Beckmann's mixture versus Beckmann reaction

Novel tricyclic systems. Oxazole, thiazole, and imidazole analogs of the amitriptyline type

“…Isomerization of Oxazole Ketones and Hydrolysis of Types 5. 2-Methyl-5,6-dihydro-4H-benzo [3,4]cyclohepta[l,2d]oxazol-4-one (8). The crude mixture of 4 and 5 (120 g) obtained as shown above was dissolved in 250 ml of concentrated H2SO4.…”

“…Extraction of this AcOEt solution with 3 M aqueous AcOH, basification (ice-NaOH) of the acid extracts, and reextraction with CH2CI2 yielded 780 g of the crude carbinol intermediate, which in turn was treated in EtOH (6.5 1.) with HC1 gas (10 l./hr, 4 hr, 25°). Evaporation of the EtOH and the usual work-up [50% KOH-ice, ether extraction, and distillation, bp 207-210°(0.025 mm)] yielded 614 g (83%) of the cis-trans mixture of products.…”

“…After 18 hr at 25°, 1.25 1. of 1 N NaOH was added and the biphasic mixture was concentrated to 2 1. The basic product (320 g, 95%>) was then obtained via conven- 2-Methyl-5-(4-methyl-l-piperazinyl)-5,6-dihydro-4/f-benzo- [3,4]cyclohepta[l,2-d]oxazole (70). A solution of 3.5 g (0.0164 mol) of 9, 9.6 g (0.96 mol) of IV-methylpiperazine, and 12.5 g (0.715 mol) of p-toluenesulfonic acid in 50 ml of xylene was refluxed for 3 hr under a Dean-Stark trap.…”

“…(CiSH29Cl2N302) C. , N. Miscellaneous Reactions. 2-Methyl-5,6-dihydro-4H-benzo- [3,4]cyclohepta[l,2-d]oxazol-5-one (9). Dropwise, 27 ml of 30%> H2O2 was added to a stirred (10°) solution of 33 (26.9 g, 0.136 mol) in HCOOH (54 ml) over 30 min.…”

“…Formic or trifluoroacetic acid, which should yield the unsubstituted or the trifluoromethyl-substituted oxazoles, cannot be utilized, in harmony with the mechanistic considerations. 4 While the transformations 4 -•• 6 and .4 -* 7 (an oxazole to thiazole or imidazole) are not completely unprecedented,6 neither are they well-known preparative reactions; hence, we think it is appropriate to draw attention to the usefulness of 4-acyloxazoles as synthetic intermediates. The same could be said about the acid-catalyzed isomerization 4 -8.7…”