A KETENE S,S-ACETAL DERIVATIVE, A PROCESS FOR MANUFACTURING THEREOF AND A METHOD FOR CURING MYCOSIS BY ADMINISTERING IT

Abstract: A novel ketene S,S-acetal derivative which is useful as an antimycotic agent and an agricultural chemical of fungicidal, plant growth regulating or insecticidal properties represented by the general formula (I): (in which R₁ represents a hydrogen atom, a wherein R represents a hydrogen atom; an alkyl group having 1 to 8 carbon atoms; a cycloalkyl group having 3 to 6 carbon atoms; a methylene group; a lower alkenyl group; a lower alkyl group substituted by a halogen atom, a cyano group, a lower alkoxyl group, a lower alkylthio group; a carbamoyl group, an acyl group, or an alkenoyloxy group; a phenyl group represented by halogen atom, a straight or branched chain lower alkyl group, a lower alkoxyl group which may be substituted by one or more halogen atoms, a phenoxy group or a methylenedioxy group, and m represents an integer of 1 to 3); a benzyl group; a methylenedioxybenzyl group; a phenoxyalkyl group; a phenoxyalkyl group substituted by a halogen atom; a naphthyl group; or a substituted or unsubstituted pyridyl group.

Description: This invention relates to ketene S,S-acetal derivatives useful as antimycotic agents and agricultural chemicals. EP-A-61794 discloses antimicrobial imidazole derivatives and EP-A-80103 discloses azolylvinyldithioacetals. The present invention relates to ketene S,S-acetal derivatives represented by the general formula (I): wherein R represents a hydrogen atom; an alkyl group having 1 to 8 carbon atom; a cycloalkyl group having 3 to 6 carbon atoms; a methylene group; a lower alkenyl group; a lower alkyl group substituted by a halogen atom, a cyano group, a lower alkoxyl group, a lower alkylthio group, a carbamoyl group, an acyl group, or an alkenoyloxy group; a phenyl group represented by (in which R₁ represents a hydrogen atom, a halogen atom, a straight or branched chain lower alkyl group, a lower alkoxyl group which may be substituted by one or more halogen atoms, a phenoxy group or a methylenedioxy group, and m represents an integer of 1 to 3); a benzyl group; a methylenedioxybenzyl group; a phenoxyalkyl group; a phenoxyalkyl group substituted by a halogen atom; a naphthyl group; or a substituted or unsubstituted pyridyl group. The compounds represented by the general formula (I) are useful as antimycotic agents and agricultural chemicals; in particular, not only fungicides and plant growth regulators but also insecticides. The substituent R in the above general formula (I) includes a hydrogen atom; straight or branched chain alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, neo-pentyl, n-hexyl or n-octyl; cycloalkyl groups such as cyclopropyl or cyclohexyl; a methylene group; lower alkenyl groups such as vinyl or allyl; lower alkyl groups substituted by a halogen atom such as chloromethyl or dichloroethyl; lower alkyl groups substituted by a cyano group such as cyanomethyl; lower alkyl groups substituted by a lower alkoxyl such as methoxymethyl or methoxyethyl or a lower alkylthio group such as methylthiomethyl; lower alkyl groups substituted by a carbamoyl group such as carbamoylmethyl; lower alkyl groups substituted by an acyl group; lower alkyl groups substituted by an alkenoyloxy groups such as acryloylmethyl; phenyl groups represented by (in which R₁ represents a hydrogen atom, a halogen atom, a straight or branched chain lower alkyl group, a lower alkoxyl group which may be substituted by one or more halogen atoms, a phenoxy group or a methylenedioxy group, and m represents an integer of 1 to 3); a benzyl group; a methylenedioxybenzyl group; a phenoxyalkyl group such as phenoxymethyl; a phenoxyalkyl group substituted by a halogen atom; a naphthyl group; or a substituted or unsubstituted pyridyl group. The compound represented by the general formula (I) of this invention can be synthesized, for example, by the process shown below: wherein R is as defined above, and X represents a halogen atom, a mesyloxy or a tosyloxy group. The compound represented by the general formula (I) can be obtained by reacting 1-cyanomethylimidazole represented by the structural formula (II) with carbon disulfide in the presence of a base and a solvent to form an intermediate represented by the structural formula (IV), and reacting the intermediate with a compound represented by the general formula (III) without isolating same. As the solvent usable in the invention, any solvent may be used as long as it does not inhibit the progress of the reaction, and there can be exemplified, for example, alcohols such as methanol, ethanol or isopropanol, dimethylsulfoxide, dimethylformamide, hexamethylenephosphoroamide or water. These solvents can be used alone or as a mixture thereof. As the base usable in this invention, there can be exemplified sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide and potassium t-butoxide. These can be used in solid state or in solution. Although it is sufficient that the reaction temperature is selected in the range of 0 o to 100 o C, it is particularly preferable to carry out the reaction at a temperature near room temperature. It is sufficient that the reaction time is properly selected in the range of 0.5 to 24 h. It is sufficient that the amount of the base used is selected in the range of 2 to 4 moles per mole of 1-cyanomethylimidazole represented by the structural formula (IV). It is sufficient that after completion of the reaction, the reaction solution is treated in the usual way. For example, the reaction product is extracted and separated with a suitable solvent and can then be purified by recrystallization or column chromatography. The compound represented by the general formula (I) is often obtained as a mixture of two kinds of the geometrical isomers shown below. The aforesaid mixture of Z and E isomers can often be isolated into the two isomers by a suitable separation method, for example, recrystallization or chromatography. This invention includes the geometrical isomers, i.e., the E and Z isomers, and all mixtures of the two isomers in any ratio. Typical examples of the compounds represented by the general formula (I) are shown in Table 1. Preferred compounds are those wherein R represents a lower alkyl group, a lower alkyl group substituted by a lower alkoxyl or alkylthio group, or in which R₁ represents a halogen atom, especially chlorine or bromine atom, or a straight or branched chain lower alkyl group, especially methyl, and m represents an integer of 1 to 3. Examples of this invention are shown below. Example 1 Synthesis of 2-(1-imidazolyl)-2-(4-isobutyl-1,3-dithiolan-2-ylidene)acetonitrile (Compound Nos. 8 and 9) To a mixed solution of 0.55 g (0.005 mole) of 1-cyanomethylimidazole, 0.4 g (0.005 mole) of carbon disulfide and 10 ml of dimethyl sulfoxide was added 0.8 g (0.014 mole) of potassium hydroxide powder with stirring, and the reaction was carried out at room temperature for 1 h. Then, 1.5 g (0.006 mole) of 1,2-dibromo-4-methylpentane was added dropwise with stirring, and the resulting solution was subjected to reaction for 2 h. After completion of the reaction, 20 ml of water was added to the reaction solution, after which the resulting mixture was subjected to extraction with ethyl acetate, and the organic layer was washed with water and dried. The solvent was distilled off and the residue was purified by silica gel chromatography to obtain 0.45 g of the Z isomer and 0.3 g of the E isomer individually in the form of colorless crystals. The Z isomer (Compound No. 8): melting point 73.3 o C, yield 34%. The E isomer (Compound No. 9): melting point 118.1 o C, yield 23%. Example 2 Synthesis of 2-(1-imidazolyl)-2-(4-chloromethyl-1,3-dithiolan-2-ylidene)acetonitrile (Compound No. 25). To a mixed solution of 0.55 g (0.005 mole) of 1-cyanomethylimidazole, 0.4g (0.005 mole) of carbon disulfide and 10 ml of dimethyl sulfoxide was added 0.8 g (0.014 mole) of potassium hydroxide powder with stirring, and the reaction was carried out at room temperature for 1 h. Then, 1.4 g (0.006 mole) of 1,2-dibromo-3-chloropropane was added dropwise with stirring, and the resulting solution was subjected to reaction for 2 h. After completion of the reaction, 20 ml of water was added to the reaction solution, after which the resulting mixture was subjected to extraction with ethyl acetate, and