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Chinese Chemical Letters 19 (2008) 11671170

www.elsevier.com/locate/cclet

Practical reduction of imines by NaBH4/alumina under

solvent-free conditions: An efficient route to secondary amine
Foad Kazemi a,*, Ali Reza Kiasat b, Ebrahim Sarvestani b
a

Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45195, Iran
Chemistry Department, College of Science, Shahid Chamran University, Ahvaz 61357-4-3169, Iran
Received 27 March 2008

Abstract
Sodium borohydride supported on alumina reduces imines to the corresponding secondary amines in high to excellent isolated
yields under solvent-free conditions. Noteworthy is that highly chemoselective reactions were achieved in the presence of other
functional groups such as halogen, nitro, and cyano groups.
# 2008 Foad Kazemi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Imine; Secondary amine; Solvent free; Reduction; Sodium borohydride

Heterogeneous organic reactions have proven useful to chemists in the laboratory as well as in the industrial
context. These reactions are effected by the reagents immobilized on the porous solid supports and have advantages
over the conventional solution phase reactions because of the good dispersion of active reagent sites, associated
selectivity and easier work-up [1,2]. Alumina, an inorganic polymeric material used commonly for column
chromatography, is very interesting in organic solids which are used as support in organic reactions, due to its surface
properties that suggest a very rich chemistry may occur there [3].
From the fundamental point of view, reduction of imines to the corresponding amines represent one of the most
widely used and valuable functional group transformations in synthetic organic chemistry, since amines constitute
important precursors to compounds that are of much interest in pharmaceutical and agricultural industries [4,5]. This
transformation is effected using metal hydrides such as LiAlH4 [6], Bu2SnClH [7], (g-C5H5)2MoH2 [8],
RuHCl(PPh3)3 [9], CaH2/ZnX2 [10], silane/MoO2Cl2 [11] or catalytic hydrogenation [12], mainly under
heterogeneous reaction conditions. However, methods using metal hydrides which have a moisture-sensitive
character should be carried out in a dried organic solvent and/or an inert gas, and in the case of hydrogenation, the
reaction should be undertaken with an expensive catalyst in an anhydrous organic solvent under high pressure. Other
methods such as metallic reagents in an organic solvent [13], electrochemical or enzymatic reductions are of less
general application [14].

* Corresponding author.
E-mail address: kazemi_f@iasbs.ac.ir (F. Kazemi).
1001-8417/$ see front matter # 2008 Foad Kazemi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2008.06.043

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F. Kazemi et al. / Chinese Chemical Letters 19 (2008) 11671170

Sodium borohydride, as a kind of common reducing agent, has been used widely in organic synthesis. There are
several reported in the literature for reduction of imines by sodium borohydride [6,1517] or its modified form such as
Zn(BH4)2 supported on silica gel [18], NaBH3CN [19] or NaBH(OAc)3 in organic solvent [20]. In 2005, a report by
Cao etal. outlined [21] the reduction of imines by sodium borohydride using PEG400 as catalyst. However, many of
these methods involve the use of expensive and stoichiometric amounts of reagents or catalysts, suffer from poor
chemoselectivity, strongly acidic conditions and also require extended reaction times. Therefore, the development of a
new and efficient protocol for this transformation by sodium borohydride under mild and more convenient conditions
is still needed.
1. Experimental
All reduction products are known compounds and are identified by comparison of their physical and spectral data
with those of authentic samples. The required imines were prepared by treatment of the corresponding carbonyl
compounds with the appropriate amines as previously reported procedure [22,23]. NaBH4 and Al2O3 were purchased
from Fluka and Merck. The purity determination of the products and reaction monitoring were accomplished by TLC
on silica gel polygram SILG/UV 254 plates.
1.1. General procedure
Al2O3 (1.40 g) and NaBH4/(0.114 g, 3 mmol) were crushed together in a mortar so as to form an intimate mixture.
A neat imine (1 mmol) and five drops of methanol were added to this mixture. The reaction mixture was ground for
5 min. The progress of reaction was monitored by TLC using etherCCl4. Then the reaction mixture was poured into
ether (10 ml) and filtered through a sintered glass funnel. The fitter cake was washed thoroughly with portions of ether.
The organic layer was dried over anhydrous sodium sulfate and solvent evaporated under reduced pressure to afford
the TLC and 1H NMR pure products in 8098% isolated yields.
2. Results and discussions
In this paper we report more efficient, simple, practical, and mild reduction of imines using NaBH4 supported on
alumina in solvent-free conditions:
ArCHNAr

NaBH4 =Al2 O3

!

grinding 5min

ArCH2 NHAr
8098%

NaBH4 supported on alumina was prepared by simply cogrinding alumina (1.4 g) with NaBH4 (3 mmol) in an
agate mortar. In this simple and efficient method the starting imines were reduced to the corresponding secondary
amines in a mortar with grinding by a pestle in the presence of supported NaBH4 on alumina and little drops of
methanol. The feasibility of the present reduction of imine was first examined using N-benzylideneaniline as a model
substrate. Thus, N-benzylideneaniline (1 mmol) was thoroughly mixed with NaBH4/Al2O3 (3 mmol based on
NaBH4, 1.514 g) and five drops of methanol in a mortar with a pestle and in an ambient air environment at room
temperature and N-phenylbenzylamine was obtained in 85% yield within 5 min. It can be emphasized that the
reaction is clean, the work-up is straightforward and, from economical and environmental points of view, absence of
solvent is favorable.
With the first successful result in hand, reduction of other imines with NaBH4/Al2O3 was carried out under similar
reaction conditions. The results obtained are presented in Table 1. As shown in the table, highly chemoselective
reduction of imines was achieved in the presence of other sensitive functional groups such as halogen, nitro, and cyano
groups. It should be pointed out that in the absence of Al2O3, the reaction was sluggish and a considerable amount of
starting material was recovered unchanged. It is noteworthy that, an attempted gram scale reduction of Nbenzylideneaniline resulted in the formation of N-phenylbenzylamine without appreciable decrease in the yield as
compared to that obtained by the small scale experiment.
In conclusion, reduction of imines with NaBH4/Al2O3 in solvent-free conditions is a rapid, manipulatively simple,
selective and environmentally friendly protocol when compared to the conventional solution phase or heterogeneous
condition, and should utility in contemporary organic synthesis.

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Table 1
Facile reduction of various imines to the corresponding secondary amine by NaBH4/alumina under solvent free
No

Substrate

Product

Yield (%)a,b,c

85

80

98

98

85

98

95

92

a
b
c

Products were identified by compares of their physical and spectral data with those of authentic samples.
Isolated yields.
Molar ratio of imine to NaBH4 was 1:3.

Acknowledgment
Partial support for this work by Chamran University Research Council are gratefully acknowledged.
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