CA1073464A - Polymeric quaternary ammonium compounds - Google Patents
Polymeric quaternary ammonium compoundsInfo
- Publication number
- CA1073464A CA1073464A CA279,168A CA279168A CA1073464A CA 1073464 A CA1073464 A CA 1073464A CA 279168 A CA279168 A CA 279168A CA 1073464 A CA1073464 A CA 1073464A
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- CA
- Canada
- Prior art keywords
- rii
- riii
- compound
- riv
- grams
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
- A01N33/02—Amines; Quaternary ammonium compounds
- A01N33/12—Quaternary ammonium compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/12—Preparations containing hair conditioners
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
- C08G73/0206—Polyalkylene(poly)amines
- C08G73/0213—Preparatory process
- C08G73/0226—Quaternisation of polyalkylene(poly)amines
Abstract
ABSTRACT OF THE DISCLOSURE
Polymeric quaternary ammonium compounds having linear chain which terminate in quaternary ammonium moieties, which are part of the linear polymeric chain rather than appendages to or part of branches on such chain, thereby making further chain propogation impossible.
Polymeric quaternary ammonium compounds having linear chain which terminate in quaternary ammonium moieties, which are part of the linear polymeric chain rather than appendages to or part of branches on such chain, thereby making further chain propogation impossible.
Description
~07346~
Specification This invention relates to a new class of micro-biocidal agents. More particularly, this invention relates to linear quaternary ammonium polymers in which the quater-nary ammonium moieties are part of the linear polymeric chain rather than appendages to, or part of branches on ~-~
the linear chain. Even more particularly, this invention relates to such linear polymeric quaternary chains in which the chains terminate in quaternary ammonium moieties, thereby making further chain propogation impossible. Such polymers ~-may, therefore, be called "capped" polymers.
The products of this invention can be made by either a two step reaction or a one step reaction. --In the first step of the two step reaction a difunctional tertiary amine is condensed with slightly more than the molar equivalent of a 1,4-dihalo-2-butene, after which the unreacted dihalo compound is removed, and the reaction is completed in a second step by adding a calculated quantity of monofunctional tertiary amine to react with the halogen termini of the polymer quaternary.
An excess of the dihalo compound is required in the first step for the purpose of producing polymer with ha~Qgen termini.
If the difunctional amine is represented by N(R') (Rl'~ ZN (R') (R'') and the 1,4-dihalo-2-butene by X-CH2-CH=CH-CH2-X, where X is a halogen, then if the 1,4-dihalo-2-butene were not in e~cess, the first step of the reaction would be represented by the chemical equation:
_ -- .: .: , - -~073~6~
n (R') (R'') N-Z-N (R') (R'') + n X-CH2-CH-CHCH2X
~ r+ + I
t N R' R'' Z N R' R'' - CH2 -CH = CH - CH2 - - 2nX~
_ n Where X is a halogen such as chlorine or bromine, Z re-presents either (1) a divalent alihpatic radical of from 2 to 10 carbon atoms containing from 0 to 2 ethylenic double bonds and from 0 to 2 hydroxyl substituents, and R' and R'' may be either (A) the same or different and either (a) alkyl group of from 1 to 20 carbon atoms having from 0 to 2 hydroxyl substituents, (b) benzyl, (c) benzyl in ~-which the benzene ring has one alkyl substituent of from
Specification This invention relates to a new class of micro-biocidal agents. More particularly, this invention relates to linear quaternary ammonium polymers in which the quater-nary ammonium moieties are part of the linear polymeric chain rather than appendages to, or part of branches on ~-~
the linear chain. Even more particularly, this invention relates to such linear polymeric quaternary chains in which the chains terminate in quaternary ammonium moieties, thereby making further chain propogation impossible. Such polymers ~-may, therefore, be called "capped" polymers.
The products of this invention can be made by either a two step reaction or a one step reaction. --In the first step of the two step reaction a difunctional tertiary amine is condensed with slightly more than the molar equivalent of a 1,4-dihalo-2-butene, after which the unreacted dihalo compound is removed, and the reaction is completed in a second step by adding a calculated quantity of monofunctional tertiary amine to react with the halogen termini of the polymer quaternary.
An excess of the dihalo compound is required in the first step for the purpose of producing polymer with ha~Qgen termini.
If the difunctional amine is represented by N(R') (Rl'~ ZN (R') (R'') and the 1,4-dihalo-2-butene by X-CH2-CH=CH-CH2-X, where X is a halogen, then if the 1,4-dihalo-2-butene were not in e~cess, the first step of the reaction would be represented by the chemical equation:
_ -- .: .: , - -~073~6~
n (R') (R'') N-Z-N (R') (R'') + n X-CH2-CH-CHCH2X
~ r+ + I
t N R' R'' Z N R' R'' - CH2 -CH = CH - CH2 - - 2nX~
_ n Where X is a halogen such as chlorine or bromine, Z re-presents either (1) a divalent alihpatic radical of from 2 to 10 carbon atoms containing from 0 to 2 ethylenic double bonds and from 0 to 2 hydroxyl substituents, and R' and R'' may be either (A) the same or different and either (a) alkyl group of from 1 to 20 carbon atoms having from 0 to 2 hydroxyl substituents, (b) benzyl, (c) benzyl in ~-which the benzene ring has one alkyl substituent of from
2 to 20 carbon atoms, (d) benzyl in which the benzene ring has from 1 to 5 methyl substituents; (B) R' and R'' taken together with N form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms, or (C) R' and R'' taken together with N may be combined with oxygen to form a N-morpholino group; or (2) Z represents two divalent ethylene radicals, in which case RII is absent and R' represents (a) an aliphatic radical of from 1 to 20 carbon atoms having from 0 to 2 hydroxyl substituents, (b) ~ ^~
benzyl, (c) benzyl in which the benzene ring has one alkyl substituent of from 2 to 20 carbon atoms, or (d) benzyl in which the benzene ring has from 1 to 5 methyl substituents; or (3) Z represents three divalent ethylene radicals, in which case RI and RII are both absent.
However, in the presence of a relatively small excess of 1,4-dihalo-2-butene, the terminal atoms of the linear polymeric product of the first step are halogen atoms, the product being:
107346~
G +
X CH2 CH = CH-CH2 ~N R R'' - Z - N R R - CH2CH-CH-CH2J X
where the symbols have the same value or meaning as above. n Since these linear polymeric chains contain active halogen termini, the chains can be made to propogate if more difunctional tertiary amine is added to the reaction ~-container already holding an excess of 1,4-dihalo-2-butene.
However, if the unreacted dihalobutene is extracted and a monofunctional tertiary amine is added to the reaction container after the excess dichloro compound is removed, then it reacts with the two terminal halogen atoms of the linear chain to form two terminal quaternary moieties.
This latter reaction constitutes the second step of the two step process of the present invention, and may be represented as follows:
X CH2 CH 2 CH CH2 ~ N R' R'' Z N R' R'' -CH2CH~CH-CH~ X
+ 2 N (R''') (RIV) (RV) {
CH2 - CH = CH CH2 ~ N R''' RIV RV
n where the symbols have the same value or meaning as above.
The following examples are illustrative of the two step process.
Example 1 To 42.6 grams of 1~4-bis-(dimethylamino)-2-butene (0.3 mole) dissolved in 100 ml. of water, there was added dropwise 50.0 grams of 1,4-dichloro-2-butene (0.4 mole) with constant stirring. The rate of addition was maintained lOq346~
at a rate to keep the exothermic reaction at a temperature of 60C to 70C. ~hen addition was complete, the reaction mixture was heated on a steam bath at about ~0C to 95C
for more than two hours. Then it was cooled to 20C and extracted with three 100 ml. portions of ethyl ether to remove the unreacted 1,4-dichloro-2-butene, and the resi-due warmed in vacuo to remove ether from the layer con-taining the polyquatern~ary.
The polyquaternary aqueous layer was analyzed for total chlorine, and also for ionic chloride. The dif-ference represented the quantity of terminal chlorine atoms on the polymeric chains.
