Processes for producing 1-substituted 2-cyanoimidazole compounds

Abstract: A process for producing 1-substituted-2-cyanoimidazole compounds is described, which comprises undergoing a sulfamoylation reaction and an isomerization reaction of a 2-cyanoimidazole compound represented by formula (II) and a compound represented by formula (III) in the presence of at least one base selected from carbonates of alkali metals and bicarbonates of alkali metals and a polar solvent to produce a 1-substituted-2-cyanoimidazole compound represented by formula (I-b). The substituents in formulae are specifically defined in the specification.

Description: Field of the Invention The present invention relates to processes for producing 1-substituted-2-cyanoimidazole compounds useful as agricultural and horticultural fungicides. Background of the Invention The 1-substituted-2-cyanoimidazole compounds are disclosed in EP-A-298196. Some methods for producing the 1-substituted-2-cyanoimidazole compounds have been proposed therein. However, none of these proposals includes the processes of the present invention. EP-A-298196 discloses that (a) isomer mixtures of 1-substituted-2-cyanoimidazole compounds including compounds represented by formula (I-a), and also formula (I-b) of the present invention, can be prepared by sulfamoylating 2-cyanoimidazole compounds represented by formula (II) of the present invention and that (b) the isomer mixtures can be separated by selective hydrolysis. Furthermore, JP-A-4-120063 discloses that only imidazole compounds represented by formula (I-b) of the present invention can be selectively separated from the isomer mixtures by using a solvent and an acid catalyst. However, EP-A-298196 and JP-A-4-120063 do not disclose the process of the present invention described below producing only imidazole compounds represented by formula (I-b) selectively by sulfamoylating and isomerizing the compounds represented by formula (II). In the process for selectively separating and collecting compounds represented by formula (I-b) from isomer mixtures of 1-substituted-2-cyanoimidazole compounds disclosed in EP-A-298196 and JP-A-4-120063, compounds represented by formula (I-a) are hydrolyzed and the process is thus disadvantageous in that its yield does not exceed the ratio of the isomers of the compounds represented by formula (I-b) and that the post-treatment is complicated. EP-A-0337103 discloses a process for producing 1-substituted-2-cyanoimidazole compounds. In one example, 4-chloro-2-cyano-1-dimethylsulfamoyl-5-propylimidazole is produced by the following procedure. 4(5)-chloro-2-cyano-5(4)-n-propyl imidazole is reacted with dimethylsulfamoyl chloride in the presence of anhydrous potassium carbonate and a relatively large quantity (about 15 litres/kg of the starting imidazole compound) of acetonitrile with heating under reflux. After completion of the reaction, the acetonitrile is removed by distillation from the reaction mixture, and water is poured into the residue followed by extraction with methylene chloride, washing with water and drying. After removal of the methylene chloride by distillation and standing the residue overnight, one of the two isomers decomposes back to form the starting material, 4(5)-chloro-2-cyano-5(4)-n-propylimidazole, whilst the target isomer, 4-chloro-2-cyano-1-dimethylsulfamoyl-5-n-propylimidazole, remains. In another example disclosed in EP-A-0337103, 4-chloro-2-cyano-1-dimethylsulfamoyl-5-phenylimidazole is produced by the following procedure. 4(5)-chloro-2-cyano-5(4)-phenylimidazole is reacted with dimethylsulfamoyl chloride in the presence of anhydrous potassium carbonate and a relatively large quantity (about 14 litres/kg of the starting imidazole compound) of acetone with heating under reflux. After completion of the reaction, the reaction mixture is poured into water and extracted with ethyl acetate, followed by washing with water, drying and distillation of the ethyl acetate to produce equal quantities of the two isomers. After allowing the mixture to stand, the target isomer, 4-chloro-2-cyano-1-dimethylsulfamoyl-5-phenylimidazole, is isolated by silica gel chromatography. Also, the imidazole starting material was recovered, indicating that the other isomer had decomposed. EP-A-0337103 also discloses that the reaction of introducing -SO 2 N(CH 3 ) 2 group to the starting compound including tautomers yields either one of the two isomers or a mixture thereof, depending upon the starting compound, the reaction process of from the starting compound through the product, the reaction conditions, and the like. However, there is no specific teaching as to how these parameters might be selected to achieve production of a particular isomer. Summary