The mechanisms of the Schmidt reaction of acetophenones and the benzyne cyclization of 3-(2-bromobenzyloxy)aniline

The present study was undertaken in an attempt to further elucidate Schmidt reactions of acetophenones. The Excess Acidity method of Cox and Yates was applied to Schmidt reaction data obtained by others, who measured rates of nitrogen evolution for a variety of protonated acetophenones and substituted acetophenones in strong sulfuric acid solvents. These computations explored the involvement of potential nucleophiles (hydrazoic acid, water, bisulfate ion and combinations) in the rate-determining step (rds).;The Excess Acidity treatment showed that for all ketones studied, hydrazoic acid acts as a nucleophile, with water molecules simultaneously acting as proton transfer agents by a hydrogen-bonding process in the rds. This was illustrated by linear plots in the Excess Acidity treatment, indicating an A2-type hydrolysis mechanism, in solvent sulfuric acid concentrations that were less than 90% (low-acidic region). The transition state was presumed to have a linear or cyclic structure. Further evidence for this mechanism was provided by the nonobservance of intermediates in this acid concentration range. Electron-donating substituted acetophenones reacted faster than electron-withdrawing substituted acetophenones.;Identification of potential intermediates was attempted by following the reaction by time-resolved ;In the high-acidity region (sulfuric acid concentration of 98.82%), the Excess Acidity plots became curved, indicating a change in the mechanism. In 98.82% sulfuric acid, no intermediate was observed using NMR spectroscopy for electron-withdrawing substituted acetophenones. Second-order kinetics (with respect to the ketone and hydrazoic acid) was observed.;The research in part II of this dissertation involved synthesizing 3-aminodibenzo(b,d)pyran by the benzyne cyclization. A mixture of isomeric 3-aminodibenzo(b,d)pyran (36% yield) and 1-aminodibenzo(b,d)pyran in a ratio of 3:1 and other unidentified products were obtained. An intramolecular Pschorr cyclization of 3-nitrodibenzo(b,d)pyran in 68% sulfuric acid in the presence of copper (II) nitrate and copper (II) oxide gave 3-nitrodibenzo-(b,d)pyran as a single product (85% yield). This served as an authentic sample of the desired product. Thin layer chromatography of the benzyne mixture indicated closely eluting components. Quantitative analysis of the components was obtained by high pressure liquid chromatography on a Waters Delta Prep 3000 preparative chromatograph using ethylacetate/hexane as the eluting solvent.;Various reaction pathways that may lead to the various components include: (1) The ambient ion can add to the benzyne via the para and ortho carbon giving the two isomers 3- and 1-aminodibenzo(b,d)pyrans respectively. (2) Nucleophilic addition of amide ion or water to the initially formed benzyne, instead of cyclization. (3) Reduction of the triple bond of the initially formed benzyne by the hydrogen generated. (Abstract shortened by UMI.).