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Publication numberUS3898284 A
Publication typeGrant
Publication dateAug 5, 1975
Filing dateFeb 25, 1974
Priority dateSep 24, 1973
Publication numberUS 3898284 A, US 3898284A, US-A-3898284, US3898284 A, US3898284A
InventorsRobert Andrew Bauman
Original AssigneeColgate Palmolive Co
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Ether-linked quaternary ammonium compounds
US 3898284 A
Novel quaternary ammonium compounds containing one large aliphatic group, and an adamantyl group linked to the quaternary nitrogen by an ether group.
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Description  (OCR text may contain errors)

United States atent 1 Bauman Aug. 5, 1975 ETHER-LINKED QUATERNARY [58] Field of Search 260/567.6, 468 G, 584 R, AMMONIUM COMPOUNDS 260/584 A, 567.6 M, 501.15, 459

75 I t R b t A d B N l nven or a i auman ew [56] References Cited UNITED STATES PATENTS [73] Assignee: Colgate-Palmolive Company, New I York N.Y 3,663,617 5/1972 Pedrazzoli 260/563 P Filedl 1974 Primary E.\'amir'1erBernard Helfin No Assistant Examiner.lames Reamer Attorney, Agent, or FirmRobert L. Stone; Murray Related Application Data M. Grill; Herbert S. Sylvester [63] Continuation-impart of Ser. No. 400,097, Sept. 24,

1973, which is a continuation of Ser. No. 39,536, [57] ABSTRACT May 21, 1970, abandoned.

Novel quaternary ammonium compounds containing [52] us. Cl- 260/567 6 424/329, 424/54 one large aliphatic group, and an adamantyl group 26O/50L15;260/459 linked to the quaternary nitrogen by an ether group. [51] Int. Cl. C07c 87/00 4 Claims, N0 Drawings 1 EITHER-LINKED QUATERNARY AMMONIUM COMPOUNDS The present application is a continuation-in-part of copending application Ser. No. 400,097, filed Sept. 24, 1973 which is a continuation of patent application Ser. 39,536 filed May 21, 1970, now abandoned.

The present invention relates to novel quaternary ammonium compounds represented by the general formula:

wherein R is l-adamantyl (C H R is an aliphatic chain containing -18 carbon atoms, n is an integer from 2 to 3 and X is a compatible anion such as the halides (Cl,Br',l), sulfates (i.e., methyl sulfate), nitrate, aryl sulfonates, etc. These quaternary compounds possess superior antimicrobial, anti-caries, and anticalculus activity.

The adamantyl radical is derived from tricyclo[3.3.1.l "']decane showing four fused chair cyclohexane rings as follows:

Typical examples of the quaternary ammonium compounds which may be used in this invention are:

2-( l -adamantyloxy)ethyldimethyldodecyl ammonium bromide,

2-( l -adamantyloxy)ethyldimethyltetradecyl ammonium bromide,

2-( l-adamantyloxy)ethyldimethyldecyl ammonium chloride,

2-( l-adamantyloxy)ethyldimethylhexadecyl ammo- 1 nium chloride, 2-( l -adamantyloxy)ethyldimethyloctadecyl ammonium chloride, 3-( l -adamantyloxy)propyldimethyldodecyl ammonium bromide. Other halides such as the iodides and analogous compounds such as the sulfates, nitrate, aryl sulfonates, etc., may also be employed herein as effective antibactericides.

It has been observed that the compounds generally described by the foregoing formula are particularly effective against a wide range of organisms including the gram positive organisms such as Staphylococcus aureus; Streptococcus mitis, sanguis and mutans; Bacillus subtilis; Corynbacterium acnes; and especially effective against fungi, such as Candida albicans, Trichophyton mentogrophytes and Aspergillus niger, and against Escherichia coli which is a gram negative bacteria. Compounds wherein R is a benzyl radical in lieu of instant higher alkyl radical would be devoid of antibacterial activity.

