REVIEWS
DOI: 10.1002/adsc.201400940
Recent Advances in Transition Metal-Catalyzed Hydrogenation
of Nitriles
Dattatraya B. Bagala and Bhalchandra M. Bhanagea,*
a
Department of Chemistry, Institute of Chemical Technology, Matunga, Mumbai 400 019, India
Fax: (+ 91)-22-24145614; phone: (+ 91)-22-3361-1111/2222; e-mail: bm.bhanage@gmail.com or
bm.bhanage@ictmumbai.edu.in
Received: September 25, 2014; Revised: November 25, 2014; Published online: && &&, 0000
Abstract: Amines are important building blocks pos-
sessing various applications in agrochemicals, the
fine chemical industry, pharmaceuticals, materials
science and biotechnology. The catalytic hydrogena-
tion of nitriles is an important reaction for the one-
step synthesis of diverse amines. However, significant
amounts of side product formation during the course
of the reaction is a major issue. In recent years, an
enormous amount of work has been reported using
both homogeneous and heterogeneous transition
metal complex catalysts for the selective reduction of
nitriles. Transition metal catalysts are the most cru-
cial factor that controls the selectivity in this reac-
tion. Therefore, transition metal catalysts are the
central point of this review. We have also briefly dis-
cussed the effect of reaction parameters, selectivity
to different substrate structures and reaction mecha-
nisms. This review provides an overview of recent
1 Introduction
Amines are versatile intermediates and precursors in
the synthesis of various natural products, pharmaceut-
icals, dyes, pigments, agrochemicals and polymers.[1–4]
Among the amines, the terminal primary amines are
the most useful, but their selective synthesis is a chal-
lenging task due to their high reactivity. In particular,
the selective catalytic hydrogenation of nitriles repre-
sents an atom-economic and valuable route to pri-
mary amines. However, the reduction of nitriles to
the corresponding amines has been less investigated
so far compared to reductions of C=C, C=O, C=N
and NO2 bonds. This is primarily due to the high
redox potential of nitriles compared to other carbox-
ylic acid derivatives and the low C CN bond dissocia-
tion energy, which leads to undesired reductive decya-
nations, side reactions via fragmentation to alkyl radi-
cals and cyanide anions; and the instability of imine/
iminium intermediates under the reaction conditions,
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developments in transition metal-catalyzed nitrile re-
duction along with examples which highlight its vast
potential in organic transformations.
1 Introduction
2 Catalytic Reductions of Nitriles
2.1 Ruthenium
2.2 Rhodium Complexes
2.3 Palladium Complexes
2.4 Iridium Complexes
2.5 Platinum Complexes
2.6 Other Transition Metal Complexes
3 Conclusion and Outlook
Keywords: amines; chemoselectivity; heterogeneous
catalysis; homogeneous catalysis; hydrogenation; ni-
triles
which results in alcoholysis, transimination or reduc-
tive polymerization pathways.[5]
Conventionally, nitriles are reduced using stoichio-
metric amounts of metal hydrides,[6,7] either lithium
aluminium hydride (LiAlH4) at room temperature,
sodium borohydride (NaBH4) at higher temperatures
or in the presence of heterogeneous catalysts based
on nickel,[8] palladium,[9] cobalt,[10] etc. Metal hydride
reagents are effective, however; they are not environ-
mentally benign due to the coproduction of stoichio-
metric amounts of waste metal salts. The heterogene-
ous metal catalysts demonstrate low selectivity to-
wards primary amines and significant amounts of sec-
ondary and tertiary amines are formed.[11] It also has
limitations with respect to functional group tolerance
and the use of excess ammonia needed for high che-
moselectivity.[12]
Hydrogenation of nitriles to primary amines (A) is
usually accompanied by the formation of secondary
amines (B) and even tertiary amines (C) as shown in
Scheme 1. The reaction of the primary amine 3 with
1
 Dattatraya B. Bagal and Bhalchandra M. Bhanage
Dattatraya B. Bagal complet-
ed his M.Sc. degree in organ-
ic chemistry from the Univer-
sity of Pune in 2008. After
working as a research chem-
ist at Sai Life Sciences Ltd.
Pune, India for two years, he
moved to the Institute of
Chemical Technology (for-
merly UDCT), Mumbai in
2010 to begin his Ph.D. pro-
gramme under the supervi-
sion of Prof. Bhalchandra M. Bhanage. His Ph.D. re-
search focuses on the development of greener cata-
lytic systems for hydrogenation reactions. In 2012,
he was awarded a DAAD research fellowship to
carry out research at the University of Regensburg,
Germany with Prof. Oliver Reiser. At Regensburg
University he was engaged in the development of
new chemical reactions using visible light photore-
dox catalysis, with a particular focus on trifluorome-
thylation reactions.
the imine intermediate 2 gives the secondary imine 4
with elimination of ammonia. Subsequent reduction
of the secondary imine 4 gives the diamine 5. Further-
more, the secondary amine reacts with the imine in-
termediate 2 with exclusion of ammonia followed by
reduction, which results in the formation of tertiary
amines 6. The formation of significant amounts of
side products such as secondary imines/amines and
tertiary amines lowers the selectivity and overall atom
efficiency of the reaction. The selectivity of the re-
spective amines depends on the structure of the sub-
strate, the nature and amount of the catalyst, basic
and acidic additives, the reaction medium, and other
reaction parameters. Among these factors, the nature
of the catalyst appears to be the most important for
Scheme 1. Hydrogenation of nitriles and possible side reactions.
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Bhalchandra M. Bhanage ob-
tained his doctorate from
Pune University in 1996. He
spent more than one year at
Tohoku University, Japan
(1997–1998), and four years
at Hokkaido University,
Japan (2000–2003) as a post-
doctoral fellow with Prof. M.
Arai. In 2004, he joined the
Institute of Chemical Tech-
nology, Mumbai, India as
professor of industrial and engineering chemistry.
His current research interest includes developing
novel catalytic systems for carbonylation, CO2 fixa-
tion for valuable chemicals, hydrogenation, hydro-
formylation, various coupling reactions, amination
reactions, etc. He is also working on nanomaterials,
enzymatic catalysis and the use of non-conventional
techniques like ultrasound and microwaves for vari-
ous reactions.
determining the selectivity. Apparently, there are two
possibilities to improve the chemoselectivity towards
the primary amine: (i) a low concentration of imine 2
is desirable to suppress formation of the secondary
amine and (ii) the equilibrium between 2 and 4
should be shifted towards 2 by the addition of ammo-
nia or an appropriate base.
Until now, very few examples of an efficient reduc-
tion of nitriles have been reported. There seems to be
no review exclusively dedicated to the nitrile reduc-
tion in the scientific literature with a comprehensive
and critical assessment of catalytic methods so far,
except for the review published by Bellefon and
Fouilloux in 1994.[13] Recently, Bellers group pub-
lished an excellent review entitled “Catalytic hydroge-
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 REVIEWS Recent Advances in Transition Metal-Catalyzed Hydrogenation of Nitriles

