Studies on the benzoxazine series. Part 1. Preparation and 1H and 13C nuclear magnetic resonance structural study of some substituted 3,4-dihydro-2H-1,3-benzoxazines

Abstract

In addition to the parent compounds nine methyl-substituted 3,4-dihydro-2H-1,3-benzoxazines with and without N-methyl substitution were prepared. The former contain usually but minor amounts of the open-chain tautomer, too. The conformations and configurations of the oxazine rings were solved on the basis of ¹H and ¹³C n.m.r. data which were best explained by assuming the N-methyl group predominantly axial in 3,4-dihydro-3-methyl-2H-1,3-benzoxazines. The oxazine ring prefers a half-chair form where the 4ax′-and 4eq′-methyl groups are practically equally stable. Hence, 3,4-dihydro-4-methyl-2H-benzoxazine is a 54 : 46 and the corresponding 3-methyl derivative an 8 : 92 mixture of the 4eq′ and 4ax′ forms. The 2,2,3,4-tetramethyl derivative is not conformationally homogeneous either. Substituent effects on ¹³C n.m.r. chemical shifts were found to be especially useful in configurational and conformational analysis and gave an excellent fit between observed and calculated shift values.