An Eight-Step Continuous-Flow Total Synthesis of Vitamin B1
Meifen Jiang,
Minjie Liu,
Weijian Li,
Yingqi Xia,
Fen-Er Chen
Affiliations
Meifen Jiang
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China; Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, Shanghai 200433, China; School of Science, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China
Minjie Liu
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China; Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, Shanghai 200433, China
Weijian Li
Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, Shanghai 200433, China
Yingqi Xia
Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, Shanghai 200433, China
Fen-Er Chen
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China; Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, Shanghai 200433, China; School of Science, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China; Corresponding author.
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 B1 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 B1 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.
