Selective ruthenium-catalyzed hydration of nitriles to amides in pure aqueous medium under neutral conditions

Article abstract of DOI:10.1002/chem.200800847

A study was conducted to demonstrate that water-soluble ruthenium(II) complexes can be used as catalysts for the hydration of nitriles in pure aqueous media and under neutral conditions. The hydration of benzonitrile was investigated as a model reaction and the ruthenium precursor was added to a 0.33_M aqueous solution of benzonitrile at 100°C, while the reaction was monitored by gas chromatography. All the complexes checked, were found to be active and selective catalysts in the hydration process, providing benzamide as a specific reaction product. The most relevant results were obtained by using ruthenium complexes, bearing a nitrogen-containing ligand, which led to appropriate production of benzamide. The most effective ruthenium complex was found to be an efficient catalyst for the selective hydration of a large number of other nitriles.

Full text of DOI:10.1002/chem.200800847

COMMUNICATION
DOI: 10.1002/chem.200800847
Selective Ruthenium-Catalyzed Hydration of Nitriles to Amides in Pure
Aqueous Medium UnderNeutral Conditions
Victorio Cadierno,* Javier Francos, and JosØ Gimeno*[a]
Hydration of nitriles to generate the corresponding
amides is an important transformation from both academic
and industrial points of view. Amides not only constitute
versatile building blocks in synthetic organic chemistry,[1]
but also exhibit a wide range of industrial applications[2,3]
and pharmacological interest.[4] Nitrile hydration can be con-
ventionally achieved in the presence of strong acid or base
catalysts,[1,5] but major drawbacks of these classical methods
are: 1) the harsh conditions usually required which pre-
cludes the presence of sensitive functional groups, and 2)
the reactions are difficult to stop at the amide stage and fur-
ther hydrolysis to the carboxylic acid often takes place, es-
pecially in basic media (see Scheme 1). Moreover, from an
ed to date, only a few complexes can act as selective cata-
lysts to form amides.[6] Relevant examples, among others,
are: the Murahashiꢀs ruthenium dihydride [RuH2
the Parkinsꢀs platinum hydride [PtH(PMe2OH)-
{(PMe2O)2H}],[9] the acetylacetonate complex cis-[Ru-
(acac)
2(PPh2py)2] (py=pyridyl)[10] and the recently described
RhI-based system [{Rh
(m-OMe)(cod)}2]/PCy3 (cod=1,5-cy-
N
AHCTREUNG
AHCTREUNG
A
ACHTREUNG
A
ACHTREUNG
clooctadiene, Cy=cyclohexyl),[11] all of them showing a re-
markable activity. In contrast to these catalytic processes
performed in organic solvents, and despite the growing in-
terest to develop environmentally benign and safety process-
es, metal catalysts able to promote such a transformation in
pure aqueous media are much scarcer (water is one of the
best choices to replace organic solvents because of its low
cost, availability, and nontoxic nature).[12,13] Moreover, the
practical application of these homogeneous catalysts, includ-
ing rhodium,[14] palladium,[15] iridium,[16] molibdenum,[17]
nickel,[18] and zinc[19] complexes,[20] shows serious drawbacks
mainly due to their low activities and very limited scope of
the substrates.
Scheme 1. Nitrile hydration and amide hydrolysis reactions.
All these facts prompted us to search for more efficient
and versatile catalysts. Thus, following with our interest in
ruthenium-catalyzed reactions in aqueous media,[21] herein
we report that the readily available[22] and water-soluble
industrial perspective, the final neutralization step, either in
the acid- or base-catalyzed reactions, leads to extensive salt
formation with inconvenient product contamination and pol-
lution effects.
