A kinetic study on SNAr reactions of 1-aryloxy-2,4-dinitrobenzenes (1a–1h) with a series of cyclic secondary amines in 80 mol% water – 20 mol% DMSO at 25.0 ± 0.1 °C is reported. The plots of kobsd versus amine concentration curve upward except for the reactions of substrates possessing a strong electron-withdrawing group in the leaving aryloxide with strongly basic piperidine. The curved plots indicate that the reactions proceed through both uncatalytic and catalytic routes. Linear Brønsted-type plots have been obtained for the uncatalyzed and catalyzed reactions of 1-(4-nitrophenoxy)-2,4-dinitrobenzene (1a) with βnuc = 0.84 and 0.78, respectively. The Yukawa–Tsuno plot for the uncatalyzed reactions of 1a–1h with piperidine results in an excellent linear correlation with ρ = 1.66 and r = 0.31. In contrast, rate constants for catalyzed reactions are independent of the electronic nature of the substituent in the leaving group. The current SNAr reactions have been proposed to proceed via a zwitterionic intermediate (MC±) that partitions to products through uncatalytic and catalytic routes. The catalyzed reaction from MC± has been concluded to proceed through a concerted mechanism with a six-membered cyclic transition state (TScycl) rather than via a stepwise pathway with a discrete anionic intermediate (MC−), the traditionally accepted mechanism. Medium effects on the reactivity and reaction mechanism are discussed. Particularly, hydrogen bonding of the amines to water precludes formation of kinetically significant dimers found in some aprotic solvents; no explicit role for water in the catalytic transition state is required or proposed. The specific stabilization of the leaving aryloxides substituted with strong electron-withdrawing groups accounts for the lack of the catalytic pathway in these systems (1a–1c) with piperidine nucleophile.
Michael-type Reactions of 1-(X-substituted phenyl)-2-propyn-1-ones with Alicyclic Secondary Amines in MeCN and H2O: Effect of Medium on Reactivity and Transition-State Structure