nation of carboxylic acid esters, amides, and nitriles

with homogeneous catalysts”, containing a short sec-
tion on the catalytic reduction of nitriles.[14] However,
they have not presented a comprehensive assessment
of the overall area of nitrile hydrogenation. More-
over, nitrile reduction has been scarcely investigated
in comparison with C=C, C=N, and NO2 reductions.
The various factors that control the selectivity, the
lack of previous research, the low selectivity towards
primary amines and the significant amounts of secon-
dary amine formation, are the main reasons for this.
Therefore, considering all these aspects, we describe
here the recent developments in nitrile reduction with
homogeneous and heterogeneous transition metal cat- Scheme 2. Hydrogenation of benzonitrile by amido-rutheni-
um complexes.
alyst in detail.

2 Catalytic Reductions of Nitriles

2.1 Ruthenium

Ruthenium complexes have attracted great attention

so far owing to their excellent performances in terms
of activity and selectivity compared to other transition
metals used for the catalytic hydrogenation of nitriles.

2.1.1 Ruthenium Complexes

Among the earliest reports, in 1969 Dewhirst dis-
closed RuCl2(PPh3)3 and RuH2(PMePh2)4 as catalysts
for nitrile reduction.[15] Later, Bianchini and Psaro ex-
plored the immobilised heterogeneous [(sulphos)-
Ru(NCMe)3](OSO2CF3)/SiO2 7 and [(sulphos)-
Ru(NCMe)3](OSO2CF3) 8 [(sulphos) = O3S(C6H4)-
CH2C(CH2PPh2)3] as catalysts for the hydrogenation
of benzonitrile.[16] On employing the silica-supported
heterogeneous complex 7 at 100 8C in THF as a sol-
vent, the secondary imine was obtained as a major
product (87%). In contrast, on using homogeneous
complex 8, the secondary amine was obtained in 65%
yield along with the primary amine (34%). However,
on decreasing the temperature to 70 8C, the secondary
imine was obtained exclusively in excellent yield
(98%) within 1.5 h.
Later in 2002, Hidai and co-workers synthesised
amidoruthenium complexes 9, 10 and used them for
the selective reduction of benzonitrile in the presence
of PCy3 (PCy3 = tricyclohexylphosphine).[17] On apply-
ing these complexes, benzylamine was obtained as
a major product; however the presence of additional
base (t-BuONa) improves the conversion (98%) and
selectivity towards benzylamine (up to 92%). More-
over, they observed that the product distribution was
significantly affected by the substituent on the amide
ligand (Scheme 2).
Scheme 3. Reduction of nitriles by using an in situ generated
ruthenium/DPPF catalytic system.
Subsequently, Bellers group developed two appro-
priate catalytic systems by applying [Ru(cod)-methyl-
allyl]2 as precursor and DPPF [1,2-bis-(diphenylphos-
phino)ferrocene] 11 or PPh3 (triphenylphosphine) 12
as ligand for the hydrogenation of nitriles (Scheme 3
and Scheme 4).[18,19] Various reaction parameters such
as the effect of various ruthenium precursors, differ-
ent organic and inorganic bases, pressure and temper-
ature were studied. The catalytic systems were appli-
cable for the hydrogenation of various aromatic ni-
triles with electron-donating and electron-withdraw-
ing groups in ortho- and para-positions, heteroaromat-
ic substrates as well as alkyl nitriles also give
excellent yield and selectivity towards the primary
amine.
Furthermore, the same group explored the rutheni-
um/N-heterocyclic carbene catalytic system for the
hydrogenation of various nitriles at ambient condi-
tions (Scheme 5).[20] This was the first example for
Ru/N-heterocyclic carbene-catalyzed selective reduc-
tions of CN triple bonds. To investigate the influence
of the ligand structure on the reduction of benzoni-
trile, the authors studied various imidazolium salts as
N-heterocyclic carbene precursors. The mesitylene-

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a decrease in the yield of benzyl amine was observed.

