An NMR conformational study of ring- and N-inversion, and prototropic tautomerism in stereoisomeric 2-[arylamino(imino)]-4a,5,6,7,8,8a-hexahydro-(4H)-1,3,4-benzoxadiazines

Abstract

The tautomeric cis and trans 2-arylamino-4a,5,6,7,8,8a-hexahydro-(4H)-1,3,4-benzoxadiazines 12a,b-15a,b and the cis and trans 3N,4N-dimethyl-2-phenyl imino analogues 10 and 11 were synthesized. Based on the 15N and 13C NMR chemical shifts, the amino form was unambiguously found to be predominant in each tautomeric compound 12a,b-15a,b. X-Ray crystallographic analysis also proved the predominance of the amino structure in the solid state. Estimations of the vicinal H-H coupling constants at room temperature indicated that the O-in conformer was slightly predominant in cis amino compounds 14a,b-15a,b, except the 3N,4N-dimethyl imino compound 11, which was found to adopt an anancomeric O-in conformation. NOE experiments and low temperature 13C NMR measurements together with X-ray crystallographic analysis were used to elucidate the N-inversion and conformational preference of the N-methyl substituents in cis and trans 3N,4N-dimethyl-2-phenyliminoperhydro-1,3,4-benzoxadiazines 10 and 11. In the solid state the X-ray crystallographic structure of 10 indicated that the N4-methyl is orientated axially and that the N3-methyl is coplanar with the O-C2-N3-N4 segment of the hetero ring. The same conformational preference was also found in solution for both 10 and 11.