US3910971A

US3910971A - Bacteriostatic compounds

Info

Publication number: US3910971A
Application number: US488110A
Authority: US
Inventors: Jerry H Hunsucker
Original assignee: Commercial Solvents Corp
Current assignee: Commercial Solvents Corp
Priority date: 1974-07-12
Filing date: 1974-07-12
Publication date: 1975-10-07
Anticipated expiration: 1992-10-07

Abstract

Compounds corresponding to the formula:

where R is an aliphatic hydrocarbon group of from 7 to 17 carbon atoms and X is a halogen atom are effective bacteriostats.

Description

United States Patent [1 1 Hunsucker [451 Oct. 7, 1975 BACTERIOSTATIC COMPOUNDS [75] Inventor: Jerry H. Hunsucker, Terre Haute,

Ind.

[73] Assignee: Commercial Solvents Corporation,

Terre Haute, Ind.

221 Filed: July 12,1974

21 Appl.No.:488,1l0

[52] US. Cl. 260/404; 424/312; 424/311 [51] Int. Cl? C07C 69/62; CO7C 69/63 [58] Field of Search 260/404 Loury et al., Chem. Ab., Vol. 43, (1949), 7940a-f. Schneider et al., Chem. Ab., Vol. 51, (1957), 10752h.

Kyi et al., Chem. Ab., Vol. 51, (1957), 10752i. Kyi, Chem. Ab., Vol. 52, (1958), 7146fg.

Primary ExaminerPatrick P. Garvin Attorney, Agent, or Firm-Robert H. Dewey; Howard E. Post [57] ABSTRACT Compounds corresponding to the formula:

where R is an aliphatic hydrocarbon group of from 7 to 17 carbon atoms and X is a halogen atom are effective bacteriostats.

8 Claims, No Drawings BACTERIOSTATIC COMPOUNDS BACKGROUND OF THE INVENTION This invention relates to a method of controlling the growth of bacteria.

In a particular aspect, this invention relates to a method of controlling the growth of bacteria by applying a bacteriostat to them or to the environment inhabited by them.

Long-chain quaternary ammonium compounds are well-known in the art. However, previously known compounds have been characterized by having the long alkyl chain attached directly to the nitrogen atom.

SUMMARY OF THE INVENTION It is an object of this invention to provide a method of controlling the growth of bacteria.

It is a second object of this invention to provide quaternary ammonium compounds believed to be novel.

Other objects will be apparent to those skilled in the art from the description herein.

It I is the discovery of this invention to provide a method for controlling the growth of bacteria by applying to them or the environment inhabited by them a quaternary ammonium ester compound corresponding to the formula:

where R is an aliphatic hydrocarbon group of from 7 to 17 carbon atoms and X is a halogen atom.

DETAILED DISCUSSION The compounds contemplated by the present invention include but are not limited to: (Z-Lauroyloxy-l,1-dimethylethyl)trimethylammonium iodide (Z-Myristoyloxy-1,1-dimethylethyl)trimethylammonium iodide (2-Octanoyloxy-1 1-dimethylethyl)trimethylam' monium iodide (2-Palmitoyloxy- 1 ,1-dimethylethyl)trimethylammonium iodide.

Thes compounds are readily prepared by methods known in the art, i.e. 2-dimethy1amino-2-methy1-1- propanol (DMAMP) is esterified with a fatty acid represented by the formula RCOOH under esterification conditions. Suitable fatty acids include but are not limited to caprylic, lauric, myristic, palmitic and stearic acids. Myristic acid is particularly preferred. These acids are all commercially available and the usual commercial grades are suitable for the practice of this invention. The commercial grade materials are not highly purified however and contain significant amounts of related fatty acids, some of which are unsaturated. It is within the embodiment of this invention therefore that R in the formula can be provided by a mixture of saturated or unsaturated fatty acids having from about 8 to about 18 carbon atoms.

The amino ester obtained as described above is treated with an alkyl halide to provide the quaternary ammonium halide salt of the amino-ester. A suitable carbon atoms, preferably a methyl halide. The halogen atom can be fluorine, chlorine, bromine or iodine. Preferred alkyl halides include methyl chloride and methyl iodide. The latter is particularly preferred.

