An efficient and practical protocol for catalytic hydrolysis of nitriles by a copper(I) complex in water

Article abstract of DOI:10.1002/adsc.201100812

The cuprous complex - Cu₄I₄(H₂O) ₄ - has been isolated and employed for the catalytic hydrolysis of arenecarbonitriles, cinnamonitrile, and arylacetonitriles to the corresponding amides in pure water in high yields of up to 98%. The catalyst can be easily recovered and reused without loss of catalytic activity at least five times. Oxindole could be prepared successfully by one-pot domino protocols based on this method. Copyright

Full text of DOI:10.1002/adsc.201100812

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DOI: 10.1002/adsc.201100812
An Efficient and Practical Protocol for Catalytic Hydrolysis of
Nitriles by a Copper(I) Complex in Water
Zhengkai Li,a Lixia Wang,a and Xiangge Zhoua,b,*
a
Institute of Homogeneous Catalysis, College of Chemistry, Sichuan University, Chengdu 610064, Peopleꢀs Republic of
China
Fax : (+86)-28-8541-2904; e-mail: zhouxiangge@scu.edu.cn
State Key Laboratory of Physical Chemistry of Solid Surface, Xiamen University, Xiamen 361005, Peopleꢀs Republic of
b
China
Received: October 19, 2012; Published online: February 23, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100812.
Abstract: The cuprous complex – Cu4I
(H2O)4 – has
ings still existed with these catalytic systems: difficulty
in catalyst/product separation and necessity of special
handling of microorganisms or metal complexes.[9]
Furthermore, the reaction media were in general or-
ganic solvents or mixed solvents, and expensive
metals such as ruthenium, platinum and rhodium
were usually needed. Reports on the homogeneous
complex-catalyzed transformation in pure aqueous
media are scarce.[6f,g,j,10] To the best of our knowledge,
a Cu(I)-catalyzed conversion of nitriles to amides has
not been reported.[2a,11]
been isolated and employed for the catalytic hy-
drolysis of arenecarbonitriles, cinnamonitrile, and
arylacetonitriles to the corresponding amides in
pure water in high yields of up to 98%. The catalyst
can be easily recovered and reused without loss of
catalytic activity at least five times. Oxindole could
be prepared successfully by one-pot domino proto-
cols based on this method.
Keywords: amides; copper; hydrolysis; nitriles;
water
In continuation of our studies on copper-catalyzed
reactions in water,[12] herein is reported a highly effi-
cient and practical protocol for the catalytic hydroly-
sis of nitriles to amides by Cu(I) in water. It has the
following advantages compared with the reported
The hydrolysis of nitriles is of synthetic significance methods: water is used as sole solvent without addi-
for the preparation of amides, which are versatile syn- tion of other acids or bases, the product amide can be
thetic intermediates used in the production of phar- separated by simple filtration without complicated
macological products, polymers, detergents, lubricants work-up procedures, the catalyst is easily available
and drug stabilizers.[1] For instance, more than 2ꢁ105 with high catalytic abilities and can be easily recov-
ton of acrylamide are produced by the hydrolysis of ered and reused at least five times without loss of cat-
acrylonitrile every year.[2] Normally, the classical pro- alytic activities, furthermore, the catalytic system can
cess of nitrile hydrolysis is carried out in a sequence be applied to large-scale reactions.
