26 (1 H, dd, J=8.4 & 5.4 Hz), 7.72 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.6 (2 H, :l 0 m ) IR (Nujol): 3180 cm 1 (2) S-Methyl-N-ethyl-N'-methyl-N'-(3-pyridylmethyl)iso-thiourea (yellow oil) NMR (CDC13) S: 1.16 (3 H, t, J=7.5 Hz), 2.36 (3 H, .l5 s), 2.93 (3 H, s), 3.56 (2 H, q, J=7.5 Hz), 4.64 (2 H, s), 7.26 (1 H, dd, J=8.4 & 5.4 Hz), '7.63 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.6 (2 H, m) (3) Title compound (viscous oil) 20 NMR (CDC13) 8: 1.34 (3 H, t, J=7.5 Hz), 2.82 (3 H, s), 3.1-3.6 (2 H, m), 4.43 (2 H, s), 6.52 (1 H, s), 7.32 (1 H, dd, J=8.4 & 5.4 Hz), 7.58 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.7 (2 H, m), 9.3-9.8 (1 H, br) 25 IR (neat): 3220 cm 1 -m3- 134p991 .
Example 16 1-n-Butylamino-1-[N-methyl-N-(3-pyridylmethyl)]-amino-2-nitroethylene (Compound 34) The steps (1), (2) and (3) of Example 13 were repeated except that N-methyl-N-(3-pyridylmethyl)amine and n-butyl isothiocyanate were used in lieu of N-ethyl-N-(3-pyridylmethyl)amin.e and methyl isothiocyanate, respec-tively, to give the following compounds in the respective steps.
J.0 (1) N-n-Butyl-iH'-methyl-N'-(3-pyridylmethyl)thiourea (pale yellow oil) NMR (CDC13) &: 0.93 (3 H, t, J=7.8 Hz), 1.2-1.9 (4 H, m), 3.06 (3 H, s), 3.4-3.9 (2 H, m), 5.21 (2 H, s), 5.5-6.1 (1 H, br), 7.28 (1 H, dd, 7_5 J=8.4 & 5.4 Hz), 7.74 (1 H, dt, J=8.4 & 1.5 Hz), ;8.4-8.7 (2 H, m) IR (neat): 3270 cm 1 (2) S-Methyl-N-n-butyl-N'-methyl-N'-(3-pyridylmethyl)-isothiourea (ye:llow oil) :'.0 NMR (CDC13) &:0.90 (3 H, t, J=7.8 Hz), 1.1-1.9 (4 H, m), 2.30 (3 H, s), 2.85 (3 H, s), 3.49 (2 H, t, J=6.8 Hz), 4.56 (2 H, s), 7.23 (1 H, dd, J~=8.4 & 5.4 Hz), 7.60 (1 H, dt, J=8.4 &
1. 5 H:~ ) , 8. 4-8. 6 ( 2 H, m) :?5 ( 3 ) Title compound ( viscous oil ) NMR (CDC13) b: 0.94 (3 H, t, J=7.8 Hz), 1.2-1.9 (4 H, m), 2.80 (3 H, s), 3.34 (2 H, m), 4.42 (2 H, s), 6.59: (1 H, s), 7.34 (1 H, dd, J=8.4 &
5.4 Hz), 7.58 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.7 (2 H, m), 9.4-9.9 (1 H, br) IR (neat): 3210 cm 1 Example 17 1-Methylamino-1-[N-(2-methoxyethyl)-N-(3-pyridyl-methyl)]amino-2-nitroethylene (Compound 35) .LO The steps (1), (2) and (3) of Example 13 were repeated except that N-(2-methoxyethyl)-N-(3-pyridyl-methyl)amine was used. in lieu of N-ethyl-N-(3-pyridyl-methyl)amine to give the following compounds in the respective steps.
.l5 (1) N-Methyl-N'-(2-methoxyethyl)-N'-(3-pyridylmethyl)-thiourea (colorless viscous oil) NMR (CDC13) &: 3.33 (s, Me0), 3.50 (m, CH2CH2), 5.20 (s, i~ ~ -CH2N, 7.26 (br s, NH) N-0 (2) S-Methyl-N-methyl-N'-(2-methoxyethyl)-N'-(3-pyridyl-methyl)isothiourea (oil) NMR (CDC13) 2.27 (s, MeS), 3.23 (s, MeN), 3.30 &:

(s, M~~O), 3.52 (m, CH2CH2), 4.66 (s, ~ ~-CH2) N

25 (3) Title compound (yellow viscous oil) - ms - 1 3 4 0 9 9 1 NMR (CDC13) b: 3.06 (d, MeN), 3.35 (s, Me0), 3.43 (m, CH2CH2) , 4.53 (s, ;(' ,-CH2N) , 6.55 (s, JN
=CHN02), 9.10 (br s, NH) Example 18 1-Allylamino-1-[N-methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene (~~ompound 36) The steps (1), (2) and (3) of Example 13 were repeated except that N-methyl-N-(3-pyridylmethyl)amine and allyl isothiocyan.ate were used in lieu of N-ethyl-N-(3-pyridylmethyl)amine a.nd methyl isothiocyanate, respectively, to give the following compounds in the respective steps.
(1) N-Allyl-N'-methyl-N'-(3-pyridylmethyl)thiourea m.p.: 82-84°C
NMR (CDC13) S: 3.07 (3 H, s), 4.34 (2H, m), 5.0-5.4 (2H, m), 5.21 (2H, s), 5.6-6.3 (2 H, m), 7.27 (1 H, dd, J=8.4 & 5.4 Hz), 7.73 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.6 (2 H, m) IR (Nujol): 3280 cm 1 (2) S-Methyl-N-allyl-N'-methyl-N'-(3-pyridylmethyl)iso-thiourea (yellow oil) NMR (CDC13) &: 2.30 (3 H, s), 2.90 (3 H, s), 4.1-4.3 (2 H, m), 4.62 (2 H, s), 4.9-5.3 (2 H, m), 5.7-6.3 (1 H, m), 7.26 (1 H, dd, J=8.4 & 5.4 Hz), 7.62 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.7 (2 H, m) (3) Title compound (oil) NMR (CDC13) b: 2.81 (3 H, s), 3.9-4.2 (2 H, m), 4.43 (2 H, s), 5.1-5.6 (2 H, m), 5.7-6.2 (1 H, m), 6.55 (1 H, s), 7.35 (1 H, dd, J=8.4 &
5.1 Hz), 7.60 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.7 (2 H, m), 9.4-9.9 (1 H, br) Example 19 7.0 1-iso-Propylamino-1-[N-methyl-N-(3-pyridylmethyl)]-amino-2-nitroethylene (Compound 37) The steps (Zr), (2) and (3) of Example 13 were repeated except that N-methyl-N-(3-pyridylmethyl)amine and iso-propyl isothiocyanate were used in lieu of N-ethyl-:L5 N-(3-pyridylmet:hyl)amine and methyl isothiocyanate, respectively, to give the following compounds in the respective steps.
(1) N-iso-Propyl-N'-methyl-N'-(3-pyridylmethyl)thio-urea m.p.. 135-:L36°C
NMR (CDC13) &: 1.26 (6 H, d, J=6.3 Hz), 3.03 (3 H, s), 4.4-4.9 (1 H, m), 5.21 (2 H, s), 5.0-5.5 (1 H, br), 7.27 (1 H, dd, J=8.4 & 5.1 Hz), 7.74 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.7 (2 H, 05 m) IR (Nujol): 3200 cm 1 1340991 ' (2) S-Methyl-N-iso-propyl-N'-methyl-N'-(3-pyridylmethyl)-isothiourea (oil) NMR (CDC13) S: 1..07 (6 H, d, J=6.3 Hz), 2.30 (3 H, s), 2.84 (3 H, s), 3.6-4.1 (1 H, m), 4.50 (2 H, s), 7.23 (1 H, dd, J=8.4 & 5.1 Hz), 7.61 (1 H, dt, J'=8.4 & 1.5 Hz), 8.4-8.6 (2 H, m) (3) Title compound m.p.: 119-121°C
J.0 NMR (CDC13) 6: 1.31 (6 H, d, J=6.6 Hz), 2.83 (3 H, s), 3.5-4.0 (1 H, m), 4.44 (2 H, s), 6.52 (1 H, s), 7.33 (1 H, dd, J=8.4 & 5.1 Hz), 7.57 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.7 (2 H, m), 8.9-9.4 (1 H, br d, J=9.6 Hz) 1-5 IR (Nujol): 3080 cm 1 Example 20 1-Benzylamino-1-[N-methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene (Compound 38) The steps (1), (2) and (3) of Example 13 were repeated except that N-methyl-N-(3-pyridylmethyl)amine and benzyl isotlziocyanate were used in lieu of N-ethyl-N-(3-pyridylmetlzyl)amine and methyl isothiocyanate, respectively, to give the following compounds in the respective steps.
(1) N-Benzyl-N'-methyl-N'-(3-pyridylmethyl)thiourea 1 340 gg ~
(pale yellow oil) NMR (CDC13) 8: 3.03 (3 H, s), 4.90 (2 H, d, J=5.1 Hz), 5.21 (2 H, s), 6.10 (1 H, br), 7.1-7.5 (6 H, m), T.74 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.6 (2 H, m) IR (neat): 3250 cm 1 (2) S-Methyl-N-benzyl-N'-methyl-N'-(3-pyridylmethyl)iso-thiourea (oil) NMR (CDC13) S: 2'..29(3 s), 2.92 H, s), 4.62 H, (3 _~0 (2 H, s), 9:.77(2 s), 7.1-7.5 (6 H, m), H, 7.59 (1 H, dt, J=8.4 & 1.5 Hz), 8.4-8.7(2 H, m) (3) Title compound (oil) NMR (CDC13) 8: 2.78 (3 H, s), 4.36 (2 H, s), 4.53 .l5 (2 H, d, J=~6.0 Hz), 6.56 (1 H, s), 7.1-7.5 (7 H, m), 8.3=8.5 (1 H, m), 8.57 (1 H, dd, J=5.2 & 1.5 Hz), 9.7-10.2 (1 H, br) Example 21 1-Methylamino-1-[N-methyl-N-(3-quinolylmethyl)]-20 amino-2-nitroethylene (Compound 39) The steps (1), (2) and (3) of Example 13 were repeated except that N-methyl-N-(3-quinolylmethyl)amine was used in lieu of N-ethyl-N-(3-pyridylmethyl)amine to give the following compounds in the respective steps.
~5 (1) N-Methyl-N'-methyl-N'-(3-quinolylmethyl)thiourea 1340991 .
m.p.. 138-139°C
NMR (CDC13) b: 3.09 (s, MeNCH2), 3.18 (d, J=5 Hz, MeNH), 5.35 (s, NCH2), 6.00 (br, NIi), 7.4-7.9 (m, 3 H, quinoline-H3), 8.0-8.2 (m, 2 H, quinol.ine-H2), 8.33 (d, J=2 Hz, 1 H, quinoline-H:1 ) IR (Nujol): 3200, 1545, 1530, 1495, 1445, 1375, 1335, 1240, 1050 cm 1' (2) S-Metyl-N-metyl-N'-methyl-N'-(3-quinolylmethyl)iso-thiourea (oil) NMR (CDC13) b: 2.33 (s, MeS), 2.89 (s, MeNCH2), 3.28 (s, MeN=), 4.73 (s, NCH2);: 7.2-7.9 (m, 3 H, quinolin.e-H3), 7.9-8.2 (m, 2 H, quinoline-H2), 8.85 (d, J=2 Hz, 1 H, quinoline-H1) ~.5 IR (neat): 1600, 1490, 1370, 1340, 1060, 1020, 755 cm (3) Title compound m.p.: 145-157°C
NMR (CDC13) 8: 2.85 (s, MeNCH2), 3.08 (d, J=6 Hz, MeNH), 4.58 (s, NCH2), 6.59 (s, =CHN02), 7.5-7.95 (m, 3 H, quinoline-H3), 7.95-8.25 (m, 2 H, quinoline-H2), 8.81 (d, J=2 Hz, 1 H, quinoline-H.1), 9.80 (br, NH) IR (Nujol): 1590, 1545, 1405, 1310, 1280, 1230 cm-1 1 3 4(~ 99 1 ' Example 22 1-Metylamino-1-[N-methyl-N-[1-(3-pyridyl)ethyl]]-amino-2-nitroet'hylene (Compound 40) The steps (1), (2) and (3) of Example 13 were repeated except that N-methyl-N-[1-(3-pyridyl)ethyljamine was used in lieu of N-ethyl-N-(3-pyridylmethyl)amine to give the following compounds in the respective steps.
(1) N-Methyl-N'-methyl-N'-[1-(3-pyridyl)ethyl]thiourea (pale yellow viscous oil) NMR CDC13) &: 1.56 (d, J=7 Hz, MeCH), 2.76 (s, MeNCH2), 3.18 (d, J=5 Hz, MeNH), 6.30 (br, NH), '7.04 (q, J=7 Hz, MeCH), 7.28 (dd, J=7 and 5 Hz, 1 H, pyridine-H1), 7.70 (m, 1 H
pyridine-H1), 8.5 (m, 2 H, pyridine-H2) IR (neat): 3270, 1550 (sh.), 1530, 1480, 1420, 1375, 1340, 1295 cm 1 (2) S-Methyl-N-methyl-N'-methyl-N'-[1-(3-pyridyl)-ethyl]thiourea (oil) NMR (CDCL3) &: 1.54 (d, J=7 Hz, MeCH), 2.31 (s, MeS), 2.63 (s, MeNCH2), 3.27 (s, MeN=), 5.66 (q, J~=7 Hz, MeCH), 7.24 (dd, J=5 & 8 Hz, 1 H, pyridine-H1), 7.62 (m, 1 H, pyridine-H1), 8.48 (dd, J=5 & 2 Hz. 1 H, pyridine-H1), 8.59 (d, J=2 Hz, 1 H, pyridine-H1) ~'.5 IR (neat): 2910, 1600, 1415, 1390, 1370, 1235, 1340991 '~
1070, 1010, 710 cm 1 (3) Title compound (viscous oil) NMR (CDC13) b: 1.70 (d, J=7 Hz, MeCH), 2.63 (S, MeN), 3.02 (d, J=5 Hz, MeNH), 4.93 (q, J=7 Hz, M~eCH), 6.50 (s, =CHN02), 7.33 (dd, J=5 & 8 Hz, 1 H, pyridine-Hl), 7.60 (m, 1 H, pyridine-H1), 8.6 (m, 2 H, pyridine-H2), 9.77 (br, :NH) IR (neat): 1585, 1420, 1400, 1340, 1240, 1020, 750 cm 1 Example 23 1-[2,2-Dime'thyl-1-(3-pyridylmethyl)]hydrazino-1-methylamino-2-nitroethylene (Compound 41) (1) In 30 mI of toluene was dissolved 2.5 g of 1,1-dimethyl-2-(3-pyridylmethyl)hydrazine followed by addition of 1.2 g of methyl isothiocyanate and the mixture was refluxed for 1 hour. The reaction mixture was concentrated and the resulting crystals are collected by filtration, washed with ethyl ether and 2:0 dried. The pro~~edure gave 2.6 g of 1,1-dimethyl-4-methyl-2-(3-pyridylmethyl)thiosemicarbazide as white prisms.
m.p.: 101-102°C
NMR (CDC13) &: 2.45 (s, Me2N), 3.17 (d, J=5 Hz, MeNH), 5.28 (s, CH2N), 7.20 (dd, J=8 and 5 Hz, 1 H, pyridine-H1), 7.89 (m, 1 H, pyridine-Hl.), 8.10 (br, NH), 8.50 (dd, J=5 & 2 Hz, 1 Hf, pyridine-H1), 8.62 (d, J=2 Hz, 1 H, pyridine:-H1 ) IR (Nujol): 3200, 1514, 1420, 1370, 1320, 975 cm 1 (2) 0.52 g of 60o sodium hydride was washed with petroleum ether and suspended in 20 ml of dry tetra-hydrofuran, followed by addition of 2. 9 g of 1,1-di-methyl-4-methyl-2-(3-pyridylmethyl)thiosemicarbazide as :l0 prepared according to (1). The mixture was stirred at 50°C for 2 hours. After cooling and addition of 1.8 g of methyl iodide, the mixture was stirred at room temperature (25°C) for 2 hours and, then., concentrated.
To the residue was added 50 ml of ethyl acetate and the :l5 insoluble matter was filtered off. The filtrate was dried over MgS04 and concentrated to give 2.2 g of S-methyl-1,1-dimethyl-4-methyl-2-(pyridylmethyl)isothi-osemicarbazide as oil.
NMR (CDC13) b: 2.41 (s, MeS), 2.60 (s, Me2N), 3.06 20 (s, MeN), 4.30 (s, CH2N), 7.18 (dd, J=5 & 8 Hz, 1 H, pyridine-H1), 7.60 (m, 1 H, pyridine-H1), 8.10 (dd, J=5 & 2 Hz,.l H, pyridine-H1), 8.21 (d, J=2 Hz, pyridine-H1) IR (neat): 1600, 1420, 1240, 1020, 710 cm 1 25 (3) To 2.2 g o:E S-methyl-1,1-dimethyl-4-methyl-2-134099 1 ' (pyridylmethyl)isothi.osemicarbazide prepared in (2) was added 10 ml of nitromethane and the mixture was refluxed for 7 hours. The reaction mixture was concentrated and subjected to silica gel column chromatography using chloroform-methanol (5:1) as an eluent. The procedure gave 1.0 g of the title compound as yellow prisms.
m.p.: 109-110°C
NMR (CDC13) 8: 2..62 (s, Me2N), 3.16 (d, J=6 Hz, MeN), 4.43 (s, CH2N), 6.43 (s, =CHN02), 7.27 _0 (dd, J=8 & S Hz, 1 H, pyridine-H1), 7.60 (m, 1 H, pyridine-H1), 8.5-8.65 (m, 2 H, pyridine-H2; ) _, 10 .1 ( br , NH ) IR (Nujol): 1585,' 1405, 1340, 1315, 1235 cm 1 Example 24 .~5 1-Methylamino-1-[N-(n-propyl)-N-(3-pyridyl methyl)]a.mino-2-nitroethylene (Compound 42) The steps (1), (2) and (3) of Example 13 were repeated except that N-n-propyl-N-(3-pyridylmethyl)a.mine was used in lieu of N-ethyl-N-(3-pyridylmethyl)amine to ;00 give the following cevmpounds in the respective steps.
(1) N-Methyl-N'-(n-propyl)-N'-(3-pyridylmethyl)thiourea (pale yellow viscous oil) NMR (CDC13) 8: 0.90 (t), 1.4-1.9 (m), 3.16 (d.
MeN), 3.42 (t), 5.15 (s), 5.87 (br s, NH), ~5 7.26 (dd), 7.74 (dt), 8.46-8:60 (m, 2 H) 1340991 .
IR (neat): 3270, 1525, 1340, 1235, 1020, 710 cm 1 (2) S-Methyl-N-:methyl-N'-(n-propyl)-N'-(3-pyridyl-methyl)isothiourea (yellow oil) NMR (CDC13) &: 0.84 (t), 1.33-1.80 (m), 2.29 (s, MeS), 3.23 (s, MeN), 3.26 (t), 4.55 (s), 7.22 (dd), 7.56 (dt), 8.43-8.60 (m, 2 H) IR (neat): 1600, 1425, 1210, 715 cm 1 (3) Title compound (yellow viscous oil) NMR (CDC13) b: 0.86 (t), 1.40-1.90 (m, 2 H), 2.95-3.30 (m, 2 H), 3,05 (d, MeN), 4.53 (s, 2 H), 6.55 (s, =CHN02), 7.34 (dd), 7.66 (dt), 8.43-8.66 (m, 2 H), 9.56 (br d, NH) Example 25~
1-[N-(n-Butyl-N-(3-pyridyl)]amino-1-methylamino-2-nitroethylene (Compound 43) The steps (1), (2) and (3) of Example 13 were repeated except that N-(n-butyl)-N-(3-pyridylmethyl)amine was used in lieu of N-ethyl-N-(3-pyridylmethyl)amine to give the following compounds in the respective steps.
(1) N-(n-Butyl)-N-(3-pyridylmethyl)-N'-methylthiourea (pale yellow viscous oil) NMR (CDC13) 8: 0.90 (t), 1.1-1.8 (m, 4 H), 3.15 (d, MeN), 3.30-3.56 (m), 5.13 (s), 5.82 (br s, NH), 7.25 (dd), 7.73 (dt), 8.43-8.60 (m, 2 ~: 5 H ) - 125 - 1 .3 4 0 9 9 1 IR (neat): 3280, 1525, 1345, 1230, 1030, 710 cm 1 (2) S-Methyl-N-methyl-N'-(n-butyl)-N'-(3-pyridylmethyl-isothiourea (yellow oil) NMR (CDC13) S: 0.86 (t), 1.03-1.70 (m, 4 H), 2.28 (s, MeS), 3.23 (s, MeN), 3.30 (t), 4.54 (s).
7.22 (dd), 7.56 (dt), 8.40-8.56 (m, 2 H) IR (neat): 1605, 1425, 1190, 1020, 715 cm 1 (3) Title compound (viscous oil) NMR (CDC13) 8: 0.90 (t), 1.06-1.80 (m, 4 H), ~.0 2.96-3.23 (m, 2 H), 3.07 (d, MeN), 4.40 (s), 6.56 (s, =CHN02), 7.33 (dd), 7.60 (dt), 8.46-8.66 (m, 2 H), 9.82 (:br d, NH) Example 26 1-[N-Benzyl-N-(3-pyridylmethyl)]amino-1-methyl-amino-2-nitroet:hylene (Compound 44) The steps (1), (2) and (3) of Example 13 were repeated except that N-benzyl-N-(3-pyridylmethyl)amine was used in lieu of N-ethyl-N-(3-pyridylmethyl)amine to give the following compounds in the respective steps.
0 (1) N-Benzyl-N-(3-pyridylmethyl)-N'-methylthiourea m.p.. 141-143°C (white prisms) (2) S-Methyl-N-methyl-N'-benzyl-N'-(3-pyridylmethyl)-isothiourea (yellow oil) NMR (CDC13) 8: 2.32 (s, MeS), 3.26 (s, MeN), 4.45 :?5 (s), .4.52 (s), 7.06-7.36 (m, 6 H), 7.50 (dt), 1~4o9s~
8.36-8.53 (m, 2 H) IR (neat): 1600, 1425, 1180, 1020, 700 cm 1 (3) Title compound m.p.. 118-119°C (pale yellow scales) NMR (CDC13) 8: 3.16 (d, J=5 Hz, MeN), 4.22 (s, CH2 and CH2), 6.53 (s, - CHN02), 7.06-7.60 (m, 7 H), 8.40 (b~r s), 8.60 (br d), 9.76 (br d, J=5 Hz, NH) IR (Nujol): 1590, 1520, 1450, 1360, 1280 cm 1 1.0 Example 27 1-Amino-1-[N-(6-chloro-3-pyridylmethyl}-N-methyl]-amino-2-nitroet:hylene (Compound 45) (1) In 200 ml of EtOH was dissolved 5.0 g of 1,1-bis-(methylthio)-2-:nitroethylene with heating and a solu-7.5 tion containing 4.7 g of N-(6-chloro-3-pyridylmethyl)-N-methylamine in 50 ml of EtOH was added dropwise on reflux in 3 portions at 30-minute intervals. After completion of d:ropwise addition, the mixture was further refluxed for 3 hours and the EtOH was then ?0 distilled off. The residue was subjected to silica gel column chromatography using CHC13-MeOH (20:1) as an eluent. The procedure gave 3.5 g of 1-[N-(6-chloro-3-pyridylmethyl)-1~-methyl]amino-1-methylthio-2-nitro-ethylene as a ycsllow viscous oil.
:?5 NMR (CDC13) 8: 2.46 (s, MeS), 3.03 (s, MeN), 4.76 - 127 - ~ 3 4 0 9 9 (s, CH2), 6..76 (s, =CHN02), 7.35 (d), 7.60 (dd), 8.30 (d) IR (neat): 1750, 1540, 1260, 1100, 1020 cm 1 (2) In 20 ml of MeOHf was dissolved 1.1 g of 1-[N-(6-chloro-3-pyridylmethyl)-N-methyl)amino-1-methylthio-2-nitroethylene prepared in (1), followed by addition of 1.0 ml of 25~ aqueous. ammonia, and the mixture was stirred at room temperature for 1 hour. The resulting crystals were collected by filtration, washed with a 7.0 small amount of MeOH and dried to give 0.85 g of the . title compound as pale yellow scales.
m.p.: 206-207°C
NMR (DMSO-.d6) s: 3.03 (s, MeN), 4.65 (s, CH2), 6.60 (s, =CHN02), 7.45 (d), 7.68 (dd), 8.31 7.5 (d), 8.92 (br s, NH2) IR (Nujol): 3280, 3140, 1625, 1580, 1420, 1225 cm Example 28 1-(6-Chloro-3-pyridylmethyl)amino-1-dimethylamino-:'.0 2-nitroethylene (Compound 46) (1) In 50 ml of EtOH was dissolved 3.3 g of 1,1-bis-(methylthio)-2-:nitroethylene and 2.2 ml of a 40%
aqueous solution of dimethylamine was added dropwise in 2 portions at 30-minute intervals under refluxing.
:?5 After completion of dropwise addition, the mixture was -its- 1340991 further refluxed for 30 minutes. Then, the EtOH was distilled off and they residue was subjected to silica gel column chromatography using CHC13-MeOH (20:1) as an eluent. The procedure gave 1.0 g of 1-dimethylamino-1-methylthio-2-nitroethylene as a yellow oil.
NMR (CDC13) &: 2..46 (s, 3 H), 3.21 (s, 6 H), 6.69 (s, 1 H) (2) The 1-dimethylamino-1-methylthio-2-nitroethylene (1.0 g) prepared in (1) and 1.0 g of 6-chloro-3-pyridyl-i0 methylamine were refl.uxed in 30 ml of EtOH for 2 hours.
The EtOH was then distilled off and the residue was subjected to silica gel column chromatography using CHC13-MeOH (10:1) as an eluent. 'The crystals obtained were recrystallized from EtOH to recover 0.82 g of the .5 title compound as pale yellow crystals.
m.p.: 124-125°C
NMR (CDC13) &: 2.99 (s, 6 H), 4.53 (d, J=5.4 Hz, 2 H), 6.46 (s, 1 H), 7.34 (d, J=8.4 Hz, 1 H), 7.72 (dd, J'=8.4 & 2.4 Hz, 1 H), 8.35 (d, 20 J=2.4 Hz, 1 H), 9.2-9.8 (br, 1 H) IR (Nujol): 1585, 1440, 1380, 1260 cm 1 Example 29 1-(2,6-Dichloro-3-pyridylmethyl)amino-1-methylamino-2-nitroethylene (Compound 47) 25 NHCH~
I
OZNCHI=C- NHCHz / \~--CQ
N
CQ

-129_ 1340991 A mixture of 1.2', g (0.007 mole) of (2,6-dichloro-3-pyridylmethyl)amine: and 1 g (0.007 mole) of 1-methyl-amino-1-methylthio-2-~nitroethane was refluxed in 50 ml of EtOH for 6 hours. After cooling, the reaction mixture was concentrated and the resulting crystals were collected by filtration, washed with CH2C12 and a small amount of EtOH in that order and dried. The procedure gave 0.53 g' of the title compound as a white powder.
1.0 m.p.. 211-213°C (decompn.) NMR (DMSO-d6) &: 2.83 (br, 3 H), 4.50 (br d, 2 H), 6.43 (s, 1 H), 7.58 (d, J=8.5 Hz), 7.80 (d, J=8.5 Hz), 7.0-7.93 (br, NH), 9.50-10.50 (br, IHH) 15 IR (Nujol): 3170, 1630, 1580, 1375, 1210 cm 1 Example 30 1-Amino-1-[N-(2,6-dichloro-3-pyridylmethyl)-N-methyl]amino-2-:nitroethylene (Compound 48) NHZ
I
20 0NCH=C-NCHZ
I

