US3068239A - Benzothiazole-, benzoxazole- and benzimidazole-2-thioacrylates and process - Google Patents

Description

b a/a BENZOTETHIAZGLE, BENZQXAZOLE- AND EENZ- IMiDAZLE-2=THEQACRYLATES AND PRQCELlS Lee A. Miller, Dayton, Ohio, assigns-r to Monsanto Chemical tlonipany, St. Louis, Mo., a corporation of Delaware No Drawing. Filed Dec. 28, 1959, Ser. No. $62 .lli

12 Claims. (Cl. 26ti3l6) ZOECCOOY in which X is selected from the class consisting of -S, -O and NH-, Y is an alkyl radical of from 1 to 5 carbon atoms, and Z is selected from the class consisting of Y, hydrogen and aryl radicals of from 6 to carbon atoms.

The presently provided compounds are thus alkyl esters of acrylic acid wherein at the 3-position of the acrylic acid there is carried a substituent which is a benzothiazoylthio radical, or a benzoxazolylthio radical or a benzirnidazolylthio radical and wherein the 3-position may or may not carry an alkyl or aryl substituent. Thus when Z of the above formula is hydrogen the compounds are alkyl 3-(2-benzothiazolylthi0)acrylates, or 3-(2-benzoxazolylthio acrylates or 3- (2-benzirnidazolylthio acrylates.

The mercapto-substituted polynuclear heterocyclic compounds which are presently employed are Z-mercaptobenzothiazole, Z-benzoxazolethiol or 2-benzimidazolethiol.

The acetylenic carboxylates which are reacted with the above mercapto-substituted compounds are 1 to 5 C alkyl esters of propiolic acid wherein there may or may not be present at the 3-position of the propiolic acid an aliphatic or aromatic substituent. Examples of the present useful acetylenic esters are the alkyl propiolates such as the methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, amyl, isoamyl, or tert-amyl propiolates; the alkyl tetrolates such as the methyl, ethyl, propyl, butyl or amyl tetrolates; the alkyl Z-pentynoates such as the methyl or butyl Z-pentyonate or the ethyl or isopropyl 4-ethyl 2- pentynoate, the alkyl Z-hexynoates such as methyl or propyl Z-hexynoate; the arylpropiolates such as ethyl or amyl phenylpropiolate or 2-, 3-, or 4-tolylpropiolate and methyl or butyl wnaphthylpropiolate; the alkyl Z-heptynoates such as ethyl or butyl Z-heptynoate or methyl, ethyl or isobutyl 6-methyl 2-heptynoate; the alkyl 2-octynoates such as methyl or propyl 2-octynoate, etc.

Examples of compounds prepared according to the presently provided process are, e.g., methyl, ethyl, amyl 3-(2-benzothiazolylthio)acrylate, ethyl, propyl or butyl (Z-benzoxazolylthio)acrylate; butyl, isoamyl, or methyl 3-(2-benzimidazolylthio)acrylate; methyl or ethyl 3-(2- benzothiazolylthio)-2-butenoate; methyl or butyl 3-(2- benzoxazolylthio)-2-butenoate; butyl or amyl 3-(2-benz- 3,0h8,239 Patented Dec. Il, 1962 imidazolylthio)-2-butenoate; methyl or ethyl 3-(2-benzothiazolylthio)-2-pentenoate, butyl or methyl 3-(2-benzoxazolylthio)-2-buter1oate, amyl or butyl 3-(2-benzimidazolylthio)-2-pentenoate, methyl or ethyl 3-(2-benzoxazolylthio)-2-pentenoate, amyl or isopropyl 3-(2-benzothiazolylthio)-2-hexenoate, ethyl or methyl S-(Z-benzoxazolylthio)-2-hexenoate, amyl or methyl 3-(2-benzimidazolylthio)-2-hexencate, methyl or ethyl 3-(2-benzothiazolylthio)-2-heptenoate, butyl or isopropyl 3-(2- benzoxazolylthio)-2-heptenoate, butyl or propyl 3-(2-benzothiazolylthio)-2 octenoate, methyl or ethyl S-(Z-benzoxazolylthio)-2-octenoate, methyl or ethyl 3-(2 -benzothiazolylthio) 3 -phenylacrylate, ethyl or isopropyl 3 (2- benzoxaz olylthio)-3-phenylacrylate, methyl or butyl 3-(2- benzothiazolylthio)-3-(2-tolyl)acrylate, ethyl or propyl 3- (Z-benzothiazolylthio -3- (4-ethylphenyl) acryl ate, methyl or ethyl 3-(2-benzothiazolylthio)-3-(;3-naphthyl) acrylate, ethyl or propyl 3-(2-benzoxazolylthio)-3-(ot-naphthyl)- acrylate, butyl or methyl 3-(2-benzimidazolylthio)-3-(B- naphthyl)acrylate, etc.

