GB641909A - A process for the manufacture of organic nitrogen-containing compounds - Google Patents

Abstract

Amides of the formula <FORM:0641909/IV (b)/1> are obtained by reacting a compound of the formula <FORM:0641909/IV (b)/2> in a basic medium with a compound of the formula R4.NH.Y and acidifying the product; R1, R2, R3 and R4 are the same or differen and are hydrogen or a hydrocarbon residue, and Y is the complement of an amino acid or peptide or functional derivative thereof such that the group R4.NH retains its basic function unimpaired. In particular, the compound R4.NH.Y may be written as <FORM:0641909/IV (b)/3> where R5 and R6 are the same or different and are hydrogen or a hydrocarbon residue and Z is a carboxyl, ester, amide, substituted amide or nitrile group. R3 with either R1 or R2 may form a ring and Z may itself be a polyamide or peptide group. Preferably, of the pairs R1, R2 and R5, R6, one of each pair is hydrogen, R2 is hydrogen, methyl or phenyl, and the compound R4.NH.Y is a derivative of glycine, glutamic acid or tyrosine. The group Y-N= in the product may be derived from glycine, tyrosine, glutamic acid, tryptophane, ornithine, methionine or phenylglycine. The reaction is believed to take place with the intermediate formation of a salt of a dithiocarbamic acid with the base used, i.e. <FORM:0641909/IV (b)/4> where M is the base (inorganic or organic). Tertiary organic bases such as triethylamine and triethylphosphine are suitable, or alternatively two or more molecular proportions of the compound R4.NH.Y may be used. On acidifying the reaction mixture, the dithiocarbamate decomposes into the desired amide and carbon disulphide. In the examples, 2-thio-thiazolone is reacted with (1) glycine ethyl ester; (2) glycylglycine ethyl ester; (3) glycylglycylglycine ethyl ester; (4) triglycylglycine ethyl ester; (5) phenylalamine methyl ester, and (6) tyrosine methyl ester; 4-methyl-2-thio-thiazolone is reacted with glycine and with diethyl glutamate, in the latter case the product being isolated as its p-tolylthiocarbonyl derivative by treatment with p-tolylthiocarbonyl chloride; 4-phenyl-2-thiothiazolone is reacted with glycylglycine ethyl ester. It is stated that tolylthiocarbonylalanylglutamic di-ethyl ester may also be prepared from tolylthiocarbonylalanine ester by conversion into the acid chloride (via the free acid) and treatment of this with diethyl glutamate. 2-Thio-thiazolone is obtained by treatment of the compound <FORM:0641909/IV (b)/5> with mineral acid. 4-Phenyl-2-thio-thiazolone is produced by acidifying an aqueous solution of a dithio-carbamate of the formula <FORM:0641909/IV (b)/6> where M is an inorganic or organic cation.