In 30 ml o:E MeOH was dissolved 0.9 g (0.003 g mole) of 1-(N-(2;6-dichloro-3-pyridylmethyl)-N-methyl]-amino-1-methyltlzio-2-nitroethylene, followed by addition 25 of 0.6 ml (0.00.45 mole) of 25% aqueous ammonia at 50°C, -i3o- 1340991 and the mixture was stirred at the same temperature for 1 hour. After cooling, the reaction mixture was concentrated and the resulting crystals were collected by filtration, washed with a small amount of EtOH and dried. The procedure: gave 0.7 g of the title compound as a white powder.
m.p.. 214-215°C (decompn.) NMR (DMSO-d6) S: 3.05 (s, 3 H), 4.63 (s, 2 H), 6.56 (s, 1 H), 7.46-7.70 (m, 2 H), 8.90 (br s, NH2) IR (Nujol): 3350, 1610, 1565, 1410, 1290, 1220 cm Example 31 1-Amino-1-[N-(6-chloro-3-pyridylmethyl)-N-i propyl]amino-2-nitroethylene (Compound 49) NHZ
I
O~NCH=C-NCHz -~CQ
CIi 3 CIICHs In 8 ml of EtOH was dissolved 0.59 g (0.00196 mole) of 1-[N-(6-chloro-3-pyridylmethyl)-N-i-propyl]-amino-1-methylt:hio-2-nitroethylene, followed by addi-tion of 0.20 ml of 25% aqueous ammonia. The mixture was stirred at :room temperature for 2 hours and 40 minutes. The reaction mixture was concentrated and the residue was subjected to silica gel (100 g) column -13,- 1 34Q 99 1 chromatography using MeOH-CHC13 (1:7) as an eluent to give the title compound as oil. The oil was triturated with Et20 and the resculting powder was collected by filtration, washed with Et20 and dried. The procedure gave 0.19 g of the title compound.
NMR (DMSO-d6) b: 1.13 (d, J=7 Hz, Me2CH), 4.30 (septet, J=~7 Hz, Me2CH), 4.62 (s, CH2), 6.50 (s, =CHN02), 7.49 (d, J=8 Hz, 1 H), 7.69 (dd, J=8 & 2 Hz, 1 H), 8.30 (d, J=2 Hz, 1 H), 9.04 (br, NH2) IR (Nujol): 1610, 1540, 1280, 1230, 1100 cm 1 Example 32 1-(6-Chloro-3-pyridylmethyl)amino-1-(N-ethyl-N-methyl)amino-2-nitroeahylene (Compound 50) C.fI 3 I
N-CHzCfl3 I
OZNCEi= C- NHCfi2 - ~CQ
~N
The step (2) of Example 28 was repeated except that 1-(N-ethyl-N-met.hyl)amino-1-methylthio-2-nitro-ethylene was used in lieu of 1-dimethylamino-1-methyl-thio-2-nitroethylene to give the title compound as pale yellow crystals.
m.p.: 87-88°C
NMR (CDC13) 8: 1.18 (t, J=6.5 Hz, 3 H), 2.89 (s, 3 H), 3.23 (q, J=6.5 Hz, 2 H), 4.46 (d, J=5.7 - 132 - ? 3 4 0 9 9 Hz, 2 H), E~.53 (s, 1 H), 7.34 (d, J=8.4 Hz, 1 H), 7.69 (dd, J=8.4 & 2.4 Hz, 1 H), 8.33 (d, J=2.4 Hz, 1. H), 9.5-10.0 (br, 1 H) IR (Nujol): 1600, 1460 cm-1 Example 33 1-(6-Chloro-3-pyridylmethyl)amino-1-hydrazino-2-nitroethylene (Compou.nd 51) NHNHZ
OZNCH=C-NHCHz - CQ
7. 0 The reaction procedure of Example 3 was repeated except that 1-(6-chloro-3-pyridylmethyl)amino-1-methyl-thin-2-nitroethylene and hydrazine hydrate.were used in lieu of 1-methylthio-1-(3-pyridylmethyl)amino-2-nitro-l.5 ethylene and aqueous methylamine solution, respectively.
The procedure gave the title compound as pale yellow crystals.
m.p.. 188-190°C (decompn.) NMR (DMSO-d6) b: 4.43 (br s, 2 H), 4.3-5.2 (br, 2 20 H), 6.49 (s, 1 H), 7.50 (d, J=8.4 Hz, 1 H), 7.81 (dd, J=8.4 & 2.4 Hz, 1 H), 8.39 (d, J=2.4 Hz, 1 H), 9.9-10.8 (br, 1 H) IR (Nujol): 3260, 1650, 1560, 1450 cm 1 Example 34 :?5 1-(6-Chloro-3-pyridylmethyl)amino-1-(2,2-dimethyl-1-hydrazino)-~2-nitroethylene (Compound 52) NHN(CH3) Z
OzNCff=C-NHCHz ~ \ CQ
-N
The reaction procedure of Example 6 was repeated except that 6~-chloro-3-pyridylmethylamine was used in lieu of 3-pyridylmeahylamine to give the title compound as pale brown. prisms.
m.p.: 170-172"C
NMR (DMSO-D6) &: 2.59 (S, 6 H), 4.43 (d, J=6.6 Hz, 2 H), 6.2-6.7 (br, 1 H), 7.47 (d, J=8.4 Hz, 1 H), 7.79 (dd, J=8.4 & 2.4 Hz, 1 H), 8.38 (d, J=2.4 Hz, 1 H), 8.0-8.5 (br, 1 H), 9.9-10.5 (br, 1 H) IR (Nujol): 3200, 1590, 1560, 1460, 1390, 1350 cm Example 35 1-(6-Chloro-3-~pyridylmethyl)amino-1-(2-methoxycar-bonyl)hydrazino-2-nitroethylene (Compound 53) NHNffC00CH3 OZNCH==C-NHCHz ~ ~ CQ
-N' To a solution of 0.4 g (0.0016 mole) of 1-(6-chloro-3-pyridylmet.hyl)amino-1-hydrazino-2-nitro-ethylene in 15 ml of DMF was added 0.14 ml (0.0018 - 134- ~ 3 4 0 9 9 mole) of methyl chloroformate and the mixture was stirred at room temperature for 30 minutes. The DMF
was distilled off und~.er reduced pressure and the residue was subjected, to silica gel column chromato-graphy using EtOH-CHC:13 (1:7) as an eluent. The procedure gave 0.14 g' of the title compound as a pale yellow solid.
m.p.. 198-201°C (decompn.) NMR (DMSO-~d6) b: 3.67 (s, 3 H), 4.48 (br d, J=6 :!0 Hz, 2 H), 6.43 (s, 1 H), 7.52 (d, J=8.4 Hz, 1 H), 7.80 (dd, J=8.4 & 2.4 Hz, 1 H), 8.38 (d, J=2.4 Hz, 1 H), 9.1-9.6 (br, 1H), 10.0-10.9 (br, 1 H) IR (Nujol): 3110, 1740, 1570, 1455 cm 1 7.5 Example 36 1-(6-Chloro-3-pyridylmethyl)amino-1-(2-methyl-aminocarbonyl)hydrazino-2-nitroethylene (Compound 54) I
O;: NCH=C-NHCHz / ~ CQ
?, o To a solution of 0.3 g (0.0012 mole) of 1-(6-chloro-3-pyridy:Lmethyl)amino-1-hydrazino-2-nitro-ethylene in 5 m:L of DMF was added 0.15 ml (0.0025 mole) of methyl isocyanate and the mixture was allowed to 25 stand at room temperature for 2 hours. The DMF was - 135 - ~ 3 4 0 9 9 1 distilled off under reduced pressure and the residue was purified by silica gel column chromatography. The procedure gave 0.08 c~ of the title compound as a white solid.
m.p.: 190-192°C (decompn.) NMR (DMSO-d6) 8: 2.63 (d, J=4.5 Hz, 3 H), 4.49 (br d, J=6.0 Hz, 2 H), 6.47 (s, 1 H), 6.5-6.8 (br d, J=4.5 Hz, 1 H), 7.51 (d, J=8.4 Hz, 1 H), 7.82 (d.d, J=8.4 & 2.4 Hz, 1 H), 8.10 (s, .LO 1 H), 8.40 (d, J=2.4 Hz, 1 H) IR (Nujol): 3200, 1680, 1550, 1455, 1380 cm 1 Example 37 1-Methylamino-1-[N-methyl-N-[2-(3-pyridyl)ethyl]-amino]-2-nitroethylen.e (Compound 55) :l5 NHMe CI2NCH=C-NCH2CHz The steps (1), (2) and (3) of Example 13 were repeated except that N-methyl-N-[2-(3-pyridyl)ethyl]-20 amine was used .in lieu of N-ethyl-N-(3-pyridylmethyl)-amine to give t'.ne following compounds in the respective steps.
(1) N-Methyl-N'-methyl-N'-[2-(3-pyridyl)ethyl]thiourea m.p.: 104-105°C
~5 NMR (CDC13) 8: 3.02 (m, CH2-pyridine), 3.04 (s, 134t~991 MeNCH2), 4.10 (m, CH2N), 5.90 (br d, J=5 Hz, NH), 7.26 (dd, J=5 & 8 Hz, 1 H), 7.67 (m, 1 H), 8.50 (m, 2 H) (2) S-Methyl-N-methyl.-N'-methyl-N'-[2-(3-pyridyl)-ethyl]isothiourea (yellow brown oil) (Note: After adclition of 60o sodium hydride (oil), the mixture was stirred at 50°C for 1 hour.) NMR (CDC13) S: 2:.15 (s, MeS), 2.84 (m, CH2-pyridine), 2.93 (s, MeNCH2), 3.21 (s, MeN=), 3.61 (m, NC:H2), 7.20 (dd, J=5 & 8 Hz, 1 H), 7.53 (m, 1 H), 8.45 (m, 2 H) (3) Title compound (yellow viscous oil) NMR (CDC13) s: 2.93 (d, J=5 Hz, MeNH), 2.96 (s, MeNCH2), 2.97 (m, CH2-pyridine), 3.50 (m, 1:~ MeNCH2), 6.52 (s, =CHN02), 7.27 (dd, J=5 & 8 Hz, 1 H), 7.57 (m, 1 H), 8.50 (m, 2 H), 9.67 (br, NH) Example 38 1-Dimethylamino-1-(N-methyl-N-3-pyridylmethyl)-amino-2-nitroethylene (Compound 56) and 1,1-bis(N-methyl-N-3-pyridylmethyl)amino-2-nitroethylene (Compound 57) N(CH3) s:
I
02NCH=C-NCHa (Compound 56) 134099' ' Cfi:
N -- CH z - ~ ~~ ! Compound 57 ) N
02NCH=C-- NCHZ -N

A mixture of 2.0 g (0.012 mole) of 1-dimethylamino-1-methylthio-2-nitroe~thylene and 1.5 g (0.012 mole) of N-methyl-N-3-pyridylmethylamine was stirred at 120°C
for 40 minutes. The reaction mixture was subjected to j_0 column chromatography, elution being carrid out with MeOH-CHC13 (1:10) to give two fractions containing the desired compounds, respectively. One of the fractions was further purified by silica gel column chromatography using MeOH-CHC13 (1:10) and acetone-CHC13 (2:1) in succesion, whereby 0.40 g of the title compound (Comp-7. 5 ound 56) was obtained. as pale yellow crystals. The other fraction 'was also chromatographed on a silica gel column and eluted with MeOH-CHC13 (1:10) and acetone-CHC13 (2:1) in that order to give 0.35 g of the title compound (Compound 57) as a yellow oil.
(Compound 56) m.p.: 103-105°C
NMR (CDC13) b: 2.81 (s, 3 H), 2.98 (s, 6 H), 4.44 (s, 3 H), 6.41 (s, 1 H), 7.33 (dd, J=8.4 &
5.1 Hz, 1 H), 7.64 (dt, J=8.4 & 1.5 Hz, 1 H), 8.4-8.7 (m, 2 H) 1 34p gg 1 IR (Nujol): 154_'., 1520, 1450, 1300, 1265 cm 1 (Compound 57) NMR (CDC13) b: 2.83 (s, 6 H), 4.48 (s, 4 H), 6.52 (s, 1 H), T.34 (dd, J=8.4 & 5.1 Hz, 2 H), 7.62 (dt, J'=8.4 & 1.5 Hz, 2 H), 8.4-8.8 (m, 4 H) Example 39 1-[N-(6-Chloro-3-pyridylmethyl)-N-methyl]amino-1-dimethylamino-2-nitroethylene (Compound 58) N;CH3) Z
I
OZNCff=C-N-CH2 / \~CQ
N
CHI
A mixture of 1.6 g (0.0099 mole) of 1-dimethylamino-1-methylthio-2-:nitroethylene and 1.4 g (0.0089 mole) of 7.5 N-(6-chloro-3-pyridylmethyl)-N-methylamine was stirred at 80°C for 3 hours. The reaction mixture was subjected to silica gel column chromatography using MeOH-CDC13 (1:10) twice and acetone-CHC13 (2:1) once to give 0.33 g of the title compound as pale yellow crystals.
a!0 m.p.: 110-:L12 °C
NMR (CDC13) &: 2.79 (s, 3 H), 2.97 (s, 6 H), 4.40 (s, 2 H), 6.38 (s, 1 H), 7.36 (d, J=8.4 Hz, 1 H), 7.72 (dd, J=8.4 & 2.4 Hz, 1 H), 8.30 (d, J=2.4 Hz, 1 H) 25 IR (Nujol): 1545, 1520, 1460, 1300, 1260 cm 1 - 139 - 1 3 4 0 9 9 1 v Example 40 1-Amino-1-[N-(6-~chloro-3-pyridylmethyl)-N-ethyl]-amino-2-nitroethylene: (Compound 59) NHz OzNCH==C- NCHZ ~ \~--CQ
N

(1) In 200 ml of EtOH was dissolved 9.68 g of 1,1-bis-(methylthio)-2-nitroethylene with heating, and a solution of 6.66 g (0.039 mole) of N-(6-chloro-3-pyridyl-J.0 methyl)-N-ethylamine in 30 ml of EtOH was added dropwise on reflux. After 45 hours of refluxing, the EtOH was distilled off and the residue was subjected to silica gel (420 g) column chromatography using EtOH-CHC13 (1:20) as an eluent. The procedure gave 2.28 g of J.5 crude 1-[N-(6-c~hloro-3-pyridylmethyl)-N-ethyl]amino-1-methylthio-2-nitroethylene as a brown oil.
NMR (CDC13) b: 1.24 (t, J=7 Hz, CH2CH3), 2.46 (s, MeS), 3.52 (q, J=7 Hz, CH2CH3), 4.72 (s, CH2-p:yridine), 6.82 (s, =CHN02), 7.31 (d, J=8 ~.'0 Hz, 1 H), 7.57 (dd, J=8 & 2 Hz, 1 H), 8.30 (d, J~=2 Hz, 1 H) (2) In 30 ml o:E EtOH was dissolved 2.16 g of crude 1-[N-(6-chloro-3-pyridylmethyl)-N-ethyl]amino-1-methyl-thio-2-nitroethylene prepared in (1), followed by ~'.5 addition of 0.766 ml of 25s aqueous ammonia. The -mo- 1 34p 99 1 mixture was stirred at room temperature for 3 hours.
The solvent was distilled off and the residue was subjected to silica c~el (200 g) column chromatography, elution being carriecl out with MeOH-CHC13 (1:5). The procedure gave 0.69 g of the title compound as a pale yellow viscous oil. This product was triturated with ether, filtered and dlried to give 0.57 g of the title compound as white powdery crystals.
m.p.:159-161°C
:LO NMR (CDC13-DMSO-~d6 [4:1]) s: 1.22 (t, J=7 Hz, CH2CH3), 3.43 (q, CH2CH3), 4.62 (s, CH2-pyridine),.6.61 (s, =CHN02), 7.38 (d, J=8 Hz, 1 H), T.62 (dd, J=8 & 2 Hz, 1 H), 8.30 (d, J=2 Hz, 1 H), 8.97 (br, NH2) .L5 IR (Nujol): 1610, 1565, 1455, 1445, 1305, 1235 cm Example 41 1-[N-(6-Chloro-3-pyridylmethyl)-N-ethyl]amino-1-methylamino-2-nitroet.hylene (Compound 60) :>.0 NIICH3 ~~ CQ
()zNCH=C- NCH2 CHzCH3 N
The steps (1), (2) and (3) of Example 37 were repeated except that N-(6-chloro-3-pyridylmethyl)-N-:?5 ethylamine was used in lieu of N-methyl-N-[2-(3-~340991 ;
pyridyl)ethyl]am.ine to give the following compounds in the respective steps.
(1) N-(6-Chloro-:3-pyridylmethyl)-N-ethyl-N~methylthiourea (yellow crysi_als) m.p.. 133-134°C
NMR (CDCL3) s: 1..16 (t, J=? Hz, CH2CH3), 3.15 (d, J=5 Hz, MeN), 3.50 (q, J=7 Hz, CH2CH3), 5.12 (s, CH2-pyridine), 5.84 (br d, J=5 Hz, NH), 7.30 (d, J==8 Hz, 1 H), 7.80 (dd, J=8 & 2 Hz, 1 H), 8.27 (d, J=2 Hz, 1 H) (2) S-Methyl-N-(6-chl.oro-3-pyridylmethyl)-N-ethyl-N'-methylisothiourea (yellow brown oil) NMR (CDC13) 8: 1..09 (t, J=7 Hz, CH2CH3), 2.29 (s, MeS), 3.21 (s, MeN=), 3.38 (q, J=7 Hz, CH CH ), 4.49 (s, CH
-2 3 -2-Pyridine), 7.27 (d, J=8 Hz, 1 H), T.61 (dd, J=8 & 2 Hz, 1 H), 8.30 (d, J=2 Hz, 1 H) (3) Title compound (white crystals) m.p.. 83-84°C
~R (CDC13) 8: 1..20 (t, J=7 Hz, CH2CH3), 3.08 (d, J=5 Hz, MeN'H), 3.18 (q, J=7 Hz, CH2CH3), 4.40 (s, CH2-pyridine), 6.54 (s, =CHN02), 7.39 (d, J=$ Hz, 1 H:), 7.63 (dd, J=8 & 2 Hz, 1 H), 8.33 (d, J=~2 Hz, 1 H), 9.79 (br d, J=5 Hz, NH) IR (Nujol): 1595, 1530, 1455, 1340, 1270, 1240 cm 1340gg ~

Example 42 1-[N-(6-Methoxy-~3-pyridylmethyl)-N-methyl]amino-1-methylamino-2-nitroethylene (Compound 61) HHCIt3 I
OZNCH=C-N-CIIZ ~ \~OCH3 Cti3 In 20 ml of DMF was dissolved 0.67 g (0.0026 mole) of 1-[N-(6-chloro-3-pyridylmethyl)-N-methyl]amino-1-methylamino-2-nitroet.hylene followed by addition of 1.00 g of a 28% solution of sodium methoxide in metha-.LO nol. The mixture was, stirred at 100°C for 5.5 hours.
The methanol and DMF were distilled off and the residue was diluted with aqueous sodium chloride solution and extracted with CH2C12. The extract was dried over MgS04 and the CH2C12 was distilled off. The residue .L5 was subjected to silica gel (230 g) column chromato-graphy using Me~OH-CHC13 (1:5) as an eluent to give 0.22 g of a brown viscous oil. A small amount of ether was added to the oil and the mixture was cooled and tri-turated. The resulting crystals were diluted with ether, filtered and dried to give 0.128 g of the title compound as white - pale brown crystals.
m.p.: 77-78°C
NMR (CDC13) &: 2.75 (s, MeN), 3.07 (d, J=5 Hz, MeNH), 3.93 (s, OMe), 4.30 (s, CH2-pyridine), ~5 6.53 (s, =C:HN02), 6.78 (d, J=8 Hz, 1 H), 7.45 (dd, J=8 & 2 Hz, 1 H), 8.05 (d, J=2 Hz, 1 H), 9.80 (br, N'H) IR (Nujol): 1605, 1455, 1310, 1250, 1025 cm 1 Example 43 1-Methylamino-1-[N-methyl-N-(4-pyridylmethyl)]-amino-2-nitroethylene (Compound 62) NIiCH3 OzNCH= C- NCH2 . ~ \\N
I
0o CHI
The steps (1), (2) and (3) of Example 37 were repeated except that N-methyl-N-(4-pyridylmethyl)amine was used in lieu of N-methyl-N-[2-(3-pyridyl)ethyl]-amine to give the following compounds in the respective steps.
(1) N-Methyl-N'-methyl-N'-(4-pyridylmethyl)thiourea m.p.: 123-124°C
NMR (CDC13) b: 3.07 (s, MeNCH2), 3.16 (d, J=5 Hz, MeNH), 5.19 (s, CH2), 6.29 (br d, J=5 Hz, NH), '7.19 (m, 2 H), 8.52 (m, 2 H) (2) S-Methyl-N-methyl-N'-methyl-N'-(4-pyridylmethyl)iso-thiourea (brown oil) NMR (CDC13) &: 2.30 (s, MeS), 2.87 (s, MeNCH2, 3.27 (s, MeN=), 4.59 (s, CH2), 7.18 (m, 2 H), 8.54 (m, 2 H) (3) Title compound m.p.: 145-146°C
NMR (CDC13) &: 2.88 (s, MeNCH2), 3.07 (d, J=5 Hz, MeNH), 4.43 (s, CH2), 6.54 (s, =CHN02), 7.21 (m, 2 H), 8.65 (m, 2 H), 9.78 (br, NH) IR (Nujol): 1600, 1565, 1455, 1435, 1410, 1320, 1260 cm 1 Example 44 1-Methylamino-1-[N-methyl-N-(2-pyridylmethyl)]-amino-2-nitroethylene (Compound 63) NIiCII3 I
OzNCII=C-NCHZ
N-The steps (1), (2) and (3) of Example 37 were repeated except that N-methyl-N-(2-pyridylmethyl)amine was used in lies of N-methyl-N-[2-(3-pyridyl)ethyl]-amine to give t)ne following compounds in the respective steps.
(1) N-Methyl-N'~-methyl-N'-(2-pyridylmethyl)thiourea (yellow brown viscous oil) NMR (CDC13) s: 3.15 (d, J=5 Hz, MeNH), 3.31 (s, MeNCH,Z), 4.90 (s, CH2), 7.15-7.6 (m, 3 H, pyridine-H2 & NH), 7.73 (t, J=7 Hz, 1 H), 8.55 (d, J=5 Hz, 1 H) (2) S-Methyl-N-methyl-N'-methyl-N'-(2-pyridylmethyl)-iscthiourea (brown oil) IT~Ftt (Cir~.i~) o: 2.3u (s, IYieS),2.9i (s, rleriCrizj,, 3.28 (s, MeN=), .4.77 (s, c:H2),7.05-7.45 (m, 2 H), 7.67 (m, 1 H), 8.56(d, J=5 Hz, 1 H) (3) Title compound m.p.: 96-97°C
NMR (CDC13) s: 2.96 (s, MeNCH2), 3.08 (d, J=5 Hz, MeNH), 4.53 (s, CH2), 6.57 (s, =CHN02, 7.30 (m, 2 H), 7.78 (m, 1 H), 8.63 (m, 1 H), 9.61 ( br , :NH ) _, IR (Nujol): 1580, 1545, 1425, 1380, 1280 cm 1 Example 45 1-[N-metho.xy-N-(3-pyridylmethyl)]amino-1-methyl-amino-2-nitroethylene (Compound 64) i 02NCli=C-NCH2 The steps (1), (2) and (3) of Example 37 were repeated except that O-methyl-N-(3-pyridylmethyl)-hydroxylamine was used in lieu of N-methyl-N-[2-(3-pyridyl)ethyl]amine to give the following compounds in the respective steps.
(1) N-Methoxy-:N-(3-pyridylmethyl)-N'-methylthiourea (provide, however, that acetonitrile was used as 1 340 99 ~
the reaction solvent. and the reaction was conducted at 50°C for 5 hours) m.p.: 95-96°C
NMR (CDC13) 8: 3.15 (d, J=5 Hz, 3 H), 3.63 (s, 3 H), 5.32 (s, 2 H), 7.03-7.46 (br, NH), 7.27 (dd, J=8 & 5 Hz, 1 H), 7.86 (dt, J=8 & 2 Hz, 1 H), 8.56 (dd, J=5 & 2 Hz, 1 H), 8.66 (d, J=2 Hz, 1 H) (2) S-Methyl-N-~methox:y-N-(3-pyridylmethyl)-N'-methyl-isothiourea (pale yellow oil) NMR (CDC13) b: 2.23 & 2.45 (each s, total 3 H), 3.26 & 3.32 (each s, total 3 H), 3.40 & 3.50 (each s, total 3 H), 4.08 & 4.52 (each s, total 2 H), 7.20-7.43 (m, 1 H), 7.76 (m, 1 H), 8.50-8.76 (m, 2 H) (3) Title compound m.p. 100-101°C
NMR (CDC13) b: 3.18 (d, J=5 Hz, 3 H), 3.45 (s, 3 H), 4.30 (s, 2 H), 6.90 (s, 1 H), 7.33 (dd, J=8 & 5 Hz, 1 H), 7.73 (dt, J=8 & 2 Hz, 1 H), 8.56-8.73 (m, 2 H), 9.73 (br, NH) IR (Nujol): 1613, 1460, 1360, 1250, 1080 cm 1 Example 46 1-(N-Formy:l-N-methyl)amino-1-[N-methyl-N-(3-pyridyl-methyl)]amino-2-nitroethylene (Compound 65) t34099 ~
CHO
NCH
I
OZNCH= C- NCHz Cff3 N
In 10 ml of dry THF was suspended 0.1 g of petroleum ether-washed 60% sodium hydride, followed by addition of 0.51 g (0.0023 mole) of 1-methylamino-1-[N-methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene.
The mixture was stirred at room temperature overnight.
Then, under ice-coolin 0.6 g, g of formic acetic anhydride was added and the mixaure was stirred at that temperature for 1 hour. The solvent was distilled off and the residue was diluted with 30 ml of water, neutralized with NaHC03 and extracted with CH2C12 (30 ml x 3). The extract was dried over MgS04, the CH2C12 was removed by distillation and the residue was subjected to silica gel column chromatography, elution being carried out with MeOH-CHC13 (1:5). The procedure gave 0.25 g of the title compound as pale yellow prisms.
m.p.: 97-98°C
NMR (DMSO-~d6) b: 2.93 (s, 3 H), 3.03 (s, 3 H), 4.62 (br, 2 H), 6.86 (s, 1 H), 7.42 (dd, J=8 & 5 Hz, 1 H), 7.73 (br d, J=8 Hz, 1 H), 8.25 (s, 1 H), 8.55 (br, 2 H) IR (Nujol): 1700, 1560, 1350, 1285, 1260, 890 cm 1 Example 47 -14s- 1 34p 99 ~
N2-Methoxy-2-nit.ro-N1-(3-pyridylmethyl)acetamidine (Compound 66) n /

a To 3 ml of isobu.tyl alcohol was added 0.75 g (0.0033 mole) of 1-methylthio-1-(3-pyridylmethyl)amino-2-nitroethylene, followed by addition of 0.56 g of O-methylhydroxylamine hydrochloride at 100-110°C.
Then, a solution of 0.93 ml of triethylamine in 1 ml of isobutyl alcohol was added dropwise at the same temperature with stirring over a period of 30 minutes.
After completion of dropwise addition, the reaction mixture was allowed to cool to room temperature and the solvent was distilled off. The residue was purified by silica gel colw:nn chromatography [eluents: MeOH-CHC13 (1:3) in the first run and MeOH-CHC13 (1:10) in the second run] to give 0.23 g of the title compound as yellow crystals.
m.p.: 77-78°C
NMR (CDC13) 8: 3.86 (s, 3 H), 4.37 (d, J=6.3 Hz, 2 H), 5.04 (s, 2 H), 5.2-5.8 (br, 1 H), 7.32 (dd, .J=8.4 & 5.1 Hz, 1 H), 7.65 (dt, J=8.4 &
1.5 Hz, 1 H), 8.4-8.8 (2 H, m) Example 48 1-(2-Metho:xyethyl)amino-1-[N-methyl-N-(3-pyridyl-methyl)]amino-2-nitroethylene (Compound 67) NHCfi2CHzOCH3 I
02NCH= C~- NCHZ

The steps (1), (2) and (3) of Example 13 were repeated except that N-methyl-N-(3-pyridylmethyl)amine and (2-methoxy)ethyl isothiocyanate were used in lieu of N-ethyl-N-(3-pyrid.ylmethyl)amine and methyl isothio-cyanate, respectively, to give the following compounds in the respective steps.
(1) N-(2-metho:xyethyl)-N'-methyl-N'-(3-pyridylmethyl)-thiourea (colorless oil) NMR (CDC13) s: 3.06 (s, 3 H), 3.36 (s,. 3 H), 3.57 (t, J=5.1 Hz, 2 H), 3.91 (dt, J=5.1 & 5.1 Hz, 2'H), 5.21 (s, 2 H), 5.9-6.3 (br, 1 H), 7.28 (dd, .1=8.4 & 5.1 Hz, 1 H), 7.75 (dt, J=8.4 &
1.5 H;z, 1 H), 8.5-8.7 (m, 2 H) (2) S-Methyl-N-(2-methoxyethyl)-N'-methyl-N'-(3-pyridyl-methyl)isothiou:rea (yellow oil) NMR (CDC13) &: 2.30 (s, 3 H), 2.88 (s, 3 H), 3.37 (s, 3 H), 3.4-3.8 (m, 4 H), 4.59 (s, 2 H), 7.25 (dd, J=8.4 & 5.1 Hz, 1 H), 7.62 (dt, J=8.4 & 1.5 Hz, 1 H), 8.4-8.7 (m, 2 H) ( 3 ) Title compound m.p. 55-57"C