Reaction of the present mercapto-substituted polynuclear heterocyclic compounds with the acetylenic esters takes place in the presence or absence of basic or acidic catalysts. Basic catalysts useful in the process include organic bases such as pyridine, the quaternary ammonium salts or bases such as trimethylbenzylammonium hydroxide, the alkali and alkali metal hydroxides or basically reacting salts thereof such as sodium, potassium, lithium, calcium, or magnesium hydroxide, carbonates or acetate; alkali or alkali metal alcoholates such as sodium methylate, etc. Examples of useful acidic catalysts are acid reacting metallic salts, such as cuprous or cupric, stannous or stannic, ferrous or ferric acetates, sulfates or chlorides, organic or inorganic acids such as acetic, sulfuric, phosphoric or oxalic acid, etc. While I prefer to use as a catalyst a material which is soluble in the mixture of the two reactants such solubility of the catalyst in the reactants is not a necessary property of the catalyst.

According to the invention the presently provided heterocyclic thioalkenoates are readily prepared by simply mixing the mercapto compound with the acetylenic ester in the presence or absence of either the acidic or basic catalyst and in the presence or absence of an inert diluent or solvent and allowing the resulting reaction mixture to stand at ordinary or increased temperatures until formation of the substituted olefinic ester has occurred. Useful solvents or diluents are e.g., benzene, xylene, dioxane, dichlorobenzene or hexane. Depending on the nature of the individual reactants and of the catalyst employed, the reaction may occur under varying conditions of temperature and pressure. For optimum yields, it is advantageous to heat the reaction mixture at temperature of, say, from approximately 60 C. to the refluxing temperature of the reaction mixture.

Inasmuch as molecular equivalents of the mercapto compound and the acetylenic ester are involved in the formation of the presently provided substituted olefinic esters, it is advantageous to employ stoichiometric proportions of the two reactants. If desired, however, any excess of either reactant may be employed since any unreacted material is readily separated from the product.

It has been observed that in the reactions with the 2- benzimidazolethiol, the product is generally a mixture of the isomeric alkyl 3-,(2-benzimidazolylthio)alkenoates.

aeeaaas and the alkyl 3-[l-(2-mercaptobenzimidazole)]acrylates It will be noted that (11) is formed by addition of the acetylenic ester at the imino radical of the thiol rather than at the mercapto radical. There is a preferental tendency for (I); so that (II) is present in minor amounts. While (11) may be removed from the reacton mixture by customary isolating procedures, e.g., close fractional distillation, extraction or fractional crystallization, for most purposes it is unnecessary to provide (1) in a pure form. That it is because the crude (I), i.e., the reaction product which consists essentially of (I), is useful directly for a wide variety of industrial and agricultural purposes.

The presently provided alkyl 3-(2-benzothiazoylthio)- alkenoates or 3-(2-benzoxazolylthio)ialkenoates or the 3- (Z-benzimidazolylthioalkenoates and mixtures of the latter with the isomeric alkyl 3[1-(Z-mercaptobenzimidazole)1- acrylates are stable, rather high-boiling viscous liquids or waxy to crystalline solids which are useful as lubricant additives, as vulcanization accelerators for rubbers, as copolymerizing monomers with vinyl compounds in synthetic resin and plastics manufacture, and as biological toxicants, e.g., as herbicides, bacteriostats, fungistats and insecticides. They are particularly valuable as pre-emergent herbicides in that they possess a specificity of effect so that they can be used as de-weeders without adversely affecting the crop. The benzothiazolylthio compounds are noteworthy in that they serve as crab grass eradicants without killing or substantially injuring the lawn grasses.

The invention is further illustrated by, but not limited to, the following examples:

a eaeeer 'JSH Example 1 A mixture consisting of 8.4 g. (0.1 mole) of methyl propiolate and 50 ml. of benzene was added continuously to a mixture consisting of 16.7 g. (0.1 mole) of 2-mercaptobenzothiazole, 100 ml. of benzene and 1 ml. of 40% methanolic trimethylbenzylammonium methoxide. The reaction mixture, which darkened immediately, was heated at reflux for 12 hours. It was then dissolved in 100 ml. of ether and washed with two 50 ml. portions of saturated aqueous ammonium chloride. Evaporation of the organic solvents gave as residue a brown slurry. This was distilled through a small Vigreux column to give the substantially pure methyl 3-(2-benzothiazolylthio)- acrylate, B.P. 171-172 C./0.5 mm., M1. 68-70 C., which analyzed 52.51% carbon and 3.60% hydrogen as against 52.56% and 3.61%, the respective calculated values.

