An experimental and theoretical study of intramolecular regioselective oxidations of 6-substituted 2,3-dimethylquinoxaline derivatives

作者：Peralta Cruz Javier^*; Diaz Fernandez Monica; Avila Castro Alberto; Ortegon Reyna David; Ariza Castolo Armando^*

来源：New Journal of Chemistry, 2016, 40(6): 5501-5515.

DOI：10.1039/c5nj03282b

An experimental and theoretical study of the regioselective Riley oxidation was conducted on a series of 2,3-dimethyl-6-substituted-quinoxalines bearing EWG (NO2, CN, CF3, Cl, Br, F, COOH, COOMe, COPh) and EDG (2,3-dimethylquinoxaline, OMe, OH, NH2) substituents. The nitrogen lone pair of electrons of the symmetric benzopyrazine moiety initiates the oxidation and promotes nucleophilic competition between the two active sites to give carbaldehyde regioisomers a and b. The mesomeric effect provides the dominant contribution to the regioselectivity. The compounds were characterized by NMR, measuring the H-1, C-13, pfg-HSQC, pfg-HMBC, and N-15, H-1 correlation signals established by pfg-HMQC. The nucleophilic reactivity of nitrogen was evaluated by H-1 NMR titration and analyzed using Perrin linearization to determine the reactivity ratio, Delta K, of the N4 and N1 nitrogen atoms. The structures were optimized using density functional theory at the omega B97XD/6-311G++(d,p) level of theory. The highest occupied molecular orbitals modeled using the HF/6-311G++(d,p) functionals revealed an asymmetric electron density that confirmed the asymmetric nucleophilicity of the nitrogen centers. These values agreed with the experimentally measured Delta K ratios. The PM6 theoretical calculations of the heats of formation of the mesomeric forms and intermediates of (2,3-dimethyl-6-substituted-quinoxalines)-SeO2 allowed us to identify the reaction routes that minimized energy expenditures. The regioselectivities were explained in terms of the energetic diagrams of the regioisomers. All compounds evaluated indicated a preference toward forming regioisomer b, except for the derivative bearing the EDG substituent (2,3-dimethylquinoxaline) which displayed a preference for regioisomer a.

• 出版日期2016-6-1