Metal ion catalysis and inhibition in nucleophilic substitution reactions of 4-nitrophenyl nicotinate and isonicotinate with alkali metal ethoxides in anhydrous ethanol

Abstract

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 pseudofirst- 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- embered cyclic transition state TS 3 or TS 4. 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 TS 2. 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.