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Publication numberUSRE34185 E
Publication typeGrant
Application numberUS 07/606,222
Publication dateFeb 23, 1993
Filing dateOct 31, 1990
Priority dateMar 8, 1985
Fee statusPaid
Publication number07606222, 606222, US RE34185 E, US RE34185E, US-E-RE34185, USRE34185 E, USRE34185E
InventorsDavid R. Amick
Original AssigneeRohm And Haas Company
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Stabilization of non-aqueous solutions of 3-isothiazolones
US RE34185 E
Abstract
Non-aqueous solutions of 3-isothiazolones are stabilized against chemical decomposition by using organic hydroxylic solvents. These compositions exhibit bactericidal, fungicidal and algaecidal properties.
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Claims(8)
    I claim: .[.1. A method for stabilizing a 0.5 to about 10% by weight solution of an isothiazolone of the formula: ##STR3## wherein Y is an unsubstituted alkyl of 1 to 8 carbon atoms, an unsubstituted or halo substituted alkenyl or alkynyl of 2 to 8 carbon atoms, an unsubstituted cycloalkyl of 5 to 8 carbon atoms, benzyl, aralkyl selected from 3,4-dichlorobenzyl, 4-methoxybenzyl or 4-chlorobenzyl or substituted aryl selected from 3,4-dichlorophenyl or 4-methoxyphenyl; R is halo; R1 is hydrogen, halogen or (C1 -C4)alkyl which consists of formulating a solution of the isothiazolone by dissolving the isothiazolone in from about 90 to about 99% by weight of dipropylene
  1. glycol, polypropylene glycol, 1,5-pentadiol or benzyl alcohol..]. .[.2. The method of claim 1 wherein the isothiazolone is 5-chloro-2-methyl-4-isothiazolin-3-one..]. .[.3. The method of claim 1 wherein the solvent is dipropylene glycol..]. .[.4. A stabilized solution consisting essentially of from 0.5 to 10% by weight of a compound of the formula: ##STR4## wherein Y is an unsubstituted alkyl of 1 to 8 carbon atoms, an unsubstituted or halo substituted alkenyl or alkynyl group of 2 to 8 carbon atoms, an unsubstituted cycloalkyl of 5 to 8 carbon atoms, benzyl, or 3,4-dichloro phenyl or 4-methoxy phenyl
    R is halo; R1 is hydrogen, halogen or (C1 -C4) alkyl, and from 90 to 99.5% by weight of dipropylene glycol, polypropylene glycol,
  2. 1,5-pentanediol or benzyl alcohol..]. .[.5. The solution of claim 4 wherein the isothiazolone is 5-chloro-2-methyl-4-isothiazolin-3-one..]. .[.6. The solution of claim 4 wherein the solvent is dipropylene
  3. glycol..]. .Iadd.7. A method for stabilizing a 0.5 to about 10% by weight solution of an isothiazolone of the formula: ##STR5## wherein Y is an unsubstituted alkyl of 1 to 8 carbon atoms, an unsubstituted or halo substituted alkenyl or alkynyl of 2 to 8 carbon atoms, an unsubstituted cycloalkyl of 5 to 8 carbon atoms, benzyl, aralkyl selected from 3,4-dichlorobenzyl, 4-methoxybenzyl or 4-chlorobenzyl or substituted aryl selected from 3,4-dichlorophenyl or 4-methoxyphenyl; R1 is halo; R is hydrogen, halogen or (C1 -C4) alkyl which consists of formulating a solution of the isothiazolone by dissolving the isothiazolone in from about 90 to about 99% by weight of dipropylene glycol, polypropylene glycol, 1,5-pentadiol or benzyl alcohol. .Iaddend.
  4. .Iadd.8. The method of claim 7 wherein the isothiazolone is 5-chloro-2-methyl-4-isothiazolin-3-one. .Iaddend. .Iadd.9. The method of claim 7 wherein the solvent is dipropylene glycol. .Iaddend. .Iadd.10. A stabilized solution consisting essentially of from 0.5 to 10% by weight of a compound of the formula: ##STR6## wherein Y is an unsubstituted alkyl of 1 to 8 carbon atoms, an unsubstituted or halo substituted alkenyl or alkynyl group of 2 to 8 carbon atoms, an unsubstituted cycloalkyl of 5 to 8 carbon atoms, benzyl, or 3,4-dichloro phenyl or 4-methoxy phenyl
    R1 is halo; R is hydrogen, halogen or (C1 -C4) alkyl, and from 90 to 99.5% by weight of dipropylene glycol, polypropylene glycol,
  5. 1,5-pentanediol or benzyl alcohol. .Iaddend. .Iadd.11. The solution of claim 10 wherein the isothiazolone is 5-chloro-2-methyl-4-isothiazolin-3-one. .Iaddend. .Iadd.12. The solution of claim 10 wherein the solvent is dipropylene glycol. .Iaddend.
  6. .Iadd. A method for stabilizing a 0.5 to about 10% by weight solution of an isothiazolone of the formula: ##STR7## wherein Y is an unsubstituted alkyl of 1 to 8 carbon atoms, an unsubstituted or halo substituted alkenyl or alkynyl of 2 to 8 carbon atoms, an unsubstituted cycloalkyl of 5 to 8 carbon atoms, benzyl, aralkyl selected from 3,4-dichlorobenzyl, 4-methoxybenzyl or 4-chlorobenzyl or substituted aryl selected from 3,4-dichlorophenyl or 4-methoxyphenyl; R1 is halo; R is hydrogen, halogen or (C1 -C4) alkyl which consists of formulating a solution of the isothiazolone by dissolving the isothiazolone in from about 90 to about 99% by weight of a solvent selected from the group consisting of ethylene glycol, dipropylene glycol, polypropylene glycol, 1,5-pentanediol, propylene glycol, diethylene glycol, and triethylene glycol, in the absence of water. .Iaddend.
  7. .Iadd. . A stabilized solution consisting of essentially from 0.5 to 10% by weight of a compound of the formula: ##STR8## wherein Y is an unsubstituted alkyl of 1 to 8 carbon atoms, an unsubstituted or halo substituted alkenyl or alkynyl group of 2 to 8 carbon atoms, an unsubstituted cycloalkyl of 5 to 8 carbon atoms, benzyl, or 3,4-dichlorobenzyl, 4-methoxybenzyl; R1 is halo; R is hydrogen, halogen or (C1 -C4) alkyl, and from 90 to 99% by weight of a solvent selected from the group consisting of ethylene glycol, dipropylene glycol, polypropylene glycol, 1,5-pentanediol, propylene glycol, diethylene glycol and triethylene glycol, said solution containing no
  8. water. .Iaddend. .Iadd.15. The solution of claim 14 wherein said compound is 5-chloro-2-methyl-4-isothiazoline-3-one. .Iaddend.
Description

