Metal Ion Catalysis and Inhibition in Nucleophilic Substitution Reactions of 4-Nitro-phenyl Nicotinate and Isonicotinate with Alkali Metal Ethoxides in Anhydrous Ethanol

摘要

A kinetic study is reported on nucleophilic substitution reactions of 4-nitrophenyl nicotinate 5 and isonicotinate 6 with alkali metal ethoxide EtOM (M = K, Na, and Li) in anhydrous ethanol at 25.0 ±0.1 °C. Plots of pseudo-first-order rate constant k_(obsd) vs. EtOM concentration exhibit upward curvature for the reactions of 5 and 6 with EtOK and EtONa but are almost linear for those with EtOLi. Dissection of k_(obsd) into k_(EtO~-) and k_(EtOM)(i.e., the second-order rate constant for the reaction with dissociated EtO~- and ion-paired EtOM, respectively) has shown that k_(EtOK) ≥ k_(EtONa) > k_(EtO~-) but k_(EtOLi) < k_(EtO~-). It has been concluded that K~+ and Na~+ ions catalyze the reactions by increasing the electrophilicity of the carbonyl carbon atom through formation of a 4-membered cyclic transition state TS3 or TS4. However, M~+ ion catalysis has been found to be much less significant for the reactions of 5 and 6 than for the corresponding reactions of 4-nitrophenyl picolinate 4, which was reported to proceed through a 5-membered cyclic transition state TS2. Although 5 and 6 are significantly more reactive than 4-nitrophenyl benzoate 3, the reactions of 5 and 6 result in smaller k_(EtOK)/k_(EtO~-) ratios than those of 3. The electron-withdrawing ability of the nitrogen atom in the acyl moiety of 5 and 6 has been suggested to be responsible for the increase in reactivity and the decrease in the k_(EtOK)/k_(EtO~-) ratio.