Phenoxyalkanol as a stabilizer for isothiazolones

Abstract: Phenoxyalkanols are used to stabilize isothiazolone concentrates.

Description: This invention concerns the stabilization of 3-isothiazolone compositions and also their preparation and use in controlling living organisms. EP-A-194466 of Guilini Chemie discloses a methylparaben, propylparaben and propylene glycol containing composition for antimicrobial and antioxidative stabilization of cosmetics, which contains a list of compounds including optionally isothiazolone and also optionally 2-phenoxyethanol. There is no suggestion that the phenoxyethanol would act as a stabilizer for the isothiazolone if the two were present together, nor is there any disclosure of the presence of phenoxyethanol in an isothiazolone concentrate. Until now typical means for stabilization of isothiazolones against thermal degradation or storage degradation has generally been by metal salts, formaldehyde or formaldehyde releasers, and other stabilizers suggested in, EP-A-315464. EP-A-349788 discloses stabilizing isothiazolones with various solvents such as acetates, propionates or butyrates of monoalkyl or dialkyl ethers, carbonic acid alkyl esters, carbonic acid dialkyl amides and alkylene carbonates. Phenoxyalkanols are not disclosed. Both formaldehyde or formaldehyde-releasers and salt stabilization of isothiazolones have some drawbacks. In certain applications it is desirable to avoid addition of certain stabilizers by virtue of their volatility, decomposition under high heat, higher cost, difficulty in handling, potential toxicity, and the like. The present invention provides in one aspect a method of stabilizing a 3-isothiazolone of the formula wherein Y is (C₁-C₁₈)alkyl or (C₃-C₁₂)cycloalkyl each optionally substituted with one or more of hydroxy, halo, cyano, alkylamino, dialkylamine, arylamino, carboxy, carbalkoxy, alkoxy, aryloxy, alkylthio, arylthio, haloalkoxy, cycloalkylamino, carbamoxy, or isothiazolonyl; an unsubstituted or halo-substituted (C₂-C₈) alkenyl or alkynyl; a (C₇-C₁₀)aralkyl optionally substituted with one or more of halogen, (C₁-C₄)alkyl or (C₁-C₄)alkoxy; or an aryl optionally substituted with one or more of halogen, nitro, (C₁-C₄)alkyl, (C₁-C₄)alkyl-acylamino, carb(C₁-C₄)alkoxy or sulfamyl; and R and R¹ is each independently H, halogen or (C₁-C₄) alkyl; comprising incorporating therewith an effective amount of a phenoxyalkanol, preferably by dissolving said 3-isothiazolone in the phenoxyalkanol. In a further aspect the invention provides an isothiazolone concentrate composition, preferably in the form of a solution, and comprising from 75 to 99.9% by weight of a phenoxyalkanol, and a 3-isothiazolone as defined above, and no water or other stabilizer. The 3-isothiazolones of interest include those disclosed in U.S.-A-3,523,121 and 3,761,488 as represented by the following formula: wherein Y is hydrogen; an alkyl or substituted alkyl of 1 to 18 carbon atoms, preferably from 4 to 10 carbon atoms; an unsubstituted or halogen substituted alkenyl or alkynyl of 2 to 8 carbon atoms, preferably from 2 to 4 carbon atoms; a cycloalkyl or substituted cycloalkyl of 3 to 12 carbon atoms, preferably from 5 to 8 carbon atoms; an aralkyl or halogen-, lower alkyl-, or lower alkoxy-substituted aralkyl or up to 10 carbon atoms; or an aryl or halogen-, lower alkyl-, or lower alkoxy-substituted aryl of up to 10 carbon atoms; and X and X¹ are hydrogen, halogen, or a (C₁-C₄)alkyl. Representative Y substituents include methyl, ethyl, propyl, isopropyl, butyl, hexyl, octyl, cyclohexyl, benzyl, 3,4-dichlorophenyl, 4-methoxybenzyl, 4-chlorobenzyl, 4-methoxyphenyl, 4-chlorophenyl, phenethyl, 2-(4-chlorophenyl)ethyl, hydroxymethyl, chloromethyl, chloropropyl, hydrogen. Where the expression "lower" is employed in conjunction with terms, such as alkyl, alkoxy, etc., it is intended to indicate that the alkyl or alkyl portion thereof has 1 to 4 carbon atoms, i.e., (C₁-C₄). By a substituted alkyl group is meant an alkyl group