Extreme acidity and basicity can be avoided by using
transition-metal complexes. Activation of the CꢀN bond
occurs through coordination to the metal atom, thus enhanc-
ing the rate of the hydration step.[6,7] However, despite the
high number of metal-mediated hydration of nitriles report-
ruthenium(II) complexes [RuCl
PTA=1,3,5-triaza-7-phosphaadamantane),
arene)(PTA-Bn)] (3a–d; PTA-Bn=1-benzyl-3,5-diaza-1-
azonia-7-phosphaadamantane chloride), [RuCl
2(h6-arene)-
(DAPTA)] (4a–d; DAPTA=3,7-diacetyl-1,3,7-triaza-5-
phosphabicyclo[3.3.1]nonane) and [RuCl
2(h6-arene)-
(TPPMS)] (5a–d; TPPMS=meta-sulfonatophenyl)diphenyl-
A
ACHTREUNG
ACHTREUNG
AHCTREUNG
AHCTREUNG
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
phosphane sodium salt)can be used as catalysts for the hy-
dration of nitriles in pure aqueous media and under neutral
conditions. Among them, the hexamethylbenzene derivative
[a] Dr. V. Cadierno, J. Francos, Prof. Dr. J. Gimeno
Departamento de Química Orgµnica e Inorgµnica
Instituto Universitario de Química Organometµlica “Enrique Moles”
(Unidad Asociada al CSIC), Universidad de Oviedo
Juliµn Clavería 8, 33006 Oviedo (Spain)
Fax : (+34)98-510-3446
[RuCl
N
N
activity and an unprecedented tolerance to functional
groups.[23]
E-mail: vcm@uniovi.es
Firstly, the hydration of benzonitrile was studied as a
model reaction. Thus, in a typical experiment, the ruthenium
precursor (5 mol% of Ru) was added to a 0.33m aqueous
jgh@uniovi.es
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under http://dx.doi.org/10.1002/chem.200800847.
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highest rate was achieved with the hexamethylbenzene de-
rivative 3d (turnover frequency (TOF)=9.9 hÀ1; entry 8). In
contrast, with the sulfonated species 5a–d longer reaction
times (48 h) were required to attain good conversions (69–
93% yield; entries 13–16). This seems to indicate that nucle-
ophilic attack of water on the metal-coordinated nitrile may
be facilitated by hydrogen bonding with the nitrogen-con-
taining ligands.[24,25] It is worth noting that within the four
series of catalysts studied, appreciable differences in activity
were observed in function of the arene ligand used. The rate
order observed, that is, C6Me6 >1,3,5-C6H3Me3 >p-cymene>
C6H6, indicates clearly that higher performances are found
for the more sterically demanding and electron-rich arenes.
The most active complex, that is, 3d, was found to be an
efficient catalyst for the selective hydration of a large
number of other nitriles, proving the wide scope and syn-
thetic utility of this catalytic transformation. Thus, as ob-
served for benzonitrile, other aromatic and heteroaromatic
substrates could be selectively transformed into the corre-
sponding amides regardless of their substitution pattern and
electronic nature (see Table 2). The reactions, which were
all performed with a 5 mol% catalyst loading, led to the de-
solution of benzonitrile at 1008C, the course of the reaction
being monitored by gas chromatography. The results are
summarized in Table 1.