of the Invention An object of the present invention is to provide a process for producing 1-substituted-2-cyanoimidazole compounds without employing selective hydrolysis. A still further object of the present invention is to enhance the proportion of isomers of the desired compound represented by formula (I-b) described below. The inventors made extensive studies on the objects. As a result, it was found that an isomerization reaction can provide 1-substituted-2-cyanoimidazole compounds represented by formula (I-b) as the desired compound selectively and in a high yield. Thus, the present invention has been worked out. In addition, these and other objects of the present invention have been achieved by a process for producing 1-substituted-2-cyanoimidazole compounds represented by the following formula (I-b), which comprises undergoing a sulfamoylation reaction and an isomerization reaction of a compound represented by the following formula (II) and a compound represented by the following formula (III) in the presence of at least one base selected from carbonates of alkali metals and bicarbonates of alkali metals and a polar solvent: wherein R 1 and R 2 each represents an alkyl group; X represents a phenyl group which may be substituted or an alkyl group which may be substituted; and Y represents a chlorine atom or a bromine atom; wherein X and Y each has the same meaning as defined above; Hal-SO 2 N(R 1 )R 2 wherein Hal represents a halogen atom; and R 1 and R 2 each has the same meaning as defined above; and wherein the solvent is gradually distilled off during the sulfamotylation reaction and the isomerisation reaction. Detailed Description of the Invention Examples of substituents on the phenyl group which may be substituted represented by X include halogen atoms (e.g., fluorine, chlorine, bromine, iodine), C 1-3 alkyl groups (e.g. methyl, ethyl, propyl), and C 1-3 alkoxy groups (e.g. methoxy, ethoxy, propoxy). The number of the substituents on the phenyl group is from 1 to 5. If there are two or more substituents, they may be the same or different. Examples of substituents on the alkyl group which may be substituted represented by X include halogen atoms (e.g. fluorine, chlorine), a phenyl group, and C 1-3 alkoxy groups. The number of the substituents on the alkyl group is one or more. If there are two or more substituents, they may be the same or different. The alkyl moiety of the alkyl group which may be substituted represented by X include C 1-8 straight-chain or branched alkyl groups. Examples thereof include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, and an octyl group. Specific examples of the groups represented by X include a phenyl group; a 2-, 3- or 4-fluorophenyl group; a 2-, 3- or 4-chlorophenyl group; a 2-, 3- or 4-bromophenyl group; a 2-, 3- or 4-methylphenyl group; a 2-, 3- or 4-ethylphenyl group; a 2-, 3- or 4-propylphenyl group; a 2-, 3- or 4-methoxyphenyl group; a 2-, 3- or 4-ethoxyphenyl group; a 3,4-dichlorophenyl group; a 3,4-dimethylphenyl group; a 3,4-dimethoxyphenyl group; a 3-methyl-4-methoxyphenyl group; a 3-chloro-4-methylphenyl group; a 3-chloro-4-methoxyphenyl group; a tert-butyl group; and a 1,1-dimethylpropyl group. The alkyl group represented by R 1 or R 2 include C 1-12 alkyl groups. Examples of the C 1-12 alkyl groups include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a sec-butyl group, an isobutyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group. Among these, R 1 and R 2 are each preferably a methyl group. Examples of the halogen atom represented by Hal include a chlorine atom, a bromine atom, and an iodine atom. Among these, Hal is preferably a chlorine atom. The compound represented by formula (II) has the following tautomers: In accordance with the process of the present invention, a sulfamoylation reaction and an isomerization reaction are carried out between a compound represented by formula (II) and a compound represented by formula (III) in the presence of a specific base and a polar solvent. Since the compounds represented by formula (II) have tautomers, the progress of the sulfamoylation reaction of the compounds represented by formula (II) produces a compound represented by the following formula (I-a) besides a compound represented by formula (I-b) in the progressing reaction system: wherein R 1 , R 2 X and Y each has the same meaning as defined above. Therefore, the process of the present invention comprise undergoing a sulfamoylation reaction of the compound represented by formula (II) and at the same time an isomerization reaction, which isomerizes the produced compound represented by formula (I-a) to a compound represented by formula (I-b), in the presence of at least one base selected from carbonates