The calculations showed that the equivalent of .03 moles of chlorine terminal atoms remained in the poly-quaternary chains. Therefore, 4.75 grams of octyl dimethyl amine (0.03 mole) was added to the aqueous layer, and the mixture heated on a steam bath for two more hours at about 90C to 95C. The reaction mixture was analyzed for total polymer quaternary content, and the concentration was adjusted to 50% active polyquaternary.
The experiment was repeated using petroleum ether instead of ethyl ether to extract the excess dichloro compound.
The similar results indicated that any inactive organic solvent may be used to extract the unreacted 1,4-dichloro-2-butene.
Example 2 In addition to the compound of Example 1, the following ~Icapped~ polymers were made by substituting other tertiary amin~es for octyl dimethyl amine, using the procedure of Example 1. They were as follows:
... . ,. . ., . - .
~0734691 (a) the polymeric quaternary formed by the reaction of 1,4-bis-(dimethylamino)-2-butene and 1,4-dichloro-2-butene, capped by decyl dimethyl amine (b) the polymeric quaternary formed by the reaction of 1,4-bis-(dimethylamino)-2-butene and 1,4-dichloro-2-butene, capped by dodecyl dimethyl amine (c) the polymeric product formed by the reaction of 1,4-bis~(dimethylamino)-2-butene and 1,4-dichloro-2-butene, capped by tetradecyl dimethyl amine .
(d) the polymeric product formed by the reaction of 1,4-bis-(dimethylamino)-2-butene and 1,4-dichloro-2-butene, capped by hexadecyl dimethyl amine ~xample 3 The following tertiary amines were also used to cap the polymeric quaternary of 1,4-bis-(dimethylamino) - 2-butene and 1,4-dichloro-2-butene, using the procedure shown in example 1:
(a) Propyl dimethyl amine, (b) butyl dimethyl amine, (c) pentyl dimethyl amine, (d) hexyl dimethyl amine, (e) dibutyl methyl amine, (f) didecyl methyl amine, (g) di-octyl methyl amine, (h) quinoline, (i) isoquinoline, (j) hexamethylene tetramine, and (k) triethanolamine.
Microbiocidal evaluations were made as follows:
Example 4 Each potential microbiocidal capped quaternary ammoniu~ polymer to be tested was dissolved in distilled water to the test concentration, and was added aseptically to previously sterilized cotton-stoppered 125 ml. Erlenmeyer flasks.
lOq3~64 One set of flasks containing the potential micro-biocide at concentrations of 25 ppm, 50 ppm, 75 ppm, 100 ppm, 150 ppm, 200 ppm, 250 ppm, and 300 ppm was inoculated by introducing into each flask 0.5 ml. of a 1/10 nutrient broth dilution of a 24 hour nutrient broth culture of Aerobacter aerogenes. Another set of test flasks containing the poten-tial microbiocide at similar concentrations was inoculated by introducing into each flask 0.5 ml. of a 1/10 nutrient broth culture of Pseudomonas aeruginosa.
At intervals of 30, 60 and 180 minutes following inoculation, a 1 ml. aliquot was withdrawn from each flask and added to 9 ml. of steril azolection/"Tween 80" ("Tween 80"
is a trade mark) neutralizer from which tenfold serial dilutions were prepared in the sterile neutralizer solution.
Agarplates were prepared from 1 x 10 2 and 1 x 10 3 dilutions.
Simultaneously with each set of test flasks, a con-trol of sterile distilled water was similarly inoculated and aliquots were taken at the same time intervals and plated a 1 x 10 4, 1 x 10 5, and 1 x 10 6 dilutions.
A comparison of the surviving organisms for various test concentrations of the test material at different time intervals was made and tabulated.
The test results were as follows:
Table 1 Numher of survivors of A. Aerogenes following expo-sure to various capped polyquaternaries at different concen-trations for varying periods of time.
73~6~, Compound Concentration No. of SurviVing Organisms/ml x 102 in ppm__After 30 Min.60 Min. 180 Min.
Example 1 50 45 10 0 Example 2~a) 50 72 9 0 Example 2(b) 50 24 6 0 Example 2(c~ 50 37 14 0 Example 2(d) 50 56 29 0 Untreated Control 45,000 55,000 111,000 Table 2 Number of survivors of P. seruginosa following exposure to various capped polyquaternaries at different concentrations for varying periods of time.
Compound Concentration No, of Surviving Organisms/ml x 102 in ppmAfter 30 Min.60 Min. 180 ~5in.
20 Example 150 940 466 0 Example 2(a~ 50 750 205 0 - Example 2(b) 50 695 137 0 Example 2(c) 50 746 150 0 1~3~6~
Compound Concentration No. of Surviving Organisms/ml x 10 in ppmAfter 30 Min. 60 Min. 180 min.
Example 2(d) 50 746 176 0 Untreated Control 40,000 65,000 90,000 The results of these tests show that the "capped"
polyquaternary ammonium products are very effective micro-biocides in concentrations at least as low as 50 ppm.
The above-described procedure comprises a two-step synthesis. In the first step 1,4-dihalo-2-butene is reacted with slightly less than a molar quantity of a di-tertiary amine. Under the conditions of this reaction, polymerization proceeds until the diamine is depleted.
Because of the initial excess of dihalo butene over diamine in the reaction mixture, the polymeric chains have termini of halogen atoms, thereby making the ends of the chain re-active toward the addition of more amine. After the unre-acted dichlorobutene is removed by extraction at the com-pletionof the first step, a calculated quantity of mono-tertiary amine is added to the polymeric residue for thesecond step of the synthesis.
The chemical quaternization which ensues from the above reaction results in the formation of polymers with quaternary ammonium termini. Since these quaternized ends of the chain are incapable of further chain propogation re-actions with dihalobutene, the polymer is said to be "capped"
in the second step.
1073~L64 The second step mentioned above merely "caps" the polymeric products of the first step. Therefore, the chain lengths and molecular weights of the product are determined in the first step. Since the polymerization of the first step proceeds in a sustained fashion until all of the di-amine is exhausted, the chain lengths are comparatively long because the number of condensations is comparatively high.
Furthermore, since the propogation of chains is permitted ~-to proceed uninterruptedly under conditions where each chain has equal probability to participate in the propogation re- `
action, the product of the first step, and subsequently the product of the second step, is a mixture of polymeric pro-ducts whose chain lengths and molecular weights fall within a comparatively narrow range. -However, capped polymeric quaternary ammonium compounds can also be made by a one-step synthesis in which both ditertiary amine and monotertiary amine are mixed simultaneously with the 1,4-dihalo-2-butene, there being about a 1:1 ratio of halogen equivalents to the total number of tertiary amine equivalents. The molar ratio of diamine to monoamine in the initial reaction mixture is about 2:1 to about 30:1. The reaction takes placea~ reflux temperature, which is usually between about 50C - 70C, while the reaction -time may vary depending on the reactants as well as the temperature, but is usually about 1 to 10 hours.
In both the one step and two step syntheses the terminal halogen atoms of a chain may participate in chain propogation reactions by being displaced by one of the amine groups of a diamine, thereby making a quaternary nitrogen.
,.
1073~6~
Chain propogation is possible because the second amine of the diamine is capable of reacting with another dihalo molecule.
However, in the single-step procedure, there is also an al-ternative route. The terminal halogen of a chain may also react with a monoamine, instead of a diamine. The reaction with a monoamine gives rise to a quaternary ammonium terminus which is incapable of further chain propogation by reaction with a dihalo molecule. In this manner, any chain may -become "capped" while other chains are propogating.
Therefore, the product in which both diamine and monoamine --are used in the initial reaction mixture, is the resultant of two competing reactions, one a propogation reaction when the diamine reacts with the terminal halogen and the other a "capping" reaction, when the monoamine reacts with the halogen.
In the one step procedure, because of the presence of monoamine during chain propogation there is always a possibility that a chain termination reaction will occur and terminate chain propogation abruptly. Therefore, every chain cannot grow uninterruptedly. Some chains will con-tinue to grow while others will terminate, depending on whether the terminal halogen reacts with a diamine or monoamine.