This application is a continuation-in-part application of U.S. Ser. No. 709,755, filed Mar. 8, 1985, now abandoned.

This invention relates to solvent stabilized solutions of 3-isothiazolones, their preparation, compositions containing them, and their use in controlling living organisms.

Isothiazolones of the present invention are represented by the following structural formula: ##STR1## wherein

Y is an unsubsituted or substituted alkyl of from 1 to 8 carbon atoms, an unsubstituted or halo substituted alkenyl or alkynyl of 2 to 8 carbon atoms, and, preferably, from 2 to 4 carbon atoms, an unsubstituted or substituted cycloalkyl of from 5 to 8 carbon atoms, an unsubstituted or substituted aralkyl or an unsubstituted or substituted aryl;

R hydrogen, halo, or a (C1 -C4)alkyl and R1 is hydrogen, halogen or (C1 -C4)alkyl.

Representative Y substituents include methyl, ethyl, propyl, isopropyl, butyl, hexyl, octyl, cyclohexyl, benzyl, 3,4-dichlorobenzyl, 4-methoxybenzyl, 4-chlorobenzyl, 3,4-dichlorophenyl, 4-methoxyphenyl, hydroxymethyl, chloromethyl, chloropropyl and the like.

In many instances it is desirable to completely or eliminate water, salt, and nitrate levels in isothiazolone biocides. For example, certain emulsions or dispersions require biocidal protection and are sensitive to shock resulting in a precipitate when salts, especially those containing divalent ions, are added. This precipitation precludes the use of biocides containing appreciable salt levels, especially in situations where mechanical stirring is not feasible.

In oils and fuels it is desirable to have a substantially water-free and salt-free environment. Water in contact with the organic matter in fuel creates conditions suitable for biological growth and the formation of sludge. Also, salts in oils and fuel result in ignition deposits which lead to clogging and corrosion of various mechanical components.

In some cosmetic formulations, it is also important to have low water and salt content. Eliminating nitrate salts avoids the possibility of nitrosamine formation. Nitrosamines are suspected carcinogens.

This invention is directed to stable biocidal isothiazolone compositions in which (1) water is substantially eliminated, (2) neutralizing salt content is eliminated and (3) nitrate stabilizer salts are substantially reduced.

