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.