CS218553B2 - Method of making the alkylesters of the substituted 5-phenylsulfinyl-2-benzimidazolcarbam acid - Google Patents

Abstract

1428933 5 - Phenylsulphinyl - 2 - benzimidazolylcarbamic acid esters HOECHST AG 28 June 1974 [7 July 1973] 28793/74 Heading C2C Novel compounds of Formula I: wherein R is C 1-4 alkyl, R<SP>1</SP> is H, Cl, Br, C 1-4 alkyl or CH 3 O, and R<SP>2</SP> is H, Cl, Br or CH 3 , are prepared by oxidation of a compound of Formula II Pharmaceutical compositions in conventional forms for oral administration having anthelmintic activity comprise an above novel compound and a carrier therefor.

Description

The invention relates to substituted alkyl esters

5-fenylsulfinyI-2-benzimidazolecarbamic acid of formula I ^with tot-C-NH-COOR

R ^H (I) wherein is

R is C 1 -C 4 alkyl. carbon, especially methyl, ethyl, propyl, isopropyl, butyl, sec-butyl. tert-butyl, preferably methyl and ethyl,

R 1 is chlorine, bromine, methoxy or C 1 -C 4 alkyl;

R 2 is chloro, bromo or methyl.

The present invention provides a process for the preparation of substituted 5-phenylsulfinyl-2-benzimidazolecarbamic acid alkyl esters of formula (I) wherein R, R 1 and R ² are as defined above, characterized in that the phenylthio derivative of formula (II),

H (II) wherein

R 1 and R ² majli above meanings, is oxidized působenlm oxidizers.

Suitable oxidizing agents are preferably equivalent amounts of hydrogen peroxide in an organic acid, preferably glacial acetic acid, peracids such as peracetic acid, pertrifluoroacetic acid or metachloroperbenzoic acid, or nitric acid or chromic acid in glacial acetic acid, or sols of these acids, furthermore permanganates, hypochlorites, perchlorates, periodates and nitrogen oxides.

The reaction may conveniently be carried out by adding 30% hydrogen peroxide to a suspension of the substituted phenylthio derivative of the formula II in glacial acetic acid and stirring at room temperature until a clear solution is obtained. It can also be operated at elevated temperatures of up to about 70 ° C. The resulting sulfoxide is precipitated by adding water to the reaction solution. The precipitate formed is collected by filtration.

The corresponding phenylthio derivative, which serves as the starting material, is obtained by reacting a substituted 5-phenylthio-o-phenylenediamine with S-methylthiourea and an alkyl chloroformate.

The substituted 5-phenylsulfinyl-2-benzimldazolecarbamic acid alkyl esters of the present invention are valuable chemotherapeutics and are useful in combating parasitic diseases in humans and animals. They are particularly effective against a large number of helminths such as Haemonchus, Trichostrongylus, Ostertagia, Strongyloides, Cooperia, Chabertia, Oesophagostomum, Hyostrongylus, Ankylostoma, Askaris and Heterakis,

Especially pronounced is the efficacy against the chordates (Strongylidae) in the intestinal and gastric tract, which are mainly attacked by ruminants. Attacking these animals with these parasites leads to considerable economic damage. The compounds according to the invention are therefore used in particular in veterinary medicine.

Depending on the nature of the disease, the active compounds of the formula I are administered in doses of between 0.5 and 50 mg per kg of body weight for 1 to 14 days.

For oral administration, tablets, coated tablets, capsules, powders, granules or pastes which contain the active substances together with customary carriers and auxiliaries such as starch, powdered cellulose, talc, magnesium stearate, sugar, gelatin, calcium carbonate, finely dispersed silicic acid, carboxymethylcellulose or the like.

For parenteral administration, suitable solutions are, for example, oily solutions which are prepared using sesame oil, castor oil or synthetic triglycerides, optionally with surfactants such as sorbitol fatty acid esters. Also suitable are aqueous suspensions which are prepared using ethoxylated sorbitol fatty acid esters, optionally with the addition of thickeners, such as polyethylene glycol or carboxymethylcellulose.

The concentration of the active compounds according to the invention in the preparations produced is preferably 2 to 20% by weight for the purposes of the veterinary medicament, and 20 to 80% by weight for the human medicament.

Example 1

5- (2,5-Dichloro-phenylsulfinyl) -2-benzimidazolylcarbamic acid methyl ester

A mixture of 75 g of 5- (2,5-dichlorophenylthio) -2-benzimidazolylcarbamic acid methyl ester, 750 ml of glacial acetic acid and 250 ml of 30% hydrogen peroxide is stirred at room temperature until a clear solution is obtained, which requires 1.5 liters of water are then added, the mixture is briefly heated to 80 DEG C. and, after cooling, the precipitate is filtered off. -benzimidazolylcarbamic acid, m.p. 285 DEG C. (decomposition).

The following compounds were prepared in an analogous manner:

1) 5- (2,5-dichlorophenylsulfinyl) -2-benzimidazolylcarbamic acid isopropyl ester, m.p. 265 DEG C. (with decomposition), is obtained from 5- (2,5-dichlorophenylthio) -2-benzimidazolylcarbamic acid isopropyl ester.

2) from 5- (2-methyl-5-tert-butylphenylthio) -2-benzimidazolylcarbamic acid methyl ester to give 5- (2-methyl-5-tert-butylphenylsulfinyl) -2-benzimidazolylcarbamic acid methyl ester, m.p. 236 ° C ( decomposition);

3) 5- (2-methyl-5-tert-butylphenylsulfinyl) -2-benzimidazolylcarbamic acid isopropyl ester of melting point is obtained from 5- (2-methyl-5-tert-butylphenylthio) -2-benzimidazolylcarbamic acid isopropyl ester.

241 ° C (dec.).

Claims (1)

SUBJECT OF THE INVENTION A process for preparing substituted alkyl esters 5-phenylsulfinyl-2-benzimidazolecarbamic acid of formula I, R ² chlorine, bromine or methyl, characterized in that the fenylthioderívát formula II in which A represents R is C 1 -C 4 alkyl, R ( ^{1) is} chlorine, bromine, methoxy or (C1-C4) -alkyl; R ¹ , R ¹ and R ² are as defined above and act as an oxidizing agent.