Tenn William J, Murphy John L, Bim-Merle Jessica K, Brown Jason A, Junia Adam J, Price Malea A, Nagorski Richard W
Department of Chemistry, Illinois State University, Normal, IL 61790-4160, USA.
J Org Chem. 2007 Aug 3;72(16):6075-83. doi: 10.1021/jo070603u. Epub 2007 Jul 13.
The kinetic study of the aqueous reaction, between pH 10 and 14, of eight N-(hydroxymethyl)benzamide derivatives in water at 25 degrees C, I = 1.0 M (KCl), has been performed. In all cases, the reaction proceeds via a specific-base-catalyzed deprotonation of the hydroxyl group followed by rate-limiting breakdown of the alkoxide to form aldehyde and amidate (E1cB-like). Such a mechanism was supported by the lack of general buffer catalysis and the first-order dependence of the rate of reaction at low hydroxide concentrations and the transition to zero-order dependence on hydroxide at high concentration. A rho-value of 0.67 was found for the Hammett correlation between the maximum rate for the hydroxide independent breakdown of the deprotonated carbinolamide (k1) and the substituent on the aromatic ring of the title compounds. Conversely, the substituents on the aromatic ring of the amide portion of the carbinolamide had only a small effect on the Ka of the hydroxyl group indicating that the amide group does not strongly transmit the electronic information of the substituents. These observations led to the conclusion that the major effect of electronic changes on the amide of carbinolamides is reflected in the nucleofugality of the amidate once the alkoxide is formed and not in the pKa of the hydroxyl group of the carbinolamide.
对8种N-(羟甲基)苯甲酰胺衍生物在25℃、I = 1.0 M（KCl）的水中，pH值在10至14之间的水相反应进行了动力学研究。在所有情况下，反应通过羟基的特定碱催化去质子化进行，随后醇盐进行限速分解以形成醛和酰胺酸盐（类E1cB）。这种机制得到了缺乏一般缓冲催化以及在低氢氧化物浓度下反应速率的一级依赖性和在高浓度下对氢氧化物的零级依赖性转变的支持。对于去质子化的甲醇酰胺（k1）的与氢氧化物无关的分解的最大速率与标题化合物芳香环上的取代基之间的哈米特相关性，发现ρ值为0.67。相反，甲醇酰胺酰胺部分芳香环上的取代基对羟基的Ka只有很小的影响，表明酰胺基团不会强烈传递取代基的电子信息。这些观察结果得出结论，电子变化对甲醇酰胺酰胺的主要影响反映在醇盐形成后酰胺酸盐的离去能力上，而不是反映在甲醇酰胺羟基的pKa上。
