Electrospray and Leidenfrost droplet accelerated reactions were used as a predictive tool for estimating the outcome of microfluidic synthesis as demonstrated by Wleklinski et al. Rapid analysis by electrospray-mass spectrometry (ESI-MS) also provided immediate feedback on reaction outcomes in flow reactions. Significant reaction acceleration was observed in electrospray relative to the corresponding bulk reaction. This rapid reaction screening and analysis method has allowed for the detection of previously unreported outcomes in the reaction between 5-chloro-2-(methylamino)benzophenone and haloacetyl chloride (halo = Cl or Br) in the continuous synthesis of diazepam. In our current study, a more detailed extension of the previous work, we report acceleration factors that are solvent dependent; additional byproducts that were observed on the microfluidic scale that were absent in the droplet reactions. Gaining insight from this combined droplet and microfluidic screening/rapid ESI-MS analysis approach, we have helped guide the synthesis of diazepam and showcased the potential of this method as a reaction optimization and discovery tool. Informed by these new insights, diazepam was synthesized in a high-yield two-step continuous flow process.

中文翻译：

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液滴加速反应筛选引导的地西p多步流合成，并从快速质谱分析中获得机理上的见解

电喷雾和莱顿弗罗斯特液滴加速反应被用作预测微流体合成结果的预测工具，如Wleklinski等人所证实。通过电喷雾质谱（ESI-MS）进行的快速分析还提供了有关流动反应中反应结果的即时反馈。相对于相应的本体反应，在电喷雾中观察到显着的反应加速。这种快速的反应筛选和分析方法已经可以检测出在连续合成地西epa中5-氯-2-（甲基氨基）二苯甲酮与卤代乙酰氯（卤代= Cl或Br）之间的反应中以前未曾报道过的结果。在我们当前的研究中，对先前工作进行了更详细的扩展，我们报告了取决于溶剂的加速因子。液滴反应中没有的在微流体规模上观察到的其他副产物。从这种结合的液滴和微流体筛选/快速ESI-MS分析方法中获得的见识，我们帮助指导了地西epa的合成，并展示了该方法作为反应优化和发现工具的潜力。有了这些新见识，就可以在高产率的两步连续流工艺中合成地西epa。