Hydrogenation of heteroaromatic nitriles and aromatic dinitriles by heterogeneous or homogeneous ruthenium catalysts derived from [Ru3(CO)12]

Article abstract of DOI:10.1016/j.ica.2017.04.051

The use of the complex [Ru₃(CO)₁₂] (1) as a catalyst precursor (0.1?mol%) at 200?°C, 60?psi of H₂, along with triphenylphosphine (TPP) generated ruthenium nanoparticles (Ru-Nps); this occurred in the presence of pyridine-nitriles leading to a variety of hydrogenation (secondary amine, imine, or imidazole) products, depending of the pyridine-nitrile used, under similar reaction conditions. This relates to relatively good to modest yields, determined by the substituents in the corresponding pyridine. In sharp contrast, the use of aromatic dinitriles did not generate Ru-Nps at 140?°C, 150?psi of H₂ and TPP, but allowed the homogeneous catalytic hydrogenation of the 1,4- and 1,3-dicyanobenzenes, to yield the corresponding CN-substituted secondary amine or imine. The main products were characterized by different analytical methods and spectroscopic techniques.

Full text of DOI:10.1016/j.ica.2017.04.051

Inorganica Chimica Acta 464 (2017) 55–58
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Research paper
Hydrogenation of heteroaromatic nitriles and aromatic dinitriles by
heterogeneous or homogeneous ruthenium catalysts derived from
[Ru3(CO)12]
⇑
Juventino J. García , Nora Pérez-Lezama, Alma Arévalo
Facultad de Química, Universidad Nacional Autónoma de México, México D. F. 04510, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
The use of the complex [Ru3(CO)12] (1) as a catalyst precursor (0.1 mol%) at 200 °C, 60 psi of H2, along
with triphenylphosphine (TPP) generated ruthenium nanoparticles (Ru-Nps); this occurred in the pres-
ence of pyridine-nitriles leading to a variety of hydrogenation (secondary amine, imine, or imidazole)
products, depending of the pyridine-nitrile used, under similar reaction conditions. This relates to rela-
tively good to modest yields, determined by the substituents in the corresponding pyridine. In sharp con-
trast, the use of aromatic dinitriles did not generate Ru-Nps at 140 °C, 150 psi of H2 and TPP, but allowed
the homogeneous catalytic hydrogenation of the 1,4- and 1,3-dicyanobenzenes, to yield the correspond-
ing CN-substituted secondary amine or imine. The main products were characterized by different analyt-
ical methods and spectroscopic techniques.
Received 22 April 2017
Accepted 25 April 2017
Available online 27 April 2017
Keywords:
Nitriles
Pyridines
Hydrogenation
Ruthenium
Catalysis
Ó 2017 Elsevier B.V. All rights reserved.
Heterocycles
1. Introduction
duction of primary amines usually involves the production of sec-
ondary amines and imines for the production of tertiary amines.
The use of hydrogen in chemical transformations is generically
known as hydrogenation. In the case of nitriles as substrates,
hydrogenation yields different products in consecutive and parallel
reactions (primary, secondary, and tertiary amines and corre-
sponding imines), which are useful in a variety of important appli-
cations in industry and academia [1]. Since many amines are
important building blocks of more complex molecules, efficient,
selective and versatile hydrogenation for nitriles are important
for their preparation, preferentially by catalytic methods [2].
Therefore, using homogeneous or heterogeneous catalysis faces
pros and cons; catalytic methods are by far the better option for
environmental reasons.
