A sustainable and scalable protocol for synthesizing variously functionalized sulfonamides, from amines and sulfonyl chlorides, has been developed using environmentally responsible and reusable choline chloride (ChCl)‐based deep eutectic solvents (DESs). In ChCl/glycerol (1:2 mol mol–1) and ChCl/urea (1:2 mol mol–1), these reactions yield up to 97% under aerobic conditions at ambient temperature within 2–12 h. The practicality of the method is exemplified by the sustainable synthesis of an FFA4 agonist and a key building block en route to anti‐Alzheimer drug BMS‐299897. A subtle interplay of electronic effects and the solubility characteristics of the starting materials in the aforementioned DESs seem to be responsible for driving the reaction successfully over the hydrolysis of sulfonyl chlorides. The procedure’s eco‐friendliness is validated by quantitative metrics like the E‐factor and the EcoScale, with products isolated by extraction or filtration after decantation.

中文翻译：

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用于可持续磺酰胺合成的可切换低共熔溶剂


使用对环境负责且可重复使用的氯化胆碱（ChCl）基低共熔溶剂（DES）开发了一种可持续且可扩展的方案，用于从胺和磺酰氯合成各种功能化的磺酰胺。在 ChCl/甘油 (1:2 mol mol–1) 和 ChCl/尿素 (1:2 mol mol–1) 中，这些反应在环境温度有氧条件下 2-12 小时内产率高达 97%。该方法的实用性通过 FFA4 激动剂和抗阿尔茨海默病药物 BMS-299897 的关键构建模块的可持续合成得到了例证。上述 DES 中电子效应和起始材料溶解度特性之间的微妙相互作用似乎是成功推动磺酰氯水解反应的原因。该程序的生态友好性通过 E 因子和 EcoScale 等定量指标进行验证，产品在倾析后通过萃取或过滤进行分离。