Solvent-Free Cyclocondensation of Lactim Ethers with Anthranilic Acid under Microwave Irradiation

Abstract

Microwave irradiation greatly improves the results of the cyclocondensation between anthranilic acid and lactim ethers derived from 2,5-piperazinediones in terms of reaction times, yields and stereocenter integrity, leading to pyrazino[2,1-b]quinazoline-3,6-diones. The microwave-assisted reaction was also much better than the thermal one when applied to a bis-lactim ether, leading to the corresponding pentacyclic pyrazino [2,1-b:5,4-b¢]diquinazoline-5,13-dione in excellent yield, and it also improved the preparation of compounds containing the ring system of the anti-MDR natural product N-acetylardeemin.

Microwave-Assisted Synthesis of Quinazolines and Quinazolinones: An Overview

“…This reaction was relatively neglected in the past, due to its low yields and the possibility of epimerization of stereocenters adjacent to carbonyl groups Advani, 1973, 1974;Caballero et al, 1998) when performed under thermal and solvent-free conditions. Cledera et al improved the earlier protocol by utilizing MWI in the cyclocondensation of anthranilic acid with lactim ethers, preparing pyrazino[2,1-b]quinazoline-3,6-diones (Cledera et al, 2004). When the tetracyclic ardeemin fragment 94 was reacted with anthranilic acid (77) under MW conditions (600 W) for 3 min, a 6:1 mixture of the diastereoisomeric deprenylardeemins 95 and 96 in 48% overall yield was obtained (Scheme 35).…”