Enzyme-electrochemical continuous flow cascades synthesis of substituted benzimidazoles

• Ting-Ting Shi^a,b
• Shu-Zhan Wang^a
• Zhao Yang^c
• Yilin Wang^a
• Chengkou Liu^a
• Wei He^*a
• Zheng Fang^*a,d
• Kai Guoa^d

• ^aCollege of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, P. R. China.
• ^bDepartment of Chemistry, Bengbu Medical College, 233030, P. R. China.
• ^cSchool of Engineering, China Pharmaceutical University, No.639 Longmian Avenue, Nanjing 211198, China
• ^dState Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 211816, P. R. China.

A green and efficient method for the synthesis of substituted benzimidazoles has been developed in a two-step continuous flow system. Enzyme-electrochemical cascade reactions between aromatic alcohols with o-phenylenediamines is reported. The reaction was performed under mild reaction conditions with air as “green” oxidant and oxidase as biocatalyst. Alcohols oxidation and substituted benzimidazoles formation were integrated into a single operation which is usually accomplished separately. The scale up experiment was completed successfully in continuous flow system which offers an industrially relevant, practical and efficient method.

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