A Convenient Procedure for the Synthesis of Novel Modified 3-Substituted 1H-Quinoxaline-2-thiones via Side-Chain Lithiation of 3-Alkyl-1H-quinoxa­line-2-thiones

Abstract

3-Methyl-1H-quinoxaline-2-thione (1) has been doubly lithiated, at nitrogen and at the 3-methyl group, with n-butyllithium at -78 °C in THF. The resulting dilithium reagent obtained reacts with a variety of electrophiles (iodomethane, iodoethane, 1-bromobutane, D₂O, benzaldehyde, anisaldehyde, 2-hexanone, cyclohexanone, benzophenone, phenyl isothiocyanate) to give the corresponding modified 3-substituted 1H-quinoxaline-2-thiones 4-13 in high yields. Similarly, double lithiation of 3-ethyl- (4) and 3-propyl-1H-quinoxaline-2-thiones (5), followed by reaction with some electrophiles gave the corresponding modified 3-substituted derivatives 15-19 in high yields. Treatment of some of the products with trifluoroacetic acid in dichloromethane at room temperature led to formation of substituted 2,3-dihydrothieno[2,3-b]quinoxalines in good yields.

Key words

quinoxalines - lithiation - electrophilic additions - cyclizations - heterocycles - sulfur

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1

Current address: G. A. El-Hiti, Department of Chemistry, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK.