NaBH4/C: A Convenient System for Reductive Amination of Aldehydes

Abstract

In this context, NaBH₄ in the presence of activated charcoal has been used for thereductive aminationofa varietyof aldehydes withanilines. The reductive amination reactions have been performed within 60-100 min in THFunder reflux conditionsin high to excellent yields of products (85-90%).

Introduction

The reductive aminationreaction is a suitable procedure for the preparation of amines from their corresponding of aldehydes. Because, other approaches such as: the reduction of nitro, cyano, azide, carboxamide compounds or the alkylation of amines are often problemssuch as: harsh reaction conditions, overalkylation, low chemical selectivity and generally poor yields. The reductive aminationreactionhas been carried out by sodium borohydridewith different reducing system^1-15.But, in continuing our efforts for the development of new reducing systems ^16-28,in this context, we have reported the reductive amination reaction of aldehydes with anilines by NaBH₄/C system in THF.

Results and Discussions

In the past, we have distributed some application of activated charcoal as catalyst in different reducing system such as: NaBH₄/C for the reduction of carbonyl compounds²⁷and the reduction of nitro arenes²⁸.Recently, we have reported Zn(BH₄)₂/C is an efficient reducing system for the reduction of carbonyl compounds²⁰. Here in, we have used NaBH₄/C as convenient system for reductive amination of aldehydes with anilines.For this goal, the model reaction has been performed by reductive amination of benzaldehydeand aniline. This reaction was carried outwith different molar ratio of the benzaldehyde/aniline/charcoal/NaBH₄in different solvents for the optimazition reaction conditions. Our experiments have been shown that using 0.5 gof activated charcoalin THF (5 mL) under reflux conditions is the best conditions to complete the reductive amination of benzaldehye (1 mmol) and aniline (1 mmol) to N-benzylaniline. The reductive aminationwas completed within 60 min with 85% yields of product as shown in scheme 1.

Scheme 1

The various structurally different aldehydes and anilines have been used by this reducing system.Experiments have been shown the correspondingsecondary amines were obtained in excellent yields (85-90%) within 60-100 min(Table 1); therefore the efficiency of this protocol was further examined for the reductive amination of aldehydes. The influence of activated charcoal is not clear but we have reported ^26-27 sodium borohydride is slowly decomposed by activated charcoal. Consequently, it is liberated hydrogen gas in situ. Thus, the generated molecular hydrogen accelerate the reduction reaction.

Table 1. Reductive Amination of Aldehydes (1 mmol) with Anlines (1 mmol) by NaBH4 (1 mmol) in the presence of charcoal(0.5 g) in THF (5 mL) under reflux conditions.

Experimental

The products were characterized by their ¹H NMR (400 MHzBruker)or IR (PerkinElmer FT-IR RXI) and comparison with authentic samples (melting or boiling points). TLC was applied for the purity determination of substrates, products and reaction monitoring over silica gel 60 F₂₅₄ aluminum sheet.

Reductive amination of banzaldehyde and aniline with NaBH₄/Charcoal system (typical procedure)

In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a solution of benzaldehyde (0.106 g, 1 mmol), aniline (0.093 g, 1 mmol) and activated charcoal(0.5 g) was preparedin THF (5 mL). Then the NaBH₄ (0.036 g, 1 mmol) was added to the reaction mixture and stirred under reflux conditions. TLC monitored the progress of the reaction (eluent; CCl₄/Ether: 5/2). The reaction was filtered after completion within 60 min. Evaporation of the solvent and short column chromatography of the resulting crude material over sil­ica gel (eluent; CCl₄/Ether: 5/2) afforded the N-benzylaniline (0.l53 g, 85% yield, Table 1, entry 1).

Conclusion

In this research, we have shown that the NaBH₄/charcoalis convenient system for the reductive amination of a variety of aldehydes and anilines to their corresponding secondary amines. The reduction reactions were accomplished with NaBH₄ (1 mmol) and activated charcoal (0.5 g) in THFunder reflux conditions.High efficiency of the reduction reactions and easy work-up procedure makes as an attractive new protocol for reductive amination of aldehydes.

Acknowledgements

The authors gratefully appreciated the financial support of this work by the research council of Islamic Azad University branch of Mahabad.

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