[4 + 2]Cycloaddition of monocyclic imidazole derivatives with electron-deficient acetylenes

Abstract

1-Alkylidene- and 1-arylmethylene-amino-4-aryl-2-mercapto-1H-imidazole derivatives 2–11 react with dimethyl acetylenedicarboxylate (DMAD) in hot chlorobenzene to give the corresponding retro-Diels–Alder products 1-alkylidene- and 1-arylmethylene-amino-2-mercapto-lH-pyrrole-3,4-dicarboxylate derivatives 19–26 and benzonitriles 27 in high yield. No intermediate Diels–Alder adducts could be isolated from these substrates. 1 -Amino-2-methylthio-4-phenyl-lH-imidazole 1 gives dimethyl 1-[1,2-bis(methoxycarbonyl)vinylamino]-2-methylthio-4-phenyl-1H-1,3-diazepine-5,6-dicarboxylate 28 in addition to dimethyl 1-amino-2-methylthio-1H-pyrrole-3,4-dicarboxylate 18, with the ratio 18:28 ranging from 2:1 to 3:1 under the same reaction conditions. At lower temperature, however, the former cycloadduct is obtained as the sole product in acetonitrile. No cycloaddition to these imidazole derivatives is observed with ethyl propiolate or with bis(trimethylsilyl)acetylene even under forced conditions. Any changes in the substituents or their positions on the imidazoles 2–11 that otherwise successfully give rise to the cycloaddition decidedly inhibited the reaction. Among a number of di- and tri-substituted imidazole derivatives employed as substrates, only a limited number bearing an amino or alkylidene- or arylmethylene-amino, a substituted mercapto, and an aryl group at the 1-, 2- and 4-position, respectively, can produce the corresponding pyrroledicarboxylates through the retro-Diels–Alder reaction.