球磨-点击化学反应:无溶剂绿色反应方式

Ball-Milled Click Chemistry:A Solvent-Free Green Chemistry

点击化学因反应简单、选择性高、产物单一、且无有害副产物的优点被广泛使用。作为诺贝尔化学奖项,点击化学最初被设计用于水相或绿色有机溶剂。然而在实际应用中,受限于反应物溶解性,点击化学常在极性高的有毒溶剂中进行。溶剂的使用不仅违背了绿色化学的初衷,还增加了生产成本。为了解决这些问题,球磨引起的机械化学被用来实现点击化学反应。机械化学作为一种新型的反应方式,无需溶剂。球磨-点击化学反应具有额外的优点,例如缩短反应时间、降低反应温度、减少催化剂的使用等。本文通过综述整理,报道了球磨条件下点击化学反应的研究进展,包括CuAAc、Diels-Alder、胺-异硫氰酸酯反应、胺-硫醇反应和氧氮自由基偶联反应。为了给读者提供实际操作的指导,本文也包含了球磨机选择指南,液体/固体辅助研磨物质的加入,以及影响反应转化率因素的探究,包括催化剂的选择、添加剂的加入、研磨球大小的选择、化学计量学的探讨、和球磨时间的影响。

Click chemistry won the Noble Prize in 2022 due to easy synthesis,high selectivity,single product,and no toxic side product.Click chemistry was originally designed as green chemistry to work in aqueous solutions or environmentally friendly organic solvents.However,due to the poor solubility of reactants,polar and toxic solvents are usually required to use.The solvent used violates the concept of green chemistry,as well as increases the cost.These issues hinder click chemistry to be a state-of-art green chemistry.One of the solutions to optimize click chemistry is to avoid using any solvent.Herein,ball-milled mechanochemistry does not limit reactants'solubility and could avoid solvent use.Ball-milled mechanochemistry is a new kind of chemical reaction that is conducted in a ball mill,is induced by mechanical force,and needs no solvent or a minimal amount of solvent.As a new way of organic synthesis,ball-milled mechanochemistry could easily achieve the low-energy carbon-heteroatom bonds,which constitute the linkages in click chemistry.Therefore,it could integrate with click chemistry and achieves ball-milled click chemistry.In comparison to traditional solution click chemistry,ball-milled click chemistry avoids solvent use.Moreover,it is even superior in the ways that the reaction time is shortened,the reaction temperature is lowered,and the catalyst used is simplified.In this review,ball-milled click chemistry examples are reported as much as the authors can find,including CuAAc,Diels-Alder,amine and isothiocyanate reactions,amine thiol reactions,and nitroxide radical coupling reactions.To provide readers with a better ball-milled click chemistry manual,this paper also contains ball mill machine choice guidance,liquid-assisted grinding choice guidance,and factors impacting ball-milled click chemistry conversion,including catalyst choice,additive choice,ball choice,stoichiometry,and milling time.