Reactivity of 4H-3,1-benzoxazin-4-ones towards nitrogen and carbon nucleophilic reagents: Applications to the synthesis of new heterocycles

Abstract

6,8-Dibromo-(4H)-3,1-benzoxazinone 1a was synthesized and allowed to react with some nitrogen nucleophiles namely, hydroxylamine hydrochloride, 4-aminoacetophenone, o-phenylenediamine, sulfanilamide, sulfamethoxazole, semicarbazide hydrochloride and ethanolamine to afford 3-substituted-4(3H)-quinazolinones 2-8, 10-12 and triazolo[2,3-c]quinazoline 9. 6-Bromo(4H)-3,1-benzoxazin-4-one 1b was also synthesized and converted into 3-amino-4(3H) quinazolinone 13 by reaction with hydrazine hydrate. The latter product was utilized to construct new heterocyclic systems namely, triazino[2,3-c] quinazoline 14 and thiazole derivative 16. An interesting heterocyclic transformation occurred on treatment of benzoxazinone 1a with malononitrile in presence of sodium ethoxide to give quinoline derivative 18 which reacted with phenyl isocyanate to yield oxazinoquinoline 19. The reaction of benzoxazinone 1a with Grignard' reagents afforded unexpected products 20 and 21 whereas Friedel-Crafts reaction of the same oxazinone with some aromatic hydrocarbons namely, benzene, ethylbenzene, m- and p-xylenes afforded either two benzophenone derivatives 20 and 22 or 23 and 24 in case of less bulky hydrocarbons i.e., benzene and ethylbenzene or only one product 25 and 26 in case of more bulky m- and p-xylenes. Oxazinone ring cleavage occurred when barbituric and/or thiobarbituric acid reacted with benzoxazinone 1a in refluxing pyridine to give the corresponding 5-arylidene derivatives 27a,b.