Rapid reduction of nitriles to primary amines with nickel boride at ambient temperature

Article abstract of DOI:10.1081/SCC-120003619

Reduction of a variety of nitriles to their corresponding primary amines can be achieved with nickel boride generated in situ in dry ethanol at ambient temperature. The reductions are very rapid and chemoselective.

Full text of DOI:10.1081/SCC-120003619

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RAPID REDUCTION OF NITRILES TO PRIMARY AMINES
WITH NICKEL BORIDE AT AMBIENT TEMPERATURE
Jitender M. Khurana a & Gagan Kukreja a
a Department of Chemistry, University of Delhi, Delhi, 110 007, India
Version of record first published: 16 Aug 2006.
To cite this article: Jitender M. Khurana & Gagan Kukreja (2002): RAPID REDUCTION OF NITRILES TO PRIMARY AMINES WITH
NICKEL BORIDE AT AMBIENT TEMPERATURE , Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:8, 1265-1269
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SYNTHETIC COMMUNICATIONS, 32(8), 1265–1269 (2002)
RAPID REDUCTION OF NITRILES TO
PRIMARY AMINES WITH NICKEL
BORIDE AT AMBIENT TEMPERATURE1
*
Jitender M. Khurana and Gagan Kukreja
Department of Chemistry, University of Delhi,
Delhi-110 007, India
ABSTRACT
Reduction of a variety of nitriles to their corresponding
primary amines can be achieved with nickel boride generated
in situ in dry ethanol at ambient temperature. The reductions
are very rapid and chemoselective.
Sodium borohydride is a milder reducing agent than lithium alu-
minium hydride (LAH), is comparatively inexpensive, easier to handle
and can also be employed in protic solvents.2 Whereas LAH offers little
selectivity in reductions, sodium borohydride does not normally reduce
groups like ester, nitro, amides and nitriles. The reducing behaviour of
sodium borohydride undergoes a drastic change with the addition of tran-
sition metal salts.3 Among these, Ni(II) salts have drawn wide attention in
the modification of sodium borohydride reactivity.4 Nickel boride, pre-
pared in situ, was initially used as a catalyst for various reductions
under hydrogen atmosphere. Nickel boride has been reported as a catalyst
*Corresponding author.
1265
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1266
KHURANA AND KUKREJA
in the reduction of nitriles under hydrogen atmosphere.5 The yields are
very poor even after prolonged reaction times e.g., only 56% of benzoni-
trile was reduced under hydrogen atmosphere (30 psi) after 48 h using
nickel boride as catalyst. The focus has shifted more recently to its appli-
cations as a reducing agent rather than as a catalyst.6 Nickel boride, pre-
pared under different conditions, is reported to behave differently in its
reactions. Recently Caddick et al.7 have reported that nitriles are reduced
to secondary amines with nickel boride generated in situ from nickel (II)
chloride and sodium borohydride. Primary amines can be obtained only as
protected primary amines by adding trapping agents like acetic anhydride
and di-tert-butyl bicarbonate.
We report herein a simple and convenient procedure for the reduction
of the robust cyano group in aromatic nitriles 1 to primary amines 2 directly
in high yields with nickel boride at ambient temperature. The nickel boride
was generated in situ from dry nickel(II) chloride and sodium borohydride
and the reductions were carried out in dry ethanol. The reductions are very
rapid and are complete in ꢀ5 min, as monitored by thin layer chromatog-
raphy, using 1 : 1 : 3 molar ratio of substrate to nickel(II) chloride to sodium
borohydride, Eq. (1).
(1)
Our results are summarised in Table 1. Reductions carried out with
hydrated NiCl2 and/or 95% ethanol gave lower yields of the correspond-
ing primary amines. There was very little reduction of benzonitrile with
sodium borohydride alone even after 24 h and also benzonitrile was recov-
ered unchanged when treated with nickel(II) chloride only. The reductions
are thus undoubtedly proceeding due to the involvement of both reagents
i.e., the nickel boride formed in situ. Ethanol is the solvent of choice and
primary amines are obtained by a simple work-up procedure. Reductions
were slower in tetrahydrofuran and dimethylformamide, and also
yielded a complex mixture with lower yields of the corresponding primary
amines.
Small amounts of secondary amines 3 were also formed in the reac-
tions. The formation of secondary amines could not be eliminated com-
pletely despite attempting reactions under different conditions.8 The
secondary amines were formed from the primary amines obtained initially
as confirmed by an independent reaction of benzyl amine with nickel boride.

