Resources Contact Us Home
Browse by: INVENTOR PATENT HOLDER PATENT NUMBER DATE
 
 
Stabilization of non-aqueous solutions of 3-isothiazolones
RE34185 Stabilization of non-aqueous solutions of 3-isothiazolones
Patent Drawings:

Inventor: Amick
Date Issued: February 23, 1993
Application: 07/606,222
Filed: October 31, 1990
Inventors: Amick; David R. (Chalfont, PA)
Assignee: Rohm and Haas Company (Philadelphia, PA)
Primary Examiner: Rivers; Diana G.
Assistant Examiner:
Attorney Or Agent: Fein; Michael B.
U.S. Class: 548/213
Field Of Search: 548/213; 514/372
International Class:
U.S Patent Documents: 3870795; 4067878; 4188376; 4241214; 4281136; 4396413
Foreign Patent Documents: 0166611; 0194146; 5140726; 56-99401; 2004747A
Other References: Lachman et al., "The Theory and Practice of Industrial Pharmacy", 2nd ed., Lea & Febiger, Philadelphia, 1976, pp. 32-43..









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.
Claim: 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 orhalo 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 or4-methoxyphenyl; R is halo; R.sup.1 is hydrogen, halogen or (C.sub.1 -C.sub.4)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..]. .[.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. Astabilized 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 carbonatoms, an unsubstituted cycloalkyl of 5 to 8 carbon atoms, benzyl, or 3,4-dichloro phenyl or 4-methoxy phenyl

R is halo; R.sup.1 is hydrogen, halogen or (C.sub.1 -C.sub.4) alkyl, and from 90 to 99.5% by weight of dipropylene glycol, polypropylene glycol,

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

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 alkynylof 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.sup.1 is halo; Ris hydrogen, halogen or (C.sub.1 -C.sub.4) 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 benzylalcohol. .Iaddend.

.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 consistingessentially 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 cycloalkylof 5 to 8 carbon atoms, benzyl, or 3,4-dichloro phenyl or 4-methoxy phenyl

R.sup.1 is halo; R is hydrogen, halogen or (C.sub.1 -C.sub.4) alkyl, and from 90 to 99.5% by weight of dipropylene glycol, polypropylene glycol,

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.

.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 8carbon 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.sup.1 is halo; R ishydrogen, halogen or (C.sub.1 -C.sub.4) 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.

.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 groupof 2 to 8 carbon atoms, an unsubstituted cycloalkyl of 5 to 8 carbon atoms, benzyl, or 3,4-dichlorobenzyl, 4-methoxybenzyl; R.sup.1 is halo; R is hydrogen, halogen or (C.sub.1 -C.sub.4) alkyl, and from 90 to 99% by weight of a solvent selected from thegroup consisting of ethylene glycol, dipropylene glycol, polypropylene glycol, 1,5-pentanediol, propylene glycol, diethylene glycol and triethylene glycol, said solution containing no

water. .Iaddend. .Iadd.15. The solution of claim 14 wherein said compound is 5-chloro-2-methyl-4-isothiazoline-3-one. .Iaddend.
Description: This invention relates to solvent stabilizedsolutions 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 5to 8 carbon atoms, an unsubstituted or substituted aralkyl or an unsubstituted or substituted aryl;

R hydrogen, halo, or a (C.sub.1 -C.sub.4)alkyl and R.sup.1 is hydrogen, halogen or (C.sub.1 -C.sub.4)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, chloropropyland 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 aprecipitate 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 oilsand 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 ahydroxy 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 R.sup.1 are hydrogen or lower alkyl, such as methyl, ethyl, propyl, butyl, pentyl and the like and X is--(CH.sub.2).sub.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 dipropyleneglycol, 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.degree. 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 divalentnitrate 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 15to 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, diethyleneglycol, 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-formaldehydecontaining 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 saltswhich 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 aby-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 arepreferred, 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 dissolvesand 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 ______________________________________ Isothiazoline 0.5-10 89-99.5 0-1.0 Preferred 3.0-10.0 89.0-97.0 0-1.0 Most Preferred 6.0-10.0 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 oilpreservatives, 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 amineprecursors 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 tothe 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.degree. C. causes an acceleration effect so that one week is equivalent to about 3 months at 25.degree. C.; two weeks is equivalent to about 6 months; three weeks is equivalent to 9 months; and fourweeks is equivalent to about 12 months, and so on. The temperature of 65.degree. C. causes an acceleration effect so that one week is equivalent to about 7 months at 25.degree. C.; two weeks is equivalent to 14 months; three weeks is equivalent to 21months; 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.degree. C. or about 2 weeks at 65.degree. 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.degree. C. ("No H.sub.2 O") (1% AI to start)

______________________________________ 2 2 4 6 Solvent 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) Propyleneglycol 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.degree. C. (1% AI to start)

______________________________________ 1 2 3 4 Organic 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 nonitrate, 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 mixturewas stirred and cooled (.ltoreq.15.degree. C.) as 15 g of triethylamine was added dropwise over 20 min. Five minutes after the addition was completed the ET.sub.3 N. HCl salt was removed by filtration to afford a toluene solution of A.I. as thefiltrate. A 22.3 gm portion of the toluene solution was mixed with 25 gm of 1% Cu(NO.sub.3).sub.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 solutionwas rotovapped 1 hr at 55.degree. 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(NO.sub.3).sub.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.degree. C. 65.degree. C. ______________________________________ 7.5 .gtoreq.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.

* * * * *
 
 
  Recently Added Patents
Box with foldable sidewalls and locking mechanisms with overload protection
Seizure detection using coordinate data
On-chip radial cavity power divider/combiner
Composite lamination using array of parallel material dispensing heads
Method of verifying key validity and server for performing the same
Node device
Adjustable breast support apparatus
  Randomly Featured Patents
Method for the manufacture of a semiconductor device and a semiconductor device obtained through it
Hydrocarbon-soluble magnesium-aluminum compositions
Memory controller for non-homogenous memory system
Electroviscous fluid
LCD monitor
Power steering system
Surface configuration of a vehicle, toy and/or other replicas
Method for roughening ceramic substrate surface and method for manufacturing printed circuit board using surface-roughened ceramic substrate
Lightning protection fastener, aircraft assembly, and method of manufacturing aircraft assembly component
Process and design for producing inside coils