Aldehydes, Amides, and Nitriles to Amines

A popular and effective method for converting aldehydes to amines is through a reductive amination protocol. Typically, the aldehyde and amine react to form an intermediate imine or imininm ion and then a reducing agent (i.e., sodium triacetoxyborohydride) is added to carry out the reduction of the intermediate species to afford the amine. The reaction is accelerated in the presence of acetic acid (0.1 -3 equivalents). Reviews (a) Baxter, E. W. Reitz, A. B. Org. React. 2002, 59, 1-714. (b) Hutchins, R. O. In Comprehensive Organic Synthesis Trost, B. M. Fleming, I., Eds. Pergamon Press Oxford, U. K., 1991 Vol. 8, Chapter 1.2 Reduction of C=N to CHNH by Metal Hydrides, pp. 25-54. 

2 Lithium Aluminum Hydride Reduction of an Amide See section 4.3.1 for a description of lithium aluminum hydride (LAH). 

A solution of LAH (1.0 M in ether, 36.5 mL, 36.5 mmol) was cooled to 0 °C, and a solution of the cyanoethyl indole (2.78 g, 16.3 mmol) was added slowly. Then, the solution was heated at reflux for 3 h. It was cooled to 0 °C and quenched by dropwise addition of water (20 mL) followed by 1 N sodium hydroxide (40 mL). The phases were separated, and the aqueous phase was extracted with ether. The combined organic phases were washed with brine and then dried (potassium hydroxide). Evaporation of the solvent gave 2.6 g (92%) of homotryptamine as a yellow oil, which solidified on standing. The hydrochloride was prepared by dissolving the amine in a minimum of ethanol and then a saturated solution of hydrogen chloride in ether was added until no additional salt formation was observed. The hydrochloride was recrystallized from ethanol. 

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