1340991 ' NMR (CDC13) 6: 2.79 (s, 3 H), 3.3-3.7 (m, 4 H), 3.41 (s, 3 H), 4.43 (s, 2 H), 6.53 (s, 1 H), 7.35 Edd, J'=8.4 & 1.5 Hz, 1 H), 7.60 (dt, J=8.4 & 1.~~ Hz, 1 H), 8.5-8.7 (m, 2 H), 9.4-9.9 (br, 1 H) Example 49 1-[N-(4-Chlorobe:nzyl)-N-methyl]amino-1-methylamino-2-nitroethylene (Compou.nd 68) I
l0 OZNCH=C-N-CHZ ~ ~ CQ

(1) In 50 ml of dry THF was dissolved 4.69 g (0.0205 mole) of N-(4-chlorobenzyl)-N-methyl-N'-methylthiourea, followed by addition of 0.82 g of 60o sodium hydride (oil). The mixture was refluxed for 1 hour. Then, under cooling with ice-water and stirring, 1.277 ml of methyl iodide was added dropwise and after completion of dropwise addition, the mixture was further stirred at room temperature for 45 minutes. The THF was distilled off and the. residue was diluted with water (about 50 ml), saturated with sodium chloride, and extracted with AcOEt (100 ml x 3). The extract was dried over MgS04 and the solvent was distilled off to give 5.11 g of crude S-methyl-N-(4-chlorobenzyl)-N-methyl-N'-methylisoth,iourea as a colorless - pale yellow oil.
NMR (CDC13) s: 2.28 (s, MeS), 2.80 (s, MeNCH2), 3.26 (s, Me:N=), 4.53 (s, CH2), 7.14 & 7.31 ( each d, J=-9 Hz , each 2 H ) (2) To 4.98 g (0.0205 mole) of S-methyl-N-(4-chloro-benzyl)-N-methyl-N'-methylisothiourea prepared in (1) was added 25 ml of ni.tromethane and the mixture was refluxed for 6.5 hours. The nitromethane was distilled off and the residue was subjected to silica gel (240 g) column chromatography using MeOH-CHC13 (1:10) as an eluent to give 5.23 g~ of an orange-colored oil. To this oil were added small amounts of EtOH and ether and the mixture was cooled in a dry ice-acetone bath and triturated to give crystals. After addition of ether, the crystals were collected by filtration, washed with ether and dried. The procedure gave 3.69 g of the title compound as pale yellow cyrstals.
m.p.: 98-99°C
NMR (CDC13) s: 2.79 (s, MeNCH2), 3.05 (d, J=5 Hz, MeNH), 4.34 (s, CH2), 6.53 (s, =CHN02), 7.17 & 7.3.8 (each d, J=8 Hz, each 2 H), 9.79 (br, NH) IR (Nujol): 1450, 1310, 1235, 1070, 1025 cm 1 Example 50 1-Amino-1-(4-chlorobenzyl)amino-2-nitroethylene (Compound 69) NHz CQ
OZNCH:=C-NH-CHz To 2.59 g (0.01 mole) of 1-(4-chlorobenzyl)amino-1-methylthio-2-nitroethylene were added 45 ml of EtOH, 10 ml of THF and 1.02 g of 25% aqueous ammonia and the mixture was stirred apt an external temperature of 60°C
for 5.5 hours. During this period, 1.02 g each of 250 aqueous ammonia was added after 1, 2 and 3 hours of reaction. The reaction mixture was ice-cooled and stirred, whereupon crystals separated out. The crystals were.collect.ed by filtration, washed with EtOH
and ether in that order, and dried. The procedure gave 1.11 g of the title compound as white crystals.
m.p.. 215-216°C (decompn.) NMR (DMSO-~d6) b: 4.47 (d, J=7 Hz, CH2), 6.45 (s, =CHN02), 7.34 & 7.44 (each d, J=9 Hz, each 2 H), 8.02 (br, NH2), 9.25 (br, NH) IR (Nujol): 3100, 1560, 1430, 1405, 1195, 1030 cm Example 51 1-(4-Chlorobenzyl)amino-1-methylamino-2-nitro-ethylene (Compound 70) i9HCH3 02NCff=C- NHCH= CQ

~3409~'~
In 100 ml of EtOH on reflux was dissolved 2.59 g (0.01 mole) of 1-(4-chlorobenzyl)amino-1-methylthio-2-nitroethylene, and with refluxing continued, a solution of 1.94 g of 40% aqueous methylamine solution in 10 ml of EtOH was added dropwise over a period of 50 minutes.
After completion of dropwise addition, the mixture was further ref luxed for 15 minutes , at the end of which time it was coo:Led with ice-water, whereupon crystals separated out. The crystals were collected by filtra-tion, washed wii_h EtO:H and ether in that order, and dried. The procedure gave 1.66 g of the title compound as white crystals.
m.p.. 219-220°C (decompn.) NMR (DMSO-d6) 8: 2.88 (br d, J=3 Hz, Me), 4.43 (d, J==6 Hz, CH2), 6.43 (s, =CHN02), 7.40 (s, 4 H), 7.7 (br, MeNH), 9.9 (br, HNCH2) IR (Nujol): 1455" 1425, 1375, 1360, 1215, 995 cm 1 Example 52 1-(4-Chlorobenzy7L)amino-1-dimethylamino-2-nitro-ethylene ( Compou.nd 71 )~
N(CH3)z 02NCH= C- NIiCH2 ~ \ C~
In 100 ml of EtOH was dissolved 2.59 g (0.01 mole) of 1-(4-chlorobenzyl)a.mino-1-methylthio-2-nitroethylene 1340991_ with heating. Then, with refluxing and stirring, a solution of 2.25 g of 50$ aqueaus dimethylamine solution in 10 ml of EtOH was added dropwise over a period of 35 minutes. After completion of dropwise addition, the mixtures was further stirred and refluxed for 2.5 hours. The solvent was then distilled off and the residue was diluted with ether and triturated, whereupon crystals separated. After addition of EtOH
and ether (about 1:5), the crystals were collected by filtration, washed with ether and dried. The procedure gave 1.21 g of the title compound as white crystals.
m.p.: 133-135°C
NMR (CDC13) b: 2.91 (s, Me2N), 4.45 (d, J=6 Hz, CH2), 6.51 (s, =CHN02), 7.30 (s, 4 H), 9.79 (br, a~H) IR (Nujol): 1620, 1500, 1435, 1420, 1370, 1220, 1195 ~~m 1 Example 53 1-Dimethylamino-1-[N-formyl-N-(3-pyridylmethyl)]-amino-2-nitroet:hylene (Compound 72) N(CH3)z 02NCH=C-N-CHz N
CHO
In 10 ml o:E dry THF was suspended 0.1 g of 600 sodium hydride (oil) followed by addition of 0.56 g (0.0025 mole) of 1-di.methylamino-1-(3-pyridylmethyl)-amino-2-nitroethylene, and the mixture was stirred at room temperature overnight. Then, under ice-cooling, 0.7 g of formic acetic anhydride was added, followed by stirring at the same temperature for 2 hours. The solvent was distilled, off and the residue was diluted with 30 ml of water, neutralized with NaHC03 and extracted with CH2C12 (30 ml x 3). The extract was dried over MgSO4, the: solvent was distilled off and the residue was subjected. to silica gel column chromatogra-phy using MeOH-CHC13 (1:5) as an eluent. The procedure gave 0.2 g of the title compound as a pale yellow viscous oil.
NMR (DMSO-~d6) s: 2.90 (s, 6 H), 4.40-5.06 (m, 2 H), 6.73 (s, 1 H), 7.33 (dd, J=8 & 5 Hz, 1 H), 7.75 (br d, J=8 Hz, 1 H), 8.26 (s, 1 H), 8.55 (br, 2 H) IR (neat): 1685, 1570, 1500, 1350, 1270 cm 1 Example 54 1-Methylam.ino-1-[N-methyl-N-(2-pyrazinyl)methyl)amino-2-nitroethylene (Compound 73) btNCH=C-N-CHz . I . . -N

The steps (1), (2) and (3) of Example 13 were -156- 134099 1 _ repeated except that N-methyl-N-(2-pyrazyl)methylamine was used in lieu of N-ethyl-N-(3-pyridylmethyl)amine to give the following compounds in the respective steps.
(1) N-Methyl-N'-methyl-N'-(2-pyrazyl)methyl]thiourea m.p.: 123-124°C
NMR (CDC13) 8: 3.17 (d, J=5 Hz, 3 H), 3.26 (s, 2 H), 5.12 (sc, 2 H), 6.42 (br, 1 H), 8.53 (s, 2 H), 8.72 (~;, 1 H) (2) S-Methyl-N-methyl-N'-methyl-N'-[(2-pyrazyl)methyl]-isothiourea (pale yellow oil) NMR (CDC13) &: 2.32 (s, 3 H), 2.98 (s, 3 H), 3.26 (s, 3 H), 9:.76 (s, 2 H), 8.45-8.66 (m, 3 H) (3) Title compound m.p.: 132-133°C
NMR (CDC13) b: 2!.93 (s, 3 H), 3.09 (d, J=5 Hz, 3 H), 4.56 (s., 2 H), 6.60 (s, 1 H), 8.62 (s, 3 H), 9.60 (br, 1 H) IR (Nujol): 3150, 1580, 1410, 1280, 1240, 1020, 990 cm 1 Example 55 1-(2,2-Dimethyl-~l-hydrazino)-1-[N-methyl-N-(3-pyridyl-methyl]amino-2-nitroe:thylene (Compound 74) NHN(CH3)Z
( O~hfCH=C-N-CHZ

934099 ~ f A mixture of 4.3 g (0.024 mole) of 1-(2,2-dimethyl-1-hydrazino)-1-methyl.thio-2-nitroethylene and 3.6 g of N-methyl-N-(3-pyridyl.methyl)amine was stirred at 90-100°C for 4 hours, after which it was subjected to silica gel column chromatography using MeOH-CHC13 (1:10) as an eluent. The resulting crystals were washed with ether and. dried to give 0.7 g of the title compound. NMR of this product showed that it was a 3:2 mixture of the title compound and N2-dimethylamino-N1-methyl-2-nitro-:N1-(3-pyridylmethyl)acetamidine.
m.p.: 80-82°C
NMR.(CDC13) S: 2.40 (s, 2.4 H), 2.59 (s, 3.6 H), 2.87 (s, 1.2 H), 2.90 (s, 1.8 H), 4.61 (s, 0.8 H), 4.63 (s, 1.2 H), 6.00 (s, 0.8 H), 6.47 (s, 0.6 H), 7.15-7.45 (m, 1 H), 7.45-'7.80 (m, 1 H), 8.45-8.70 (m, 2 H), 10.1-:10.5 (br s, 0.6 H) IR (Nujol): 3130, 1585, 1570, 1445, 1425 cm 1 Example 56 1-Amino-1-[N-(6-chloro-3-pyridylmethyl)-N-n-propyl]-amino-2-nitroetlzylene (Compound 75) Nfiz I
OzNCH=C-N-CH2 ~ ~~ cl N
CH2CH~CH3 In 40 ml of EtOH was dissolved 2.83 g (0.0094 1 34p gg' .
mole) of 1-[N-(6-chloro-3-pyridylmethyl)-N-n-propyl]-amino-1-methylt~hio-2-nitroethylene followed by addition of 0.96 ml of 25°s aqueous ammonia. The mixture was stirred at room temperature for 3 hours. The resulting crystals were collected by filtration, washed with small amounts o:f EtOH and ether in that order, and dried to give 1.35 g of the title compound as pale yellow crystals.
m.p: 185-186°C (decompn.) NMR (DMSO-d6) 6: 0.87 (t, J=7 Hz, CH2CH3), 1.59 (sextet, J=7 Hz, CH2CH3), 3.31 (t, J=7 Hz, NCH2C132), 4.68 (s, CH2-pyridine), 6.59 (s, =CHNO;Z), 7.50 (d, J=8 Hz, 1 H), 7.71 (dd, J=8 & 2 H:~, 1 H), 8.31 (d, J=2 Hz, 1 H), 8.99 ( br , tJH2 ) IR (Nujol): 1615, 1550, 1455, 1335, 1320, 1300, 1285 cm 1 Example 57 1-[N-(6-Ch:Loro-3-pyridylmethyl)-N-n-propyl]amino-1-methylamino-2-n_Ltroethylene (Compound 76) O;:NCH=C-N-CHz CQ

The steps (1), (2) and (3) of Example 13 were repeated except that 1~1-(6-chloro-3-pyridylmethyl)-N-n--159- 1 3 40 g g 1 propylamine was used in lieu of N-ethyl-N-(3-pyridyl-methyl)amine to give the following compounds in the respective steps.
(1) N-(6-Chloro-3-pyridylmethyl)-N-n-propyl-N'-methyl-thiourea (pale yellow crystals) m.p.: 95-96°C
NMR (CDC13) &: 0.89 (t, J=8 Hz, CH2CH3), 1.63 (sextet, J=~8 Hz, CH2CH3), 3.17 (d, J=5 Hz, MeN), 3.36 (t, J=8 Hz, CH2CH2N), 5.16 (s, CH2-pyridine), 5.87 (br q, J=5 Hz, NH), 7.30 (d, J=8 Hz, 1 H), 7.78 (dd, J=8 & 2 Hz, 1 H), 8.30 (d, J=~2 Hz, 1 H) (2) S-Methyl-N-(6-ch.loro-3-pyridylmethyl.)-N-n-propyl-N'-methylisothiourea (yellow oil) (provided, however, that after addition of 60s sodium hydride (oil), the mixture was stirred at 50°C
for 1 hour.) NMR (CDC13) 8: 0.85 (t, J=7 Hz, CH2CH3), 1.55 (sext,~t, J=7 Hz, CH2CH3), 2.26 (s, MeS), 3.21 (s, M~~N=), 3.29 (t, J=7 Hz, CH2CH2N), 4.52 (s, C:H2-pyridine), 7.26 (d, J=8 Hz, 1 H), 7.60 (dd, J=8 & 2 Hz, 1 H), 8.30 (d, J= 2 Hz, 1 H) (3) Title compound (pale yellow - pale brown crystals) (provided, however, that the reaction mixture was refluxed in nitromethane for 34 hours.) m.p.: 102-103°C
NMR (CDC13) S: C1.88 (t, J=7 Hz, CH2CH3), 1.63 (sextet, J=-7 Hz, CH2CH3), 3.04 (t, J=7 Hz, CH2CH2N), 3.08 (d, J=5 Hz, MeN), 4.40 (s, CH2-pyridine), 6.54 (s, =CHN02), 7.38 (d, J=8 Hz, 1 H), T.60 (dd, J=8 & 2 Hz, 1 H), 8.33 (dd, J=2 Hz,, 1 H), 9.78 (br q, J=5 Hz, NH) IR (Nujol): 1590, 1520, 1450, 1350, 1270, 1245, 1095 cm 1 Example 58 1-[N-(6-Chloro-3-pyridylmethyl)-N-i-propyl]amino-1-methylamino-2-nitroet.hylene (Compound 77) NI'ICII3 OZNCEi=C-N-Cfi2 CQ
CI:13 CIiCII3 N
The steps (1), (2) and (3) of Example 13 were repeated except that N-(6-chloro-3-pyridylmethyl)-N-i-propylamine was used in lieu of N-ethyl-N-(3-pyridyl-methyl)amine to give the following compounds in the respective step .
(1) N-(6-Chloro-3-pyridylmethyl)-N-i-propyl-N'-methyl-thiourea (pale yellow crystals) m.p.. 92-93°C
~ (CDC13) s: 1.17 (d, J=7 Hz, Me2CH), 3.12 (d, -i6i-J=5 Hz, Merf), 4.87 (s, CH2), 5.08 (septet, J=7 Hz, Me~,CH), 5.80 (br q, J=5 Hz, NH), 7.30 L.
(d, J=8 Hz, 1 H), 7.65 (dd, J=8 & 2 Hz, 1 H), 8.27 (d, J=-2 Hz, 1 H) (2) S-Methyl-N-(6-chloro-3-pyridylmethyl)-N-i-propyl-N'-methylisothiourea (pale brown ail) (provided, however, that after addition of 600 sodium hydride (oil), the mixture was stirred at 50°C
for 1 hour.) NMR (CDC13) b: 1..20 (d, J-7 Hz, Me2CH), 2.23 (s, MeS), 3.10 (s, MeN=), 4.24 (s, CH2-pyridine), 4.44 (septe:t, J=7 Hz, Me2CH), 7.23 (d, J=8 Hz, 1 H), 7.56 (dd, J=8 & 2 Hz, 1 H), 8.30 (d, J=2 Hz, 1 H) (3) Title compound (white - pale brown crystals) (provided, however, that the reaction mixture was refluxed in nitrometh.ane for 130 hours.) m.p.: 119-120°C
NMR (CDC13) S: 1.31 (d, J=7 Hz, Me2CH), 3.04 (d, J=5 Hz, MeN), 3.79 (septet, J=7 Hz, Me2CH), 4.20 (s, CH:2), 6.56 (s, =CHN02), 7.30 (d, J=8 Hz, 1 H), 7.56 (dd, J=8 & 2 Hz, 1 H), 8.30 (d, J=2 Hz, 1 H), 9.78 (br q, J=5 Hz, NH) IR (Nujol): 1590, 1450, 1360, 1335, 1270, 1235, 1105 cm 1 Example 59 1-[N-(6-Chloro-?~-pyridyl)-N-methyl]amino-1-methyl-amino-2-nitroethylene~ (Compound 78) OzNCH=C-N ~ ~~,CQ
I N

(1) In 50 ml of acet.onitrile, 4.0 g (0.028 mole) of 2-chloro-5-methylamin.opyridine and 3.7 g of methyl isothiocyanate 'were refluxed for 52.5 hours and the reaction mixtrue was concentrated. To the residue were added 30 ml of ice-water and 2 ml of 3N-HC1, followed by extraction with AcOEt (50 ml x 3). The extracts were pooled, washed successively with 3N-HC1 (4 times), aqueous sodium ~~hloride solutian (4 times) and aqueous sodium hydrogen carbonate solution (once), and dried over MgS04. Th~~ AcOEt was distilled off under reduced pressure and after addition of ether, the crystals were collected by filtration and dired to give 2.8 g of N-(6-chloro-3-pyridyl)-N-methyl-N'-methylthiourea as white crystals.
m.p.: 87.5-88°C
NMR (CDC13) &: 3.09 (d, J=4.5 Hz, 3 H), 3.65 (s, 3 H), 5.3-6.0 (m, 1 H), 7.47 (d, J=8.4 Hz, 1 H), 7.61 (d~d, J=8.4 & 2.4 Hz, 1 H), 8.33 (d, J=2.4 Hz, 1 H) - 163 - 1 3 t p 9 9 1 (2) In 10 ml of dry tetrahydrafuran was suspended 0.9 g of 60$ sodium hydride (oil) which had been washed twice with petroleum ether, and with stirring, a solution of 2.5 g (0.012 mole) of N-(6-chloro-3-pyridyl)-N-methyl-N'-methylthi.ourea in 30 ml of dry tetrahydro-furan was added dropwise. After completion of dropwise addition, the mixture was stirred at 50°C for 0.5 hour.
Then, at room temperature, 2.2 g of methyl iodide was added dopwise and the mixture was further stirred for 3 hours. The reaction mixture was concentrated under reduced pressure and after addition of 50 ml of iced water and 3 ml of 3N-HC1, the concentrate was extracted with AcOEt (50 ml x 3). The extracts were pooled, washed with water (twice) and dried over MgS04.
Finally, the AcOEt was distilled off under reduced pressure to recover 2.6 g of crude S-methyl-N-(6-chloro-3-pyridyl)-N-methyl-N'-methylisothiourea as a brown oil.
NMR (CDC13) b: 2.07 & 2.38 (each s, 3 H), 3.06 &
3.27 (each s, 3 H), 3.17 & 3.30 (each s, 3 H), 6.9-7.6 (m, 2 H), 7.90 & 8.24 (each d, J=3.0 Hz, 1 H) (3) In 40 ml o:E nitromethane, 2.6 g (0.011 mole) of S-methyl-N-(6-c)zloro-3-pyridyl)-N-methyl-N'-methyliso-thiourea was re:Eluxed for 63 hours. The reaction 1 34p gg ~

mixture was them concentrated and the residue was subjected to silica c~el column chromatography using hexane-acetone (1:2) as an eluent. The resulting crystals were washed with ether and dried to give 1.3 g of the title compound as pale yellow crystals.
m.p.: 108-109°C
NMR (CDC13) &: 2:.75 (d, J=5.1 Hz, 3 H), 3.30 (s, 3 H), 6.63 (s., 1 H), 7.2-7.6 (m, 2 H), 8.2-8.3 (m, 1 H), 9~.6-10.3 (m, 1 H) IR (Nujol): 3120, 1600 cm-1 Example 60 1-Methylamino-1-[N-methyl-N-(3-pyridyl)]amino-2-nitroethylene (Compound 79) .NHCH3 I
OZNCII=C- N
CII~ N
The steps (1), (2) and (3) of Example 59 were repeated except that 3-methylaminopyridine was used in lieu of 2-chloro-5-methylaminopyridine to give the following compounds in the respective steps.
(1) N-Methyl-N'-methyl-N'-(3-pyridyl)thiourea (white crystals) m.p.: 93-94°C
NMR (CDC13;1 8: 3.08 (d, J=4.5 Hz, 3 H), 3.69 (s, 3 H), 5.2-5.8 (m, 1 H), 7.47 (dd, J=8.1 & 4.7 ~ 34~ 99 ~
Hz, 1 H), 7.64 (dt, J=8.4 & 2.3 Hz, 1 H), 8.4-8.8 (m, 2 H) (2) S-Methyl-N-methyl-N'-methyl-N'-(3-pyridyl)isothio-urea (red brown oil) NMR (CDC13) 8: 2.01 & 2.37 (each s, 3 H), 3.05 &
3.27 (each s, 3 H), 3.17 & 3.29 (each s, 3 H), 6.9-7.6 (m, 2 H), 8.0-8.6 (m, 2H) (3) Title compound (pale brown crystals) m.p.: 113-114°C
NMR (DMSO-d6) 6: 2.66 (d, J=5.1 Hz, 3 H), 3.29 (s, 3 H), 6.53 (s, 1 H), 7.41 (dd, J=8.4 & 4.5 Hz, 1 H), 7.5-7.8 (m, 1 H), 8.2-8.7 (m, 2 H), 9.4-10.0 (m, 1 H) IR (Nujol): 3190, 3140, 1595 cm 1 Example 61 1-[N-(6-Chloro-3-pyridylmethyl)-N-methyl)amino-1-ethylamino-2-nitroethylene (Compound 80) NHCHzCH3 ()zNCH=C-N-CHz CQ

Using N-(6~-chloro-3-pyridylmethyl)-N-methylamine and ethyl isoth:iocyanate in lieu of N-ethyl-N-(3-pyridyl-methyl)amine and methyl isothiocyanate, respectively, the reaction steps (1), (2) and (3) of Example 13 were followed to give the following compounds in the respective - 166 - ~ 3 4 0 9 9 1 ' steps.
(1) N-(6-Chloro-3-pyridylmethyl)-N~ethyl-N-methylthiourea (white crystals) m.p. 82-83°C
NMR (CDC13) &: 1..24 (t, J=7 Hz, CH2CH3), 3.04 (s, MeN), 3.72 (dq, J=5 & 7 Hz, CH2CH3), 5.22 (s, CH2-pyridine), 5.66 (br, NH), 7.33 (d, J=8 Hz, 1H), 7.79 (dd, J=8 & 2 Hz, 1H), 8.33 (d, J=2 Hz, 1 H) 1.0 (2) S-Methyl-N-(6-chloro-3-pyridylmethyl)-N'-ethyl-N-methylisothiourea (brown oil) NMR (CDC13) 8: 1.12 (t, J=7 Hz, CH2CH3), 2.30 (s, MeS), 2.87 (s, MeNCH2), 3.51 (q, J=7 Hz, CH2CH3), 4.52 (s, CH2-pyridine), 7.30 (d, J=8 1.5 Hz, 1 H), 7.62 (dd, J=8 & 2 Hz, 1 H), 8.33 (d, J=2 Hz, 1 H) (3) Title compound (white - pale yellow crystals) m.p.: 132-133°C
NMR (CDC13) 6: 1.33 (t, J=7 Hz, CH2CH3), 2.80 (s, 20 MeN), 3.38 (dq, J=5 & 7 Hz, CH2CH3), 4.40 (s, CH2-p:yridine), 6.49 (s, =CHN02), 7.38 (d, J=8 Hz, 1 H), 7.59 (dd, J=8 & 2 Hz, 1 H), 8.30 (d, J-=2 Hz, 1 H), 9.51 (br t, J=5 Hz, NH) IR (Nujol): 1600, 1535, 1445, 1305, 1290 cm 1 25 Example 62 1-[N-(2,6-I)imethyl-4-pyridylmethyl)-N-methyl]amino-1-methylamino-2~-nitroe~hylene (Compound 81) I
OZNCH==C-N-CHZ ~ ~N
I

The steps (1), (2) and (3) of Example 13 were repeated except that N-(2,6-dimethyl-4-pyridylmethyl)-N-methylamine was used in lieu of N-ethyl-N-(3-pyridyl-methyl)amine to give the following compounds in the respective steps.
(1) N-(2,6-dim~~thyl-4-pyridylmethyl)-N-methyl-N'-methyl-thiourea (white crystals) m.p.: 207-208°C
NMR (CDC13) s: 2.49 (s, pyridine-Me x 2), 3.09 (s, MeNCH,~), 3.18 (d, J=5 Hz, MeNH), 5.10 (s, CH2-pyridine), 5.91 (br q, J=5 Hz, NH), 6.86 ( s ~ pyridine-H2 ) (2) S-Methyl-N--(2,6-dimethyl-4-pyridylmethyl)-N-methyl-N'-methylisothiourea (brown oil) (provide, however, that after addition of 60~
sodium hydride (oil), the mixtrue was stirred at 50°C
for 1 hour and at ref:Lux temperature for 1 hours.) NMR (CDC13) 8: 2..30 (s, MeS), 2.50 (s, pyridi.en-Me x 2), 2.86 (s, MeNH), 3.27 (s, MeN=), 4.53 (s, pyridine-CH2), 6.84 (s, pyridine-H2) (3) Title compound (~rhite crystals) m.p.: 131-133°C
NMR (CDC13) 8: 2.53 (s, pyridine-Me x 2), 2.87 (s, MeNCH2), 3.05 (d, J=5 Hz, MeNH), 4.34 (s, -i6s- 1 340 99 1 CH2), 6.54 (s, =CHN02), 6.83 (s, pyridine-H2) IR (Nujol): 157C!, 1460, 1395, 1310, 1230 cm 1 Example 63 1-[N-(2-chloro-3-pyridylmethyl)-N-methyl]amino-1-methylamino-2-nitroet.hylene (Compound 82) N1~CH3 I
OzNCH=C-N-CHz The steps (1), (2) and (3) of Example 13 were repeated except that N-(2-chloro-3-pyridylmethyl)-N-methylamine was used in lieu of N-ethyl-N-(3-pyridyl-methyl)amine to give the following compounds in the respective steps.
(1) N-(2-chlor~o-3-pyridylmethyl)-N-methyl-N'-methyl-thiourea (white crystals) m.p.: 143-144°C
NMR (CDC13) b: 3.17(s, MeNCH2),3.18 (d, J=5 Hz, MeNH), 5.29 (s, CH2), 5.98 (br J=5 Hz, q, NH), '7.26 (dd, J=8 & 5 Hz, 1 H), 7.66 (d, J=8 & 1 Hz, 1 H), 8.31 (dd, J=5 & 1 Hz, 1 H) (2) S-Methyl-N-(2-chloro-3-pyridylmethyl)-N-methyl-N'-methylisothiourea (pale yellow oil) (provided, however, that after addition of 60%
sodium hydride (oil), the mixture was stirred at 50°C
f or 1 hour . ) - 169 - 1 3 4 p 9 NMR (CDC13) &: 2.29 (s, MeS), 2.95 (s, MeNCH2), 3.26 (s, MeN=), 4.67 (s, CH2-pyridine), 7.24 (dd, J=8 & 5 Hz, 1 H), 7.62 (dd, J=8 & 1 Hz, 1 H), 8.32 (dd, J=5 & 1 Hz, 1 H) (3) Title compound (pale yellow crystals) (provided, however, that the reaction mixture was refluxed in nitromethane for 2.25 hours) As determined :by NMR, the purity of this product was found to be about 7 5 0 .
m.p.: 106-113°C
NMR (CDC13) &: (for the title compound only) 2.90 (s, MeNCH.2), 3.04 (d, J=5 Hz, MeNH), 4.50 (s, CH2), 6.54 (s, =CHN02), 7.37 (dd, J=8 & 5 Hz), 7.68 (dd, J=8 & 1 Hz), 8.43 (dd, J=5 & 1 Hz), 9.78 (br q, J=5 Hz, NH) IR (Nujol): 1560, 1450, 1405, 1310, 1260 cm 1 Example 64 1-(6-Chlor~~-3-pyridylmethyl)amino-1-methylamino-1-methylamino-2-n.itroethylene (Compound 28) 2o NHCII3 I
OZNCH=C- NHCHz CQ
-N
The steps (1), (2) and (3) of Example 8 were repeated except that 6-chloro-3-pyridylmethylamine was used in lieu of N-mEahyl-N-3-pyridylmethylamine to give the following compounds in the respective steps.
(1) N-(6-Chloro-3-pyridylmethyl)-N'-methylthiourea (white crystals) -mo- 134099 ~
m.p.: 133-134°C
NMR (CDC13) b: 3.01 (d, J=5 Hz, Me), 4.80 (d, J=6 Hz, CH2), 7.25 (br, NHCH3), 7.32 (d, J=8 Hz, 1 H), 7.66 (br t, J=6 Hz, NHCH2), 7.78 (dd, J=8 & 2 Hz, 1H), 8.37 (d, J=2 Hz, 1 H) (2) S-Methyl-N~-(6-chloro-3-pyridylmethyl)-N'-methyliso-thiourea (oil) NMR (CDC13) b: 2.39 (s, MeS), 2.93 (s, MeN), 4.22 (br, 1~H), 4.50 (s, CH2), 7.27 (d, J=8 Hz, 1 H), 7.69 (dd, J=8 & 2 Hz, 1 H), 8.39 (d, J=2 Hz, 1 H) (3) Title compound (white - pale yellow crystals) This product was found to be in agreement with Compound 28 according to Example 10 in melting point, NMR, IR and TLC Rf.
Example 65 l-Methylam:ino-1-[N-methyl-N-(2-thiazolyl)]amino-2-~~itroethylene (Compound 83) NHCI~e ,s i CZa'Cli=C-P1 -~~
i CHI
The steps (1), (2) and (3) of Example 59 were repeated except than 2-methylaminothiazole was used in lieu of 2-chloro-5-methylaminopyridine to obtain the following compounds in the respective steps.

