Stabilized aqueous amide antimicrobial composition

Aqueous antimicrobial compositions which comprise a halogenated amide antimicrobial, such as 2,2-dibromonitrilopropionamide, a water miscible organic solvent such as a straight chain polyalkylene glycol (e.g., polyethylene glycol 200) or an ether thereof (e.g., a mono- or di- lower alkyl and/or phenyl ether) and water are stabilized against decomposition of the halogenated amide antimicrobial by the addition of a quaternary salt stabilizer, such as methyl triphenyl phosphonium bromide, benzyl triethyl ammonium bromide, etc. The compositions, so stabilized, exhibit reduced rates of decomposition of the halogenated amide antimicrobial relative to the corresponding non-stabilized aqueous compositions.

BACKGROUND OF THE INVENTION 
This invention relates to stabilized aqueous antimicrobial compositions 
which comprise a halogenated amide as the active (i.e., antimicrobial) 
ingredient and to processes for their preparation. 
Halogenated amides such as 2,2-dibromonitrilopropionamide are useful as 
antimicrobials in various applications. See, for example, Nolan et al., 
U.S. Pat. No. 2,419,888; Schmidt et al., U.S. Pat. No. 3,493,658; and CIBA 
S.A. Belgian Pat. No. 668,336. Certain halogenated amides are useful in 
the finishing of textiles, as taught by Chance et al., U.S. Pat. Nos. 
3,350,164 and 3,403,174. Others are useful as slimicides in aqueous 
systems such as paper pulp and cooling towers and as sterilizing agents 
for drycleaning fluids. See, for example, Wolf, U.S. Pat. No. 3,647,610; 
Wolf, U.S. Pat. No. 3,649,166; Wolf et al., 
"2,2-Dibromo-3-Nitrilopropionamide, A Compound with Slimicidal Activity", 
Applied Microbiology, Vol. 24, No. 4, pp. 581-584 (1972); and Moyle et 
al., U.S. Pat. No. 3,928,575. 
In the storage, shipment and use of such antimicrobial agents, it is often 
desirable to employ the antimicrobial agent in the form of a liquid 
concentrate composition wherein the halogenated amide antimicrobial is 
dissolved in a mixture of an organic solvent and water. However, the 
presence of water in such compositions often accelerate decomposition of 
the halogenated amide antimicrobial. See, for example, U.S. Pat. No. 
3,689,660 and "Rates and Products of Decomposition of 
2,2-Dibromo-3-Nitrilopropionamide", Exner et al., J. Agr. Food Chem., Vol. 
21, No. 5, pp. 838-842 (1973). Accordingly, in order to obtain adequate 
stability for many purposes, it has heretofore been necessary to resort to 
essentially anhydrous liquid concentrate compositions and it has therefore 
been necessary to essentially exclude water from the ingredients used in 
the preparation thereof. 
Consequently, it is desirable to provide a means of reducing the adverse 
impact of water upon the aforementioned liquid concentrate compositions 
and to thereby provide (a) aqueous halogenated amide antimicrobial 
compositions having improved stability and (b) simplified, economical 
processes for the preparation of stable liquid concentrate compositions. 
SUMMARY OF THE INVENTION 
It has now been found that the rate of decomposition of the halogenated 
amide antimicrobial in the aforementioned aqueous liquid concentrate 
compositions is substantially reduced by the addition of a quaternary 
ammonium or phosphonium salt. Thus, in one aspect the instant invention is 
a stabilized aqueous antimicrobial composition, which comprises a water 
miscible organic solvent; water; a halogenated amide antimicrobial; and a 
stabilizing amount of a quaternary ammonium or phosphonium stabilizer. 
Typically, such composition has a pH of from about 2 to about 5 
(preferably from about 3 to about 4). 
In another aspect the instant invention is a process for preparing an 
aqueous halogenated amide antimicrobial composition wherein the aqueous 
component of such composition comprises the aqueous reaction medium in 
which the halogenated amide antimicrobial was prepared. Such process 
comprises the steps of: 
(a) preparing the halogenated amide antimicrobial by the acid catalyzed 
reaction of a non-halogenated amide with halogen in aqueous solution; 
(b) dissolving the resulting aqueous reaction mixture in a water miscible 
organic solvent; and 
(c) adding to the reaction mixture, or to the water miscible organic 
solvent solution thereof, a stabilizing amount of a quaternary ammonium or 
phosphonium stabilizer. 
