First-principles study of the reaction mechanism governing the SNAr of the dimethylamine on 2-methoxy-5-nitrothiophenes

Abstract

The SNAr mechanism invoked in this work concerned the substitution reaction of the methoxy group by a secondary amine on the 2-methoxy-5-nitrothiophene and 2-methoxy-3,5-dinitrothiophene molecules. We performed theoretical DFT and TD-DFT calculations. It was examined by theoretical DFT calculations. The hypothesis of a zwitterion formation during the kinetically determining step has been confirmed. However, our calculations have shown that the structure of this reaction intermediate is much more diffuse than commonly accepted. Its geometry can be described as one situation in which the nitrogen of the nucleophilic entity is not totally bound to the carbon, whereas the oxygen of the leaving group prepares to be separated from the substrate. The transition state corresponding to the formation of the zwitterion has a barrier of 17.78 kcal mol−1 in methanol. Three pathways have been studied to describe the second step, leading to the formation of methanol or methoxyammonium. The most probable pathway uses, in a first sequence, a second amine molecule to convert the zwitterion, a dipolar compound, into a hydrogen-bonding association of a carbanion located on the carbon C5 carrying the nitro group and an ammonium with a weak activation barrier of 2.25 kcal mol−1. The electron density supplement provided by the nucleophile is stored at the oxygen atoms of the 5-nitro group in position α of the sulfur atom. The presence of a second nitro group in position β modifies the structure of this carbanion by locating the negative charge on the carbon C3 carrying the second nitro. To visualize the reaction mechanism, we propose an innovative technique called reactive internal reaction coordinate that traces the reaction pathway in a 3D figure as a variation of the energy according to the most active internal coordinates in the transition-state zone of influence.