Dramatic rate acceleration by a diphenyl-2-pyridylphosphine ligand in the hydration of nitriles catalyzed by Ru(acac)2 complexes

Article abstract of DOI:10.1021/om050792b

New ruthenium(II) complexes having acac (=acetylacetonato) and diphenyl-2-pyridylphosphine as ligands proved to be excellent catalysts for hydration of nitrites to amides under neutral conditions. Among the ruthenium complexes examined, cis-Ru(acac)₂(PPh₂py)₂ exhibited the highest activity, with a turnover frequency of up to 20 900 (mol of amide) / ((mol of catalyst) h).

Full text of DOI:10.1021/om050792b

© Copyright 2005
Volume 24, Number 26, December 19, 2005
American Chemical Society
Communications
Dramatic Rate Acceleration by a
Diphenyl-2-pyridylphosphine Ligand in the Hydration of
Nitriles Catalyzed by Ru(acac)2 Complexes
Toshiyuki Oshiki,*,† Hitoshi Yamashita,† Kensuke Sawada,†
Masaru Utsunomiya,‡ Kazunari Takahashi,‡ and Kazuhiko Takai*,†
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology,
Okayama University, Tsushima, Okayama 700-8530, Japan, and C4 Derivatives Technology
Laboratory, Petrochemicals R&TD Division Research Center, Mitsubishi Chemical
Corporation, Kurashiki 712-8094, Japan
Received September 14, 2005
Summary: New ruthenium(II) complexes having acac
()acetylacetonato) and diphenyl-2-pyridylphosphine as
ligands proved to be excellent catalysts for hydration of
nitriles to amides under neutral conditions. Among the
ruthenium complexes examined, cis-Ru(acac)2(PPh2py)2
exhibited the highest activity, with a turnover frequency
of up to 20 900 (mol of amide)/((mol of catalyst) h).
catalysts.2d,e Among them, Murahashi’s ruthenium sys-
tem3 and Parkins’s platinum complexes4 are well-known
to exhibit high yields and high turnover numbers.
Recently reported heterogeneous catalysts also im-
proved the synthetic efficiency for the preparation of
amides.5
Here we describe new Ru(acac)2 complexes having a
diphenyl-2-pyridylphosphine ()PPh2py; 1) ligand that
act as extremely active homogeneous catalysts for the
hydration of nitriles. Phosphine 1 is one of the most
extensively studied P,N hybrid ligands,6 due to its
The catalytic hydration of nitriles is an ideal atom-
economical reaction and sustainable method for the
preparation of amides. Metalloenzyme1a and heteroge-
neous transition-metal catalysts1b have been employed
in the large-scale industrial production of amides from
nitriles. A variety of homogeneous catalysts have also
been investigated:1c,d main-group zinc catalysts,2a late-
transition-metal catalysts,2b,c and early-transition-metal
(2) For recent examples, see: (a) Kopylovivh, M. N.; Kukushkin, V.
Y.; Hauka, M.; Frausto da Silva, J. J. R.; Pombeiro, A. J. L. Inorg.
Chem. 2002, 41, 4798. (b) Fung, W. K.; Huang, X.; Man, M. L.; Ng, S.
M.; Hung, M. Y.; Lin, Z.; Lau, C. P. J. Am. Chem. Soc. 2003, 125, 11539.
(c) Jiang, X.; Minnaard, A. J.; Feringa, B. L.; de Vries, J. G. J. Org.
Chem. 2004, 69, 2327. (d) Breno, K. L.; Pluth, M. D.; Tyler, D. R.
Organometallics 2003, 22, 1203. (e) Breno, K. L.; Pluth, M. D.; Landorf,
C. W.; Tyler, D. R. Organometallics 2004, 23, 1738.
* To whom correspondence should be addressed. Fax: +81-86-
251-8094. E-mail: oshiki@cc.okayama-u.ac.jp (T.O.); ktakai@
cc.okayama-u.ac.jp (K.T.).