the organic layer was washed with water and dried. The solvent was distilled off and the residue was purified by silica gel chromatography and recrystallized from ethyl acetate-n-hexane to obtain 0.8 g of the desired compound in the form of colorless crystals: melting point 96.2 o C, yield 62%. Example 3 Synthesis of 2-(1-imidazolyl)-2-(4-methylidene-1,3-dithiolan-2-ylidene)acetonitrile (Compound No. 23) In 10 ml of tetrahydrofuran were dissolved 0.52 g (0.002 mole) of the 2-(1-imidazolyl)-2-(4-chloromethyl-1,3-dithiolan-2-ylidene)acetonitrile obtained in Example 2 and 0.31 g of 1,8-diazabicyclo-[5,4,0]-7-undecene, and the reaction was carried out with heating under reflux for 1 h. After the reaction solution was allowed to cool, the deposited salt was separated by filtration and the filtrate was concentrated to obtain crude crystals, which were then recrystallized from ethyl acetate-n-hexane to obtain 0.35 g of the desired compound in the form of crystals: melting point 115.7 o C, yield 79%. Example 4 Synthesis of 2-(1-imidazolyl)-2-[4-(2,4-dichlorophenyl)-1,3-dithiolan-2-ylidene]acetonitrile (Compound Nos. 52 and 53) To a mixed solution of 0.55 g (0.005 mole) of 1-cyanomethylimidazole, 0.4 g (0.005 mole) of carbon disulfide and 10 ml of dimethyl sulfoxide was added 0.8 g (0.014 mole) of potassium hydroxide powder with stirring, and the reaction was carried out at room temperature for 1 h. Then, 2.0 g (0.006 mole) of 2',4'-dichloro-1,2-dibromoethylbenzene was added dropwise with stirring, and the resulting solution was subjected to reaction for 2 h. After completion of the reaction, 20 ml of water was added to the reaction solution, and the resulting mixture was subjected to extraction with ethyl acetate, and the organic layer was washed with water and dried. The solvent was distilled off and the residue was purified by silica gel chromatography to obtain 0.25 g of the Z isomer and 0.5 g of the E isomer individually in the form of a yellow viscous substance: yield (total yield of the Z and E isomers) 42%, melting points 110.5 o C (the Z isomer) and 100.4 o C (the E isomer). Example 5 Synthesis of 2-(1-imidazolyl)-2-[4-(2-isopropylphenyl)-1,3-dithiolan-2-ylidene]acetonitrile (Compound No. 47) To a mixed solution of 0.55 g (0.005 mole) of 1-cyanomethylimidazole, 0.4 (0.005 mole) of carbon disulfide and 10 ml of dimethylformamide was added 0.8 g (0.014 mole) of potassium hydroxide powder, and the reaction was carried out with stirring at room temperature for 1 h. Then, 1.8 g (0.006 mole) of 2'-isopropyl-1,2-dibromoethylbenzene was added dropwise with stirring, and the resulting solution was subjected to reaction for another 2 h. After completion of the reaction, 20 ml of water was addd to the reaction solution, and the resulting mixture was subjected to extraction with ethyl acetate, and the organic layer was washed with water and dried. The solvent was distilled off and the residue was purified by silica gel chromatography to obtain the desired compound in the form of a light-yellow oily substance: n 16 / D 1.6196, yield 34%. Example 6 Synthesis of 2-(1-imidazolyl)-2-[4-(2-chlorophenyl)-1,3-dithiolan-2-ylidene]acetonitrile (Compound Nos. 34 and 35) To a mixed solution of 2.2 g (0.02 mole) of 1-cyanomethylimidazole, 1.60 g (0.02 mole) of carbon disulfide and 10 ml of dimethyl sulfoxide was added 3.0 g (0.05 mole) of potassium hydroxide powder, and the reaction was carried out with stirring at room temperature for 1 h. Then, 4.2 g (0.02 mole) of 2'-chloro(1,2-dichloroethyl)benzene was added dropwise with stirring, and the resulting solution was subjected to reaction for another 2 h. After completion of the reaction, 20 ml of water was added to the reaction solution, after which the resulting mixture was subjected to extraction with ethyl acetate, and the organic layer was washed with water and dried. The solvent was distilled off and the residue was purified by silica gel chromatography to obtain 2.0 g of the Z isomer and 2.4 g of the E isomer individually in the form of light-yellow crystals. The Z isomer: melting point 119.4 o C, yield 31%. The E isomer: melting point 141.5 o C, yield 38%. Example 7 Synthesis of 