Typically, the aforementioned process also involves a pH adjustment step 
such that the composition resulting from such process has a pH of from 
about 2 to about 5, preferably from about 3 to about 4. 
As used herein, the term "water miscible" means that the organic solvent is 
soluble in water (i.e., mixes or blends uniformly with water) at least to 
the degree required to achieve the desired solvent to water ratio in the 
aqueous composition and preferably such solvent is soluble in water in all 
proportions. 
The terms "antimicrobial compound" and "halogenated amide antimicrobial" 
are used interchangeably herein and refer to halogenated amides which 
function as biocides (i.e., compounds which inhibit the growth of, or 
kills, microorganisms such as bacteria, molds, slimes, fungi, etc.). 
The term "stabilizing amount" as employed herein refers to an amount of 
stabilizer sufficient to measurably reduce the decomposition rate of the 
halogenated amide antimicrobial in the aqueous antimicrobial composition. 
The aforementioned reduction in the decomposition rate of the halogenated 
amide antimicrobial is, of course, relative to the decomposition rate 
encountered with a corresponding aqueous antimicrobial composition in the 
absence of the stabilizer under the same test conditions. Such reduction 
is deemed to be "measurable" if it is detectible (and reproducible) by the 
iodometric test method which is described hereinafter in conjunction with 
the working examples. 
The aqueous antimicrobial compositions of the invention are useful as 
slimicides in aqueous systems such as paper pulping processes and cooling 
towers and as sterilizing agents for drycleaning fluids. Such compositions 
exhibit improved stability toward decomposition of the halogenated amide 
antimicrobial for extended periods under a wide variety of storage, 
packaging and handling conditions. They are easily handled and can be 
employed in the above applications pursuant to conventional techniques 
such as those described in U.S. Pat. No. 3,689,660. 
The indicated process for preparing the aqueous antimicrobial composition 
is advantageous in that suitably stable compositions can be prepared 
without separation of the halogenated amide antimicrobial from the aqueous 
medium in which it was prepared.

DETAILED DESCRIPTION OF THE INVENTION 
Halogenated amide antimicrobials employed in the practice of this invention 
are alpha-haloamides; that is, compounds which contain an amide 
functionality (i.e., a moiety of the formula --C(O)--N&lt;) and which have at 
least one halogen atom on a carbon atom located adjacent to (i.e., in the 
alpha position relative to) the carbonyl group (i.e., the --C(O)-- group) 
of such amide functionality. Advantageously such halogenated amide 
antimicrobials are halogenated nitrilopropionamides or halogenated malonic 
diamides having the formula: 
##STR1## 
wherein: X is hydrogen, halogen or a cyano radical, i.e., --C.tbd.N, 
(preferably hydrogen, chlorine or bromine); 
each R group is independently hydrogen, a monovalent "saturated hydrocarbon 
radical" or an inertly substituted monovalent "saturated hydrocarbon 
radical" or the two R groups are, jointly, a divalent "saturated 
hydrocarbon radical", or an inertly substituted divalent "saturated 
hydrocarbon radical", which, taken with the adjacent nitrogen atom, forms 
a heterocyclic ring having from 4 to about 10 ring members; and 
R.sub.1 is a cyano radical (i.e., --C.tbd.N) or an amido radical having the 
formula: 
##STR2## 
wherein R is as hereinbefore defined. (Preferably R.sub.1 is a cyano 
radical.) 
As used herein, the term "saturated hydrocarbon radical" refers to a 
hydrocarbon radical which is free from aliphatic carbon to carbon 
unsaturation. Thus, such term includes radicals such as alkyl, cycloalkyl, 
aryl, alkylaryl, arylalkyl, cycloalkylaryl, etc., and excludes radicals 
such as alkenyl, cycloalkenyl, alkynyl and the like. 
As used herein, the term "inertly substituted saturated hydrocarbon 
radical" refers to a "saturated hydrocarbon radical" having one or more 
chain linkage or substituent which is "inert" in the sense that such chain 
linkage or substituent does not readily react with the ingredients of the 
aqueous antimicrobial composition. Suitable inertly substituted saturated 
hydrocarbon radicals thus include, for example, haloalkyl, haloaryl, 
halocycloalkyl, aminoalkyl, aminoaryl, aminocycloalkyl, hydroxyalkyl, 
hydroxyaryl, hydroxycycloalkyl, cyanoalkyl, cyanoaryl, cyanocycloalkyl, 
and the like. 