Example 2 To a reaction vessel there were charged 15.0 g. (0.1 mole) of 2-benzimidazolethiol, 9.2 g. (0.11 mole) of methyl propiolate and 100 ml. of benzene. Upon addition of 1 ml. of trimethylbenzylammonium hydroxide (catalyst) to the mixture, darkening was noted and the temperature of the reaction mixture rose exotherrnally to about 45 C. In order to assure complete reaction the whole was then refluxed for 12 hours. At the end of that time the black reaction mixture was evaporated to give a dark brown, pasty solid which could not be recrystallized from methanol. Diflicul-ty in crystallization 4 was due to the presence in a product of the following two isomers:

amount of (II), i.e., methyl 3-[l-(Z-mercaptobenzimida- Zole) acrylate.

and

CSH

Example 3 When a catalytic quantity (1 ml.) of trimethyl-benzylammonium hydroxide was added to a mixture consisting of 15.1 g. (0.1 mole) of 2- benzoxazolethiol, 9.2 g. (0.11 mole) of methyl pro-piola-te and ml. of benzene, the mixture blackened and spontaneously warmed to 45 C. The whole was then heated at reflux for 12 hours. Upon evaporation of the solvent there was obtained a black oil which solidified upon standing. Repeated recrystallization from methanol gave the substantially pure methyl 3-(2-benzoxazo1ylthio) acrylate, buff needles, M.P. 93.5- 95.0" C., which analyzed 56.14% carbon and 4.10% hydrogen as against 56.16% and 3.86% the respective calculated values for C H NO S. Infrared analysis showed the presence of the -C=N structure at 1590 cmf the presence of C-O- ester structure at 1230 and 1220 cmf and the presence of 4 adjacent protons at 755 and 750 CDT-1.

Example 4 This example shows evaluation of the methyl 3-(2-benzothiazolylthio)acrylate of Example 1 as a pre-emergent herbicide. Briefly, the chemical is applied in spray form to soil seeded to representative grasses and broad-leaf plants.

Aluminum pans, 13" x 9" x 2", were filled with a good grade of top soil which had been screened through a A" wire mesh and mixed with sand in a preparation of two parts of the top soil to one part of the sand. The soil surface was then compacted to a depth of from the top of the pan. Twenty seeds each of morning glory, wild oat, crab grass, rye grass, radish, sugar beet, barnyard grass, wild buckwheat, and pigweed were then scattered on the soil surface and covered with soil to the pan top.

The present herbicidal solution was prepared by dissolving 0.4 g. of the methyl 3-(2-benzothiazolylthio)-- acrylate in 20 cc. of acetone. Ten ml. of this solution was diluted with water to 30 cc. Application of this quantity of the solution to said pans is calculated to correspond to the use of 25 lbs. of the test compound per acre. The planted pans were then placed in an exhaust hood and sprayed first with 30 cc. of an aqueous solution of a liquid fertilizer and 0.1% solution of octamethyl pyrophosphoramide. The liquid fertilizer was employed to give a uniform nutrition level and the amide was employed to prevent insect injury. Two pans were then respectively sprayed with the 25 lb. per acre solutionof the test compound. One of the pans which had been planted and treated with the liquid fertilizer and octamethyl pyrophosphoramide in the same manner was set aside to be used as a blank. The three pans were then placed in /2 of water and allowed to absorb moisture through perforated bottoms until the soil surface was completely moist. The pans were then transferred to a wet sand bench in the greenhouse, and maintained there for ten days under ordinary conditions of sunlight and watering.

Observation of the pans at the end of that time showed that those which had been sprayed with the 25 lb. per acre solution of the methyl 3-(2-benzothiazolylthio)- acrylate showed complete to very pronounced suppression of crab grass and pigweecl; however, the radish, morning glory, wild buckwheat, wild oats, rye grass and barnyard grass had emerged and showed no evidence of phytotoxicity. Also, all of the types of seeds which had been planted in the pan which had not been sprayed with the methyl 3-(2-benzothiazolylthio)acrylate had emerged and the plants were in excellent condition. Accordingly, when used at the rate of 25 lbs. per acre, the methyl 3-(2-benzothiazolylthio)acrylate is an unusually effective preemergent herbicide in that it prevents emergence and growth of crab grass and pigweed without having any adverse effect on wild oats, rye grass, and mustard.