of distinct steps upon treatment with strong inorganic
Initially, the catalytic hydrolysis of benzonitrile was
acid or base, however, further hydrolysis to carboxylic selected as a model reaction, and the reaction condi-
acids is a serious problem in many cases. Meanwhile, tions were optimized. As shown in Table 1, CuI exhib-
the formation of a large amount of salts after neutrali- ited low catalytic abilities to form only traces of
zation also limits its applications.[3] Therefore, the cat- amide product, which might be partially caused by
alytic hydrolysis of nitriles seems to be an ideal ap- the low solubility of the catalyst in water (Table 1,
proach, which fits well for either atom economy or entry 1). Then, several kinds of ligands which were
sustainable development. Some metalloenzyme and usually applied in coupling reactions and some other
transition metal catalysts have already been employed transition metals were tested, and the catalyst formed
for this purpose.[4–8] For example, Yamadaꢀs NHase by CuI and ammonia was found to be superior to
catalyst,[5] Murahashiꢀs ruthenium system,[1d,6b,c] Par- others in giving a moderate yield of 55% (Table 1, en-
kinsꢀs platinum complexes,[6e,g,7] and other Ru[6p] and tries 2–10). Interestingly, decreasing the amount of
Rh catalysts[8] were reported to exhibit remarkable ammonia resulted in an improvement of the catalytic
activities in the catalysis. However, several shortcom- activity. For example, when the molar ratio between
584
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Adv. Synth. Catal. 2012, 354, 584 – 588

An Efficient and Practical Protocol for Catalytic Hydrolysis of Nitriles
Table 1. Catalytic hydrolysis of benzonitrile in water.[a]
Entry [Cu]
Ligand
Time [h] Yield [%][b]
1
2
3
4
5
6
7
8
CuI
CuI
CuI
CuI
CuI
–
21
21
21
21
21
21
<2
36[c]
41[c]
32[c]
51[c]
50
Figure 1. X-ray structure of complex 2.
L1
L2
L3
L4
Table 2. Catalytic hydrolysis of benzonitrile by Cu4I4ACHTUNGTRENNUNG(H2O)4
in water.[a]
Complex 1
CuSO4·5H2O NH3·H2O 21
33[d]
38[d]
25[d]
55[d]
63[e]
70[f]
Entry Temp. [8C] Catalyst Loading [mol%] Yield [%][b]
NiCl2·6H2O
FeCl3·6H2O
CuI
CuI
CuI
NH3·H2O 21
NH3·H2O 21
NH3·H2O 21
NH3·H2O 21
NH3·H2O 21
1
2
3
4
5
6
100
120
80
100
100
100
2.5
2.5
2.5
2
1
0.5
97
95
87
94
93
82
9
10
11
12
[a]
Reaction conditions: benzonitrile (1 mmol), Cu-catalyst
(0.025 mmol) in H2O (5 mL).
Isolated yield.
[Cu]/ligand=1:1.
[Cu]/ligand=1:2.
[a]
[b]
[c]
[d]
[e]
[f]
Reaction conditions: benzonitrile (1 mmol), Cu4I
(0.025 mmol), H2O (5 mL), 21 h.
Isolated yield.
4ACHTUNGTRENNUNG(H2O)4
[b]
[Cu]/ligand=1:1.
[Cu]/ligand=1:0.5.
AHCTUNGTRE(GNNNU H2O)4 could be easily dissolved in water, and exhibit-
CuI and ammonia was reduced from 1:2, 1:1 to 1:0.5, ed high catalytic abilities with up to 97% yield. The
the yields increased from 55%, 63% to 70% (Table 1, effects of reaction temperature were studied, and
entries 10–12). This phenomenon suggested to us that 1008C was suitable for the catalysis, a lower tempera-
the most effective catalytic species during the reaction ture resulted in a decreased yield (Table 2, entries 1–
might not be the complex formed by CuI with ammo- 3). Comparison of different catalyst loadings indicated
nia. Thus, the complex formed by CuI and ammonia that 2.5 mol% was suitable for the reaction.
in a 1: 0.5 molar ratio in water was isolated, and the
Furthermore, after the reaction, when the mixture
crystals of the novel complex 2 suitable for X-ray had cooled to a low temperature of around 58C,
single crystal determination were fortunately ob- a number of colorless crystals appeared as shown in
tained.