Table 1. Ru-catalyzed hydration of benzonitrile to benzamide in water.[a]
Table 2. Hydration of aromatic nitriles catalyzed by 3d in water.[a]
[b]
[d]
Entry
Catalyst
S [mgmLÀ1
]
t [h]
Yield [%][c]
TOF [hÀ1
]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
2a
2b
2c
2d
3a
3b
3c
3d
4a
4b
4c
4d
5a
5b
5c
5d
50.0
10.1
33.3
9.1
16.0
12.5
13.5
25.0
6.319
6.39
9.0
8.39
6.348
5.0
9
8
5
4
10
4
98
99
99
99
99
99
99
99
1.0
2.2
98
2.2
2.2
2.5
4.0
5.0
2.0
5.0
5.0
9.9
[c]
Entry
Substrate (Ar)
t [h]
Yield [%][b]
TOF [hÀ1
]
1
2
33
4
5
6
7
8
9
Ph
2-C6H4F
6H4F
4-C6H4F
2-C6H4Cl
2
2
2
2
99 (86)
99 (88)
99 (83)
98 (85)
9.9
9.9
9.9
9.8
-C
4
2
397 (81)
1
1
398 (68)
1
2
399 (82)
4
399 (78)
2
5
2
)399 (83
2
1
1
398 (79)
399 (80)
)399 (83
1
15
2
6.5
3
6H4Cl -C
98 (77)
98 (79)
19.6
19.6
99
98
4-C6H4Cl
2-C6H4Br
6.5
8
2.5
3
6H4Br -C
99 (91)
99 (89)
19.8
9.9
98
69
10
11
12
4-C6H4Br
<1
<1
<1
<1
3-C6H4NO2
2-Me-4-C6H4NO2
6H4Me
6.6
6.6
48
48
48
81
85
93
99 (74)
5.0
10.0
5.6
-C 133
14
15
16
17
18
19
20
21
22
4-C6H4Me
98 (71)
99 (84)
99 (80)
6.6
96 (76)
96 (82)
98 (75)
9.8
4.0
9.9
[a] Reactions performed under N2 atmosphere at 1008C using 1 mmol of
benzonitrile (0.33m in water). [Substrate]/[Ru] ratio=100:5. [b] Solubility
of the catalyst in water at 208C. [c] Yield of benzamide determined by
GC. [d] Turnover frequencies ((mol product/mol Ru)/time) were calculat-
ed at the time indicated in each case.
2-C6H4OH
3-C6H4OMe
4-C6H4OMe
4-C6H4SMe
3-C6H4NH2
C6F5
4-C6F4NH2
4-C6H4C(=O)Me
6H4C(=O)H
4-C6H4C(=O)OEt
4-C6H4CꢀCSiMe3
piperonyl
9.6
19.2
19.6
6.5
6.6
All the complexes checked were found to be active and
selective catalysts in the hydration process providing benz-
amide as the unique reaction product (benzoic acid was not
234-C
6.6
91 (69)
98 (79)
97 (85)
96 (89)
6.6
24
25
26
27
28
29
18.2
1.3
9.7
3.8
G
detected by GC in the crude reaction mixtures). As shown
in the table, no direct solubility/activity relationship was ob-
served. Interestingly, the nature of the phosphine ligand
played a crucial role on the efficiency of the process. Thus,
the best results were obtained using complexes 2,3,4a–d, all
bearing a nitrogen-containing ligand (PTA, PTA-Bn or
DAPTA), which led to benzamide in almost quantitative
yield (ꢁ98%) after 2–19 h (entries 1–12). Among them, the
1-naphthyl
5-Me-2-furyl
2-Ttienyl
5
)399 (83
399 (81)
6.6
[a] Reactions performed under N2 atmosphere at 1008C using 1 mmol of
the corresponding nitrile (0.33m in water). [Substrate]/[Ru] ratio=100:5.
[b] Yield of the amide determined by GC (isolated yields are given in
brackets). [c] Turnover frequencies ((mol product/mol Ru)/time) were
calculated at the time indicated in each case.
6602
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Homogeneous Catalysis
COMMUNICATION
sired products in ꢁ91% GC yield after 1–5 h. Subsequent
purification by column chromatography on silica gel provid-
ed analytically pure samples of the amides which were iso-
lated in 68–91% yield. Concerning the tolerance of func-
tional groups, this methodology is compatible with the pres-
ence of halide (entries 2–10, 20 and 21), nitro (entries 11
and 12), hydroxy (entry 15), ether (entries 16, 17, and 26),
thioether (entry 18), amino (entries 19 and 21), ketone
(entry 22), aldehyde (entry 23), ester (entry 24), and alkyne
(entry 25) substituents on the aromatic ring. Such a generali-
ty had never been demonstrated in aqueous media. Al-
though a longer reaction time was required (15 h), it is
worth noting the selective formation of 4-(trimethylsilanyl-
(entry 15). Sulfonyl groups are also tolerated in this transfor-
mation (entry 6).