Many homogeneous catalysts based in transition metals have
been used for nitrile hydrogenation; in fact, the area has been
recently reviewed [3]. However, compared to other functional
groups such as C@C, C@O, C@N, the group C„N has been some-
what less explored. Some relevant examples of the most used met-
als are ruthenium [4], cobalt [5], and nickel [6]. Many of the above
systems cited for ruthenium involve the preparation of multi-den-
tate ancillary ligands, such as pincers and tridentate ligands, as
well as more elaborate ligands to improve selectivity [7]. The pro-
The hydrogenation of dinitriles has also been studied, dating
back to the 1960s by Freidlin and Sladkova [8], using heteroge-
neous catalysts of Ni and Co-Raney, with low to moderate yields
from diamine derived from the 1,4- and 1,3-dicyanobenzene, but
no reactivity found for the 1,2-dicyanobenzene, using high pres-
sure for H2 (1200–1700 psi) at 100 °C. A later variation of this pro-
cedure using Ni-Raney to yield p-cyano-benzylamine from 1,4-
dicyanobenzene was patented [9], followed by a related patent in
the field for the hydrogenation of 1,3-dicyanobenzene to yield o-
xylendiamine in high yield, using a Pd-Ru catalyst supported in
Al2O3 [10]. Other selected examples of heterogeneous hydrogena-
tion of dinitriles include the Rh/Al2O3 catalyst by Ishizaka and
co-workers [11] and a recent example using a stable cobalt catalyst
on inorganic supports [12]. There are very few reports dealing with
the homogeneous hydrogenation of dinitriles, except for recent
reports including the use of iron-pincer compounds by Beller
et al. The scope included aliphatic and aromatic dinitriles [13], plus
studies in which Hou and coworkers catalyzed the Rh asymmetric
hydrogenation of dicyanoalkenes [14].
Our group has been interested in the hydrogenation of organon-
itriles and dinitriles, including the use of homogeneous nickel cat-
alysts [6b], and heterogeneous systems based on ruthenium
nanoparticles [15]. In this vein, we report our findings using [Ru3(-
CO)12] (1) as a catalyst precursor with triphenylphosphine (TPP) to
⇑
Corresponding author.
E-mail address: juvent@unam.mx (J.J. García).
http://dx.doi.org/10.1016/j.ica.2017.04.051
0020-1693/Ó 2017 Elsevier B.V. All rights reserved.

56
J.J. García et al. / Inorganica Chimica Acta 464 (2017) 55–58
generate ruthenium nanoparticles (Ru-Nps) in the presence of pyr-
idine-nitriles, leading to the production of corresponding hydro-
genation products: the expected secondary amine, imine, or
imidazole. In contrast, the same catalytic precursors in the pres-
ence of 1,4- and 1,3-dicyano-benzenes produced the corresponding
CN-substituted secondary amine or imine by a homogeneous
pathway.
trast in reactivity between the 4- and 3-positions in pyridines [16],
such that position 4- is prone to a nucleophilic substitution com-
pared with position 3-, consequently achieving a completely
reduced product (BPA). It is worthy to mention that the reaction
was established in both cases under the same reaction conditions,
as nanoparticles were being formed in each case and reactivity was
being inhibited with a mercury drop test. The corresponding Ru-
Nps (4.74 avg.) was isolated and characterized by TEM, with the
corresponding micrograph presented in Fig. 2.
Considering these results, we decided to explore the reactivity
of the same catalytic system, but using 2-cyanopyridine as a sub-
strate. The reactivity found is illustrated in Scheme 3.
2. Results and discussion
Optimized reaction conditions used 1 as the catalytic precursor,
and 4-cyanopyridine, as in Scheme 1, with a variety of tempera-
tures, H2 pressures, and reaction time using as reference the ones
previously reported by our group in closely related catalytic sys-
tems [15], but also considering avoid high reaction temperatures.
The catalytic hydrogenation of 4-cyanopyridine by Ru-Nps gen-
erated in situ from [Ru3(CO)12]/TPP gave excellent results (94%)
towards the formation of the secondary amine bis(pyridin-4-
ylmethyl)amine (BPA), with a small amount of corresponding
imine (1-(pyridin-4-yl)-N-(pyridin-4-ylmethylene)methanamine)
(PPA). The use of a mercury drop test inhibited the reaction, as
expected for nanoparticles being formed; thus, the presence of
Ru-Nps (4.64 avg.) was confirmed by transmission electron micro-
scopy (TEM), Fig. 1.
Considering the reactivity that was found, we assessed the same
reaction using 3-cyanopyridine, with exactly the same reaction
conditions as with 4-cyanopyridine, yet the results creating a dif-
ferent product ratio as depicted in Scheme 2.
The difference in reactivity found between 4-cyanopyridine and
3-cyanopyridine can be explained in terms of the well-known con-
The reaction produced the imidazole 2,20,200-(1H-imidazole-
2,4,5-triyl)tripyridine with a 66% yield, and a total conversion of
78%. This transformation has not yet been reported using a ruthe-
nium catalyst during the nitrile hydrogenation, but has been
reported for nickel by our group [17], probably following a clo-
sely-related mechanism; this may involve the production of the
secondary imine, followed by the insertion of a nitrile and a series
of cyclization steps to yield the corresponding imidazole. This reac-
tion was inhibited by a mercury drop test, and Ru-Nps (4.41 avg.)
were isolated and characterized (see SI).
