Homogeneous hydrogenation of nitriles catalyzed by molybdenum and tungsten amides

Article abstract of DOI:10.1021/cs5004646

Low-valent molybdenum and tungsten amides M(NO)(CO)(PNP) {M = Mo, 1a; W, 1b; PNP = N(CH₂CH₂PⁱPr₂) ₂} were found to be active catalysts for the hydrogenation of various nitriles to the corresponding imines, primary amines, and N-substituted imines with high selectivity for the latter type of product. A wide range of p-and m-substituted aromatic nitriles-p-methyl, p-methoxy, p-bromobenzonitriles; 3-trifluoromethylbenzonitrile, m-and p-disubstituted benzonitrile; the heterocyclic 2-thiophencarbonitrile; and the aliphatic nitriles cyclohexylcarbonitrile and benzylcyanide-could be hydrogenated at 140 °C and 60 bar H₂ in THF with high yields. TOFs were found to be between 0.4 and 36 h^-1.

Full text of DOI:10.1021/cs5004646

Letter
pubs.acs.org/acscatalysis
Homogeneous Hydrogenation of Nitriles Catalyzed by Molybdenum
and Tungsten Amides
Subrata Chakraborty and Heinz Berke*
Institute of Chemistry, University of Zurich, 8057, Zurich, Switzerland
̈
̈
S
* Supporting Information
ABSTRACT: Low-valent molybdenum and tungsten amides M(NO)(CO)-
(PNP) {M = Mo, 1a; W, 1b; PNP = N(CH2CH2PiPr2)2} were found to be active
catalysts for the hydrogenation of various nitriles to the corresponding imines,
primary amines, and N-substituted imines with high selectivity for the latter type
of product. A wide range of p- and m-substituted aromatic nitrilesp-methyl, p-
methoxy, p-bromobenzonitriles; 3-trifluoromethylbenzonitrile, m- and p-
disubstituted benzonitrile; the heterocyclic 2-thiophencarbonitrile; and the
aliphatic nitriles cyclohexylcarbonitrile and benzylcyanidecould be hydrogenated at 140 °C and 60 bar H2 in THF with high
yields. TOFs were found to be between 0.4 and 36 h−1.
KEYWORDS: nitrile hydrogenation, secondary imines, molybdenum, tungsten, amides
articularly challenging in homogeneous catalysis research is
based catalyst, which was found to be active in the
1
Pthe hydrogenation of nitriles resulting in the production hydrogenation of various aliphatic and aromatic nitriles forming
of amines and imines, which are useful synthetic precursors for
pharmaceuticals and agrochemicals.2,3a,b Often, the catalytic
hydrogenation of nitriles displays low selectivities forming
imines and amines, and the amines could consist of a mixture of
primary, secondary, and tertiary amines.3 The imines are
intermediates on the way to amines, which can subsequently
react with the formed primary or secondary amines by
expulsion of NH3 to give new N-substituted imines and
enamines, respectively. Concomitant hydrogenation of these
leads to formation of the secondary and tertiary amines
(Scheme 1). Alternatively, the secondary and tertiary amines
could be formed via direct hydrogenolysis of gem diamines.3a
a mixture of N-substituted imines (d) and secondary amines
(e) along with tertiary amines (f).8 In most cases of these
hydrogenations the secondary amine (e) was the predominant
type of product. Related to this possibility of secondary amine
formation, a challenging goal would be to find ways to direct
the hydrogenation of nitriles to the production of secondary
imines.9 Indeed, in a recent report, Milstein and co-workers
have demonstrated that the hydrogenation of nitriles in the
absence and presence of added amines could selectively yield
secondary imines under mild and neutral pH conditions
employing PNN-based Ru pincer complexes as catalysts.10
Moreover, Sabo-Etienne et al. have observed formation of N-
benzylidene-1-phenylmethaneamine during the hydrogenation
of benzonitrile and were able to obtain this compound
selectively when the reaction was carried out in the absence
of a solvent.11
Scheme 1. General Scheme for the Hydrogenation of Nitriles
to Form Primary, Secondary and Tertiary Amines via Imine
Intermediates
Today’s chemistry focuses on cheaper, greener, and atom-
economic ways to carry out organic transformations.12,13 In this
respect, iron, molybdenum, and tungsten catalysts would be
appropriate alternatives to those with precious metal centers
reaching a new stage of homogeneous catalysis with the issue of
“Cheap Metals for Noble Tasks”.14 These metals are earth-
abundant, have low toxicity, and are environmentally benign. In
fact, recently we were able to demonstrate the catalytic
efficiency of suitably substituted molybdenum- and tungsten-
based catalysts in imine hydrogenations15,16 and in related
hydrosilylations of various aldehydes and ketones.17
However, reports on homogeneous nitrile hydrogenations
are rare. They normally require precious metal catalysts, such as
ruthenium,4 rhodium,1b and iridium,5 which may also invoke a
toxicity issue. In 2008, Beller and co-workers reported
ruthenium phosphine catalysts based on dppf6 or PPh37 ligands
for the hydrogenation of a variety of aromatic and aliphatic
nitriles showing high catalytic activity with selectivities for
primary amines, albeit these reactions required the addition of
KOtBu as a base. Our group has recently developed a rhenium-
In a previous publication,15 we demonstrated that
molybdenum and tungsten amide complexes M(NO)(CO)-
Received: April 8, 2014
Revised: May 28, 2014
© XXXX American Chemical Society
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Letter
(PNP) {M = Mo, 1a; W, 1b; PNP = N(CH2CH2PiPr2)2}
(Figure 1) enable heterolytic splitting of H2-producing bound
Table 1. Hydrogenation of Aromatic and Aliphatic Nitriles
Catalyzed by 1a and 1b
Figure 1. Catalysts for nitrile hydrogenation.