Interestingly, although water is not an ideal solvent to per-
form microwave-assisted synthesis,[27] preliminary studies
have shown that the catalytic activity of complex 3d can be
Table 4. Hydration of nitriles catalyzed by 3d in water under MW irradi-
ation.[a]
[c]
Entry
Substrate (R)
t [min]
Yield [%][b]
TOF [hÀ1
]
1
2[d]
2[e]
32-C
4
5
6
7
8
Ph
Ph
Ph
15
75
45
30
30
30
15
30
45
20
40
40
96
98
95
96
98
98
95
98
99
99
96
99
76.8
15.7
126.7
38.4
39.2
39.2
76.0
39.2
26.4
59.4
28.8
29.7
ACHTREUNG
6H4F
6H4F -C
À
the C Si bond took place and 2) the CꢀC bond remained
3
completely unreacted despite of the known ability of ruthe-
nium complexes to promote alkyne hydration processes.[26]
4-C6H4F
3
3
6H4Cl -C
6H4Me -C
4-C6H4Me
6H4OM-eC
(CH2)2Ph
(CH2)2OPh
Table 3. Hydration of alkyl-nitriles catalyzed by 3d in water.[a]
9
10
11
3
ACHTREUNG
AHCTREUNG
[a] Reactions performed under N2 atmosphere using 1 mmol of the corre-
sponding nitrile (0.33m in water). [Substrate]/[Ru] ratio=100:5. A CEM
Discoverꢂ S-Class microwave was used (80W, 1508C, with cooling to op-
timize the power). [b] Yield of the amide determined by GC. [c] Turn-
over frequencies ((mol product/mol Ru)/time) were calculated at the
time indicated in each case. [d] Reaction performed at 1008C. [e] Reac-
tion performed with a [Substrate]/[Ru] ratio=100:1.
[c]
Entry
Substrate (Alk)
t [h]
Yield [%][b]
TOF [hÀ1
]
1
2
3Cy
4
5
6
7
8
9
10
11
12
13(
14
15
16
n-C5H11
n-C6H13
5
8
98 (83)
95 (77)
3.9
2.4
5
98 (80) .9
2
4
6
3
CH2-4-C6H4Cl
CH2OPh
CH2SO2Ph
97 (84)
99 (90)
99 (87)
95 (83)
9.7
5.0
3.3
3.2
CH2NPh
CH2-2-Thienyl
(CH2)2Ph
(CH2)2OPh
(CH2)3Ph
A
6
accelerated by using microwave (MW) irradiation (see
Table 4). For example, using the same substrate/Ru ratio
(100:5), a TOF value of 76.8 hÀ1 could be reached in the hy-
dration reaction of benzonitrile (entry 1 in Table 4) versus
9.9 hÀ1 under conventional heating (entry 1 in Table 2).
More interestingly, the use of MW irradiation allows the re-
duction of the catalyst loading. Thus, using only 1 mol% of
3d, benzonitrile could be transformed into benzamide in
95% GC yield after only 45 min leading to a TOF value of
126.7 hÀ1 (entry 3in Table 4). Such a TOF value has never
been reached in aqueous media under neutral condi-
tions.[14–20]
399 (81)
397 (85)
2
5
6.6
6.5
G
U
99 (86)
97 (79)
96 (77)
9.9
3.9
3.8
G
CH=CH2
Z)-CH=CHEt
(E)-CH=CHPh
(E)-CH=CH-4-C6H4Cl
5-norbornen-2-yl[d]
5
397 (80)
2
2
6.5
95 (75)
98 (82)
9.5
9.8
6.4
[d]
396 (78)
[a] Reactions performed under N2 atmosphere at 1008C using 1 mmol of
the corresponding nitrile (0.33m in water). [Substrate]:[Ru] ratio=100:5.
[b] Yield of the amide determined by GC (isolated yields are given in
brackets). [c] Turnover frequencies ((mol product/mol Ru)/time) were
calculated at the time indicated in each case. [d] Both as a mixture of the
corresponding endo and exo isomers in ca. 3:2 ratio.