having one or more of its hydrogen atoms replaced by another substituted group. Examples of the substituted alkyl groups with characterize 3-isothiazolones of this invention include hydroxyalkyl, haloalkyl, cyanoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, carboxyalkyl, carbalkoxyalkyl, alkoxyalkyl, aryloxyalkyl, alkylthioalkyl, arylthioalkyl, haloalkoxyalkyl, cycloalkylaminoalkyl, such as morpholinoalkyl, piperidinoalkyl, pyrrolidonylalkyl, and the like, carbamoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, isothiazolonylalkyl. By a substituted aralkyl group is meant an aralkyl group having one or more of the hydrogen atoms on either the aryl ring or the alkyl chain replaced by another substituent group. Examples of the substituent aralkyl groups which characterize 3-isothiazolones of this invention include halogen-, lower alkyl-, or lower alkoxy-substituted aralkyl groups. By a substituted aryl group is meant an aryl group, such as benzene, naphthalene, or pyridine, having one or more of the hydrogen atoms on the aryl ring replaced by another substituent group. Examples of such substituent groups include halogen, nitro, lower alkyl, lower alkyl-acylamino, lower carbalkoxy, sulfamyl. Preferred isothiazolones are 5-chloro-2-methyl-3-isothiazolone, 2-methyl-3-isothiazolone, 2-octyl-3-isothiazolone, 4,5-dichloro-2-cyclohexyl-3-isothiazolone and 4,5-dichloro-2-octyl-3-isothiazolone. The present invention also encompasses the use of a phenoxyalkanol, preferably phenoxyethanol or phenoxyisopropanol, to stabilise an isothiazolone, and a method of preventing or inhibiting the growth of bacteria, fungi or algae in a locus subject or susceptible to contamination thereby, comprising incorporating therewith an effective amount of an isothiazolone stabilised with a phenoxyalkanol, preferably phenoxyethanol or phenoxyisopropanol. Generally the isothiazolone stabilised according to the present invention is in the form of a dissolved concentrate, preferably being dissolved in the phenoxyalkanol itself. The resultant solution may additionally comprise up to about 25% by weight of adjuvant selected from the group consisting of surfactant, inorganic salt, polymeric dispersant, humectant, viscosity modifier, and freezing point depressant. Preferably the concentrate contains less than 5% by weight of water, and more preferably it contains no water. When it is desired to package the isothiazolone with only the stabilizer and no other organic solvent or water present the amount of stabilizer or mixture of stabilizers employed will be from 75 percent to 99.9 percent. The isothiazolone may be present in a bulk form or packaged or encapsulated in some manner, including a form for controlled release. The ratio of isothiazolone to phenoxyalkanol is preferably from 0.1:99.9 to 25:75. For certain uses, such as shipping of large quantities, more concentrated solutions may also be utilized. Preferred phenoxyalkanols are phenoxyethanol and phenoxyisopropanol. This invention permits the stabilization of isothiazolones wherein the previously necessary stabilization salts are substantially reduced and even eliminated. Uses of these new organically stabilized microbicides are typically at any locus subject to contamination by bacteria, fungi or algae. Typical loci are aqueous systems such as water cooling, laundry rinse water, oil systems such as cutting oils, oil fields where microorganisms need to be killed or where their growth needs to be controlled. The microbicide compositions of this invention containing reduced levels of salt or no salt are advantageous over salt stabilized isothiazolones described in the art and are the microbicides of choice where salts pose a problem. For example, certain emulsions upon the addition of a salt may coagulate. The compositions of this invention avoid this problem and therefore can be used in emulsions such as photographic emulsions, coating emulsions, (e.g. paints) to form solid protective or decorative films; electronic