Carboxamide groups partial hydrolysis

Pyridazinecarboxamides are prepared from the corresponding esters or acid chlorides with ammonia or amines or by partial hydrolysis of cyanopyridazines. Pyridazinecarboxamides with a variety of substituents are easily dehydrated to nitriles with phosphorus oxychloride and are converted into the corresponding acids by acid or alkaline hydrolysis. They undergo Hofmann degradation to give the corresponding amines, while in the case of two ortho carboxamide groups pyrimidopyridazines are formed. 

Treatment of 1-cyanoformamidinebenzhydrazide (11) with boiling acetic acid produces 2-phenyl-l,3,4-oxadiazole-5-carboxamide (12) with elimination of NH3 and partial hydrolysis of the CN group, together with 3-cyano-5-phenyl-1,2,4-triazole (13).51 The thermal... 

From 94, several compounds were generated such as the 3-thioalkyl compounds 96 (40-67%) by reaction with alkyl bromides. Intermediate 94 was also treated with HCl, iodine, 1,3-dibromopropane or with ethyl chlorocar-bonate affording the mercaptane 97 (68%), the disulfide 98 (45%, n = 0), compound 99 (37%, = 3) and the thiocarbonate 100 (67%), respectively. By a partial hydrolysis of the nitrile group with H2SO4 at reflux, carboxamides lOla-b (92%) were prepared from 96. The same reagents 96 can be transformed into methyl esters 102 (Scheme 26). 

The general approach for carboxyl protection is esterification. The simplest solution, the use of methyl or ethyl esters, is suitable for semipermanent blocking, although the commonly applied process of unmasking, alkaline hydrolysis, is far from unequivocal. It is accompanied by racemization, partial hydrolysis of carboxamide groups in the side chain of asparagine and glutamine residues and by several other side reactions which are initiated by proton abstraction (Cf. Chapter VII). Nevertheless, perhaps because of the attractively simple esterification of amino acids... 

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