-m- 1 34p gg' (1) N-Methyl-N'-methyl-N'-(2-thiazolyl)thiourea (white crystals) (~?rovided that the reaction mixture was refluxed ~n toluene for 8 hours and the product was purified by silica gel column chromatography) m.p.: 68-69°C
NMR (CDC13) 8: 3.24 (d, J=4 Hz, 3 H), 3.95 (s, 3 H), 6.69 (d, J=4 H, 1 H), 7.42 (d, J=4 Hz, 1 H), 11.95 (br, 1 H) (2) S-Methyl-N-methyl-N'-methyl-N'-(2-thiazolyl)isothio-area (pale yellow o:il) NMR (CDC13) 8: 2.33 (s, 3 H), 3.41 (s, 3 H), 3.75 (s, 3 H), 6.74 (d, J=4 Hz, 1 H), 7.40 (d, J=4 Hz, 1 H) (3) Title compound (pale yellow crystals) ;provided that the reaction was conducted for 25 hours and the product was concentrated to give crystals) m.p.: 155-156°C
NMR (CDC13): 2.98 (d, J=5 Hz, 3 H), 3.42 (s, 3 H), 6.71 (s, 3 H), 6.91 (d, J=4 Hz, 1 H), 7.36 (d, J=4 Hz, 1 H), 9.87 (br, 1 H) 7:R (Nujol): 30.50, 1610, 1500, 1400, 1320, 1260, 1100, 1010 cm-1 .~,xample 66 ? 34p gg ~
1-Methylamino-1-[N-methyl-N-(6-methyl-3-pyridyl)]-amino-2-nitroethylene (Compound 84) NH~~t(3 ~~2~1~t1=~ l1 ~ ~ /~~~~3 ''- /N
ru~
(1.) In a solution of 1.9 g NaOH in 30 ml water was dissolved 4.3 g (0.02 mole) of 2-methyl-5-methylamino-~~yridine oxalate and the solution was extracted with :~cOEt (50 ml, 30 ml x 2). The AcOEt layers were combined, washed with water and dried over MgS04.
After concentration, 30 ml of toluene and 1.8 g of methyl isothiocyanate were added to:the concentrate and the mixture was refluxed for 8 hours. Then, 0.8 g of methyl isothiocyanate was further added and the mixture was refluxed for 7.5 hours. The reaction mixture was cooled to -20°C and the resulting crystals were collected x~y filtration, washed with cold toluene and dried. The procedure gave 2.2 g of N-methyl-N'-methyl-N'-(6-methyl-3-pyridyl)thiourea as white crystals.
m.p.. 134-135°C
NMR (CDC13) S: 2.62 (3 H, s), 3.06 (3 H, d, J=4.2 Hz), 3.66 (3 H, s), 5.2-5.9 (1 H, m, NH), 7.30 (1 H, d, J=8.4 Hz), 7.49 (1 H, dd, J=8.4 & 2.7 Hz), 8.42 (1 H, d, J=2.7 Hz) -m3- 1340 99 i (2) The reaction procedure of Example 59 (2) was repeated except that N-methyl-N'-methyl-N'-(6-methyl-3-pyridyl)thiourea was used in lieu of N-(6-chloro-3-pyridyl)-N-methyl-N'-methylthiourea to give S-methyl-N-methyl-N'-methyl-N'-(6-methyl-3-pyridyl)isothiourea as oil.
NMR (CDC13) S: 2.01 & 2.37 (3 H, each s), 2.49 &
2.53 (3 H, each s), 3.04 & 3.17 & 3.24 & 3.30 (6 H, each s), 6.9-7.6 (2 H, m), 8.0-8.5 (1 H, m) (3) The reaction procedure of Example 59 (3) was repeated except that S-methyl-N-methyl-N'-methyl-N'-(6-methyl-3-pyridyl)isothiourea was used in lieu of :~-methyl-N-(6-chloro-3-pyridyl)-N-methyl-N'-methyliso-~hiourea and that the reaction was conducted for 23 hours. The procedure gave the title compound as yellow-brown crystals.
rn. p. : 120-121 °C
1JMR (CDC13) 8: 2.57 (3 H, s), 2.65 (3 H, d, J=5.4 ~3z), 3.30 (3 H, s), 6.67 (1 H, s), 7.23 (1 H, d, ~=8.7 Hz), 7.39 (1 H, dd, J=8.4 & 2.7 Hz), 8.38 (1 H, d, J=2.7 Hz), 9.7-10.4 (1 H, m, NH ) :LR (Nujol): 31'10, 1600 cm 1 Example 67 -m4- 1 3 40 99 1 1-[N-(6-chloro-3-pyridyl)-N-methyl]amino-1-ethyl-am.iru~--2-nitroethylene (Compound 85) 02~~C;H=C-N ~~C~
''-N
CHI
The steps (1), (2) and (3) of Example 59 were reioeated except that ethyl isothiocyanate was used in lieu of methyl isothiocyanate to give the following compounds in the respective steps.
(1) N-(6-Chloro-3-pyridyl)-N-methyl-N'-ethylthiourea (yellow oil) (provided that the reaction mixture was refluxed in toluene for 78 hours and the product was purified by silica gel column chromatography) NMR (CDC1~) 8: 1.13 (3 H, t, J=6.6 Hz), 3.4-3.9 (2 H, m), ?.63 (3 H, s), 5.0-5.8 (1 H, br), 7.46 (1 H, d, J=8.4 Hz), 7.61 (1 H, dd, J=8.4 &
2.7 Hz), 8.33 (1 H, d, J=2.7 Hz) (2) S-Methyl-N-(6-chloro-3-pyridyl)-N-methyl-N'-ethyl-isotl~iourea ( yellow oil ) NMR (CDC13) &: [main component~~~76s] 1.23 (3 H, t, J=7.2 Hz), 2.04 (3 H, s), 3.28 (3 H, ), 3.53 (2 H, q, J=7.2 Hz), 6.9-7.6 (2 H, m), 8.2?. (1 H, d. J=2.7 Hz) [a small amount '3099' c~:~ isomer~~~240], 2.73 (3 H, s), 3.13 (3 H, ), 3.1-3.4 (2 H, m), 7.89 (1 H, d, J=2.7 Hz) ;3) Title compound (pale yellow crystals) (provided that the reaction was conducted for 64 hours and the reaction mixture was concentrated to give crystals) rn.p.: 118-119°C
td'~R (CDC13) s: 1.19 (3 H, t, J=7.5 Hz), 3.00 (2 H, dt, J=7.5 & 6.3 Hz), 3.29 (3 H, s), 6.61 (1 H, s), 7.3-7.6 (2 H, m), 8.1-8.4 (1 H, m) TR (Nujol): 3200, 1605, 1375, 1300 cm 1 Example 68 1-(N-(5-Bromo-3-pyridylmethyl)-N-methyl]amino-1-methylamino-2-nitroethylene (Compound 86) N((c~jl~ ~ Br C~2 NC(i-C-~;-CEI2 °-N
CHs The steps (1), (2) and (3) of Example 13 were repeated except that crude N-(5-bromo-3-pyridylmethyl)-PI-methylamine was used in lieu of N-ethyl-N-(3-pyridyl-methyi)amine to give the following compounds in the respective steps.
(1) N-(5-Bromo-3-pyridylmethyl)-N-methyl-N'-methylthio-urea (pale yellow o.il) - X34099 ~
(provided that the product was purified by silica gel column chromatography) NMR (CDC13) 8: 3.05 (s, MeNCH2), 3.19 (d, J=5 Hz, MeNH), 5.24 (s, CH2), 5.88 (br q, J=5 Hz, NH), 7.91 (m, 1 H), 8.47 (d, J=2 Hz, 1 H), 8.62 (d, J=2 Hz, 1 H) ;2) S-Methyl-N-(5-bromo-3-pyridylmethyl)-N-methyl-N'-methyl:isothiourea (oil) NMR (CDC13) &: 2,31 (s, MeS), 2.88 (s, MeNCH~), 3.26 (s, I~IeN=), 4.56 (s, CH2), 7.77 (m, 1 H), 8.47 (d, .J=2 Hz, 1 H), 8.60 (d, J=2 Hz, 1 H) (3) Title compound (pale yellowish brown crystals) m.p.: 116-117°C
NMR (CDC1.~) 8: 2.84 (s, MeNCH2), 3.08 (d, J=5 Hz, MeNH), 4.42 (s, CH2), 6.54 (s, =CHN02), 7.76 (m, 1 H), 8.48 (d, J=2 Hz, 1H), 8.68 (d, J=2 Hz, 1 H), 9.72 (br q, J=5 Hz, NH) IR (Nujol): 1595, 1465, 1425, 1405, 1260 cm 1 Example 69 1-Methylamino-:1-[N-methyl-N-(2-methylthio-3-pyridyl-methyl)]amino-2-nitroethylene (Compound 87) ~21YC~~rC 11-CH2 i N
Cfi3 Cti3~

1 34~ gg 1 The steps (1), (2) and (3) of Example 13 were repeated except that N-(2-methylthio-3-pyridylmethyl)-N-methylamine was used in lieu of N-ethyl-N-(3-pyridyl-rnethyl)amine to give the following compounds in the respective steps.
(1) N-Methyl-N'-methyl-N'-(2-methylthio-3-pyridylmethyl)-thiourea (white - pale yellow crystals) m.p.: 105-106°C
1JMR (CDC13) b: 2.61 (s, MeS), 3.15 (d, J=5 Hz, MeNH), 3.17 (s, MeNCH2), 5.00 (s, CH2), 5.77 (br, NH), 7.01 (dd, J=8 & 5 Hz, 1 H), 7.36 (dd, J=8 ~ 1 Hz, 1 H), 8.40~(dd, J=5 & 1 Hz, 1 H) (2) S-Methyl-N-met:hyl-N'-methyl-N'-(2-methylthio-3-pyridylmethyl)isothiourea (yellow oil) NMR (CDC13) &: 2.28 (s, MeS), 2.59 (s, pyridine-SMe), 2.8'9 (s, MeNCH_,), 3.27 (s, MeN=), 4.53 - -(s, CH2), 6.98 (dd, J=8 & 5 Hz, 1 H), 7.40 (dd, J=8 .& 1 Hz, 1 H), 8.37 (dd, J=5 & 1 Hz, 1 H ) (3) Title compound (pale yellow crystals) m.x>.: 131-132°C
NMR (CDC13) 8: 2.60 (s, MeS), 2.84 (s, MeNCH2), 3.03 (d, J=5 Hz, MeNH), 4.34 (s, CH2), 6.57 (s, =CHNO~), 7.07 (dd, J=8 & 5 Hz, 1 H), 7.43 (dd, J=8 & 1 Hz, 1 H), 8.46 (dd, J=5 & 1 Hz, 1 H) IR (Nujol): 1600, 1530, 1395, 1375, 1245 cm 1 Fxarnple 70 1-Methylamino-1-[N-methyl-N-(4-thiazolyl)methyl]-amino-2-nitroethylene (Compound 88) r~rrr~r~
o2ac~i=c-~;-c~;Z -~-~~
n cH~
The steps (1), (2) and (3) of Example 13 were repeated except that N-methyl-N-(4-thiazolyl)methyl-amine was used in lieu of N-ethyl-N-(3-pyridylmethyl)-amine to give the following compounds in the respective ,steps .
(1) N-Methyl-N'-methyl-N'-(4-thiazolylmethyl)thiourea foil, crystallized ~on standing in a refrigerator) (provided that the product was purified by silica gel column chromatography) NMR (CDC13) &: 3.15 (d, J=5 Hz, MeNH), 3.30 (s, MeNCH~), 4.98 (s, CH2), 6.87 (br, NH), 7,38 (d, J=2 Hz, 1 H), 8.81 (d, J=2 Hz, 1 H) (2) S-Methyl-N-methyl-N'-methyl-N'-(4-thiazolylmethyl)-i.sothiourea (oil) NMR (CDC1.I) 8: 2.31 (s, MeS), 2.91 (s, MeNCH2), 3.27 (s, 1"4eN=), 4.79 (s, CHI), 7.17 (m, 1 H), 3.80 (d, J=2 Hz, 1 H) (3) Title compound (yellow crystals) (provided that the reaction was conducted for 4.5 hours) m.p.: 155-156°C
NMR (DMSO-~3~) .5: 2.89 (s, MeNCH2), 2.98 (d, J=5 Fez, MeNH), 4.60 (s, CHI), 6.55 (s, =CHN02), 7.70 (d, J=2 Hz, 1 H), 8.95 (br q, J=5 Hz, 1 H), 9.12 (d, J=2 Hz, 1 H) ZR (Nujol): 1580, 1530, 1290, 1270, 1255 cm 1 Example 71 :L,1-bis(6-~~hloro-3-pyridylmethyl)amino-2-nitro-ethylene (Compound 89) NHCH2~C1 ~0 NCH=~-NHCH2 ~ C1 (1) A mixture ~~f 7.0 g (0.042 mole) of 1,1-bis(methyl-thio)-2-nitroet:zylene, 4.5 g of N,O-dimethylhydroxyamine hydrochloride a:nd 80 ml of EtOH was refluxed and 6.4 ml of Et3N was added dropwise over 1 hour. After completion of dropwise addition, the mixture was further refluxed for 2 hours. T:he reaction mixture was then concentrated and the resulting crystals were filtered off. The filtrate was co:ncentratd and the residue was subjected to silica gel c~~lumn chromatography using EtOH-CHC13 (1:301 as the eluent. The procedure gave 1.0 g of - iso -1-(N-methyl-N-methoxy)amino-1-methylthio-2-nitroethylene as a yellow oil.
NMR (CDCl_~) b: 2.43 (3 H, s), 3.26 (3 H, s), 3.68 (3 H, s), 7.16 (lH,s) (2) A mixture of 0.8 g (0.0045 mole) of 1-(N-methyl-N-methoxy)amino-1-methylthio-2-nitroethylene, 0.7 g of (6-chloro-3-pyridylmethyl)amine and 30 ml of EtOH was refluxed for 4 hours. The resulting crystals were collected by filtration and dried to give 150 mg of the title compound as crystals.
m.p.. 238-240°C (decompn.) NMR (DPdSO-d6) S: 4.53 (4 H, d, J=5.7 Hz), 6.51 (1 :3, s), 7.50 (2 H, d, J=8.7 Hz), 7.76 (2 H, ~3d, J=8.7 & 2.4 Hz), 8.37 (2 H, d, J=2.4 Hz), 9.7-10.8 (2 H, br) IR (Nujol): 3240, 1620, 1575, 1460, 1395, 1220 ~~m Example 72 1-[N-(6-Chloro-3-pyridyl)-N-ethyl]amino-1-methyl-amino-2-nitroethylene (Compound 90) ~rlcf~3 o2NCtf=c-;; ~"-c~
-N

(1) In 30 ml of toluene was dissolved 2.4 g (0.015 hole) of 2-chloro-5-ethylaminopyridine, followed by :addition ef 3.4 g of methyl isocyanate. The mixture was refluxed for 15 hours. After cooling, the .resulting crystals were collected by filtration, washed with a small amount of Et20 and dried. The procedure c3ave 3.0 g of N-(6-chloro-3-pyridyl)-N-ethyl-N'-methyl-urea as pale yellow crystals.
m.p.. 135-136°C
N~ (CDC13) b: 1.11 (t, J=7 Hz, 3 H), 2.75 (d, J=5 Hz, 3 H), 3.72 (q, J=7 Hz, 2 H), 4.36 (br, 1 H), 7.40 (d, J=8 Hz, 1 H), 7.59 (dd, J=8 & 3 Hz, 1 H), 8.28 (d, J=3 Hz, 1 H) (2) In 30 ml of CH3CN was dissolved 1.5 g (0.007 mole) «f N-(6-chloro-3-py:ridyl)-N-ethyl-N'-methylurea, :followed by addition of 3.1 g of phosphorus penta-sulfide . The mixture was ref luxed for 3 hours . The .insoluble matter was then filtered off and the filtrate was concentrated and diluted with 20 ml of water. The mixture was neutralized with NaHC03 and extracted with CH2C12 (50 ml x 3) and the extract was dried over I,9gS04. After concentration, the residue was purified by silica gel column chromatography to recover 0.52 g of N-(6-chloro-3-pyridyl)-N-ethyl-N'-methylthiourea as Z~ale yellow crystals.