circuitry, wood, metals, plastics, fibers, membranes, carpet backings, ceramics where surfaces need to be coated or protected, adhesives, caulks, and sensitive emulsions. Salt free compositions are useful in fuel systems such as diesel fuel, gasoline, kerosene, certain alcohols, and the like, because they eliminate the possibility of salt deposits on component parts. Another reason for eliminating salts is to avoid an environment in which corrosion can occur. For example, chloride salts (among others) have a corrosive effect on many metals and are to be avoided where possible. In water treatment systems where low cation and anion levels are important, this is especially true. Those familiar with the art in various areas where biological growth needs to be controlled will quickly recognize those applications where significant reduction of or elimination of salts will be desired. In many cases it is necessary to eliminate interactions between the stabilizing salts and other components of the system or formulation components which otherwise could reduce the performance or value of such systems. Because isothiazolone microbicides are so active, the low levels required to achieve satisfactory microbicidal protection mean that there is very little phenoxyalkanol present in the overall system requiring protection, so that it is not likely to interfere with other components in the system, or with systems upon which the protected system will be applied. Potential areas of general application include disinfectants, sanitizers, cleaners, deodorizers, liquid and powder soaps, skin removers, oil and grease removers, food processing chemicals, dairy chemicals, food preservatives, animal food preservatives, wood preservation, paint, lazures, stains, mildewcides, hospital and medical antiseptics, metal working fluids, cooling water, air washers, petroleum production, paper treatment, paper mill slimicides, petroleum products, adhesives, textiles, pigment slurries, latexes, leather and hide treatment, petroleum fuel, laundry sanitizers, agricultural formulations, inks, mining, nonwoven fabrics, petroleum storage, rubber, sugar processing, tobacco, swimming pools, cosmetics, toiletries, pharmaceuticals, chemical toilets, household laundry products, diesel fuel additives, waxes and polishes and many other applications where water and organic materials come in contact under conditions which allow the growth of undesired microorganisms. In some cosmetic formulations, it is also important to have low water and salt content. Eliminating nitrate salts avoids the possibility of nitrosamine formation with any amines present in the formulation. Removal or reduction of multivalent cations from the biocide may also eliminate the known possibility of creating physical incompatibility problems in certain cosmetic formulations caused by precipitation of salts or complexes. It is known in the art that the performance of microbicides can frequently be enhanced by combination with one or more other microbicides. In fact, there have been numerous examples of synergistic combinations. Thus, other known microbicides may be combined advantageously with the stabilized isothiazolones of this invention. Isothiazolones are used in oil field water treatment, 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, or admixed with plastics. The products of this invention are especially useful as preservatives for the following: 1. Cosmetics, as nitrates present can be substantially reduced or eliminated: under certain conditions in the presence of amines or amine precursors, nitrates may form 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 divalent cations are those contained in a wide variety of products, such as paints, cosmetics, floor polishes and binders. 