Scheme 4. Reduction of nitriles using the [Ru(cod)methyl-
ACHTUNGREallyl]2/PPh3 catalyst.
based imidazolium salts (carbenes 1 and 2) gave the
best catalystic activity. Interestingly, further increasing
the bulkiness at the 2,6-positions of the aryl substitu-
ent by isopropyl groups (carbenes 5 and 6) gave de-
creased conversion. However, on changing the N-sub-
stituent of the imidazolium salts from aryl to alkyl,
Using the optimised reaction conditions, the hydroge-
nation of substituted benzonitriles proceeded in good
to excellent yields under mild reaction conditions
(40–80 8C) within 6–16 h. In particular, electron-rich
aryl nitriles are suitable substrates for this reaction.
However, the substrate scope of the parent Ru/car-
bene catalyst is lower compared to that of the Ru/
phosphine systems.[18,19]
In 2012, Bruneau et al. explored for the first time
the use of ruthenium-benzylidene and ruthenium-in-
denylidene catalysts for the selective hydrogenation
of nitriles into the corresponding primary amines
(Scheme 6).[21]
It was observed that the absence of base leads to
the reduction of olefinic bond; however the presence
of t-BuOK further favours the reduction of the nitrile
to the amine and strongly inhibits the formation of
secondary amines. The amount of catalyst used was
also important in this conversion, when the amount of
catalyst was lowered to 1 mol%, the reduction of the
nitrile did not occur and only the olefinic bond was
fully hydrogenated. This result indicated that not only
the presence of base was important, but also the
amount of catalyst used in the reaction. These cata-

Scheme 5. Ruthenium-catalyzed hydrogenation of nitriles by applying Ru/N-heterocyclic carbene complexes.

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 REVIEWS Recent Advances in Transition Metal-Catalyzed Hydrogenation of Nitriles
Scheme 6. Hydrogenation of benzonitrile and methyl (E)-
11-cyanoundec-2-enoate catalyzed by ruthenium-alkylidene
complexes.
lysts are not only active for the hydrogenation of aro-
matic nitriles but also for that of long-chain aliphatic
nitriles. Their selective transformation from renewa-
ble plant oil into industrially applicable a,w-linear
amino esters in high yields has been achieved at 80 8C
under 20 bar of hydrogen pressure with the addition
of t-BuOK in the presence of catalyst 17.
In 2013, Beller and co-workers explored the selec-
tive transfer hydrogenation of nitriles to the primary
amines catalyzed by the [{Ru(p-cymene)Cl2}2]/DPPB
system.[22] Various reaction parameters such as the ef-
fects of various phosphine ligands and the effects of
bases and different alcohols as hydrogen source were
screened. Among the alcohols, 2-butanol was found
to be the best hydrogen donor with a 79% yield of
the primary amine. The catalytic system is applicable
for the transfer hydrogenation of a variety of aromat-
ic and aliphatic nitriles giving good to excellent yields
of the corresponding amines. The authors claim that
the protocol is the most general transfer hydrogena-
tion methodology demonstrated to date (Scheme 7).
Later in the same year, Bellers group investigated
the domino ruthenium-catalysed transfer hydrogena-
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Scheme 7. Transfer hydrogenation of nitriles with various al-
cohols as hydrogen source.
tion of nitriles with subsequent N-monoalkylation by
using alcohols.[23] A variety of aromatic, heteroaro-
matic, aliphatic, and disubstituted nitriles was con-
verted with isopropanol into the secondary amines
with excellent yields of up to 99%. The effects of dif-
ferent alcohols such as ethanol, 2-butanol, and 2-pen-
tanol were studied on the transfer hydrogenation of
benzonitrile, resulting in N-monoalkylation of benzo-
nitrile to form the corresponding secondary amines in
low to excellent yields (Scheme 8). The proposed
mechanism for the N-monoalkylation reaction pro-
ceeds with hydrogenation of nitrile 19 by using
RuCl2(PPh3)3 with isopropanol and sodium hydroxide
as the base to give primary amine 21. Whilst isopro-
panol is dehydrogenated to acetone, the acetone fur-
ther reacts with 21 through reductive amination to
give the desired secondary imine 22 by releasing
water as a side product. Finally, imine 22 is subse-
quently hydrogenated to furnish the desired secon-
dary amine 20.
Following this work, recently Beller and co-workers
reported the hydrogenation of various aliphatic and
aromatic nitriles to the corresponding primary amines
in high to excellent yields.[24] The combination of
[Ru(cod)(methylallyl)2] and imidazolylphosphine li-
gands generate active homogeneous catalyst systems,
which allow the hydrogenation of linear, branched,
and cyclic aliphatic nitriles as well as aromatic nitriles
(Scheme 9).
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Scheme 9. Catalytic hydrogenation of various aromatic and

aliphatic nitriles.

