A Simple and Convenient Procedure for Lithiation and Side-Chain Substitution of 2-Alkyl-4-(methylthio)quinazolines and 2-Alkyl-4-methoxyquinazolines

Abstract

2-Methyl-4-(methylthio)quinazoline has been lithiated, in the 2-methyl group, with n-BuLi at -78 °C in THF. The lithium reagent thus obtained reacts with a variety of electrophiles (iodomethane, iodoethane, D₂O, benzaldehyde, 4-anisaldehyde, hexan-2-one, acetophenone, benzophenone, cyclohexanone) to give modified 2-substituted 4-(methylthio)quinazolines in excellent yields. Similarly, lithiation of 4-methoxy-2-methylquinazoline followed by reactions with various electrophiles gave the corresponding modified 2-substituted 4-methoxyquinazolines in excellent yields. Lithiations of 2-ethyl-4-(methylthio)quinazoline, 4-(methylthio)-2-propylquinazoline, 2-ethyl-4-methoxyquinazoline and 4-methoxy-2-propylquinazoline, followed by reactions with a range of electrophiles, behave in a similar manner to give the corresponding modified 2-substituted derivatives in good yields.

Key words

lithiation - side-chain - substitution - 2-alkyl-4-(methylthio)quinazoline - 2-alkyl-4-methoxyquinazoline - electrophiles

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Permanent address: G. A. El-Hiti, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt.