Organic Chemistry Portal



Sodium Hypophosphite as a Bulk and Environmentally Friendly Reducing Agent in the Reductive Amination

Fedor Kliuev, Anton Kuznetsov, Oleg I. Afanasyev, Sofiya A. Runikhina, Ekaterina Kuchuk, Evgeniya Podyacheva, Alexey A. Tsygankov and Denis Chusov*

*A.N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, Moscow 119991, Russian Federation, Email:

F. Kliuev, A. Kuznetsov, O. I. Afanasyev, S. A. Runikhina, E. Kuchuk, E. Podyacheva, A. A. Tsygenkov, D. Chusov, Org. Lett., 2022, 24, 7717-7721.

DOI: 10.1021/acs.orglett.2c02807

see article for more reactions


The nontoxic, stable, environmentally benign, and easily available NaH2PO2 promotes reductive amination with E factors around 1. The reaction demonstrated a great compatibility with a wide range of functional groups.

see article for more examples

proposed mechanism

scale-up experiment

General procedure for the substrate scope study

A 12 mL glass tube with a screw-cap wrapped by sealing tape (to avoid oxidation of chemicals in air, but on a scale-up experiment there is no difference between sealing with a septum and refluxing) was charged with stirring bar, sodium hypophosphite monohydrate (0.5 equiv., 0.5 mmol), amine (1.25 equiv., 1.25 mmol) and carbonyl compound (1 equiv., 1 mmol). The tube was placed into a preheated oil bath (at the indicated temperature) and stirring was continued for 19 h. Then the tube was cooled down to the room temperature. The reaction mixture was washed with 3 mL of DCM, placed into an ultrasonic bath for 10 minutes and then centrifugated (10 minutes, 8000 rpm). The residue was purified by column chromatography or vacuum distillation.

Key Words

reductive amination, sodium hypophosphite, green chemistry

ID: J54-Y2022