2-(1-imidazolyl)-2-[4-(2-chlorophenyl)-1,3-dithiolan-2-ylidene]acetonitrile (Compound Nos. 34 and 35) To a mixed solution of 2.2 g (0.02 mole) of 1-cyanomethylimidazole, 1.60 g (0.02 mole) of carbon disulfide and 10 ml of dimethyl sulfoxide was added 3.0 g (0.05 mole) of potassium hydroxide powder, and the reaction was carried out with stirring at room temperature for 1 h. Then, 6.0 g (0.02 mole) of 2'-chloro(1,2-dibromoethyl)benzene was added dropwise with stirring, and the resulting solution was subjected to reaction for another 2 h. After completion of the reaction, 20 ml of water was added to the reaction solution, after which the resulting mixture was subjected to extraction with ethyl acetate, and the organic layer was washed with water and dried. The solvent was distilled off and the residue was purified by silia gel chromatography to obtain 0.3 g of the Z isomer and 1.3 g of the E isomer individually in the form of light-yellow crystals. The Z isomer: melting point 119.4 o C, yield 5%. The E isomer: melting point 141.5 o C, yield 20%. Example 8 Synthesis of 2-(1-imidazolyl)-2-[4-(2-chlorophenyl)-1,3-dithiolan-2-ylidene]acetonitrile (Compound Nos. 34 and 35) To a mixed solution of 2.2 g (0.02 mole) of 1-cyanomethylimidazole, 1.60 g (0.02 mole) of carbon disulfide and 10 ml of dimethyl sulfoxide was added 3.0 g (0.05 mole) of potassium hydroxide powder, and the reaction was carried out with stirring at room temperature for 1 h. Then, 6.6 g (0.02 mole) of 2'-chloro(1,2-dimesyloxyethyl)benzene was added dropwise with stirring, and the resulting solution was subjected to reaction for another 2 h. After completion of the reaction, 20 ml of water was added to the reaction solution, after which the resulting mixture was subjected to extraction with ethyl acetate, and the organic layer was washed with water and dried. The solvent was distilled off and the residue was purified by silica gel chromatography to obtain 1.3 g of the Z isomer and 1.8 g of the E isomer individually in the form of light-yellow crystals. The Z isomer: melting point 119.4 o C, yield 20%. The E isomer: melting point 141.5 o C, yield 28%. The compounds of this invention are antimycotic agents useful for preventing fungous infection of human beings and animals. For example, these compounds can be used for curing mycoses such as local mycotic infection, mucosal mycotic infection or systemic mycotic infection which are caused by Dermatophytes such as Microsporum, Epidermophyton or Trichophyton and Candida. The compounds of this invention can be mixed with conventional chemotherapeutically acceptable diluents or carriers and if desired, other excipients, and can be used in pharmaceutical forms such as solutions, creams, suppositories, ointments or tablets. When used as antimycotic agents, the compounds of this invention can be used as local liniments in pharmaceutical forms such as creams, ointments or solution. When they are used in the form of an endermic solution, their practical concentration is considered to be suitably 0.1% or more. The present drugs may be used, of course, in an admixture with other antibacterial agents such as amphotericin B, nystatin, trichomycin, variotin or clotrimazole. Further, the compounds of this invention are useful as agricultural and horticultural fungicides. For example, they are very effective against various phytopathogenic diseases, e.g., rice blast ( Piricularia oryzae ); powdery mildew of barley and wheat ( Erysiphe graminis ), and other powdery mildews of various host plants such as that of cucumber ( Sphaerotheca fulginea ), that of apple ( Podosphaera leucotricha ) and that of grape ( Uncinula necator ); rust of wheat ( Puccinia vecondita ); Crown rust of oats ( Puccinia coronate ) and rust of other host plants: late blight of tomato ( phytophthora capsici ) and phytophthora rot of other host plants. When the compound of this invention is used as active ingredient in an agricultural and a horticultural fungicide, the fungicide is prepared into a formulation suitable for use in a conventional manner as an agricultural chemical. For example, the fungicide is prepared in the form of dust, granules, fine granules, wettable powder, emulsifiable concentrate, oily