The anti-microbial nature of the instant novel compounds was shown by a standard test tube serial dilution test in which an appropriate number of test tubes of broth containing decreasing concentrations of the test agent was innoculated with the test organism. After a suitable period of incubation, the tubes were examined for the presence or absence of growth. The activity of the test agent was the lowest concentration which inhibited the growth of the organism and is expressed as the minimal inhibitory concentration in ug/ml.

These dilution tests evidence the effectiveness of compounds of the invention against bacteria and fungi.

When used against bacteria or fungi, compounds of the instant invention may be applied directly to the surface to be protected or may be dissolved in a pharmaceutical carrier. Typically, an effective amount, e.g., 0.1 to about 10 percent by weight of the compound, is included in an inert carrier and a dispersing or surfaceactive agent. Alternatively, an effective amount, e.g., 0.1 to about 10 percent by weight may be incorporated into a solid carrier which may be inert, such as talc, clay, diatomaceous earth, flour, etc.

When compounds of the instant invention are intended for use in compositions which reduce formation of caries and inhibit formation of oral calculus, they are typically incorporated in oral preparation in effective amounts up to about 5 percent by weight, preferably 0.025-1 percent and most preferably 0.5-0.5 percent by weight of the oral preparation. Typically, the oral preparation is a dentifrice, such as a dental cream tablet or powder, containing as a vehicle about 20-95 percent by weight of a water-insoluble polishing material, preferably including water-insoluble phosphate such as dicalcium phosphate, tricalcium phosphate, trimagnesium phosphate. The dentrifrice may also include water; binders such as glycerine, sorbitol, propylene glycol and polyethylene glycol 400; detergents; gelling agents such as lrish moss and sodium carboxy methyl cellulose; additional antibacterial agents; coloring or whitening agents; preservatives; silicones; chlorophyll compounds; additional ammoniated materials; flavoring or sweetening materials; and compounds which provide fluorine-containing ion such as sodium fluoride, stannous fluoride and sodium monofluorophosphate- The oral preparation may also be a liquid such as mouth rinse which typically contains 20-99 percent by weight of an aqueous lower aliphatic alcohol, preferably having about l-30 percent by weight alcohol, such as ethanol, n-propyl, or isopropyl alcohol.

Such oral preparations are typically applied by brushing the teeth or rinsing the oral cavity for 30-90 seconds at least once daily. Typical oral preparations of the invention which can be applied in this manner are set forth below.

3,898,284 3 4 PL uct was then extracted from the suspension with four EXAM E 500-ml. portions of ether. The ether extract was washed twice with 200-ml. portions of water and once Dental Cream with saturated sodium sulfate solution. The ether ex- I d l h M d a h l tract was dried over sodium sulfate and combined with ;f ;'f,'! ;;{,1f y ecy y 050 the similar extract obtained from the other half of the gf n detergent 538 original reaction mixture. After removal of the solvent isg g the product was distilled in vacuum through an I8" carlwxymelhyl 9611111058 Vigreux column. Distillate collected at ll8-l20 28223:: 223:5: 8:28 10 (1.6T) was homogenous and free of starting materials Calcium carbonate (precipitated) 5.00 by GC (Apiezon L column).