(3) (a) Murahashi, S.-I.; Sasao, S.; Naota, T. J. Org. Chem. 1992,
57, 2521. (b) Murahashi, S.-I.; Naota, T. Bull. Chem. Soc. Jpn. 1996,
69, 1805.
† Okayama University.
‡ Mitsubishi Chemical Corporation.
(1) For reviews, see: (a) Schultz, B. In Enzyme Catalysis in Organic
Synthesis; Drauz, K., Waldmann, H., Eds.; Wiley-VCH: Weinheim,
Germany, 2002; p 699. (b) Weissermel, K.; Arpe, H.-J. Industrial
Organic Chemistry, 4th ed.; Wiley-VCH: Weinheim, Germany, 2003;
p 310. (c) Tani, K.; Kataoka, Y. In Catalytic Heterofunctionalization;
Togni, A., Gru¨tzmacher, H., Eds.; Wiley-VCH: New York, 2001; p 171.
(d) Kukushkin, V. Y.; Pombeiro, A. J. L. Inorg. Chim. Acta 2005, 358,
1.
(4) (a) Ghaffar, T.; Parkins, A. W. Tetrahedron Lett. 1995, 36, 8657.
(b) Ghaffar, T.; Parkins, A. W. J. Mol. Catal. A 2000, 160, 249.
(5) (a) Mori, K.; Yamaguchi, K.; Mizugaki, T.; Ebitani, K.; Kaneda,
K. Chem. Commun. 2001, 461. (b) Solhy, A.; Smahi, A.; Badaoui, H.
E.; Elaabar, B.; Amoukal, A.; Tikad, A.; Sebti, S.; Macquarrie, D. J.
Tetrahedron Lett. 2003, 44, 4031. (c) Yamaguchi, K.; Matsushita, M.;
Mizuno, N. Angew. Chem., Int. Ed. 2004, 43, 1576.
(6) Newkome, G. R. Chem. Rev. 1993, 93, 2067.
10.1021/om050792b CCC: $30.25 © 2005 American Chemical Society
Publication on Web 11/18/2005

6288 Organometallics, Vol. 24, No. 26, 2005
Communications
Scheme 1. Preparation of Ru(acac)2(K2-PPh2Py)
(2)
accessibility. Among the hybrid ligands for homogeneous
catalytic reactions,7 the P,N hybrid ligands have at-
tracted considerable attention, especially in late-transi-
tion-metal catalysts.8 Grotjahn and co-workers have
reported that ruthenium complexes having a bifunc-
tional P,N ligand exhibited an enzyme-like enhance-
ment of rate and selectivity in the anti-Markovnikov
hydration of terminal alkynes.9 Grotjahn’s ruthenium
catalysts were inactive for hydration of a nitrile group;
however, the P,N ligand system seemed promising as a
potential hydration catalyst for other multiple bonds.
Therefore, we prepared new ruthenium complexes hav-
ing the phosphine 1 and acac ligand.10
Figure 1. Molecular structures of 2 (left) and 3 (right).
Scheme 2. Preparation of cis-Ru(acac)2(PPh2Py)2
(3)
A new Ru(acac)2-PPh2py complex was prepared by
a modifying the procedure for Ru(acac)2(PR3)2 estab-
lished by Bennett and Ernst.11 Treatment of Ru(acac)2-
(η2-C8H14)2
with 1 in a mixed solvent of THF and
11b
comparable to those reported for cis-Ru(acac)2(PR3)2.11
The O(2)-Ru-P(1) angle (163.10(5)°) deviates from the
ideal 180°, whereas the O(1)-Ru-O(3) and O(4)-Ru-
N(1) angles are close to 180°. The small bite angle
(69.80(6)°) for P(1)-Ru-N(1) is ascribed to the forma-
tion of the four-membered chelate ring. The Ru-P(1)
and Ru-N(1) distances are shorter than those reported
for RuCl2(κ2-PPh2Py)(CO)2 (Ru-P ) 2.322(2) Å and
Ru-N ) 2.119(6) Å).10a The ligand 1 strongly co-
ordinates to the Ru(acac)2 unit as compared to the
RuCl2(CO)2 unit.
