MICHAEL ADDUCTS IN THE REGIOSELECTIVE SYNTHESIS OF N-SUBSTITUTED AZOLES

Michael adducts of azoles (4-phenyl-, 4-methyl- and 4-nitroimidazole, 4-methylbenzimidazole, 1,2,4-triazole and theophylline) are shown to b e valuable substrates for obtaining the N-substituted derivatives of t he parent heterocycles by a quaternization-Hofmann elimination sequenc e. The effectiveness of the procedure is dependent on the regiochemica l outcome of the first, N-protective step, i.e. the Michael addition. By choosing the appropriate Michael acceptor, alkylating agent and dep rotection conditions, the thermodynamically less stable regioisomers o f N-substituted azoles have been obtained in high yields.