In summary, a novel catalytic system for the selective hy-
dration of organonitriles to amides in aqueous media and
under neutral conditions, namely [RuCl
N
N
As shown in Table 3, this aqueous process is not restricted
to aromatic nitriles, the hydration of substrates containing
Bn)] (3d), has been discovered. The following features of
complex 3d merit special mention: 1) it represents a rare ex-
ample of ruthenium species able to perform nitrile hydra-
tions in water;[23] 2) it has shown a remarkable activity,
being the most efficient catalyst reported to date in aqueous
media; and 3) it has demonstrated an unprecedented toler-
ance to functional groups. All these facts confer the synthet-
ic methodology reported herein genuine potential for practi-
cal application in organic chemistry.[28] It is also worth
noting that the effect of microwaves on the catalytic nitrile
hydration process has been explored for the first time, the
rate enhancement observed deserving a more detailed study.
À
alkyl CN bonds being readily (ꢂ8 h) and efficiently
(ꢁ95% GC yields) achieved under the standard reaction
conditions. Remarkably, the industrially important hydration
of acrylonitrile proceeded cleanly using 3d to afford acryl-
amide in 96% GC yield after 5 h (77% isolated yield;
entry 12).[3] Neither hydration of the carbon carbon double
À
bond nor polymerization of acrylonitrile and/or acrylamide
occurred. The same behavior was also observed for the re-
lated a,b-unsaturated nitriles cis-2-pentenenitrile (entry 13),
cinnamonitrile (entry 14), and 4-chlorocinnamonitrile
Chem. Eur. J. 2008, 14, 6601 – 6605
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6603

V. Cadierno, J. Gimeno, and J. Francos
gashima, M. Yohda, M. Odaka, J. Inorg. Biochem. 2001, 83, 247–
253.
[8] a) S.-I. Murahashi, S. Sasao, E. Saito, T. Naota, J. Org. Chem. 1992,
57, 2521–2523; b) S.-I. Murahashi, S. Sasao, E. Saito, T. Naota, Tet-
rahedron 1993, 49, 8805–8826; c) S.-I. Murahashi, H. Takaya, Acc.
Chem. Res. 2000, 33, 225–233.
Efforts to assess the scope, limitations and synthetic applica-
tions of this aqueous transformation under MW irradiation,
as well as a complete mechanistic study, are now underway
in our laboratory.
[9] a) T. Ghaffar, A. W. Parkins, Tetrahedron Lett. 1995, 36, 8657–8660;
b) J. Akisanya, A. W. Parkins, J. W. Steed, Org. Process Res. Dev.
1998, 2, 274–276; c) T. Ghaffar, A. W. Parkins, J. Mol. Catal. A
2000, 160, 249–261; d) X.-B. Jiang, A. J. Minnaard, B. L. Feringa,
J. G. de Vries, J. Org. Chem. 2004, 69, 2327–2331.
[10] T. Oshiki, H. Yamashita, K. Sawada, M. Utsunomiya, K. Takahashi,
K. Takai, Organometallics 2005, 24, 6287–6290.
[11] A. Goto, K. Endo, S. Saito, Angew. Chem. 2008, 120, 3663–3665;
Angew. Chem. Int. Ed. 2008, 47, 3607–3609.
[12] One of the challenges of todayꢀs chemists is to move away from
highly volatile, environmentally harmful, and/or biologically incom-
patible organic solvents; see, for example: a) J. M. DeSimone, Sci-
ence 2002, 297, 799–803; b) W. M. Nelson in Green Solvents for
Chemistry, Perspectives and Practice, Oxford University Press, New
York, 2003; c) R. A. Sheldon, Green Chem. 2005, 7, 267–278;
d) D. J. Adams, P. J. Dyson, S. J. Taverner in Chemistry in Alternative
Reaction Media, Wiley, New York, 2004; e) C. K. Z. Andrade, L. M.
Alves, Curr. Org. Chem. 2005, 9, 195–218.
Experimental Section
General procedure for the catalytic reactions: Under a nitrogen atmos-
phere, the ruthenium catalyst 3d (31 mg, 5 mol% of Ru), water (3 mL)
and the corresponding nitrile (1 mmol) were introduced into a sealed
tube and the reaction mixture stirred at 1008C for the indicated time
(see Tables 1–3). The course of the reaction was monitored by regular
sampling and analysis by GC. After elimination of the solvent after re-
duced pressure, the crude reaction mixture was purified by column chro-
matography over silica gel using diethyl ether as eluent. The identity of
the resulting amides was assessed by comparison of their 1H and 13C{1H}
NMR spectroscopic data with those reported in the literature and by
their fragmentation in GC/MS.