- is2 - 1 3 4 0 9 9 ~
rn.p.. 110-111°C
L~lI~iR (CDC1.~) b: 1.20 (t, J=7 Hz, 3 H), 3.06 (d, J=5 Hz, 3 H), 4.22 (q, J=7 Hz, 2 H), 5.42 (br, 1 H), 7.40-'7.70 (m, 2 H), 8.28 (d, J=3 Hz, 1 H) (3) The reaction procedure of Example 59 (2) was repeated except that N-(6-chloro-3-pyridyl)-N-ethyl-N'-r~ethj~lthiourea 'was ,used in lieu of N- ( 6-chloro-3-pyridyl ) -V-methyl-N'-methylthiourea to give S-methyl-N-(6-chloro-3-pyridyl)-N-ethyl-N'-methylisothiourea as a pale ~~ellow oil.
NMR (CDC1;) S: 1.06-1.43 (m, 3 H), 2.02 & 2.39 J
(each.~s, :3 H), 3.03 & 3.30 (each s, 3 H), 3.46-3.93 (m, 2 H), 6.90-7.53 (m, 2 H), 7.88 & 8.20 (each d, J=3 Hz, 1 H) ~4) The reaction procedure of Example 59 (3) was repeated except that S-methyl-N-(6-chloro-3-pyridyl)-N-ethyl-N'-methylisothiourea was used in lieu of S-methyl-N-(6-c~hloro-3-pyridyl)-N-methyl-N'-methyliso-t.hiourea to give the title compound as pale yellow ~~rystals .
m.p.: 95-96°C
r~r~ (cDCl,3) s: 1.23 (t, J=7 Hz, 3 H), 2.71 (d, J=5 13z, 3 Fi), 3.75 (q, J=7 Hz, 2 H), 6.67 (s, 1 H), 7.26-'7.53 (m, 2 H), 8.20 (d, J=3 Hz, 1 H), 10.05 (br, 1 H) 1 34Q gg 1 w - 1$3 -ZR (N-.zjol): 3100, 1600, 1505, 1320, 1220, 1170, 1120, 1020 cm~~l Example 73 1-[N-(6-Chloro-3-pyridyl)-N-n-propyl]amino-1-methyl-amino-2-nitroethylene (Compound 91) NfICH~
V2llClA- C lY ~~ ~~CInL
CHZCH2Cn3 The steps (1), (2), (3) and (4) of Example 72 were repeated except that 2-chloro-5-n-propylaminopyridine eras used in lieu of 2-chloro-5-ethylaminopyridine to «btain the following compounds in the respective steps.
(1) N-(6-Chloro-3-:pyridyl)-N-n-propyl-N'-methylurea (pale yellow crystals) m.p.: 84-85°C
NMR (CDC13) b: 0.87 (t, J=7 Hz, 3 H), 1.26-1.80 (m, 2 H), 2.75 (d, J=5 Hz, 3 H), 3.62 (t, J=7 Hz, 2 H), 4.40 (br, 1 H), 7.38 (d, J=8 Hz, 1 H), '7.65 (dd, J=8 & 3 Hz, 1 H), 8.28 (d, J=3 Hz, 1 H ) (2) N-(6-Chloro-3-pyridyl)-N-n-propyl-N'-methylthiourea ;pale yellow crystals) m.p. : 145-146°C
2dtAR (CDC13) b: 0.90 (t, J=7 Hz, 3 H), 1.40-1.93 (m, 2 H), 3.07 (d, J=5 Hz, 3 H), 4.12 (t, J=7 Hz, 2 H), 5.33 (br, 1 H), 7.40-7.70 (m, 2 H), 8.30 (d, J=3 Hz, 1H) (3) S-Methyl-N-(6-chloro-3-pyridyl)-N-n-propyl-N'-methyl-i.sothiourea (pale yellow oil) I:fMR (CDC13) s: 0.80-1.10 (m, 3 H), 1.40-1.90 (m, 2 H), 2.01 & 2.37 (each s, 3 H), 3.00 & 3.28 (each s, 3 H), 3.36-3.83 (m, 2 H), 6.90-7.53 (m, 2 H), 7.86 & 8.18 (each d, J=3 Hz, 1H) (4) Title compound (pale yellow crystals) m.p.: 94-95°C
NMR (CDC13) s: 0.95 (t, J=7 Hz, 3 H), 1.43-1.93 (m, 2 H), 2.68 (d, J=5 Hz, 3 H), 3.61 (t, J=7 Hz, 2 H), 6.69 (s, 1 H), 7.26-7.50 (m, 2 H), 8.21 (d, J=3 Hz, 1 H), 10.06 (br, 1 H) IR (Nujol): 3100, 1590, 1520, 1360, 1310, 1225, x_120, 1020 cm~ 1 Exampla 74 1-[N-n-Butyl-N-(6-chloro-3-pyridyl)]amino-1-methyl-amino-2-nitroethylene (Compound 92) NNCh ~zi~C~1==(.-iv ~ ~Cnt, ~112C~2C~121n13 The steps (1), (2), (3) and (4) of Example 72 were repeated except that 2-chloro-5-n-butylaminopyridine ~3~ngg ~ .
mas used in lieu of 2-chloro-5-ethylaminopyridine to give the following compounds in the respective steps.
(1) N-n-Butyl-:~1-(6-chloro-3-pyridyl)-N'-methylurea l paJ_e yellow oil ) 1.JMR. (CDC1.,) s: 0.86-1.06 (m, 3 H), 1.10-1.73 (m, 4 J
H), 2.75 (d, J=5 Hz, 3 H), 3.66 (t, J=7 Hz, 2 H), 4.30 (d, J=5 Hz, 1 H), 7.40 (d, J=8 Hz, 1 H), 7.60 (dd, J=8 & 3 Hz, 1 H), 8.29 (d, J=3 Hz, 1 H) (2) N-n-Butyl-:~1-(6-chloro-3-pyridyl)-N'-methylthiourea (pale yellow crystals) (provided that the reaction was conducted in toluene for 1 hour) m.p.: 129-130°C
NMR {CDC13) b: 0.90 (t, J=7 Hz, 3 H), 1.10-1.83 (m, 4 H), 3.07 (d, J=5 Hz, 3 H), 4.15 (t, J=7 Hz, 2 H), 5.52 (d, J=5 Hz, 1 H), 7.36-7.70 (m, 2 H), 8.25 (d, J=3 Hz, 1 H) (3) S-Methyl-N-n-butyl-N-(6-chloro-3-pyridyl)-N'-methyl-isothiourea (pale yellow oil) NMR (CDC13) 8: 0.80-1.06 (m, 3 H), 1.10-1.80 (m, 4 H), 2.00 ~& 2.36 (each s, 3 H), 3.00 & 3.27 (each s, 3 H), 3.42-3.82 (m, 2 H), 6.90-7.50 (m, 2 H), 7.86 & 8.18 (each d, J=3 Hz, 1 H) (4) Title compound (pale yellow crystals) -1g6 - 1 3 4 0 9 9 1 m.p.: 87-88°C
NMR (CDC13) b: 0.93 (t, J=7 Hz, 3 H), 1.10-1.85 (m, 4 H), 2.68 (d, J=5 Hz, 3 H), 3.65 (t, J=7 l~z, 2 H), 6.69 (s, 1 H), 7.26-7.52 (m, 2 H), 8.21 (d, J=3 Hz, 1 H), 10.05 (br, 1 H) IR (Nujol): 3100, 1590, 1520, 1360, 1310, 1250, 1120, 1020 cm-1 Example 75 1-[N-(6-Chloro-3-pyridyl)-N-ethyl]amino-1-ethyl-amino-2-nitroethylene (Compound 93) NHCH~CH~ _ ~2l'Cll= V if t \'~-N
Ci(ZCh3 The steps (1), (2) and (3) of Example 59 were repeated except that 2-chloro-5-ethylaminopyridine and ethyl isothiocyanata_ were used in lieu of 2-chloro-5-methylaminopyridine and methyl isothiocyanate, respect-.i.vely, to give the following compounds in the respect-:ive steps.
(1) N-(6-Chloro-3-pyridyl)-N-ethyl-N'-ethylthiourea pale red crystals) (provided that the reaction was conducted in toluene for 66 'hours ) m.p.: 84-86°C
NMR (CDC1.3) S: 1.11 (3 H, t, J=7.1 Hz), 1.19 (3 H, t, J=7.2 MHz), 3.63 (2 H, dq, J=5.6 & 7.1 Hz), x.21 (2 H, q, J=7.1 Hz), 4.9-5.5 (1 H, m, NH), 7.4-'7.7 (2 H, m), 8.29 (1 H, d, J=2.4 Hz) (2i S-Methyl-N-(6-chloro-3-pyridyl)-N-ethyl-N'-ethyl-isothiourea (oil) NMR (CDC13) 6: 1.0-1.6 (6 H, m), 2.00 & 2.38 (3 H, each s, ), 3.1-4.5 (4 H, m), 6.8-7.6 (2 H, m), 7.7-8.5 (1 H, m) (3) Title compound (pale yellow crystals) m.p: 105°C
NMR (CDC13) 8: 1.0-1.5 (6 H, m), 2.94 (2 H, dq, J=5.2 & 7.0 Hz), 3.74 (2 H, q, J=7.1 Hz), 6.65 (1 H, s), 7.2-7.6 (2 H, m), 8.1-8.4 (1 H, m), 9.6-10.2 (1 H, m, NH) TR (Nujol): 3110, 1600 cm 1 Example 76 1-Methylamino-1-[N-methyl-N-(5-trifluoromethyl-3-pyr.idyl)]amino-2-nitroethylene (Compound 94) CZ~ICH==C-~~
-N
Cli (1) The reaction procedure of Example 59 (1) was I:epeated except that 3-methylamino-5-trifluoromethyl--1g$_ 1 3 4 Q 9 9 ~
pyridine was used in lieu of 2-chloro-5-methylamino-pyridine (refluxed .in toluene for 61.5 hours) to give :N-methyl-N'-methyl-N'-(5-trifluoromethyl-3-pyridyl)thio-urea as pale brown crystals.
rn.p.: 86-90°C
tiMR (CDC13) 8: 3.12 (3 H, d, J=4.2 Hz), 3.67 (3 H, s), 5.3-5.8 (1 H, m, NH), 7.8-8.0 (1 H, m), 8.77 (1 H, d, J=2.1 Hz), 8.88 (1 H, br s) (2) A mixture of 0.2 g (0.0008 mole) of N-methyl-N'-methyl-N'-(5-trifluoromethyl-3-pyridyl)thiourea, 0.3 g of methyl iodide and 10 ml of CH3CN was stirred at room temperature for 13.5 hours. Then, 0.3 g of methyl iodide was further added and the mixture was stirred :Eor 18.5 hours. The reaction mixture was concentrated and the residue was diluted with 50 ml of AcOEt and aqueous sodium hydrogen carbonate solution. After :shaking, the mixture was subjected to phase separation.
~t'he AcOEt layer was washed with aqueous sodium chloride solution, dried over MgSO~, and concentrated. The pracedure gave 0.2 g of crude S-methyl-N-methyl-N'-methyl-N'-(5-trifluoromethyl-3-pyridyl)isothiourea as oil.
(3) A mixture of 0.2 g of crude S-methyl-N-metyl-N'-methyl-N'-(5-trifluoromethyl-3-pyridyl)isothiourea and 10 ml of CH 3N02 was ref luxed for 36 . 5 hours . The - is9 -991 ~
reaction mixture was concentrated and the residue was :>ubjected to silica gel column chromatography using Y~exane-acetone (2:1) as the eluent. The procedure gave 'L8 mg of the title compound as yellow-brown crystals.
m.p: 114-115°C
t~ (CDC13) 8: 2.81 (3 H, d, J=5.1 Hz), 3.36 (3 H, s), 6.63 (1 H, s), 7.5-7.7 (1 H, m), 8.5-8.7 (2 H, m), 9.6-10.1 (1 H, m, NH) Example 77 1-[N-(6-Chloro-3-pyridyl)-N-methyl]amino-1-n-propyl-amino-2-nitroethylene (Compound 95) y'HCHZCH2CH3 OZ~;CH=C-Pd --i CHI
The steps (1), (2) and (3) of Example 59 were ~:epeated except that n-propyl isothiocyanate was used .ln lieu of methyl isothiocyanate to give the following compounds in the respective steps.
(1) N-(6-Chloro-3-pyridyl)-N-methyl-N'-n-propylthiourea (yellow oil) (provided that the reaction mixture was refluxed in toluene for 121 hours and the product was purified by ailica gel column chromatography) NMR (CDC13) 6: 0.86 (3 H, t, J=6.6 Hz), 1.2-1.8 (2 H, m), 3.63 (3 H, s), 3.4-3.9 (2 H, m), 5.1-5.7 (1 H, br), 7.45 (1 H, d, J=8.4 Hz), 7.61 (1 H, dd, J=8.4 & 2.7 Hz), 8.34 (1 H, d, T=2.7 Hz) (2) S-Methyl-N-(6-chloro-3-pyridyl)-N-methyl-N'-n-propyl-isothiourea (yellow oil) NMR (CDC13) 6: [major component~~~74%] 0.96 (3 H, t, J=7.5 Hz), 1.3-1.9 (2 H, m), 2.03 (3 H, s), 3.28 (3 H, s), 3.47 (2 H, t, J=7.5 Hz), 7.25 (1 H, d, J=8.4 Hz), 7.45 (1 H, dd, J=8.4 & 2.7 Hz), 8.23 (1 H, d, J=2.7 Hz) [minor component (isomer)~~~26°s] 2.38 (3 H, s), 3.14 (3 H,. s), 3.0-3.4 (2 H, m), 6.9-7.4 (2 H, m) i4) Title compound (oil) NMR (CDC13) b: 0.93 (3 H, t, J=7.2 Hz), 1.59 (2 H, tq, J=7.2 & 7.2 Hz), 2.95 (2 H, dt, J=6.0 &
7.2 Hz), 3.30 (3 H, s), 6.60 (1 H, s), 7.2-7.6 (2 H, m), 8.23 (1 H, d, J=3.0 Hz), Q.6-10.1 (1 H, br) jR (neat): 3110, 2950, 1595, 1450, 1360 cm~l Rxample 78 J.-(6-Chloro-3-;pyridyl)amino-1-methylamino-2-nitro-c~thylene (Compound 96) NHCii~
I
C2l~Cli- C lYH
''-N
( 'L 1 p. mixture of 3 . 9 g ( 0 . 0303 mole ) of 5-amino-2-chloropyridine, 5.0 g of 1,1-bis(methylthio)-2-nitro-ethylene and 80 ml of ethylbenzene was heated at 130°C
:for 2 hours. The ethylbenzene was distilled off under red~.~ced pressure and the crystalline residue was washed with AcOEt and subjected to silica gel column chromato-graphy using EtOH-CHC13 (1:30) as the eluent to recover crude crystals. These crystals were recrystallized srom AcOEt, washed with ether and dried. The procedure gave 0.5 g of 1-(6-chloro-3-pyridyl)amino-1-methylthio-~-nitroethylene as pale yellow crystals.
m.p.: 169-171°C
rlNR (CDC13) 8: 2.42 (3 H, s), 6.70 (1 H, s), 7.41 (1 H, d, ,J=9.0 Hz), 7.65 (1 H, dd, J=9.0 &
2.4 Hz), 8.41 (1 H, d, J=2.4 Hz), 11.3-11.8 (1 H, br) (2) In 25 ml of EtOH was dissolved 0.42 g (0.00171 mole) of 1-(6-chloro-3-pyridyl)amino-1-methylthio-2-nitroethylene, followed by addition of 0.2 g of a 40%
solution of methylamine in methanol. The mixture was refluxed for 1.5 hours. The solvent was distilled off <<nd the crystalline residue was washed with AcOEt and 3r.ied to recover 0.:33 g of the title compound as white crysl_als .
m.p.: 185°C (decompn.) NMR (DMSO-dE~) .5: 2.94 (3 H, d, J=5.4 Hz), 6.24 (1 H, s), 7.57 (1 H, d, J=9.0 Hz), 7.80 (1 H, dd, J=9.0 & 2.7 Hz), 8.34 (1 H, d, J=2.7 Hz), 8.8-9.7 ('1 H, br), 9.2-10.3 (1 H, br) iR (Nujol): 31'50, 1635, 1210 cm-1 Example 79 1-Methylamino-1-[N-methyl-N-(6-methyl-3-pyridyl-methyl)]amino-2-nit:roethylene (Compound 97) NHCII3 _ I
02NCH=C-N-CH2 ~ // Cfi3 I N
CiI3 The steps (1), (2) and (3) of Example 13 were t~epeated except that crude N-methyl-N-(6-methyl-3-pyridylmethyl)amine was used in lieu of N-ethyl-N-(3-pyridylmethyl)amine to give the following compounds :in the respective steps.
~1) N-Methyl-N'-methyl-N'-(6-methyl-3-pyridylmethyl)-thiourea (pale pink crystals) m.p.: 120-122°C
PdMR (CDC1.1) 8: 2.53 (s, pyridine-Me), 3.06 (s, MeNCH?), 3.16 (d, J=5 Hz, MeNH), 5.16 (s, CHI), 6.14 (br q, J=5 Hz, NH), 7.15 (d, J=8 Hz, 1 H), 7.64 (dd, J=8 & 2 Hz, 1H), 8.40 (d, .J=2 Ha, 1H) (2) S-Methyl-N-methyl-N'-methyl-N'-(6-methyl-3-pyridyl-methyl)isothiou:rea (oil) NMR (CDC13) 6: 2.31 (s, MeS), 2.53 (s, pyridine-Me), 2.81 (s, MeNCH2), 3.25 (s, NeN=), 4.53 (s, CH2), 7.1:L (d, J=8 Hz, 1 H), 7.48 (dd, J=8 &
2 Hz, 1 H), 8.40 (d, J=2 Hz, 1 H) 13) Title comp~~und (yellow crystals) m.p.: 102-103°C
NMR (CDC13) b: 2.57 (s, pyridine-Me), 2.80 (s, MeNCH2), :3.08 (d, J=5 Hz, MeNH), 4.39 (s, CH2), 6.54 (s, =CHN02), 7.21 (d, J=8 Hz, 1 H), 7.48 (dd, J=8 & 2 Hz, 1 H), 9.78 (br, NH) TR ENu7o1): 1600, 1550, 1310, 1250, 1090 cm 1 Example 80 L-[N-(6-Fluoro~-3-pyridylmethyl)-N-methyl]amino-1-r~ethylamino-2-nitroethylene (Compound 98) NIiCH3 I
02NCH=C-N-CHz~F
t Y
CIi 3 The steps (1), (2) and (3) of Example 13 were :repeated except that crude N-(6-fluoro-3-pyridylmethyl)-).~-methylamine was used in lieu of N-ethyl-N-(3-pyridyl-methy:l)amine to give the following compounds in the respective steps.
(1) N-(6-Fluor~~-3-pyridylmethyl)-N-methyl-N'-methylthio-urea (colorless oil) (provided that the reaction was conducted in CHC13 overnight and t:he product was purified by silica gel column chromato~~raphy) NMR (CDC13) &: 3.04 (3 H, s, MeNCH2), 3.18 (3 H, d, MeIVH), 5.22 (2 H, s, CH2), 6.88 (1 H, br, NH), '7.93 (1 H, dd, J=8.4 & 2.7 Hz), 8.54 (1 H, ddd, J-=8 . 4, 2 . 4 & 8 . 4 Hz ) , 8 .15 ( 1 H, d, .J=2.4 Hz) (2) S-Ldethyl-N-(6-fluoro-3-pyridylmethyl)-N-methyl-N'-methylisothiour~ea (oil) NMR (CDC13) s: 2.30 (3 H, s, MeS), 2.83 (3 H, s, MeNCH2), :3.24 (3 H, s, MeN=), 4.53 (2 H, s, CH2), 6.90 (1 H, dd), 7.72 (1 H, ddd), 8.12 (1 H, d) (3) Title compound (pale brown crystals) In,p, : 100-L00. 5°C
tdMR (CDC1_,) b: 2.78 (3 H, s, MeNCH2), 3.07 (3 H, ~3, MeINH) , 4. 39 ( 2 H, s, CH., ) , 6. 52 ( 1 H, s, CHN02), '7.00 (1 H, dd, J=8.4 & 2.7 Hz), 7.71 (1 H, ddd, J=8.4, 2.4 & 8.4 Hz), 8.14 (1 H, d, J=;z.4 Hz), 9.74 (1 H, br, NH) -195- ~ 3'~ 0 9 9 IR (tduj.~l): 1593, 1548, 1477, 1465, 1437, 1405, 1390, 1310, 1250, 1230, 1165, 1083, 1029 cm 1 Example 81 1-[N-Ethyl-N-(6-fluoro-3-pyridylmethyl)]amino-1-methylamino-2-nitroethylene (Compound 99) NHCH3 _ C121~'CH=C-T.-CHZ ~~-F
~\
I ~=y (1) In 30 ml of CHzCN was dissolved 4.2 g of 700 aquewus ethylamine .solution and 3.0 g (0.016 mole in terms of pure product) of crude (6-fluoro-3-pyridyl)methyl bromide was added bropwise thereto under ice-cooling.
The mixture was allowed to stand at room temperature overnight and the CH3CN was distilled off. The residue Was diluted with 20 ml of water and extracted with CHC13 (30 ml). The extract was dried over MgS04 and the CHC1., was distilled off to recover 1.38 g of red J
c_~il. This oil was dissolved in 30 ml of CHC13, followed by addition of 0.68 g of methyl isothiocyanate.
~~he mixture was stirred at room temperature for 3 hours. The reaction mixture was treated with activated ::arbon and concentrated and the residue was subjected to silica gel column chromatography using AcOEt-hexane f3.5:1) as the eluent. The procedure gave 0.6 g of ~i~1--ethyl-N- ( 6-f luoro-3-pyridylmethyl ) -N' -methyl-:.hiourea as colorless crystals.
m.p.: 123-124°C
NMR (CDC13) &: 1.18 (3 H, t, CH2CH3), 3.19 (3 H, 3, Me:NH), 3.48 (2 H, q, CH2CH3), 5.15 (2 H, s, pyridine-CH_,), 5.70 (1 H, br, NH), 6.92 (1 G
:3, dd, J=8.4 & 2.7 Hz), 7.96 (1 H, ddd, J=8.4, 2.4 & 8.4 Hz), 8.15 (1 H, d, J=2.4 Hz) !2) The reaction procedure of Example 13 (2) was repeated except that N-ethyl-N-(6-fluoro-3-pyridyl-rnethyl)-N'-methylthiourea was used in lieu of N-rnethyl-N'-ethyl-N'-(3-pyridylmethyl)thiourea to give :~-methyl-N-ethyl-N-(6-fluoro-3-pyridylmethyl)-N'-methy-lisothiourea as a pale brown oil.
NMR (CDC13) b: 1.08 (3 H, t, CH2CH3), 2.29 (3 H, s, MeS), 3.22 (3 H, s, MeN=), 3.36 (2 H, q, CH2CH3), 4.49 (2 H, s, CH2), 6.87 (1 H, dd), 7.71 (1 H, ddd), 8.11 (1 H, d) (3) The reaction procedure of Example 13 (3) was repeated except that S-methyl-N-ethyl-N-(6-fluoro-3-pyridylmethyl)-N'-methylisothiourea was used in lieu of S-methyl-N-methyl-N'-ethyl-N'-(3-pyridylmethyl)isothi-urea to give the title compound as oil.
NMR (CDC1.,) S: 1.19 (3 H, t, CH2CH3), 3.08 (3 H, J

134099 ~
d, ~Ie:NH3 . 16 ( q, CH?CH3 4 ( 2 ) 2 H, ) , . H, , 37 s, CHI), i5.54 (1 s, =CHN02), 6.98 (1 H, H, dd,J=8.4 & 2.7 Hz), 7.80 (1 H, ddd, J=8.4, 2.4 & 8.4 Hz), 8.15 (1 H, d, J=2.4 Hz) IR (neat): 3230, 1593, 1510, 1480, 1395, 1335, 1235, 1120, 1020 cm 1 Example 82 1-[N-(6-Bromo-:3-pyridylmethyl)-N-methyl]amino-1-methylamino-2-nitroethylene (Compound 100) w NHCII3 Oza,CH=C;-a-CH2-,~~Br N

.The steps (1), (2) and (3) of Example 13 were repeated except that crude N-(6-bromo-3-pyridylmethyl)-N-methylamine was used in lieu of N-ethyl-N-(3-pyridyl-methyl)amine to give the following compounds in the respective steps.
(1) N-(6-Bromo-3-pyridylmethyl)-N-methyl-N'-methyl-thiourea (white crystals) (provided that the product was purified by silica gel column chromatography) m.p.: 107-108°C
NMR (CDC13) &: 3.04 (3 H, s), 3.18 (3 H, d, J=4.8 Hz). 5.19 (2 H, s), 5.6-6.1 (1 H, br), 7.46 (1 H, d, J=8.4 Hz), 7.66 (1 H, dd, J=8.4 &
2.4 Hz), 8.29 (1 H, d, J=2.4 Hz) (2) S-Methyl-N-(6-bromo-3-pyridylmethyl)-N-methyl-N'-n~ethylisothiourea (colorless oil) NMR (CDC13) S: 2.29 (3 H, s), 2.84 (3 H, s), 3.23 (3 H, s), 4.50 (2 H, s), 7.3-7.6 (2 H, m), '3.29 (1 H, d, J=2.4 Hz) (3) Title compound (pale brown crystals) m.p.: 130-131°C
NMR (CDC13) 8: 2.80 (3 H, s), 3.06 (3 H, d, J=5.4 Hz), 4.36 (2 H, s), 6.51 (1 H, s), 7.35-7.70 (2 H, m), 8.2-8.4 (1 H, m)., 9.4-10.0 (1 H, br) IR (Nujol): 3200, 1580, 1390, 1280, 1245, 1205, _, 1075 cm '' Example 83 1-[N-(6-Bromo-3-pyridylmethyl)-N-ethyl]amino-1-methyl.amino-2-nitroethylene (Compound 101) NHCH
l OZ«CH=C-I'I-CHz-~~~Br N

The steps (1), (2) and (3) of Example 13 were repeated except that crude N-(6-bromo-3-pyridylmethyl)-1~-ethylamine was used in lieu of N-ethyl-N-(3-pyridyl-methyl)amine to give the following compounds in the respective steps.
(11 N-(6-Bromo-3-pyridylmethly)-N-ethyl-N'-methylthio-area (pale yellow crystals) m.p.: 130-131°C
NP4R ( CDC1.1 ) s : 1.18 ( 3 H, t, J=7 . 8 Hz ) , 3 . 18 ( 3 H, d, J=5.0 Hz), 3.46 (2 H, q, J=7.8 Hz), 5.12 (2 H, s), 5.5-6.0 (1 H, br), 7.46 (1 H, d, J=8.7 Hz), 7.69 (1 H, dd, J=8.7 & 2.1 Hz), 8 . 2.9 ( 1 H, d, J=2 .1 Hz ) .;2) S-Methyl-N-(6-bromo-3-pyridylmethyl)-N-ethyl-N'-methylisothiour~ea ( r~rellow oil ) tJMR (CDC13) &: 1.08 (3 H, t, J=6.3~Hz), 2.29 (3 H, s), 3.21 (3 H, s), 3.36 (2 H, q, J=6.3 Hz), 4.46 (2 H, s), 7.3-7.6 (2 H, m), 8.28 (1 H, br s) (31 Title compound (provided that the reaction was conducted for 38 rvours ) m.p.: 79-80°C
NMR (CDC13) &: 1.18 (3 H, t, J=6.3 Hz), 3.06 (3 H, d, J=5.7 Hz), 3.16 (2 H, q, J=6.3 Hz), 4.34 (2 H, s), 6.53 (1 H, s), 7.3-7.7 (2 H, m), 8.30 (1 H,, br s), 9.5-10.1 (1 H, br q, J=5.7 Hz ) - ZOO - ~ 3 4 0 9 9 1 IR (Nujol): 3200, 1580, 1240, 1080 cm 1 Example 84 1-[N-(2-Chloro-5-thiazolylmethyl)-N-methyl]amino-1-methylamino-2-nitroethylene (Compound 102) N II CH 3 ~----N
0 2 NCH = C- N - CH 2 ~~S ~ CQ
I

The steps (1), (2) and (3) of Example 13 were :repeated except that crude N-(2-chloro-5-thiazolylmethyl)-N-methylamine was used in lieu of N-ethyl-N-(3-pyridyl methyl)amine to give the following compounds in the :respective steps.
(1) N-(2-Chloro-5-thiazolylmethyl)-N-methyl-N'-methyl-thiourea (white - pale brown crystals) (provided that a silica gel column was used for purification) m.p.: 129-131°C
~1MR (CDC13) &: 3.06 (s, MeNCH2), 3,16 (d, J=4 Hz, MeNH), 5.21 (s, CHI), 5.83 (br, NH), 7.48 (s, thiazole-H ) !2) S-Methyl-N-(2-chloro-5-thiazolylmethyl)-N-methyl-N'-methylisothiourea (yellow oil) NMR (CDC13) s: 2.30 (s, MeS), 2.90 (s, MeNCH2), 3.24 (s, MeN=), 4.50 (s, CHI), 7.39 (s, thia.zole-H ) (3) Title compound (pale brown crystals) m.p.: 131-133°C
NMR (CDC13) b: 2.84 (s, MeNCH2), 3.09 (d, J=5 Hz, MeN=), 4.49 (s, CH2), 6.51 (s, =CHN02), 7.50 (s~ thiazole-H). 9.66 (br, NH) IR (Nujol): 1585, 1395, 1260, 1070, 1050, 1025 cm Example 85 1-[N-(2-Chloro-5-thiazolylmethyl)-N-ethyl]amino-7.-methylamino-2-nit:roethylene (Compound 103) NIfCH3 GZNCH=C-N-CHZ ~ CQ
I

The steps (1), (2) and (3) of Example 13 were :repeated except that crude N-(2-chloro-5-thiazolylmethyl)-N-ethylamine was used in lieu of N-ethyl-N-(3-pyridyl-methyl)amine to give the following compounds in the 1_espective steps.
(1) N-(2-Chloro-5-thiazolylmethyl)-N-ethyl-N'-methyl-thi.ourea (white crystals) m.p.: 116-118°C
NMR (CDC1.~) b: 1.19 (t, J=7 Hz, CH2CH3), 3.16 (d, J=4 Hz, MeNH), 3,44 (q, J=7 Hz, CH2CH3), 5.15 (s, thiazole-CHI), 5.79 (br, NH), 7.47 ;thiazole-H) (2) S--Methyl-N-(2-chloro-5-thiazolylmethyl)-N-ethyl-I'd' -m~~thylisothiourea ( oil ) NMR (CDC13) b: 1.11 (t, J=7 Hz, CH2CH3), 2.28 (s, ~IeS), 3.26 (s, MeN), 3.40 (q, J=7 Hz, CH2CH3), 4.50 (s, thiazole-CHI), 7.39 (s, _hiazole-H) (3) Title compound (pale brown crystals) (provided that the reaction was conducted for 24 hours ) .
m.p.. gl-92°C (110-:L12°C after recrystallization from AcOEt-hexane) NMR (CDC1:3) b: 1.18 (t, J=7 Hz, CH2CH3), 3.07 (d, J=5 Hz, MeNH), 3.17 (q, J=7 Hz, CH2CH3), 4,46 (s, thiazole-CH2), 6.52 (s, =CHN02), 7.47 (s, thiazole-H), 9.75 (br, NH) IR (Nujol): 1585, 1450, 1405, 1360, 1255, 1225, :L050 cm 1 Example 86 1-(2-Chloro-5-thiazolylmethyl)amino-1-dimethyl-amirxo-2-nitroethylene (Compound 104) and 1,1-bis~2-chloro-5-thiazolylmethyl)amino-2-nitroethylene (Compound 105) N ~Cfi3) Z N
02NCIi=C--NH--CII2 ~~CQ

(Compound 104) ~j N
NHCII~ ~~.CQ
~ ii O~NCII=C--NHC:H2 -~~CQ (Compound 105) A mixture of 0.60 g (0.0037 mole) of 1-dimethyl-- amino-1-methylthio-2-nitroethylene, 0.55 g of 2-chloro--thiazolymethylamine and 30 ml of EtOH was refluxed for 1.5 hours. After cooling, the resulting crystals of 1-N-(2-chloro-5-thiazolylmethyl)amino-1-methylthio-2-nitroethylene (0.20 g) were filtered off and the filtrate was concentrated and subjected to silica gel column '~h.romatography 'using EtOH-CHC13 (1:10) as the eluent.
'.Che procedure gave 0.07 g of the title compound (Compound 104) and 0.034 g of the title compound (Compound 105).
(1-(2-Chloro-5-thiazolylmethyl)amino-1-methylthio-2-nitroethylene) m.p.: 150-152°C
NMR (CDC13) &: 2.49 (3 H, s), 4.78 (2 H, d, J=6.0 Hz), 6.58 (1 H, s), 7.52 (1 H, s), 10.3-10.8 (1 H, br) (Compound 104) m.p.: 101-102°C
NMR (CDC13) b: 2.97 (6 H, s), 4.58 (2 H, d, J=6.3 Hz), 6.51 (1 H, s), 7.50 (1 H, s), 9.3-9.8 (1 H, br) IR (Nujol): 3100, 1585, 1380, 1255, 1030 cm 1 (Compound 105) m.p.: 211°C (decompn.) NMR (DMSO-d6) ~: 4.5-4.8 (4 H, m), 6.63 (1 H, s), 7.63 (2 H, s) IR (Nujol): 3120, 1610, 1210, 1040 cm 1 Example 87 1 -(2-Chloro-.5-thiazolylmethyl)amino-1-methylamino-2-nitroethylene (Compound 106) ~HCfi3 ~
oNca==c-N:.-cli2 ~~c~
.~ mixture of 0.19 g (0.00072 mole) of the 1-(2 ~~hloro-5-thiazolylmethyl)amino-1-methylthio-2-nitroethylene prepared in Example 86 and 25 ml of EtOH was heated at 70°C. Then 0.1 g of a 40% aqueous solution of methylamine was added and the mixture was stirred at 70°C for 0.5 hour. The EtOH was distilled off, and after addition of ~~cOEt, the crystalline residue was filtered and ~~ried. The procedure gave 0.12 g of~the title compound ~~s white crystals.
m.p.: 181°C (decompn.) NMR (DMSO-d6) b: 2.83 (3 H, d, J=5.1 Hz), 4.63 (2 ~~i, d, J=6.3 Hz), 6.57 (1 H, s), 7.66 (1 H, ~), 7.3-8.1 (1 H, br), 9.6-10.4 (1 H, br) -ZOS- 1 ~ 4 0 0 9 1 IR (Nujol): 3140, 1620, 1415, 1210 cm 1 Example 88 1-(6-Chloro-3-pyridylmethyl)amino-1-dimethylamino-2-nitroethylene (Compound 46) N(.CIf3) I
02NCH=C-NH-CH2 ~--.~CQ
-N
(1) A mixture of 4.32 g (0.0303 mole) of 6-chloro-3-pyridylmethylamine, 20 ml of water and 1.78 g of sodium ~~ydroxide was stirred at room temperature and 2.37 ml of carbon disulfide was added dropwise. After completion of dropwise addition, the mixture was further stirred at 50°C for 1 hour. After cooling with ice-water, 3.49 ml of ethyl chlorocarbonate was added dropwise at about 5°C, After completion of dropwise addition, the mixture was stirred at 50°C for 1 hour. After cooling, the reaction mixture was saturated with sodium chloride rind extracted with Et20 (50 ml x 3), and the extract waa dried over MgSO,~. Then, the Et20 was distilled off j~o recover 5.38 g of crude (6-chloro-3-pyridyl)methyl isothiocyanate as oil.
NMR (CDCl.~) b: 4.77 (s, CH2), 7.39 (d, J=8 Hz, 1 H), 7.70 (dd, J=8 & 2 Hz, 1 H), 8.36 (d, J=2 Hz, 1 H) ( 2 ) A ~nixture of 5 .16 g of a 50% aqueous solution of dim~thylamine and 3~D ml of CH3CN was stirred under cooling with ice-water. Then, a solution of 5.29 g (0.0287 mole in terms of pure product) of crude (6-chloro-3-pyridyl)-methyl isothiocyanate in 30 ml of CH3CN was added c.ropwise thereto. After completion of dropwise addition, the mixture was stirred at room temperature f:or 15 minutes. The CH.,CN was distilled off and the J
residue was diluted with aqueous sodium chloride ,ol.ution and extracted with CH2C12 (50 ml x 3). The extract was dried over MgS04 and the CH2C12 was distilled off, whereupon crystals were obtained. After addition of Et?O, t'he crystals were collected by filtration, dried a:nd recrystallized from AcOEt. The ~,rr~cedure gave 3.82 g of N-(6-chloro-3-pyridylmethyl)-i~1'-dimethylthiourea as yellow crystals.
:m.p.: 139-141°C
NMR (CDC13) b: 3.27 (s, Me2N), 4.88 (d, J=5 Hz, CH2), 6.17 (br t, J=5 Hz, NH), 7.27 (d, J=8 Hz, 1 F-I) , 7.76 (dd, J=8 & 2 Hz, 1 H) , 8.25 (d, J=2 Hz, 1 H) (3) To 3.00 g (0.013 mole) of N-(6-chloro-3-pyridyl-methyl)-N'-dimethylthiourea was added 32 ml of dry THF, followed by addition of 0.52 g of 60% sodium hydride.
The mixture was stirred at 50°C for 15 minutes. After cooling with ice-water, 0.814 ml of methyl iodide was added dropwise and the mixture was stirred at room temperature for 20 minutes. The THF was distilled off and the residue was diluted with aqueous sodium chloride solution and extracted with AcOEt (50 ml x 3). The extract was dried o er MgS04 and the AcOEt was distilled ~~f__. The procedure gave 3.30 g of crude S-methyl-N-(6-chloro-3-pyridylmethyl)-N'-dimethylisothiourea as U11.
NMR (CDC13) 6: 2.30 (s, MeS), 2.98 (s, Me2N), 4.69 (s, CHI), 7.25 (d, J=8 Hz, 1 H), 7.65 (dd, J=8 & 2. Hz, 1 H), 8.37 (d, J=2 Hz, 1 H) ( 4 ) To 3 . 2 4 g ( 0 . 013 3 mole in terms of pure products ) of crude S-methyl-N-(6-chloro-3-pyridylmethyl)-N'-dimethyliso-thiourea was added 14.5 ml of CH3N02 and the mixture was refluxed with stirring for 14.5 hours. The CH3N02 ~~as then distilled off and the residue was subjected to ~~ilica gel (240 g) column chromatography using MeOH-~~HC13 (1:5) as the eluent to recover an oil. This oil was dissolved in AcOEt, the AcOEt was distilled off, and the residue was allowed to stand, whereupon crystals separated out. After addition of Et20, the crystals ~~ere recovered by filtration, washed with Et20 and dried. The procedure gave 2.30 g of the title compound His pale yellow crystals. This product was in agreement -2os- ~ 3 4 0 9 9 1 with Compound 46 obtained in Example 28 in melting point, NMR and IR spectra and TLC Rf.
Example 89 1-(6-Chloro-3-;pyridyl)amino-1-dimethylamino-2-nitro-~_thylene (Compound 107) NOCH3) Z
I
U2'~CH=C-I~H ,-~ -CQ
N
A mixture of 1.5 g (0.0093 mole) of 1-dimethylamino-1-methylthio-2-nitr~oethylene and 1.1 g of 5-amino-2-c:hloropyridine was 'heated at 110-120°C with stirring for 1 hour. After cooling, the reaction mixture was subjected to silica gel column chromatography using rtOH-CHC13 (1:40) as the eluent to recover 0.38 g of the title compound as pale brown crystals. The NMR
,spectrum of this product showed that it was a 1:1 mixture of the title compound and N2-(6-chloro-3-pyridyl)-N'-dimethyl-2-nitroacetamidine.
m.p.: 122-123°C
NMR (CDC1.~) &: 2.86 (3 H, s), 3.10 (3 H, s), 5.17 (1 H, s), 6.68 (0.5 H, s), 7.09 (0.5 H, dd, J=9.0 & 2.7 Hz), 7.24 (0.5 H, d, J=9.0 Hz), 7.3-7.6 (1 H, m), 7.86 (0.5 H, d, J=2.7 Hz), 8.22 (0.5 H, d, J=2.7 Hz), 10.8-11.2 (0.5 H, br 1 - 209 - ~ 3 ~ O 9 IR (Nujol): 3100, 1395, 1280 cm 1 Example 90 1-[N-(6-Methoxy-3-pyridyl)-N-methyl]amino-1-methyl-amino-2-nitroethylene (Compound 108) NHCH3 _ I
O, NCH==C-N ~ ~~ OCH3 ' N

