Berton Mateo, Sheehan Kevin, Adamo Andrea, McQuade D Tyler
Department of Chemical and Life Sciences Engineering, Virginia Commonwealth University, Biotech Eight, 737 N. 5th St., Box 980100, Richmond, VA 23219, USA.
Zaiput Flow Technologies, 300 2nd Avenue, Waltham, MA 02451, USA.
Beilstein J Org Chem. 2020 Jun 19;16:1343-1356. doi: 10.3762/bjoc.16.115. eCollection 2020.
Magnesium organometallic reagents occupy a central position in organic synthesis. The freshness of these compounds is the key for achieving a high conversion and reproducible results. Common methods for the synthesis of Grignard reagents from metallic magnesium present safety issues and exhibit a batch-to-batch variability. Tubular reactors of solid reagents combined with solution-phase reagents enable the continuous-flow preparation of organomagnesium reagents. The use of stratified packed-bed columns of magnesium metal and lithium chloride for the synthesis of highly concentrated turbo Grignards is reported. A low-cost pod-style synthesizer prototype, which incorporates single-use prepacked perfluorinated cartridges and bags of reagents for the automated on-demand lab-scale synthesis of carbon, nitrogen, and oxygen turbo magnesium bases is presented. This concept will provide access to fresh organomagnesium reagents on a discovery scale and will do so independent from the operator's experience in flow and/or organometallic chemistry.
有机金属镁试剂在有机合成中占据核心地位。这些化合物的新鲜度是实现高转化率和可重复结果的关键。由金属镁合成格氏试剂的常见方法存在安全问题,且批次间存在差异。固体试剂与溶液相试剂的管式反应器能够实现有机镁试剂的连续流制备。报道了使用镁金属和氯化锂的分层填充床柱来合成高浓度的快速格氏试剂。展示了一种低成本的豆荚式合成器原型,它包含一次性预填充的全氟化物小柱和试剂袋,用于在实验室规模上自动按需合成碳、氮和氧的快速镁碱。这一概念将在探索规模上提供获取新鲜有机镁试剂的途径,并且这样做将独立于操作人员在流动化学和/或有机金属化学方面的经验。