In 2007, Morris and co-workers reported the use of

ruthenium hydride complexes for the hydrogenation
of benzonitrile.[28] They prepared the Ru hydride com-
plex by treating RuHCl(PPh3)3 31 with {PPh2[(o-
C6H4)CH2NHCH2]}2 32 in THF which resulted in an
Scheme 8. Ruthenium-catalyzed reduction and N-monoalky- isomeric mixture of trans-RuHCl{ethP2(NH)2} 33
lation of nitriles: substrate scope and reaction mechanism. (Scheme 10). After activation with t-BuOK, the com-
plex 33 shows excellent activity for the hydrogenation
of benzonitrile to benzylamine in toluene. Employing
dihydrogen complex Ru(H2)2H2(PCy3)2 27 gives less
2.1.2 Ruthenium Hydride Complexes conversion as compared to complex 33.[26] Neverthe-
less, when complex 27 is mixed with complex 33 or 34
The early development in nitrile hydrogenation and base, it gives an excellent conversion thus making
by ruthenium hydride catalysts was made by
Pez and Grey, using complexes
[(Ph3P)Ph2P(C6H4)RuH2 K+(Et2O)·C10H18]2 25 and
[(Ph3P)(Ph2P)RuH2 K+·diglyme]2 26.[25] Applying
these complexes, substrates like acetonitrile, stearoni-
trile, trimethylacetonitrile, and benzonitrile were hy-
drogenated along with the ester. Later in 2004, Beatty
and Paciello patented the nitrile hydrogenation using
0.1 mol% of [RuH2(H2)2(PCy3)2] 27 at 50–70 bar H2
and a temperature between 80 and 100 8C.[26] In the
same year, Frediani and co-workers explored various
Ru complexes RuH2(CO)2 [P(n-Bu)3]2 28,
RuH2(CO)2(PPh3)2 29, and RuH2(PPh3)3 30 for the
hydrogenation of nitriles.[27] However all these com-
plexes provide N,N-dibenzylamine as a product in Scheme 10. Hydrogenation of benzonitrile with complexes
moderate yield together with the primary amines. 33, 27 or 34.

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RuH2(PhCN)2(PCyp3)2 37 was difficult to isolate and

Scheme 11. Hydrogenation of benzonitrile by complex 35.
an even more active system. The complex
RuHCl{tmeP2(NH)2} 34 where tmeP2(NH)2 =
{PPh2[(o-C6H4)CH2NHCMe2 ]}2 is a less active cata-
lyst for this reaction. It was also observed that adding
KH as base to the reaction mixture using complex 33
led to a shorter reaction time.
In 2010, the Sabo-Etienne group reported the hy-
drogenation of benzonitrile into benzylamine cata-
lyzed by a Ru bis(dihydrogen) complex incorporating
tricyclopentylphosphines under mild reaction condi-
tions.[29] A series of experiments was performed at
both the stoichiometric and catalytic levels to gain in-
formation on the mechanism of the nitrile reduction.
It was observed that precatalyst 35 is converted with
one or two equivalents of benzonitrile to give the cor-
responding cyclometallated imine complexes 36 and
38 as the resting state of the catalyst (Scheme 11). A
key step in this system is ortho-directed C H activa-
tion within the aryl group, which induces fast cyclo-
metallation and trapping of the intermediate imine to
generate 38. The reduction of benzonitrile to benzyla-
mine was achieved successfully with complexes 35,
36 and 38 under mild reaction conditions
(Table 1). However, the dihydride complex
was readily converted to 38 at ambient temperature.
Leitner and co-workers investigated a ruthenium
hydride complex with pincer ligands for nitrile reduc-
tion.[30] With this catalytic system, various aliphatic
and aromatic nitriles were hydrogenated to the corre-
sponding primary amines in 36–96% yield under opti-
mised reaction conditions. To furnish this conversion,
relatively high pressure, high temperature, and long
reaction time were necessary. It was observed that ad-
dition of a small amount of water (5 equiv. relative to
the catalyst) provided increased conversions and se-
lectivity towards primary amines (Scheme 12).
In 2014, Williams and co-workers reported a ruthe-
nium bis(pyrazolyl)borate scaffold 40 that enables co-
operative reduction reactivity in which boron and
ruthenium centres work in concert to effect selective
nitrile reduction.[31] Various aromatic, aliphatic, and
heterocyclic nitriles are smoothly reduced to corre-
sponding primary amines under the optimised condi-
tions (Scheme 13A). Both electron-poor and electron-
rich substrates can be reduced in high yield. Ketone
groups are known to react with NaBH4, the reduction
of nitriles in the presence of ketone group illustrates
the high-yielding double reduction for the synthesis of
amino alcohols. A similar double reduction is ob-
served in the reaction of a,b-unsaturated nitriles to
give alkylamines. Reactions of nitriles appended to ar-
omatic heterocycles afforded complicated results. For
example, pyridine is compatible with the conditions.
In contrast, more electron-rich heterocyclic systems
are not reduced but rather selectively monohydrated

Table 1. Hydrogenation of benzonitrile (BN) towards ben-

zylamine (I) and dibenzylimine (II).[a]

Conv. of BN [%] Product Ratio of I:II

Catalyst Solvent 2h 24 h 2h 24 h
35 pentane 94 94 94:6 94:6
35 THF 56 96 96:4 99:1
35[b] THF 62 98 22:77 96:4
35 none 84 97 0.1:99.9 89:11
36 THF 68 97 96:4 99:1
38 THF 68 96 98:2 99:1
[a]
Catalyst 35, 36 or 38 (0.5 mol%), 22 8C, 3 bar H2, THF. Scheme 12. Hydrogenation of nitriles with the non-classical
[b]
0.2 mol% catalyst. ruthenium hydride pincer complex.

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Scheme 13. A) Ruthenium bis(pyrazolyl)borate-catalyzed reduction of nitriles. B) Proposed reaction mechanism for nitrile
reductions.