The solid-state six-coordinate structure is consistent
with that observed in solution. Four nonequivalent
methyl signals of two acac ligands appeared at δ 1.78,
1.92, 1.95, and 2.20 in the 1H NMR spectra. A variable-
temperature 1H NMR experiment revealed that 2
maintains a six-coordinate structure from 25 to 75 °C
in C6D6 solution.
The nitrogen atom of 1 that is coordinated to the
ruthenium center proved to be labile. Treatment of
2 with 1 equiv of 1 in C6D6 afforded cis-Ru(acac)2-
(PPh2py)2 (3) quantitatively (Scheme 2). Complex 3 was
also prepared by the reaction of Ru(acac)2(isoprene)12
with 2 equiv of 1. Two phosphorus atoms coordinated
to the ruthenium center (δ 57.9 in 31P{1H} NMR). The
slightly distorted octahedral structure of 3 was revealed
by X-ray crystallographic analysis.14 The bond elonga-
tion of Ru-O lengths trans to the phosphorus atoms
(Ru-O(2) ) 2.089(1) Å and Ru-O(4) ) 2.103(1) Å) is
attributed to the trans influence of the PPh2py ligands
(Ru-O(1) ) 2.066(2) Å and Ru-O(3) ) 2.064(2) Å).
Catalytic hydration of nitriles was examined using
benzonitrile as a substrate (Table 1). Treatment of a
mixture of benzonitrile with the catalyst 2 and water
in 1,2-dimethoxyethane at 180 °C for 3 h afforded
water at 30 °C gave Ru(acac)2(κ2-PPh2py) (2) in 78%
yield (Scheme 1). Attempts to prepare 2 from the diene
complexes Ru(acac)2(2,3-dimethyl-1,3-butadiene)11a and
Ru(acac)2(isoprene)12 failed.
An X-ray crystallographic analysis revealed that 2 has
a monomeric discrete molecular structure (Figure 1).13
The structural parameters for the Ru(acac)2 unit are
(7) For reviews, see: (a) Slone, C. S.; Weinberger, D. A.; Mirkin, C.
A. Prog. Inorg. Chem. 1999, 48, 233. (b) Braunstein, P.; Naud, F.
Angew. Chem., Int. Ed. 2001, 40, 680.
(8) For recent examples, see: (a) Mueller, C.; Lachicotte, R. J.; Jones,
W. D. Organometallics 2002, 21, 1975. (b) Kuriyama, M.; Nagai, K.;
Yamada, K.; Miwa, Y.; Taga, T.; Tomioka, K. J. Am. Chem. Soc. 2002,
124, 8932. (c) Braunstein, P. J. Organomet. Chem. 2004, 689, 3953.
(d) Kno¨pfel, T. E.; Aschwanden, P.; Ichikawa, T.; Watanabe, T.;
Carreira, E. M. Angew. Chem., Int. Ed. 2004, 43, 5971. (e) Yu, J. O.;
Lam, E.; Sereda, J. L.; Rampersad, N. C.; Lough, A. J.; Browning, C.
S.; Farrar, D. H. Organometallics 2005, 24, 37. (f) Abdur-ashid, K.;
Guo, R.; Lough, A. J.; Morris, R. H. Song, D. Adv. Synth. Catal. 2005,
347, 571. (g) Wu, J.; Ji, J.-X.; Chan, A. S. C. Proc. Natl. Acad. Sci.
2005, 102, 3570. (h) Pamies, O.; Dieguez, M.; Claver, C. J. Am. Chem.
Soc. 2005, 127, 3646. (i) Ito, M.; Kitahara, S.; Ikariya, T. J. Am. Chem.
Soc. 2005, 127, 6172.
(9) (a) Grotjahn, D. B.; Incarvito, C. D.; Rheingold, A. L. Angew.
Chem., Int. Ed. 2001, 40, 3884. (b) Grotjahn, D. B.; Lev, D. A. J. Am.
