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DOI: https://doi.org/10.6023/A26050173

研究论文

机械化学促进的次磺酰胺与酚及富电子芳烃氧化偶联反应

  • 卢训博 ,
  • 黄政豪 ,
  • 叶俊桃 ,
  • 周善研 ,
  • 周舒婷 ,
  • 郑琬霖 ,
  • 孙嘉琦 ,
  • 赵智博 ,
  • 黄国玲
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  • 岭南师范学院化学化工学院 广东湛江 524048

收稿日期: 2026-05-24

  网络出版日期: 2026-07-16

基金资助

国家自然科学基金(No.22101106)资助项目.

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Mechanochemical Oxidative Coupling of Sulfenamides with Phenols and Related Electron-Rich Aromatic Partners for the Synthesis of Sulfilimines

  • Lu Xunbo ,
  • Huang Zhenghao ,
  • Ye Juntao ,
  • Zhou Shanyan ,
  • Zhou Shuting ,
  • Zheng Wanlin ,
  • Sun Jiaqi ,
  • Zhao Zhibo ,
  • Huang Guoling
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  • School of Chemistry and Chemical Engineering, Lingnan Normal University, Zhanjiang, Guangdong 524048
†These authors contributed equally to this work.

Received date: 2026-05-24

  Online published: 2026-07-16

Supported by

National Natural Science Foundation of China (No. 22101106).

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摘要

硫亚胺是一类重要的高价含硫氮化合物,在有机合成、药物化学和功能分子构建中具有广泛应用。次磺酰胺作为易得且结构可调的S(II)合成子,已被用于多种硫官能团化反应,但相关转化多依赖传统溶液相条件,仍存在溶剂用量较大、反应时间较长和后处理负担较重等问题。本文发展了一种NFSI促进的次磺酰胺与酚及相关富电子芳香底物的机械化学氧化偶联反应。该反应在无溶剂、无添加剂的球磨条件下进行,20 min内即可完成,并能兼容不同硫端取代基、N-酰基以及多种酚类和富电子芳香底物。除酚类底物外,萘酚、吲哚和1,3,5-三甲氧基苯等富电子芳香体系也可顺利参与反应。代表性产物可在3 mmol规模下无需柱层析分离获得,所得硫亚胺还可进一步发生烷基化、氧化衍生。与代表性溶液相方法相比,部分可比底物的反应时间可由1 h或10 h缩短至20 min。对照实验表明,球磨促进作用并不只是来源于热效应;绿色指标分析显示,该方法在反应阶段具有较低的PMI、E-factor和溶剂强度。

关键词： 机械化学; 次磺酰胺; 硫亚胺; 氧化偶联; 无溶剂合成

本文引用格式

卢训博 , 黄政豪 , 叶俊桃 , 周善研 , 周舒婷 , 郑琬霖 , 孙嘉琦 , 赵智博 , 黄国玲 . 机械化学促进的次磺酰胺与酚及富电子芳烃氧化偶联反应[J]. 化学学报, 0 : 0 . DOI: 10.6023/A26050173

Abstract

Sulfilimines are valuable tetravalent sulfur-nitrogen compounds with broad applications in synthetic chemistry, medicinal chemistry, and sulfur-containing functional molecules. Although sulfenamides have emerged as useful and readily accessible S(II) synthons for sulfur functionalization, most related transformations are still conducted under conventional solution-phase conditions, often with considerable solvent use, longer reaction times, and additional purification burden. Herein, we report an NFSI-promoted mechanochemical oxidative coupling of sulfenamides with phenols and related electron-rich aromatic partners for the rapid synthesis of sulfilimines. In a typical procedure, a sulfenamide substrate (1.0 equiv.), an aromatic coupling partner (1.2 equiv.), and NFSI (1.2 equiv.) were charged into a stainless-steel milling jar and subjected to ball milling at 450 rpm under solvent-free and additive-free conditions. The milling program consisted of forward rotation for 5 min, a 2 min pause, and reverse rotation for 5 min, and this sequence was repeated twice to give a total effective milling time of 20 min. Under the optimized conditions, sulfenamides bearing diverse sulfur-side substituents and N-acyl groups were converted into the corresponding sulfilimines in generally good yields. The aromatic coupling partner scope covered substituted phenols, naphthol, indole, and 1,3,5-trimethoxybenzene, indicating that the reaction is applicable to different electron-rich aromatic systems. A representative 3 mmol-scale experiment afforded the desired product without flash column chromatography, and a modified scale-up protocol using 1.2 equiv. of NFSI, 2-MeTHF as a liquid-assisted grinding additive, and prolonged milling improved the yield to 82%. The resulting sulfilimines could be further derivatized through O- or N-alkylation, and selected alkylated products underwent subsequent sulfur-center oxidation. Preliminary radical-trapping and solvent-free stirring control experiments suggested that a radical-chain-dominated pathway is unlikely and that ball milling promotes the reaction beyond simple thermal activation. Comparisons with representative solution-phase procedures and green-metrics analysis revealed clear reaction-stage advantages in reaction time, solvent intensity, and material efficiency. This method provides a concise mechanochemical approach to sulfilimines from readily available sulfenamides.

Key words： Mechanochemistry; Sulfenamides; Sulfilimines; Oxidative coupling; Solvent-free synthesis

参考文献

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