The preferred compositions contain from about 3 to about 10% by weight of one or more isothiazolones, no water, 0 to 1% of a stabilizing salt, and a stabilizing amount of hydroxy solvent(s) which may be present in an amount up to about 99.5% of a hydroxy solvent or mixture of said solvents. It is to be understood that water could be added to the compositions of this invention but that the stability would be lower than those containing no water.

The stabilizing hydroxy solvents of this invention are selected from those having the following structural formula: ##STR2## wherein R and R1 are hydrogen or lower alkyl, such as methyl, ethyl, propyl, butyl, pentyl and the like and X is --(CH2)n -- where n is an integer of 1 to 4 and y is an integer of from 2 to about 150.

.[.Preferred stabilizing solvents include benzyl alcohol, dipropylene glycol, polypropylene glycol and 1,5-pentanediol..]. .Iadd.The stabilizing hydroxy solvent(s) useful in this invention are selected from the group consisting of dipropylene glycol, polypropylene glycol, 1,5-pentadiol, propylene glycol, ethylene glycol, diethylene glycol, triethylene glycol, and benzyl alcohol. .Iaddend.

The stabilizing solvent is generally employed in an amount of from about 89 to about 99.5% by weight of the composition, with the most preferred amount depending on the amount of isothiazolone desired.

Prior to this discovery it was known to employ organic solvents with metal nitrates (See especially U.S. Pat. No. 3,870,795, Col. 3, lines 39-54). However, the solvents were not known to be useful as stabilizers. U.S. Pat. No. 3,870,795, Col. 4, lines 35-45 discloses that non-aqueous solutions containing about 15% of 5-chloro-2-methyl-3-isothiazolone/2-methyl-3-isothiazolone (93:7) in dipropylene glycol completely decomposed in 28 days at 50 C.

U.S. Pat. Nos. 4,241,214 and 4,396,413 describe metal salt complexes of I, supra and their use as effective biocidal agents. Current commercial products containing products of formula I, supra are sold as aqueous solutions containing divalent nitrate salts which serve as stabilizers for the isothiazolones which would otherwise decompose upon storage.

Japanese Pat. No. 1,318,306 claims stabilizing an isothiazolone (with high amounts (7%) of stabilization salts) and 2-hydroxymethyl-2-nitro-1,3-propanediol with a diol solvent. Also, the water content is identified as being in the range of 15 to 75%. However, 2-hydroxymethyl-2-nitro-1,3-propanediol is a known formaldehyde releaser, which is known to stabilize isothiazolones (Lee U.S. Pat. Nos. 4,165,318 and 4,129,448). This patent then describes the diols used-ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol or polypropylene glycol. However, our tests show that ethylene glycol, propylene glycol and polyethylene glycol (triethylene glycol) are much less effective in the non-formaldehyde containing compositions.

This invention permits the stabilization of isothiazolones without employing stabilization salts. It should be understood that the use of small amounts of stabilizing salts is also within the scope of this invention. Useful stabilization salts which can be employed are those disclosed in U.S. Pat. Nos. 3,870,795 and 4,067,878. Preferred stabilization salts fall into two groups:

(1) Metal nitrates, where the metal is barium, cadmium, calcium, chromium, cobalt, copper, iron, lead, lithium, magnesium, manganese, mercury, nickel, sodium, silver, strontium, tin, zinc and the like; and

(2) Copper (2+) salts where the anion is halide, sulfate, nitrate, nitrite, acetate, chlorate, perchlorate, bisulfate, bicarbonate, oxalate, maleate, carbonate, or phosphate.

Previously in the preparation of the 3-isothiazolones, it was desired to partially neutralize the intermediate isothiazolone hydrochloride salt to obtain a more stable product; this resulted in the formation of a "neutralization salt" as a by-product. This invention eliminates the neutralization salt, as the hydrogen chloride formed in the preparation of the isothiazolones is removed by treating the isothiazolone hydrochloride salt with an organic base. Tertiary organic bases are preferred, for example, trialkylamines such as trimethylamine, triethylamine, tripropylamine and the like, also cyclic tertiary amines such as pyridine and the like. While an inorganic salt can be used to neutralize the hydrogen chloride, it dissolves and reacts very slowly in the "all organic" formulation, and results in the formation of a neutralization salt which is undesirable.

