ISOTHIOCYANOBENZIMIDAZOLES

摘要

1435376 Benzimidazolyl - isothiocyanates E R SQUIBB & SONS Inc 31 May 1973 [2 June 1972] 26036/73 Heading C2C Novel compounds I and salts thereof in which R1 is hydrogen, C 1-7 alkyl optionally substituted by halogen or aryl as defined below, mono- or bi-cyclic aryl optionally substituted by halogen, NO 2 , CF 3 , alkoxy, optionally substituted amido or alkyl as defined above, alkoxycarbonyl, aryloxycarbonyl, dialkylaminoalkyl, acyl or carbamoyl or a 2-thiazolin-2-yl or 5,6 - dihydro - 4H - 1,3 - thiazin - 2 - yl radical optionally substituted by C 1-7 alkyl, halogen, di-C 1-7 alkylamino-alkyl or aryl as defined above. R2 is a saturated or unsaturated N, S or O containing heterocycle having 6 members and 1 and 2 hetero-atoms and optionally substituted by C 1-7 alkyl, halogen or di-C 1-7 alkylaminoalkyl and R3 is hydrogen, C 1-7 alkyl, halogen or C 1-7 alkoxy are prepared by reaction of a corresponding amino-benzimidazole (II) with a thiocarbamic derivative Hal-CS-Y where Hal is chlorine or bromine and Y is chlorine, bromine or dialkylamino (preferably thiophosgene). Compounds I (R1 = H, Bu, B 3 , EtOCO, Et-NH-CO-, B 3 O-CO-, B 3 -CO, Me 2 N- (CH 2 ) 2 -, 5,6 - dihydro - 4H - 1,3 - thiazin - 2- yl, 2 - thiazolin - 2 - yl or 5 - phenyl - 2 - thiazolin-2-yl, R2 = pyridyl, pyrimidyl, pyrazinyl, 2-methyl-pyridyl or 2-ethyl-pyridyl, R3 = H, Br, Pr or PrO) are prepared. Amino benzoxazole derivatives (II) are prepared by reduction of the corresponding nitro derivative. The nitro benzimidazoles of Formula V in which R 1 is hydrogen are prepared by (1) reaction of an R3 and nitro substituted o-phenylenediamine with an acid chloride R2-CO-Cl to form an amide which undergoes intermolecular condensation or (2) reaction of an R3 and nitro substituted o-phenylenediamine with an aldehyde R2-CHO to form a Schiffs base which is cyclized by intermolecular condensation. Replacement of hydrogen by a substituent R1 in the benzimidazole is carried out by (1) reaction with a halide R1'-X in which X is chlorine or bromine and R1' is R1 other than hydrogen or the specified thiazoline or thiazine group or (2) formation of a metal salt of the nitrobenzimidazole (V) by reaction with a metal hydride and reaction with a haloalkylisothiocyanate S = C = N-A-X where A is a chain of 2 or 3 carbon atoms optionally substituted by C 1-7 alkyl, halogen, di-C 1-7 alkylaminoalkyl or aryl. 2 - (2 - Thienyl) - 5 - benzimidazolyl, 2 - (2- furyl) - 5 - benzimidazolyl, 1 - (2 - thiazolin - 2- yl) - 2 - methyl - 5 (and 6) - benzimidazolyl and 1 - (2 - dimethylaminoethyl) - 2 - (2 - furyl) - 5- (and 6)-benzimidazolyl esters of isothiocyanic acid are also prepared as illustrations of the above methods. Compounds I are anthelmintic agents and disinfectants and form with a carrier or diluent a pharmaceutical composition or animal feed.