The use of MM/QM calculations of 13 C and 15 N chemical shifts in the conformational analysis of alkyl substituted anilines

The calculation of the 13 C and 15 N NMR chemical shifts by a combined molecular mechanics (Pcmodel 9.1/MMFF94) and ab initio (GIAO (B3LYP/DFT, 6‐31 + G(d)) procedure is used to investigate the conformations of a variety of alkyl substituted anilines. The 13 C shifts are obtained from the GIAO isotropic shielding (Ciso) with separate references for sp 3 and sp 2 carbons (δc = δref − Ciso). The 15 N shifts are obtained similarly from the GIAO isotropic shielding (Niso) with reference to the 15 N chemical shift of aniline. Comparison of the observed and calculated shifts provides information on the molecular conformations. Aniline and the 2,6‐dialkylanilines exist with a rapidly inverting symmetric pyramidal nitrogen atom. The 2‐alkylanilines have similar conformations with the NH 2 group tilted away from the 2‐alkyl substituent. The N , N ‐dialkylanilines show more varied conformations. N , N ‐dimethylaniline has a similar structure to aniline, but N ‐ethyl, N ‐methylaniline, N , N ‐diethylaniline, and N , N ‐diisopropylaniline are conformationally mobile with two rapidly interconverting conformers. In contrast, the anilines substituted at C 2 and the nitrogen atom exist as one conformer where the steric interaction between the C 2 substituent and the N substituent determines the conformation. In 2‐methyl‐ N ‐methylaniline, the nitrogen atom is pyramidal as usual with the N ‐methyl opposite to the 2‐methyl, but in 2‐methyl‐ N , N ‐dimethyl aniline, the NMe 2 group is now almost orthogonal to the phenyl plane. This is also the case with 2‐methyl‐ N , N ‐diethylaniline and 2,6‐diisopropyl‐ N , N ‐dimethylaniline. The comparison of the observed and calculated 15 N chemical shifts confirms the above findings, in particular the pyramidal conformation of aniline and the above observations with respect to the conformations of the N , N ‐dialkylanilines.