Chem. Soc. 2004, 126, 12232.
(10) Several ruthenium complexes bearing 1 were prepared. (a)
Olmstead, M. M.; Maisonnet, A.; Farr, J. P.; Balch, A. L. Inorg. Chem.
1981, 20, 4060. (b) Maisonnet, A.; Farr, J. P.; Olmstead, M. M.; Hunt,
C. T.; Balch, A. L. Inorg. Chem. 1982, 21, 3961. (c) Schutte, R. P.;
Rettig, S. J.; Joshi, A. M.; James, B. R. Inorg. Chem. 1997, 36, 5809.
(d) Caballero, A.; Jalon, F. A.; Manzand, B. R. Chem. Commun. 1998,
1879. (e) Rida, M. A.; Coperet, C.; Smith, A. K. J. Organomet. Chem.
2001, 628, 1. (f) Lalrempuia, R.; Carroll, P. J.; Kollipara, M. R. J. Chem.
Sci. 2004, 116, 21.
(11) (a) Ernst, R. D.; Mele´ndez, E.; Stahl, L. Ziegler, M. L. Organo-
metallics 1991, 10, 3635. (b) Bennett, M. A.; Chung, G.; Hockless, D.
C. R.; Neumann, H.; Willis, A. C. J. Chem. Soc., Dalton Trans. 1999,
3451. (c) Bennett, M. A.; Byrnes, M. J.; Willis, A. C. Organometallics
2003, 22, 1018. (d) Bennett, M. A.; Byrnes, M. J.; Kovacik, I. J.
Organomet. Chem. 2004, 689, 4463. (e) Bennett, M. A.; Byrnes, M. J.;
Chung, G.; Edwards, A.; Willis, A. C. Inorg. Chim. Acta 2005, 358,
1692.
(12) Mele´ndez, E.; Ilarraza, R.; Yap, G. P. A.; Rheingold, A. L. J.
Organomet. Chem. 1996, 522, 1.
(13) Crystal data for 2:
triclinic, P1h (No. 2), a ) 11.0230(8) Å, b ) 11.207(1) Å, c ) 12.7551(8)
Å, R ) 72.3808(7)°, â ) 67.497(5)°, γ ) 81.631(1)°, V ) 1386.6(2) Å3, Z
) 2, Dcalcd ) 1.456 g cm-3, µ(Mo KR) ) 6.59 cm-1, 11 393 reflections
measured, R1 ) 0.036, wR2 ) 0.089.
C
27H28NO4PRu‚0.5C6H5CH3; T ) 150 K,
(14) Crystal data for 3: C44H42N2O4P2Ru; T ) 150 K, triclinic, P1h
(No. 2), a ) 10.224(1) Å, b ) 10.799(2) Å, c ) 17.946(3) Å, R )
75.988(10)°, â ) 88.433(10)°, γ ) 81.196(6)°, V ) 1899.7(5) Å3, Z ) 2,
Dcalcd ) 1.444 g cm-3, µ(Mo KR) ) 5.43 cm-1, 15 740 reflections
measured, R1 ) 0.034, wR2 ) 0.109.

Communications
Organometallics, Vol. 24, No. 26, 2005 6289
Table 1. Hydration of Benzonitrile Catalyzed by
Ruthenium Complexesa
Table 3. Catalytic Hydration of Various Nitriles
Catalyzed by 3a
entry
cat.
additive time (h) yield (%)
1
2
2
3
none
none
none
none
1
1
35
98
100
66
99
0
2
3
3
0.17
24
4
cis-Ru(acac)2(PPh3)2
2
5
0.17
3
6b
7
3
none
none
none
none
1
RuCl2(κ2-PPh2py)(CO)2
[Ru(CO)2(PPh2py)]3
RuCl2(p-cymene)(PPh2py)
RuCl2(κ2-PPh2py)(CO)2
[Ru(CO)2(PPh2py)]3
3
0
8
9
10
11
3
25
3
0
61
3
3
1
3
a Reaction conditions: benzonitrile (1 mmol), water (2 mmol),
catalyst (0.02 mmol, 2 mol % per benzonitrile), additive (0.02
mmol), DME (0.5 mL), 180 °C. b Toluene was used as a solvent.
