Synthesis 2005(17): 2951-2961  
DOI: 10.1055/s-2005-916036
PAPER
© Georg Thieme Verlag Stuttgart · New York

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

Keith Smith*, Gamal A. El-Hiti, Amany S. HegazyCentre for Clean Chemistry, Department of Chemistry, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK
Fax: +44(1792)295261; e-Mail: k.smith@swansea.ac.uk;
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Publication History

Received 17 May 2005
Publication Date:
23 September 2005 (eFirst)

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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