Cyclization of Isothiosemicarbazones. I. A New Route to 2-Mercapto-imidazole Derivatives and 4-Substituted Imidazoles

Some 1-arylmethyleneamino-2-mercapto-4-aryl-1H-imidazole derivatives were prepared by the condensation of isothiosemicarbazones of aromatic carbonyl compounds with phenacyl bromides. The 1,2,5-trisubstituted isomers were obtained by substitution of dl-α-bromophenylacetaldehyde for phenacyl bromide in this condensation. The reaction of isothiosemicarbazones of aliphatic carbonyl compounds with phenacyl bromides produced a dark, complex mixture from which the corresponding 1-alkylideneamino-2-mercapto-4-aryl-1H-imidazoles and 3,5-disubstituted 1,2,4-triazines were isolated in poor yields, with the latter being a main product or a sole heterocyclic product depending on the reaction conditions. Reductive cleavage of the cyclized products with zinc dust in acetic acid-acetic anhydride solution gave 1-acetyl-4-aryl-1H-imidazoles, which were readily hydrolyzed to 4-aryl-1H-imidazoles. The susceptibility to acid hydrolysis of the arylmethyleneamino group was dependent on the extent of conjugation between the azomethine double bond and the adjacent aromatic rings. Hydrazinolysis of the azomethine double bond yielded 1-amino-2-mercapto-4-aryl-1H-imidazoles in high yields. Their structures were established on the basis of NMR, IR, UV, and mass spectra as well as elemental analyses. Differentiation between 1,2,4- and 1,2,5-trisubstituted imidazoles was discussed.