Acknowledgements
[13] For references dealing with stoichiometric and catalytic organic syn-
thesis in aqueous media, see: a) Aqueous-Phase Organometallic Cat-
alysis: Concepts and Applications (Eds.: B. Cornils, W. A. Herr-
mann), Wiley-VCH, Weinheim, 1998; b) Aqueous Organometallic
Catalysis (Eds.: I. T. Horvµth, F. Joó), Kluwer, Dodrecht, 2001;
c) C.-J. Li, T. H. Chan in Comprehensive Organic Reactions in Aque-
ous Media, Wiley, New York, 2007; d) Organic Reactions in Water:
Principles, Strategies and Applications (Ed.: U. M. Lindstrçm),
Blackwell, Oxford, 2007.
This work was supported by the Ministerio de Educación y Ciencia
(MEC) of Spain (Project CTQ2006-08485/BQU and Consolider Ingenio
2010 (CSD2007-00006)). J.F. and V.C. thank MEC and the European
Social Fund for the award of a Ph.D. grant and a “Ramón y Cajal” con-
tract, respectively.
Keywords: amides · homogeneous catalysis · hydration ·
nitriles · ruthenium
[14] The catalytic system [{Rh
N
N
fonatophenyl)phosphine sodium salt) has been employed in the hy-
dration of acetonitrile to acetamide, in water at 808C, under basic
conditions (TOF values up to 207 hÀ1): M. C. K.-B. Djoman, A. N.
Ajjou, Tetrahedron Lett. 2000, 41, 4845–4849.
[1] a) The Chemistry of Amides (Ed.: J. Zabicky), Wiley-Interscience,
New York, 1970; b) The Amide Linkage: StructuralSignificance in
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C. M. Breneman, J. F. Liebman), Wiley, New York, 2000.
[2] I. Johansson in Kirk-Othmer Encyclopedia of Chemical Technology,
Vol. 2 ,.5th ed., Wiley, New York, 2004, pp. 442–463.
[3] Acrylamide is one of the most important commodity chemicals and
is used in coagulators, soil conditioners, and stock additives for
paper treatment and paper sizing, and for adhesives, paints, and pe-
troleum recovering agents. Hydration of acrylonitrile, by using
copper or enzymatic catalysis, produces annually more than 2”105
tons of acrylamide, representing the main route for the manufacture
of this chemical. See, for example: H. Yamada, M. Kobayashi,
Biosci. Biotechnol. Biochem. 1996, 60, 1391–1400, and references
therein.
[15] The complex [PdCl(OH)
N
N
found to catalyze the selective hydration of acetonitrile and acrylo-
nitrile to the corresponding amides, in water at 768C, under acidic
conditions (TOF values up to 29 hÀ1): a) G. Villain, G. Constant, A.
Gaset, P. Kalck, J. Mol. Catal. 1980, 7, 355–364; b) G. Villain, P.
Kalck, A. Gaset, Tetrahedron Lett. 1980, 21, 2901–2904; c) G. Vil-
lain, A. Gaset, P. Kalck, J. Mol. Catal. 1981, 12, 103–111.
[16] The iridium(I) complex [IrH(CO)(TPPTS)3] was able to catalyze
R
the selective hydration of several nitriles, in water at 1008C, under
neutral conditions (TOF values up to 14 hÀ1): C. S. Chin, S. Y. Kim,
K.-S. Joo, G. Won, D. Chong, Bull. Korean Chem. Soc. 1999, 20,
535–538.
[17] Complex [MoCp’2(OH)
(H2O)] (Cp’=h5-C5H4Me) was used as cata-
E
lyst for the selective hydration of several nitriles, in water at 808C,
under neutral conditions (TOF values up to 5 hÀ1): a) K. L. Breno,
M. D. Pluth, D. R. Tyler, Organometallics 2003, 22, 1203–1211;
b) K. L. Breno, M. D. Pluth, C. W. Landorf, D. R. Tyler, Organome-
tallics 2004, 23, 1738–1746; c) T. J. Ahmed, L. N. Zakharov, D. R.
