Rearrangement of N-acyl-3,4-dihydro-1H-2,1-benzoxazines to 2-substituted-4H-3,1-benzoxazines through a retro-Diels–Alder extrusion of formaldehyde

Abstract

NAcyl-3,4-dihydro-1H-2,1-benzoxazines (3) undergo a thermal decomposition involving loss of formaldehyde in a retro-Diels–Alder reaction. The resultant N-acylazaxylylenes (4) undergo a 6π electrocyclisation to give 2-substituted-4H-3,1-benzoxazines (5) rather than a 4π electrocyclisation to give the N-acyl-1,2-dihydrobenzazetes (6). Compounds 5 have been fully characterised spectroscopically and their data is inconsistent with that reported previously by other workers for what are purported to be the same compounds. 2-Methyl-4H3,1-benzoxazine (5b) and other 2-alkyl-substituted compounds undergo facile hydrolysis to o-aminobenzyl esters (9) which rearrange to the thermodynamically more stable o-hydroxymethylanilides (10). 2-Phenyl-4H-3,1-benzoxazine (5a) is relatively stable to hydrolysis but undergoes a novel photochemical ring opening (> 254 nm) to give the N-benzoylazaxylylene (12) which can be trapped with alcohols giving o′-alkoxymethylbenzanilides (11). In cyclohexanol at 160 °C, the intermediate in the thermal rearrangement of 3a to 5a, N-benzoylazaxylylene (12), was trapped as o′-cyclohexyloxymethylbenzanilide (11b). The rearrangements in mesitylene are unimolecular with activation energies of 35, 37 and 42 kcal mol^–1 for 3a, 3c and 3d, respectively. The extrusion and electrocyclisation reaction pathways for N-acetyl-3,4-dihydro-2,1-benzoxazine (3b) have been modelled using AM1 molecular orbital theory which predicts both a non-synchronous transition state for the retro-Diels–Alder reaction and the preferred mode of ring closure to be the 6π rather than the 4π electrocyclisation.