E sa? phosphate d'hydme &5 Analysis: 'Neutral equivalent: 223.4, calcd; 226.9, Water 22.15 found. A solution of 580 g. (2.6 moles) of l-( 2 dimethylaminoethoxy) adamantane and 720 g. (2.6 Tween 80 Pclyoxyethylene moles ethylene oxide) sorbitan monooleate. 5 ole .'ot etradecane' 5 l acetone was re II] S Hl fluxed for 40 hours. Thehot solution was treated with EXAMPLE 2 Norite and allowed to crystallizefAfter a second recrystallization from acetone and drying in vacuum at Mouthwash 20 room temperature, 1036 g. material was obtained (80 percent of theory); m.p. l33-l35.. 2'"aqamamYlWYlethyhetladecyldimehyl Analysis: Calcd. for C l-l Br ON: C, 67.17; H, ammonium bromide 0.05 Nonionic detergent (Pluronic F-68)* 1.00 Ethyl alcohol (containing flavor) 15.00 F d; C 67 2]; H, 1090; B 1596 Glycerine Saccharin Water 73.73 EXAMPLE'4 -i Block polymer of 80% polyoxyethylene and 20% polyoxypropylene. The dodecyl ho,m0,log was prepard by the piocdure of Example 3, yielding hygroscopic crystals having a The quaternary ammonium ethers of instant invenmelting Point when y 0f Ugo-130C and the followtion can be prepared by a two-step method of reacting mg analysis:

a l'haloadamantane with dimethyl aminoethanol to v V v form a tertiary amino ether and subsequently quaterd a Ca'culated msmg with an alkyl halide or ester of sulfuric or of Bromine .l6.91 .16.91'

arenesulfonic acid (i.e. methyl toluene sulfonate) as illustrated by the following equations wherein R and R Although this invention has been described with refhave the aforedefined meanings. erence to specific examples, it will be apparent to one i? 1 I l. RBr HOCH -CH -lII R-O-(Cl-l I +l-lBr on s CH on 9H3 1 1i 1: x 2. RO(CH R X R0(CH2 2'? CH 2 CH 3 The following examples illustrate the manner in skilled in the artthat Ivarious modifications may be which compounds of this invention are prepared. made thereto which fall within its scope What is claimed' E AM E x PL 3 l. A chemical compound'havmg the structural for- Preparation of 2(l -adamantyloxy)ethyldimethyltetl R()(CH N(CH R X- h i R i 1- radecylammonium brom d adamantyl, R is a long chain alkyl group of 10 18 car- A mixture of 600 9 l'bl'ofhoadamahtahe bon atoms, n is an integer from 1 to 3, and X is an anion and 1250 8- (14 moles) 2d1methy]amlhethah| was selected from the group consisting of chloride, brostirred and reflu 48 h011r5- At this time the reac' mide, iodide, methyl sulfate, nitrate and aryl sulfon ates.

tion mixture was divided in two and each portion A chemical compound as e forth claim worked up as follows: Half the mixture was poured into h i X i a h 1id 2 l. water and extracted three times with 500 ml. por- 3, 2-(1k d l h ldi d d l a trons of ether. The ether solution was extracted three i b id times with portions of a solution of 300 ml. concen- 4, 2-(1k d m l h idi i h l d yl trated hydrochloric acid in 2.2 l. water. This aqueous monium b id acidic extract was then treated witha solution of 360 g. sodium hydroxide in l I. water. The liberated prod-

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3663617 *Jun 4, 1970May 16, 1972Rech Et D Applic Scient Et Med1-(adamantylmethyloxy) - 2 - hydroxy-3-substituted amino propanes and acid addition salts thereof
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4046873 *Feb 25, 1974Sep 6, 1977Colgate Palmolive CompanyAlicyclic amido-quaternary ammonium anti-bacterial agents
US4654175 *May 12, 1982Mar 31, 1987Xerox CorporationQuaternary ammonium, charging, electrography, developers
US5066414 *Mar 6, 1989Nov 19, 1991The Procter & Gamble Co.Quaternary ammonium salt containing ester linkage; antistatic agents
US5851513 *Feb 3, 1998Dec 22, 1998Colgate Palmolive CompanyAntiplaque oral composition and method
U.S. Classification564/281, 514/901, 562/84, 558/27, 424/54, 514/835
International ClassificationA61K8/41, A61Q11/00
Cooperative ClassificationA61Q11/00, A61K8/416, Y10S514/835, Y10S514/901
European ClassificationA61Q11/00, A61K8/41L