Motivated by these results, we assessed the reactivity of 1,4-,
1,3-, and 1,2-aryl-dinitriles with the same catalytic precursor, the
dinitriles having lower reaction temperatures, along with shorter
possible reaction times as represented in Scheme 4.
The reactivity found for the 1,4- and 1,3-dicyanobenzenes can
be explained based on the difference in reactivity between the 4-
and 3-positions in benzenes (para and meta, respectively); thus,
position 4- is prone to a nucleophilic substitution having an elec-
tron-withdrawing substituents compared with position 3-; there-
Scheme 2. Reactivity of RuNps with 3-cyanopyridine.
Scheme 1. Optimized reaction conditions with 4-cyanopyridine.
Diameter of RuNps (nm)
Fig. 1. TEM image of RuNps in the reduction of 4-cyanopyridine.

J.J. García et al. / Inorganica Chimica Acta 464 (2017) 55–58
57
Diameter of RuNps (nm)
Fig. 2. TEM image of RuNps in the reduction of 3-cyanopyridine.
other products
imine
amine
Scheme 3. Reactivity of RuNps with 3-cyanopyridine.
Fig. 3. Use of ruthenium catalytic precursors at 140 °C, 150 psi H2, and at 24 h.
Considering this result, and that the hydrogenation of aromatic
dinitriles behaves like a homogeneous system, we envisioned sev-
eral possible catalytic species being formed using 1 as a catalytic
precursor, along with TPP and H2 [18]. Thus, we independently
prepared the following compounds by the reported methods and
tested them as catalytic precursors: [Ru3(CO)9(PPh3)3] [19], [H4-
Ru4(CO)12] [20], and [Ru(H)2(CO)(PPh3)3] [21]. The results for the
hydrogenation of 1,4-dicyanobenzene are summarized in Fig. 3.
As seen in Fig. 3, the complex [Ru(H)2(CO)(PPh3)3] produced
similar reactivity and product distribution, and was likely one of
the active catalytic precursors after mixing 1 with TPP and H2.
An experiment using [Ru(H)2(CO)(PPh3)3] and 1,4-dicyano benzene
in a 1:1 ratio allowed us to detect two new hydrido-phosphine
compounds formed in solution, that may in turn be related to some
intermediates during catalysis (see SI, Fig. S8).
Scheme 4. Reactivity of aromatic dinitriles.
fore having a better yield towards the hydrogenated product: the
secondary amine. In addition, the 1,2-dicyanobenzene did not
showed any reactivity at all, as previously observed in our group
with nickel catalysts [6b], so we speculate that this substrate
may act as a bidentate ligand itself, blocking coordination sites
more efficiently than the 1,3- and 1,4-dicyanobenzenes, and
consequently inhibiting any further reaction.
Another important aspect of the reactivity in dicyanobenzenes
was the assessment for the presence of Ru-Nps; to our surprise,
the hydrogenation reaction of 1,4- and 1,3-dicyanobenzenes was
not inhibited by a mercury drop test. Despite this, we centrifuged
reaction mixtures and studied them with TEM, in which no metal-
lic nanoparticles were found, only crystals from the final Ru-
complexes.
3. Conclusions
We demonstrated that catalytic hydrogenation of mono-
cyanopyridines can be made with [Ru3(CO)12] as a precursor of
Ru-Nps formed in situ, to produce a particular product that is
highly dependent on the substitution in the pyridine ring: a sec-
ondary amine was achieved for 4-cyano pyridine, while the sec-
ondary imine for 3-cyanopyridine was achieved in both high
yields, and a trisubstituted imidazole in the case of 2-cyanopy-
ridine with a good yield. The hydrogenation of 1,4- and 1,3-
dicyanobenzenes using 1 was achieved with milder conditions:

58
J.J. García et al. / Inorganica Chimica Acta 464 (2017) 55–58
temperature and shorter reaction times via a homogeneous cat-
alytic system, leading to the formation of a corresponding sec-
ondary amine as a major product.