hydrides and protons. Compounds 1a,b were found active
catalysts in such bifunctional hydrogenations of N-aryl-
substituted imines with hydride transfer to the Cimine atom
and proton transfer to the Nimine atom; however, N-alkyl-
substituted secondary imines could not be hydrogenated. This
was explained in terms of the indicated metal-based “ionic”
catalytic reaction course. The alkyl-substituted imine/amine
pairs generally possess high basicities, and the amines of type c
are more basic than the corresponding imines of type b
(Scheme 1). Therefore, the more basic product amines are
anticipated to consume a significant proportion of the protons
and in this way hinder imine activation by protonation.
Furthermore, the alkyl amines would also be stronger ligands
and could block the metal centers by coordination. Aryl-
substituted imine/amine pairs are expected to show generally
lower basicities, but the aryl imines of type b of Scheme 1
would be the stronger bases and could be activated by
protonation to form iminium cations ready for hydride transfer
generating amines of type c.16 Therefore, catalytic aryl nitrile
reductions are expected to initially lead to primary amines,
which provide the perspective to form in a subsequent reaction
secondary N-aryl,alky-substituted imines of type d (Scheme 1),
which as derived in the beginning of this paragraph are
expected to be reluctant to undergo hydrogenations with the
given set of catalysts. With this in mind, we commenced to
investigate challenging highly selective catalytic nitrile hydro-
genations.
Herein, we communicate the first examples of molybdenum
(1a)- or tungsten amide (1b)-catalyzed homogeneous hydro-
genation of nitriles leading prevalently to formation of
secondary imines (d). The synthetic versatility of imines
promises a broad application range for them in laboratory and
industrial processes.18 Therefore, we believe that the formation
of secondary imines as predominant products from readily
available nitriles has a considerable synthetic potential.
Both complexes 1a and 1b were applied in these
homogeneous nitrile hydrogenations requiring no additive or
cocatalyst. Formation of a mixture of products was observed,
but dibenzylimines (d) (Scheme 1) were strongly prevailing in
the range of products. Product admixtures of minor amounts
were benzylimines (b) and benzylamines (c), but dibenzyl-
amines (e) or tertiary amines (f) were not detected either as
products or as reaction intermediates, as revealed by GC/MS
probing. Apparently, the higher N-substituted imines (d) are
formed via attack of the intermediate imines (b) by the primary
amines (c) producing gem-diamines followed by expulsion of
ammonia.
Initially, hydrogenation of benzonitrile was carried out at
room temperature with a loading of 5 mol % of the catalyst 1a
under 60 bar H2 in THF. However, the GC/MS analyses
revealed after 14 h the formation of only 3% N-
benzylidenebenzylamine (Table 1, entry 1, first row). When
the temperature was raised to 140 °C with otherwise the same
a
Unless otherwise stated, 5 mg of the catalyst 1a or 1b, 20 equiv
substrate relative to catalyst, 140 °C temperature, 60 bar H2, and 2 mL
of THF as solvent were used as reaction conditions. Initial TOFs
were determined after 30 min by GC/MS. Conversions and
selectivity were determined by GC/MS on the basis of substrate
consumption. At room temperature TOF was determined after
initial 1 h. 150 °C temperature was used. ND = initial TOFs were not
determined. Sel = selectivity.
b
c
d
e
f
conditions, an initial TOF of 36 h−1 could be achieved,
corresponding to a conversion of 90% after an initial 30 min.
The reaction was completed in <4 h, yielding 10% benzylimine
and 90% N-benzylidenebenzylamine (Table 1, entry 1, middle
row). No benzylamine could be detected as revealed by GC/
MS analysis. Exploring the scope of this catalytic reaction by
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application of a variety of nitriles, the reaction of 4-
methylbenzonitrile and 4-methoxybenzonitrile resulted under
the same conditions (60 bar H2 and 140 °C) and with a loading
of 5 mol % of 1a in THF in the formation of N-(4-
methylbenzylidene)-1-(p-tolyl)methanamine and N-(4-methox-
ybenzylidiene)-1-(4-methoxyphenyl)methanamine, respec-
tively, showing complete conversion in <6 h (90% and 93%
selectivity of the secondary imine; entries 2 and 3). Compound
1a was also found to be active in the hydrogenation of the
sterically more hindered 3-trifluoromethylbenzonitrile, which
was completely converted to the corresponding primary amine
of type c and to the secondary imine of type d with 22% and
78% selectivity, respectively (Table 1, entry 4). In the
hydrogenation of p-bromobenzonitrile, applying 1a (5 mol
%) as a catalyst at 140 °C under 60 bar H2 in THF (Table 1,
entry 5), a selectivity of 96% was observed for the generation of
the corresponding N-(4-bromobenzylidene)-1-(4-
bromophenyl)methaneamine.