solution, aerosol, floating dust, fumigants, preparations suitable for vaporizing the active ingredient by heat or other physical means or tablets by mixing the compound of the invention with adjuvants, and is applied to stalks and leaves of vegetables, flowering plants, crops for industrial use, fruit trees and other trees as it is or after diluted to a suitable volume with water. Although in this invention the dosage of the active ingredient varies depending on the kind of the compound, plant to be treated or the way of using, it can be selected in the range of 5 to 500 g per 10 ares. When applied, the compound of this invention can also be used in combination with other agricultural chemicals, fertilizers or plant nutrients which can be used similarly to the compound. For example, when a phytopathogenic disease is controlled by using an agricultural and horticultural fungicide comprising the compound of this invention as active ingredient, the fungicide can be made into a multiple-purpose preventing and curing agent by mixing therewith an agent for preventing and curing other diseases and/or vermin insects which break out simultaneously with the aforesaid disease. Some Test Examples and Formulation Examples are given below in order to demonstrate the usefulness of the compounds of this invention. Test Example 1 Test for antifungal activity against Trichophyton mentagrophytes In 1 liter of water were dissolved 10 g of peptone and 4.0 g of glucose and the resulting solution was adjusted to pH 6.0, after which a drug containing 50 ppb (1% DMSO solution) of each active ingredient was added. Into a 3.5  cm Petri dish was poured 30 ml of the thus obtained Sabouraud medium to prepare an agar plate. Then, the inoculum of the fungus precultured was poured onto the plate in an amount of 0.1 ml per Petri dish. The thus prepared plates were incubated at 28 o C for 4-6 days. The test was carried out in duplication for each compound and the results per dish evaluated macroscopically are shown in Table 2. Test Example 2 Curing effect test against trichophytosis which was artificially infected in guinea pigs Hartley strain white male guinea pigs (400 to 600 g) were used as test animals. The hair in three spots on the back of each guinea pig was sheared and then removed in a circle having a diameter of about 3 cm by use of depilatory cream, after which the skin in the depilated spots was lightly rubbed with sandpaper. The thus treated spots were inoculated with 0.1 ml (10⁶ spores/spot) of culture of Trichophyton mentagrophytes IFO-5466 strain grown on Sabouraud glucose agar media. Each test drug prepared by using polyethylene glycol 300 as base was applied to the inoculation spots once daily for 11 consecutive days in an amount of 0.2 ml per inoculation spot, starting 72 h after the inoculation. The evaluation was conducted by macroscopical judgement and reverse culture test. a) Macroscopical judgement: After the inoculation, the alleviation and development of symptoms in the above-mentioned spots were observed every day for 15 days. The results are shown in Table 3. 0: No symptom was observed. 1: A few small erythemas were observed. 2: Erythemas were insularly scattered or fused into one, and rubefaction was observed around them. 3: Scales were observed, and then formation of a thick lesion was observed. 4: Lesion reached an extreme stage with bleeding. The results obtained are shown in Table 3. b) Reverse culture test Each guinea pig was sacrified 15 days after the inoculation, after which the skin in the whole inoculation spots was cut off and the skin cut-off was further cut into small pieces (about 5 mm square). The pieces thus prepared were placed on Sabouraud glucose agar medium containing 20 i.u./ml of penicillin G and 40 µg/ml of streptomycin, and then cultured at 27 o C for 2 weeks. The evaluation was carried out by investigating the colonies. The results obtained are shown in Table 4. Test Example 3 Controlling Effects on Powdery Mildew of Barley Young barley plants (variety: Kanto No. 6, 2-leaf stage) cultivated in porcelain pots (12 cm in diameter) were inoculated by conidia of Erysiphe graminis graminis F.Sp. hordei, the causal fungus of