Furthermore, some chains are terminated quite early, leaving only short chains, whereas other chains are terminated only after having undergone a large number of propogation reactions, thereby leaving long chains. Termi-nation occurs in a statistically random fashion. Therefore, the chain lengths vary from very short to very long, and 1073~6~
the molecular weights vary from low to high, over a com-paratively wide range.
The difunctional tertiary amine may be represented ~ -by the structural formula:
RI\ RII
N - Z - N :-RI RI
For purposes of clarification, Z represents either (1) ~-a divalent aliphatic radical of from 2 to 10 carbon atoms containing from 0 to 2 hydroxyl substituents and from 0 to .~.
2 ethylenic double bonds, and RI and RII may either be (A) the same or different and may be either (a) an alkyl group of from 1 to 20 carbo~ atoms having from 0 to 2 hydroxyl substituents, (b) benzyl, (c) benzyl in . .
which the benzene ring has one alkyl substituent of from 2 to 20 carbon atoms, and (d) benzyl in which the benzene ring has from 1 to 5 methyI substituents; (B) RI and RII, taken together with N, form a saturated or :
unsaturated heterocyclic ring of from 5 to 7 atoms; or (C) RI and RII, taken together with N, may be combined with an oxygen atom to form a N-morpho~i~ogroup; or (2) Z represents two divalent ethylene radicals, in which case RII is absent and RI represents (a) an ali-phatic radical of from 1 to 20 carbon atoms having from ~ :~
0 to 2 hydroxyl substituents, (b) benzyl, (c) benzyl in which the bezene moiety has an alkyl substituent of from 2 to 20 carbon atoms, or (d) benzyl in which the benzene moiety has from 1 to 5 methyl substituents; or , . ... - - ... -, - , , .. . . : , ~0~3~6~
benzyl, (c) benzyl in which the benzene ring has one alkyl substituent of from 2 to 20 carbon atoms, or (d) benzyl in which the benzene ring has from 1 to 5 methyl substituents; or (3) Z represents three divalent ethylene radicals, in which case RI and RII are both absent.
However, in the presence of a relatively small excess of 1,4-dihalo-2-butene, the terminal atoms of the linear polymeric product of the first step are halogen atoms, the product being:
107346~
G +
X CH2 CH = CH-CH2 ~N R R'' - Z - N R R - CH2CH-CH-CH2J X
where the symbols have the same value or meaning as above. n Since these linear polymeric chains contain active halogen termini, the chains can be made to propogate if more difunctional tertiary amine is added to the reaction ~-container already holding an excess of 1,4-dihalo-2-butene.
However, if the unreacted dihalobutene is extracted and a monofunctional tertiary amine is added to the reaction container after the excess dichloro compound is removed, then it reacts with the two terminal halogen atoms of the linear chain to form two terminal quaternary moieties.
This latter reaction constitutes the second step of the two step process of the present invention, and may be represented as follows:
X CH2 CH 2 CH CH2 ~ N R' R'' Z N R' R'' -CH2CH~CH-CH~ X
+ 2 N (R''') (RIV) (RV) {
CH2 - CH = CH CH2 ~ N R''' RIV RV
n where the symbols have the same value or meaning as above.
The following examples are illustrative of the two step process.
Example 1 To 42.6 grams of 1~4-bis-(dimethylamino)-2-butene (0.3 mole) dissolved in 100 ml. of water, there was added dropwise 50.0 grams of 1,4-dichloro-2-butene (0.4 mole) with constant stirring. The rate of addition was maintained lOq346~
at a rate to keep the exothermic reaction at a temperature of 60C to 70C. ~hen addition was complete, the reaction mixture was heated on a steam bath at about ~0C to 95C
for more than two hours. Then it was cooled to 20C and extracted with three 100 ml. portions of ethyl ether to remove the unreacted 1,4-dichloro-2-butene, and the resi-due warmed in vacuo to remove ether from the layer con-taining the polyquatern~ary.
The polyquaternary aqueous layer was analyzed for total chlorine, and also for ionic chloride. The dif-ference represented the quantity of terminal chlorine atoms on the polymeric chains.
The calculations showed that the equivalent of .03 moles of chlorine terminal atoms remained in the poly-quaternary chains. Therefore, 4.75 grams of octyl dimethyl amine (0.03 mole) was added to the aqueous layer, and the mixture heated on a steam bath for two more hours at about 90C to 95C. The reaction mixture was analyzed for total polymer quaternary content, and the concentration was adjusted to 50% active polyquaternary.
The experiment was repeated using petroleum ether instead of ethyl ether to extract the excess dichloro compound.
The similar results indicated that any inactive organic solvent may be used to extract the unreacted 1,4-dichloro-2-butene.
Example 2 In addition to the compound of Example 1, the following ~Icapped~ polymers were made by substituting other tertiary amin~es for octyl dimethyl amine, using the procedure of Example 1. They were as follows:
... . ,. . ., . - .
~0734691 (a) the polymeric quaternary formed by the reaction of 1,4-bis-(dimethylamino)-2-butene and 1,4-dichloro-2-butene, capped by decyl dimethyl amine (b) the polymeric quaternary formed by the reaction of 1,4-bis-(dimethylamino)-2-butene and 1,4-dichloro-2-butene, capped by dodecyl dimethyl amine (c) the polymeric product formed by the reaction of 1,4-bis~(dimethylamino)-2-butene and 1,4-dichloro-2-butene, capped by tetradecyl dimethyl amine .
(d) the polymeric product formed by the reaction of 1,4-bis-(dimethylamino)-2-butene and 1,4-dichloro-2-butene, capped by hexadecyl dimethyl amine ~xample 3 The following tertiary amines were also used to cap the polymeric quaternary of 1,4-bis-(dimethylamino) - 2-butene and 1,4-dichloro-2-butene, using the procedure shown in example 1:
(a) Propyl dimethyl amine, (b) butyl dimethyl amine, (c) pentyl dimethyl amine, (d) hexyl dimethyl amine, (e) dibutyl methyl amine, (f) didecyl methyl amine, (g) di-octyl methyl amine, (h) quinoline, (i) isoquinoline, (j) hexamethylene tetramine, and (k) triethanolamine.
Microbiocidal evaluations were made as follows:
Example 4 Each potential microbiocidal capped quaternary ammoniu~ polymer to be tested was dissolved in distilled water to the test concentration, and was added aseptically to previously sterilized cotton-stoppered 125 ml. Erlenmeyer flasks.
lOq3~64 One set of flasks containing the potential micro-biocide at concentrations of 25 ppm, 50 ppm, 75 ppm, 100 ppm, 150 ppm, 200 ppm, 250 ppm, and 300 ppm was inoculated by introducing into each flask 0.5 ml. of a 1/10 nutrient broth dilution of a 24 hour nutrient broth culture of Aerobacter aerogenes. Another set of test flasks containing the poten-tial microbiocide at similar concentrations was inoculated by introducing into each flask 0.5 ml. of a 1/10 nutrient broth culture of Pseudomonas aeruginosa.
At intervals of 30, 60 and 180 minutes following inoculation, a 1 ml. aliquot was withdrawn from each flask and added to 9 ml. of steril azolection/"Tween 80" ("Tween 80"
is a trade mark) neutralizer from which tenfold serial dilutions were prepared in the sterile neutralizer solution.
Agarplates were prepared from 1 x 10 2 and 1 x 10 3 dilutions.
Simultaneously with each set of test flasks, a con-trol of sterile distilled water was similarly inoculated and aliquots were taken at the same time intervals and plated a 1 x 10 4, 1 x 10 5, and 1 x 10 6 dilutions.
A comparison of the surviving organisms for various test concentrations of the test material at different time intervals was made and tabulated.
The test results were as follows:
Table 1 Numher of survivors of A. Aerogenes following expo-sure to various capped polyquaternaries at different concen-trations for varying periods of time.
73~6~, Compound Concentration No. of SurviVing Organisms/ml x 102 in ppm__After 30 Min.60 Min. 180 Min.