4.2.4. Procedure for catalytic hydrogenation of dicyanobenzenes: 1,4-
dicyanobenzene
1,4-dicyanopyridine
(0.3 g,
2.34 mmol),
1
(1.5 mg,
0.0023 mmol), TPP (1.8 mg, 0.007 mmol) and THF (25 mL) charged
in a 100-mL Parr reactor, as it was closed and then pressurized out
of the dry box with H2 (150 psi). Afterward, the reaction vessel was
heated to 140 °C for 24 h. Soon after, the reactor was cooled down
4. Experimental section
to room temperature and vented into a hood; 1
mixture was directly analyzed by GC–MS.
lL the reaction
4.1. General considerations
Unless otherwise noted, all manipulations were performed
using standard Schlenk techniques in an inert-gas/vacuum double
manifold or under an argon atmosphere (Praxair 99.998) in an
MBraun UniLab glovebox (<1 ppm H2O and O2). All liquid reagents
were purchased as reagent grades and degassed before use. All
organic nitriles, [Ru3(CO)12] and TPP were purchased from Sigma-
Aldrich and stored in a glovebox before use, while dried with stan-
dard techniques. Deuterated solvents were purchased from Cam-
bridge Isotope Laboratories and stored under 4 Å molecular
sieves for 24 h before use. NMR spectra were recorded at room
temperature on a 300 MHz Varian Unity spectrometer unless
otherwise noted. 1H NMR spectra (d parts per million) are reported
relative to their residual protio-solvent. GC–MS determinations
were performed using an Agilent Technologies G3171A equipped
with the following column: 5% phenylmethylsilicone,
30 m * 0.25 mm * 0.25 mm. Catalytic experiments were carried out
in a 100-mL stainless steel Parr T315SS reactor. Elemental analyses
(EAs) were performed by USAII-FQ-UNAM or USAI-UNAM using a
PerkinElmer microanalizer 2400. Transmission electron micro-
scopy (TEM) micrographs were determined on a Jeol-2010 micro-
scope equipped with a lanthanum hexaboride filament operating
at an accelerating voltage of 200 kV. Samples for TEM observations
were prepared by placing a thin film of the heptanes Ru-NPs solu-
tion in a holey carbon grid. Metal particle size distribution was
estimated at about 200 particles, assuming a spherical shape, and
found in an arbitrary chosen area in enlarged micrographs.
4.2.5. Procedure for the catalytic hydrogenation of 1,3- and 1,2-
dicyanobenzenes
Following a similar procedure as described for 1,4-dicyanoben-
zene, both substrates were used in separate experiments, although
the 1,2-dicyanobenzene did not react. Mercury drop experiments
were done similarly in the presence of two mercury drops.
Acknowledgements
We thank CONACYT (178265) and DGAPA-UNAM (IN-202516)
for their financial support. N. P-L also thanks CONACYT for a grad-
uate studies grant.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.ica.2017.04.051.
References
[1] S.A. Lawrence, Amines: Synthesis Properties and Applications, Cambridge
University Press, Cambridge, UK, 2005.
[2] S. Werkmeister, K. Junge, M. Beller, Org. Process Res. Dev. 18 (2014) 289–302.
[3] D.B. Bagal, B.M. Bhanage, Adv. Synth. Catal. 357 (2015) 883–900.
[4] Selected examples are: (a) T. Li, I. Bergner, F. N. Haque, M. Zimmer-De Iuliis, D.
Song, R. H. Morris, Organometallics 26 (2007) 5940–5949.;
(b) R. Reguillo, M. Grellier, N. Vautravers, L. Vendier, S. Sabo-Etienne, J. Am.
Chem. Soc. 132 (2010) 7854–7855;
(c) A. Mukherjee, D. Srimani, Y. Ben-David, D. Milstein, ChemCatChem. 9
(2017) 559–563;
(d) R. Adam, E. Alberico, W. Baumann, H.-J. Drexler, R. Jackstell, M. Beller,
Chem. Eur. J. 22 (2016) 4991–5002;
4.2. Catalytic experiments
(e) R. Adam, C.B. Bheeter, R. Jackstell, M. Beller, ChemCatChem. 8 (2016) 1329–
1334.
