Standardization and Control of Grignard Reactions in a Universal Chemical Synthesis Machine using online NMR.
Standardization and Control of Grignard Reactions in a Universal Chemical Synthesis Machine using online NMR.
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DOI：
10.1002/anie.202106323
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发表时间：
2021-10-18
期刊：
影响因子：
--
通讯作者：
Emmerling F
中科院分区：
文献类型：
--
作者：
Bornemann-Pfeiffer M;Wolf J;Meyer K;Kern S;Angelone D;Leonov A;Cronin L;Emmerling F
化学文献的一个大问题是它在精确的操作参数方面没有标准化，并且在没有专业知识的情况下很难进行真实的时间校正。缺乏背景意味着难以重复，因为许多步骤都是模糊的，因此依赖于隐性知识。在这里，我们提出了在线NMR集成到一个自动化的化学合成机（CSM又名。能够使用通用编程语言进行小分子合成的“Chemputer”），以允许自动分析和动态调整反应。该系统进行了验证和基准，通过使用格氏反应，这是因为它们在合成中的重要性选择。使用在线NMR对系统进行真实的实时监测，并在反应期间连续测量光谱。这表明，在Chemputer中进行的合成可以响应于反馈而动态控制，从而根据用户需求优化反应条件。通过在线NMR扩展了通用化学合成平台，以允许在运行中调整编码的反应。该方法被证明对类的格氏反应，在苛刻的条件下显示出强大的分析结果。真实的实时过程分析和直接反馈控制算法的使用增强了考虑现有偏差的可用合成公式的可用性。
A big problem with the chemistry literature is that it is not standardized with respect to precise operational parameters, and real time corrections are hard to make without expert knowledge. This lack of context means difficult reproducibility because many steps are ambiguous, and hence depend on tacit knowledge. Here we present the integration of online NMR into an automated chemical synthesis machine (CSM aka. “Chemputer” which is capable of small‐molecule synthesis using a universal programming language) to allow automated analysis and adjustment of reactions on the fly. The system was validated and benchmarked by using Grignard reactions which were chosen due to their importance in synthesis. The system was monitored in real time using online‐NMR, and spectra were measured continuously during the reactions. This shows that the synthesis being done in the Chemputer can be dynamically controlled in response to feedback optimizing the reaction conditions according to the user requirements. A universal chemical synthesis platform was extended by online NMR to allow adjustments of the encoded reactions on the fly. The approach was demonstrated on the class of Grignard reactions showing robust analytical results under harsh conditions. Real‐time process analytics and the use of straightforward feedback control algorithm enhance the usability of available synthesis formula considering existing deviations.
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影响因子：
18.3
作者：
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Buchwald, Stephen L.
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