Example 1 50 45 10 0 Example 2~a) 50 72 9 0 Example 2(b) 50 24 6 0 Example 2(c~ 50 37 14 0 Example 2(d) 50 56 29 0 Untreated Control 45,000 55,000 111,000 Table 2 Number of survivors of P. seruginosa following exposure to various capped polyquaternaries at different concentrations for varying periods of time.
Compound Concentration No, of Surviving Organisms/ml x 102 in ppmAfter 30 Min.60 Min. 180 ~5in.
20 Example 150 940 466 0 Example 2(a~ 50 750 205 0 - Example 2(b) 50 695 137 0 Example 2(c) 50 746 150 0 1~3~6~
Compound Concentration No. of Surviving Organisms/ml x 10 in ppmAfter 30 Min. 60 Min. 180 min.
Example 2(d) 50 746 176 0 Untreated Control 40,000 65,000 90,000 The results of these tests show that the "capped"
polyquaternary ammonium products are very effective micro-biocides in concentrations at least as low as 50 ppm.
The above-described procedure comprises a two-step synthesis. In the first step 1,4-dihalo-2-butene is reacted with slightly less than a molar quantity of a di-tertiary amine. Under the conditions of this reaction, polymerization proceeds until the diamine is depleted.
Because of the initial excess of dihalo butene over diamine in the reaction mixture, the polymeric chains have termini of halogen atoms, thereby making the ends of the chain re-active toward the addition of more amine. After the unre-acted dichlorobutene is removed by extraction at the com-pletionof the first step, a calculated quantity of mono-tertiary amine is added to the polymeric residue for thesecond step of the synthesis.
The chemical quaternization which ensues from the above reaction results in the formation of polymers with quaternary ammonium termini. Since these quaternized ends of the chain are incapable of further chain propogation re-actions with dihalobutene, the polymer is said to be "capped"
in the second step.
1073~L64 The second step mentioned above merely "caps" the polymeric products of the first step. Therefore, the chain lengths and molecular weights of the product are determined in the first step. Since the polymerization of the first step proceeds in a sustained fashion until all of the di-amine is exhausted, the chain lengths are comparatively long because the number of condensations is comparatively high.
Furthermore, since the propogation of chains is permitted ~-to proceed uninterruptedly under conditions where each chain has equal probability to participate in the propogation re- `
action, the product of the first step, and subsequently the product of the second step, is a mixture of polymeric pro-ducts whose chain lengths and molecular weights fall within a comparatively narrow range. -However, capped polymeric quaternary ammonium compounds can also be made by a one-step synthesis in which both ditertiary amine and monotertiary amine are mixed simultaneously with the 1,4-dihalo-2-butene, there being about a 1:1 ratio of halogen equivalents to the total number of tertiary amine equivalents. The molar ratio of diamine to monoamine in the initial reaction mixture is about 2:1 to about 30:1. The reaction takes placea~ reflux temperature, which is usually between about 50C - 70C, while the reaction -time may vary depending on the reactants as well as the temperature, but is usually about 1 to 10 hours.
In both the one step and two step syntheses the terminal halogen atoms of a chain may participate in chain propogation reactions by being displaced by one of the amine groups of a diamine, thereby making a quaternary nitrogen.
,.
1073~6~
Chain propogation is possible because the second amine of the diamine is capable of reacting with another dihalo molecule.
However, in the single-step procedure, there is also an al-ternative route. The terminal halogen of a chain may also react with a monoamine, instead of a diamine. The reaction with a monoamine gives rise to a quaternary ammonium terminus which is incapable of further chain propogation by reaction with a dihalo molecule. In this manner, any chain may -become "capped" while other chains are propogating.
Therefore, the product in which both diamine and monoamine --are used in the initial reaction mixture, is the resultant of two competing reactions, one a propogation reaction when the diamine reacts with the terminal halogen and the other a "capping" reaction, when the monoamine reacts with the halogen.
In the one step procedure, because of the presence of monoamine during chain propogation there is always a possibility that a chain termination reaction will occur and terminate chain propogation abruptly. Therefore, every chain cannot grow uninterruptedly. Some chains will con-tinue to grow while others will terminate, depending on whether the terminal halogen reacts with a diamine or monoamine.
Furthermore, some chains are terminated quite early, leaving only short chains, whereas other chains are terminated only after having undergone a large number of propogation reactions, thereby leaving long chains. Termi-nation occurs in a statistically random fashion. Therefore, the chain lengths vary from very short to very long, and 1073~6~
the molecular weights vary from low to high, over a com-paratively wide range.
The difunctional tertiary amine may be represented ~ -by the structural formula:
RI\ RII
N - Z - N :-RI RI
For purposes of clarification, Z represents either (1) ~-a divalent aliphatic radical of from 2 to 10 carbon atoms containing from 0 to 2 hydroxyl substituents and from 0 to .~.
2 ethylenic double bonds, and RI and RII may either be (A) the same or different and may be either (a) an alkyl group of from 1 to 20 carbo~ atoms having from 0 to 2 hydroxyl substituents, (b) benzyl, (c) benzyl in . .
which the benzene ring has one alkyl substituent of from 2 to 20 carbon atoms, and (d) benzyl in which the benzene ring has from 1 to 5 methyI substituents; (B) RI and RII, taken together with N, form a saturated or :
unsaturated heterocyclic ring of from 5 to 7 atoms; or (C) RI and RII, taken together with N, may be combined with an oxygen atom to form a N-morpho~i~ogroup; or (2) Z represents two divalent ethylene radicals, in which case RII is absent and RI represents (a) an ali-phatic radical of from 1 to 20 carbon atoms having from ~ :~
0 to 2 hydroxyl substituents, (b) benzyl, (c) benzyl in which the bezene moiety has an alkyl substituent of from 2 to 20 carbon atoms, or (d) benzyl in which the benzene moiety has from 1 to 5 methyl substituents; or , . ... - - ... -, - , , .. . . : , ~0~3~6~
(3) Z represents three divalent ethylene radicals in which case RI and RII are both absent.
The monotertiary amine may be represented by the structural formula:
RIII _ N - RIV -RV .-where (1) RIII is an aliphatic radical of from 1 to 20 carbon atoms, having from 0 to 2 hydroxyl substituents, and RIV and RV may be either (a) the same or different and represent an aliphatic radical having from 1 to 4 carbon atoms with from 0 to 1 hydroxyl substituents; (b) -~
taken together with N to form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; (c) taken to-gether with N, and combined with an oxygen atom to form a N-morpholino group; or where (2) RIII, R V, RV and N
taken together, may represent quinoline, isoquinoline or hexamethylene tetramine.
The following examples exemplify the second procedure:
Example 5 -522 grams of morpholine (6 moles) were cooled to : -20C and 125 grams of 1,4-dichloro-2-butene (1 mole) were added dropwise with constant stirring and cooling to keep the temperature at 50C - 60C. The entire addition took about 1 hour, and stirring was continued for about one more hour. While stirring, 150 grams of water was poured into the reaction mixture, followed by 200 grams of 50~ sodium hydroxide solution, then the mixture was allowed to separate.
~073~6~
The organic layer was removed, and the unreacted morpholine was removed by distillation under reduced pressure.
The residue was washed with water and filtered, yielding a yellow solid melting at 79C - 83C. This was 1,4-bis-(N-morpholino)-2-butene. -Since the purpose of the excess morpholine was to act as an acid acceptor, the experiment was repeated, but with 212 grams of sodium carbonate (2 moles) replacing the excess 174 grams of morpholine (4 moles). The yield of 1,4-bis-(N-morpholino)-2-butene was about the same as the previous synthesis. ~;
This reaction was repeated using 0.1 mole of 1,4-dichloro-2-butene and 0.6 mole of the following amines in place of morpholine: piperidine, homopiperidine, diethanolamine, dimethylamine, dipropylamine, dibutylamine, di-(2-ethylhexyl) amine, dioctylamine, didecylamine, didodecylamine, N-methyl propylamine, N-methyl butylamine, N-methyl hexylamine, N-methyl octylamine, N-methyl decylamine, N-methyl dodecylamine. All of these 1,4-bis-amino-2-butenes were liquids, and were recovered from their aqueous mixtures by partitioning.