powdery mildew. The day after inoculation, the plants were treated on a turn table by spraying solutions (200 ppm) of the present compounds by a spray gun. The treated plants were kept at 25 o C for 6 days in a greenhouse and the development of lesions was assessed. The controlling effects of the compounds were calculated in comparison with the untreated plots. The criteria for the controlling effects are: 4; 100 - 95% control 3; 94 - 80% control 2; 79 - 60% control 1; 59 - 0% control The results are shown in Table 5. Test Example 4 Controlling Effects on seed-borne Fusarium Cucumber seeds infested with Fusarium oxysporum f.sp. cucumerinum were soaked in solutions (200 ppm) of the present compounds for 20 h. The treated seeds were then placed on a selective medium for Fusarium spp. (Komada medium). After a week-incubation at 25 o C, the mycelial growth around the treated seeds was assessed and the controlling effects were calculated in comparison with the untreated plots. The criteria for controlling effects are the same as in Test Example 3. The results are shown in Table 6. The recipes shown below as Formulation Examples 1 to 3 are for medical purposes. For these purposes, the various adjuvants and constituents to be used should be of pharmaceutically acceptable grade. In Formulation Examples 1 to 3, all parts are by weight. Formulation Example 1 Compound 35 1 part Polyethylene glycol 300 95 parts These ingredients are mixed to prepare an endermic solution. Formulation Example 2 Compound 53 2 parts Polyethylene glycol 400 40 parts Polyethylene glycol 1500 58 parts These ingredients are mixed with heating to obtain a solution, which is then colled to prepare an ointment. Formulation Example 3 Copmpound 38 2 parts 1,2-Propanediol 5 parts Glycerol stearate 5 parts Spermaceti 5 parts Isopropyl myristate 10 parts Polysorbate 60 4 parts A mixture of these compounds is heated and then cooled, after which 69 parts of water is added with stirring to prepare a cream. In addition to the pharmaceutical formulations described above, a preparation in pharmaceutically usable forms such as injections or tablets is possible. The recipes shown in Formulation Examples 4 to 7 are for agricultural chemicals. In these examples, all parts are by weight as in Formulation Examples 1 to 3. Formulation Example 4 Wettable powder Compound 12 50 parts Mixture of diatomaceous earth and clay 45 parts Polyoxyethylene nonylphenyl ether 5 parts These ingredients are homogeneously mixed and then pulverized to prepare a wettable powder. Formulation Example 5 Emulsifiable concentrate Compound 23 20 parts Tetrahydrofuran 20 parts Xylene 45 parts Mixture of polyoxyethylene nonylphenyl ether and alkyl benzenesulfonate 15 parts These ingredients are homogeneously mixed to prepare an emulsifiable concentrate. Formulation Example 6 Dust Compound 29 4 parts Mixture of diatomaceous earth, clay and talc 95 parts Calcium stearate 1 part These ingredients are homogeneously mixed and then pulverized to prepare a dust. Formulation Example 7 Granules Compound 46 3 parts Mixture of bentonite and clay 92 parts Calcium lignin sulfonate 5 parts These ingredients are homogeneously mixed and then pulverized, after which an adequate amount of water is added, and the resulting mixture is sufficiently kneaded and then granulated to prepare granules.

Claims: Claims for the following Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE A ketene S,S-acetal derivative represented by the general formula (I): wherein R represents a hydrogen atom; an alkyl group having 1 to 8 carbon atoms; a cycloalkyl group having 3 to 6 carbon atoms; a methylene group; a lower alkenyl group; a lower alkyl group substituted by a halogen atom, a cyano group, a lower alkoxyl group, a lower alkythio group, a carbamoyl group, an acyl group, or an alkenoyloxy group; a phenyl group represented by (in which R₁ represents a hydrogen atom, a halogen atom, a straight or branched chain lower alkyl group, a lower alkoxyl group which may be substituted by one or more halogen atoms, a phenoxy group or a methylenedioxy group, and m represents an integer of 1 to 3); a benzyl group; a methylenedioxybenzyl group; a phenoxyalkyl group; a