Reductive amination of aldehydes by NaBH4 in the presence of NaH2PO4.H2O

Article abstract of DOI:10.13005/ojc/300138

Thereductive aminationofa variety of aldehydes withanilines has been carried out by NaBH₄/NaH₂PO₄.H₂O as new reducing systemswithin 55-100 min in THFunder reflux conditionsin high to excellent yields of products (85-92%).

Full text of DOI:10.13005/ojc/300138

ISSN: 0970-020 X
CODEN: OJCHEG
2014, Vol. 30, No. (1):
Pg. 299-302
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Reductive Amination of Aldehydes by
NaBH4 in the Presence of NaH2PO4.H2O
HOJJAT AREFI and DAVOOD SETAMDIDEH*
Department of Chemistry, College of Sciences, Mahabad Branch,
Islamic Azad University, Mahabad, Iran.
*Corresponding author e-mail: d.setamdideh@mahabad-iau.ac.ir
http://dx.doi.org/10.13005/ojc/300138
(Received: December 30, 2013; Accepted: February 01, 2014)
ABSTRACT
Thereductive aminationofa varietyof aldehydes withanilines has been carried out by NaBH4/
NaH2PO4.H2Oas new reducing systemswithin 55-100 min in THFunder reflux conditionsin high to
excellent yields of products (85-92%).
Key words: NaBH4, NaH2PO4.H2O, Reductive amination, Aldehydes, Amines.
INTRODUCTION
system such as: NaBH4/cellulose sulfuric Acid/
EtOH1, NaBH4-amberlyst15 2, NaBH4-silica chloride3,
NaBH4-silica-gel-supported sulfuric acid , NaBH4-
4
The reduction of nitro, cyano, azide,
carboxamide compounds is common routes for
the synthesis of amines. Also, this goal has been
achieved by the alkylation of amines.These methods
for the preparation of secondary amines are
often problemssuch as harsh reaction conditions,
overalkylation, low chemical selectivity and generally
poor yields. Other approach is reductive amination
reaction in a single operationi.ereductive amination.
The reductive aminationhas been carried out
by sodium borohydride under different reducing
H3PW12O40 5, NaBH4/guanidine hydrochloride /H2O 6,
NaBH4/Bronsted acidic ionic liquid (1-butyl-3-methyl
imidazoliumtetrafluoroborate [(BMIm)BF4]) 7, NaBH4
8
9
or LiAlH4/LiClO4/diethyl ether NaBH4-PhCO2H ,
NaBH4-NiCl210,Ti(O-i-Pr)4-NaBH411, NaBH4-wet-clay-
microwave 12, NaBH4/Mg(ClO4)213, NaBH4/B(OH)3
14
or Al(OH)3 NaBH4/Ga(OH)315.In continuing our
efforts for the development of new reducing systems
16-26,in this context, we have carried outthe reductive
amination reaction of aldehydes with anilinesby
NaBH4/NaH2PO4.H2O system in THF.

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AREFI & SETAMDIDEH, Orient. J. Chem., Vol. 30(1), 299-302 (2014)

AREFI & SETAMDIDEH, Orient. J. Chem., Vol. 30(1), 299-302 (2014)
301
RESULTS AND DISCUSSIONS
shown in Table 1. The influence of NaH2PO4.H2O is
not clear but we observed sodium borohydride slowly
The model reaction has been selected by is liberated hydrogen gas in situ in the presence
reductive amination of benzaldehyde with aniline. of NaH2PO4.H2O. Consequently, the generated
This reaction was performedwith different molar ratio molecular hydrogen combines with more easily
of the benzaldehyde/aniline/NaH2PO4.H2O/NaBH4in hydride attack, thus accelerates the rate of reduction
different solvents for the selection of appropriate reaction.
conditions.Experiments have been shown that using
1eq. of NaH2PO4.H2Oin THF (3 mL) under reflux
conditionsis the best conditions to complete the
reductive amination of benzaldehye (1 mmol) and
ExPERIMENTAL
1
IR and H NMR spectra were recorded
aniline (1 mmol) to N-benzylaniline. The reductive on PerkinElmer FT-IR RXI and 400 MHz Bruker
amination completes within 55 min with 92% yields spectrometers, respectively. The products were
of product as shown in scheme 1.
characterized by their 1H NMR or IR spectra and
By using the various structurally different aldehydes comparison with authentic samples (melting or
and anilines, the efficiency of this protocol was boiling points). TLC was applied for the purity
further examined. Experiments have been shown determination of substrates, products and reaction
the correspondingsecondary amines were obtained monitoring over silica gel 60 F254 aluminum sheet.
in excellent yields (85-92%) within 55-100 min as
CHO
NH2
NaBH4 (1 mmol), NaH2PO4.H2O (1 mmol)
THF (3 mL), reflux, 55 min, 92%
+
CH2 NH
Scheme 1:
Reductive amination of banzaldehyde and
aniline with NaBH4/NaH2PO4.H2O system (typical
procedure)
CONCLUSION
In this context, we have shown that the
NaBH4/NaH2PO4.H2O3 as reducing system is efficient
for the reductive amination of a variety of aldehydes
and anilines to their corresponding secondary
amineas. Reduction reactions were carried out
with NaBH4 (1 mmol) and NaH2PO4.H2O(1 mmol)
in THFunder reflux conditions.Highefficiency of the
reduction reactions and easy work-up procedure
makes as an attractive new protocol for reductive
amination of aldehydes.
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
NaH2PO4.H2O(0.14, 1 mmol) was preparedin THF
(3 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 55 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.l66
g, 92% yield, Table 1, entry 1).
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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