The role of the ortho-aminomethyl functional group in phenyl boronic acids for sugar complexation is a topic of debate. To decipher its effect on the kinetics of boronate ester formation, we first performed pseudo-first-order kinetics analyses at five pH values up to 4 mM in fructose, revealing a first-order kinetic dependence upon fructose. Under these conditions, the reaction is in equilibrium and does not reach completion, but at 50 mM fructose saturation is achieved, revealing zero-order dependence upon fructose. This indicates rate-determining creation of an intermediate prior to reaction with fructose, which we propose involves leaving group departure of inserted solvent. Furthermore, the region of kinetics displaying zero-order dependence has a kinetic isotope effect of 1.42, showing involvement of a proton transfer in the leaving group departure. The ratio of forward and reverse rate constants branching from the intermediate shows that fructose is several thousand times more nucleophilic than the solvent. Overall, the data support a mechanism where the ortho-aminomethyl group lowers the pK a of the proximal boronic acid and acts as a general acid (as an ammonium) to facilitate leaving group departure. Consequently, by microscopic reversibility the resulting amine must perform general base catalysis to deliver fructose.

中文翻译：

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邻氨基甲基官能化苯基硼酸中硼酸酯的形成速率


苯基硼酸中的邻氨基甲基官能团在糖络合中的作用是一个有争议的话题。为了解读其对硼酸酯形成动力学的影响，我们首先在果糖中在五个 pH 值（最高 4 mM）下进行了伪一级动力学分析，揭示了对果糖的一级动力学依赖性。在这些条件下，反应处于平衡状态并且未达到完成，但在 50 mM 果糖时达到饱和，揭示了对果糖的零级依赖性。这表明在与果糖反应之前中间体的速率决定生成，我们建议涉及插入溶剂的离去基团离开。此外，显示零级依赖性的动力学区域具有 1.42 的动力学同位素效应，表明质子转移参与了离去基团的离开。从中间体分支的正向和反向速率常数的比率表明，果糖的亲核性比溶剂高数千倍。总体而言，数据支持一种机制，其中邻氨基甲基降低近端硼酸的 pK a 并充当通用酸（作为铵）以促进离去基团的离开。因此，通过微观可逆性，所得胺必须进行一般碱催化以递送果糖。