A kinetic study is reported for reactions of 2‐methoxy‐3‐X‐5‐nitrothiophenes 1a–d (X = SO2CH3, CO2CH3, CONH2, H) with piperidine in different solvents at 20°C. It is shown that the reactions take place through a SNAr mechanism with the initial nucleophilic addition step being rate limiting. The satisfactory Hammett correlations (log k1 vs. σnormalp−) obtained in the present system confirms that a 3‐X substituent exerts an effect on the 2‐position of the same type as that exerted from the 5‐position. The second‐order rate constants associated with these reactions are employed to determine the electrophilicity parameters E of the thiophenes 1a–d according to the relationship log k (20°C) = s(E + N) (Angew. Chem., Int. Ed. Engl. 1994, 33, 938–957). The E values of 1a–d are found to cover a range from −21.33 to −17.18, going from 1d, the least reactive, to 1a, the most reactive thiophene. Interestingly, a linear correlation (r2 = 0.9910) between the electrophilicity parameters E determined in this work and the Hammett's σnormalp− constants values has been observed and discussed. On the other hand, we have found that the reported rate constants of some thiophenes 1 complexation by the methoxide ion in methanol are 3.5–73.5 times higher than predicted by Mayr's approach.

Combined experiments and modelling rationalize the large influence of solvent composition on pyrrolidine nucleophilicity.

Second-order rate constants (k 1 ) have been measured spectrophotometrically for reactions of 2-methoxy-3-X-5-nitrothiophene 1a-c (X = NO 2 , CN, and COCH 3 ) with secondary cyclic amines (pyrrolidine 2a, piperidine 2b, and morpholine 2c) in CH 3 CN and 91:9 (v/v) CH 3 OH/CH 3 CN at 20 • C. The experimental data show that the rate constants (k 1 ) 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 = SO 2 CH 3 , CO 2 CH 3 , CONH 2 , and H) are linearly related to the pK a 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 (r 2 = 0.9726) between the experimental (log k exp ) and the calculated (log k calcd ) values for the -complexation reactions of these 12 electrophiles with methoxide ion in methanol has been observed and discussed. K E Y W O R D S electrophilicity parameters, kinetics, Mayr relationship, substituted thiophenes 2 EXPERIMENTAL MaterialsThe thiophenes 1 was prepared, as previously described. 7,8 All the amines 2 (morpholine, piperidine and pyrrolidine) were commercial products (Merck, Darmstadt-Germany) and were redistilled before use whenever necessary.Acetonitrile and methanol HPLC grade >99.9% (Merck, Darmstadt-Germany) were available of the highest quality and used without further purification.All spectrophotometric measurements were carried out using a spectrophotometer (UV-1650 Shimadzu, Japan) equipped with a Peltier temperature controller (model TCC-240 A), which is able to keep to temperature within 0.1 K. 582