Table 2. Catalytic Hydration of Benzonitrilea
amt of cat. amt of H2O temp time yield
a Reaction conditions: nitrile (1 mmol), 3 (0.002 mmol, 0.2 mol
% per nitrile), H2O (4 mmol), DME (0.5 mL), 180 °C. b 0.04 mmol
of 3 was used. c Determined by GC.
entry cat.
(mol %)
(equiv)
(°C) (min) (%) TOFd
1
3
3
3
3
3
3
4
0.20
0.024
0.024
0.20
2.00
0.50
0.50
2
180
180
180
180
150
80
10 99
10 38
2970
11400
20900
2640
222
2
2
3
4
10 85
However, at 180 °C, benzamide was obtained in only
10% yield by catalyst 4. Complex 3 is thermally stable
and therefore can act as a catalyst at high temperature
with high TOF.
4b
5
2
10 88
10 74
210 trace
210 10
2
6
4
0
6
7c
excess
180
a Reaction conditions: benzonitrile (1 mmol), DME (0.5 mL).
b Ligand 1 was added (1:3 ) 4:1). c The reaction conditions were
the same as in Feringa’s report,2c except for the temperature. d In
units of (mol of amide)/((mol of catalyst) h).
The results of the catalytic hydration of various kinds
of nitriles are summarized in Table 3. Hydration of
substituted aromatic nitriles gave corresponding amides
in almost quantitative isolated yields under similar
neutral conditions. Industrially important nicotinamide
could be prepared from 3-cyanopyridine in 99% yield.
Complex 3 was also effective for hydration of less
reactive aliphatic nitriles;5c nonanamide was obtained
from nonanonitrile in 93% yield under conditions similar
to those for aromatic nitriles. The catalytic hydration
proved to be affected by the presence of unsaturated
C-C bonds. For example, the hydration of cinnamo-
nitrile needed 90 min to proceed to completion. 5-Hex-
enenitrile was hydrolyzed; however, the amount of the
catalyst should be increased. Hydration of 5-hexyne-
nitrile with a catalytic amount of 3 did not proceed, and
85% of 5-hexynenitrile was recovered. The catalytic
reactivity toward alkynes with 3 shows a sharp contrast
to that observed with reported ruthenium catalysts
which promote the alkyne hydration without affecting
the coexisting nitrile groups.9,15 Hydration of trichloro-
acetonitrile and sterically crowded pivalonitrile with 3
went to completion within 30 min to give the corre-
sponding amides.
benzamide in 98% yield along with recovered benzo-
nitrile in 2% yield, and no organic byproduct was
detected (entry 2). The hydration catalyzed by 3 pro-
ceeded to completion within 10 min (0.17 h) (entry 3).
This remarkable rate acceleration by ligand 1 was
demonstrated by comparison with the hydration cata-
lyzed by a triphenylphosphine analogue of 3 (entry 4).
The rapid hydration was also observed when 1 molar
equivalent of 1 was added to the reaction mixture of
entry 2 (entry 5). Reported Ru-PPh2py complexes were
also examined for the hydration of benzonitrile. A κ2-
P,N bidentate complex, RuCl2(κ2-PPh2py)(CO)2,10a was
inactive for the hydration and two η1-P-coordinated
complexes, [Ru(PPh2py)(CO3)]310b and RuCl2(p-cymene)-
(PPh2py),10f were slightly effective (entries 7-9). Addi-
tion of 1 to the reaction mixture of entry 8 improved
the yield of benzamide, although the reactivity was still
low (entry 11). These results indicate that the Ru(acac)2
fragment was also important for the high catalytic
activity.
