DE1795692A1 - PROCESS FOR THE PREPARATION OF 2 (4'-THIAZOLYL) -BENZIMIDAZOLE - Google Patents

Description

PATENT ADVOCATE DR.-ING. LOTTERHOS FRANKFURT (MAIN) 1 T Q Π C Q ANNASTRASSE 19 I / <J Ό Q 3 A

TELEPHONE: (0i11) 5550i1 TELEGRAMS: LOMOSAPATENT LA N D E S Z E NT R A L BA N K 500 0714? POSTSCHECK ACCOUNT FFM. 1 (SCT

Y / ho FRANKFURT (MAIN) _f

Chinoin Gyogyszer es Vegyeszeti Termekek Gyära Rt. Budapest TV, To utca 1-5, Hungary

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Process for the preparation of 2- (4'-thiazolyl) -benzimidazole.

The invention relates to a process for the preparation of 2- (4'-thiazolyl) benzimidazole the formula:

From BE-PS 599 143 it is known that 2- (4'-thiazolyl) -benzimidazole baw. the alkyl derivatives of which can be used successfully for the treatment or prophylaxis of helminthiasis.

To prepare 2- (4'-thiazolyl) -benzimidazole, either o-phenymiamine is reacted with thiazole-4-carboxylic acid or with thiazole-4-aldehyde or o-hitraniline with thiazole-4-carboxylic acid chloride in pyridine, and that The open-chain product obtained is subjected to ring closure after reduction with hydrogen at acidic pH. The yields achieved here are only about 64 %.

The invention relates to a new method of manufacture of 2- (4'-thiazolyl) -benzimidazole of the formula I, which thereby

309822/1121

is characterized in that 2- (2-chloro-4'-thiazolyl) benzimidazole the formula:

II Cl

hydrogenated with hydrogen in the presence of palladium.

The hydrogenation is preferably atm and at 4 to 5 at a temperature of 70 to 120 ⁰ C. It delivers the end product in more than 90% yield and an excellent degree of purity.

The 2- (2'-chloro-4 ^l -thiazolyl) -benzimidazole used according to the invention as a starting product is made by reacting o-nitroaniline or p-phenylenediamine with a reactive carboxylic acid derivative - preferably the carboxylic acid chloride - the 2-chloro-4-thiazolecarboxylic acid and - after reduction of the existing nitro group to the amino group with hydrogen in the presence of Raney nickel, if o-nitroaniline was assumed - ring closure obtained.

Further details of the method according to the invention are the Examples can be found.

example 1

2.5 g of 2- (2 ^l -chloro-4 ^l -thiazolyl) -benzimidazole are hydrogenated in the presence of 0.3 g of palladium black in 150 ecm of aqueous ethanol and 5-4 atmospheres on a water bath. When the hydrogen uptake has ended, the catalyst is filtered off, the pH is adjusted to 6 with sodium bicarbonate, the precipitate which has separated out is filtered off and washed and dried. The obtained 2- (4'-thiazolyl) benzimidazole melting at 298 301 ⁰ C. (recrystallization from Essigester)

Analysis: C # - 59.54} E% - 3.69; N% »21.04; S% = 15.98 calc .: C% - 59.68; B% - 3.5; N% - 20.88; 0% = 15.93

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Example 2

800 mg of 2- (2'-chloro - ^ '- thiazolyl) -benzimidazole are hydrogenated in 1J, 4-ecm methanol at 55 ⁰ O in the presence of 0.17 ß pallium black and 8.4 ecm 5 n-sulfuric acid . The uptake of hydrogen takes 15 hours. The reaction mixture is filtered and the filtrate is adjusted to pH 7.5 with concentrated ammonium hydroxide solution. Filtered off, the precipitated "crystals, washed with water and dried to give 0.62 g of 2- (4 -'- thiazolyl) benzimidazole, which at 298 -. 304- ⁰ C melts yield 91%. -

Analysis: G% = 59.54-; H% »3.69; Έ% = 21.04-; S% * 15.98 calc .: QP / o <* 59.58; H% = 3.5 Y Wo = 20.88; S% = 15.93

The product contains only traces of chlorine. äk

The novel 2- (2'-OhIOr ^ ¹ -thiazolylO-benzimidazole used as starting product according to the invention can be prepared as follows:

1 g of 2-chloro-4-thiazol-carboxylic acid is heated with 5.7 ^{cc of} thionyl chloride boil for 2 hours and iV evaporated to dryness to -chloro ^ - ^ - thiazol-carboxylic acid chloride (b.p. 114- - 116 ⁰ C) obtained, which is dissolved in 15 ecm benzene, treated with 0.84 g o-uraniline in 10 ecm benzene and evaporated to dryness after heating to boiling for 5 hours. The residue is taken up in 100 ecm methanol (hot), treated with animal charcoal and filtered. This gives 1.25 g of yellow ■ 'm crystalline N- (o-Mtrophenyl) -2-chloro-4-thiazol-carboxamide. Bp: 160 - 161 ⁰ C.

Further quantities of the product are obtained from the mother liquor.

1 g of N- (o-Mtrophenyl) -2-chloro- ^ thiazole-carboxamide is in 26 ecm Methanol in the presence of 0.5 S Raney-Fickel to give M- (o-aminophenyl) -2-chloro-4-thiazole-carboxamide hydrogenated. The solution obtained is mixed with 5 ecm of conc. Hydrochloric acid and 5 ecm of water and heated to boiling for 4 hours. From the reaction mixture After cooling, a salt falls, which is filtered off, in

30.9822 / ΠΜ -

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10 cc of water dissolves -and- with sodium carbonate at pH 6.5 is obtained as a base, which is filtered off, washed and dried, Pas obtained. 2 - (2'-chloro-4 · thiazolyl) benzimidazole melting at 210-215 ⁰ O .

The mother liquor / will produce additional quantities of the product! obtain.

30 9 82 2 ΠT2.

Claims (1)

planned departure registration from P 16 7Q, 379-0-44 ''
Chinoin ... Claim. Process for the preparation of 2- (4 ^l -thiazolyl) - "benzimidazole of the formula: characterized in that 2- (2'-Ohlor- ^ ¹ -thiazolyl) -benzimidazole of the formula: hydrogenated with hydrogen in the presence of palladium. 309822/1121