The compounds of this invention are relatively insoluble in water but they are soluble in most organic solvents, at least to a moderate extent. Such organic solvents include esters, ketones, lower aliphatic alcohols, chlorinated hydrocarbons, aliphatic and aromatic hydrocarbons, etc. They are suitable for use at concentrations generally above 500 pug/ml. A concentration of about 1-10 mg/ml is preferred for most applications. The compounds have a low order of toxicity in mammals. The are useful for controlling the growth of bacteria in a wide variety of applications among which can be cited recirculating cooling waters, cutting oils, drilling muds, starch adhesives and preservatives for water based paints. A particularly preferred application is to employ the compound as a disinfectant for hard surfaces, such as walls, floors, counters etc. The compounds are especially suitable as disinfectants for farm buildings, e. g. those used for cattle, horses, poultry and the like. The compounds are easily applied as sprays,

dusts or by brushing as described by H. L. Wehrmeister, US. Pat. No. 3,509,260 which is incorporated herein by reference thereto. Because of their low water solubility the compounds advantageously form an antibacterial film on surfaces to which they are applied.

The invention will be better understood with reference to the following examples. It is understood that these examples are intended for illustration only and it is not intended that the invention be limited thereby.

EXAMPLE 1 DMAMP g (1.07 mole) and commercial grade myristic acid 232 g (the acid had an equivalent weight of 232) were charged to an esterification vessel equipped with an agitator, distillation column, decanter head, thermometer and heat source. Toluene sulfonic acid 2 g was added as a catalyst. The mixture was heated with agitation to about to about C until the acid number was less than 20. It was cooled and another 5 ml of DMAMP (about 5 g) was added and the mixture was again heated to 171C for 2 /2 hours. The acid number was about 15. Toluene, about 40 ml, was added and stripped to remove any remaining water. The residue was washed with an equal volume of 50 percent sodium hydroxide solution. Petroleum ether, 350 ml, was added and the mixture was separated. The petroleum ether was separated by evaporation and .distillation at 1mm. The product cut distilled at l50l56. It had a neutral equivalent of 340.3 compared with a theoretical value of 330.1. It was concluded that the product was the myristic acid ester of DMAMP (2-dimethylamino-2-methyl-l-propyl myristate).

A 32.75 g portion of the ester, prepared as described above, and 14.20 g of methyl iodide were mixed with 50 g of chloroform in a reaction vessel equipped with a reflux condenser. The mixture was heated for 60 minutes at reflux and was then cooled. It was mixed with an equal volume of diethyl ether and chilled in a freezer myristoyloxy- 1 1 -dimethylethyl )-trimethylammonium iodide, m.p. 168.4 having a nitrogen content of 3.42

percent and iodine 25.89 percent.

The product had an LD of 600 mg/kg by oral administration to mice, an LD of 1000 mg/kg and an LD of 2000 mg/kg.

The compound was tested for anti-bacterial and antifungal activity by the streak plate test, which is known in the art. The test substance was incorporated into several portions of an agar medium at several known concentrations and the mixtures were placed in Petri dishes. Then steaks of test organisms were applied to the surface of the medium, the dishes were incubated under growth-promoting conditions, and then examined for growth of organisms. The results are reported as the Inhibition End-point Range, the lower figure signifying a concentration that allows growth and the upper being a concentration that inhibits growth. The ranges for a variety of organisms are given in the table. It was concluded that the compound exhibited powerful anti-bacterial activity but only slight anti-fungal activity.

The compound is employed as a spray for disinfecting buildings and pens used for housing animals. An emulsion is prepared by dissolving about 10 g of the product prepared as described above in 100 ml of kerosene, adding 2 g of emulsifying agent and adding gradually to 1 liter of water at 80C with agitation. The resulting emulsion is used for spraying.

EXAMPLE 2 The lauric acid ester of DMAMP was prepared by mixing 200 g of commercial grade lauric acid with 125 g of DMAMP and 2 g of toluene sulfonic acid in a reaction vessel equipped with an agitator, heat source, thermometer, distillation column and a decanter head. Toluene was added to assist in removel of water as the azeotrope. The mixture was heated at about l15-120C until the acid number was 28 and 22 ml of water had been removed. The product was purified by distilling through a Vigreaux distillation column at a liquid temperature of about 150-160C and a pressure of 1 mm. The fraction distilling at l52l57 was taken as the product. It had a neutral equivalent of 354 and an acid number of 35.5.

A 29.9 g (0.1 mole) portion of the ester obtained above was mixed with chloroform 50 ml in a 500 ml flask equipped with an agitator, thermometer and reflux condenser. Methyl iodide 15 g was added slowly with agitation then heated at reflux for about an hour at about 65C. The product was then cooled and an equal amount of anhydrous ether was added resulting in a heavy precipitate. After chilling at -5 the mixture was filtered and the solids were then recrystallized from acetone, slurried with ether and filtered. There was obtained (2-lauroyloxy-1,1-dimethyethyl)trimethylammonium iodide, m.p. 146, N 3. 15 percent compared with theoretical 3.08 percent.

