Kinetics and quantification of the electrophilic reactivities of substituted thiophenes and structure‐reactivity relationships

Abstract

AbstractSecond‐order rate constants (k1) have been measured spectrophotometrically for reactions of 2‐methoxy‐3‐X‐5‐nitrothiophene 1a‐c (X = NO2, CN, and COCH3) with secondary cyclic amines (pyrrolidine 2a, piperidine 2b, and morpholine 2c) in CH3CN and 91:9 (v/v) CH3OH/CH3CN at 20°C. The experimental data show that the rate constants (k1) values exhibit good correlation with the parameters of nucphilicity (N) of the amines 2a‐c and are consistent with the Mayr's relationship log k (20°C) = s(E + N). We have shown that the electrophilicity parameters E derived for 1a–c and those reported previously for the thiophenes 1d‐g (X = SO2CH3, CO2CH3, CONH2, and H) are linearly related to the pKa values for their gem‐dimethoxy complexes in methanol. Using this correlation, we successfully evaluated the electrophilicity E values of 12 structurally diverse electrophiles in methanol for the first time. In addition, a satisfactory linear correlation (r2 = 0.9726) between the experimental (log kexp) and the calculated (log kcalcd) values for the σ‐complexation reactions of these 12 electrophiles with methoxide ion in methanol has been observed and discussed.