Employing the same testing procedure, but using morning glory, wild oat, brome grass, rye grass, radish, sugar beet, foxtail, crab grass, pigweed, soybean, wild buckwheat, tomato and sorghum as the test seeds, the methyl 3-(2-benzoxazolylthio)acrylate of Example 3 was also found to give complete to very pronounced suppression of crab grass and pigweed. However, with this compound there was not the pronounced specificity which was exhibited by the methyl 3-(2-benzothiazolythio) acrylate; for in addition, wild oat and rye grasses were pronouncedly suppressed brome grass and sugar beets were moderately injured, and morning glory, foxtail, and soybean were slightly injured. There was no effect on radish, wild buckwheat, tomato and sorghum. Accordingly, the methyl 3-(2-benzoxazolylthio)acrylate is a preemergent herbicide which is effective against the narrow leafed plants, generally, while not substantially harming the broad leaf plants.

When employing the same testing procedure with the product of Example 2, i.e., the mixture of methyl 3-(2- benzimidazolylthio)-acrylate and methyl 3-[1-(2-mercaptobenzimida2ole)] acrylate completely different results were obtained. This product was found to inhibit germination and growth of several broadleaf plants, e.g., morning glory, sugar beets and tomato, while not at all affecting wild oat, brome grass, rye grass, foxtail, and crab grass.

Example 5 This example shows evaluation of the methyl 3-(2-benzothiazolylthio)acrylate of Example 1 and the methyl 3- (Z-benzoxazolylthio)acrylate of Example 3 against mosquito larvae. The following procedure was employed:

Culture tubes (rimless, 25x200 mm.) were respectively filled with 70 cc. of distilled water. Acetone solutions (1.0%) of the test compounds were then respectively pipetted ipto the culture tubes in a quantity calculated to give a p.p.m. concentration of either the compound of Example 1 or the compound of Example 3 in each of said tubes. Each tube was rubber-stoppered and shaken vigorously to facilitate complete mixing. To each tube of the resulting test solutions there was then added approximately 25 yellow fever mosquito (Aedes aegypti Linne) larvae, and the test solutions, with their larvae content, were allowed to stand for 24 hours at room temperature. Observation of the tubes of larvae at the end of that time showed 100% kill of larvae in the tubes containing either the compound of Example 1 or the compound of Example 3.

Example '6 This example describes testing of the methyl 3-(2- benzothiazolylthio) acrylate of Example 1 against Monilim'a fructicola, the causal agent of brown rot of stone fruits. The following procedure was used:

A spore suspension of the organism was prepared from a 7 day old culture thereof on a slant of an agar culture medium by removing said spores with a rubber policeman from the slant and suspending them in distilled water. The concentration of spores was adjusted to about 40,000 per ml. of Water. The test compound was added to water in a concentration calculated to give 50 parts of the compound per million parts of Water. An 0.02 ml. aliquot of each of the resulting solutions was pipetted respectively into duplicate wells of a depressed glass slide and al: lowed to evaporate to dryness. Then an 0.1 ml. aliquot of the above spore suspension was pipetted into each well. The concentration of the test compound in each well was thus lowered to 10 parts per million parts of diluent. The slides were then incubated in a moist chamber for 18 hours at 25 C. Inspection of the slides at the end of this time showed no germination of spores in the presence of the 10 ppm. concentration of the test compound, i.e., on the slides in which said methyl 3-(2-benzothiazolylthio)acrylate had been deposited; whereas there was profuse spore germination on controls, i.e., on slides in which none of said compound had been deposited.

Example 7 This example shows testing of the methyl 3-(2-benzothiazolylthio)acrylate of Example 1 against the fungus Aspergilln's niger. The following procedure was used:

An inoculum preparation of Aspergillus niger SN-lll was prepared by adding 10 ml. of sterile distilled Water to a 7-day old, Sabourards dextrose agar slant culture thereof anddislodging the spores into the water with a transfer needle.

Culture media was prepared by respectively adding 18 ml. of Sabourards dextrose agar to 18x150 mm. straight side test tubes, capping with metal culture tube caps, and sterilizing in an autoclave for fifteen minutes at 121 C.

A stock solution of the test compound was prepared by respectively dissolving mg. of said test compound in 10 ml. of acetone: at 1% acetone solution of the compound was thus obtained.

Using a sterile 5 ml. pipette, 2 m1. of said 1% solution was transferred to a tube of melted, sterile culture media prepared as described above. A dilution of 1 part of test compound per 1,000 parts of agar resulted. This was further diluted with additional sterile agar to give a 100 ppm. concentration of the test compound in the agar. The thus-diluted agar was then poured into sterile Petri dishes and allowed to harden.

