Ester amide exchange ammonia

Mechanistically, one could envision a process initiated by ester/amide exchange brought about by the cyanoacetic ester with ammonia (22 27). Amide 27 could then... 

Tiazofurine (142) is an antimetabolite with antineoplastic activity. It preferentially affects leukemic lymphocytes over normal cells due to selective activation by formation of its adenine dinucleotide by transformed cells. Of the syntheses available, one starts by conversion of iniidate 138 to methyl 2,5-anhydroallonothioate (139). Next, condensation with ethyl 2-amino-2-cyanoac-etate leads to the thioamide which undergoes thiol addition to the nitrile function to produce the amminothiazolecarboxyester system of 140 directly. Sodium nitrite in aqueous hypophosphorus acid eliminates the superfluous amino group via the diazonium transformation to give 141. This synthesis of tiazofurine (142) concludes by ester amide exchange in methanolic ammonia [48]. 

When using cyanoacetic esters instead of aldehydes, the Guareschi-Thorpe pyridine synthesis assembles pyridines 155 by the condensation of acetoacetic esters 153 with cyanoacetic esters 154 in the presence of ammonia. A variation of this method involves the reaction of cyanoacetic ester 156 with 3-diketone 157 in the presence of ammonia to generate 2-hydroxypyridine 158." The mechanism of this reaction has been studied, and it was initiated by an ester/amide exchange on cyanoacetic ester 156 with... 

In order to produce high yields of ester in this manner it is necessary to remove the by-product ammonia (or amine) either by heating or combining with mineral acid, eg, H2SO4 or HCI. Recent work has shown that acidic ion-exchange resins can be used in place of mineral acids for converting sensitive unsubstituted amides (76). The stmctural relationships involved in esterification of amides are shown in Table 2 (77). 

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