Continuous flow for enantioselective cyanohydrin synthesis

• Published in: Catalysis science & technology Vol. 12; no. 1; pp. 3356 - 3362
• Main Authors: Stradomska, Dominika, Coloma, José, Hanefeld, Ulf, Szyma ska, Katarzyna
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 23.05.2022
• Subjects: Benzaldehyde; Chemical synthesis; Continuous flow; Enantiomers; Enzyme activity; Enzymes; Flow stability; Flow velocity; Microreactors; Shear forces; Structural hierarchy; Substrates
• ISSN: 2044-4753; 2044-4761
• DOI: 10.1039/d2cy00054g

Enantiomerically pure cyanohydrins are of great importance in the chemical and pharmaceutical industries. Their synthesis is possible through the use of highly selective hydroxynitrile lyases. In this work, an R -selective hydroxynitrile lyase ( At HNL) from Arabidopsis thaliana was immobilized inside a silica microreactor with a tortuous and hierarchical pore structure. After immobilization, the enzyme activity was tested for benzaldehyde 1a , and its analogs 4-fluorobenzaldehyde 1b , 4-methoxybenzaldehyde 1c and 4-(trifluoromethyl)benzaldehyde 1d . With their different degrees of reactivity they also display a different susceptibility to the racemic chemical background reaction. It was shown that the use of a flow microreactor suppressed the background reaction even for the most susceptible substrate 1d . Furthermore, the use of a flow microreactor enabled high substrate conversion (9095%) while maintaining a high enantiomeric excess (90-98%) with residence times of 3 to 30 min. The productivity, which depended on substrate reactivity and flow rate, was evaluated by space-time-yield (STY) and reached a value from 60 g L −1 h −1 to 1290 g L −1 h −1 . Additionally it was demonstrated that the stability of the immobilized enzyme depends on the flow rates used and thus on the shear forces acting inside the microreactor and interfacial effects associated with them. Enantiomerically pure cyanohydrins are of great importance in the chemical and pharmaceutical industries and can be efficiently obtained under flow-through conditions using structured microreactors.