Tyler, Organometallics 2007, 26, 5179–5187.
[4] See, for example: a) S. Rivara, A. Lodola, M. Mor, A. Bedini, G.
Spadoni, V. Lucini, M. Pannacci, F. Fraschini, F. Scaglione, R.
Ochoa Sanchez, G. Gobbi, G. Tarzia, J. Med. Chem. 2007, 50, 6618–
6626; b) A. Bhattacharya, B. P. Scott, N. Nasser, H. Ao, M. P.
Maher, A. E. Dubin, D. M. Swanson, M. P. Shankley, A. D. Wicken-
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[5] Methoden Org. Chem. (Houben Weyl) 4th ed. 1952-, Vol. E5(2),
1985, pp. 1024–1031.
[6] a) An excellent and recent review on metal-mediated and metal-cat-
alyzed nitrile hydration is available: V. Yu. Kukushkin, A. J. L. Pom-
beiro, Inorg. Chim. Acta 2005, 358, 1–21; b) for a general review on
the reactivity of metal-activated nitriles, see: V. Yu. Kukushkin,
A. J. L. Pombeiro, Chem. Rev. 2002, 102, 1771–1802.
[18] The dimeric nickel species [{Ni
N
N
propylphosphino)ethane) was successfully applied in the selective
hydration of acetonitrile, benzonitrile and dicyanobenzenes, in water
at 120–1808C, under neutral conditions (TOF values up to 14 hÀ1):
a) M. G. Crestani, A. ArØvalo, J. J. García, Adv. Synth. Catal. 2006,
348, 732–742; b) C. Crisóstomo, M. G. Crestani, J. J. García, J. Mol.
Catal. A 2007, 266, 139–148.
[19] Catalytic systems composed of Zn(NO3)2·6H2O and a ketoxime
A
[7] The use of enzymes (nitrile hydratases) also represents an appealing
alternative to the classical methods. For recent reviews on this topic,
see: a) M. Kobayashi, S. Shimizu, Curr. Opin. Chem. Biol. 2000, 4,
95–102; b) I. Endo, M. Nojori, M. Tsujimura, M. Nakasako, S. Na-
were found to catalyze the selective hydration of nitriles, in reflux-
ing water/nitrile 1:1 mixtures, under neutral conditions (TOF values
up to 45 hÀ1): M. N. Kopylovich, V. Yu. Kakushkin, M. Haukka,
6604
www.chemeurj.org
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 6601 – 6605

Homogeneous Catalysis
COMMUNICATION
J. J. R. Frafflsto da Silva, A. J. L. Pombeiro, Inorg. Chem. 2002, 41,
4798–4804.
[25] a) The ability of the free ligands PTA, PTA-Bn, or DAPTA
(5 mol%) to catalyze the hydration of benzonitrile was checked.
Thus, after 48 h at 1008C benzamide was formed in <14% GC
yield, confirming that ruthenium species are the real catalysts in this
[20] The heterogeneous system Ru(OH)x/Al2O3 was also found to cata-
lyze the selective hydration of nitriles to amides in water at 1408C
(TOF values up to 5 hÀ1): K. Yamaguchi, M. Matsushita, N. Mizuno,
Angew. Chem. 2004, 116, 1602–1606; Angew. Chem. Int. Ed. 2004,
43, 1576–1580.
[21] a) V. Cadierno, S. E. García-Garrido, J. Gimeno, Chem. Commun.
2004, 232–233; b) V. Cadierno, P. Crochet, S. E. García-Garrido, J.
Gimeno, Dalton Trans. 2004, 3635–3641; c) V. Cadierno, S. E.