The compound was tested for toxicity by oral administration to mice. It had an LD of 500 mg/kg, LD of 900 mg/kg and LD of 1700 mg/kg. When tested by the streak plate method it exhibited strong antibacterial activity against a variety of bacteria, as shown in the table, but only slight activity against fungi.

EXAMPLE 3 The experiment of Example 2 was repeated in all essential details except that commercial grade palmitic acid 256 g was substituted for lauric acid and the mixture was heated at about 170-l90C. There was obtained 2-dimethylamino-2-methyl-1-propyl palmitate having an acid number of 23.4.

A 36 g portion of the ester obtained above was reacted with methyl iodide 15 g as described in Example 2. There was obtained (2-palmitoyloxy-1,1- dimethylethyl )trimethylammonium iodide, m. p. 170.8C.

It was tested for acute oral toxicity in mice. The LD was 800 mg/kg; the LD was 1490 mg/kg; and the LD was 3200 mg/kg.

The product was tested for anti-bacterial activity by the streak plate test. The results are shown in the table. The compound was only slightly active against fungi.

The product is employed as a disinfectant by forming an emulsion in the manner described in Example 1 to provide concentration of above about 500 ug/ml to control the growth of bacteria after applying to a hard surface.

EXAMPLE 4 DMAMP 118 g (1 mole) and commercial grade caprylic acid 131 g (1 mole) were dissolved in 35 ml of toluene. The mixture was heated under reflux at about 140-165 until 20 ml distillate was recovered and no more was being collected. The pressure was then reduced to 10 mm and distillation was continued to about C to strip off toluene and water. The pressure was then reduced to about 1 mm and the main product fraction was recovered at a liquid temperature of about 106-109. There was obtained 2-dimethylamino-2- methyl-l-propyl caprylate, neutral equivalent 247.9 compared with theoretical 244.

A portion of the product obtained above was reacted with methyl iodide as described in Example 2. There was obtained (2-octanoyloxy-l,l-dimethylethyl)trimethylammonium iodide, m.p. l35.8. The nitrogen content was 3.98 percent compared with theoretical 3.77, and the iodine content was 32.91 percent compared with theoretical 34.23 percent.

The product was tested for acute oral toxicity in mice. The LD was 800 mg/kg; the LD was 1160 mg/kg; and LD was 1700 mg/kg.

The product was tested for anti-bacterial activity by the streak plate test. The results are given in the table. It showed only slight activity against fungi.

The product is used as a disinfectant at a concentration of greater than about 1000 ug/ml to control the growth of bacteria.

ANTI-BACTERIAL ACTIVITY Inhibition End Point, ug/m1 ANTI-BACTERIAL ACTIVITY-Continued Inhibition End Point, ,t /mi EXAMPLE NO. l

Pasteurella pscudotuberculosis 1-5 5-10 100-500 100-500 Pseudomonas aruginosa l000 500-1000 l000 lOO Shigella dysenteriac -10 -50 50-100 1000 Gaffkya tetrugena l-5 Micrococcus flavus 0.1-0.5

I claim: 10 3. A compound of claim 1 wherein R is an aliphatic l. A compond corresponding to the formula: group f 1 1 arbon atoms,

4. A compound of claim 1 wherein R is an aliphatic o CH group of 13 carbon atoms.

5 5. A compound of claim 1 wherein R is an aliphatic group of 15 carbon atoms.

3 6. A compound of claim 1 wherein R is provided by i a mixture of saturated and unsaturated fatty acids, the

acids having from about 8 to about 18 carbon atoms.

where R is an aliphatic hydrocarbon group of from 7 to 17 carbon atoms and X is a halogen atom. 20 7. A compound of claim 1 wherein X is iodine.

2. A compound of claim 1 wherein R IS an aliphatic A compound of claim 1 wherein X is chlorine group of 7 carbon atoms. 1

Claims

1. A COMPOUND CORRESPONDING TO THE FORMULA:

2. A compound of claim 1 wherein R is an aliphatic group of 7 carbon atoms.

3. A compound of claim 1 wherein R is an aliphatic group of 11 carbon atoms.

4. A compound of claim 1 wherein R is an aliphatic group of 13 carbon atoms.

5. A compound of claim 1 wherein R is an aliphatic group of 15 carbon atoms.

6. A compound of claim 1 wherein R is provided by a mixture of saturated and unsaturated fatty acids, the acids having from about 8 to about 18 carbon atoms.

7. A compound of claim 1 wherein X is iodine.

8. A compound of claim 1 wherein X is chlorine.