Figure 2 (right). After simple filtration, the amide
As shown in Figure 1, the molecular structure re- product could be obtained in high purity just by wash-
vealed that this complex consists of a tetranuclear ing with a small amount of water and drying under
[Cu
4ACHTUNGTRENNUNG(m3-I)4ACHTUNGTRENNUNG(H2O)4] core in which the four copper ions vacuum. The obvious different solubilities of benz-
are linked by I bridges, and the remaining coordina-
AHCTUNGTRENNUNG
tion sites were occupied by water molecules, respec- mixture without additives and by-products during cat-
tively.[12] The addition of small amount of ammonia alysis made the work-up procedure easy to perform.
seemed to be essential for the formation of this com-
plex.
On the other hand, the simple work-up procedure
also reminded us of the possibility of the reuse of the
This complex was then applied in the catalysis, and catalyst. Indeed, after filtration, the filtrate containing
the results are listed in Table 2. As expected, Cu4I4 the water-soluble catalyst could be reused for the next
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Zhengkai Li et al.
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Table 3. Hydrolysis of various nitriles catalyzed by the com-
plex Cu4I
(H2O)4 in water.[a]
4ACHTUNGTRENNUNG
Entry
Nitrile
Product
Yield [%][b]
97
1
2
3
86
89
Figure 2. Catalytic hydrolysis of benzonitrile to benzamide:
(left) reaction mixture, (right) benzamide crystals appeared
after cooling the reaction mixture.
4
92
run again, and the yields remained quite stable at
around 95% even after reused five times.
5
95
98
95
83
82
95
Considering the broad application and large
demand of amides in many fields, especially as a raw
material for making pharmacological products and
drug stabilizers, we tried to conduct a scale-up prepa-
ration study of benzamide based on the above opti-
mized conditions. Actually, the reaction conditions
and relevant processing parameters of 100 g of benzo-
nitrile in a 1 L volume sealed retort were optimized
and the final yield also reached 96%.
6
7
8
Next, the scope of nitrile substrates was surveyed.
As exemplified in Table 3, Cu4I4ACTHNUTRGNE(UNG H2O)4 was in general
effective in the selective hydrolysis of different nitriles
to the corresponding amide products in good to excel-
lent yields ranging from 63% to 98%. The substrates
bearing electron-donating groups gave better results
than those bearing electron-withdrawing groups. Fur-
thermore, the catalytic system exhibited tolerance
with some functional groups including halides, ether,
and nitro groups (Table 3, entries 2, 3, 7, 8, 9 and 14).
Hydrolysis of cinnamonitrile also afforded cinnama-
mide as expected with an intact C=C double bond in
90% yield (Table 3, entry 12). Remarkably, this cata-
lytic system could effectively convert nicotinonitrile
to nicotinamide in 95% yield, which was usually more
difficult to be hydrolyzed than common nitriles
(Table 3, entry 10). Furthermore, as shown in Table 3,
the hydrolysis of arylacetonitriles was efficiently (ꢀ
87% isolated yield) achieved under the standard reac-
tion conditions (Table 3, entries 13 and 14). We evalu-
ated this catalyst for the hydration of an alphatic ni-
trile, acetonitrile (Table 3, entry 15), which produced
the corresponding acetamide in moderate yield.
9
10
11
12
82
90
13
14
95
89
63
15
CH3CN
[a]
Reaction conditions: nitrile (1 mmol), Cu4I
(0.025 mmol), H2O (5 mL), 1008C, 21 h.
Isolated yields.
