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

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 . Plots of pseudo-first-order rate constant 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 into and (i.e., the second-order rate constant for the reaction with dissociated and ion-paired EtOM, respectively) has shown that > but . It has been concluded that and ions catalyze the reactions by increasing the electrophilicity of the carbonyl carbon atom through formation of a 4-membered cyclic transition state or . However, 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 . Although 5 and 6 are significantly more reactive than 4-nitrophenyl benzoate 3, the reactions of 5 and 6 result in smaller 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 ratio.