A Facile Synthesis of 2-Substituted-4(3H)-Quinazolinones

Abstract

As part of a synthetic programme currently underway in these laboratories, a mild procedure for the preparation of 4-quinazolinones 2 was required. Several methods are available^1,2 for the synthesis of such ring systems, but these often require the use of fairly extreme conditions. During a study on the interaction of aromatic ortho cyano and acetamido groups, it was found that brief exposure of 2-acylaminobenzo-nitriles 1 to 5N hydrochloric acid followed by basification gave the desired quinazolinones 2, generally in good yield (see Table). The use of 5N hydrochloric acid appears to be critical as more dilute acid requires longer reaction times and produces a mixture of the required quinazolinone and the corresponding 2-acylaminobenzamide. It is interesting to note that 2-acetamidobenzamide is not converted into 2-methyl-4(3H) quinazolinone under the same reaction conditions, and therefore any mechanism which invoes th intermediacy of 2-acylamino-benzamides can be excluded.