The aforementioned halogenated amide antimicrobials of the formula I thus 
include brominated nitrilopropionamides (i.e., compounds of the formula I 
wherein R.sub.1 is a cyano radical), such as 
2-bromo-3-nitrilopropionamide, 2-bromo-2,3-dinitrilopropionamide, 
2,2-dibromo-3-nitrilopropionamide, 
N-(n-butyl)-2-bromo-3-nitrilopropionamide; 
N,N-dimethyl-2,2-dibromo-3-nitrilopropionamide, 
2-chloro-2-bromo-3-nitrilopropionamide, 
N-(n-propyl)-2-iodo-2-bromo-3-nitrilopropionamide, 
N-methyl-N-ethyl-2-fluoro-2-bromo-3-nitrilopropionamide, 
N-phenyl-2-cyano-2-bromo-3-nitrilopropionamide, 
N-cyclohexyl-2,2-dibromo-3-nitrilopropionamide, 
N-benzyl-2-bromo-3-nitrilopropionamide, 
N-(2,2-dibromo-3-nitrilopropionoyl)-piperidine and the like. 
The aforementioned halogenated amide antimicrobials of the formula I also 
include mono- and di-bromo-malonic diamides (i.e., compounds of the 
formula I wherein R.sub.1 is an amido radical as hereinbefore described), 
such as 2-bromomalonic diamide, 2,2-dibromomalonic diamide, 
N-methyl-N'-ethyl-2-chloro-2-bromomalonic diamide, 
N-phenyl-2-iodo-2-bromomalonic diamide, and the like. 
Among the aforementioned halogenated amide antimicrobials, those wherein, 
in the formula I, R.sub.1 is a cyano radical, X is hydrogen, chlorine or 
bromine and each R is independently hydrogen, lower alkyl (e.g., an alkyl 
group of from 1 to about 6 carbon atoms) or phenyl are preferred, 
especially those of the formula I wherein each R independently is hydrogen 
or methyl and X is hydrogen or bromine. Such halogenated amide 
antimicrobials include 2-bromo-3-nitrilopropionamide, 
2,2-dibromo-3-nitrilopropionamide, N-methyl-2-bromo-3-nitrilopropionamide, 
N-phenyl-2-bromo-2-chloro-3-nitrilopropionamide, 
N-methyl-2,2-dibromo-3-nitrilo-propionamide, 
N,N-dimethyl-2-bromo-3-nitrilopropionamide, 
N,N-diethyl-2,2-dibromo-3-nitrilopropionamide, and 
N,N-dimethyl-2,2-dibromo-3-nitrilopropionamide. 
Also of particular interest are the dibrominated nitrilopropionamides 
(i.e., the halogenated amide antimicrobials of the formula I wherein X is 
bromine and R.sub.1 is cyano) wherein each R independently is hydrogen, 
lower alkyl or phenyl. Such compounds include 
2,2-dibromo-3-nitrilopropionamide, 
N-(n-butyl)-2,2-dibromo-3-nitrilopropionamide, 
N,N-dimethyl-2,2-dibromo-3-nitrilopropionamide, 
N-phenyl-N-methyl-2,2-dibromo-3-nitrilopropionamide and the like; 
especially 2,2-dibromo-3-nitrilopropionamide. 
The aqueous antimicrobial compositions of the invention normally contain 
from about 1 to about 25 percent by weight of the hereinbefore described 
halogenated amide antimicrobial based upon the total weight of the 
composition. However, the decomposition of the halogenated amide 
antimicrobials has been observed to be more pronounced when the aqueous 
compositions contain less than about 20 percent by weight of the 
antimicrobial on a total weight basis. Thus, stabilized aqueous 
antimicrobial compositions which, by virtue of the relatively more 
pronounced benefits of stabilization, are of particular interest comprise 
from about 1 to about 15, preferably from about 1 to about 10, most 
preferably from about 1 to about 5, weight percent of the total 
composition. 