In transition-metal-catalyzed hydration of nitriles, it
has been considered that a nitrile is activated upon
coordination to a vacant site of a transition-metal center,
and then, nucleophilic attack of water to the coordinated
nitrile occurs.1c,d,3,16 To clarify the mechanism catalyzed
by Ru(acac)2-PPh2Py complexes, stoichiometric hydra-
tion of cis-Ru(acac)2(PPh2py)(PhCN) (5) was examined.
To our surprise, the coordinated benzonitrile was not
hydrolyzed by treatment of 5 with an excess amount of
water in DME at 180 °C for even 24 h. In contrast, a
Complex 3 exhibited a remarkably high activity, even
at a low concentration of the catalyst (Table 2). The
hydration of benzonitrile catalyzed by 3 in DME af-
forded benzamide in 85% yield, and a TOF of 20900 was
achieved (entry 3). The catalytic activity decreased
slightly when 1 was added to the reaction mixture of
entry 1 (entry 4). The conversion was reduced signifi-
cantly by decreasing the reaction temperature. Complex
3 gave a trace amount of benzamide at 80 °C (entry 6),
whereas almost quantitative formation of benzamide
was reported by the platinum catalyst PtH(PPh2OH)-
(PPh2O)2H (4), at a similar reaction temperature.2c,4
Complex 4 has been known to be a highly active
catalyst; for example, hydration of benzonitrile pro-
ceeded with a TOF of up to 518 at about 90 °C.4
(15) Suzuki, T.; Tokunaga, M.; Wakatsuki, Y. Org. Lett. 2001, 3,
735.
(16) (a) Erxleben, A.; Mutikainen, I.; Lippert, B. J. Chem. Soc.,
Dalton Trans. 1994, 3667. (b) Nagao, H.; Hirano, T.; Tsuboya, N.;
Shiota, S.; Mukaida, M.; Oi, T.; Yamasaki, M. Inorg. Chem. 2002, 41,
6267.

6290 Organometallics, Vol. 24, No. 26, 2005
Communications
Scheme 3. Plausible Mechanism for the Catalytic
Hydration of Benzonitrile
exclude the possibility of the formation of the C-bonded
acac complex. However, to our knowledge there are no
reports on a ruthenium complex having a C-bonded acac
ligand. The vacant coordination site for coordination of
nitriles would be generated by the dissociation of an
oxygen atom caused by the trans influence of the PPh2py
ligand. For 3, the elongation of the Ru-O bond trans
to the PPh2py ligand was revealed by X-ray analysis.
The generated vacant site should be occupied in the
presence of 1 (Table 2, entry 4). Nucleophilic addition
of water was promoted by coordination to the PPh2py
ligand (Scheme 3, B).19
Acknowledgment. This work was supported by a
Grant-in Aid for Scientific Research on Priority Areas
(No. 14078219, “Reaction Control of Dynamic Com-
plexes”) from the Ministry of Education, Culture, Sports,
Science, and Technology of Japan and the COE program
of Okayama University.
quantitative formation of benzamide was observed when
the reaction was conducted in the presence of 2 mol %
of 5 in DME at 180 °C for 3 h. These experiments
suggest that the bis(acac) complex 5 is not the active
species for this hydration but acts as a precatalyst. The
precatalyst 5 could convert to the active species in the
presence of an excess amount of benzonitrile.
These preliminary results indicate that the active
species would be the complex A bearing a monodentate
acac ligand (Scheme 3). A bidentate O-bonded acac
ligand is known to isomerize to a monodentate O-bonded
ligand17 or C-bonded mode.17a,18 Complexes 3 and 5
could be converted to O-bonded A in the presence of an
excess amount of benzonitrile. At this point, we cannot
Supporting Information Available: Text and figures
giving synthetic procedures, characterization data, and ORTEP
drawings and CIF files giving X-ray crystallographic data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OM050792B
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(19) A similar mechanism for the attack of water assisted by a
nitrogen-containing ligand was proposed by Grotjahn in the hydration
of alkynes.9
(17) (a) Komiya, S.; Kochi, J. K. J. Am. Chem. Soc. 1977, 99, 3695.
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