Theoretical Study On Catalytic Amination Of C - H Bond To Nitrogen Heterocyclic Compounds By Ferrous Bromide

Benzimidazoles and indoles are very important N-heterocycles. They have been widely used in the synthesis of pharmaceutical and dye industry. The classical methods to assemble benzimidazoles and indoles involve the reactions of o-phenylenediamine with aldehydes, carboxylic acids, and N-alkylation of benzimidazoles. These methods are easy-to-operate but not suitable for regioselective synthesis. Consequently, metal-catalyzed amination was developed, which performed well in regioselective synthesis. However, the mechanism was investigated rarely.In this paper, the mechanism of FeBr2-catalyzed arylazides to produce benzimidazoles and indoles was studied theoretically. The reason to choose FeBr2to be catalyst was price and environmental friendly, although many other transition metals are good catalysts. Detailed content includes:1. In the first chapter, the value and synthesis methods of N-heterocycles were showed. Among these methods we focused on metal-catalyzed C-H amination, which was introduced from intra-and intermoleculer amination. In the second chapter, theoretical base and computer methods were introduced, including:Schrodinger equation, Hartree-Fork equation, density functional thereory (DFT), transition state theory (TST), intrinsic reaction coordinate (IRC), and solvent effect.2. In the third chapter, mechanism of benzimidazoles catalyzed by FeBr2was investigated, suggesting that the reaction between FeBr2and azides was stepwise. FeBr2was coordinated to Na of azides, extruding N2to generate metal-nitrene. Metal-nitrene attacked sp2C to form C-N barrerless. Fianlly, products benzimidazoles were obtained by a tautomerization process.3. In the fourth chapter, mechanism and regioselectivity of indoles catalyzed by FeBr2was investigated. Metal-nitrene was generated from the reaction between FeBr2and azides, which attacked sp3C-H to form C-N by a concerted H-shift transition state where the H shifted to the N atom from the sp3C. As a result,3,3-disubstituented indole was obtained, which could produce2,3-disubstituented indole by a selectively tautomerization of the substituents. Our DFT calculation showed that the migration aptitude was H>Ph>Et>Me, and the electronic properties of the Ph influenced the migration slightly. This result was in agreement with the related experiment.