In the composition of this invention, the aforementioned halogenated amide 
antimicrobial is dissolved in a mixture of water and a water miscible 
organic solvent. Suitable organic solvents include any water miscible 
organic solvent in which the halogenated amide antimicrobial is at least 
partially soluble. Preferably the organic solvent is one in which the 
halogenated amide antimicrobial is soluble at normal room temperature 
(i.e., from about 20.degree. to about 25.degree. C.) to the extent of at 
least about 5 parts by weight of the antimicrobial in about 95 parts by 
weight of the solvent. The most preferred water miscible organic solvents 
are those in which the antimicrobial is soluble to the extent of at least 
about 10 (especially at least about 20) parts by weight of the 
antimicrobial in about 80 parts by weight of the solvent at normal room 
temperatures (i.e., from about 20.degree. to about 25.degree. C.). 
Advantageously, the organic solvent is a polyalkylene glycol or an ether 
thereof, especially a normally liquid straight chain polyalkylene glycol 
or a mono- or di-saturated hydrocarbyl ether thereof wherein the term 
"saturated hydrocarbyl" refers to a monovalent saturated hydrocarbon 
radical as hereinbefore defined. 
Generally, such polyalkylene glycols and polyalkylene glycol ethers have a 
weight average molecular weight (Mw) of from about 75 to about 1000. Such 
average molecular weights are hereinafter designated for the particular 
glycols involved by placing a numeral representing the weight average 
molecular weight after the glycol name. 
Of particular interest in the practice of the invention are the 
polyalkylene glycols of the ethylene, trimethylene or tetramethylene 
series and the mono- and di-lower (e.g., containing from 1 to about 6 
carbon atoms) saturated hydrocarbyl ethers thereof. Examples of such 
particularly advantageous solvents include polyethylene glycols, 
trimethylene glycols, tetramethylene glycols and the mono- and di-lower 
saturated hydrocarbyl (e.g., C.sub.1 to about C.sub.6 alkyl and phenyl) 
ethers of such glycols. 
Examples of the aforementioned polyalkylene glycols and ethers include 
1,4-butanediol, triethylene glycol, polyethylene glycol 200, tetraethylene 
glycol, polyethylene glycol 400, diethylene glycol dimethyl ether, 
diethylene glycol phenyl ether, diethylene glycol ethyl phenyl ether, 
polytrimethylene glycol 200, diethylene glycol, triethylene glycol methyl 
ether and polyethylene glycol 600. 
Preferably, the polyalkylene glycol or ether ingredient is a polyethylene 
glycol, or a mixture of polyethylene glycols, having Mw of from about 175 
to about 250. Most preferably the polyalkylene glycol ingredient is 
polyethylene glycol 200. 
The amount of the aforementioned water miscible organic solvent employed in 
the practice of the invention is not particularly critical. 
Advantageously, however, a sufficient amount is employed to prevent 
precipitation of the halogenated amide antimicrobial during shipping, 
storage and use of the aqueous antimicrobial composition. The amount of 
the organic solvent desirably employed will thus depend upon such factors 
as the solubility of the halogenated amide antimicrobial in the organic 
solvent, the desired concentration of the halogenated amide antimicrobial 
in the composition, and the like. However, as a general rule the organic 
solvent constitutes from about 5 to about 90, preferably from about 10 to 
about 80, more preferably from about 25 to about 75, most preferably from 
about 35 to about 70, percent by weight of the total antimicrobial 
composition. 
As has been noted, any of the aforementioned water miscible organic 
solvents can be suitably employed in the practice of this invention to 
dissolve the aforementioned halogenated amide antimicrobial. However, it 
has been found (and such finding constitutes the subject matter of a 
commonly owned application by George A. Burk, Charles A. Wilson and 
Charles E. Reineke, filed even date herewith) that the aforementioned 
problem of halogenated amide decomposition under aqueous conditions is 
substantially more pronounced in the presence of salts of organic acids 
and/or glycols having a molecular weight of less than about 70 gram per 
mole; both of which, for example, are potentially common minor impurities 
in many commercially available unpurified polyalkylene glycols and ethers 
thereof. Thus, the benefits attributable to the herein disclosed 
stabilizers are relatively more pronounced in those stabilized aqueous 
antimicrobial compositions which employ organic solvents containing the 
aforementioned impurities or which contain such impurities from some other 
source. 
The amount of water contained by the aqueous antimicrobial composition of 
the invention is likewise not particularly critical to the practice of the 
invention. However, as a general rule the compositions of the invention 
employ water in an amount of from about 5 to about 90, preferably from 
about 10 to about 85, more preferably from about 15 to about 70, most 
preferably from about 20 to about 60 weight percent based upon the weight 
of the total antimicrobial composition. 
