Reduction of Phenylacetonitriles to Phenethylamines
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Optimum Reduction of Nitriles Using NaBH4 and CoCl2 in 2:1 THF:H2O
The following is a representative procedure. A pink solution of CoCl2.6H2O (0.445 g, 1.87 mmol) and benzonitrile (1.92g, 18.6 mmol) in THF (66 ml, distilled) and water (33 ml) was stirred vigorously and cooled intermittently with an ice-water bath while NaBH4 (1.40 g, 37.1 mmol) was added in portions over 8 min. The reaction was exothermic, producing a black precipitate and copious quantities of hydrogen. TLC analysis after 50 min indicated traces of starting material, so additional NaBH4 (0.41g) was added. After a total time of 2h 28% NH4OH solution (2ml) was added and the mixture transferred to centrifuge tubes. After centrifugation the supernatant (two liquid phases) was decanted and the sediment washed with more of the same solvent mixture. The combined supernatants were concentrated at reduced pressure to remove the bulk of THF, then the aqueous residue was extracted with 4 x 40 ml of DCM. The combined DCM layers were dried (MgSO4) and concentrated to afford benzylamine (1.82g 91%) as a pale oil, identical in every respect with an authentic sample.
Karel: NaBH4/CoCl2 does reduce phenylacetonitriles, but in case of an ortho-substituted substrate (4-bromo-2,5-dimethoxyphenylacetonitrile) my yields were only about 20% (the rest being unreacted nitrile). Using 10 mmol (2.56g) of the nitrile allowed for the recycling of 2.11g after separation of amine product. Instead using AlH3 in THF[2] for the reduction of 4-bromo-2,5-dimethoxyphenylacetonitrile gave a 90% yield of 2C-B.
References
[1] J. Am. Chem. Soc. 108, 67-72 (1986)
[2] J. Am. Chem. Soc. 90, 2927-2938 (1968)