Typical formulation ranges are illustrated in the following Table I (all percentages are parts by weight)

              TABLE I______________________________________      Hydroxy Solvent                 Stabilization Salt______________________________________Isothiazoline0.5-10         89-99.5    0-1.0Preferred3.0-10.0     89.0-97.0    0-1.0Most Preferred6.0-10.0     89.0-93.7    0.3-1.0______________________________________

Solutions of isothiazolones are used as watercooling system microbicides, as preservatives for aqueous dispersions or organic polymers, as wood pulp white water slimicides, as cosmetic preservatives, as cutting oil, jet fuel, and heating oil preservatives, and the like. Solutions of isothiazolones are also applied to a solid substrate, such as fabric, leather, or wood, as a preservative.

The products of this invention are especially useful as preservatives for the following: 1. Cosmetics, as it eliminates or substantially reduces the presence of nitrates which under certain conditions in the presence of amines or amine precursors may lead to the formation of nitrosoamines. 2. Oils and fuels, since added salts and moisture are eliminated or minimized thus preventing potential corrosion, deposition or sludge formation 3. Emulsions and dispersions that are sensitive to the addition of salts. Examples of these emulsions and dispersions are those contained in a wide variety of products, such as paints, cosmetics, floor polishes and binders.

The following examples will further illustrate this invention, but are not intended to limit it in any way. All parts and percentages are by weight and all temperatures in degrees Centrigrade, unless otherwise stated.

Our studies show that the temperature of 55 C. causes an acceleration effect so that one week is equivalent to about 3 months at 25 C.; two weeks is equivalent to about 6 months; three weeks is equivalent to 9 months; and four weeks is equivalent to about 12 months, and so on. The temperature of 65 C. causes an acceleration effect so that one week is equivalent to about 7 months at 25 C.; two weeks is equivalent to 14 months; three weeks is equivalent to 21 months; four weeks is equivalent to 28 months, and so on. Any product which does not show signs of decomposition in one year (4 weeks at 55 C. or about 2 weeks at 65 C.) is considered to be a stable product.

Example 1

Stability (by HPLC) of 5-chloro-2-methyl-4-isothiazolin-3-one in Organic Solvents at 65 C. ("No H2 O") (1% AI to start)

______________________________________           2      2        4     6Solvent         days   weeks    weeks weeks______________________________________(a) Dipropylene glycol               P      P      P     P(b) Polypropylene glycol               P      P      P     P    (MW = 2000)(c) 1,5-Pentanediol P      P      P     F(d) Propylene glycol               P      P      F     F(e) Ethylene glycol P      P      F     F(f) Diethylene glycol               P      P      F     F(g) Triethylene glycol               P      P      F     F(h) 2,3-Pentanediol P      F      F     F______________________________________ AI (Active Ingredient determined by HPLC (HPLC = High Pressure Liquid Chromatography) P = essentially no loss of AI F = AI totally decomposed
Example 2

Stability (by HPLC) of 5-chloro-2-methyl-4-isothiazolin-3-one in Organic Solvents (90%) with 10% Water at 65 C. (1% AI to start)

______________________________________          1       2        3     4Organic Solvent          week    weeks    weeks weeks______________________________________(a) Dipropylene glycol              P       P      P     F(b) Benzyl alcohol P       P      P     P(c) 15-Pentanediol P       P      P/F   F(d) Propylene glycol              P       F      --    --(e) Ethylene glycol              P       F      --    --(f) Diethylene glycol              P       P/F    F     --(g) Triethylene glycol              P/F     F      --    --(h) 2,4-Pentanediol              P       F      --    --(i) Triethylene glycol,              F       --     --    --    dimethyl ether(j) Acetonylacetone              P/F     F      --    --(k) Dimethylsulfoxide              F       --     --    --______________________________________ P/F = 20-80% of AI decomposed (by HPLC)
EXAMPLE 3

Hair Shampoo--Nitrate and Nitrite Free

A solution containing 3% active isothiazolines N-methyl-5-chloroisothiazolin-3-one and N-methylisothiazolin-3-one, 2% NaCl, 3% water in dipropylene glycol is used as a preservative for a hair shampoo. The biocide solution will contain no nitrate, nitrite or nitrosamines. The shampoo is treated with biocide solution to provide 20 ppm of active biocide. The resultant shampoo contains no nitrosamine and has no nitrate to react with amines in the shampoo composition.

Example 4

Preparation of a 7.5% Formulation of Active Ingredient (A.I.)