giving the corresponding amides. The mechanism for
these reactions involves the addition of methanol (sol-
vent) to a ruthenium-coordinated nitrile, and the
amide products are formed upon aqueous work-up.
Furthermore, this platform has yielded new insights
into the cooperative reactivity of ruthenium and
boron by showing a plausible scenario of how these
two centres can work together as an activating group
(ruthenium) and a hydride donor (boron)
(Scheme 13A).
In the plausible reaction mechanism, the bridging
amine ligand is replaced by an incoming substrate,
and the borohydride group of 43 is regenerated by
a hydride from NaBH4 (Scheme 13B). It was observed
by 1H coupled 11B NMR spectroscopy that treatment
of 41 with a stoichiometric portion of NaBH4 in
MeOH-d4 results in the formation of (MeO)4B, un-
reacted BH4 and a catalyst doublet, which indicates
that a (pz)2BH2 43 intermediate is formed.
2.2 Rhodium Complexes
In 1979, Yoshida, Okano, and Otsuk explored rhodi-
ACHTUNGREum(I) hydrides for the first time for the selective hy-
drogenation of nitriles to the corresponding primary
amines under ambient conditions.[32] Using RhH[P(i-
Pr)3]3 44 and Rh2H2(m-N2{P(cyclohexyl)3}4 45 various
aromatic and aliphatic nitriles could be hydrogenated
to the amines with excellent yield (up to > 99%). It
was observed that complex 45 is less efficient than
complex 44 under the optimised reaction conditions.
On applying complex 45 for the hydrogenation of
a,b- and b,g-unsaturated nitriles, the olefinic bond
was reduced more readily than that of the nitrile
group (Scheme 14).
In 2004, Eckerts group explored the Rh complex
44 for the selective reduction of benzonitrile and phe-
nylacetonitrile in THF and CO2-expanded THF at
room temperature by molecular hydrogen.[33] It was

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Scheme 15. Hydrogenation of benzonitrile to benzylamine.

studied in detail. It was observed that the amount of

Scheme 14. Hydrogenation of nitriles by complex 44 and 45.
Table 2. Rh-catalyzed hydrogenation of benzonitrile and
phenylacetonitrile in THF and CO2-expanded THF.[a]
Substrate CO2 Pressure [bar]
benzonitrile 0 47
benzonitrile 20
phenylacetonitrile 0 95
phenylacetonitrile 20
[a]
Reaction conditions: catalyst 44 (0.01 mmol), THF, H2
(20 bar), temperature 23–25 8C, 20 h.
observed that, employing benzonitrile as substrate,
the yield of the primary amine was increased by the
addition of CO2 (Table 2). The increase of primary
amine yield under CO2 pressure may be due to the in
situ separation of the primary amine from the metal
centre, which remains in solution. The carbamic acid
and/or ammonium carbamates formed under CO2
pressure during the course of the reaction were sepa-
rated as a white solid and the homogeneous catalyst
remained in the solution.
acidic additive, the type of organic solvent, the palla-
dium metal and the temperature determine the selec-
tivity to the primary amine in this hydrogenation.
Later in 2008, the same group reported the selec-
tive reduction of benzyl cyanide to 2-phenylethyl-
ACHTUNGREamine over palladium on carbon at 40 8C and 6 bar
hydrogen pressure.[35] Under the optimised reaction
conditions complete conversion of benzyl cyanide was
observed, however, lower isolated yield (40%) and se-
lectivity (45%) to primary amine were achieved than
in the previous report on benzonitrile reduction.[34]
The lower yield and selectivity to 2-phenylethylamine
was due to the weak adsorption of the 2-phenylethyli-
mine on Pd(111) compared to benzaldimine and also
Yield [%] due to the different structures of their minimal energy
conformers.
61 For the first time, the use of supercritical carbon di-
oxide (scCO2) in the hydrogenation of benzonitrile
96 over Pd and other metal catalysts was explored by
Chatterjee and Kawanami.[36] Without any additive,
benzonitrile was hydrogenated to benzylamine with
high conversion (90.2%) and selectivity (90.9%) using
the Pd/MCM-41 46 as a catalyst (Scheme 16). The
product distribution was found to depend on different
reaction parameters such as CO2 and H2 pressures,
temperature and the nature of the support. Simple
tuning of the CO2 pressure resulted in the formation

2.3 Palladium Complexes

In 2005, the group of Hegeds reported the liquid-

phase heterogeneous catalytic hydrogenation of ben-
zonitrile (BN) to benzylamine (BA) under mild reac-
tion conditions.[34] The catalytic system works under
mild reaction condition over supported palladium cat-
alysts (Pd/C), in a mixture of two immiscible solvents
(e.g., water/dichloromethane) and in the presence
of sodium dihydrogen phosphate (NaH2PO4)
(Scheme 15). The effects of various reaction parame-
ters such as the acidic additives, different supported
Pd catalysts, the catalyst concentration, organic sol-
vents, the pressure and the temperature have been Scheme 16. Hydrogenation of different nitriles in scCO2.

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Scheme 17. Hydrogenation of nitriles catalyzed by complex

47.

ambient hydrogen (1.0 MPa H2), solvent free reaction

and effective catalyst recyclability (up to 4 times)
compared with homogeneous catalyst systems
(Figure 2).
Arai and co-workers reported the hydrogenation of
benzonitriles by Pd/Al2O3 48 in the presence of pres-
surised CO2 and H2O.[38] It was observed that the se-
lectivity for benzylamine was enhanced significantly
in the presence of CO2 and water. However, in ab-
sence of CO2 and water, full conversion of benzoni-
Figure 1. Effect of CO2 pressure on the conversion and se- trile was observed with lower selectivity towards ben-
lectivity of benzonitrile hydrogenation over a) Pd/MCM-41 zylamine.
and b) Pd/C. (Reproduced from ref.[36] with permission of Notably, the absence of water in reaction medium
The Royal Society of Chemistry). led to deactivation of the catalyst by accumulation of
carbamate salt on the surface of the catalyst. The de-
veloped catalytic system is advantageous due to the
of the secondary amine, dibenzylamine, which was as- selective production of benzylamine in different sol-
sisted by the interaction of CO2 with the reactant and
also by an acidic support for carbon, instead of the
neutral MCM-41. Under the studied experimental
conditions, Pd/C was deactivated easily; whereas com-
plex 46 can be reused for up to 5 recycle runs
(Figure 1).
In 2012, Wang and co-workers reported the highly
efficient heterogeneous Pd@mpg-C3N4 47 catalytic
system for selective reduction of nitriles providing
good to excellent conversion with remarkable selec-
tivity (up to 99%) without additives.[37] On employing
complex 47 under optimized reaction conditions, ali-
phatic nitriles give selectively the tertiary amines,
except for cyclohexanecarbonitrile which gives the
secondary amine in 99% selectivity, whereas aryl ni-
triles lead the formation of secondary amines
(Scheme 17). These authors have also screened vari-
ous heterogeneous Pd catalysts such as Pd/TiO2, Pd/
CeO2 and Pd/Al2O3 which result in the formation of Figure 2. Recyclability study of complex 47 for hydrogena-
secondary amines as the major product. The devel- tion of butyronitrile. (Reproduced from ref.[37] with permis-
oped protocol is more advantageous due to the use of sion of Elsevier).