Example 6 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles~ and 1.49 grams of triethanolamine (0.01 moles) were dissolved in about 55.5 grams of water in a round-bottom flask fitted with a s~irrer and reflux condenser, and 25.63 grams of 1,4-dichloro-2-butene (0.205 moles) were added slowly while the mixture was stirred. The reaction mixture was heated to 60 - 70C and maintained at that temperature, 1~73~6~ -with stirring, for about 6 hours. The reaction was 98%
complete, as indicated by ionic chloride analysis. The residue contained about 50% by weight of active material.
The procedure of Example 6 was repeated several times using different proportions of reactants, as follows:
', fO73~16~
~ _ In ~1k a~ o k a)~ Q~ Q ~ k ~1 Q~ ~~ kt~
k~r ~a~ _I ~1 1~
XCO oer o _1 o er W
~q bq U~
ou~ q k ~1k Q~ I e ,~ k (~1 0~ O
~1~ ~Q~ k ~ k co ~r ~;~r ~~ o o .. .. ..
X CO o _I o o o o W
Lg b~
~n O ~ O
kb' k~' k S~ :
Q ~ ~
~r o~7 ~ 1`
~ ~ts~ -Xco o. oOD O L~
W~--co--~-- ~D
_I~ Q~ k~ k el~ ~
ou ~3 a~ ~-1~
Xao o . o ~ o _I
-- U~
- - ~
t`k ~
a~s~ kh ~3 ~ k Q~ ~ u~
~~ O C~
f~. .~, . . .
Xc~oo ~DO 1`
W~_~--~-- U7 a) :
~ .
R~
O
k ~ ~ ~ .
rl k O
,1 _i O
~ 0 ~1 R
- --I ~) --I 3 - 107346~
The procedure of Example 6 was again repeated, except that the following reactants were used:
Example 12 A cf ~77efhl//4m/~ -A 28.4 grams of 1,4-bis ~imcnth~lami~o-2-butene (0.2 moles) 1.94 grams of N-methyl morpholine (0.02 moles) 26.25 grams of 1,4-dichloro-2-butene (0.21 moles) 56.6 grams of water Example 13 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) --2.00 grams of N-methyl piperidine (0.02 moles) 26.25 grams of 1,4-dichloro-2-butene ~0.21 moles) 56.7 grams of water Example 14 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.06 grams of N-methyl homopiperidine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 molès) 56.7 grams of water Example 15 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 1.7 grams of N-methyl pyrrolidine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) -~
56.6 grams of water Example 16 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.02 grams of butyldimethylamine (0.02 moles) ? 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 56.9 grams of water .. . . . . .
~73gG~
::;
Example 17 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.3 grams of pentyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.2 grams of water Example 18 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.58 grams of hexyldimethylamine (0.02 moles) 26.5 grams ofl, 4-dichloro-2-butene (0.21 moles) 57.5 grams of water Example 19 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.86 grams of heptyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.8 grams of water - -Example 20 -28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 3.14 grams of octyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 58.1 grams of water Example 21 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 3.42 grams of nonyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 58.3 grams of water 1~ ~ 6 Example 22 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 3.7 grams of decyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 58.6 grams of water Example 23 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 3.98 grams of undecyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 58.9 grams of water -Example 24 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles)
The monotertiary amine may be represented by the structural formula:
RIII _ N - RIV -RV .-where (1) RIII is an aliphatic radical of from 1 to 20 carbon atoms, having from 0 to 2 hydroxyl substituents, and RIV and RV may be either (a) the same or different and represent an aliphatic radical having from 1 to 4 carbon atoms with from 0 to 1 hydroxyl substituents; (b) -~
taken together with N to form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; (c) taken to-gether with N, and combined with an oxygen atom to form a N-morpholino group; or where (2) RIII, R V, RV and N
taken together, may represent quinoline, isoquinoline or hexamethylene tetramine.
The following examples exemplify the second procedure:
Example 5 -522 grams of morpholine (6 moles) were cooled to : -20C and 125 grams of 1,4-dichloro-2-butene (1 mole) were added dropwise with constant stirring and cooling to keep the temperature at 50C - 60C. The entire addition took about 1 hour, and stirring was continued for about one more hour. While stirring, 150 grams of water was poured into the reaction mixture, followed by 200 grams of 50~ sodium hydroxide solution, then the mixture was allowed to separate.
~073~6~
The organic layer was removed, and the unreacted morpholine was removed by distillation under reduced pressure.
The residue was washed with water and filtered, yielding a yellow solid melting at 79C - 83C. This was 1,4-bis-(N-morpholino)-2-butene. -Since the purpose of the excess morpholine was to act as an acid acceptor, the experiment was repeated, but with 212 grams of sodium carbonate (2 moles) replacing the excess 174 grams of morpholine (4 moles). The yield of 1,4-bis-(N-morpholino)-2-butene was about the same as the previous synthesis. ~;
This reaction was repeated using 0.1 mole of 1,4-dichloro-2-butene and 0.6 mole of the following amines in place of morpholine: piperidine, homopiperidine, diethanolamine, dimethylamine, dipropylamine, dibutylamine, di-(2-ethylhexyl) amine, dioctylamine, didecylamine, didodecylamine, N-methyl propylamine, N-methyl butylamine, N-methyl hexylamine, N-methyl octylamine, N-methyl decylamine, N-methyl dodecylamine. All of these 1,4-bis-amino-2-butenes were liquids, and were recovered from their aqueous mixtures by partitioning.
Example 6 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles~ and 1.49 grams of triethanolamine (0.01 moles) were dissolved in about 55.5 grams of water in a round-bottom flask fitted with a s~irrer and reflux condenser, and 25.63 grams of 1,4-dichloro-2-butene (0.205 moles) were added slowly while the mixture was stirred. The reaction mixture was heated to 60 - 70C and maintained at that temperature, 1~73~6~ -with stirring, for about 6 hours. The reaction was 98%
complete, as indicated by ionic chloride analysis. The residue contained about 50% by weight of active material.
The procedure of Example 6 was repeated several times using different proportions of reactants, as follows:
', fO73~16~
~ _ In ~1k a~ o k a)~ Q~ Q ~ k ~1 Q~ ~~ kt~
k~r ~a~ _I ~1 1~
XCO oer o _1 o er W
~q bq U~
ou~ q k ~1k Q~ I e ,~ k (~1 0~ O
~1~ ~Q~ k ~ k co ~r ~;~r ~~ o o .. .. ..
X CO o _I o o o o W
Lg b~
~n O ~ O
kb' k~' k S~ :
Q ~ ~
~r o~7 ~ 1`
~ ~ts~ -Xco o. oOD O L~
W~--co--~-- ~D
_I~ Q~ k~ k el~ ~
ou ~3 a~ ~-1~
Xao o . o ~ o _I
-- U~
- - ~
t`k ~
a~s~ kh ~3 ~ k Q~ ~ u~
~~ O C~
f~. .~, . . .
Xc~oo ~DO 1`
W~_~--~-- U7 a) :
~ .
R~
O
k ~ ~ ~ .
rl k O
,1 _i O
~ 0 ~1 R
- --I ~) --I 3 - 107346~
The procedure of Example 6 was again repeated, except that the following reactants were used:
Example 12 A cf ~77efhl//4m/~ -A 28.4 grams of 1,4-bis ~imcnth~lami~o-2-butene (0.2 moles) 1.94 grams of N-methyl morpholine (0.02 moles) 26.25 grams of 1,4-dichloro-2-butene (0.21 moles) 56.6 grams of water Example 13 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) --2.00 grams of N-methyl piperidine (0.02 moles) 26.25 grams of 1,4-dichloro-2-butene ~0.21 moles) 56.7 grams of water Example 14 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.06 grams of N-methyl homopiperidine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 molès) 56.7 grams of water Example 15 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 1.7 grams of N-methyl pyrrolidine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) -~
56.6 grams of water Example 16 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.02 grams of butyldimethylamine (0.02 moles) ? 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 56.9 grams of water .. . . . . .