The steps (1), (2) and (3) of Example 59 were repeated except that 2-methoxy-5-methylaminopyridine was used in lieu of 2-chloro-5-methylaminopyridine to give the following compounds in the respective steps.
ll) N-(6-Methoxy-3-pyridyl)-N-methyl-N'-methylthiourea (white crystals) (,provided that the reaction was conducted in toluene) m.p.: 115.5-116°C
NMR (CDC13) 3.06 (3 H, d, J=4.5 Hz), 3.65 (3 8: H, s), 3.97 (3 s), 5.2-5.8 H, NH), 6.86 H, (1 m, (1 H, d, J=8.7Hz), 7.46 (1 dd, J=9.0 &
H, 3.0 Hz), 8.08 (1 H, d, J=2.4 Hz) (2) S-Methyl-N-(6-methoxy-3-pyridyl)-N-methyl-N'-methyl-i.sothiourea (pale yellow oil) ZtMR (CDC13) &: 2.01 (3 H, s), 3.18 (3 H, s), 3.28 (3 H, s), 3.93 (3 H, s,), 6.72 (1 H, d, J=9.0 Hz), 7.43 (1 H, dd, J=9.0 & 3.0 Hz), 8.02 (1 H, d, J=2.4 Hz) (3) Title compound (yellow crystals) (provided that the reaction was conducted for 16 Hours) m.p.: 131-132°C
13MR (CDC13) b: 2.65 (3 H, d, J=5.4 Hz), 3.27 (3 H, s), 3.96 (3 H, s), 6.07 (1H, s), 6.82 (1 H, d, J=9.0 :Hz), 7.43 (1 H, dd, J=8.4 & 3.0 Hz), 8.04 (1 H, d, J=2.7 Hz), 9.8-10.4 (1 H, m) IR (Nujol): 3130, 1590 cm 1 Rxample 91 1-[N-(6-Chloro-3-pyridyl)-N-methyl]amino-1-methyl-ami.no-2-ethoxycarbonyl-2-nitroethylene (Compound 109) S
CH3CH200C- C= C- N ~ ~ CQ
I I ' N
NOz CH3 A mixture of 2.0 g (0.0087 mole) of S-methyl-N-(6-chloro-3-pyridyl)-N-methyl-N'-methylisothiourea and ~1.0 g of ethyl nitroacetate was stirred with heating at ~)0-100°C for 6 hours. After cooling, a small amount of ,scetone was added and the resulting crystals were ::ollected by filtration, washed with acetone and dried.
~~he procedure gave 0.3 g of the title compound as white -211_ 134099 ~
rystals. From the filtrate, acetone was distilled off ~~nd the residue was further stirred with heating at 5~0-100°C for 16 hours. The procedure gave a furhter crop (0.2 g) of the title compound.
m.p.. 225-227°C (decompn.) tZMR (DMSO-d6) S: 1.10 (3 H, t, J=6.9 Hz), 2.89 (3 H, s), 3.45 (3 H, s), 3.93 (2 H, q, J=7.3 Hz), 7.60 (1 H, d, J=8.4 Hz), 7.75 (1 H, dd, J=8.1 & 2.7 Hz), 8.30 (1 H, d, J=2.1 Hz), 9.31 (1 H, br s) iR (Nujol): 3190, 1675, 1630 cm 1 Example 92 L--[N-(6-Chloro-3-pyridylmethyl)-N-methyl]amino-1-(N-formyl-N-methyl)amino-2-nitroethylene (Compound 110) , CHO
I
N-Cii3 _ I
OZNCH=C-N-CHZ ~ " C.0_ I y The reaction procedure of Example 46 was repeated except that 1-[N-(6-chloro-3-pyridylmethyl)-N-methyl]-~m:ino-1-methylamino-2-nitroethylene was used in lieu of 1-methylamino-1-[N-methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene to give the title compound as a yellow resinous mass.
NMR (DMSO-d~~) &: 2.92 (s, 3 H), 3.03 (s, 3 H), -212- 1 3 ~ 0 9 9 1 4.60 (br, 2 H), 6.86 (s, 1 H), 7.48 (d, J=8 Hz, 1 H', 7.80 (dd, J=8 & 2 Hz, 1 H), 8.23 (s, 1 H), 8.38 (d, J=2 Hz, 1 H) IR (neat): 1690, 1560, 1490, 1350, 1270, 1100 cm-1 Example 93 .-[N-(6-Chloro-3-pyridylmethyl)-N-ethyl]amino-1-~;N-formyl-N-methyl)amino-2-nitroethylene (Compound 111) CHO
I
td-CH3 _ ~32NCH=C-N-CIIa ~ ; CD
. I N

The reaction procedure of Example 46 was repeated except that 1-[N-(6-chloro-3-pyridylmethyl)-N-ethyl]-amino-1-methylamino-2-nitroethylene was used in lieu of 1-methylamino-1-[N-methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene to give the title compound as a yellow resinous mass.
t~MR (DMSO-d6) &: 1.13 (t, J=7 Hz, 3 H), 3.00 (s, 3 H), 3.10-3.53 (m, 2 H), 4.60 (br, 2 H), 6.96 (s, 1 H), 7.48 (d, J=8 Hz, 1 H), 7.82 (dd, J=8 & 2 Hz, 1 H), 8.20 (s, 1 H), 8.39 (d, J=2 Hz, 1 H) TR (neat): 1685, 1560, 1480, 1340, 1240, 1100 cm 1 Example 94 1-[N-(6-Chloro-3-pyridyl)-N-methyl]amino-1-(N-formyl-tt-n~ethyl)amino-2-nitroethylene (Compound 112) 1 340 gg ~

CHO
I
N-CH3 _ I
02NCH=C-N ~ ~ CQ
N
CIi3 ThE reaction procedure of Example 46 was repeated except that 1-[N-(6-chloro-3-pyridyl)-N-methyl]amino-1-ma_thylamino-2-nitroethylene was used in lieu of 1-raethylamino-1-[N-methyl-N-(3-pyridylmethyl))amino-2-nitroethylene to give the title compound as yellow crystals.
ro.p.: 134-135°C
tJNiR (DMSO-d6) ~s: 2.73 & 2.89 (each s, 3 H) , 3.32 &
3.39 (each s, 3 H), 7.03 & 7.10 (each s, 1 H), 7.46 ~ 7.57 (each d, J=8 Hz, 1 H), 7.83 &
7.92 (each dd, J=8 & 2 Hz, 1 H), 8.35 & 8.70 (each s, 1 H), 8.37 & 8.44 (each d, J=2 Hz, 1 H) ..R (Nujol): 1685, 1560, 1305, 1280, 1250, 1135 cm Example 95 1-[N-(6-Chloro-3-pyridylmethyl)-N-formyl]amino-1-dimethylamino-2-nitroethylene (Compound 113) NCCH3) I
OZNCH= C-N- CH2 ~Y>--CQ
CEiO

_214_ 1 3 40 g g The reaction procedure of Example 46 was repeated except that 1-N-~(6-chloro-3-pyridylmethyl)amino-1-di-methylamino-2-ni.troethylene was used in lieu of 1-methylamino-1-[tt-met.hyl-N-(3-pyridylmethyl)]amino-2-r~itroethylene to give the title compound as pale yellow cr~~stals.
m. p. : 105-1.06 °C:
NMR (DMSO-ct5) d: 2.93 (s, 6 H), 4.33-5.10 (m, 2 H), 6.72 (s, 1 H), 7.42 (d, J=8 Hz, 1 H), 7.8U (dd, J=8 & 2 Hz, 1 H), 8.23 (s, 1 H), 3.36 (d, J=2 Hz, 1 H) TR (Nujol); 1700, 1565, 1490, 1350, 1270, 1205, 1100 c:m 1 Example 96 7.5 I~ 7 : 3 mixture of '1-( 6-chloro-3-pyridylmethyl ) -amino-1-(N-formyl-N-methyl)amino-2-nitroethylene (Compound 114) a.nd 1-(N-(6-chloro-3-pyridylmethyl)-N-formyl]amino-1-methylamino-2-nitroethylene (Compound L15) i Id -CH 3 _ OZNCH=C-NIICI12 ~ " CQ
NT (Compound 114) NHCfi3 02~1CH=C~-N-CII2 ~-~ -CQ
CHO
(Compound 115) In 10 ml of DME was suspended 0.1 g of 60°s sodium hydride, previously washed with petroleum ether, and a :~oJ.ution of 0.6 g (0.0025 mole) of 1-N-(6-chloro-3-~~yridylmethyl)amino-1-methylamino-2-nitroethylene in 5 ml of DMF was added dropwise. The mixture was stirred :LO at room temperature for 1 hour. After cooling, 0.7 g of formic acetic anhydride was added and the mixture was stirred under ice-cooling for 5 hours and, then, at :room temperature for 20 hours. The DMF was distilled off under reduced pressure and the residue was diluted :L5 ;pith 20 ml of saturated aqueous sodium hydrogen carbo-nate solution and extracted with CH~C1~ (20 ml x 3).
'~he extract was dried over MgS04 and the CH2C12 was ~~istilled off. Finally, the residue was subjected to ,silica gel column chromatography using EtOH-CHC13 0 (1:10) as the eluent. The procedure gave 0.15 g of a ~:3 mixture of the title compounds (Compound 114 and t;ompound 115) as white crystals.
m.p.: 80-85°C
tJMR (DMSO-d6) 6: (Compound 114) 3.05 (s, 3 H), :?5 -216_ 1 3 4 a 9 9 1 4.53 (d, J=6 Hz, 2 H), 6.76 (s, 1 H), 7.49 ;d, J'=8 Hz, 1 H), 7.86 (dd, J=8 & 2 Hz, 1 H), 8.30 (s, 1 H), 8.42 (d, J=2 Hz, 1 H), 9.45 (br, 1 H) (Compound 115) 2.95 (d, J=5 Hz, 3 H), 4.83 (s, 2 H), 6.66 (s, 1 H), 7.46 (d, J=8 Hz, 1 H), 7.86 (dd, J=8 & 2 Hz, 1 H), 8.30 (s, 1 H), 8.42 (d, J=2 Hz, 1 H), 9.45 ;br, 1 H) IR (Nujol): 3200, 3100, 1685, 1600, 1340, 1250, 1080, 1040 cm-1 Example 97 1-(6-Chloro-3-pyridylmethyl)amino-1-methylamino-2-Esthoxycarbonyl-2-nitroethylene (Compound 116) CIf3CH200C-C=C-NH-CH2 ---~CQ
---N

A mixture of 1.4 g (0.0061 mole) of S-methyl-N-(6-chloro-3-pyridylmethyl)-N'-methylisothiourea obtained in Example 64 (2) and 2.7 g of ethyl nitroacetate was stirred with heating at 75-80°C for 3 hours. After cooling, the crystals were collected by filtration, washed with CH3CN and dried. The procedure gave 1.1 g of the title compound as white crystals.
m.p.. 231-233°C (decompn.) 1~MR (DMSO-dE) 6: 1.07 (3 H, t, J=7 Hz), 2.86 (3 H, br s), 3.94 (2 H, q, J=7 Hz), 4.47 (2 H, br s), 7.51 (1 H, d, J=8 Hz), 7.82 (1 H, dd, J=8 d: 2.7 Hz), 8.38 (1 H, d, J=2.7 Hz), 9.10-9.60 (,2 H, br s) .IR (Nujol): 3250, 1660, 1500, 1320, 1230 cm 1 Example 98 1-iu-Chloro-3-pyridylmethyl)amino-1-methylamino-2-methanesulfonylthiocarbamoyl-2-nitroethylene (Compound :117 ) 1o NHCffa S
CH3SO:zNHC-C=C-NH-CHZ ~~CQ
II I ~N
S NOz In 50 ml of CH.~CN was dissolved 0.50 g (0.002 mole) of 1-(6-chloro-3-pyridylmethyl)amino-1-methyl-amino-2-nitroethylene, followed by addition of 0.30 g (0.002 mole) of methanesulfonyl isothiocyanate. The mixture was stirred at room temperature for 2 hours.
'.rhe CH.,CN was distilled off and the residue was purified by silica gel column chromatography. The procedure gave 0.25 g of the title compound as yellow crystals.
m.p.: 129-131°C
NMR (DMSO-dE~) &: 2.76-3.00 (each d, MeN), 3.51 &
3.55 (each s, MeSO~), 4.36-4.70 (each d), 12.20-13.23 (each s) IR (Nujol): 3200, 1640, 1340, 1140, 920 cm 1 217a 1340gg1 Example 99 1-N-(6-Bromo-3-pyridylmethyl)amino-1-methylamino-2-nitroetylene ( Compound 118 ) OZNCH=C - NH - C:HZ ~ ~ Br N
The steps (7.), (2) and (3) of Example 13 were repeated except that 6-bromo-3-pyridylmethylamine was used in lieu of N-ethyl-N--(3-pyridylmethyl)amine, to give the following compounds in the respective steps. ._ (1) N-(6-Bromo-3-pyridylmethyl)-N'-methylthiourea (white crystals) (provided that P;tzO-THF (3:1) was used as the reaction solvent) m.p.. 117-118°C
NMR(DM50-d6)8: 2.$5 (d,J=5Hz,MeN), 4.67 (d,J=6Hz,CHZN), 7.54 (d,J=8Hz, 1H), 7.6 (br, MeNI-i), 7.69 (dd, J= 8 & 2 Hz, 1H), 7.93 (t, J=EiHz,CH2NH), 8.32 (d,J=2Hz, 1H) (2) S-Methyl-N-~6-Bromo-3-pyridylmethyl)-N'-methyl-isothiourea (yel7_ow oil) NMR(CDCe3)8: 2.40 (s,MeS), 2.93 (s,MeN=), 4.34(br,NH), 4.47 (S,CHZN), 7.42 (d,J=8Hz,lH), 7.61 (dd,J=8 & 2Hz,lH), 8.36 (d,J=2Hz,lHJ
(3) Title compound (pale brown crystals) m.p.. 184-186°C (decompn.) 217b 1 3 4 0 9 9 1 NMR(DMSO-d6)cS: 2.87 (br.MeN), 4.47 (d,J=6Hz,CH2N), 6.46 (s,=CHNOZ), 7. G1 (d,J=8Hz,lH), 7.72 (dd,J=8 & 2Hz,lH), 8.40 (d,J=2Hz,lH) IR (Nujol): 1G1~~, 1575, 1455, 1370, 1230, 1200 cm-1 Example 100 1-N-(6-Bromo-3-pyridylmethyl)amino-1-(N-formyl-N-methyl)amino-2-nitroethylene (Compound 119) and 1-[N-(6-bromo-3-pyridylme~thyl)-N-formyl]amino-1-methylamino-2-nitroethylene (Compound 120) CHO
I

/ ~ - gr OZNCH=C- NHCH~; ~~ (Compound 119) N

OZNCH=~ N - CH2- / ~ Br (Compound 120) I
CHO
The reaction. procedure of Example 96 was repeated except that 1-N-(6-bromo-3-pyridylmethyljamino-1-methylamino-2-nitroethylene was used in lieu of 1-N-(6-chloro-3-pyridylmethyl)amino-1-methylamino-2-nitro-ethylene. To the oil obtained through the purification of silica gel column. chromatography, was added a small amount of AcOEt and Et20, followed by cooling with dry ice-acetone bath to give a mixture (90:10) of the title compounds (Compou.nd 119 and Compound 120) as pale brown powder. And, the filtrate was concentrated to give a 1340991_ 217c mixture (90:60) of the title compounds (Compound 119 and Compound 120) as viscous product.
(the 90:10 mixture of Compounds 119 and 120) m.p.. 115-127"C
NMR(CDCB3)8: (Compound 119) 3.13 (s,MeN), 9.48 (d,J=6Hz,CH2N), 6.57 (s,=CHNOz), 7.53 (m,2H,pyridine -H2), $.33 (S,2H,CH0 and pyridine-H), 9.46 (br,NH) IR (Nujol): 1E~90, 1620, 1250, 1240, 10$0 cm-1 (the 90:60 mixture of Compounds 119 and 120) NMR(CDC23)8: (Compound 120) 3.01 (d,J=SHz,MeN), 4.73 (s,CH2N), 6.36 (s,=CHNOZ), 7.53 (br s,2H,pyridine-H2), 8.34 (br s,2H,C:HO and pyridine-H1), 9.35 (br,NH) IR (neat): 16Ec0, 1605, 1450, 1350, 1250, 1080 cm-1 Example 101 1-[N-(2-Ct-loro-5-thiazolylmethyl)-N-methyl)amino-1-(N-formyl-N-met:hyl)amino-2-nitroethylene (Compound 121) CHO
I

02NCH=GL- N - CHa ~S~ C2 CH;;
The reaction procedure of Example 46 was repeated except that 1-[N-(2-chloro-5-thiazolylmethyl)-N-methyl)amino-1-meth,ylamino-2-nitroethylene was used in lieu of 1-meth~~lamino-1-[N-methyl-N-(3-pyridylmethyl)-amino-2-nitroet:hylene, to give the title compound as pale yellow resinou~~ product.

217d 1340991 NMR(DMSO-d6)8: 2.92 (s,3H,MeNCH2), 2.99 (s,3H,MeNCiiO), 4.74 (br s,2H,CH;), 6.90 (s,lH,=CHNOz), 7.71 (s,lH, thiazole-H), 8.1~i (s,lH,CHO) IR (neat): 1695,. 15Ei5, 1490, 1340, 1270, 1042 cm-1 Example 102 1-[N-(2-Chloro-5-thiazolylmethyl)-N-ethyl)amino-1-(N-formyl-N-methyl)amino-2-nitroethylene (Compound 122) CHO
I

OZNCH=G~ N - CHZ - S ~ Ce The reaction procedure of Example 46 was repeated except that 1-[N--(2-c:hloro-5-thiazolylmethyl)-N-ethyl]amino-1-mei:hylamino-2-nitroethylene was used in lieu of 1-methylamino--1-[N-methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene, to give the title compound as yellow crystals.
m.p.. 99-100°C.
NMR(DMSO-d6)8: 1.15 (t,3H,CHZCH3), 2.98 (s,3H,MeN), 3.32 (q,2H,CHzCH3), 4.76 (br s,2H,thiazole-CH2), 7.02 (s,lH, =CHN02), 7.72 (s,lH,t.hiazole-H), 8.17 (s,lH,CHO) IR (Nujol): 1698, 1577, 1557. 1470, 1448, 1352, 1315, 1270, 1053 cm-1 Example 103 1-N-(2-Chlo~:o-5--thiazolylmethyl)amino-1-[N-formyl-N-methyl)amina-2-n:itroethylene (Compound 123) and 1-[N-(2-217e 1 3 4 0 9 9 1 chloro-5-thiazolylmethyl)-N-formyl]amino-1-methylamino-2-nitroethylene (Cc>mpound 124) CFiO
I
I'1 -' C H 3 N
02NCH=C- NHCH;z ~, Com ound 123 ( P ) S

OzNCH=C- N - CH2 --~~ ( Com ound 124 ) S~C~ p CHO
The reaction procedure of Example 100 was repeated except that 1-N-~2-chloro-5-thiazolylmethyl)amino-1-methylamino-2-nit:roet:hylene was used in lieu of 1-N-(6-bromo-3-pyridylmethyl.)amino-1-methylamino-2-nitroethylene, to give the title compound (Compound 124) as crystals and a mixture (70:30;1 of the title compounds (Compound 123 and Compound 124) as viscous product.
(Compound 124) m.p.. 125-126°C
NMR(CDCe3)8: 3.01 (3H,d,J=6.0 Hz), 4.82 (2H,s), 6.38 (lH,s), 7.49 (lH,,s), 8.30 (lH,s), 9.0-9.6 (lH,br) IR (Nujol): 3220, 1fi75, 1620, 1245, 1100, 1050 cm-1 (the 70:30 mixture of: Compounds 123 and 124) NMR(CDCe3)8: (Compound 123) 3.16 (3H,s), 4.63 (2H,d,J=5.7 Fiz), 6.57 (lH,s), 7.49 (lH,s), 8.35 (lH,s), 9.1-9.6 (lH,br) IR (neat): 3220, 1680, 1605, 1480, 1250, 1045 cm-1 217f 1 3 4 0 9 9 1 Example 104 1-[N-(5-Bronco-3-pyridylmethyl)-N-methyl]amino-1-(N-formyl-N-methyl)a.mino-2-nitroethylene (Compound 125) CHO

02NCH=C- N - CH2 -~~~ -- Br The reaction, procedure of Example 46 was repeated except that 1-[N-~(6-bromo-3-pyridylmethyl)-N-methylJamino-1-metylamino-2-nitroethylene was used in lieu of 1-methylamino-1-[N-methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene, to give the title compound as yellow resinous product.
(provided that THF-DMF was used as the reaction solvent) NMR(DMSO-ds)8: 2.93 (s,3H), 3.02 (s,3H), 4.3-4.9 (m,2H), G.87 (s,=CHN02), 7.68 (br s,2H), 8.23 (s,CHO), 8.3-8.5 (m,lH) IR (neat): 1685 cm-1 Example 105 1-[N-(6-Bromo-3-pyridylmethyl)-N-ethylJamino-1-(N-formyl-N-methyl)a~mino-2-nitroethylene (Compound 126) 217g 34p gg ~
CHO

OZNCH=C- N - CIi2 --t~~- Br The reaction procedure of Example 46 was repeated except that 1-[N--(6-bromo-3-pyridylmethyl)-N-ethyl]amino-1-methylamino-2-nitroethylene was used in lieu of 1-methylamino-1-[N--methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene, to give the title compound as yellow crystals.
m.p.. 105-108°C
NMR(DMSO-d6)8: 1.13 (t,J=7.2 Hz,3H), 3.00 (s,3H), 3.1-3.7 (m,2H), 4.3-4.9 (m,2H), 6.97 (s,=CHN02), 7.5-7.9 (m,2H), 8.21 (s,CHO), 8.~~8 (br s,lH) IR (Nujol) : 170'_ cm-1 Example 106 1-N-(6-Bromo-3-pyridylmethyl)amino-1-dimethylamino-2-nitroethylene (Cc>mpou.nd 127) I

I
02NCH=C- NHCH2 -~~~~--Br '- N
The steps (1), (2), (3) and (4) of Example 88 were repeated except that 6-bromo-3-pyridylmethylamine was used 217h 1 3 4 0 g g 1 in lieu of 6-chloro-3-pyridylmethylamine, to give the following compounds in the respective steps.
(1) (6-Bromo-3-F~yridyl)methyl isothiocyanate (yellow oil) (provided that after completion of dropwise addition of ethyl chloroca~rbonate, the mixture was stirred at 50°C
for 4 hours) NMR(CDCQ3)8: 4.73 (s,2H), 7.43-7.70 (m,2H), 8.35 (br s,lH) (2) N-(6-Bromo-?'-pyridylmethyl)-N'-dimethylthiourea (white crystals) (provided that the product was purified by silica gel column chromatography using EtOH-CHCB3 (1:10) as the eluent) m.p.. 124-125°C
NMR(CDCQ3)8: 3.27 (s,6H), 4.85 (d,J=5 Hz,2H), 6.32 (br t,J=5Hz,lH), 7.40 (d,J=8Hz,lH), 7.66 (dd,J=8 & 2 Hz,lH), 8.21 (d,J=2Hz,lH) (3) S-Methyl-N-(6-bromo-3-pyridylmethyl)-N'-dimethyl-isothiourea (yell.ow oil) NMR(CDCe3)8: 2.30 (s,3H), 3.00 (s,6H), 4.66 (s,2H), 7.38 (d,J=SHz,lH), 7.~~5 (dd,J=8 & 2 Hz,lH), 8.35 (d,J=2 Hz,lH) (4) Title compound (pale yellow crystals) (provided that the reaction was conducted for 20 hours, and the product was purified by silica gel column chromatography and recrystallized from CH3CN.
m.p.. 158-159°C

21~i 1 3 4 0 9 9 1 NMR(CDCeg)cS: 2.92 (s,6H), 4.45 (d,J=6 Hz,2H), 6.50 (s,lH), 7.48 (d,J=8 Hz,lH), 7.60 (dd,J=8 & 2 Hz,lH), 8.33 (d,J=2 Hz,lH), 9.70 (br,lH) IR (Nujol): 3100, 1580, 1550, 1440, 1300, 1260, 1040 cm-1 Example 107 1-[N-(6-Bromo-3-;pyridylmethyl)-N-formyl]amino-1 dimethylamino-2-nitroethylene (Compound 128) I

02NCH=~ N - CHz -~~ ~Br CHO
The reaction procedure of Example 46 was repeated except that 1-N-(6-bromo-3-pyridylmethyl)amino-1-dimethylamino-2-n.itroc~thylene was used in lieu of 1-methylamino-1-[N-methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene, to give the title compound as pale yellow crystals.
(provided that the reaction was conducted in DMF) m.p.. y6-y-I"C; _ NMR(DMSO-d6)S: 2.92 (s,6H), 9.30-5.06 (m,2H), 6.73 (s,lH), 7.50-7.80 (m,2H) 8.23 (s,lH), 8.35 (br s,lH) IR (Nujol): 1700, 1565, 1490, 1345, 1270, 1080 cm-1 Example 108 1-Amino-1-[N-~(6-bromo-3-pyridylmethyl)-N-methyl]amino-2-nit:roethylene (Compound 129) 217j 02NCH=C- N - CHZ -f~~ -Br N