4ACHTUNGTRENNUNG(H2O)4
Finally, the catalytic system together with the help
[13]
À
[b]
of our formerly developed C N coupling catalyst
were successfully applied in the synthesis of oxindole,
which is one of the useful lactam derivatives used in
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Adv. Synth. Catal. 2012, 354, 584 – 588

An Efficient and Practical Protocol for Catalytic Hydrolysis of Nitriles
A. Greenberg, C. M. Breneman, J. F. Liebman), Wiley,
New York, 2000; c) I. Johansson, in: Kirk-Othmer En-
cyclopedia of Chemical Technology, Vol. 2. 5th edn.,
Wiley, New York, 2004, pp 442–463; d) S.-I. Murahashi,
H. Takaya, Acc. Chem. Res. 2000, 33, 225–233; e) V. Y.
Kukushkin, A. J. L. Pombeiro, Chem. Rev. 2002, 102,
1771–1802; f) V. Y. Kukushkin, A. J. L. Pombeiro,
Inorg. Chim. Acta 2005, 358, 1–21; g) P. K. Mascharak,
Coord. Chem. Rev. 2002, 225, 201–214; h) T. C. Harrop,
P. K. Mascharak, Acc. Chem. Res. 2004, 37, 253–260.
Scheme 1. Synthesis of oxindole by our Cu-catalyzed proto-
col.
[2] a) R. Opsahl, in: Encyclopedia of Chemical Technology,
Vol. 2, (Ed.: J. I. Kroschwitz), Wiely, New York, 1991,
pp 346–356; b) K. Ingvosersen, J. Kamphuis, in:
Enzyme Catalysis in Organic Synthesis, Vol. 1 (Eds.: K.
Drauz, H. Waldmann), VCH, Weinheim, 1995, pp 365–
392.
[3] Methoden der Organischen Chemie (Houben Weyl), 4th
edn. Vol. E5(2), Georg Thieme Verlag, Stuttgart, 1985,
pp 1024–1031.
[4] a) B. Schultz, in: Enzyme Catalysis in Organic Synthe-
sis, (Eds.: K. Drauz, H. Waldmann), VCH, Weinheim,
2002, p 699; b) K. Weissermel, H.-J. Arpe, Industrial
Organic Chemistry, 4th edn., VCH, Weinheim, 2003,
p 310.
[5] M. Kobayashi, T. Nagasawa, H. Yamada, Trends Bio-
technol. 1992, 10, 402–408.
the drug and polymer industry.[14] As show in
Scheme 1, oxindole could be prepared in a total yield
of 76% by a one-pot reaction with Cu4I
complex 1 as catalysts.
4ACHTUNGRTNE(NUNG H2O)4 and
In conclusion, an efficient copper-catalyzed proto-
col for the hydrolysis of nitriles to amides in water
under neutral condition has been disclosed. This ap-
proach represents an important complement to the
hydrolysis of nitriles and exhibits potential usage in
industry. We envision that the fuctionalization of ni-
trile-containing polymers may be realized using the
present hydrolysis strategy.
[6] a) J. Chin, J. H. Kim, Angew. Chem. 1990, 102, 580–
582; Angew. Chem. Int. Ed. Engl. 1990, 29, 523–525;
b) S.-I. Murahashi, S. Sasao, E. Saito, T. Naota, J. Org.
Chem. 1992, 57, 2521–2523; c) S.-I. Murahashi, S.
Sasao, E. Saito, T. Naota, Tetrahedron 1993, 49, 8805–
8826; d) J. H. Kim, J. Britten, J. Chin, J. Am. Chem.
Soc. 1993, 115, 3618–3622; e) T. Ghaffar, A. W. Parkins,
Tetrahedron Lett. 1995, 36, 8657–8660; f) C. S. Chin,
S. Y. Kim, K.-S. Joo, G. Won, D. Chong, Bull. Korean
Chem. Soc. 1999, 20, 535–538; g) M. C. K. Djoman,
A. N. Ajjou, Tetrahedron Lett. 2000, 41, 4845–4849;
h) T. Ghaffar, A. W. Parkins, J. Mol. Catal. A 2000, 160,
249–261; i) M. N. Kopylovich, V. Y. Kukushkin, M.
Haukka, J. J. R. Frafflsto da Silva, A. J. L. Pombeiro,
Inorg. Chem. 2002, 41, 4798–4804; j) K. L. Breno, M. D.
