一种有机卤化物的原子经济性电合成策略

doi:10.1016/S1872-2067(25)64796-6

摘要/Abstract

摘要：

有机卤化物是合成药物、农化品和聚合物的关键试剂. 其工业生产常用卤素单质(Cl₂/Br₂), 但存在两大问题: (1)产生强酸性、有害的氢卤酸副产物; (2)卤素原子利用率低(≤ 50%). 作为替代的卤化试剂, N-氯代丁二酰亚胺(NCS)与N-溴代丁二酰亚胺(NBS)理论上可实现卤素原子100%转移, 从而消除卤素污染. 然而, 当前NCS/NBS的合成仍依赖卤素单质, 同样产生含卤废弃物. 因此, 亟需开发高电流密度下原子高效的NCS/NBS电化学合成与分离方案.

本文采用负载型RuO_x催化剂(RuO_x/TiO₂/Ti), 以氯化钾、溴化钾及丁二酰亚胺为原料, 在间歇和连续反应器中实现了NCS和NBS的选择性电合成. X射线衍射(XRD)、X射线光电子能谱(XPS)以及扫描电镜能谱映射(SEM-EDS)结果表明, 新合成的催化剂中Ru以+3至+4的氧化态均匀的分布在载体表面. 在间歇式反应器中, 合成NCS的法拉第效率(FE)可达91.0%, 总电流密度为317 mA/cm²; 合成NBS时, 在58.5 mA/cm²的电流密度下, FE为81.3%. 原位拉曼光谱结果表明, RuO_x的晶体结构在反应过程中没有明显改变. 对反应后的催化剂进行XRD、XPS以及SEM-EDS表征发现, 其结构以及RuO_x的价态与分布均没有明显的改变. 机理研究表明, NCS的形成可能通过多相催化反应和均相串联反应两种路径; NBS的生成则遵循Langmuir-Hinshelwood机理, 其中质子耦合电子转移为决速步. 此外, 本文构建了NCS和NBS的连续电催化合成与原位分离装置, 在12000 s内生成0.77 g NCS, 15000 s内生成0.81 g NBS, 质量纯度均大于95%. 进一步以丙酮为底物, 分别与NCS和NBS进行卤化反应, 成功制备克级药物中间体1-卤代丙酮, 且丁二酰亚胺回收率超95%.

综上, 本文成功构建了一种结合连续电化学合成与原位分离技术的NBS/NCS制备新体系, 实现了有机卤化物的高原子经济性、环境友好型合成. 该策略通过流动化学装置实现卤化试剂的原位电合成与即时分离, 同时规避了传统卤素路线中的原子经济性差和污染大的两大核心缺陷. 此项技术将绿色电化学合成与过程强化工程创新结合, 为医药、农药及高分子材料领域提供兼具原子效率与环保特性的卤化新平台.

关键词: 电催化, 过程强化, 卤化反应, 有机卤化物合成, N-氯代丁二酰亚胺, N-溴代丁二酰亚胺

Abstract:

Existing organic halide synthesis routes typically employ elemental halogens (X₂, X = Cl or Br), leading to low atom economy and significant environmental pollution. In this work, we developed an atom efficient electrosynthesis and separation strategy for halogenation reagents — N-chlorosuccinimide (NCS) and N-bromosuccinimide (NBS) — at high current densities. Faradic efficiency (FE) of 91.0% and 81.3% was achieved for NCS and NBS generation on RuO_x/TiO₂/Ti in a batch cell, respectively. Electrosynthesis of NCS likely involves both heterogeneous catalytic and homogeneous tandem pathways, while NBS is likely formed in a Langmuir-Hinshelwood mechanism with a proton-coupled electron transfer as the rate-determining step. A coupled continuous electrocatalytic synthesis and in situ separation setup was developed for the efficient production of NCS and NBS, which yielded 0.77 g of NCS in 12000 s and 0.81 g of NBS in 15000 s, both with relative purity exceeding 95%. The halogenation of acetone using NCS and NBS enabled gram-scale production of the key intermediate in organic synthesis, 1-halogenacetone, with over 95% recovery of succinimide.

Key words: Electrocatalysis, Process intensification, Halogenation reaction, Organic halides synthesis, N-chlorosuccinimide, N-bromosuccinimide

刘翼维, 常晓侠, 徐冰君. 一种有机卤化物的原子经济性电合成策略[J]. 催化学报, 2025, 78: 170-181.

Yiwei Liu, Xiaoxia Chang, Bingjun Xu. An atom-efficient electrosynthesis strategy for organic halides[J]. Chinese Journal of Catalysis, 2025, 78: 170-181.

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链接本文: https://www.cjcatal.com/CN/10.1016/S1872-2067(25)64796-6

https://www.cjcatal.com/CN/Y2025/V78/I11/170

图/表 6

Fig. 1. (a) XRD profiles of synthesized RuOx/TiO2/Ti and IrOy/TiO2/Ti. (b) XPS spectra of synthesized RuOx/TiO2/Ti and IrOy/TiO2/Ti. SEM images with elemental mapping of synthesized RuOx/TiO2/Ti (c) and IrOy/TiO2/Ti (d).

Fig. 2. (a) Reaction scheme of electrosynthesis of NCS and NBS (X = Cl, Br). Impact of reaction conditions on FE and current density in electrocatalytic synthesis of NCS (b,d) and NBS (c,e). Effect of the applied potential in NCS (b) and NBS (c) synthesis. Effect of pH in NCS (d) and NBS (e) synthesis. In (d) and (e), H2SO4 (aq), KH2PO4 (aq), K2SO4 (aq), H3BO3-KB(OH)4 (aq) and KOH (aq) were used for regulating pH from 1 to 13.

Fig. 3. Impact of reaction conditions on FE and current density in electrocatalytic synthesis of NCS (a,b) and NBS (c,d). Effect of the C(KX) (X = Cl or Br) in NCS (a) and NBS (c) synthesis. Effect of m(succinimide) in NCS (b) and NBS (d) synthesis. Synthesis of NCS and NBS was carried out at 1.2 and 1.0 V, respectively, at pH = 7.

Fig. 4. CVs curves under different m(succinimide) in NCS (a) and NBS (c) synthesis. CVs curves under different C(KX) in NCS (b, X = Cl) and NBS (d, X = Br) synthesis. Scanning rate: 50 mV/s. The anode solution was prepared by 16 mL 0.1 mol/L K2SO4.

Fig. 5. (a) Schematic diagram of the experimental setup. (b) Continuous synthesis and in-situ separation of NCS under constant 120 mA electrolysis. Geometric area of anode: 0.9 cm2. Liquid flow rate: 40 mL/min. The added feedstock aqueous contained 3 mol/L KCl and 0.75 g/10 mL succinimide. (c) Continuous synthesis and in-situ separation of NBS under constant 100 mA electrolysis. Geometric area of anode: 0.9 cm2. Liquid flow rate: 40 mL/min. The added feedstock aqueous contained 1 mol/L KBr. The anode and reference electrode in the continuous reactor are 2 cm apart, while the separation is 0.2 cm in the batch cell. Thus, the internal IR correction was conducted in the continuous reactor. IR-uncorrected data are included in Fig. S12(b), (c). The anolyte was maintained at room temperature during the electrolysis process.

Fig. 6. (a) Performance in halogenation reaction of acetone with NCS and NBS. (b) Existing and electrocatalysis-coupled routes for halogenated acetone.

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