
八步连续流全合成维生素B1工艺研究
Meifen Jiang, Minjie Liu, Weijian Li, Yingqi Xia, Fen-Er Chen
工程(英文) ›› 2024, Vol. 32 ›› Issue (1) : 226-232.
八步连续流全合成维生素B1工艺研究
An Eight-Step Continuous-Flow Total Synthesis of Vitamin B1
维生素B1作为一种抗利尿和抗氧化剂被广泛应用于医疗保健和食品行业,以维持神经传导、心脏和胃肠道的正常功能。本研究报道了由市售2-氰基乙酰胺进行的维生素B1的八步连续流全合成工艺。本研究提出的连续流工艺基于化学、工程和设备设计的创新基础,与间歇釜式工艺相比,生产的性能和安全性均有所提高。本文使用各种微通道流反应器、微混合器、连续分离设备和连续过滤器等装置,对连续流合成工艺中的问题和挑战进行了精确的研究和控制,包括混合、意外堵塞、溶剂切换、放热反应和避免副反应等。维生素B1全合成的连续流工艺总停留时间约为3.5小时,产品纯度高,分离产率为47.7%。该八步连续流动技术方案至少涉及绿色化学的六个关键准则。因此,连续流技术的应用对于提高生产安全性、减少废物污染,尤其是提高批量操作的生产效率至关重要。
Vitamin B1 is widely applied in the healthcare and food industry as an antineuritic and antioxidant to maintain the normal functioning of nerve conduction, the heart, and the gastrointestinal tract. This study reports on an integrated eight-step continuous-flow synthesis of vitamin B 1 from commercially available 2-cyanoacetamide. The proposed continuous-flow process is based on advances in chemistry, engineering, and equipment design, and affords improved performance and safety compared with batch-mode manufacturing. Several challenges were precisely investigated and controlled, including mixing, unexpected clogging, solvent switches, an exothermic reaction, and the prevention of side reactions, using various micro-channel flow reactors, mixers, separators, and continuous filters. Vitamin B 1 was produced with a separated yield of 47.7% and high purity, with a total residence time of about 3.5 h. This eight-step continuous-flow protocol enables technology involving up to six of the key principles of green chemistry. Hence, the application of flow technology is of paramount importance for improving security, reducing waste, and, in particular, improving the efficiency of batch operations that require several days for manufacturing.
Vitamin B1 / Continuous-flow synthesis / Micro-reactor / Continuous manufacturing
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