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Aldehydes or ketones are used to monoalkylate amines by treatment with ammonia or a primary/secondary amine in the presence of a reducing agent such as sodium cyanoborohydride (NaBH₃CN). The carbonyl is attacked by the amine, releasing water to make an iminium ion that is reduced by NaBH₃CN to form a higher substituted amine.

Lab Tips:

NaBHCN is selectively reactive with iminium ions at mildly acidic pH. ^[1] Hydrogen gas over a nickel catalyst can be used to reduce the imine formed from ammonia and a carbonyl compound. ^[2]
An alternative reducing agent is sodium triacetoxyborohydride (NaBH(OAc)₃), which can be used to alkylate primary and secondary amines (including aniline derivatives and amino acid esters). ^[3,4]
Zinc borohydride (Zn(BH₄)₂) in the presence of silica works well for unsaturated aldehydes and ketones. ^[5]
A combination of Zn(BH₄)₂ and ZnCl₂ works well for aromatic aldehydes. ^[6]

_{1. Borch, R. F., Bernstein, M. D., Durst, H. D. Cyanohydridoborate anion as a selective reducing agent. J. Am. Chem. Soc. 1971, 93(12), 2897-2904.
2. McMurry, J. (2000). Organic Chemistry (5th ed.). Pacific Grove, CA: Brooks/Cole.
3. Abdel-Magid, A.F. et al. Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures (1). J. Org. Chem. 1996, 61(11), 3849-3862.
4. Ramanjulu, J. M., Joullie, M. M. N-alkylation of amino acid esters using sodium triacetoxyborohydride. Synth. Commun. 1996, 26(7), 1379-1384.
5. Ranu, B.C., Majee, A., Sarkar, A. One-pot reductive amination of conjugated aldehydes and ketones with silica gel and zinc borohydride. J. Org. Chem. 1998, 63(2), 370-373.
6. Bhattacharyya, S., Chatterjee, A., Williamson, J. S. Reductive amination with zinc borohydride. Safe route to fluorinated benzylamines. Synth. Commun. 1997, 27(24), 4265-4274.}

Reagents: NaBH₃CN, Mildly Acidic Conditions
Reactant: Aldehyde or Ketone, Ammonia or 1°/2° Amine
Product: 1°, 2° or 3° Amine
Type of Reaction: Nucleophilic Addition and Reduction
Bond Formation: C-N

Mechanism

Ammonia (CAS 7664-41-7)

Amine

NaBH₃CN (CAS 25895-60-7)

Acid

Mechanism

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Related Reactions

Related Compounds