The stabilizers employed in the practice of this invention are quaternary 
ammonium or phosphonium compounds (i.e., compounds which comprise a 
quaternized nitrogen or phosphorus atom having four covalent bonds with 
two, three of four distinct organic radicals and an ionically bonded 
neutralizing anion). Such stabilizers thus include N,N,N,N-tetra(saturated 
hydrocarbyl)ammonium or phosphonium salts such as benzyltriethyl ammonium 
bromide, methyltriphenylphosphonium bromide, etc.; 
N,N-dihydrocarbyl-containing saturated heterocyclic quaternary ammonium or 
phosphonium salts (i.e., wherein the two remaining nitrogen or phosphorus 
covalent bonds are satisfied by a single divalent organic radical 
containing, for example, 4 or 5 carbon atoms in the ring structure) such 
as N,N-dimethylpyrrolidinium bromide, N,N-diethylpiperazinium iodide, 
N,N-dimethylpiperidinium chloride, N,N-dibutylmorpholinium chloride, the 
corresponding quaternary phosphonium salts, etc.; and 
N-hydrocarbyl-containing unsaturated (e.g., aromatic) quaternary ammonium 
or phosphonium salts (i.e., wherein the three remaining or phosphorus 
covalent bonds are satisfied by a single trivalent organic radical, e.g., 
being divalent on one atom thereof and monovalent on another) such as 
N-hexadecylpyridinium chloride, N-(n-butyl)pyridinium bromide, etc. 
The quaternary ammonium or phosphonium stabilizers preferably employed in 
the practice of this invention comprise a quaternized nitrogen or 
phosphorus atom having four monovalent saturated hydrocarbon radicals 
covalently bonded thereto (saturated hydrocarbon radical being as 
hereinbefore defined) and having a neutralizing anion associated therewith 
(e.g., ionically bonded thereto). Such preferred quaternary ammonium or 
phosphonium stabilizers can thus be represented by the formula: 
EQU (R.sub.2).sub.4 Q.sup..sym..crclbar. A 
wherein: 
Q.sup..sym. is a quaternized atom of nitrogen or phosphorus; 
each R.sub.2 group is independently a monovalent saturated hydrocarbon 
radical (such as alkyl, aryl, alkylaryl, alkylarylalkyl, arylalkyl, 
cycloalkyl, etc.), typically containing from 1 to about 25 carbon atoms; 
and 
A.sup..sym. is a neutralizing anion such as a halide (e.g., chloride, 
bromide, or iodide; especially chloride or bromide), bisulfate ion, an 
acetate ion, etc. 
Examples of the aforementioned preferred quaternary ammonium or phosphonium 
salts include tetraalkyl ammonium salts such as tetramethyl-, tetraethyl-, 
tetra-n-butyl-, tetrahexyl-, and trioctylmethyl-, dodecyltrimethyl-, 
hexadecyltriethyl-, and tridecylmethylammonium chlorides, bromides, 
iodides, bisulfates, acetates, etc.; arylalkylammonium salts, such as 
tetrabenzylammonium chloride, benzyltrimethyl-, n-C.sub.12-18 
alkyldimethylbenzyl, benzyltriethyl-, benzyltributyl-, n-C.sub.12-18 
alkyldimethyl(ethylbenzyl)- and phenethyltrimethylammonium chlorides, 
bromides, iodides, etc.; arylammonium salts such as 
triphenylmethylammonium bromide, trimethylnaphthylammonium bromide, 
p-methylphenyltrimethylammonium chloride, etc.; and the corresponding 
phosphonium salts. 
The hereinbefore described quaternary ammonium or phosphonium stabilizer is 
employed in the practice of the invention in a "stabilizing amount", which 
term is defined hereinbefore. Advantageously, such stabilizer is employed 
in an amount sufficient to reduce by at least about 20 percent (preferably 
by at least about 30 percent and most preferably by at least about 40 
percent) the amount of antimicrobial compound which decomposes during 
about 15 days (preferably about 30 days) of storage at 50.degree. C. Such 
decomposition reduction is, of course, relative to that which occurs under 
the same conditions in the absence of the aforementioned stabilizer. In 
quantitative terms, the amount of stabilizer needed to achieve the desired 
degree of stabilization can vary depending upon the remainder of the 
composition (i.e., the identity and concentration of the other ingredients 
in the particular composition involved) and upon the particular stabilizer 
employed. However, as a general rule the stabilizer constitutes between 
about 0.05 and about 10, preferably between about 0.1 and about 5, most 
preferably between about 0.5 and about 2, percent by weight of the total 
composition. 