~73gG~
::;
Example 17 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.3 grams of pentyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.2 grams of water Example 18 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.58 grams of hexyldimethylamine (0.02 moles) 26.5 grams ofl, 4-dichloro-2-butene (0.21 moles) 57.5 grams of water Example 19 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.86 grams of heptyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.8 grams of water - -Example 20 -28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 3.14 grams of octyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 58.1 grams of water Example 21 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 3.42 grams of nonyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 58.3 grams of water 1~ ~ 6 Example 22 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 3.7 grams of decyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 58.6 grams of water Example 23 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 3.98 grams of undecyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 58.9 grams of water -Example 24 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles)
4.26 grams of dodecyldimethylamine (0.02 moles) ~
26.5 grams of 1,4-dichloro-2-butene (0.21 moles) ~ ~
59.2 grams of water ~ -Example 25 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.7 grams of benzyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) ~--57.6 grams of water ~
Example 26 -28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.62 grams of quinoline (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.5 grams of water .. . . . . .
iO73 Example 27 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.62 grams of isoquinoline (0.02 moles) 26,5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.5 grams of water Example 28 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.8 grams of hexamethylenetetramine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.7 grams of water Although in Examples 6 to 28 above, the difunc-tional tertiary amine 1,4-bis-dimethylamino-2-butene was -~
utilized, any of the other difunctional tertiary amines, as disclosed in Example 5, may be substituted in equivalent molar amounts. Illustrative of such other difunctional amines are, for example, 1,4-bis-(N-morpholino)-2-butene;
1,4-N,N'-dimethylpiperamine; 1,4-diazabicyclo (2.2.2) octane; N,N,N', N'-tetramethylene diamine; N,N,N',N'-tetra-(2-hydroxylpropyl)-ethylene diamine; 1,3-bis- -(dimethylamino)-2-hydroxypropane; and 1,4-di-(N-homopiperidino)-2-butene.
Furthermore, although only 1,4-dichloro-2-butene ~ -has been illustrated above, 1,4-dibromo or 1,4-diiodo-2- -butene may be substitued.
Example 29 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) ;-1.01 grams of butyldimethylamine (0.01 moles) 25.63 grams of 1,4-dichloro-2-butene (0.205 moles) 55.04 grams of water .
.
~ ~ .
1073~6~
Example 30 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 0.97 grams of N-methyl morpholine (0.01 moles) 25.63 grams of 1,4-dichloro-2-butene (0.205 moles) 55.0 grams of water Example 31 The "Broth Dilution Test" method was used to assay the antimicrobial properties of the products. In -~this method, 1.0 ml. of a solution of the material being tested was added to 9.0 ml. of a suitable broth culture medium in a test tube. A series of such test tubes was prepared so that there was presented a stepwise decrease in the concentrations being tested, from 0.1~ (1000 ppm) to 0.005% (50 ppm). Each tube was then inoculated with 0.1 ml. of either a 24-hour broth culture of test bacteria, or a 14-day aqueous spore suspension of test fungi. The -~
testing program was designed so that every concentration ~ --of every material was inoculated separately by each organism used in the test.
The test organisms employed were: ~
Escherchia coli (E. c.) Pseudomonas seruginosa (Ps. a.) Staphylococcus aureus (S. a.) Streptococcus faecalis (S. f.) Aspergillus niger (A. n.) Penicillium expansum (P. e.) After inoculation, the tubes were incubated as follows:
`` 107:~46~
72 hours at 37C for bacteria 14 days at 28C for fungi Following incubation, the tubes were examined for the presence or absence of macroscopic growth as evidenced by the presence or absence of turbidity.
The lowest concentration of the material being tested at which macroscopic growth was not evident was de-signated as the "Minimum Inhibitory Level" (M.I.L.) Table 3, following shows the M.I.L. of the pro- -ducts that were tested. The inhibitory concentrations are shown in parts per million.
Table 3 Product Synthesized Gram Positive Gram Negative Fungi in Example No. E.c. Ps.a. S.a.S.f. A n. P.e.
10001000 10001000 ~1000 ~1000 6 50 50 5050 71000 ~1000 11 50 50 5050 71000 ~1000 28 10001000 10001000 ~1000 71000 5050 ~1000 ~1000 20 27 100 500 100100 ~1000 ?1000 19 .1000100010001000 ~1000 ~1000 21 10001000 10001000 71000 ~1000 The results of these tests show that every com-pound tested has anti-bacterial properties in concentrations as low as 0.1%, and even lower in many cases.
Example 32 In order to estimate the bactericidal power of these compounds, the product prepared in Example 7 was assayed using the "~ater Treatment Test".
- -lOq~
The product was dissolved in sterile distilled water and diluted to the test concentration. Then 50 ml. of test solution was added aseptically to previously sterilized cotton-stoppered 125 ml. Erlenmeyer flasks. One set of flasks contai-ning the product at concentrations of 25 ppm, 50 ppm, 100 ppm, 150 ppm, 200 ppm, 250 ppm, and 300 ppm, was inoculated by introducing into each flask 0.5 ml. of a 1/10 nutrient broth dilution of a 24-hour nutrient broth culture of Aerobacter aerogenes. Another set of flasks containing the product at the same concentrations was inoculated by introducing into each flask 0.5 ml. of a 1/10 nutrient broth dilution of a 24-hour nutrient broth culture of Pseudomonas aeruginosa.
At intervals of 30, 60 and 180 minutes following inoculation of 1.0 ml. aliguot was withdrawn from each flask and added to 9.0 ml. of sterile azolectin/"Tween 80" ("Tween 80" is a trade mark) neutralizer from which additional ten-`fold serial dilutions were prepared in sterile neutralizer solution.
~ .
~-Nutrient agar plates were prepared from 1 x 10 and 1 x 10 3 dilutions.
Simultaneously with each set of flasks, a control of sterile distilled water was similarly inoculated and ali-quots were taken at the same time intervals at 1 x 10 4, -1 x 10 5 and 1 x 10 6 dilutions.
For additional control purposes, and also for com-parison purposes, simultaneous assays were performed with each set of flasks on "BTC 776" (trade mark), a powerful bac-tericidal agent used in water treatment, the chemical name of which is alkyl benzyl dimethyl ammonium chloride. It is manu-- . -, ~:. , -, " : ... . .
`` ~07346~
factured and sold by Qnyx Chemical Co., of Jersey City, N.J.
Table 4 shows the number ofsur,v,ivorsof Aerobacter aerogenes and Table 5 shows the number of survivors of ^^'-Pseudomonas aeruginosa ATCC 15442, following exposure at different concentrations for the indicated periods of time.
The numbers in the table must be multiplied by 1 x 102.
Concentrations of the materials being tested are given in ,-parts per million.
Table 4 ', ' .
CompoundConcentration No. of Surviving Bacteria per ml.
(Example No.) (ppm) (x 102) After 30 Min. 60 Min. 180 Min.
89 45 1 , 3~ 19 0 57 7 0 '~' 23 1.5 0 22 4 0 ,' 21 3 0 " ~, 0 20,900 26,500 28,700 - : . - .. ...
" 1073~69~
Table 4 (continued) CompoundConcentration No. of Surviving Bacteria per ml.
(Example No.) (ppm) (x 102) After 30 Min. 60 Min. 180 Min.
BTC (Control) 10 49 10 0 32 10 0 ~ '~
Table 5 Pseudomonas Aeroginosa CompoundConcentration No. o~ Surviving Bacteria per ml. ~:
(Example No.~ (ppm) (x 10 ) After 30 Min. 60 Min. 180 Min.
`: -0 92,500 91,500 91,000 BTC (Control) 10 1,260 180 0 1,380 123 0 1,460 118 0 1,450 192 0 ~0734 ~
The compounds of this invention are all very soluble in water and insoluble in organic solvents such as isopropanol, acetone, hexane, trichloroethane, toluene, and the like.
They are, furthermore, non-foaming, which is an important property because it makes these compounds suitable for use as anti-microbial agents in products and processes where the generation of foam would be undesirable.
In addition to their utilization as anti-microbal agents, the compounds of this invention are also utilizable as hair conditioning agents in shampoos and the like.