of alkali metals and bicarbonates of alkali metals and a polar solvent. For progress of the sulfamoylation reaction and the isomerization reaction, the compound represented by formula (III) is preferably used in an amount of from 1.1 to 2.1 mol per mol of the compound represented by formula (II). For production of only compound represented by formula (I-b) in a high yield, the compound represented by formula (III) is preferably added batchwise two or more times during the reaction. Examples of the batchwise addition process include various processes such as dropwise addition. In a preferred embodiment of the process, the compound represented by formula (III) is first added in an amount of from 1.0 to 1.6 mol per mol of the compound represented by formula (II). When the reaction is completed or toward the end of the reaction, the remaining amount (from 0.1 to 0.5 mol) of the compound represented by formula (III) may be added to the reaction system. The base for use in the reaction is at least one selected from carbonates of alkali metals and bicarbonates of alkali metals. Examples thereof include carbonates of alkali metals (eg potassium carbonate, sodium carbonate), and bicarbonates of alkali metals (eg potassium bicarbonate, sodium bicarbonate). Among these, carbonates of alkali metals are preferred, and potassium carbonate is particularly preferred. For progress of the sulfamoylation reaction and the isomerization reaction in the process of the present invention, a base is preferably used in an amount of from 0.75 to 2.1 equivalents per mol of the compound represented by formula (II). For production of only compound represented by formula (I-b) in a high yield, the base is preferably added batchwise two or more times during the reaction. Examples of the batchwise addition process include various processes. In a preferred embodiment, the base is first added in an amount of from 0.65 to 1.6 equivalents per mol of the compound represented by formula (II). When the reaction is completed or toward the end of the reaction, the remaining amount (from 0.1 to 0.5 equivalents) of the base may be added. Examples of the polar solvent for use in this process may be any polar solvent capable of dissolving the compound represented by formula (I-a) or (I-b) therein. Examples of the polar solvent include ketones (eg, acetone, methyl ethyl ketone, methyl isobutyl ketone), nitriles (eg, acetonitrile, propionitrile), aprotic polar solvent (eg, dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane), alcohols (eg, methanol, ethanol, propanol, butanol), and esters (eg ethyl acetate, methyl acetate). Among these, methyl ethyl ketone and ethyl acetate are preferred. The amount added of the polar solvent in this process is from 1 to 3 ℓ, preferably from 1.5 to 2 ℓ, per kg of the compound represented by formula (II). In this process, the sulfamoylation reaction and the isomerization reaction are carried out while the polar solvent is gradually distilled off. If the base and/or the compound represented by formula (III) is batchwise added for the reaction, the polar solvent is preferably distilled off after the batchwise addition. In this process, the reaction temperature of the sulfamoylation reaction and the isomerization reaction is preferably from 20°C to 110°C. If the base and/or the compound represented by formula (III) is batchwise added for the reaction, the reaction temperature before the batchwise addition of these components is from 20°C to 110°C, preferably from 60°C to 100°C, and the reaction temperature after the batchwise addition of these components is from 20°C to 110°C, preferably from 60°C to 100°C. More preferably, the reaction temperatures before and after the batchwise additions are each from 65°C to 85°C. The present invention will be further described in the following examples, but the present invention should not be construed as being limited thereto. EXAMPLE 1 Into a four-necked flask equipped with an agitator, an azeotropic dehydrator and a thermometer were charged 8.7 g of 4(5)-chloro-2-cyano-5(4)-(4-methylphenyl)imidazole, 20 mℓ of ethyl acetate, 6.6 g of potassium carbonate and 6.3 g of dimethylsulfamoyl chloride. The reaction mixture was then heated under reflux for 2 hours. To the reaction system were then added 0.6 g of potassium carbonate and 0.6 g of dimethylsulfamoyl chloride. The reaction mixture was then kept while distilling off ethyl acetate from the reaction system for one hour (yield of the desired compound: 93 mol%). After the completion of the reaction, 20 mℓ of water and 20 mℓ of ethyl acetate were poured into the reaction system. The reaction mixture was then stirred at a temperature of from 60°C to 70°C for 20 minutes to obtain slurry of the desired