SU454739A3 - Method for preparing 5 (6) -acylbenzimidazolyl alkyl carbamates - Google Patents

Description

one

A method for the preparation of new benzimidazolylcarbamic acid derivatives, which can be used in the pharmaceutical industry, of the general formula 1, is proposed.

N

ABOUT

L li N YAN-C-COR

I

n

where R means an alkyl group containing 1-4 carbon atoms;

R is alkyl containing 1-4 carbon atoms; or a phenyl group, unsubstituted or substituted by halogen, alkyl or alkoxy, containing 1-4 carbon atoms, and RCO-rpynna is attached to the benzimidazole in the 5 or 6 position, or nx salts.

The known method for the synthesis of such compounds is based on the use of S-methylisothiourea, the derivatives of which, obtained after treatment with chlorobolic acid esters, are brought into contact with the corresponding o-phenylenediamine. However, the implementation of this method in the course of training produces a toxic product such as metlmercaptan.

The proposed method is replaced by o-phenylenediamine of General formula 2

NHo

ten

where R has given values

subjected to interaction with carbalkoxyanamide of General formula 3

15

NC-UN-S-OL

20

in which R has the given meanings

with the subsequent release of the pellet product in free form or by transferring it to salt by known methods.

The reaction of the thermodynamic agent is carried out in an aqueous medium at pH 2-6, preferably 3-4.5, at 30-120 ° C. The desired pH is maintained by the addition of protic acids — organic or inorganic, for example, sulfuric, hydrochloric, phosphoric, formic or acetic acid, at 30–120 ° C. In this case, the carbalkoxy-amiamide obtained by the interaction of chloroolyl ether and technical alkali metal or alkaline earth metal cyanamide can be reacted with o-phenylenediamip of the general formula 2 without prior isolation.

Example 1. 32 g (0.224 mol) of technical calcium cyanamide are suspended in 120 ml of water for 1 hour at room temperature. 21.4 ml (26.5 g, 0.28 mol) of chlorotolic acid methyl ester is added to the suspension during 30 minutes at 20-30 ° C. After stirring for 1 hour, the reaction mixture was filtered, the filtrate was acidified with concentrated hydrochloric acid and extracted with chloroform. The combined chloro solution is dried over sodium sulfate and then evaporated in vacuo. The carbomethoxy aziamide thus obtained is an oily yellow product, which can be used in subsequent reactions without purification.

Example 2. The method is identical to that described in Example 1, but instead of methyl ester of chlorogolic acid, ethyl, propyl and isobutyl chlorotic acid ester are used, respectively. Thus, compounds of the general formula 3 are prepared in which R represents ethyl, propyl and n-butyl, respectively.

A solution of 2 g (0.022 mol) of carbomethoxycyanamnd in 5 ml of water is added with stirring to a suspension of 4.24 g (0.02 mol) of 4-beisoyl-o-phenylenediamine in 10 ml of water. Then the mixture is heated with stirring and maintained at 90-95 ° C for 45 minutes, n. In the course of the process, the pY is maintained equal to 3.5-4 by adding hydrochloric acid. Then the mixture is cooled and the precipitated precipitate is filtered off. After washing with water and drying, 4.60 g (81.5%) of 5 (6) -benzoyl-2-benzimidazolylcarbamic acid methyl ester are obtained.

Example 4. Analogously to Example 3, using instead of 4-benzoyl-o-phenyleidiamine other 4-acyl-substituted o-phenylenedialyl derivatives in an equivalent amount, instead of carbomethoxycyanamide carboethoxycyanamide and instead of hydrochloric acid sulfuric acid, the following compounds of general formula 1 are obtained:

Methylmethyl

p-Chlorophenyl The same p-Tolyl

Phenyl Ethyl

Example 5. 16 g (0.112 mol) of technical calcium cyanamide are introduced into 60 ml of water and 15 ml of ethanol and the mixture is stirred for 1.5 hours at room temperature. 10.7 ml (13.25 g, 0.14 mol) of chlorogolic acid methyl ester are poured into the suspension over a period of 20 minutes at 30–40 ° C. After additionally stirring the mass for 1 hour, the reaction mixture was filtered, 17 g (0.08 mol) of 4-benzoyl-of-phenylenediamiya was added to the filtrate, after which the pH of the mixture was adjusted to 3.5 with concentrated hydrochloric acid. Then the mixture is heated to 90-95 ° C, stirred for another 45 minutes, while the pH is maintained 3.5-4 by the addition of concentrated hydrochloric acid. After cooling, the precipitated precipitate is separated, washed with water and dried. Thus, 18.8 g (88%) of methyl 5 (6) -benzoyl-2-benzimidazolylcarbampnesic acid are obtained.

Example 6. Analogously to Example 5, instead of 4-benzoyl - o - phenylenediamine, other 4-acyl-substituted o-phenylenediamine derivatives in an equivalent amount and, if desired, place the chloro-ethyl ester of the chloro-methyl ester, to obtain the following compounds of general formula 1:

R1R

Methylmethyl

Dr. Chlorophenyl Ethyl

PhenylTo

p-Tolnl. Methil.

The subject of the invention. A process for the preparation of 5 (6) -acylbenzimidazolyl alkyl carbamates of the general formula

ABOUT

(one

d

IfО

A. and

N H d COR

n

where R denotes an alkyl group containing 1-4 carbon atoms;

R is alkyl containing i-4 carbon atoms, or a phenyl primer, unsubstituted or substituted by halogen, alkyl or alkoxygrutz containing 1-4 carbon atoms, and RCO-rpynna is attached to a benzimidazole in position 5 or 6,

or salts thereof, characterized in that the compound of the general formula

and

Yp

II

but

cd

55 where R has the given meanings

subjected to interaction with the compound of the General formula

§

NC-; sH-c: -oR

in which R has the above meanings, 65 followed by the isolation of the target product in free form or by transferring it to salt using known techniques. 2. A method according to claim 1, characterized in that the reaction is carried out in an aqueous medium. 6 3. The method according to paragraphs. 1 and 2, characterized in that the reaction is carried out at a pH of 2-6, preferably 3-4.5. 4. The method according to paragraphs. 1, 2 and 3, characterized in that the reaction is carried out at 30-120 ° C.