In addition to the hereinbefore defined ingredients, the aqueous 
antimicrobial composition of the invention can optionally contain other 
ingredients. Such optional ingredients can be inert in the sense that they 
neither inhibit nor accelerate decomposition of the antimicrobial 
compound. Alternatively, such optional ingredients can themselves be 
stabilizers for the halogenated amide antimicrobial. Thus, for example, 
the stabilized aqueous antimicrobial composition of the invention can, in 
addition to the aforementioned quaternary ammonium or phosphonium 
stabilizer, further comprise other compounds which are stabilizers in 
their own right as disclosed in commonly owned applications filed even 
date herewith. Such optional additional stabilizers thus include acids or 
anhydrides (e.g., acetic acid, ethylenediaminetetraacetic acid, succinic 
acid, succinic anhydride, glycolic acid, etc.) as disclosed by George A. 
Burk; carbamoyl or sulfamoyl compounds (e.g., N-methyl urea, N,N-diethyl 
urea, biuret, sulfamide, oxamide, N,N-dimethylformamide, caprolactam, 
N-methyl-2-pyrrolidone, dimethylhydantoin, succinimide, etc.) as disclosed 
by George A. Burk and Charles E. Reineke; cyclic ethers (e.g., 
1,4-dioxane, sym-trioxane, tetrahydrofuran, N-methyl morpholine, etc.) as 
disclosed by George A. Burk and Charles A. Wilson; aldehydes (e.g., 
formaldehyde, paraformaldehyde, vanillin, etc.) as disclosed by George A. 
Burk, Charles A. Wilson and Charles E. Reineke; and azine or nitrile 
compounds (e.g., cyanuric acid, 2-chloro-4,6-bis(ethylamino)-s-triazine, 
cyanoguanidine, succinonitrile, etc.) as disclosed by George A. Burk. The 
amount of such other stabilizer which is desirably employed varies 
depending upon a number of factors, such as the identity and amounts of 
the specific ingredients involved. However, as a general rule between 
about 0.1 and about 2, preferably between about 0.2 and about 1 percent by 
weight is employed based upon the total weight of the antimicrobial 
composition. 
The order of combination of the hereinbefore described ingredients is not 
critical to the obtention of a decreased decomposition rate relative to 
that obtained with the corresponding non-stabilized composition. However, 
in order to avoid excessive amounts of decomposition prior to 
stabilization, it is generally desirable to avoid prolonged exposure of 
the antimicrobial compound to the water in the composition prior to 
addition of the stabilizer thereto. Similarly, it is generally desirable, 
in order to retain optimum antimicrobial activity, to prepare, store, 
transport and handle the stabilized compositions of the invention at the 
lowest practicable temperature (normally ambient temperature). 
As has been noted, the hereinbefore described stabilizers have been found 
to reduce the rate of decomposition of the halogenated amide antimicrobial 
in a mixture of an organic solvent and water. A particularly beneficial 
result of such phenomenon is that suitably stable halogenated amide 
antimicrobial compositions can be prepared directly from a mixture of the 
antimicrobial and the aqueous reaction medium in which it was prepared. 
Specifically, separation of the halogenated amide antimicrobial from its 
aqueous reaction medium is conveniently eliminated by incorporating such 
reaction medium into the antimicrobial composition and by counteracting 
the adverse impact thereof by adding the aforementioned quaternary 
ammonium or phosphonium stabilizer. 
Thus, in one aspect this invention is a process for preparing the 
aforementioned stabilized aqueous antimicrobial compositions, which 
process comprises the steps of (a) preparing the halogenated amide 
antimicrobial by the acid catalyzed reaction of the corresponding 
non-halogenated amide with halogen in aqueous solution; (b) dissolving the 
resulting aqueous reaction mixture in the hereinbefore described water 
miscible organic solvent; and (c) adding to the reaction mixture, or to 
the water soluble organic solvent solution thereof, a stabilizing amount 
of the aforementioned quaternary ammonium or phosphonium stabilizer. 
