Organic synthesis by Twin Screw Extrusion (TSE): continuous, scalable and solvent-free
Organic synthesis by Twin Screw Extrusion (TSE): continuous, scalable and solvent-free
复制标题
DOI：
10.1039/c6gc03413f
复制
发表时间：
2017-03-21
期刊：
影响因子：
9.8
通讯作者：
James, Stuart L.
中科院分区：
文献类型：
--
作者：
Crawford, Deborah E.;Miskimmin, Clodagh K. G.;James, Stuart L.
机械化学提供了一种通过研磨纯试剂进行反应来减少或消除溶剂使用的方法。直到最近，这种形式的合成的一个显著缺点是扩大规模的能力有限。然而，已经表明双螺杆挤出（TSE）可以克服这个问题，如在以多kg h（-1）的量连续合成共晶体、金属有机框架（MOF）和深度共溶剂（DES）中所证明的。TSE提供了一种以连续、大规模和有效的方式进行机械化学合成的方法，其适用于制造工艺。在这里，我们强调了这种技术的潜力，通过报告四个缩合反应，Knoevenagel缩合，亚胺形成，羟醛缩合反应和迈克尔加成，产生分析纯的产品，其中大部分不需要任何合成后的纯化或分离的有机合成。每个反应在不存在溶剂的情况下进行，并且由于使用的高温，在挤出过程中水副产物作为水蒸气方便地除去。此外，Knoevenagel缩合已被详细研究，以深入了解这些机械化学反应进行的机制。结果表明，一种反应物被另一种反应物有效润湿对于在这些反应条件下发生这些反应是至关重要的。
Mechanochemistry provides a method to reduce or eliminate the use of solvents by carrying out reactions through the grinding of neat reagents. Until recently a significant drawback of this form of synthesis has been the limited ability to scale up. However, it has been shown that twin screw extrusion (TSE) may overcome this problem as demonstrated in the continuous synthesis of co-crystals, Metal Organic Frameworks (MOFs) and Deep Eutectic Solvents (DES), in multi kg h(-1) quantities. TSE has provided a means to carry out mechanochemical synthesis in a continuous, large scale and efficient fashion, which is adaptable to a manufacturing process. Herein, we highlight the potential of this technique for organic synthesis by reporting four condensation reactions, the Knoevenagel condensation, imine formation, aldol reaction and the Michael addition, to produce analytically pure products, most of which did not require any post synthetic purification or isolation. Each reaction was carried out in the absence of solvents and the water byproduct was conveniently removed as water vapour during the extrusion process due to the elevated temperatures used. Furthermore, the Knoevenagel condensation has been studied in detail to gain insight into the mechanism by which these mechanochemical reactions proceed. The results point to effective wetting of one reactant by another as being critical for these reactions to occur under these reaction conditions.