Acylanthranils. 9. Influence of Hydrogen Bonding on the Reaction of Acetylanthranil with Ammonia

Article abstract of DOI:10.1021/jo01303a019

It was shown that hydrogen bonding has a marked influence on the reaction of acetylanthranil (1) with ammonia.The product of the reaction in anhydrous benzene is 2-methylquinazolin-4-one (5, R = H) which is formed via pathway A as shown in Scheme I, but the rate of formation is unusually slow.The rate of this conversion is about 6 times faster in pyridine than in benzene.If water is added to the benzene system, the rate of reaction is increased by orders of magnitude, but the product is o-acetamidobenzamide (4, R = H) and not 5.In contrast to this result, the addition of water to the pyridine system causes a small decrease in rate and only a slight change in selectivity.These results are consistent with postulated mechanisms whereby 1 reacts with molecular clusters of ammonia, i.e. with (NH3)n in benzene, with N(H*S)3 in strong proton acceptor solvents S, and with (NH3)n*H2O in benzene plus added water.It was verified that cyclodehydration of 4 to give 5 occurs at an appreciable rate in aqueous solution at elevated temperatures and that this rate is accelerated considerably by the presence of strong base even at room temperature.It was also observed that o-acetamidobenzamide exists in at least two crystalline forms, α and β, which have different physical properties.