García-Garrido, J. Gimeno, N. Nebra, Chem. Commun. 2005, 4086–
4088; d) V. Cadierno, S. E. García-Garrido, J. Gimeno, A. Varela-
lvarez, J. A. Sordo, J. Am. Chem. Soc. 2006, 128, 1360–1370;
e) A. E. Díaz-lvarez, P. Crochet, M. Zablocka, C. Duhayon, V. Ca-
dierno, J. Gimeno, J. P. Majoral, Adv. Synth. Catal. 2006, 348, 1671–
1679; f) V. Cadierno, S. E. García-Garrido, J. Gimeno, J. Am. Chem.
Soc. 2006, 128, 15094–15095; g) V. Cadierno, J. Francos, J. Gimeno,
N. Nebra, Chem. Commun. 2007, 2536–2538; h) V. Cadierno, J.
Gimeno, N. Nebra, Chem. Eur. J. 2007, 13, 6590–6594.
transformation; b) The dimeric precursors [{RuCl
N
N
(1a–d) were also by themselves much less efficient than complexes
2,3,4a–d (up to 82% yield after 24 h at 1008C; TOF <1 hÀ1); c) one
referee suggested that HCl, generated in situ from the ruthenium
chloride complexes and water, could be responsible of the catalytic
activity observed; we have checked that HCl (5 mol%) by itself, or
associated with PTA-Bn (5 mol% of each), is completely inopera-
tive in the hydration process (<1% of benzamide is formed after
24 h at 1008C) discarding this hypothesis.
[26] For reviews on metal-catalyzed alkyne hydrations, see: a) L. Hinter-
mann, A. Labonne, Synthesis 2007, 1121–1150; b) F. Alonso, I. P.
Beletskaya, M. Yus, Chem. Rev. 2004, 104, 3079–3159.
[27] Microwave-assisted organic synthesis in water has been recently re-
viewed: D. Dallinger, C. O. Kappe, Chem. Rev. 2007, 107, 2563–
2591.
[22] Complexes 2–5 were prepared through conventional routes involv-
ing the treatment of the readily available dimeric precursors [{RuCl-
[28] We note that these reactions can be performed in a preparative
scale and that the catalyst can be recycled. Representative example:
4-Chlorobenzonitrile (2.77 g, 20 mmol), complex 3d (0.617 g,
1 mmol) and water (40 mL) were introduced, under nitrogen atmos-
phere, into a Schlenk flask fitted with a condenser. The reaction
mixture was stirred at 1008C until total consumption of the starting
material (2 h; GC monitoring). After cooling to room temperature,
the solution was set aside at 08C (ice bath) for 2 h leading to the se-
lective crystallization of 4-chlorobenzamide, which was separated
from the aqueous solution by decantation. Recrystallization from
methanol afforded 2.43g (15.6 mmol) of analytically pure 4-chloro-
benzamide (77% yield). To the recovered aqueous solution addi-
tional 4-chlorobenzonitrile (20 mmol) was added and the mixture
stirred at 1008C. Almost quantitative conversion of 4-chlorobenzoni-
trile into 4-chlorobenzamide was observed by GC after 2.5 h.
A
N
ligand (details and characterization data are given in the Supporting
Information).
[23] Only one further ruthenium catalyst active in aqueous media,
namely [RuH
G
G
ACHTREUNG
lective hydration of acetonitrile and benzonitrile at 1208C using
water/nitrile 1:1 mixtures (TOF values not available): W. K. Fung,
X. Huang, M. L. Man, S. M. Ng, M. Y. Hung, Z. Lin, C. P. Lau, J.
Am. Chem. Soc. 2003, 125, 11539–11544.
[24] Attack of water assisted by a nitrogen-containing ligand was already
ˇ
proposed in some nitrile and alkyne hydration studies: a) T. Smej-
kal, B. Breit, Organometallics 2007, 26, 2461–2464; b) D. B. Grotj-
han, V. Miranda-Soto, E. J. Kragulj, D. A. Lev, G. Erdogan, X.
Zeng, A. L. Cooksy, J. Am. Chem. Soc. 2008, 130, 20–21, and refer-
ences cited therein. See also ref. [10].
Received: May 5, 2008
Published online: June 20, 2008
Chem. Eur. J. 2008, 14, 6601 – 6605
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6605