Condensed heterotricycles: Pyrido(1,2,3-de)(1,4)benzoxazines, pyrido(1,2,3-ef)(1,5)benzoxazepines and pyrido(1,2,3-fg)(1,6) benzoxazocines

Abstract

Cyclization of N-(2-haloacyl)-8-hydroxy-l,2,3,4-tetrahydroqumolines 4-7 and 9 with alkali affords pyridobenzoxazinones 21-24 and 26 respectively and of the 4-chlorobutyramide13 with NaH, the benzoxazocinone31. Exposure of 3-chloropropionamide12 to NaH affords acrylamide 15, benzoxazepinone 28 or methyl benzoxazinone 22 or mixtures thereof under various conditions. 28 undergoes rapid base-catalysed ring contraction to 22. NaH-catalysed ring closure of acrylamide 15 affords mixtures of 22 and 28, while from the crotonamides 16 and 17, the methylbenzoxazepinones 29 and 30 are obtained preponderantly, the former amide yielding only traces of the ethyl benzoxazinone 23. 29 shows no propensity for ring contraction to give 23. The cinnamoyl derivatives 18,19 and20 are cyclized to benzyl benzoxazinones 24,27 and 25, respectively. The intermediacy of the phenyl benzoxazepinone 39 in the formation of 24 has been established by deuteration studies. Benzylidene benzoxazinone 41 is obtained from dibromocinnamamide14 and propiolamide 40. Dichloracetamides 8 and 10 undergo interesting ring closure to compounds 45-54 upon treatment with amines. The course of electrophilic reactions of the lactams depends upon the ring size.