To a 500 ml-rb flask equipped with a mechanical stirrer, thermometer, and dropping funnel were added 41.25 g of powdered N-methyl-5-chloroisothiazolin-3-one (80%)/N-methyl isothiazolin-3-one (20%) (A.I.) HCl salt and 83.75 g toluene. The mixture was stirred and cooled (≦15 C.) as 15 g of triethylamine was added dropwise over 20 min. Five minutes after the addition was completed the ET3 N. HCl salt was removed by filtration to afford a toluene solution of A.I. as the filtrate. A 22.3 gm portion of the toluene solution was mixed with 25 gm of 1% Cu(NO3)n /dipropylene glycol solution to afford a clear solution having a pH >7; the pH was adjusted to 3.57 by adding several drops of conc. HCl. This solution was rotovapped 1 hr at 55 C./20 mm Hg to remove 8.48 gms of toluene, which was replaced with 8.48 gms of dipropylene glycol to afford about 7.5% A.I., pH 2.71, and a Cu(NO3)2 level of about 0.5%.

              TABLE II______________________________________Heat-Age Stability of 7.5% AI Formulation       Weeks Aged With No Loss of AI% AI          55 C.                   65 C.______________________________________7.5           ≧5 wks                   4-5 wks______________________________________

It is to be understood that changes may be made to the examples without departing from the scope of this invention as defined by the claims.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3870795 *Feb 28, 1973Mar 11, 1975Rohm & HaasStabilization of solutions of 3-isothiazolones employing certain metal nitrates and nitrites
US4067878 *Mar 5, 1976Jan 10, 1978Rohm And Haas CompanyStabilization of solutions of 3-isothiazolones
US4188376 *Sep 15, 1978Feb 12, 1980Imperial Chemical Industries LimitedStable liquid compositions containing salts of 1,2-benzisothiazolin-3-one
US4241214 *Jul 12, 1978Dec 23, 1980Rohm And Haas CompanyMetal salt complexes of 3-isothiazolones
US4281136 *Oct 16, 1978Jul 28, 1981Givaudan Corporation2-Alkyl-3-haloisothiazolium salts and their derivatives
US4396413 *Apr 19, 1982Aug 2, 1983Rohm And Haas CompanyMetal salt complexes of 3-isothiazolones as effective biocidal agents
EP0166611A2 *Jun 26, 1985Jan 2, 1986Rohm And Haas CompanyStabilization of aqueous solutions of 5-chloro-3-isothiazolones
EP0194146A2 *Mar 6, 1986Sep 10, 1986Rohm And Haas CompanyStabilization of 5-chloro-3-isothiazolones
GB2004747A * Title not available
JP5140726B2 Title not available
JP5699401B2 Title not available
JPH05140726A * Title not available
JPS5699401A * Title not available
Non-Patent Citations
Reference
1Lachman et al., "The Theory and Practice of Industrial Pharmacy", 2nd ed., Lea & Febiger, Philadelphia, 1976, pp. 32-43.
2 *Lachman et al., The Theory and Practice of Industrial Pharmacy , 2nd ed., Lea & Febiger, Philadelphia, 1976, pp. 32 43.
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US5461150 *Dec 14, 1994Oct 24, 1995Rohm And Haas CompanyStabilization of 3-isothiazolone solutions
US5534487 *May 16, 1995Jul 9, 1996Rohm And Haas CompanyStabilization of 3-isothiazolone solutions
US5594017 *May 25, 1995Jan 14, 1997Rohm And Haas CompanyStabilization of aqueous 3-isothiazolone solutions
US6403533Jan 12, 2001Jun 11, 2002Rohm And Haas CompanyStabilized microbicide formulation
EP0721736A1Sep 14, 1995Jul 17, 1996Rohm And Haas CompanyStabilization of 3-isothiazolone solutions
EP0931541A1 *Nov 20, 1998Jul 28, 1999L'orealComposition containing a procysteine and polyol combination
Classifications
U.S. Classification548/213
International ClassificationC07D275/03, A61Q17/00, A61K8/49, A01N43/80, C07D275/02
Cooperative ClassificationA61Q5/02, A61K2800/52, A61K8/49, A01N43/80, A61Q17/005, C07D275/03
European ClassificationA01N43/80, A61K8/49, A61Q17/00F, C07D275/03
Legal Events
DateCodeEventDescription
Aug 10, 1992ASAssignment
Owner name: ROHM AND HAAS COMPANY, PENNSYLVANIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:AMICK, DAVID R.;REEL/FRAME:006208/0965
Effective date: 19850304
May 30, 1996FPAYFee payment
Year of fee payment: 8
May 18, 2000FPAYFee payment
Year of fee payment: 12