Pluth, D. R. Tyler, Organometallics 2003, 22, 1203–
1211; k) 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; l) H. Takaya, K. Yoshida, K. Isozaki,
H. Terai, S.-I. Murahashi, Angew. Chem. 2003, 115,
3424–3426; Angew. Chem. Int. Ed. 2003, 42, 3302–3304;
m) X. Jiang, A. J. Minnaard, B. L. Feringa, J. G. de V-
ries, J. Org. Chem. 2004, 69, 2327–2331; n) M. North,
A. W. Parkins, A. N. Shariff, Tetrahedron Lett. 2004, 45,
7625–7627; o) T. Oshiki, H. Yamashita, K. Sawada, M.
Utsunomiya, K. Takahashi, K. Takai, Organometallics
2005, 24, 6287–6290; p) H. B. Ammar, X. W. Miao, C.
Fischmeister, L. Toupet, P. H. Dixneuf, Organometallics
2010, 29, 4234–4238; q) V. Cadierno, J. Díez, J. Francos,
J. Gimeno, Chem. Eur. J. 2010, 16, 9808–9817; r) R. G.
lvarez, J. Díez, P. Crochet, V. Cadierno, Organometal-
lics 2010, 29, 3955–3965.
Experimental Section
General Procedure for the Catalytic Reaction
The corresponding nitrile (1 mmol), the copper catalyst
Cu4I4ACHTUNGTRENNUNG(H2O)4 (2.5 mol%), and water (5 mL) were placed in
a sealed tube and the reaction mixture was stirred at 1008C
for the indicated time (see Table 1 and Table 2). then the re-
action mixture was cooled to 58C. The crystalline product
appeared and was collected by simple filtration and dried
under vacuum to give analytically pure amide. To the filtrate
was added deionized water to 5 mL, and the mixture was
employed as the reusable catalytic system.
CCDC 842303 contains the supplementary crystallograph-
ic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
We appreciate the Natural Science Foundation of China (No.
21072132), Sichuan Provincial Foundation (08ZQ026-041),
and Ministry of Education (NCET-10-0581) for financial
support and the Analytical & Testing Centre of Sichuan Uni-
versity for NMR analysis.
References
[7] a) J. Akisanya, A. W. Parkins, J. W. Steed, Org. Process
Res. Dev. Org. Process Res. Dew. 1998, 2, 274–276;
b) X.-B. Jiang, A. J. Minnaard, B. L. Feringa, J. G. de V-
ries, J. Org. Chem. 2004, 69, 2327–2331.
[1] Books and reviews: a) The Chemistry of Amides, (Ed.:
J. Zabicky), Wiley-Interscience, New York, 1970;
b) The Amide Linkage: Structural Significance in
Chemistry, Biochemistry and Materials Science, (Eds.:
Adv. Synth. Catal. 2012, 354, 584 – 588
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
587

Zhengkai Li et al.
COMMUNICATIONS
[8] A. Goto, K. Endo, S. Saito, Angew. Chem. 2008, 120,
3663–3665; Angew. Chem. Int. Ed. 2008, 47, 3607–3609.
[9] a) K. Sugiyama, H. Miura, Y. Nakano, H. Sekiwa, T.
Matsuda, Bull. Chem. Soc. Jpn. 1986, 59, 2983–2989;
b) L. A. M. M. Barbosa, R. A. van Santen, J. Mol.
Catal. A 2001, 166, 101–121; c) K. Mori, K. Yamaguchi,
T. Mizugaki, K. Ebitani, K. Kaneda, Chem. Commun.
2001, 461–462; d) A. Solhy, A. Smahi, H. E. Badaoui,
B. Elaabar, A. Amoukal, A. Tikad, S. Sebti, D. J. Mac-
quarrie, Tetrahedron Lett. 2003, 44, 4031–4033; e) K.
Yamaguchi, M. Matsushita, N. Mizuno, Angew. Chem.
