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

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.