Typically, the aforementioned process also comprises an additional step in 
which the pH of the reaction mixture, the organic solvent solution, or the 
stabilized organic solvent solution is adjusted such that the pH of the 
antimicrobial composition is from about 2 to about 5, preferably from 
about 3 to about 4. Preferably, such pH adjustment step is performed after 
preparation of the halogenated amide and prior to dissolution of the 
reaction mixture in the organic solvent. In such instance, adjustment of 
the pH to a value of from about 5 to about 7 (preferably from about 5.5 to 
about 6.5) typically provides the antimicrobial composition with a pH 
within the desired range following the dissolution step. 
The particular reagent employed to adjust the pH in the aforementioned pH 
adjustment step is not particularly critical. However, as a general rule, 
alkali metal or alkaline earth metal carbonates or bicarbonates 
(especially sodium carbonate) are advantageously employed. 
The preparation of the halogenated amide antimicrobial (i.e., step (a) 
above) can be accomplished in any convenient conventional manner. Thus, 
for example, the halogenated amide antimicrobial can be prepared by the 
acid catalyzed reaction of the corresponding non-halogenated amide (e.g., 
cyanoacetamide, malonic diamide, and N-substituted derivatives thereof) 
with halogen (especially bromine) in aqueous solution, preferably at a 
temperature of less than about 40.degree. C. and preferably at a hydrogen 
halide (which is a reaction by-product) concentration of less than about 
20 weight percent on a total weight basis. 
Preferably, however, the initial step of such process is performed pursuant 
to the improved procedure which is disclosed by U.S. Pat. No. 3,751,444. 
In such preferred process for preparing the halogenated amide 
antimicrobial, the improved aspect comprises introducing a water-soluble 
bromate into the aqueous reaction medium. Further details relating to the 
practice of such preferred initial step are found in U.S. Pat. No. 
3,751,444, the disclosure of which is hereby incorporated by reference. 
After the halogenated amide antimicrobial has been prepared in the 
aforementioned manner, the resulting reaction mixture is dissolved in the 
hereinbefore described organic solvent. Such dissolution step is performed 
either before or after addition of the stabilizer and without isolation of 
the halogenated amide antimicrobial from the aqueous reaction medium. Any 
of the hereinbefore described water miscible organic solvents can be 
suitably employed in such dissolution step. However, as has been noted, 
the presence in such solvent of salts of organic acids and/or glycols 
having a molecular weight of less than about 70 has been observed to 
deleteriously affect the stability of the halogenated amide antimicrobial. 
Accordingly, it is preferable (in order to obtain optimum stability in the 
resulting compositions of the instant process) to employ an organic 
solvent of the hereinbefore described type which is substantially free 
both of salts of organic acids and of glycols having molecular weights of 
less than about 70 grams per mole. 
In the aforementioned process, it is generally desirable to avoid prolonged 
exposure of the halogenated amide antimicrobial to the aqueous reaction 
medium in the absence of the stabilizer in order to prevent excessive loss 
(i.e., decomposition) of the halogenated amide product prior to 
stabilization. In addition the pH adjustment step is also desirably 
accomplished without prolonged delay since the decomposition rate of the 
halogenated amide antimicrobial is generally pH dependent and since such 
decomposition rate is typically minimized within the indicated pH range. 
In addition, since the rate of decomposition of the halogenated amide 
antimicrobial increases with increased temperature, it is preferable to 
conduct the aforementioned individual process steps (and to store, 
transport and handle the resulting aqueous antimicrobial compositions) at 
ambient temperature (e.g., from about 20.degree. to about 25.degree. C.) 
or less in order to avoid excessive decomposition of the antimicrobial 
during such operations. However, it is to be noted that, in both the 
aforementioned process and the hereinbefore presented general description 
of the preparation of the compositions of the invention, the preferred 
nature of the indicated temperature and pH ranges relates only to the 
absolute amount of decomposition and is not critical to the obtention of 
(or to the relative magnitude of) the stabilizing effect provided by the 
quaternary ammonium or phosphonium stabilizer as compared to the 
corresponding non-stabilized composition. 
Naturally, in the practice of the aforementioned process, other ingredients 
such as those described hereinbefore, can be added to the aqueous 
composition either during or after its preparation pursuant to such 
process. 
The practice of the instant invention is further illustrated by the 
following examples. In such examples all weight percentages are on a total 
weight basis unless otherwise indicated and the polyethylene glycol 
employed in such examples is a commercial grade mixture of polyethylene 
glycols having a weight average molecular weight of about 200 and 
commercially available as Polyglycol E-200 from The Dow Chemical Company. 
EXAMPLE 1 
Aqueous Solution of 2,2-Dibromo-3-nitrilopropionamide in Polyethylene 
Glycol 200 Stabilized with Methyl Triphenyl Phosphonium Bromide 
This example illustrates the destabilizing effect of water upon a solution 
of 2,2-dibromo-3-nitrilopropionamide (i.e., DBNPA) in polyethylene glycol 
200 (i.e., P.E.G. 200). This example also illustrates the stabilizing 
effect of methyl triphenyl phosphonium bromide upon DBNPA in an aqueous 
P.E.G. 200 solution. 
EXAMPLE 1 
A stabilized solution of DBNPA in a mixture of P.E.G. 200 and water is 
prepared by mixing together the following ingredients in an amber bottle. 
______________________________________ 
DBNPA 2.5 g 
P.E.G. 200 23.5 g 
Water 23.5 g 
Methyl triphenyl 
phosphonium bromide 0.5 g 
______________________________________ 
Anhydrous Control (i.e., Control 1) 
In the same manner a comparative nonaqueous solution of DBNPA in P.E.G. 200 
is prepared having the following ingredients. 
Dbnpa: 2.5 g 
P.e.g. 200: 47.5 g 
Aqueous Control (i.e., Control 2) 
In the same fashion a comparative non-stabilized solution of DBNPA in a 
mixture of P.E.G. 200 and water. This comparative solution has the 
following ingredients. 
Dbnpa: 2.5 g 
P.e.g. 200: 23.75 g 
Water: 23.75 g 
After the heat of dissolution (i.e., a temperature rise of about 5.degree. 
C.) has dissipated, the initial DBNPA content of each of the three 
solutions is verified by iodometry and the amber bottles are sealed and 
placed in a constant temperature oven at 50.degree. C. Periodically the 
solutions are removed from the oven and the DBNPA content at that point in 
time is determined by iodometry. The results in terms of the DBNPA content 
(in weight percent on a total weight basis) as a function of storage time 
at 50.degree. C. are summarized in Table I below. 
In this example, the relative DBNPA content of the various antimicrobial 
compositions is determined by iodometry. In such test method, an excess of 
potassium iodide (KI) is added to the antimicrobial composition and the 
amount of elemental iodine which has been liberated from the KI (via 
oxidation of the KI by the DBNPA) is determined by titration with a 
standard solution of sodium thiosulfate. The amount of DBNPA present in 
the composition tested is then calculated on the basis of the amount of 
elemental iodine liberated thereby. 
It should be noted that since certain of the intermediate decomposition 
products of DBNPA are also oxidizing agents, the indicated test method 
does not, strictly speaking, provide an exact measure of DBNPA content. 
However, such test method does provide a measure of the amount of DBNPA 
which has completely decomposed to the ultimate non-oxidizing species and 
thus provides a relative measure of the stability of the DBNPA 
compositions tested. 
TABLE I 
______________________________________ 
DBNPA CONTENT REMAINING 
AFTER THE INDICATED STORAGE 
PERIOD AT 50.degree. C. 
Initial DBNPA 10 13 20 30 
Content Days Days Days Days 
______________________________________ 
Example 1 
5.0 4.8 4.6 4.4 4.1 
Control 1* 
5.0 4.9 4.8 4.7 4.4 
Control 2* 
5.0 4.2 3.8 3.5 3.3 
______________________________________ 
*Not an example of the invention 
As is apparent from the foregoing results, the aqueous composition (i.e., 
Control 2) exhibits substantially more DBNPA decomposition than does the 
anhydrous composition of Control 1. In addition, comparison of the DBNPA 
content data for the stabilized aqueous composition of Example 1 with that 
of the non-stabilized aqueous composition of Control 2 shows that the 
methyl triphenyl phosphonium bromide provides a substantial reduction in 
the extent of DBNPA decomposition over each of the indicated storage 
periods. 
While the practice of the invention has been illustrated with reference to 
particular embodiments and examples, it should be understood that such 
embodiments and examples are not intended to limit the scope of the 
instantly claimed invention.