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 REVIEWS Recent Advances in Transition Metal-Catalyzed Hydrogenation of Nitriles
Scheme 18. Palladium on carbon (Pd/C)-catalyzed transfer
hydrogenation of (hetero)aromatic nitriles.
vents without loss of the catalytic activity by the pal-
ladium catalyst.
More recently, Bellers group reported the catalytic
transfer hydrogenation of aromatic nitriles to the cor-
responding primary amines catalyzed by commercially
available 10% Pd/C 49 as a heterogeneous catalyst
using HCO2H-NEt3 as hydrogen donor.[39] The cata-
lytic system is applicable for the reduction of a variety
of different aromatic and heteroaromatic nitriles. The
protocol excludes the use of an autoclave, any addi-
tives and the reaction proceeds smoothly under mild
conditions giving moderate to excellent yields. Re-
markably, related functional groups such as amides
and esters were not affected under the optimised con-
ditions, thus allowing the synthesis of interesting bi-
functional building blocks. However, the present pro-
tocol was not applicable for the reduction of aliphatic
nitriles (Scheme 18).
2.4 Iridium Complexes
The first iridium-catalyzed hydrogenation of aromatic
and aliphatic nitriles was reported by Chin and
Lee.[40] Various iridium complexes such as [Ir-
ACHTUNGRE(cod)(PPh3)(PhCN)2]ClO4 50, [Ir(cod)(PPh3)2]ClO4
51, and [Ir(cod)(PhCN)2]ClO4 52 were examined for
nitrile reduction in different solvents, such as di-
chloromethane, methanol, and benzene, However
a mixture of primary, secondary and tertiary amines
was observed. The hydrogenation of nitriles in DCM
as solvent is more efficient as compared to that in
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other polar and non-polar solvents. This may be un-
derstood by the formation of non-coordinating ami-
ne·HCl salts in CH2Cl2 which cannot be formed in
other solvents. Employing complex 51, the hydroge-
nation of benzonitriles led to the formation of the ter-
tiary amine with good selectivity and conversion.
Moreover, during reaction with complex 52, decom-
position of 52 occurred forming metallic iridium pow-
ders in combination with molecular hydrogen. There-
fore, iridium metal and probably nanoparticles were
formed, which are responsible for the further reduc-
tion of the phenyl ring of benzonitrile.
2.5 Platinum Complexes
Unlike other transition metal-catalyzed reductions of
nitriles, Gu and co-workers explored the Pt nanowires
as a catalyst for the selective synthesis of secondary
amines via reductive amination of the corresponding
nitriles.[41] This catalytic system allows the synthesis of
both unsymmetrical and symmetrical secondary
amines in excellent yields (up to 95%) in the presence
or absence of additional amines, respectively.
The reaction mechanism shows a reaction between
the formed primary amine and the intermediate imine
accompanied by the expulsion of ammonia, which can
give rise to a secondary amine; however, when the in-
termediate imine couples with an aliphatic amine it
gives the corresponding unsymmetrical amine
(Scheme 19).
2.6 Other Transition Metal Complexes
Besides the platinum group metals, recently other
transition metal species have also been developed as
effective catalysts for the selective hydrogenation of
nitriles. In 2009, Lemaire and co-workers reported
a simple and efficient method for the reduction of ni-
triles into the corresponding amines (HCl salts) in
almost quantitative yield using a tetramethyldisilox-
ane/titanium(IV) isopropoxide reducing system.[42]
The protocol uses TMDS and Ti(O-i-Pr)4 in stoichio-
metric quantities for the reduction of nitriles. The
acidic work-up allows one to isolate the amine by
crystallization of the hydrochloride salt (Scheme 20).
In 2011 Berke et al. reported the homogeneous rhe-
nium(I) nitrosyl complexes for the hydrogenation of
nitriles to the corresponding symmetrical secondary
amines or tertiary amines using triethylsilane as hy-
drogen source.[43] A series of novel rhenium(I) cata-
lysts (complexes 55, 56, 59, and 60) was prepared with
the large bite angle sixantphos ligands 53, 54 and the
products were tested for the hydrogenation of nitriles
to the corresponding symmetrical secondary amines
(Scheme 21). It was observed that the addition of tri-
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 Dattatraya B. Bagal and Bhalchandra M. Bhanage REVIEWS

Scheme 19. Formation of symmetrical and unsymmetrical secondary amines from different nitriles.

Scheme 20. TMDS reduction of nitriles to amines.