REDUCTION OF NITRILES TO PRIMARY AMINES
1267
Table 1. Reduction of 1 with Nickel Boridea in EtOHb at
Ambient Temperaturec
Yieldd (%)
Entry 1
Ar
2
3
a
b
c
d
e
f
g
h
i
Ph
2-MeC6H4
4-MeC6H4
4-ClC6H4
82
84
82
85
82
86
81
64
77
83
70
85
81
82
79
81
72e
72
6
7
8
7
7
5
7
6
6
6
3
5
9
7
8
7
7e
2-ClC6H4
2,4-di-ClC6H3
3-BrC6H4
4-MeOC6H4
2-MeOC6H4
2,4-di-(MeO)C6H3
3,4-di-(MeO)C6H3
3,4-OCH2OC6H3
4-Me2NC6H4
1-C10H8
j
k
l
m
n
o
p
q
r
C6H5CH¼C(Ph)
C6H5CH¼CH
4-O2NC6H4
C6H5CH2
11
aMolar ratio–Substrate : NiCl2 : NaBH4 ¼ 1 : 1 : 3.
b20 ml of dry ethanol/g of substrate was used.
cThe starting material disappeared after 5 min. Reactions
were invariably worked up after ꢀ15 min.
dIsolated yields of chromatographically pure compounds;
products analysed by IR, NMR and/or Mass spectra.10
eThe products isolated are p-aminobenzylamine and
di( p-aminobenzyl)amine.10
However, formation of small amounts of secondary amines by other path-
ways also cannot be ruled out. Nickel boride loses its activity with time since
benzonitrile (1a) and p-chlorobenzonitrile (1d) were recovered unchanged
(2h) when treated with a preformed solution of nickel boride after 72 h. The
reductions are chemoselective as halo (chloro and bromo), methoxy,
dimethylamino, olefinic and naphthyl groups were unaffected under our
reaction conditions. It is thus obvious again that reaction products of
nickel boride reductions can be varied by changing stoichiometries and/or
reaction solvent and temperature.

1268
KHURANA AND KUKREJA
EXPERIMENTAL
Dry EtOH was prepared by the known procedure. NaBH4 (E. Merck)
was used in all the reactions. NiCl2ꢁ6H2O (Qualigens) was used after drying
in a nickel crucible in an oven at ꢀ250ꢂC until it turned golden yellow. It
was powdered and stored in a vacuum desiccator. Nitriles 1a, 1b and 1r were
obtained from commercial sources and were distilled before use. Nitriles
1c–q were prepared from their corresponding aldehydes by treatment with
hydroxylamine hydrochloride according to the reported procedure.9 The
IR spectra were recorded on a Perkin Elmer FT-IR spectrum 2000 and
NMR spectra were recorded on Hitachi FT-NMR model R-600 (60 MHz)
with TMS as the internal standard. Mass spectra were recorded on a Jeol
JMS D 300 spectrometer using the electron impact method (70 eV).
In a typical procedure, in a 100 ml conical flask mounted over a mag-
netic stirrer, fitted with reflux condenser and a mercury trap, was placed a
mixture of nitrile (9.8 mmol), anhyd. nickel (II) chloride (9.8 mmol) and dry
ethanol (20 ml). Sodium borohydride (29.4 mmol) was added very cautiously
while stirring the solution vigorously. The progress of the reaction was
monitored by TLC using benzene : ethyl acetate (90 : 10, v/v) as eluent.
After the complete disappearance of the nitrile (ꢀ5 min), the reaction mix-
ture was filtered through a celite pad after ꢀ15 min. The filtered nickel
boride precipitate was washed with ethanol (2 ꢃ 10 ml). The combined fil-
trate was diluted with water (150 ml) and extracted with ethyl acetate
(3 ꢃ 10 ml). The combined extract was dried over anhyd. MgSO4, filtered
and concentrated on a rotary vacuum evaporator. After drying under
vacuum, the product was purified by column chromatogaphy over silica
gel (20 ꢃ 2 cm; 100–200 mesh) using benzene : ethyl acetate as the eluent.
Eluate was concentrated under reduced pressure to afford the products
which were analysed by IR, NMR and mass spectra as most of these are
known products.10
ACKNOWLEDGMENT
Financial support by CSIR (Project No. 1 (1567)-99) EMR II,
NewDelhi, India for the above project is gratefully acknowledged.
REFERENCES
1. The work was presented at Annual Convention of Chemists. Haridwar,
India, Nov. 2000, Handbook, pp. C4.

REDUCTION OF NITRILES TO PRIMARY AMINES
1269
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8. Reactions of p-Chlorobenzonitrile (1d) were carried out by changing
solvent, temperature and the molar ratios of substrate to nickel
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9. Van Es, T. J. Chem. Soc. 1965, 1564.
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Received in the UK March 5, 2001