Substituents Effect on Aziridine Chemistry: N-Inversion Energy, Reactivity and Regioselectivity of Nucleophilic Ring-opening

Abstract

The N-inversion energies and nucleophilic ring-opening reactions of N-substituted aziridine compounds are investigated using B3LYP/6-31+<TEX>$G^*$</TEX> methods, where substituents (R) on the nitrogen atom has been H (1), Me (2), Ph (3), Bn (4), CHMePh (5), <TEX>$CO_2Me$</TEX> (6), COPh (7) and <TEX>$SO_2Ph$</TEX> (8). The N-inversion energy with X group are decreased as the following order: R = CHMePh (17.06 kcal/mol) <TEX>$\gt$</TEX> Me (16.97) <TEX>$\gt$</TEX> Bn (16.70) <TEX>$\gt$</TEX> H (16.64) <TEX>$\gt$</TEX> <TEX>$SO_2Ph$</TEX> (12.18) <TEX>$\gt$</TEX> Ph (8.91) <TEX>$\gt$</TEX> COPh (5.75) <TEX>$\gt$</TEX> <TEX>$CO_2Me$</TEX> (5.48). For reactivity of the ring opening toward cyanide ion, the aziridine 6 (R=<TEX>$CO_2Me$</TEX>) is shown to be the most reactive one. During the ring opening of aziridine 6 by CN<TEX>$^{\ominus}$</TEX>, the torsional OCNC angle becomes near to <TEX>$180^{\circ}$</TEX>, where the geometry allows for the effective incorporation of electrons of the nitrogen atom to the C=O bond. It would be a possible driving force for nucleophilic ring opening reaction as well as decreasing the N-inversion energy barrier. Regarding to the regioselectivity, the orientation of nucleophile in ring opening reaction appears to be different in the case of 9 and 10. The results are discussed in terms of steric/electronic effect of the <TEX>$C_2$</TEX>-substituents.