Cyclization of substituted phenyl N-(2-hydroxybenzyl)carbamates in aproticsolvents. Synthesis of 4H-1,3-benzoxazin-2(3H)-ones

The kinetics of cyclization of substituted phenyl N-(2-hydroxybenzyl)carbam ates and their N-methyl analogs, prepared by the reaction of 2-(aminomethyl )phenols with substituted phenyl chloroformates, was studied in dioxane or toluene at the temperatures 110-180 degreesC. Electron-withdrawing substitu ents in the leaving phenoxy group strongly accelerate the rate of cyclizati on (rho = 2.45 +/- 0.15) while the substituents in the other ring have virt ually no effect. The cyclization was catalyzed with triethylamine in toluen e but not in dioxane. On the basis of these results, the most convenient me thod for preparation of substituted 4H-1,3-benzoxazin-2(3H)-ones was a one- hour reflux of substituted 4-nitrophenyl N-(2-hydroxybenzyl)carbamates in d ioxane. Based on the influence of substituents, solvents (dioxane and tolue ne) and triethylamine, the reaction mechanism and structure of the transiti on state were proposed.