GB630671A - Process for the production of amino alkyl thiazole derivatives - Google Patents

Abstract

2-Aminoalkylthiazole derivatives of the general formula <FORM:0630671/IV (b)/1> wherein n is an integer, R represents hydrogen or an alkyl, aryl or aralkyl group and X is the residue of an organic carboxylic or sulphonic acid, or X and R together represent the residue of an organic dicarboxylic acid, and R1 and R2 are hydrogen or alkyl, halogenated alkyl, aryl, nuclear substituted aryl, aralkyl, halogenated aralkyl, nuclear substituted aralkyl or esterified carboxylic groups or an esterified acetic acid residue, are prepared by heating acylamidoalkyl carboxylic thioamides of the general formula X.NR.(CnH2n).CS.NH2 with aldehydes or ketones which, in one tautomeric form, have the general formula Z.CR1=CR2.OH, where N, R, R1 and R2 have the above significance and Z is a halogen. The reaction may be carried out in the presence of an acid acceptor, e.g. pyridine. The group X may be the residue of an alkyl, aryl, aralkyl or heterocyclic carboxylic or sulphonic acid residue, and a number of suitable groups are specified, e.g. a benzene sulphonyl group which contains as a substituent in the para-position or any other position with respect to the sulphonyl group a protected amino group, a substituted amino group or a group which is readily convertible to an amino group, e.g. acylamino groups such as acetylamino, dialkylamino groups such as dimethylamino, nitro, nitroso, azo, hydrazo and halo groups. Benzene sulphonamidoalkyl carboxylic thioamides other than those containing a protected amino group or a group readily convertible to an amino group may also be employed, e.g. those containing alkyl, hydroxyl and alkoxyl substituents which may be present in the para or any other position, they may contain two or more substituents in the benzene ring. When n is greater than one, the acylamido group may be carried by any carbon atom of the chain, e.g. either of the a - or b -positions of thiopropionamide or any of the a -, b -, or g -positions of thiobutyramide. When X and R together represent the residue of an organic dicarboxylic acid, the starting material is an imino thioacylamide such as g -phthalimido thio-n-butyramide. The aldehyde or ketone employed may be a monohalogenated acetaldehyde such as mono-chloroacetaldehyde, a monohalogenated acetone such as monochloro- or monobromo-acetone, a symmetrical dihalogenated acetone such as sym-dichloroacetone, a phenacyl halide such as omegachlorobromo-acetophenone, a nuclear substituted phenacyl halide such as 4-chlorophenacyl chloride, 4-methyl-phenacyl bromide, 4-hydroxyphenacyl chloride and 4-methoxyphenacyl chloride or homologues thereof such as a - bromopropiophenone, a - bromobutyrophenone, chlormethylbenzylketone and a -bromo - 4 - methoxypropiophenone, an a - or g -monohalogenated acetoacetic ester such as a -monochloro- or g -monobromoacetoacetic ester or a homologue thereof, a monohalogenated pyruvic ester such as monobromopyruvic ester or a b -monohalogenated homologue thereof. There may also be employed substances which are readily convertible into aldehydes or ketones of the above general formula, e.g. an acetal such as the dialkyl acetals of monochloro- and monobromo-acetaldehyde or an ehter such as a -b -dichloroethyl ethyl ether. When the product of the invention is a 2-(carbonamidoalkyl)-thiazole, the carboxylic acid residue may be hydrolysed off with mineral acid to form the corresponding free 2-(aminoalkyl)-thiazole, which may then be converted to any desired functional derivative thereof, e.g. by reaction with a benzene sulphonyl halide such as a benzene sulphonyl halide containing in the para position an amino group, a protected amino group or a group which is readily convertible into an amino group or a cyano group. When the thiazole derivative contains an esterified carboxyl group or an acetic ester residue substituted in the 4 and 5 positions of the thiazole ring, the groups may be hydrolysed to the free carboxyl group with aqueous alkali. In examples the following compounds are prepared : 2-(benzamido methyl)- and 2-aminomethyl-4-methyl thiazole, 2-(a -p-acetamido benzenesulphonamido)-ethyl- and 2 - (a - p - aminobenzenesulphonamido) - ethyl-4 - methylthiazole, 2 - (b - benzamidoethyl)- and 2 - (b - aminoethyl) - 4 - methyl thiazole, ethyl 2 - (benzamidomethyl) - 4 - methylthiazole carboxylate, 2 - (benzamidomethyl)- and 2 - aminomethyl - 4 - methylthiazole - 5-carboxylic acid, ethyl - (2-benzamidomethyl thiazole-4)-acetate, 2-benzamidomethyl thiazyl-4-acetic acid, ethyl 2-benzamidomethyl thiazole - 4 - carboxylate, 2 - benzamidomethyl thiazole - 4 - carboxylic acid, 2 - (a - benzamidoethyl), 2 - (g - phthalimido - n - propyl) - and 2 - (o - benzamidodecyl) - 4 - methylthiazole and 2 - a - aminoethyl) -, 2 - (g - aminopropyl)- and 2 - (o - aminodecyl) - 4 - methylthiazole. Acylamidoalkylcarboxylic thioamides of the general formula X.NR.(CnH2n).CS.NH2, wherein X, R and n have the above significance, are prepared by reacting an acylamidoalkyl cyanide with hydrogen sulphide as described in Specification 599,155.