ACHTUNGREethylsilane could increase the TOFs and suppress

over-alkylation of the amines at higher pressures with
a relatively high loading of the catalyst (Table 3).
Later in the same year, Cabrita and Fernandes re-
ported the PhSiH3/ReIO2(PPh3)2 catalytic system for
the reduction of nitriles to the corresponding primary
amines.[44] The complex ReIO2(PPh3)2 61 is highly
stable towards air and moisture. The complex 61 is Scheme 21. Complexes 55 and 56 and their splitting equili-
applicable for reduction of various nitriles in the pres- bria with 57 and 58, respectively, in acetonitrile. Structure of
the diastereomers A and B of 59 and 60.
ence of a wide range of functional groups such as Cl,
F, Br, I, CF3, OCH3, SCH3, SO2CH3 and NHTs
(Scheme 22).

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 REVIEWS Recent Advances in Transition Metal-Catalyzed Hydrogenation of Nitriles

Table 3. Hydrogenation of nitriles catalyzed by complexes

55, 56, 59 and 60.

Entry Nitrile Catalyst Yield [%] TOF [h 1]

1 Ph 55 85 198
2 Ph 56 86 198
3 Ph 59 90 198
4 Ph 60 82 196
5 3-tolyl 55 89 198
6 3-tolyl 56 87 198
7 2-thienyl 59 83 162
8 2-thienyl 60 85 160
9 3-tolyl 59 81 170
10 3-tolyl 60 80 169
11 PhCH2 55 10 176
12 cyclohexyl 55 95 198
[a]
0.5 mol% of catalyst with 25 equiv. of triethylsilane with
respect to catalyst at 75 bar H2, 140 8C in THF, 1 h.

Scheme 23. A) InCl3/NaBH4 reduction of various nitriles to

primary amines. B) Selective reductions of the carbon–bro-
mine bond by InCl3/LAB.

achieved by using either InCl3/NaBH4 in CH3CN or

InCl3/MeLAB (MeLab = lithium dimethylaminoboro-
hydride) in THF (Scheme 23B).
The photostimulated reduction of various nitriles
catalyzed by SmI2 63 has been reported by the Hoz
group.[46] They studied the reactivity of aliphatic, aro-
Scheme 22. Reduction of nitriles catalyzed by complex 61. matic and dicyano compounds using photostimulation
in the visible region. MeOH (0.2 M) is used as the
proton donor which complexes efficiently with SmI2
In 2012, Singaram and co-workers reported the re- resulting in formation of the corresponding amine.
duction of various aromatic and aliphatic nitriles by The mechanism of the reaction involves coordination
using HInCl2 62 via the in situ reduction of InCl3 of the SmI2 to the lone pair of the nitrile nitrogen fol-
using lithium aminoborohydride.[45] The reported pro- lowed by an inner sphere electron transfer. This is
tocol is simple, efficient and works under milder reac-
tion conditions for the reduction of aromatic, hetero-
aromatic, benzylic, and aliphatic nitriles to the corre-
sponding primary amines using the in-situ generated
BH3·THF (Scheme 23A). Additionally, it was demon-
strated that halides and nitrile functionalities can be
reduced in tandem by making use of the reductive ca-
pabilities of both HInCl2 and BH3·THF reducing
agents. This was demonstrated by reducing 4-(bromo-
methyl)benzonitrile to the corresponding 4-methyl-
benzylamine with an isolated yield of 61%. Selective Scheme 24. Photostimulated reduction of various nitriles
reduction of halides in the presence of nitriles was catalyzed by SmI2.

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 Dattatraya B. Bagal and Bhalchandra M. Bhanage REVIEWS

evidenced by the dependence of the yield on the

Figure 3. Influence of Cu loading in Cu-MgO catalysts to-
wards the hydrogenation of benzonitrile at 473 K with
WHSV (weight hourly space velocity) of 1 h 1. (Reproduced
from ref.[48] with permission of Elsevier).
MeOH concentration. As the concentration of the
MeOH increases, it complexes the SmI2 more inten-
sively and prevents coordination to the nitrogen lone
pair. As a result, the yield goes down (Scheme 24).
Copper, an abundant and inexpensive metal com-
pared to noble metals, has not been well explored for
nitrile reduction until now. In this regard, Branco and
co-workers for the first time reported a copper-cata-
lyzed gas-phase hydrogenation of propionitrile to the
corrosponding primary amine, i.e., propylamine as
major product.[47,48] Later in 2013, Burri et al. reported
the selective reduction of benzonitrile to benzylamine
using Cu-MgO catalysts in the absence of any addi-
tives at atmospheric pressure.[48] They have prepared
the Cu-MgO catalyst by impregnating a freshly pre-
pared MgO support using Cu(NO3)2·3 H2O as Cu pre-
cursor with Cu loadings of 4, 8, 12 and 16%, respec-
tively (Figure 3). Among them, the 12% Cu-MgO cat-
alyst shows excellent activity with 98% conversion
with 70% selectivity of benzylamine at 513 K. Worthy
of mention is that up to 100% selectivity towards the

Scheme 25. Electron transfer reduction of nitriles using SmI2-Et3N-H2O.

Scheme 26. Reduction of nitriles with NiNPs@Fe3O4-SiO2-P4VP MGs as the catalyst system.