2004, 116, 1602–1606; Angew. Chem. Int. Ed. 2004, 43,
1576–1580; f) T. Mitsudome, Y. Mikami, H. Mori, S.
Arita, T. Mizugaki, K. Jitsukawa, K. Kaneda, Chem.
Commun. 2009, 3258–3260; g) K. Yamaguchi, N.
Mizuno, Synlett 2010, 16, 2365–2382.
[10] 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; d) M. N. Kopylovich, V. Y. Kakushkin, M. Haukka,
J. J. R. F. da Silva, A. J. L. Pombeiro, Inorg. Chem.
2002, 41, 4798–4804; e) K. L. Breno, M. D. Pluth, C. W.
Landorf, D. R. Tyler, Organometallics 2004, 23, 1738–
1746; f) M. G. Crestani, A. ArØvalo, J. J. García, Adv.
Synth. Catal. 2006, 348, 732–742; g) T. J. Ahmed, L. N.
Zakharov, D. R. Tyler, Organometallics 2007, 26, 5179–
5187; h) C. Crisóstomo, M. G. Crestani, J. J. García, J.
Mol. Catal. A 2007, 266, 139–148; i) V. Cadierno, J.
Francos, J. Gimeno, Chem. Eur. J. 2008, 14, 6601–6605.
[11] Copper-catalyzed nitrile hydrolysis: a) R. Breslow, R.
Fairweather, J. Keana, J. Am. Chem. Soc. 1967, 89,
2135–2138; b) M. Ravindranathan, N. Kalyanam, S. Si-
varam, J. Org. Chem. 1982, 47, 4812–4813.
[12] K. R. Kyle, C. K. Ryu, J. A. DiBenedetto, P. C. Ford, J.
Am. Chem. Soc. 1991, 113, 2954–2965.
[13] a) Y. Wang, Z. Wu, L. Wang, Z. Li, X. Zhou, Chem.
Eur. J. 2009, 15, 8971–8874; b) L. Liang, Z. Li, X.
Zhou, Org. Lett. 2009, 11, 3294–3297; c) Z. Wu, Z
Jiang, D. Wu, H. Xiang, X. Zhou, Eur. J. Org. Chem.
2010, 1854–1857; d) Z. Wu, L. Zhou, Z. Jiang, D. Wu,
Z. Li, X. Zhou, Eur. J. Org. Chem. 2010, 4971–4975;
e) L. Yu, X. Jiang, L. Wang, Z. Li, D. Wu, X. Zhou,
Eur. J. Org. Chem. 2010, 5560–5562; f) Z. Jiang, Z. Wu,
L. Wang, D. Wu, X. Zhou, Can. J. Chem. 2010, 88, 964–
968; g) L. Wang, Z. Jiang, L. Yu, L. Li, Z. Li, X. Zhou,
Chem. Lett. 2010, 39, 764–765; h) L. Jing, J. Wei, L.
Zhou, Z. Huang, Z. Li, X. Zhou, Chem. Commun.
2010, 46, 4767–4769; i) Y. Qu, F. Ke, L. Zhou, H.
Xiang, D. Wu, X. Zhou, Chem. Commun. 2011, 3912–
3914; j) F. Ke, Y. Qu, Z. Jiang, Z. Li, D. Wu, X. Zhou,
Org. Lett. 2011, 13, 454–457.
[14] For some of recent review articles, see: a) M. T.
Aranda, P Perez-Faginas, R. Gonzalez-Muniz, Curr.
Org. Synth. 2009, 6, 325–341; b) J. Royer, M. Bonin, L.
Micouin, Chem. Rev. 2004, 104, 2311–2352; c) M. D.
Groaning, A. I. Meyers, Tetrahedron 2000, 56, 9843–
9873; d) R. Shiraki, K. I. Tadano, Rev. Heteroat. Chem.
1999, 20, 283–307; e) S. V. Ley, L. R. Cox, G. Meek,
Chem. Rev. 1996, 96, 423–442.
588
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