[5] (a) S.W. Heinzman, B. Ganem, J. Am. Chem. Soc. 104 (1982) 6801–6802;
(b) R. Adam, C.B. Bheeter, J.R. Cabrero-Antonino, K. Junge, R. Jackstell, M. Beller,
ChemCatChem. 10 (2017) 1–6.
4.2.1. Procedure for the catalytic hydrogenation of cyanopyridines: 4-
cyanopyridine
4-cyanopyridine (0.5 g, 4.8 mmol), [Ru3(CO)12
] (1) (3 mg,
0.0048 mmol), TPP (4 mg, 0.0144 mmol) and THF (25 mL) were
charged in a 100-mL Parr reactor; the reactor was closed and pres-
surized out of the dry box with H2 (60 psi). Afterward, the reaction
vessel was heated up to 200 °C for 72 h. Following this, the reactor
was cooled down to room temperature and vented into a hood;
[6] (a) E. Band, W.R. Pretzer, M.G. Thomas, E.L. Muetterties, J. Am. Chem. Soc. 99
(1977) 7380–7381;
(b) P. Zerecero-Silva, I. Jimenez-Solar, M.G. Crestani, A. Arevalo, R. Barrios-
Francisco, J.J. Garcia, App. Cat. A. Gen. 363 (2009) 230–234.
[7] Z. Lu, T.R. Williams, Chem. Comm. 50 (2014) 5391–5393.
[8] L.K. Freidlin, T.A. Sladkova, Russ. Chem. Rev. 33 (1964) 319–329.
[9] K. Miura, S. Suyama, H. Kondo, K. Morikawa, Pat JP09040630, Showa Denko K.
K., JP (1995).
[10] A. Okamoto, Pat. JP2007269645A, Mitsubishi Gas Chemical Co., JP (2007).
[11] M. Chatterjee, M. Sato, H. Kawanami, T. Yokoyama, T. Suzuki, T. Ishizaka, Adv.
Synth. Catal. 352 (2010) 2394–2398.
[12] F. Chen, C. Topft, J. Radnik, C. Kreyenschulte, H. Lund, M. Schneider, A.-E.
Surkus, L. He, K. Junge, M. Beller, J. Am. Chem. Soc. 138 (2016) 8781–8788.
[13] C. Bornschein, S. Werkmeister, B. Wendt, H. Jiao, E. Alberico, W. Baumann, H.
Junge, K. Junge, M. Beller, Nat Commun. 5 (2014) 1–11.
1 lL of the reaction mixture was directly analyzed by GC–MS. All
samples produced at the end of the hydrogenation experiments
were centrifuged (10–15 min at 5000 cycles/min) in order to
recover the corresponding ruthenium nanoparticles and further
analyzed by TEM.
4.2.2. Hydrogenation of 3-cyanopyridine and 2-cyanopyridine
An entirely similar experimental procedure as above was fol-
lowed, but using substrate 3-cyanopyridine or 2-cyanopyridine.
[14] M. Li, D. Kong, G. Zi, G. Hou, J. Org. Chem. 82 (2017) 680–687.
[15] C. Ortiz-Cervantes, I. Yañez, J.J. García, J. Phys. Org. Chem. 25 (2012) 902–907.
[16] J.A. Joule, K. Mills, Heterocyclic Chemistry, fifth ed., Wiley, 2010, pp. 115–119.
[17] J.J. Garcia, P. Zerecero-Silva, G. Reyes-Rios, M.G. Crestani, A. Arévalo, R. Barrios-
Francisco, Chem. Comm. 47 (2011) 10121–10123.
[18] C.J. Sleigh, S.B. Duckett, R.J. Mawby, J.P. Lowe, Chem. Comm. (1999) 1223–
1224.
[19] K. Dallmann, R. Buffon, J. Mol. Catal. A: Chem. 172 (2001) 81–87.
[20] S. Aime, R. Gobetto, A. Orlandi, C.J. Groombridge, G.E. Hawkes, M.D. Mantle, K.
D. Sales, Organometallics 13 (1994) 2375–2379.
4.2.3. Mercury drop test
All experiments were performed following the above-described
procedure, in addition to use of reagents; that is, two mercury
drops were added into the reaction mixture.
[21] J.J. Levison, S.D. Robinson, J. Chem. Soc. (A) (1970) 2947–2954.