Theoretical investigation of nucleophilic substitution reaction of phenyl carbonyl isothiocyanates with pyridines in gas and polar aprotic solvent.

This study focuses on the mutual interaction of substituents in the nucleophile and substrate - cross interaction constant, ρ XY , in the uncatalyzed aminolysis by substituting pyridine with phenyl carbonyl isothiocyanate. The mechanism was found to be a stepwise process with a rate-limiting breakdown of the -NCS leaving group. This stepwise reaction mechanism considers the cross-interaction constant (CIC) with rate-limiting breakdown of tetrahedral intermediate in gas and solvent phases. The corresponding Hammett coefficients are related to the substituents associated with (1) the nucleophiles (X), ρ X (-1.93 to -6.54 for the gas phase and 10.5 to 18.9 in the solvent model), and with (2) the substituents associated with the phenyl ring of the substrate (Y), ρ Y (0.41-3.48 for the gas phase and 1.83 to -10.70 for the solvent model). It also includes the Brønsted coefficient with X, β X (0.11-1.52 for the gas phase and -2.57 to 3.96 for the solvent model), and CIC values, ρ XY (0.69 for the gas phase and 0.87 for the solvent model). In this work, the NBO analysis, reaction potential, reaction electronic flux (REF), dual descriptor, and the structure-energy relationships were considered in interpreting the mechanistic criteria.