phenoxyalkyl group substituted by a halogen atom; a naphthyl group; or a substituted or unsubstituted pyridyl group. A ketene S,S-acetal derivative according to claim 1, wherein R represents in which R₁ represents a halogen atom or methyl group, and m represents an integer of 1 to 3. A ketene S,S-acetal derivative according to claim 1, which is 2-(1-imidazolyl)-2-[4-(2,4-dichlorophenyl)-1,3-dithiolan-2-ylidene]acetonitrile (E isomer). A ketene S,S-acetal derivative according to claim 1, which is 2-(1-imidazolyl)-2-[4-(2-chloro-phenyl)-1,3-dithiolan-2-ylidene]acetonitrile (E isomer). A ketene S,S-acetal derivative according to claim 1, which is 2-(1-imidazolyl)-2-[4-(2-bromo-phenyl)-1,3-dithiolan-2-ylidene]acetonitrile (E isomer). A ketene S,S-acetal derivative according to claim 1, which is 2-(1-imidazolyl)-2-[4-(4-chloro-phenyl)-1,3-dithiolan-2-ylidene]acetonitrile (E isomer). A process for producing a ketene S,S-acetal derivative according to any of claims 1 to 6, which comprises reacting 1-cyanomethylimidazole represented by the general formula (II): with carbon disulfide in the presence of a base, and then reacting the reaction product with a compound represented by the general formula (III): wherein R is as defined in claim 1 and X represents a halogen atom, a mesyloxy or a tosyloxy group. An agricultural and horticultural fungicidal composition comprising a fungicidically effective amount of a ketene S,S-acetal derivative according to any of claims 1 to 6. A pharmaceutical composition comprising a pharmaceutically effective amount of a ketene S,S-acetal derivative according to any of claims 1 to 6. Claims for the following Contracting State : AT A process for producing a ketene S,S-acetal derivative represented by the general formula (I): wherein R₁ represents a hydrogen atom; an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a methylene group; a lower alkenyl group; a lower alkyl group substituted by a halogen atom, a cyano group, a lower alkoxyl group, a lower alkylthio group, a carbamoyl group, an acyl group, or an alkenoyloxy group; a phenyl group represented by (in which R₁ represents a hydrogen atom, a halogen atom, a straight or branched chain lower alkyl group, a lower alkoxyl group which may be substituted by one or more halogen atoms, a phenoxy group or a methylenedioxy group, and m represents an integer of 1 to 3): a benzyl group; a methylenedioxybenzyl group; a phenoxyalkyl group; a phenoxyalkyl group substituted by a halogen atom; a naphthyl group; or a substituted or unsubstituted pyridyl group, which comprises reacting 1-cyanomethylimidazole represented by the general formula (II): with carbon disulfide in the presence of a base, and then reacting the reaction product with a compound represented by the general formula (III): The process of claim 1 wherein R represents in which R₁ represents a halogen atom or methyl group, and m represents an integer of 1 to 3. The process of claim 1 wherein 2-(1-imidazolyl)-2-[4-(2,4-dichlorophenyl)-1,3-dithiolan-2-ylidene]acetonitrile (E isomer) is produced. The process of claim 1 wherein 2-(1-imidazolyl)-2-[4-(2-chloro-phenyl)-1,3-dithiolan-2-ylidene]acetonitrile (E isomer) is produced. The process of claim 1 wherein 2-(1-imidazolyl)-2-[4-(2-bromo-phenyl)-1,3-dithiolan-2-ylidene]acetonitrile (E isomer ) is produced. The process of claim 1 wherein 2-(1-imidazolyl)-2-[4-(4-chloro-phenyl)-1,3-dithiolan-2-ylidene]acetonitrile (E isomer) is produced. A process for preparing an agricultural and horticultural fungicidal composition comprising mixing a fungicidically effective amount of a ketene S,S-acetal derivative produced according to any of claims 1 to 6 with usual carriers and/or diluents. A process for preparing a pharmaceutical composition comprising mixing a pharmaceutically effective amount of a ketene S,S-acetal derivative produced according to any of claims 1 to 6 with usual carriers and/or diluents.

Inventors: HASEGAWA, NOBU, IKEDA, KENICHI, KANNO, HIDEO, KONAKA, SHIGEO, MIYAGI, YUKIO, MUNECHIKA, YUKIMI, NISHIMURA, AKIRA, OHMI, TETSUTO, SOE, AKIRA, UCHIDA, MATAZAEMON
Applicants: NIHON NOHYAKU CO., LTD.
Application year: 1985
Main classification: C07D409
IPC codes: C07D521