Imidazole ammonolysis

Imidazole derivatives were not detected in the ammonolysis of aldose esters, and pyrazines only appeared in the case of the per-nicotinates of D-glucose and D-xylose, as already described. 

An analogous scheme was revealed in the ammonolysis of 1,3,4,5-tetra-O-benzoyl-jS-D-fructopyranose and 1,3,4,5,6-penta-O-acetyl-keto-D-fructose,37 with formation of the imidazole derivatives 37, 38, 40, 41, and 4(5)-(D-arabino-tetritol-l-yl)imidazole (42), which were identified by paper chromatography. 

In the reaction of ammonia with l,3,4,5-tetra-0-benzoyl-/3-n-fructopyranose, a significant proportion of benzoic acid was formed, indicating that the ammonolysis of the sugar ester occurred to a certain extent through acyloxy-group rupture. As neither the formation of imidazole nor of pyrazine derivatives (see Section VI,3, p. 124) re-... 

As previously indicated (see pp. 88-91), formation of heterocyclic compounds, mainly pyrazines, was found only in the ammonolysis of some aldose nicotinates33 35 and acetates and benzoates of ketoses.39 37 For ketose esters, whose behavior differed from that of the aldose esters, the formation of imidazole derivatives was also observed these heterocyclic compounds also result from the direct action of ammonia upon the corresponding free sugars, but the presence of the esterifying acyl groups evidently increases their ease of formation and raises their yields. 

Reactions of amines with substituted phenyl acetates are subject to a change in pathway as a function of basicity of the leaving phenoxide group. In the ammonolysis, hydrazinolysis, and imidazole-catalyzed hydrolysis of substituted phenyl acetates, both first- and second-order terms in amine are observed (Bruice and Mayahi, 1960 Bruice and Benkovic, 1964). Out of five phenyl acetate derivatives (p-NOg, m-N02, p-H, p-Cl, and p-CHs) the general-base term kz is observed with only the least acidic leaving groups, that is p-CHs, p-H, and p-Cl in the case of ammonolysis and hydrazinolysis, and p-CHj in the case of the imidazole reaction. Uncatalyzed k terms are observed with all... 

It is apparent that the formation of 2-(imidazol-4-yl)benzimidazoles 129a-d involves the ammonolysis of imidazoles 127a, c, d, g to form the corresponding o-aminoanilide derivative G as the first step. The next step involves an intramolecular nucleophilic attack by the amino group on the carbonyl group with the formation of... 

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