The four plates of agar were then respectively inoculated with one drop of the above-described inoculum preparation. Examination of the plates after a five-day incubation period showed no growth of the Aspergillus niger at the 100 ppm. concentration of the methyl S-(Z-benzothiazolylthio acrylate.

Example 8 give an 0.1% (1000 ppm.) concentration of the test compound in the agar. The 0.1% agar solution of the test compound was then poured into a Petri dish and allowed to harden. This plate was inoculated with both the Staphylococcus aureus and the Salmonella typhosa, and incubated for two days at 37 C. At the end of that time, inspection of the plate showed no growth of either organism on the plate which contained the 0.1% concentration of the test compound.

The present compositions are characterized by a high degree of efiicacy in that even in very low concentration,

e.g., in a concentration of as low as one p.p.m. they may be extremely effective against bacteria and fungi. Biological toxicant compositions containing the present compounds are advantageously obtained by first preparing a solution thereof in an organic solvent and then adding the resulting solution to water containing an emulsifying agent to form an oil-in-water emulsion. Because of their efiectiveness, they are present in the toxicant compositions in only very small concentrations, for example in concentrations of from 0.0001 percent to 1.0 percent by weight of the total weight of the emulsion. Emulsifying agents which may be employed are those customarily used in the art for the preparation of oil-in-water emulsions. Examples of emulsifying agents which may be used include alkylbenzenesulfonates, long chained polyalkylene glycols, long chained alkylsulfosuccinate, etc.

While the present compounds are most advantageously employed as biological toXicants by incorporating them into an emulsion as herein described, they may also be incorporated into solid carriers such as clay, talc, pumice or bentonite to give compositions which may be applied either to infested areas or to locale which may be subject to infestation. They may also be dissolved in liquefied gases such as the fluorochloroethanes or methyl chloride and applied from aerosol bombs containing the solution.

Biological compositions and methods employing the present heterocyclic esters are claimed in my copending, divisional applications Serial No. 197,838, filed May 28, 1962, and Serial No. 197,855, filed May 28, 1962.

What I claim is:

1. A compound of the formula in which X is selected from the class consisting of -S-, O and -NH-, in which Y is alkyl of from 1 to 5 carbon atoms, and Z is selected from the class consisting of Y, hydrogen and hydrocarbon aryl of from 6 to 10 carbon atoms.

2. A compound of the formula in which Y is alkyl of from 1 to 5 carbon atoms.

3. A compound of the formula o-s-on=onooov in which Y is alkyl of from 1 to carbon atoms.

4. A compound of the formula in which Y is alkyl of from 1 to 5 carbon atoms.

5. Methyl 3-(Z-benzothiazolylthio)acrylate.

6. Methyl 3-(2-benzimidazolylthio)acrylate.

7. Methyl 3-(2-benzoxazolylthio)acrylate.

8. The method of preparing sulfur-containing, heterocyclic olefinic esters which comprises contacting an acetylenic ester of the formula ZCECCOOY in which Z is selected from the class consisting of hydrogen, alkyl of from 1 to 5 carbon atoms and hydrocarbon aryl of from 6 to 10 carbon atoms with a mercapto-substituted heterocyclic compound of the formula C-SH where X is selected from the class consisting of --S-, -O- and -NH.

9. The method of preparing alkyl esters of heterocyclic sulfur-containing acrylates which comprises contacting an alkyl propiolate having from 1 to 5 carbon atoms in the alkyl radical with a compound of the formula gs-.. X/

where X is selected from the class consisting of -S, -O-- and NH.

10. The method of preparing methyl 3-(2-benzothiazolylthio) acrylate which comprises contacting methylpropiolate with 2-mercapto-benzothiazole in the presence of a basic catalyst and an inert diluent.

11. The method of making methyl 3-(2-benzimidazolylthio)acrylate which comprises contacting methyl propiolate with 2-benzimidazolethiol in the presence of a basic catalyst and an inert diluent.

12. The method of preparing methyl 3-(2-benzoxazolylthio)acrylate which comprises contacting methyl propiolate with Z-benzoxazolethiol in the presence of a basic catalyst and an inert diluent.

References Cited in the file of this patent UNITED STATES PATENTS 2,468,075 Jayne et al Apr. 26, 1949 2,535,876 Stewart Dec. 26, 1950 2,647,877 Dazzi Aug. 4, 1953 2,776,977 DAmico Jan. 8, 1957 2,819,965 Murray et al Jan. 14, 1958 2,861,918 Kosrnin Nov. 25, 1958

Claims (2)

1. A COMPOUND OF THE FORMULA

2. A COMPOUND OF THE FORMULA