.-..
26.5 grams of 1,4-dichloro-2-butene (0.21 moles) ~ ~
59.2 grams of water ~ -Example 25 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.7 grams of benzyldimethylamine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) ~--57.6 grams of water ~
Example 26 -28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.62 grams of quinoline (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.5 grams of water .. . . . . .
iO73 Example 27 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.62 grams of isoquinoline (0.02 moles) 26,5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.5 grams of water Example 28 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 2.8 grams of hexamethylenetetramine (0.02 moles) 26.5 grams of 1,4-dichloro-2-butene (0.21 moles) 57.7 grams of water Although in Examples 6 to 28 above, the difunc-tional tertiary amine 1,4-bis-dimethylamino-2-butene was -~
utilized, any of the other difunctional tertiary amines, as disclosed in Example 5, may be substituted in equivalent molar amounts. Illustrative of such other difunctional amines are, for example, 1,4-bis-(N-morpholino)-2-butene;
1,4-N,N'-dimethylpiperamine; 1,4-diazabicyclo (2.2.2) octane; N,N,N', N'-tetramethylene diamine; N,N,N',N'-tetra-(2-hydroxylpropyl)-ethylene diamine; 1,3-bis- -(dimethylamino)-2-hydroxypropane; and 1,4-di-(N-homopiperidino)-2-butene.
Furthermore, although only 1,4-dichloro-2-butene ~ -has been illustrated above, 1,4-dibromo or 1,4-diiodo-2- -butene may be substitued.
Example 29 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) ;-1.01 grams of butyldimethylamine (0.01 moles) 25.63 grams of 1,4-dichloro-2-butene (0.205 moles) 55.04 grams of water .
.
~ ~ .
1073~6~
Example 30 28.4 grams of 1,4-bis-dimethylamino-2-butene (0.2 moles) 0.97 grams of N-methyl morpholine (0.01 moles) 25.63 grams of 1,4-dichloro-2-butene (0.205 moles) 55.0 grams of water Example 31 The "Broth Dilution Test" method was used to assay the antimicrobial properties of the products. In -~this method, 1.0 ml. of a solution of the material being tested was added to 9.0 ml. of a suitable broth culture medium in a test tube. A series of such test tubes was prepared so that there was presented a stepwise decrease in the concentrations being tested, from 0.1~ (1000 ppm) to 0.005% (50 ppm). Each tube was then inoculated with 0.1 ml. of either a 24-hour broth culture of test bacteria, or a 14-day aqueous spore suspension of test fungi. The -~
testing program was designed so that every concentration ~ --of every material was inoculated separately by each organism used in the test.
The test organisms employed were: ~
Escherchia coli (E. c.) Pseudomonas seruginosa (Ps. a.) Staphylococcus aureus (S. a.) Streptococcus faecalis (S. f.) Aspergillus niger (A. n.) Penicillium expansum (P. e.) After inoculation, the tubes were incubated as follows:
`` 107:~46~
72 hours at 37C for bacteria 14 days at 28C for fungi Following incubation, the tubes were examined for the presence or absence of macroscopic growth as evidenced by the presence or absence of turbidity.
The lowest concentration of the material being tested at which macroscopic growth was not evident was de-signated as the "Minimum Inhibitory Level" (M.I.L.) Table 3, following shows the M.I.L. of the pro- -ducts that were tested. The inhibitory concentrations are shown in parts per million.
Table 3 Product Synthesized Gram Positive Gram Negative Fungi in Example No. E.c. Ps.a. S.a.S.f. A n. P.e.
10001000 10001000 ~1000 ~1000 6 50 50 5050 71000 ~1000 11 50 50 5050 71000 ~1000 28 10001000 10001000 ~1000 71000 5050 ~1000 ~1000 20 27 100 500 100100 ~1000 ?1000 19 .1000100010001000 ~1000 ~1000 21 10001000 10001000 71000 ~1000 The results of these tests show that every com-pound tested has anti-bacterial properties in concentrations as low as 0.1%, and even lower in many cases.
Example 32 In order to estimate the bactericidal power of these compounds, the product prepared in Example 7 was assayed using the "~ater Treatment Test".
- -lOq~
The product was dissolved in sterile distilled water and diluted to the test concentration. Then 50 ml. of test solution was added aseptically to previously sterilized cotton-stoppered 125 ml. Erlenmeyer flasks. One set of flasks contai-ning the product at concentrations of 25 ppm, 50 ppm, 100 ppm, 150 ppm, 200 ppm, 250 ppm, and 300 ppm, was inoculated by introducing into each flask 0.5 ml. of a 1/10 nutrient broth dilution of a 24-hour nutrient broth culture of Aerobacter aerogenes. Another set of flasks containing the product at the same concentrations was inoculated by introducing into each flask 0.5 ml. of a 1/10 nutrient broth dilution of a 24-hour nutrient broth culture of Pseudomonas aeruginosa.
At intervals of 30, 60 and 180 minutes following inoculation of 1.0 ml. aliguot was withdrawn from each flask and added to 9.0 ml. of sterile azolectin/"Tween 80" ("Tween 80" is a trade mark) neutralizer from which additional ten-`fold serial dilutions were prepared in sterile neutralizer solution.
~ .
~-Nutrient agar plates were prepared from 1 x 10 and 1 x 10 3 dilutions.
Simultaneously with each set of flasks, a control of sterile distilled water was similarly inoculated and ali-quots were taken at the same time intervals at 1 x 10 4, -1 x 10 5 and 1 x 10 6 dilutions.
For additional control purposes, and also for com-parison purposes, simultaneous assays were performed with each set of flasks on "BTC 776" (trade mark), a powerful bac-tericidal agent used in water treatment, the chemical name of which is alkyl benzyl dimethyl ammonium chloride. It is manu-- . -, ~:. , -, " : ... . .
`` ~07346~
factured and sold by Qnyx Chemical Co., of Jersey City, N.J.
Table 4 shows the number ofsur,v,ivorsof Aerobacter aerogenes and Table 5 shows the number of survivors of ^^'-Pseudomonas aeruginosa ATCC 15442, following exposure at different concentrations for the indicated periods of time.
The numbers in the table must be multiplied by 1 x 102.
Concentrations of the materials being tested are given in ,-parts per million.
Table 4 ', ' .
CompoundConcentration No. of Surviving Bacteria per ml.
(Example No.) (ppm) (x 102) After 30 Min. 60 Min. 180 Min.
89 45 1 , 3~ 19 0 57 7 0 '~' 23 1.5 0 22 4 0 ,' 21 3 0 " ~, 0 20,900 26,500 28,700 - : . - .. ...
" 1073~69~
Table 4 (continued) CompoundConcentration No. of Surviving Bacteria per ml.
(Example No.) (ppm) (x 102) After 30 Min. 60 Min. 180 Min.
BTC (Control) 10 49 10 0 32 10 0 ~ '~
Table 5 Pseudomonas Aeroginosa CompoundConcentration No. o~ Surviving Bacteria per ml. ~:
(Example No.~ (ppm) (x 10 ) After 30 Min. 60 Min. 180 Min.
`: -0 92,500 91,500 91,000 BTC (Control) 10 1,260 180 0 1,380 123 0 1,460 118 0 1,450 192 0 ~0734 ~
The compounds of this invention are all very soluble in water and insoluble in organic solvents such as isopropanol, acetone, hexane, trichloroethane, toluene, and the like.
They are, furthermore, non-foaming, which is an important property because it makes these compounds suitable for use as anti-microbial agents in products and processes where the generation of foam would be undesirable.
In addition to their utilization as anti-microbal agents, the compounds of this invention are also utilizable as hair conditioning agents in shampoos and the like.
.-..
