CS204999B2 - Method of producing new banzimidazole derivatives - Google Patents

Description

SUMMARY OF THE INVENTION The present invention provides a process for the preparation of novel gasoline dazole derivatives and salts thereof.

The novel benzimidazole derivatives are compounds of formula I

(I) and salts thereof, wherein

R is a C 1 -C 6 alkyl group or a C 5 -C 6 cycloalkyl group or a phenyl group optionally substituted by one or two halogen atoms,

The term C 1 -C 6 alkyl refers to aliphatic groups with straight or branched chain, for example methyl, ethyl, n-propyl, isobutyl, etc. The term C 3 -C 6 cycloalkyl may be preferably cyclopropyl, cyclobutyl, cyclopentyl and a cyclohexyl radical.

The salts of the compound of formula (I) are to be formed with inorganic or organic acids, for example hydrochloric, hydrobromic, sulfuric, acetic, formic, lactic, tartaric, etc. Salts to be used in medicine should be formed with pharmaceutically acceptable acids.

Particularly preferred derivatives of formula I are the following compounds:

1- ['(3,4-Dichlorophenylcarbamoyl) -2- (5'-nitrophuryl-2'-carbonylamino] behimidimidyl, 1-cyclohexylcarbamoyl-2- (5'-nitrophuryl-2'-carbonylamino) benzimidazoles ,

1-n-butylcarbamoy 1-2- (5‘-nitrophenyl-2-carbonylamino) benzimidazoles,

1-Phenylcarbamoyl-2- (5'-nitropuryl-2'-carbonylamino) benzimidazoles, 1-propylcarbamoyl-2- (5'-nitrophuryl-2'-carbonylamino) benzimidazoles,

1-1 (3‘-Chlorophenylcarbamoyl) -2-] -5'-nitrophthyl-2'-cellobonominominoben 2 -imidazoles, 1-methylcarbamoyl-2- (5‘-nitrophuryl-2‘-carbonylainino) benzimidazoles.

According to the invention, the compounds of the formula I are used

(I) and salts thereof, wherein

R is a C 1 -C 6 alkyl group or a C 5 -C 6 cycloalkyl group or a phenyl group optionally substituted by one or two halogen atoms, prepared by producing a compound of formula II

reacted with an isocyanate of formula III,

R_N = C = O (ΙΠ) where

R has the same meaning as above, in the presence of a solvent such as carbon tetrachloride, and then the compound of formula I obtained is optionally converted into its salts.

Compounds of formula I may be converted into their salts by generally known methods by reacting a compound of formula I with an approximately equimolar amount of acid in the presence of an organic solvent.

The compounds of formula I and their salts are excellent fungicides and can be used in both human and veterinary medicine as well as in agriculture.

Further details can be learned from the examples below without limiting the invention to these examples.

He did

6.8 g (25 millimoles) of N- (2 benz-benzimidazolyl) -5-nitroph uranecarboxylic acid amide are stirred with 60 ml of chloroform, then 4.8 g (25 millimoles) of 3,4-dichlorophenyl isocyanate are added to the solution. The reaction mixture was stirred at room temperature for 6 hours, then allowed to stand overnight and the precipitated crystals were filtered off. 1- (3,4-Dichlorophenylcarbamoyl) -2- (5‘-nitropyuryl-2-carbonylamino) benzimidazole was obtained as yellow crystals, melting at 235-237 ° C. Example 2

6.8 g (25 mmol) of N- (2 (-benzimidazolyl) -5-nitrofurancarboxylic acid amide are stirred in 60 ml of chloroform, then 3.2 g (25 mmol) of cyclohexyl isocyanate are added. The reaction mixture is stirred for 6 hours, then left to stand for one hour, the precipitated product is filtered off and washed with a small amount of chloroform. 8.0 g of 1-cyclohexylcarbamoyl-2- (5‘-nitrofuryl-2‘-carbonylamino) benzimidazole are obtained. Mp: 208-213 ° C (yellow crystals).

Example 3

6.8 g (25 mmol) of N- (2'-benzimidazolyl) -5-nitrofurancarboxylic acid amide was stirred in 60 ml of chloroform, then 2.48 g (25 mmol) of butyl isocyanate was added to the solution and the reaction mixture was stirred for 6 hours . The reaction mixture was allowed to stand overnight, the precipitated product was filtered off and washed with chloroform. 8.05 g of 1-n-butylcarbamoyl-2- (5-nitrofuryl-2'-carbonylamino) benzimidazole are obtained. The melting point of the yellow crystals is 253-259 ° C.

Example 4

6.8 g (25 µmol) of N-2‘-benzimldazolyl) -5-nitrofurancarboxylic acid amides are suspended in 60 ml of chloroform, then 3.0 g (25 mmoles) of phenylene isocyanate are added. The reaction mixture was stirred at room temperature for 6 hours, then the precipitated product was filtered off and washed with a small amount of chloroform. 8.6 g of 1-phenylcarbamoyl-2- (5'-nitrofuryl-2'-carbonylamino) benzimidazole (m.p. 253 DEG-255 DEG C.) are obtained (yellow crystals).

Example 5

6.8 g (25 millimoles) of N- (2 benz-benzimidazolyl) -5-nitro-furanecarboxylic acid amide were stirred in 60 ml of chloroform, then added.

2.15 g (25 millimoles) of propyl isocyanate. The reaction mixture was stirred at room temperature for 6 hours, then filtered and washed with a small amount of chloroform. 8.3 g of 1-propylcarbamoyl-2- (5 ' -nitrophuryl-2 ' -carbonylamino) benzimidazole are obtained. Mp: 260-262 ° C (yellow crystals).

Example 6

6.8 g (25 mmol) of N- (2 (-benzimidazolyl) -5-nitrofurancarboxylic acid amide are stirred in 60 ml of chloroform, then 3.8 g (25 mmol) of 3-chlorophenylisocyanate are added at 20.4999. (The reaction mixture was stirred at room temperature for 6 hours, filtered and washed with a small amount of chloroform to give 9.9 g of 1- (3-chlorophenylcarbamoyl) -2- (5'-nitruryl-2'-carbonylamino) benzimidazole. melting of the yellow crystals is 259-260 ° C.

Example 7

6.8 g (25 mmol) of N- (2'-benzimidazolyl) -5-nitrofurancarboxylic acid amide was stirred with 60 ml of chloroform, then 1.5 g (25 mmol) of methyl isocyanite were added and the reaction mixture was stirred at room temperature for 6 hours , then the precipitated product is filtered and washed with a small amount of chloroform to give 7.6 g of 1-methylcarbamoyl-2- (5'-nitrophuryl-2'-carbonylamino) benzimidazole, mp 267-269 ° C (yellow) crystals).

Claims (1)

Process for the preparation of the novel benzimidazole derivatives of the general formula I -m ^^ N ^ NH-CO CONHR is reacted with an isocyanate of formula III, and salts thereof, wherein r_N = C = O (III) wherein R is a C 1 -C 6 alkyl group or a C 3 -C 6 cycloalkyl group or a phenyl group optionally substituted by one or two halogen atoms, characterized in that the compound of formula II R has the same meaning as above, in the presence of a solvent, for example carbon tetrachloride, and then the compound of formula I obtained is optionally converted into its salts.