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 REVIEWS Recent Advances in Transition Metal-Catalyzed Hydrogenation of Nitriles

primary amine was achieved under the optimized con-
ditions using 12% Cu-MgO catalysts at 1 atmospheric
pressure with a WHSV (weight hourly space velocity)
of 1 h 1.
Procter and co-workers reported the reduction of
nitriles to the corresponding primary amines under
single electron transfer conditions using complex 63
(Kagans reagent) activated with Lewis bases.[50] The
catalytic system features excellent functional group
tolerance and represents an attractive alternative to
the use of pyrophoric alkali metal hydrides. The pro-
posed mechanism shows that the reaction proceeds
through the generation of imodoyl-type radicals
which form an equilibrium with the amine radical.
Subsequently single electron transfer (SET) to the
radical imine generates a carbamine anion, which un-
dergoes a protonation resulting in the formation of
the imine. In next step, a further SET to the imine
leads to the formation of an Sm3+ intermediate which
upon subsequent protonation furnishes the final prod-
uct (Scheme 25).
In 2014, Nabid et al. reported the reduction of ali-
phatic and aromatic nitriles using NiNPs@Fe3O4-SiO2-
P4VP 64 as an efficient catalyst (Scheme 26).[51] The
catalyst is applicable for the reduction of both aro-
matic and aliphatic nitriles in excellent yields. The
catalyst can be recycled for up to seven cycles by
magnetic separation without loss in activity and selec-
tivity. The catalytic system has the advantages of flexi-

Figure 4. Effect of recycling on the catalytic activity and

productivity of NiNPs@Fe3O4-SiO2-P4 VP MGs after a)
30 min (black) and b) 2 h (grey). (Reproduced from ref.[51] Figure 5. Proposed reaction mechanism: nitrile hydrogena-
with permission of John Wiley & Sons). tion by pincer PNP iron complex.

Scheme 27. Hydrogenation of aromatic and aliphatic nitriles catalyzed by complexes 65 and 66.

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 Dattatraya B. Bagal and Bhalchandra M. Bhanage REVIEWS

bility and practicality, a simple work-up process, and
easy recovery of the catalyst, and thus it can be used
for the reduction of many different carbon-nitrogen
multiple bonds. Analysis of the complex showed good
stability and recyclability, as the conversion yields for
seven runs after 30 min did not decrease significantly.
In addition, to investigate the productivity of the pre-
pared catalyst, they examined the reduction of benzo-
nitrile for seven cycles even after the completion of
the reaction (Figure 4).
The results shown in Figure 4 b demonstrate that,
after every run, the product yield does not change sig-
nificantly, which indicates the high productivity of the
catalyst.
Berke et al. demonstrated the use of low-valent
molybdenum 65 and tungsten 66 amides as active cat-
alysts for the hydrogenation of various nitriles to the
corresponding secondary imines.[52] A wide range of
para- and meta-substituted aromatic nitriles, the heter-
ocyclic 2-thiophencarbonitrile and aliphatic nitriles
could be hydrogenated giving high yields and appreci-
able selectivity towards secondary imines along with
the formation of primary imines and the primary
amines. Both complexes 65 and 66 were applied for
nitrile reduction without adding any additives/co-cata-
lysts under homogeneous conditions. However com-
plex 65 attains excellent conversions compared to
complex 66. The developed catalytic system repre-
sents a promising alternative to the precious group
metal catalysts (Scheme 27).
The very first selective nitrile hydrogenation via
a non-precious metal pincer-type PNP iron catalyst
under relatively milder reaction conditions was ac-
complished recently by Beller and co-workers. Under
the optimised conditions, various aromatic and ali-
phatic (di)nitriles were converted to the correspond-

Scheme 28. Hydrogenation of various aromatic nitriles by complex 67.

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 REVIEWS Recent Advances in Transition Metal-Catalyzed Hydrogenation of Nitriles
ing primary amines (as HCl salts) in good to excellent
yields using an iron PNP pincer complex.[53] The cata-
lytic system shows excellent functional group toler-
ance. Ester, ether, acetamido as well as amino sub-
stituents are not reduced in the presence of nitriles.
Moreover, nitriles including an a,b-unsaturated
double bond and halogenated derivatives are well tol-
erated in this reaction. The reaction is proposed to
proceed first with catalyst activation (Figure 5); it was
assumed that the loss of BH3 gives complex 71. Then,
the nitrile is hydrogenated in a concerted way by a si-
multaneous transfer of the hydride from the iron
center and the proton from the nitrogen ligand to
give the corresponding imine 73 and the amido com-
plex 72. The dihydrido species 71 is regenerated by
the addition of molecular hydrogen. The imine 73 un-
dergoes a second reaction cycle and is finally reduced
to the corresponding amine 69 (Scheme 28).
3 Conclusion and Outlook
The efficient and selective conversion of nitriles into
primary amines is a challenging task and catalysts
play a key role in selectivity for this transformation.
Indeed, numerous new catalytic systems for nitrile re-
duction have been actively developed in the last
decade. In this perspective, we have reviewed the
most recent progress in transition metal-catalyzed ni-
trile reduction. Although the reactivity of nitriles is
lower compared to that of C=C, C=O, C=N and NO2
bonds, the efficiency of transition metal catalysts is
far better than that of metal hydrides. The catalytic
reduction of nitriles to the corresponding primary
amines is highly atom-efficient; however formation of
by-products such as secondary imines/amines reduces
the significance. Nevertheless, some of the catalysts
recently developed showed high activity and excellent
selectivity towards primary amines. Selectivity to-
wards primary amines, the catalyst-product separation
and catalyst recyclability are the major problems and
there is a need for the development of various novel
strategies to solve these problems. Further develop-
ments toward the selective synthesis of primary
amines from nitriles using environmentally benign
and milder reaction conditions are expected.
Acknowledgements
The authors (D. B. Bagal) express gratitude towards Univer-
sity Grant Commission, New Delhi, India (UGC-SAP) for
providing a senior research fellowship.
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Recent Advances in Transition Metal-Catalyzed 19

Hydrogenation of Nitriles

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