Collect. Czech. Chem. Commun. 1999, 64, 515-526

Convenient Synthesis of More Complex 2-Substituted 4(3H)-Quinazolinones via Lithiation of 2-Alkyl-4(3H)-quinazolinones

Keith Smitha, Gamal A. El-Hitia,*, Mohamed F. Abdel-Megeedb and Mohamed A. Abdob

a Department of Chemistry, University of Wales Swansea, Swansea SA2 8PP, U.K.
b Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt


2-Methylquinazolin-4(3H)-one has been doubly lithiated, at nitrogen and in the 2-methyl group, with n-butylithium. The lithium reagent thus obtained reacts with a variety of electrophiles (iodomethane, D2O, phenyl isocyanate, benzaldehyde, benzophenone, cyclopentanone, 2-butanone, carvone) to give the corresponding 2-substituted derivatives in very good yields. Reaction of the dilithio reagent with acetonitrile gives an α,β-unsaturated imine by tautomerization of the initial addition product. Double lithiation of 2-ethyl- and 2-propyl-4(3H)-quinazolinones can be achieved using lithium diisopropylamide and the lithiated reagents thus obtained react with similar electrophiles to give the corresponding products in very good yields. In the reaction of the dianion of the 2-ethyl-4(3H)-quinazolinone with iodine, an oxidatively dimerised product was obtained. Lithiation of 2-unsubstituted 4(3H)-quinazolinone does not take place on C-2 under similar conditions.

Keywords: Quinazolinones; Metallation; Double lithiation; Nucleophilic additions; Ketones; Carbanions.