CS204998B2 - Method of producing new benzimidazole derivatives - Google Patents

Description

The present invention provides a process for the preparation of novel benzimidazole derivatives and their salts.

The novel benzimidazole derivatives are compounds of formula I

and salts thereof, wherein in the general formula IR ¹ is a hydrogen atom or a group of the formula

II ~ oc

O NO 2 (fi) a

R ⁵ is C 1 -C 4 alkoxycarbonyl or a group of formula II, provided that one of R ¹ and R ⁵ is a group of formula II.

The term "alkyl radical" may mean a straight or branched chain aliphatic 9 group having 1 to 6 carbon atoms (for example methyl, ethyl, n-propyl, isobutyl, etc.).

Salts of the compound of formula I may be formed with inorganic or organic acids, for example hydrochloric, hydrobromic, sulfuric, acetic, formic, lactic, tartaric, etc. Salts to be used for therapy are formed with pharmaceutically acceptable salts.

Particularly preferred derivatives of the compound of formula I are the following compounds:

1- (5-Nitro-furyl-2-carbonyl) -methoxycarbonylaminobenzimidazoles, N- (2'-benzimidazolyl) -5-nitro-2-furancarboxylic acid amides.

The present invention provides a process for preparing compounds of formula I and salts thereof wherein the meaning of R ¹ and ^R are the same as above, which is characterized in that a compound of formula IV,

where

R ⁶ is hydrogen or C 1 -C 6 alkoxycarbonyl, straight or branched chain alkyl, reacted with 5-nitro-2-furoylcarboxylic acid chloride, and then optionally converted to its salt.

In a preferred embodiment, the reaction can be carried out preferably in an organic solvent in the presence of a basic substance. If an acid ester is used, it is preferable to continuously remove the alcohol. If the reaction is carried out using the free acid, it is preferably carried out in the presence of a condensation agent (e.g. dicyclohexylcarbodiimide) in dimethylformamide.

The compounds of formula I can be converted to their salts by conventional methods by reacting a compound of formula I with an approximately equimolar amount of acid in the presence of an organic solvent.

In particular, the compounds of the formula I and their salts are excellent fungicides and can be used in both human and veterinary medicine and also in agriculture.

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

He did

19.1 g (0.1 mol) of 2-methoxycarbonyl) benzimidazole are suspended in 250 ml of dioxane and 10 g of triethylamine are added at 50-60 ° C. Then, 17.5 g (0.1 mol) of 5-nitro-2-furancarboxylic acid chloride was added to the reaction mixture over half an hour. Exothermic reactions begin. The reaction mixture was refluxed for 3 hours, then stirred at 15 ° C for half an hour and washed with water. 25.2 g of 1- (5-nitrophenyl-2-carbonyl) -2-methoxycarbonylaminobenzimidazole, m.p. 175 DEG C. (decomposition), are obtained.

13.3 g (0.1 mol) of 2-aminobenzimidazole are suspended in 250 ml of dioxane and 10 g of triethylamine are added to the solution. The reaction mixture was heated to 60 ° C and 5-nitro-2-furancarboxylic acid chloride (17.5 g, 0.1 mol) was added at this temperature. The reaction mixture was stirred at 60 ° C for 2 hours, then cooled to 15 ° C. 25.5 g of N- (2‘-benzimidazolyl) -5-nitrofurancarboxylic acid amide is obtained. Mp 240-242 ° C.

Claims (2)

OBJECT OF INVENTION A process for the preparation of novel benzimidazole derivatives of the general formula I Nt-IR ⁵ (I) and salts thereof, wherein R ¹ is a hydrogen atom or a group of formula II JOL • OC θ Ν0 _λ (II) a R ⁵ is C 1 -C 4 alkoxycarbonyl or a group of the formula II, provided that at least one of R ¹ and R ⁵ is a group of the formula II, characterized in that the compound of the formula (IV): R ⁶ is hydrogen or C 1 -C 6 alkoxycarbonyl, straight or branched chain, reacted with 5-nitro-2-furoylcarboxylic acid chloride, and then optionally converted to its salts. 2. A process according to claim 1 wherein the reaction is carried out in an organic solvent in the presence of a base.