The steps (1) and (2) ofExample 40 were repeated except that N-(6-bromo-3-pyridylmethyl)-N-methylamine was used in lieu of 1;I-(6-chloro-3-pyridylmethyl)-N-ethylamine, to give the following compounds in the respective steps.
(1) 1-[N-(6-Brorr~o-3-pyridylmethyl)-N-methyl]amino-1-methylthio-2-nitroethylene (yellow oil) (provided that the reaction was conducted for 3.5 hours) NMR(CDC~3)S: 2.47 (s,3H), 3.03 (s,3H), 4.73 (s,2H), 6.76 (s,lH), 7.36-7.6a~ (m,2H), 8.30 (br s,lH) (2) Title compound (white crystals) (provided that the reaction was conducted in MeOH for 1 hour, and the precipitated crystals were collected by filtration) m.p.. 206-207°C
NMR(DMSO-d6)S: 3.03 (s,3H), 4.63 (s,2H), 6.60 (s,lH), 7.43-7.80 (m,2H), 8.30 (br s,lH), 8.88 (br,2H) IR (Nujol): 3260, 3140, 1620, 1575, 1420, 1290, 1220 cm-1 Example 109 1-N-(2-Chloro-5-thiazolylmethyl)amino-1-dimethylamino-2-nitro~ethylene (Compound 104) 217k The steps (l), (2), (3) and (4) of Example 88 were repeated except that 2-chloro-5-thiazolylmethylamine was used in lieu of E~-chloro-3-pyridylmethylamine, to give the following compounds in the respective steps.
(1) (2-Chloro-5-~thiazolyl)methyl isothiocyanate (provided that after completion of dropwise addition of ethyl chloroc~~rbonate, the mixture was stirred at 80°C
for 3 hours) NMR(CDCe3)8: 4.82 (2H,s), 7.50 (lH,s) (2) N-(2-Chloro-~5-th.iazolylmethyl)-N'-dimethylthiourea (yellow crystals) m.p.. 125-127°C
NMR(CDCe3)cS: 3.2$ (6H,S), 4.98 (2H,d,J=6.0 Hz), 5.6-6.1 (lFi,br), 7.40 (lH,s) (3) S-Methyl-N-(2-chloro-5-thiazolylmethyl)-N-dimethylisothiourea (yellow oil) NMR(CDCe3)8: 2.31 (3H,s), 2.99 (6H,s), 4.79 (2H,s), 7.36 (lH,s) (4) Title compound (pale grey crystals) (provided that the reaction was conducted for 37°C) This product: was in agreement with Compound 104 obtained in Example 86 in melting point, NMR and IR
spectra and TLC Ftf .
Example 110 1-[N-(2-Chloro-5-thiazolylmethyl)-N-formyl]amino-1-dimethylamino-2-nitroethylene (Compound 130) OzNCH=CL- N - f~H2 -CHO
The reaction procedure of Example 46 was repeated except that 1-N-(2-chloro-5-thiazolylmethyl)amino-1-dimethylamino-2-nitroethylene was used in lieu of 1-methylamino-1-[N-methyl-N-(3-pyridylmethyl)]amino-2-nitroethylene, to give the title compound as white crystals. The NMR value of this product indicated this product was a mixture (6:1) of isomers.
m.p.. 139-142°C
NMR(CDCe3)8: 2.92 & :?.99 (total 6H, each s), 4.83 (2H,s), 6.61 & 6.34 (total lH,s), 7.45 (lH,s), 8.19 & 8.46 (total 1H, each s) IR (Nujol): 1680, 1410, 1355, 1270, 1050 cm-1 Example 111 1-[N-(6-Chloro-3-pyridylmethyl)-N-(2,2,2-trifluoroethyl)]amino-1-methylamino-2-nitroethylene ( Compound 13:1 ) OzNCH=C- N - CH2 -~~~~--Ce ~N
CHZCF;;
In 35 me of toluene, 3,79 g (0.0169 mole) of N-(6-chloro-3-pyridylmethy:l)-N-(2,2,2-trifluoroethyl)amine and 217m 1 3 4 0 ~ 9 1 2.46 g of methyl isot:hiocyanate were stirred for 18 hours under reflux. The toluene was distilled off, and the residue was dissolved in 120 mB of AcOEt, washed with 1N
HCe (two times) and aqueous sodium chloride solution in this order and dried over MgS04. The AcOEt was distilled off to give oil. To this oily product were added Et20 and hexane, followed by cooling to give crystals. After addition of hexane to the mixture, the crystals were collected by filtration and dried to give 2.78 g of N-(6-chloro-3-pyridylmethyl)-N-(2,2,2-trifluoroethyl)-N'-methylthiourea a~~ white crystals.
m.p.. 98-100°C
NMR(CDCe3)8: 3.13 (d,J=5 Hz,MeN), 4.37 (q,J=9 Hz,CF3CH2), 5.09 (s,pyridine--CHz), 6.07 (br,NH), 7.34 (d,J=8 Hz,lH), 7.67 (dd,J=8 & 2 Hz,lH), 8.26 (d,J=2 Hz,lH) The steps (2) and (3) of Example 13 were repeated except that N-(6-~chloro-3-pyridylmethyl)-N-(2,2,2-trifluoroethyl)-ri'-methylthiourea was used in lieu of N-methyl-N'-ethyl-rl'-(3-pyridylmethyl)thiourea, to give the following compounds in the respective steps.
(2) S-Methyl-N-(6-chloro-3-pyridylmethyl)-N-(2,2,2-trifluoroethyl)-ri'-methylisothiourea (pale brown oil) NMR(CDC23)8: 2.28 (s,MeS), 3.24 (s,MeN), 4.07 (q,J=9 Hz,CF3CHZ), 4.66 (s,p;yridine-CHZ), 7.28 (d,J=8 Hz,lH), 7.54 (dd,J=8 & 2 Hz,lH), 8.26 (d,J=2 Hz,lH) (3) Title compound 217n 1 3 4 Q 9 9 1 (provided that t:he reaction was conducted for 9G
hours) m.p.. 110-111°C
NMR(CDCe3)cS: 3.12 (d,J=5 Hz,MeN), 3.60 (q,J=9 Hz,CF3CH2), 4.42 (s,pyridine--CHz), 6.51 (s,=CHN02), 7.39 (d,J=8 Hz,lH), 7.60 (dd,J=8 & 2 Hz,lH), 8.33 (d,J=2 Hz,lH), 9.50 (br,NH) IR (Nujol): 159~i, 1450, 1345, 1260, 1235, 1140, 1100 cm-1 ~ 34099 1 As the object compound (I) of the invention, the following compounds can be synthesized.
(1) 1-[N-(6-Chloro-3-pyridylmethyl)-N-formyl]amino-1-(N-formyl-N-methyl)amino-2-nitroethylene (2) 1-[N-(6-Chloro-3-pyridylmethyl)-N-ethyl]amino-1-dimethylamino-2-nitroethylene (3) 1-[N-6-Chloro-3-pyridylmethyl)-N-(2-fluoroethyl)]amino-1-methylamino-2-nitroethylene (4) 1-[N-(6-Chloro-3-pyridylmethyl)-N-(2-fluoroethyl))amino-1-dimethylamino-2-nit:roethylene (5) ' 1-[N-(2-Chloro-5-thiazolylmethyl)-N-formyl)amino-1-(N-formyl-N-methyl)am.ino-2-nitroethylene (6) 1-[N-(6-Bromo-3--pyridylmethyl)-N-(2-fluoroethyl))amino-1-methylamino-2-n:itroE~thylene~.
(7) 1-[N-(6-Drorno-3-pyridylmethyl)-N-(2-fluoroethyl)]amino-1-dimethylamino-2--nitroethylene (d) 1-[N-(2-Chloro-5-tt~iazolylmethyl)-N-(2-fluoroethyl))amino-1-methylamino-2-ni.troethylene (9) 1-(N-(2-Chloro-5-thiazolylmethyl)-N-methyl]amino-1-dimethylamino-Z-ni.troethylene (10) 1-[N-(2-Chloro-5-thiazolylmethyl)-N-ethylJamino-1-dimethylamino-2-ni.troethylene (11) 1-(2-Bromo-5-thiazolylmethyl)amino-1-methylamino-2-nitroethylene (12) 1-[N-(2-Bromo-5-thiazolylmethyl)-N-formyl]amino-1-methylamino-2-nitroethylene (13) 1-[N-(2-Bromo-5-thiazolylmethyl)-N-methyl]amino-1-methylamino-2-nitroethylene (14) 1-[N-(2-Bro:mo-5-thiazolylmethyl)-N-ethyl]amino-1-methylamino-2-nitroethylene (15) 1-(2-Bromo-5-th.iazolylmethyl)amino-1-~I-formyl-N-methyl~amino-2-nitroethylene (16) 1-[N-(2-Bromo-5-thiazolylmethyl)-N-formyl]amino-1-(N-formyl-N-methyl)amino-2-nitroethylene (17) 1-[N-(2-Bromo-5--thiazolylmethyl)-N-methyl]amino-1-(N-formyl-N-methyl)amino-2-nitroethylene (18) 1-[N-(2-Brorno-5--thiazolylmethyl)-N-ethyl]amino-1-(N-formyl-N-methyl)amino-2-nitroethylene (19) 1-[N-(2-Chloro-.'i-thiazolylmethyl)-N-(2-fluoroethyll]amino-1-dimethylamino-2--niti:oethylene (20) 1-[N-(2-Bromo-5-thiazolylmethyl)-N-formyl]amino-1-dimethylamino-2-n:itroethylene (21) 1-(N-(2-Bromo-5-~thiazolylmethyl)-N-methyl]amino-1-dimethylamino-2-n:itroethylene (22) 1-[N-(2-Bromo-5-thiazolylmethyl)-N-ethyl]amino-1-dime thylamino-2-n~~ t roe~thylene (23) 1-(N-Chlorom.ethyl-N-(6-chloro-3-pyridylmethyl)]amino-1-methylamino-2-nitroethylene (24) 1-[N-(6-Brorno-3-pyridylmethyl)-N-chloromethyl]amino-1-methylamino-2-ni.troethylene (25) 1-[N-Chloromethyl-N-(2-chloro-5-thiazolylmethyl))amino-1-methylamino-2-nitroethylene (26) 1-[N-(6-Bromo-3-pyridylmethyl)-N-formyl]amino-1-(N-formyl-N-methyl)amino-2-nitroethylene (27) 1-[N-(2-Bromo-5-thiazolylmethyl)-N-(2-fluoroethyl)]amino-1-methylamino-2-nitroethylene (28) 1-[N-(2-Bromo-5-thiazolylmethyl)-N-(2-fluoroethyl)]
amino-1-dimethylamino-2-nitroethylene (29) 1-[N-(2-Chlo.ro-5-thiazolylmethyl)-N-(2,2,2-trifluoroethyl)]amino-1-methylamino-2-nitroethylene (30) 1-[N-(6-Bromo-3-pyridylmethyl)-N-(2,2,2-trifluorornethyl)]amino-1-dimethylamino-2-nitroethylene (38) 1-[N-(6-Flnoro-3-pyridylmethyl)-N-ethylJamino-1-(N-formyl-N-methyl)amin~o-2-nitroethylene (39) 1-Dimethyl~~mino-1-(6-fluoro-3-pyridylmethyl)amino-2-nitroethylene (40) 1-Dimethyl~~mina-1-[N-(6-fluoro-3-pyridylmethyl)-N-formyl]amino-2-nitroethylene (41) 1-Dimethylamino-1-[N-(6-fluoro-3-pyridylmethyl)-N-methyl]amino-2-nitroethylene (42) 1-Dimethyl~~mina-1-[N-(6-fluoro-3-pyridylmethyl)-N-ethyl]amino-2-nitroethylene Examp:Le~ (Emulsifiable concentrate) An emulsifiable concentrate was manufactured by mixing the following ingredients..
Compound 17 20 weight %
Xylene 75 weight %
Polyoxyethylene glycol ether (Nonipol 85'x) 5 weight %
Example 113 (Wettable powder) A wettable ;powder was manufactured by mixing the following ingredients.
Compound 12 20 weight %
Sodium ligninsu:lfonate 5 weight %
Polyoxyethy.lene glycol ether (Nonipol 85'a) 5 weight %
White carbon 30 weight %
Clay 40 weight %

Example 114 ( Dust ) A dust was manufactured by mixing the following ingredients.
Compound 19 3 weight White carbon 3 weight Clay 94 weight Example 115 (Granules) A granular product was prepared by admixing and granulating the following components.
Compound 25 2 weight Sodium ligninsulfonate 5 weight Clay 93 weight

Claims

1. An .alpha.-unsaturated amine of the formula:
(wherein:
one of X1 and X2 is an electron-attracting group and the other is a hydrogen atom or an electron-attracting group, wherein the said electron-attracting group is cyano, nitro, C1-9 alkoxy carbonyl, carboxyl, C6-10 aryloxy-carbonyl, heterocycleoxycarbonyl, C1-4 alkylsulfonyl which may be substituted with halogen, amino-sulfonyl, di-C1-4 alkoxyphosphoryl, C1-4 alkanoyl which may be substituted with halogen, C1-4 alkylsulfonylthiocarbamoyl, carbamoyl or halogen, or X1 and X2 together with the carbon atom to which they are attached form a ring of the formula:

R1 is a group of the formula:

[in which:
R3 is hydrogen, C1-20 alkyl, C6-10 aryl, C7-9 aralkyl, heterocycle, C1-4 alkanoyl, C6-10 aryl-carbonyl, C1-4 alkoxy-carbonyl, C6-10 aryloxy-carbonyl, heterocycleoxycarbonyl, C6-10 arylsulfonyl, C1-4 alkylsulfonyl, di-C1-4 alkoxyphosphoryl, C1-4 alkoxy, hydroxy, amino, di-C1-4 alkylamino, C1-4 alkanoylamino, C1-4 alkoxycarbonylamino, C1-4 alkylsulfonylamino, di-C1-4 alkoxyphosphorylamino, C7-9 aralkyloxy or C1-4 alkoxy-carbonyl-C1-4 alkyl; and R4 is hydrogen, C1-20 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C3-6 cycloalkenyl or C2-6 alkynyl, wherein each of the radicals defined for R4 except for hydrogen may optionally be substituted by 1 to 3 substituents selected from the group consisting of hydroxy, C1-4 alkoxy, halogen, di-C1-4 alkylamino, C1-4 alkylthio, C1-3alkanoylamino, C1-4 alkylsulfonylamino, tri-C1-4 alkylsilyl, pyridyl and thiazolyl, and each of the pyridyl and thiazolyl may further be substituted by halogen, or R3 and R4 together with the adjacent nitrogen atom constitute a cyclic amino group of the formula:
R2 is (1) hydrogen, (2) a group attached through a carbon atom selected from the class consisting of C1-4alkanoyl, C1-20 alkyl, C2-6alkenyl, C3-6cycloalkyl, C6-10aryl, C7-9aralkyl and 3- or 4-pyridyl, the said group attached through a carbon atom being optionally substituted by 1 to 3 substituents selected from the class consisting of C1-4alkylthio, C1-4alkoxy, mono- or di-C1-4alkylamino, C1-4alkoxy-carbonyl, C1-4alkylsulfonyl, halogen and C1-4 alkanoyl, (3) a group attached through an oxygen atom selected from the class consisting of C1-4 alkoxy, C3-6 cycloalkoxy, C2-4 alkenyloxy, C3-6 cycloalkenyloxy, ethynyloxy, C6-10 aryloxy, thienyloxy and hydroxy, the said group attached through an oxygen atom being optionally subsituted by 1 to 3 substituents selected from the class consisting of halogen and phenyl, or (4) a group attached through a nitrogen atom of the formula:
~
(wherein R3 and R4 have the meanings given above);
n is an integer of 0, 1 or 2;
A° is heterocycle;
wherein the heterocycle in the said heterocycle-oxycarbonyl for X1 and X2, the said heterocycle for R3, the heterocycle in the said heterocycleoxycarbonyl for R3, and the said heterocycle for A° are a member selected from the class consisting of thienyl, furyl, pyrrolyl, pyridyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, N-oxidopyridyl, pyrimidinyl, N-oxidopyrimidinyl, pyridazinyl, pyrazinyl, N-oxidopyridazinyl, benzofuryl, benzothiazolyl, benzoxazolyl, triazinyl, oxotriazinyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxozinyl, morpholinyl, 1,4-thiazinyl, 1,3-thiazinyl, piperazinyl, benzimidazolyl, quinolyl, isoquinolyl, innolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthyridinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl and phenoxazinyl, the said heterocycle being optionally substituted by 1 to 5 substituents selected from the group consisting of:

(i) C1-4alkyl, (ii) C3-6cycloalkyl, (iii) phenyl or naphthyl, (iv) C1-4 alkoxy, (v) C3-6cycloalkyloxy, (vi) phenoxy or naphthyloxy, (vii) C7-12phenylalkyloxy, (viii) C1-4alkylthio, (ix) C3-6cycloalkylthio, (x) phenylthio or naphthylthio, (xi) C7-12phenylalkylthio, (xii) mono-C1-4alkylamino, (xiii) di-C1-4alkylamino, (xiv) C3-6cycloalkylamino, (xv) anilino, (xvi) C7-12phenylalkylamino, (xvii) halogen, (xviii) C1-4alkoxycarbonyl, (xix) phenoxycarbonyl, (xx) C3-6cycloalkyloxycarbonyl, (xxi) C7-12phenylalkyloxycarbonyl, (xxii) C1-5alkanoyl, (xxiii) C1-15alkanoyloxy, (xxiv) carbamoyl, N-methylcarbamoyl, N,N-dimethyl-carbamoyl, N-ethylcarbamoyl, N,N-diethylcarbamoyl, N-phenyl-carbomoyl, pyrrolidinocarbamoyl, piperidinocarbamoyl, piperazinocarbamoyl, morpholinocarbamoyl or N-benzylcarbamoyl, (xxv) N-methylcarbamoyloxy, N,N-dimethylcarbamoyloxy, N-ethylcarbamoyloxy, N-benzylcarbamoyloxy, N,N-dibenzylcarbamoyloxy or N-phenylcarbamoyloxy, (xxvi) C1-4 alkonoylamino, (xxvii) benzamido, (xxviii) C1-4 alkoxycarbonylamino, (xxix) C7-12 phenylalkyloxycarbonylamino, (xxx) Methanesulfonylamino, ethanesulfonylamino, butanesulfonylamino, benzenesulfonylamino, toluenesulfonylamino, naphthalenesulfonylamino, trifluoromethanesulfonylamino, 2-chloroethanesulfonylamino or

2,2,2-trifluoromethanesulfonylamino, (xxxi) pyrrolidinyl, pyrrolyl, pyrazolyl, imidazolyl, furyl, thienyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, piperidinyl, pyridyl, piperazinyl, pyrimidinyl, pyranyl, tetrahydropyranyl, tetrahydrofuryl, indolyl, quinolyl, 1,3,4-oxadiazolyl, thieno[2,3-d]pyridyl, 1,2,3-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, tetrazolyl, 4,5-dihydro-1,3-dioxazolyl, tetrazolo[1,5-b]-pyridazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl or benzothienyl, -227a-(xxxii) heterocyclethio, heterocycleoxy, heterocycleamino or heterocyclecarbonylamino group which is derived by attachment of any of the heterocyclic groups (xxxi) defined above to the S, O, N atom or a carbonylamino group, (xxxiii) di-C1-4 alkylphosphinothioylamino, (xxxiv) methoxyimino, ethoxyimino, 2-fluoroethoxyimino, carboxymethoxyimino, 1-carboxy-1-methylethoxyimino, 2,2,2-trichloroethoxycarbonylmethoxyimino, 1-(2,2,2-trichloroethoxy-carbonyl)-1-methylethoxyimino, (2-aminothiazol-4-yl)methoxyimino or (1H-imidazol-4-yl)methoxyimino, (xxxv) C1-4alkylsulfonyloxy, (xxxvi) benzenesulfonyloxy or toluenesulfonyloxy, (xxxvii) diphenylphosphinothioylamino, (xxxviii) thiocarbamoylthio, N-methylthiocarbamoylthio, N,N-dimethylthiocarbamoylthio, N-ethylthiocarbamoylthio, N-benzylthiocarbamoylthio, N,N-dibenzylthiocarbamoylthio or N-phenylthio-carbamoylthio, (xxxix) trimethylsilyloxy, t-butyldimethylsilyloxy, t-butyldiphenylsilyloxy or dimethylphenylsilyloxy, (xL) trimethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl or dimethylphenylsilyl, (xLi) C1-4alkylsulfinyl, (xLii) phenylsulfinyl or naphthylsulfinyl, (xLiii) C1-4alkylsulfonyl, (xLiv) benzenesulfonyl or toluenesulfonyl, (xLv) C1-4alkoxy-carbonyloxy, (xLvi) halo-C1-4alkyl, (xLvii) halo-C1-4alkoxy, halo-C1-4alkylthio, halo-C1-4alkylsulfinyl or halo-C1-4alkylsulfonyl, (xLviii) cyano, nitro, hydroxyl, carboxyl, sulfo, phosphono, (xLix) C1-4alkyloxysulfonyl, (L) phenoxysulfonyl or tolyloxysulfonyl, (Li) C7-12 phenylalkyloxysulfonyl, and (Lii) di-C1-4 alkyloxyphosphoryl group, with the proviso that:
(a) when R2 is a hydrogen atom, then R1 is a group of the formula:
[in which R3a is hydrogen, C1-4 alkyl, C7-9 aralkyl or C1-4 alkanoyl and R4a is hydrogen, C1-4 alkyl, C1-4 alkoxy-C1-4 alkyl, (di-C1-4 alkylamino)-C1-4 alkyl, tri-C1-4 alkylsilyl-C1-4 alkyl, C2-4 alkenyl or pyridyl- or thiazolyl- C1-2 alkyl wherein the pyridyl or thiazolyl moiety may be substituted by halogen or R3a and R4a taken together with the adjacent nitrogen atom constitute pyrrolidino] and A° is pyrazinyl or thiazolyl, each of which may be substituted with halogen, C1-4 alkyl, C1-4 alkylthio, or C1-4 alkoxy or A° is pyridyl substituted with halogen, C1-4 alkyl, C1-4 alkylthio or C1-4 alkoxy, (b) when one of X1 and X2 is nitro and the other is hydrogen, R2 is hydrogen and R3a is hydrogen, then R4a is hydrogen, (di-C1-4 alkylamino)-C1-4 alkyl, tri-C1-4 alkylsilyl-C1-4 alkyl or pyridyl- or thiazolyl-C1-2 alkyl wherein the pyridyl or thiazolyl moiety may be substituted by halogen, and (c) when one of X1 and X2 is nitro and the other is hydrogen, R2 is hydrogen and R4a is hydrogen, then R3a is hydrogen, C7-9 aralkyl or C1-4 alkanoyl, or a salt thereof.

229a 2. A compound or salt as claimed in claim 1, wherein R2 is hydrogen, R1 is a group of the formula:
(wherein R3a and R4a are as defined in claim 1) and A0 is heterocycle selected from the class consisting of pyridyl, pyrazinyl and thiazolyl, the said heterocycle mentioned just above for A0 being substituted with halogen, C1-4 alkyl, C1-4-alkylthio or C1-4 alkoxy.

3. A compound or salt as claimed in claim 1, wherein R2 is other than hydrogen.

4. A compound as claimed in claim 1, wherein:
X1 is nitro;
X2 is hydrogen, C1-2alkoxycarbonyl or C1-2alkylsulfonyl-thiocarbamoyl;
R1 is amino, mono- or di-C1-4alkylamino, halo-C1-4alkylamino, N-C1-4alkyl-N-C1-2alkanoylamino, N-halo-C1-4alkyl-N-C1-2alkanoylamino or C1-2alkanoylamino;
R2 is hydrogen, C1-2alkoxy, di-C1-2alkylamino, C1-4alkyl, halo-C1-4alkyl or C1-2alkanoyl;
n is 0 or 1.;
A° is 2- or 3-thienyl, 2- or 3-furyl, 2- or 3-pyrrolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or

5-isoxazolyl, 3-, 9- or 5-isothiazolyl, 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1H- or 2H-tetrazolyl, N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, N-oxido-3- or 4-pyridazinyl, benzofuryl, benzothiazolyl, benzoxazolyl, triazinyl, oxotriazinyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, morpholinyl, 1,4-thiazinyl, 1,3-thiazinyl, piperazinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthyridinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl or phenoxyazinyl, each of which may optionally be substituted with halogen, C1-4 alkyl, halo-C1-4 alkyl, C1-4 alkoxy, halo-C1-4 alkoxy, C1-4 alkylthio or halo-C1-4 alkylthio or a salt thereof.

5. A compound as claimed in claim 1, wherein:
X1 is nitro;
X2 is hydrogen or C1-2 alkylsulfonylthiocarbamoyl;
R1 is amino, mono- or di-C1-2 alkyl amino, halo-C1-2 alkylamino, N-C1-2 alkyl-N-C1-2 alkanoylamino, N-halo-C1-2 alkyl-N-C1-2 alkanoylamino or C1-2 alkanoylamino;
R2 is hydrogen, C1-2 alkoxy, di-C1-2 alkyl amino, C1-4 alkyl, halo-C1-4 alkyl or C1-2 alkanoyl;
n is 1; and A° is pyridyl, pyrazinyl or thiazolyl, each of which may optionally be substituted with halogen, C1-4 alkyl, halo-C1-4 alkyl, C1-4 alkoxy, halo-C1-4 alkoxy, C1-4 alkylthio or halo-C1-4 alkylthio or a salt thereof.

6. A compound as claimed in claim 1, of the formula (wherein:

X2a is hydrogen, C1-4 alkoxycarbonyl or C1-4 alkyl-sulfonylthiocarbamoyl;
R2c is hydrogen, C1-3 alkanoyl, C1-4 alkyl, mono- or di-C1-4 alkoxy-C1-4 alkyl, C7-9 aralkyl, mono- or di-C1-4 alkylamino or C1-4 alkoxy;
A° is 3- or 4-pyridyl, pyrazinyl or 4- or 5-thiazolyl, each of which may optionally be substituted with halogen, C1-4 alkyl or C1-4 alkoxy;
n is 1; and R3a and R4a are as defined in claim 1), or a salt thereof.

7. A compound as claimed in claim 1, which is a compound of the formula:
(wherein:
X2a is hydrogen, C1-4 alkoxycarbonyl or C1-4 alkyl-sulfonylthoicarbamoyl;

R1d is amino, mono- or di-C1-4 alkyl amino, N-C1-4 alkyl-N-C1-3 alkanoylamino, C7-9 aralkylamino, halogenothiazolyl-C1-2 alkylamino or C1-4 alkoxy-C1-2 alkylamino;

-232a-R2c is hydrogen, C1-3 alkanoyl, C1-4 alkyl, mono- or di-C1-4 alkoxy-C1-4 alkyl, C7-9 aralkyl, mono- or di-C1-4 alkylamino or C1-4 alkoxy;
n is 0, 1 or 2; and R1f is amino, methylamino, dimethylamino or N-methyl-N-formylamino;
R2d is a hydrogen atom, formyl or C1-2 alkyl; and A e is a group of the formula:
~
[wherein Hal is a halogen atom]), or a salt thereof.

10. A compound a.s claimed in claim 1, which is a compound of the formula:
(wherein:
R1e is amino, mono- or di-C1-2 alkylamino or N-C1-2 alkyl-N-formylamino;

R2e is C1-2 alkyl or formyl; and Hal is a halogen atom), or a salt thereof.

11. A compound as claimed in claim 1 of the formula:

-234a-(wherein A is pyridyl which may be substituted by halogen;
R2 is hydrogen or C1-4alkyl;
R3 is hydrogen, C1-5alkyl or benzyl;
R4 is hydrogen, C1-5alkyl or C3-7cycloalkyl or R3 and R4, taken together with the adjacent nitrogen atom, constitute a pyrrolidinyl group or an N'-methylpiperazinyl group or a salt thereof.

12. A compound or salt as claimed in claim 1, wherein the heterocycle is selected from the following group and being optionally substituted as defined in claim 1, the group consisting of 2- or 3-thienyl, 2- or 3-furyl, 2- or 3- pyrrolyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4- or 5-isothiazolyl, 3- or 5-(1,2,4-oxadiaxolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1H- or 2H-tetrazolyl, N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, N-oxido-3- or 4-pyridazinyl, benzofuryl, benzothiazolyl, benzoxazolyl, triazinyl, oxotriazinyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, morpholinyl, 1,4-thiazinyl, 1,3-thiazinyl, piperazinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthyridinyl, purinyl, pteridinyl, -234b-dibenzofuranyl,carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl and phenoxazinyl.

13. A compound as claimed in claim 1, which is 1-[N-(6-chloro-3-pyridylmethyl)-N-methyl]amino-1-methylamino-2-nitroethylene or a salt thereof.

14. A compound as claimed in claim 1, which is 1-(6-chloro-3-pyridylmethyl)amino-1-dimethylamino-2-nitroethylene or a salt thereof.

15. A compound as claimed in claim 1, which is 1-[N-(6-chloro-3-pyridylmethyl)-N-ethyl]amino-1-methylamino-2-nitroethylene or a salt thereof.

