The Synthesis of 2-quinazolinones and Homologues

Abstract

A brief historical perspective of quinazolines is given, as well as a review of the various synthetic routes reported in the preparation of these compounds. A more detailed literature survey of the procedures involved in the synthesis of 2-quinazolinones, and 4-quinazolinones' is described. In addition their chemical and biological activities are briefly reviewed. The synthesis of new 2(1H)-quinazolinones, and 2(1H)-quinazolinethiones, by two different methods is discussed. These include a novel synthesis involving the condensation of alkoxyphenylureas with a variety of acyl chlorides in polyphosphoric acid. Cyclodehydration = of N-acyl-N'-alkoxyphenylureas, and the corresponding thioureas in polyphosphoric acid, affords another convenient route toward the preparation of these compounds. The acylated ureas were prepared by acylation of N-alkoxyphenylureas with variously substituted acyl chlorides in benzene. While the acylated thioureas were obtained by reacting certain substituted aromatic amines with p-chlorobenzoyl isothiocyanate in acetone. Attempted preparations of new tricyclic derivatives of 2-quinazolinones, such as pyrrolo[3,2,1-ij])quinazolin-2-ones, pyrrolo[3,2,1-ij]quinazolin-2-thiones, and pyrido[3,2,1-ij]quinazolin-2-ones, using a variety of solvents and cyclising agents, are described. A brief discussion is presented for the preparation of some of their homologues. These include N-alkyl derivatives of 1,2,3,4-tetrahydrocarbazole, and 5,6-dihydrobenzo[a] carbazole. The latter was subjected to periodate oxidation to afford the expanded 9-membered ring 5-alkyl-11,12-dihydro-dibenz-{[b,g]azonin-6,13-dione.