Aromatic Bromination of N-Phenylacetamide Inside CNTs. Are CNTs Real Nanoreactors Controlling Regioselectivity and Kinetics? A QM/MM Investigation

We carried out a computational investigation on the mechanism of the bromination reaction of N-phenylacetamide inside CNTs, in water, and in an aprotic solvent (ethylbenzene). A full QM and a QM/MM approach was used. In the aprotic solvent, a Wheland intermediate (ion pair formed by arenium ion and chloride) exists only for the attack in the ortho position, while the para attack proceeds in a concerted manner (concerted direct substitution). The reaction is catalyzed by the HCl byproduct, which lowers significantly the activation barriers. The ortho product is favored, in contrast to the common belief based on simple steric effects. In water solution a Wheland intermediate was located for both ortho and para attacks (the ion pair is stabilized by the polar protic solvent). The formation of the para product is favored with respect to the ortho product: 9.0 and 9.9 kcal mol(-1) are the corresponding activation barriers. Inside CNTs, as found in aprotic solvent, the Wheland-type arenium ion exists only along the ortho pathway. The initial production of the HCl byproduct activates rapidly the catalyzed mechanism that proceeds almost exclusively along the para pathway (para and ortho activation barriers are 6.1 and 17.0 kcal mol(-1), respectively). The almost exclusive para regioselectivity for the CNT-confined reaction and its acceleration with respect to water (in agreement with the experimental evidence) are due to noncovalent (van der Waals) interactions between the endohedral system and the electron cloud of the surrounding CNT. The effect of these interactions was estimated quantitatively within the UFF scheme used in our QM/MM computations, and we found that they are particularly stabilizing for the para-catalyzed process.