16. An insecticidal or miticidal composition which comprises an insecticidal or miticidal effective amount of at least one of the .alpha.-unsaturated amines as claimed in claim 1 or a salt thereof, together with a suitable carrier or carriers.

17. An insecticidal or miticidal composition which comprises an insecticidal or miticidal effective amount of a compound of the formula:

-234c-(wherein A is pyridyl which may be substituted by halogen;
R2 is hydrogen or C1-4alkyl;
R3 is hydrogen, C1-5alkyl or benzyl;
R4 is hydrogen, C1-5alkyl or C3-7cycloalkyl or R3 and R4 together with the adjacent nitrogen atom to which they are attached, constitute a pyrrolidinyl group or a 4-methyl piperazinyl group) or a salt therof, and a suitable carrier or carriers.

18. A process for preparing an .alpha.-unsaturated amine of the formula:
(wherein the symbols are as defined in claim 1) or a salt thereof, which comprises (1) reacting a compound of the formula:
or a salt thereof with a compound of the formula:

or a salt thereof, or (2) reacting a compound of the formula or a salt thereof with a compound of the formula:
or a salt thereof, or (3) reacting a compound of the formula:
or 02N - CH2C (Hal) 3 (i) with a compound of the formula:
or a salt thereof, and then reacting the resulting product with a compound of the formula:

or a salt thereof, or (ii) with a compound of the formula:

or a salt thereof, and then reacting the resulting product with a compound of the formula:
or a salt thereof, or (4) reacting a compound of the formula:
or a salt thereof with a compound of the formula:

or a salt thereof, or (5) reacting a compound of the formula:
or a salt thereof with a compound of the formula:
A o - C n H2n - Hal or a salt thereof, or (6) subjecting a compound of the formula:
or a salt thereof to hydrolysis reaction and then to decarboxylation reaction, or (7) subjecting a compound of the formula:

or a salt thereof to alkylation, acylation, alkoxycarbonylation, sulfonylation or phosphorylation, wherein in each of the above formulas, R5 is a C1-4alkyl or C7-9aralkyl;
when W1 is W2 is R1 and when W1 is R1, W2 is Y is a hydrogen atom or an alkali metal;

Hal is a halogen atom;
X3 is the electron-attracting group as defined in claim 1;
R6 is a group of the formula: -NHR3 or -NHR4;
and X1, X2, R1, R2, R3, R4, n and A 0 are as defined in claim 1.

19. A method of combatting undesirable insects or mites, which comprises applying an insecticidal or miticidal effective amount of the compound of the formula [I o] defined in any one of claims 1 to 12 or a salt thereof to the said insects or mites or their habitat.
20. A method of claim 19, wherein the compound or salt is applied as a composition of the compound or salt with a suitable carrier or carriers.
21. A method of combatting undesirable insects or mites, which comprises applying an insecticidal or miticidal effective amount of the compound of the formula [I o] defined in any one of claims 13 to 15 or a salt thereof.
22. A method of claim 21, wherein the compound or salt is applied as a composition of the compound or salt with a suitable carrier or carriers.

23. An insecticidal or miticidal composition which comprises a suitable carrier of carriers and an insecticidal or miticidal effective amount of an .alpha.-unsaturated amine of the formula:
(wherein:
one of X1 and X2 is an electron-attracting group and the other is a hydrogen atom or an electron-attracting group, wherein the said electron-attracting group is cyano, nitro, C1-4 alkoxy carbonyl, carboxyl, C6-10 aryloxy-carbonyl, heterocycleoxycarbonyl, C1-4 alkylsulfonyl which may be substituted with halogen, amino-sulfonyl, di-C1-4 alkoxyphosphoryl, C1-4alkanoyl which may be substituted with halogen, C1-4 alkylsulfonylthiocarbamoyl, carbamoyl or halogen, or X1 and X2 together with the carbon atom to which they are attached form a ring of the formula:
R1 is a group of the formula:
[in which:
R3 is hydrogen, C1-20 alkyl, C6-10 aryl, C7-9 aralkyl, heterocycle, C1-4 alkanoyl, C6-10 aryl-carbonyl, C1-4 alkoxy-carbonyl, C6-10 aryloxy-carbonyl, heterocycleoxycarbonyl, C6-10 arylsulfonyl, C1-4 alkylsulfonyl, di-C1-4 alkoxyphosphoryl, C1-4 alkoxy, hydroxy, amino, di-C1-4 alkylamino, C1-4 alkanoylamino, C1-4 alkoxycarbonyl-amino, C1-4 alkylsulfonylamino, di-C1-4 alkoxyphosphorylamino, C7-9 aralkyloxy or C1-4 alkoxy-carbonyl-C1-4 alkyl; and R4 is hydrogen, C1-20 alkyl, C3-6 cycloalkyl, C2-6-alkenyl, C3-6 cycloalkenyl or C2-6 alkynyl, wherein each of the radicals defined for R4 except for hydrogen may optionally be substituted by 1 to 3 substituents selected from the group consisting of hydroxy, C1-4 alkoxy, halogen, di-C1-4 alkylamino, C1-4 alkylthio, C1-3alkanoylamino, C1-4 alkylsulfonylamino, tri-C1-4 alkylsilyl, pyridyl and thiazolyl, and each of the pyridyl and thiazolyl may further be substituted by halogen, or R3 and R4 together with the adjacent nitrogen atom constitute a cyclic amino group of the formula:
R2 is (1) hydrogen, (2) a group attached through a carbon atom selected from the class consisting of C1-4alkanoyl, C1-20 alkyl, C2-6alkenyl, C3-6cycloalkyl, C6-10aryl, C7-9aralkyl and 3- or 4-pyridyl, the said group attached through a carbon atom being optionally substituted by 1 to 3 substituents selected from the class consisting of C1-4alkylthio, C1-4alkoxy, mono- or di-C1-4alkylamino, C1-4alkoxy-carbonyl, C1-4alkylsulfonyl, halogen and C1-4 alkanoyl, (3) a group attached through an oxygen atom selected from the class consisting of C1-4 alkoxy, C3-6 cycloalkoxy, C2-4 alkenyloxy, C3-6 cycloalkenyloxy, ethynyloxy, C6-10 aryloxy, thienyloxy and hydroxy, the said group attached through an oxygen atom being optionally substituted by 1 to 3 substituents selected from the class consisting of halogen and phenyl, or (4) a group attached through a nitrogen atom of the formula:
~
(wherein R3 and R4 have the meanings given above);
n is an integer of 0, 1 or 2;
A is heterocycle;
wherein the heterocycle in the said heterocycloxycarbonyl for X1 and X2, the said heterocycle for R3, the heterocycle in the said heterocycleoxycarbonyl for R3, and the said heterocycle for A are a member selected from the class consisting of thienyl, furyl, pyrrolyl, pyridyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, N-oxidopyridyl, pyrimidinyl, N-oxidopyrimidinyl, pyridazinyl, pyrazinyl, N-oxidopyridazinyl, benzofuryl, benzothiazolyl, benzoxazolyl, triazinyl, oxotriazinyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxozinyl, morpholinyl, 1,4-thiazinyl, 1,3-thiazinyl, piperazinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthyridinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl and phenoxazinyl, the 243~

said heterocycle being optionally substituted by 1 to 5 substituents selected from the group consisting of:
(i) C1-4 alkyl, (ii) C3-6cycloalkyl, (iii) phenyl or naphthyl, (iv) C1-4 alkoxy, (v) C3-6cycloalkyloxy, (vi) phenoxy or naphthyloxy, (vii) C7-12phenylalkyloxy, (viii) C1-4alkylthio, (ix) C3-6cyaloalkylthio, (x) phenylthio or naphthylthio, (xi) C7-12phenylalkylthio, (xii) mono-C1-4alkylamino, (xiii) di-C1-4alkylamino, (xiv) C3-6cycloalkylamino, (xv) anilino, (xvi) C7-12phenylalkylamino, (xvii) halogen, (xviii) C1-4alkoxycarbonyl, (xix) phenoxycarbonyl, (xx) C3-6cycloalkyloxycarbonyl, (xxi) C7-12phenylalkyloxycarbonyl, (xxii) C1-5alkanoyl, (xxiii) C1-15alkanoyloxy, (xxiv) carbamoyl, N-methylcarbamoyl, N,N-dimethyl-carbamoyl, N-ethylcarbamoyl, N,N-diethylcarbamoyl, N-phenyl-carbamoyl, pyrrolidinocarbamoyl, piperidinocarbamoyl, piperazinocarbamoyl, morpholinocarbamoyl or N-benzylcarbamoyl, (xxv) N-methylcarbamoyloxy, N,N-dimethylcarbamoyloxy, N-ethylcarbamoyloxy, N-benzylcarbamoyloxy, N,N-dibenzylcarbamoyloxy or N-phenylcarbamayloxy, (xxvi) C1-4alkanoylamino, (xxvii) benzamido, (xxviii) C1-4alkoxycarbonylamino, (xxix) C7-12phenylalkyloxycarbonylamino, (xxx) methanesulfonylamino, ethanesulfonylamino, butanesulfonylamino, benzenesulfonylamino, toluenesulfonylamino, naphthalenesulfonylamino, trifluoromethanesulfonylamino, 2-chloroethanesulfonylamino or 2,2,2-trifluoromethanesulfonylamino, (xxxi) pyrrolidinyl, pyrrolyl, pyrazolyl, imidazolyl, furyl, thienyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, piperidinyl, pyridyl, piperazinyl, pyrimidinyl, pyranyl, tetrahydropyranyl, tetrahydrofuryl, indolyl, quinolyl, 1,3,4-oxadiazolyl, thieno(2,3-d]pyridyl, 1,2,3-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, tetrazolyl, 4,5-dihydro-1,3-dioxazolyl, tetrazolo[1,5-b]-pyridazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl or benzothienyl, (xxxii) heterocyclethio, heterocycleoxy, heterocycleamino or heterocyclecarbonylamino group which is derived by attachment of any of the heterocyclic groups (xxxi) defined above to the S, O, N atom or a carbonylamino group, (xxxiii) di-C1-4alkylphosphinothioylamino, (xxxiv) methoxyimino, ethoxyimino, 2-fluoroethoxyimino, carboxymethoxyimino, 1-carboxy-1-methylethoxyimino, 2,2,2-trichloroethoxycarbonylmethoxyimino, 1-(2,2,2-trichloroethoxy-carbonyl)-1-methylethoxyimino, (2-aminothiazol-4-yl)methoxyimino or (1H-imidazol-4-yl)methoxyimino, (xxxv) C1-4alkylsulfonyloxy, (xxxvi) benzenesulfonyloxy or toluenesulfonyloxy, (xxxvii) diphenylphosphinothioylamino, (xxxviii) thiocarbamoylthio, N-methylthiocarbamoylthio, N,N-dimethylthiocarbamoylthio, N-ethylthiocarbamoylthio, N-benzyl-thiocarbamoylthio, N,N-dibenzylthiocarbamoylthio or N-phenylthio-carbamoylthio, (xxxix) trimethylsilyloxy, t-butyldimethylsilyloxy, t-butyldiphenylsilyloxy or dimethylphenylsilyloxy, (xL) trimethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl or dimethylphenylsilyl, (xLi) C1-4alkylsulfinyl, (xLii) phenylsulfinyl or naphthylsulfinyl, (xLiii) C1-4alkylsulfonyl, (xLiv) benzenesulfonyl or toluenesulfonyl, (xLv) C1-4alkoxy-carbonyloxy, (xLvi) halo-C1-4alkyl, (xLvii) halo-C1-4alkoxy, halo-C1-4alkylthio, halo-C1-4alkylsulfinyl or halo-C1-4alkylsulfonyl, (xLviii) cyano, nitro, hydroxyl, carboxyl, sulfo, phosphono, (xLix) C1-4alkyloxysulfonyl, (L) phenoxysulfonyl or tolyloxysulfonyl, 246~

(Li) C7-12phenylalkyloxysulfonyl, and (Lii) di-C1-4alkyloxyphosphoryl group), or a salt thereof.

24. A composition as claimed in claim 23, wherein R2 is hydrogen, R1 is a group of the formula:
(wherein R3 and R4 are as defined in claim 23) and A is heterocycle selected from the class consisting of pyridyl, pyrazinyl and thiazolyl, the said heterocycle mentioned just above for A teeing optionally substituted with halogen, C1-4alkyl, C1-4alkylthio or C1-4alkoxy.

25. An insecticidal or miticidal composition as claimed in claim 23, wherein R2 is other than hydrogen.

26. An insecticidal or miticidal composition as claimed in claim 23, wherein:
X1 is nitro;
X2 is hydrogen, C1-2alkoxycarbonyl or C1-2alkylsulfonyl-thiocarbamoyl;
R1 is amino, mono- or di-C1-4alkylamino, halo-C1-4alkylamino, N-C1-4alkyl-N-C1-2alkanoylamino, N-halo-C1-4alkyl-N-C1-2alkanoylamino or C1-2alkanoylamino;
R2 is hydrogen, C1-2alkoxy, di-C1-2alkylamino, C1-4alkyl, halo-C1-4alkyl or C1-2alkanoyl;
n is 0 or 1;
A is 2- or 3-thienyl, 2- or 3-furyl, 2- or 3-pyrrolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4-or 5-isothiazolyl, 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1H- or 2H-tetrazolyl, N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, N-oxido-3- or 4-pyridazinyl, benzofuryl, benzothiazolyl, benzoxazolyl, triazinyl, oxotriazinyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, morpholinyl, 1,4-thiazinyl, 1,3-thiazinyl, piperazinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthyridinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl or phenoxyazinyl, each of which may optionally be substituted with halogen, C1-4alkyl, halo-C1-4alkyl, C1-4alkoxy, halo-C1-4alkoxy, C1-4alkylthio or halo-C1-4alkylthio or a salt thereof.

27. An insecticidal or miticidal composition as claimed in claim 23, wherein:
X1 is nitro;
X2 is hydrogen or C1-2alkylsulfonylthiocarbamoyl;
R1 is amino, mono- or di-C1-2alkylamino, halo-C1-2alkylamino, N-C1-2alkyl-N-C1-2alkanoylamino, N-halo-C1-2alkyl-N-C1-2alkanoylamino or C1-2alkanoylamino;
R2 is hydrogen, C1-2alkoxy, di-C1-2alkylamino, C1-4alkyl, halo-C1-4alkyl or C1-2alkanoyl;
n is 1; and A is pyridyl, pyrazinyl or thiazolyl, each of which may optionally be substituted with halogen, C1-4alkyl, halo-C1-4alkyl, C1-4alkoxy, halo-C1-4alkoxy, C1-4alkylthio or halo-C1-4alkylthio or a salt thereof.

28. An insecticidal or miticidal composition as claimed in claim 23, of the formula (wherein:
X2a is hydrogen, C1-4alkoxycarbonyl or C1-4alkyl-sulfonylthiocarbamoyl;
R2c is hydrogen, C1-3alkanoyl, C1-4alkyl, mono- or di-C1-4alkoxy-C1-4alkyl, C7-9aralkyl, mono- or di-C1-4alkylamino or C1-4alkoxy;
A c is 3- or 4-pyridyl, pyrazinyl or 4- or 5-thiazolyl, each of which may optionally be substituted with halogen, C1-4alkyl or C1-4alkoxy;
n is 1; and R3 and R4 are as defined in claim 23), or a salt thereof.

29. An insecticidal or miticidal composition as claimed in claim 23, which is a compound of the formula:
(wherein:
X2a is hydrogen, C1-4alkoxycarbonyl or C1-4alkyl-sulfonylthiocarbamoyl;

R1d is amino, mono- or di-C1-4alkylamino, N-C1-4alkyl-N-C1-3alkanoylamino, C7-9 aralkylamino, halogenothiazolyl-C1-2alkylamino or C1-4alkoxy-C1-2alkylamino;
R2c is hydrogen, C1-3alkanoyl, C1-4alkyl, mono- or di-C1-4alkoxy-C1-4alkyl, C7-9aralkyl, mono- or di-C1-4alkylamino or C1-4alkoxy;
n is 0, 1 or 2; and A d is 3- or 4-pyridyl, pyrazinyl or 5-thiazolyl, each of which may optionally be substituted with halogen, C1-4alkyl or C1-4alkoxy), or a, salt thereof.

30. An insecticidal or miticidal composition as claimed in claim 23, which is a compound of formula:
~
(wherein:
X2b is hydrogen or C1-2alkylsulfonylthiocarbamoyl;
R1e is amino, mono- or di-C1-2alkylamino or N-C1-2alkyl-N-formylamino;
R2d is hydrogen, C1-2alkyl or C1-3alkanoyl; and A e is a group of the formula:
[wherein Hal is a halogen atom]), or a salt thereof.

31. An insecticidal or miticidal composition as claimed in claim 23, which is a compound of the formula:
(wherein:
X2c is hydrogen or methylsulfonylthiocarbamoyl;
R1f is amino, methylamino, dimethylamino or N-methyl-N-formylamino;
R2d is a hydrogen atom, formyl or C1-2alkyl; and A e is a group of the formula:
[wherein Hal is a halogen atom]), or a salt thereof.

32. An insecticidal or miticidal composition as claimed in claim 23, which is a compound of formulas (wherein:
R1e is amino, mono- or di-C1-2alkylamino or N-C1-2alkyl-N-formylamino;
R2e is C1-2alkyl or formyl; and Hal is a halogen atom), or a salt thereof.

33. An insecticidal or miticidal composition as claimed in claim 23, wherein the compound is of the formulae (wherein A is pyridyl which may be substituted by halogen;
R2 is hydrogen or C1-4alkyl;
R3 is hydrogen, C1-5alkyl or benzyl;
R4 is hydrogen, C1-5alkyl or C3-7cycloalkyl or R3 and R4, taken together with the adjacent nitrogen atom, constitute a pyrrolidinyl group or an N'-methylpiperazinyl group), or a salt thereof.

34. An insecticidal or miticidal composition as claimed in claim 23, wherein the heterocycle is selected from the following group and being optionally substituted as defined in claim 23, the group consisting of 2- or 3-thienyl, 2-'or 3-furyl, 2- or 3-pyrrolyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4- or 5-isothiazolyl, 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1H- or 2H-tetrazolyl, N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, N-oxido-3- or 4-pyridazinyl, benzofuryl, benzothiazolyl, benzoxazolyl, triazinyl, oxotriazinyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, morpholinyl, 1,4-thiazinyl, 1,3-thiazinyl, piperazinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthyridinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl and phenoxazinyl.

35. An insecticidal or miticidal composition as claimed in claim 23, which comprises 1-[N-(6-chloro-3-pyridylmethyl)-N-methyl]
amino-1-methylamino-2-nitroethylene or a salt thereof.

36. An insecticidal or miticidal composition as claimed in claim 23, which comprises 1-(6-chloro-3-pyridylmethyl)amino-1-dimethylamino-2-nitroethylene or a salt thereof.

37. An insecticidal or miticidal composition as claimed in claim 23, which comprises 1-[N-(6-chloro-3-pyridylmethyl)-N-ethyl]
amino-1-methylamino-2-nitroethylene or a salt thereof.

38. A method of combatting undesirable insects or mites, which comprises applying an insecticidal or miticidal effective amount of an .alpha.-unsaturated amine of the formula:
(wherein:
one or X1 and X2 is an electron-attracting group and the other is a hydrogen atom or an electron-attracting group, wherein the said electron-attracting group is cyano, vitro, C1-4 alkoxy carbonyl, carboxyl, C6-10 aryloxy-carbonyl, heterocycleoxycarbonyl, C1-4 alkylsulfonyl which may be substituted with halogen, amino-sulfonyl, di-C1-4 alkoxyphosphoryl, C1-4 alkanoyl which may be substituted with halogen, C1-4 alkylsulfonylthiocarbamoyl, carbamoyl or halogen, or X1 and X2 together with the carbon atom to which they are attached form a ring of the formula:
R1 is a group of the formula:
[in which:
R3 is hydrogen, C1-20 alkyl, C6-10 aryl, C7-9 aralkyl, heterocycle, C1-4alkanoyl, C6-10aryl-carbonyl,C1-4 alkoxy-carbonyl, C6-10 aryloxy-carbonyl, heterocycleoxycarbonyl, C6-10 arylsulfonyl, C1-4 alkylsulfonyl, di-C1-4 alkoxyphosphoryl, C1-4 alkoxy, hydroxy, amino, di-C1-4 alkylamino, C1-4 alkanoylamino, C1-4 alkoxycarbonylamino, C1-4 alkylsulfonylamino, di-C1-4 alkoxyphosphorylamino, C7-9 aralkyloxy or C1-4 alkoxy-carbonyl-C1-4 alkyl; and R4 is hydrogen, C1-20 alkyl, C3-6 cycloalkyl, C2-6alkenyl, C3-6 cycloalkenyl or C2-6 alkynyl, wherein each of the radicals defined for R4 except for hydrogen may optionally be substituted by 1 to 3 substituents selected from the group consisting of hydroxy, C1-4 alkoxy, halogen, di-C1-4 alkyl amino, C1-4 alkylthio, C1-3 alkanoylamino, C1-4 alkylsulfonylamino, tri-C1-4 alkylsilyl, pyridyl and thiazolyl, and each of the pyridyl and thiazolyl may further be substituted by halogen, or R3 and R4 together with the adjacent nitrogen atom constitute a cyclic amino group of the formula:
R2 is (1) hydrogen, (2) a group attached through a carbon atom selected from the class consisting of C1-4 alkanoyl, C1-20 alkyl, C2-6 alkenyl, C3-6 cycloalkyl, C6-10 aryl, C7-9 aralkyl and 3- or 4-pyridyl, the said group attached through a carbon atom being optionally substituted by 1 to 3 substituents selected from the class consisting of C1-4 alkylthio, C1-4 alkoxy, mono- or di-C1-4 alkyl amino, C1-4 alkoxy-carbonyl, C1-4 alkylsulfonyl, halogen and C1-4 alkanoyl, (3) a group attached through an oxygen atom selected from the class consisting of C1-4 alkoxy, C3-6 cycloalkoxy, C2-4 alkenyloxy, C3-6 cycloalkenyloxy, ethynyloxy, C6-10 aryloxy, thienyloxy and hydroxy, the said group attached through an oxygen atom being optionally substituted by 1 to 3 substituents selected from the class consisting of halogen and phenyl, or (4) a group attached through a nitrogen atom of the formula:
(wherein R3 and R4 have the meanings given above);
n is an integer of 0, 1 or 2;
A is heterocycle;
wherein the heterocycle in the said heterocycleoxycarbonyl for X1 and X2, the said heterocycle for R3, the heterocycle in the said heterocycleoxycarbonyl for R3, and the said heterocycle for A are a member selected from the class consisting of thienyl, furyl, pyrrolyl, pyridyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, N-oxidopyridyl, pyrimidinyl, N-oxidopyrimidinyl, pyridazinyl, pyrazinyl, N-oxidopyridazinyl, benzofuryl, benzothiazolyl, benzoxazolyl, triazinyl, oxotriazinyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxozinyl, morpholinyl, 1,4-thiazinyl, 1,3-thiazinyl, piperazinyl, benzimadazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthyridinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl and phenoxazinyl, the said heterocycle being optionally substituted by 1 to 5 substituents selected from the group consisting of:
(i) C1-4alkyl, (ii) C 3-6cycloalkyl, (iii) phenyl or naphthyl, (iv) C1-4 alkoxy, (v) C3-6cycloalkyloxy, (vi) phenoxy or naphthyloxy, (vii) C7-12phenylalkyloxy, (viii) C1-4alkylthio, (ix) C3-6cycloalkylthio, (x) phenylthio or naphthylthio, (xi) C7-12phenylalkylthio, (xii) mono-C1-4alkylamino, (xiii) di-C1-4alkylamino, (xiv) C3-6cycloalkylamino, (xv) anilino, (xvi) C7-12phenylalkylamino, (xvii) halogen, (xviii) C1-4alkoxycarbonyl, (xix) phenoxycarbonyl, (xx) C3-6cycloalkyloxycarbonyl, (xxi) C7-12phenylalkyloxycarbonyl, (xxii) C1-5alkanoyl, (xxiii) C1-15alkanoyloxy, (xxiv) carbamoyl, N-methylcarbamoyl, N,N-dimethyl-carbamoyl, N-ethylcarbamoyl, N,N-diethylcarbamoyl, N-phenyl-carbamoyl, pyrrolidinocarbamoyl, piperidinocarbamoyl, piperazinocarbamoyl, morpholinocarbamoyl or N-benzylcarbamoyl, (xxv) N-methylcarbamoyloxy, N,N-dimethylcarbamoyloxy, N-ethylcarbamoyloxy, N-benzylcarbamoyloxy, N,N-dibenzylcarbamoyloxy or N-phenylcarbamayloxy, (xxvi) C1-4alkanoylamino, (xxvii) benzamido, (xxviii) C1-4alkoxycarbonylamino, (xxix) C7-12;phenylalkyloxycarbonylamino, (xxx) methanesulfonylamino, ethanesulfonylamino, butanesulfonylamino, benzenesulfonylamino, toluenesulfonylamino, naphthalenesulfonylamino, trifluoromethanesulfonylamino, 2-chloroethanesulfonylamino or 2,2,2-trifluoromethanesulfonylamino, (xxxi) pyrro:lidinyl, pyrrolyl, pyrazolyl, imidazolyl, furyl, thienyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, piperidinyl, pyridyl, piperazinyl, pyrimidinyl, pyranyl, tetrahydropyranyl, tetrahydrofuryl, indolyl, quinolyl, 1,3,4-oxadiazolyl, thieno[2,3-d]pyridyl, 1,2,3-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, tetrazolyl, 4,5-dihydro-1,3-dioxazolyl, tetrazolo[1,5-b]-pyridazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl or benzothienyl, (xxxii) heterocyclethio, heterocycleoxy, heterocycleamino or heterocyclecarbonylamino group which is derived by attachment of any of the heterocyclic groups (xxxi) defined above to the S, 0, N atom or a carbonylamino group, (xxxiii) di-C1-4alkylphosphinothioylamino, (xxxiv) methoxyimino, ethoxyimino, 2-fluoroethoxyimino, carboxymethoxyimino, 1-carboxy-1-methylethoxyimino, 2.2,2-trichloroethoacycarbonylmethoxyimino, 1-(2,2,2-trichloroethoxy-carbonyl)-1-methylethoxyimino, (2-aminothiazol-4-yl)methoxyimino or (1H-imidazol-4-yl)methoxyimino, (xxxv) C1-4alkylsulfonyloxy, (xxxvi) benzenesulfonyloxy or toluenesulfonyloxy, (xxxvii) diphenylphosphinothioylamino, (xxxviii) thiocarbamoylthio, N-methylthiocarbamoylthio, N,N-dimethylthiocarbamoylthio, N-ethylthiocarbamoylthio, N-benzyl-thiocarbamoylthio, N,N-dibenzylthiocarbamoylthio or N-phenylthio-carbamoylthio, (xxxix) trimethylsilyloxy, t-butyldimethylsilyloxy, t-butyldiphenylsilyloxy or dimethylphenylsilyloxy, (xL) trimethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl or dimethylphenylsilyl, (xLi) C1-4alkylsulfinyl, (xLii) phenylsulfinyl or naphthylsulfinyl, (xLiii) C1-4alkylsulfonyl, (xLiv) benzenesulfonyl or toluenesulfonyl, (xLv) C1-4alkoxy-carbonyloxy, (xLvi) halo-C1-4alkyl, (xLvii) halo-C1-4alkoxy, halo-C1-4alkylthio, halo-C1-4alkylsulfinyl or halo-C1-4alkylsulfonyl, (xLviii) cyano, nitro, hydroxyl, carboxyl, sulfo, phosphono, (xLix) C1-4alkyloxysulfonyl, (L) phenoxysulfonyl or tolyloxysulfonyl, (Li) C7-12 phenylalkyloxysulfonyl, and (Lii) di-C1-4 alkyloxyphosphoryl group, or a salt thereof to the said insects or mites or their habitat.
39. The compound 1-(6-chloro-3-pyridylmethyl)amino-1-methylamino-2-nitroethylene, or a salt thereof.
40. The compound 1-(2-chloro-5-thiazolylmethyl)amino-1-methylamino-2-nitroethylene, or a salt thereof.
41. An insecticidal or miticidal composition as claimed in claim 23, in which the .alpha.-unsaturated amine is 1-(6-chloro-3-pyridylmethyl)amino-1-methylamino-2-nitroethylene.
42. An insecticidal or miticidal composition as claimed in claim 23, in which the a-unsaturated amine is 1-(2-chloro-5-thiazolylmethyl)amino-1-methylamino-2-nitroethylene.