Kinetic and Theoretical Studies of 3,5-Dicyanothiophene Reactivity with Cyclic Secondary Amines in Water and Acetonitrile: Quantification, Correlation, and Prediction.

The kinetics of the σ-complexation reactions of 3,5-dicyanothiophene 1 with a series of cyclic secondary amines 2a-c has been studied in water and acetonitrile at 20 °C. Through the linear free energy relationship (LFER) log k = s_N (N + E), the electrophilicity parameter E of 3,5-dicyanothiophene 1 has been determined and then integrated into the electrophilicity scale established by Mayr. Molecular dynamics (MD) simulations have been employed to elucidate the reversal in reactivity order between piperidine and pyrrolidine observed in water. Reactivity descriptors like the electronic chemical potential (μ) and the chemical hardness (η) for a series of thiophenes were calculated using the density functional theory (DFT) method. Satisfactory linear correlation (r² > 0.98) between the experimental electrophilicity parameter (E) of thiophenes 1 and 5a-c and their theoretical global electrophilicity index (ω) has been observed and discussed. In addition, we explore how the E vs. ω relationship can be used to evaluate the electrophilicity parameter E values for other thiophenes that cannot directly measure.