The chemical simulation of the "ATP-Imidazole" cycle

Abstract

The synthetic strategy inherent in the "ATP-Imidazole" cycle and centred around the vicinal disposition of -NH₂ and -CONH₂ functions, has been demonstrated with anthranilamide (2) and 1-benzyl-5-aminoimidazole-4-carboxamide (1) as regeneratable carriers involving specifically N-alkylated quinazolin-4-ones, hypoxanthines and adenines, as key intermediates. The isolation and characterization of the enamine (22) coupled with other observations has made it possible to rationalize the pathways involved in these cyclic operations. The practical utility of the synthetic strategy using regeneratable carriers has been illustrated with the synthesis of a range of 1,5-disubstituted imidazoles. whilst pathways leading to specific N-alkylation in the Natural cycle and in simulation studies are comparable, the subsequent events take place in a reverse order, primarily because of the divergence in the hydrolytic profile of the alkylated substrates. The action of dilute alkali on 3-alkylated quinazolin-4-ones leads to 2-3 rather than 3-4 bond rupture. Endeavours to promote the latter path, by blocking the 2 position gave unexpected results. 2-Methyl-3-phenacyl quinazolin-4-one gave with dilute alkali the novel aromatic tricyclic system (32) from trans-annular cyclization. On the other hand, the 2-blocked 3-benzamido quinazolin-4-ones (33) and (34) gave triazoles (35) and (36) arising from the desired 3-4 rupture followed by cyclization initiated by the resulting amidine unit. 2-Phenyl-3-benzamidoquinazolin-4-one (34) with distilled water at 200°C gave a number of products which have been identified and their formation explained.