Formation of 1,3-perhydrobenzoxazines and their N-methyl derivatives. A comparative study

Article abstract of DOI:10.1016/S0040-4020(01)96133-2

The formation of perhydro-1,3-oxazine derivatives (3) through the cyclization reaction of P-nitrobenzaldehyde with cis- (1) and trans-2-aminomethyl-1-cyclohexanol (2) or with their N-methyl derivatives (1m and 2m) were studied by ¹H NMR spectroscopy in CDCl₃. The reactions with 1 and 2 proceeded via open-chain intermediates whereas those with 1m and 2m showed no signs of these intermediates. The cyclization reactions of the N-methyl substituted cyclohexanols (1m and 2m) were much faster than those of the corresponding hydroxymethylcyclohexylamines studied earlier. The cyclization of 1 was kinetically controlled but in much lesser extent than the corresponding reaction with cis-2-hydroxymethyl-1-cyclohexylamine. These results confirmed that the cyclization reactions of P-nitrobenzaldehyde with 2-aminomethyl-1-cyclohexanols and their N-methyl derivatives parallel to those with 2-hydroxymethyl-1-cyclohexylamines and their N-methyl derivatives are not usually diastereospecific.