compound. The slurry was recovered by filtration, and then dried to obtain 11.7 g of 4-chloro-2-cyano-1-dimethylsulfamoyl-5-(4-methylphenyl)imidazole (purity: 98.2%; yield: 90.5%). EXAMPLE 2 Into a four-necked flask equipped with an agitator, an azeotropic dehydrator and a thermometer were charged 40.0 g of 4(5)-chloro-2-cyano-5(4)-(4-methylphenyl)imidazole, 80.3 mℓ of ethyl acetate, 30.6 g of potassium carbonate and 29.2 g of dimethylsulfamoyl chloride. The reaction mixture was then heated under reflux for 2 hours. To the reaction system were then added 5.1 g of potassium carbonate and 5.3 g of dimethylsulfamoyl chloride. After the addition, to the reaction system were further added 2.6 g of potassium carbonate and 2.7 g of dimethylsulfamoyl chloride. That is, potassium carbonate and dimethylsulfamoyl chloride were added batchwise two times in a total amount of 7.7 g and 8.0 g, respectively. After the batchwise addition, the mixture was reacted while distilling off ethyl acetate from the reaction system for 1.5 hours (yield of the desired compound: 90 mol%). After the completion of the reaction, 80 mQ of water and 80 mℓ of ethyl acetate were poured into the reaction system to obtain a slurry. The slurry was recovered by filtration, and then dried to obtain 55.8 g of 4-chloro-2-cyano-1-dimethylsulfamoyl-5-(4-methylphenyl)imidazole (purity: 99.0%; yield: 92.5%). EXAMPLE 3 Into a four-necked flask equipped with an agitator, an azeotropic dehydrator and a thermometer were charged 5.0 g of 4(5)-chloro-2-cyano-4-(methylphenyl)imidazole, 10 mℓ of methyl ethyl ketone, 3.6 g of potassium carbonate and 3.4 g of dimethylsulfamoyl chloride. The reaction mixture was then heated under reflux for 2 hours. To the reaction system were then added 0.3 g of potassium carbonate and 0.3 g of dimethylsulfamoyl chloride. After the addition, to the reaction system were further added 0.1 g of potassium carbonate and 0.1 g of dimethylsulfamoyl chloride. That is, potassium carbonate and dimethylsulfamoyl chloride were added batchwise two times in a total amount of 0.4 g and 0.4 g, respectively. After the batchwise addition, the reaction mixture was kept while distilling off methyl ethyl ketone from the reaction system for 1.5 hours (yield of the desired compound: 95 mol%). After the completion of the reaction, 30 mℓ of water was poured into the reaction system to obtain a slurry. The slurry was recovered by filtration, and then dried to obtain 6.8 g of 4-chloro-2-cyano-1-dimethylsulfamoyl-5-(4-methylphenyl)imidazole (purity: 99.0%; yield: 95.0%). Attention is drawn to EP-0705823 from which the present application is divided. While the invention has been described in detail and with reference to specific emdodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein.

Claims: A process for selectively producing 1-substituted-2-cyanoimidazole compounds represented by the following formula (I-b), which comprises undergoing a sulfamoylation reaction and an isomerization reaction of a compound represented by the following formula (II) and a compound represented by the following formula (III) in the presence of at least one base selected from carbonates of alkali metals and bicarbonates of alkali metals and a polar solvent: wherein R 1 and R 2 each represents an alkyl group; X represents a phenyl group which may be substituted or an alkyl group which may be substituted; and Y represents a chlorine atom or a bromine atom; wherein X and Y each has the same meaning as defined above; Hal-SO 2 N(R 1 )R 2 wherein Hal represents a halogen atom; and R 1 and R 2 each has the same meaning as defined above; and wherein the solvent is added in an amount of from 1 to 3 ℓ per kg of the compound represented by formula (II), and is gradually distilled off during the sulfamoylation reaction and the isomerization reaction. The process according to claim 1, wherein the polar solvent is methyl ethyl ketone or ethyl acetate. The process according to any preceding claim, wherein the reactions are carried out at a temperature of from 20°C to 110°C. The process according to any preceding claim, wherein said compound of the formula (III) is added batchwise two or more times during the reaction. The process according to any preceding claim, wherein said at least one base is added batchwise two or more times during the reaction.

Inventors: JONISHI HISAYOSHI, KANAMORI FUMIO, KANBAYASHI SHIGEHISA, JONISHI, HISAYOSHI, KANAMORI, FUMIO, KANBAYASHI, SHIGEHISA, Jonishi, Hisayoshi, c/o Ishihara Sangyo K., Ltd., Kanamori, Fumio, c/o Ishihara Sangyo K., Ltd., Kanbayashi, Shigehisa, c/o Ishihara Sangyo K., Ltd
Applicants: ISHIHARA SANGYO KAISHA, ISHIHARA SANGYO KAISHA LTD.
Application year: 1995
Main classification: C07D233
IPC codes: C07D233