Angewandte
Chemie
DOI: 10.1002/anie.200800366
Nitrile Hydration
I
Rh -Catalyzed Hydration of Organonitriles under Ambient
Conditions**
Akihiro Goto, Kohei Endo, and Susumu Saito*
Dedicated to Professor Ryoji Noyori on the occasion of his 70th birthday
The hydration of organonitriles is a reaction of great synthetic
significance for the preparation of organoamides (e.g.,
acrylamide and nicotinamide) in view of its broad industrial
[1]
Scheme 1. Catalytic hydration of organonitriles.
and pharmacological applications. For example, hydration
5
of acrylonitrile is used to produce more than 2 10 tons of
[2]
I
acrylamide per year. Classically the reaction proceeds in a
sequence of distinct steps upon treatment with strong
inorganic acid or base, but these methods are frequently
added. The iPrOH solution of the Rh OMe/2PCy3 catalyst
(Rh: 0.04m) was treated sequentially with benzonitrile (1a)
(1 equiv) and H O (5 equiv) at 258C under argon, and the
2
[1f]
unable to control overhydrolysis. Although several pioneer-
reaction mixture was stirred at 258C for 17 h. Subsequent
purification by column chromatography on silica gel provided
benzamide (2a) in 90% yield. The reaction mixture was not
contaminated by further hydration and/or alcoholysis prod-
ucts; in contrast, the formation of benzoic acid and/or the
ester was frequently the side reaction in several methods
[
3]
[4]
ing precedents involving molecular and heterogeneous
catalysts have been reported, in many cases, drastic conditions
including high temperatures (80–1808C) or high pressure
III [3a,d]
(
Pt
e.g., 80 psi) are required. As an exception, Co
and
II [3e,h–j,o]
complexes mediate hydration under milder con-
[
1f]
ditions; however, the substrate range applicable under
standard or ambient conditions remains unclarified. We
report here a notable advance towards expanding the
substrate scope, by demonstrating an easier to conduct and
previously described. Use of [{Rh(OH)(cod)} ] in place of
2
[{Rh(OMe)(cod)} ] resulted in a slightly lower yield (74%).
2
I
Scant reactivity was observed with other Rh complexes
including [{RhCl(cod)} ] and [Rh(acac)(cod)] (acac = acety-
2
I
milder hydration of organonitriles using a low-valent Rh -
lacetonate) under otherwise identical conditions, suggesting
that the OR (R = H, Me) component is the critical functional
group in facilitating the reaction. When we screened the
solvents, we found that protic solvents (MeOH, EtOH,
iPrOH, and tBuOH) led to rate enhancement (2a, 60–99%:
258C, 24 h), whereas aprotic solvents (dimethylacetamide
(DMA), dimethyl sulfoxide, and N-methylpyrrolidinone
(NMP)) resulted in low conversion (< 10%). Additional
experiments revealed that the yield of benzamide (2a)
depends least on the concentration of the Rh catalyst when
the hydration is carried out in iPrOH, so that we chose this
(
OMe) species as the molecular catalyst (Scheme 1).
I
The Rh catalyst was prepared by treatment of commer-
cially available [{Rh(OMe)(cod)} ] (0.01 equiv) with PCy
2
3
(
0.04 equiv) in anhydrous THF at 258C for 15 min under
argon (cod = cyclooctadiene, Cy = cyclohexyl). After the
solvent THF and residual cod had been removed by
evaporation in vacuo, oxygen-free, Ar-saturated iPrOH was
[
+]
[
*] A. Goto, Dr. K. Endo, Dr. S. Saito
Department of Chemistry, Graduate School of Science
Nagoya University
solvent for further screening. Two equivalents of PCy per
3
Chikusa, Nagoya 464-8602 (Japan)
Fax: (+81)52-789-5945
E-mail: susumu@chem.nagoya-u.ac.jp
Homepage: http://www.chem.nagoya-u.ac.jp/~susumu/
Dr. S. Saito
Institute for Advanced Research
Nagoya University
equivalent of Rh ([{Rh(OMe)(cod)} ]/PCy 1:4) was sufficient
to give reasonable yields of 2a. In contrast, the use of a 1:1
ratio slightly decreased the yield, whereas using a three- or
2
3
fourfold excess of PCy did not improve the results. Other
3
monodentate phosphines and phosphites including Ph P,
3
tBu P, 2-(2’-methyl-1,1’-biphenyl)PCy , and P(OPh) were
3
2
3
completely unsatisfactory (Rh/P = 1:2; 2a: < 10%). This is
in stark contrast to the [{RhCl(cod)} ]/P(m-C H SO Na)/
Chikusa, Nagoya 464-8601 (Japan)
+
[
] Current address:
2
6
4
3
Department of Chemistry and Biochemistry
School of Advanced Science and Engineering
Waseda University
NaOH (1:3:10) system, where the PPh derivative facilitated
3
the hydration under high pressure (80 psi) and in aqueous
[3g]
media. In comparison, 2-(1,1’-biphenyl)PCy and 2,2’-(1,1’-
2
Ohkubo, Shinjuku, Tokyo 169-8555 (Japan)
biphenyl)(PCy ) gave the product in poor yields (Rh/P = 1:2;
2
2
[
**] This work was partially supported by a Grant-in-Aid for Young
2
a: < 26%).
Finally we succeeded in reducing the loading of [{Rh-
OMe)(cod)} ] and PCy to 0.005 and 0.02equiv, respectively,
Scientists (A) and Scientific Research on the Priority Area
“Advanced Molecular Transformations of Carbon Resource” from
(
2
3
the Ministry of Education, Culture, Science, Sports and Technology
of Japan, as well as by Asahi Glass and Sumitomo Foundation. We
are grateful to Prof. K. Ishihara, M. Hatano, and Prof. D. Uemura
after increasing the amount of H O to 20–40 equiv (with
2
respect to nitrile) and by running the reaction at higher
(
Nagoya University) for the use of GC and polarimeter instruments.
dilution (Rh: 0.01–0.02m). Since the optimal conditions
Angew. Chem. Int. Ed. 2008, 47, 3607 –3609
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3607