4. Plastics, as precipitated salts which can contribute directly or indirectly to haze, opacity, or physical weakness in the surface may be substantially reduced or eliminated. The following example will further illustrate this invention, but is not intended to limit it in any way. All parts and percentages are by weight and all temperatures in degrees Centigrade, unless otherwise stated. For comparison of the stabilization of the compositions of this invention with known materials the following tests were employed: using temperature-controlled ovens, vials of solvent and isothiazolone were made up and heated for fixed periods of time. The percentage of the starting isothiazolone remaining was determined by high performance liquid chromatography (HPLC). A temperature of 55°C was used. Results were considered indicative of acceptable stability when remainder values indicated essentially no loss during the time specified for the isothiazolone or isothiazolone mixture studied. I. Stability Test for 5-Chloro-2-methyl-3-isothiazolone/2-Methyl-3-isothiazolone EXAMPLE 1 A 15% by weight solution of 5-chloro-2-methyl-3-isothiazolone/2-methyl-3-isothiazolone (4.3/1:wt/wt) was prepared in phenoxyethanol and in dipropylene glycol. The solutions were stored at 55°C and analyzed for total isothiazolone (AI) remaining after 1 and 2 weeks. Results are give in Table 1. STABILIZATION OF 5-CHLORO-2-METHYL-3-ISOTHIAZOLONE/2-METHYL-3-ISOTHIAZOLONE BY PHENOXYETHANOL AT 55°C Solvent 1 week 2 weeks Dipropylene Glycol 89 2 Phenoxyethanol 95 97

Claims: A method of stabilizing a 3-isothiazolone of the formula wherein Y is (C₁-C₁₈)alkyl or (C₃-C₁₂)cycloalkyl each optionally substituted with one or more of hydroxy, halo, cyano, alkylamino, dialkylamine, arylamino, carboxy, carbalkoxy, alkoxy, aryloxy, alkylthio, arylthio, haloalkoxy, cycloalkylamino, carbamoxy, or isothiazolonyl; an unsubstituted or halo-substituted (C₂-C₈) alkenyl or alkynyl; a (C₇-C₁₀)aralkyl optionally substituted with one or more of halogen, (C₁-C₄)alkyl or (C₁-C₄)alkoxy; or an aryl optionally substituted with one or more of halogen, nitro, (C₁-C₄)alkyl, (C₁-C₄)alkyl-acylamino, carb(C₁-C₄)alkoxy or sulfamyl; and R and R¹ is each independently H, halogen or (C₁-C₄) alkyl; comprising incorporating therewith an effective amount of a phenoxyalkanol, preferably by dissolving said 3-isothiazolone in the phenoxyalkanol. Method according to Claim 1, wherein the weight ratio of 3-isothiazolone to phenoxyalkanol is from 0.1:99.9 to 25:75. Method according to any preceding claim, wherein said 3-isothiazolone is 5-chloro-2-methyl-3-isothiazolone, 2-methyl-3-isothiazolone, 2-octyl-3-isothiazolone, 4,5-dichloro-2-cyclohexyl-3-isothiazolone or 4,5-dichloro-2-octyl-3-isothiazolone. Method according to any preceding claim, wherein the amount of water present is less than 5% by weight, preferably 0%. Method according to any preceding claim, wherein said phenoxyalkanol is phenoxyethanol and/or phenoxyisopropanol. An isothiazolone concentrate composition, preferably in the form of a solution, comprising from 75 to 99.9% by weight of a phenoxyalkanol, and a 3-isothiazolone as defined in claim 1, and no water or other stabilizer. Composition according to claim 6, wherein the weight ratio of 3-isothiazolone to phenoxyalkanol is from 0.1:99.9% to 25:75. Composition according to claims 6 or 7, wherein said 3-isothiazolone is 5-chloro-2-methyl-3-isothiazolone, 2-methyl-3-isothiazolone, 2-octyl-3-isothiazolone, 4,5-dichloro-2-cyclohexyl-3-isothiazolone or 4,5-dichloro-2-octyl-3-isothiazolone. Composition according to any one of claims 6 to 8, wherein said phenoxyalkanol is phenoxyethanol and/or phenoxyisopropanol. The use of a phenoxyalkanol, preferably phenoxyethanol or phenoxyisopropanol, to stabilise an isothiazolone. A method of preventing or inhibiting the growth of bacteria fungi or algae in a locus subject or susceptible to contamination thereby, comprising incorporating therewith an effective amount of a composition as defined in any one of claims 6 to 9.

Inventors: MATTOX JOHN ROBERT, WILLINGHAM GARY LEWIS, MATTOX, JOHN ROBERT, WILLINGHAM, GARY LEWIS
Applicants: ROHM & HAAS, ROHM AND HAAS COMPANY
Application year: 1991
Main classification: A01N43
IPC codes: A01N43, C07D275