应用量子化学反应性指数分析4,4-二苯丁腈的合成

Analyzing the Synthesis of 4,4-Diphenylbutyronitrile by Quantum Chemical Reactivity Index

摘要: 4,4-二苯丁腈是合成H₁受体激动剂Histaprodifens的重要原料之一。化学结构虽然简单，但合成它，要么合成方法简单但需要昂贵的原材料，要么原材料虽然便宜但合成条件苛刻。为了改进4,4-二苯丁腈的合成工艺，我们采用较为便宜的原材料，并通过量子化学计算获得反应的化学反应性指数，来研究和探讨反应机制并指导实验操作。本文在传统的用金属钾对二苯甲烷的烷烃基拔氢反应的方法基础上，采用间接法，即以四甲基乙二胺为起始原料，与正丁基锂发生偶合反应，形成四甲基乙二胺锂鎓盐；后再与二苯甲烷反应，形成二苯甲烷锂盐，最后与3-溴丙腈反应，完成4,4-二苯丁腈的制备。实验表明，该反应条件温和，原料易得，成本低且对环境较友好，反应总收率可达80%左右；实验表明，采用量子化学反应性指数可以分析反应的全过程，并成功地指导化学反应的操作过程。

Abstract: 4,4-diphenylbutyronitrile is a crucial raw material for synthesizing H₁ receptor agonist Histaprodifens. Despite its simple chemical structure, the synthesis process requires either expensive raw materials or harsh reaction conditions when using cheaper alternatives. To improve the synthesis of 4,4-diphenylbutyronitrile, we utilized quantum chemistry calculations to determine the chemical reactivity index and guide experimental operations while using cost-effective starting materials. In this study, we employed an indirect method based on traditional alkane hydrogen extraction reactions with metal potassium on diphenylmethane. Specifically, tetramethyl ethylenediamine was used as a starting material and combined with n-butyllithium to form N,N,N',N'-tetramethylethylenediamine lithium salt before reacting with diphenylmethane to produce diphenylmethane lithium salt. Finally, 3-bromopropionitrile was added to complete the preparation of 4,4-diphenylbutyronitrile. The results showed that this mild reaction-n condition utilizing easily obtainable raw materials had low costs and environmental impact while achieving a total yield of up to 80%. Furthermore, our experiment demonstrated that analyzing the entire reaction process through quantum chemical reactivity index could successfully guide operational procedures.