The potential of the catalyst was further probed by
employing more challenging alkyl and functionally substituted
heterocyclic nitriles. Cyclohexylcarbonitrile could be fully
hydrogenated to the corresponding primary amine and the
secondary imine with 22% and 78% selectivity, respectively,
with 5 mol % of the catalyst 1a under 60 bar H2 at 140 °C,
giving an initial TOF of 34 h−1 (Table 1, entry 6).
Benzylcyanide could also be hydrogenated, revealing the
formation of exclusively secondary imine in moderate 40%
yield after 14 h of reaction time (Table 1, entry 7). However,
the reaction was slow, with an initial TOF of only 3 h−1. 2-
Thiophencarbonitrile was hydrogenated completely to the
corresponding primary amine, and primary and secondary
imines, within 8 h (Table 1, entry 8), employing 1a as the
catalyst with an initial TOF of 4 h−1. The selectivity of the
corresponding secondary imine was 49%. Surprisingly, m- and
p-dihalosubstituted benzonitriles were also efficiently hydro-
genated using catalyst 1a. For example, 3,4-difluorobenzonitrile
exhibited complete conversions, with transformation to the
corresponding secondary imine (96%) and 4% of the primary
amine after 6 h using 5 mol % of the catalyst 1a at 140 °C
under 60 bar H2 (initial TOF of 8 h−1) (Table 1, entry 9). As
an example of lower catalytic conversion, 3-chloro-4-fluoro-
benzonitrile was found to be very sluggishly hydrogenated, with
a conversion of only 22% after 12 h under otherwise the same
conditions as in the experiments before with 46% selectivity of
the corresponding secondary imine (Table 1, entry 10).
The scope of the nitrile hydrogenations could be extended
further by applying the tungsten analogue 1b as the catalyst. As
for 1a, 5 mol % of 1b was used in the prototypic benzonitrile
hydrogenation in THF at 140 °C under 60 bar H2, which
furnished 91% conversion to the corresponding imine (b, 26%)
and dibenzylimine (d, 74%) after 14 h of reaction time, as
revealed by the GC/MS, albeit a very low TOF of 0.4 h−1 in the
first hour (Table 1, entry 1, last row). Nonetheless, only 3%
catalytic conversion of p-methylbenzonitrile to the correspond-
ing dibenzylimine N-(4-methylbenzylidene)-1-(p-tolyl)-
methaneamine could be observed after 16 h when 5 mol %
of catalyst 1b was used (140 °C, 60 bar H2) (Table 1, entry 2,
middle row). Raising the temperature to 150 °C (otherwise
keeping the same conditions) showed only little improvement
in the catalytic performance (19%, Table 1, entry 2, last row). It
was a somewhat unexpected result to find that attempts of
hydrogenations of 3-trifluoromethylbenzonitrile and 2-thio-
phencarbonitriles using 1b as a catalyst (5 mol %) did not occur
at all at 140 °C under 60 bar H2 in THF (Table 1, entries 4,
and 8). Exclusive formation of secondary N-(cyclohexylmethe-
lene)-cyclohexanemethanamine was observed when the ali-
phatic cyclohexylcarbonitrile was hydrogenated at 140 °C
under 60 bar H2 using catalyst 1b, furnishing a quite low yield
(14%) after 16 h as revealed by GC/MS (Table 1, entry 6, last
row).
To summarize, we could demonstrate for the first time the
catalytic application of non-noble molybdenum and tungsten
complexes {M(NO)(CO)(PNP) M = Mo, 1a; W, 1b} in
homogeneous hydrogenations of a variety of nitriles: p-
substituted benzonitriles; p-methyl, p-methoxy, p-bromo
benzonitriles; 3-trifluoromethylbenzonitrile, disubstituted ben-
zonitriles (meta and para), heterocyclic 2-thiophencarbonitrile,
aliphatic cyclohexylcarbonitrile, and benzylcyanide could be
converted to their corresponding secondary imines (d) with
moderate to good selectivity along with the formation of
primary imines (b) and the primary amines (c) in most of the
cases. Excellent conversions were achieved applying particularly
the molybdenum system 1a as the catalyst. This exploration
showed that middle transition element complexes when
equipped with an appropriate ligand environment are capable
of taking the role of precious platinum group metal catalysts,
and it seems therefore worthwhile to make efforts extending
this fundamental finding to optimize via ligand “tuning” of the
catalysts the activities of these catalyses.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details and the GC/MS data of the substrates and
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: hberke@chem.uzh.ch.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the Swiss National Science Foundation, the
■
University of Zurich, and Lanxess AG for financial support.
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