Claims (22)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. An anti-microbial polymeric quaternary ammonium compound or of a mixture of such compounds said compound having the formula:
wherein Z represents alkylene containing one ethylenic double bond, and RI and RII may either be (A) the same or different and may be either (a) an alkyl group of from 1 to 20 carbon atoms having from 0 to 2 hydroxyl substituents, (b) benzyl, (c) benzyl in which the benzene moiety has one alkyl substituent of from 2 to 20 carbon atoms, and (d) benzyl in which the benzene moiety has from 1 to 5 methyl substituents; (B) RI and RII, taken together with N, form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; or (C) RI and RII, taken together with N, and combined with an oxygen atom, form a N-morpholino group; where (1) RIII is an alkyl radical of from 1 to 20 carbon atoms, having from 0 to 2 hydroxyl substituents, and RIV and RV may either be (a) the same or different and represent an alkyl radical having from 1 to 4 carbon atoms with from 0 to 1 hydroxyl substituents (b) taken together with N to form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; (c) taken together with N, and combined with an oxygen atom, to form an N-morpholino group;
or where (2) RIII, RIV, RV and N, taken together, represent quinoline, isoquinoline or hexamethylene tetramine; X is either chloride or bromide; and n is a number of from 1 to 15.
wherein Z represents alkylene containing one ethylenic double bond, and RI and RII may either be (A) the same or different and may be either (a) an alkyl group of from 1 to 20 carbon atoms having from 0 to 2 hydroxyl substituents, (b) benzyl, (c) benzyl in which the benzene moiety has one alkyl substituent of from 2 to 20 carbon atoms, and (d) benzyl in which the benzene moiety has from 1 to 5 methyl substituents; (B) RI and RII, taken together with N, form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; or (C) RI and RII, taken together with N, and combined with an oxygen atom, form a N-morpholino group; where (1) RIII is an alkyl radical of from 1 to 20 carbon atoms, having from 0 to 2 hydroxyl substituents, and RIV and RV may either be (a) the same or different and represent an alkyl radical having from 1 to 4 carbon atoms with from 0 to 1 hydroxyl substituents (b) taken together with N to form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; (c) taken together with N, and combined with an oxygen atom, to form an N-morpholino group;
or where (2) RIII, RIV, RV and N, taken together, represent quinoline, isoquinoline or hexamethylene tetramine; X is either chloride or bromide; and n is a number of from 1 to 15.
2. The compound of claim 1 wherein the heterocyclic radical is N-piperidino, N-pyrrolidino, or N-homopiperidino.
3. The compound of claim 1 wherein RI and RII are methyl radicals.
4. The compound of claim 1 wherein RIII, RIV and RV
are 2-hydroxyethyl radicals.
are 2-hydroxyethyl radicals.
5. The compound of claim 1 wherein RI and RII are methyl radicals, and RIII, RIV and RV are 2-hydroxyethyl radicals.
6. The compound of claim 1 wherein Z is the divalent radical -CH2-CH=CH-CH2-.
7. The compound of claim 6 wherein RI and RII are methyl radicals.
8. The compound of claim 6 wherein RIII, RIV and RV are 2-hydroxyethyl radicals.
9. The compound of claim 6 wherein RI and RII are methyl radicals, and RIII, RIV and RV are 2-hydroxyethyl radicals.
10. A process for preparing the product of claim 1 comprising the reaction of a mixture of di-functional tertiary amine of formula RIRIIN-Z-N-RIRII and mono-functional tertiary amine of formula RIIIRIVRVN in ratio of about 2:1 to about 30:1, with a molar quantity of 1,4-dihalo-2-butene approximately equal to the molar sum of di-functional tertiary amine and mono-functional tertiary amine, so as to produce a substantially linear polymer having quaternary ammonium moieties at each end, wherein Z represents alkylene containing one ethylenic double bond and RI and RII may either be (A) the same or different and may be either (a) an alkyl group of from 1 to 20 carbon atoms having from 0 to 2 hydroxyl substituents, (b) benzyl, (c) benzyl in which the benzene moiety has one alkyl substituent of from 2 to 20 carbon atoms, and (d) benzyl in which the benzene moiety has from 1 to 5 methyl substituents; (B) RI
and RII, taken together with N, form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; or (C) RI and RII, taken together with N, and combined with an oxygen atom, form an N-morpholino group; where (1) RIII is an alkyl radical of from 1 to 20 carbon atoms, having from 0 to 2 hydroxyl substituents, and RIV and RV may either be (a) the same or different and represent an alkyl radical having from 1 to 4 carbon atoms with from 0 to 1 hydroxyl substituent (b) taken together with N to form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; (c) taken together with N, and combined with an oxygen atom, to form an N-morpholino group;
or where (2) RIII, RIV, RV and N, taken together, represent quinoline, isoquinoline or hexamethylene tetramine.
and RII, taken together with N, form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; or (C) RI and RII, taken together with N, and combined with an oxygen atom, form an N-morpholino group; where (1) RIII is an alkyl radical of from 1 to 20 carbon atoms, having from 0 to 2 hydroxyl substituents, and RIV and RV may either be (a) the same or different and represent an alkyl radical having from 1 to 4 carbon atoms with from 0 to 1 hydroxyl substituent (b) taken together with N to form a saturated or unsaturated heterocyclic ring of from 5 to 7 atoms; (c) taken together with N, and combined with an oxygen atom, to form an N-morpholino group;
or where (2) RIII, RIV, RV and N, taken together, represent quinoline, isoquinoline or hexamethylene tetramine.
11. The process of claim 10 wherein the heterocyclic radical is N-piperidino, N-pyrrolidino, or N-homopiperidino.
12. The process of claim 10 wherein RI and RII are methyl radicals.
13. The process of claim 10 wherein RIII, RIV and RV
are 2-hydroxyethyl radicals.
are 2-hydroxyethyl radicals.
14. The process of claim 10 wherein RI and RII are methyl radicals, and RIII, RIV and RV are 2-hydroxyethyl radicals.
15. The process of claim 10 wherein Z is the divalent radical -CH2-CH=CH-CH2-.
16. The process of claim 15 wherein RI and RII are methyl radicals.
17. The process of claim 15 wherein RIII, RIV and RV
are 2-hydroxyethyl radicals.
are 2-hydroxyethyl radicals.
18. The process of claim 15 wherein RI, RII, RIII are methyl radicals, and RIII, RIV and RV are 2-hydroxyethyl radicals.
19. A method of controlling the proliferation of deleterious microorganisms which comprises applying to said organisms a polymeric quaternary ammonium compound or mixtures of such compounds as claimed in claim 1.
20. A method of controlling the proliferation of deleterious microorganisms which comprises applying to said microorganisms a polymeric quaternary ammonium compound or mixture of such compounds as prepared by the process of claim 10.
21. A method of conditioning the hair which comprises applying to the hair a compound or mixture of compounds as claimed in claim 1.
22. A method of conditioning the hair which comprises applying to the hair a compound or mixture of compounds as prepared by the process of claim 10.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA279,168A CA1073464A (en) | 1977-05-26 | 1977-05-26 | Polymeric quaternary ammonium compounds |
| BE178031A BE855178A (en) | 1977-05-26 | 1977-05-27 | MICROBIOCIDAL PRODUCTS IN THE FORM OF POLYMERIC COMPOUNDS OF QUATERNARY AMMONIUM |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA279,168A CA1073464A (en) | 1977-05-26 | 1977-05-26 | Polymeric quaternary ammonium compounds |
| BE178031A BE855178A (en) | 1977-05-26 | 1977-05-27 | MICROBIOCIDAL PRODUCTS IN THE FORM OF POLYMERIC COMPOUNDS OF QUATERNARY AMMONIUM |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1073464A true CA1073464A (en) | 1980-03-11 |
Family
ID=25650095
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA279,168A Expired CA1073464A (en) | 1977-05-26 | 1977-05-26 | Polymeric quaternary ammonium compounds |
Country Status (2)
| Country | Link |
|---|---|
| BE (1) | BE855178A (en) |
| CA (1) | CA1073464A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3674640D1 (en) * | 1985-05-28 | 1990-11-08 | Ciba Geigy Ag | A WATER-BASED AQUEOUS SYSTEM. |
-
1977
- 1977-05-26 CA CA279,168A patent/CA1073464A/en not_active Expired
- 1977-05-27 BE BE178031A patent/BE855178A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| BE855178A (en) | 1977-11-28 |
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