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

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 N-15 and C-13 NMR chemical shifts, the amino form was unambiguously found to be predominant i n each tautomeric compound 12a,b-15a,b. X-Ray crystallographic analysis als o proved the predominance of the amino structure in the solid state. Estima tions of the vicinal H-H coupling constants at room temperature indicated t hat the O-in conformer was slightly predominant in cia amino compounds 14a, b-15a,b, except the 3N,4N-dimethyl imino compound 11, which was found to ad opt an anancomeric O-in conformation. NOE experiments and low temperature C -13 NMR measurements together with X-ray crystallographic analysis were use d to elucidate the N-inversion and conformational preference of the N-methy l substituents in cis and trans 3N,4N-dimethyl-2-phenyliminoperhydro-1,3,4- benzo-xadiazines 10 and II. In the solid state the X-ray crystallogaphic st ructure of 10 indicated that the N4-methyl is orientated axially and that t he N3-methyl is coplanar with the O-C2-N3-N4 segment of the hetero ring. Th e same conformational preference was also found in solution for both 10 and 11.