DOI: 10.1002/cssc.201200203
A General and Efficient Heterogeneous Gold-Catalyzed Hydration of Nitriles
in Neat Water under Mild Atmospheric Conditions
Yong-Mei Liu, Lin He, Miao-Miao Wang, Yong Cao,* He-Yong He, and Kang-Nian Fan[a]
Amides constitute one of the most important functional
groups in contemporary chemistry. They are essential for sus-
taining life, linking the amino acids in proteins such as en-
zymes. They are found in numerous natural products and are
among the most prolific moieties in pharmaceutical mole-
cules.[1] Despite their obvious importance, the majority of
amide bond syntheses require stoichiometric amounts of cou-
pling reagents, making them generally expensive and wasteful
procedures.[2] Not surprisingly, in 2007 the Pharmaceutical
Roundtable of the ACS Green Chemistry Institute declared
“amide formation avoiding poor-atom-economy reagents”
a high priority in modern organic synthesis.[3] An essentially
atom-economical method that fulfills the above described re-
quirements is the catalytic hydration of nitriles, which repre-
sents an extremely attractive sustainable technology for amide
production. A variety of metalloenzymes[4] and homogeneous
transition-metal catalysts,[5] including rhodium, platinum, ruthe-
nium, palladium, and gold complexes, have been developed
for this transformation. These systems can offer selective
amide formation under relatively mild conditions but have sev-
eral drawbacks, especially the difficulty in catalyst/product sep-
aration and the necessity of special procedures to handle mi-
croorganisms and air-sensitive metal complexes.
erably in neutral water, under convenient and mild atmospher-
ic conditions.
Catalysts based on supported gold nanoparticles (NPs) have
gained considerable attention in the past decade owing to
their unique capability to promote selective reactions at low
temperatures.[7] In particular, various supported-gold catalysts
have been reported to show catalytic activities far superior to
those of conventional platinum group metal (PGM)-based cata-
lysts for a number of industrially important processes, which is
believed to be essential for the development of alternative
and greener routes toward sustainability.[8] Herein, we report
that easily handled and ligand-free nanosized gold-decorated
TiO2 can catalyze the conversion of a large number of chemi-
cally and structurally diverse nitriles into their corresponding
amides in pure neutral water under air at near-ambient condi-
tions. The high efficiency of the catalytic system has allowed
us to extend the process to the one-pot direct synthesis of in-
dustrially important e-caprolactam (CPL) via a hydration–cycli-
zation sequence starting with 6-aminocapronitrile (ANC). This
hydration method, using a robust and reusable gold catalyst
with neat water as solvent under ambient conditions, can
make a significant contribution not only to reveal the intrinsic
catalytic potential of supported gold nanoparticles, but also to
establish a more sustainable and industrially viable process.
In the first stage of our work, benzonitrile (1) was selected
as the substrate, and the hydration was conducted in pure
water at a mild temperature of 608C under an atmosphere of
air. We initially examined the hydration of 1 over a benchmark
Au/TiO2 catalyst (average gold particle size ca. 3.5 nm, supplied
by the World Gold Council). This catalyst has been widely stud-
ied and proved to be highly active for a variety of organic
transformations,[9] including chemoselective nitro reduction,[9a]
selective alcohol oxidation,[9b] aerobic olefin epoxidation,[9c,d]
and cross-coupling reactions for carbon-nitrogen bond forma-
tion.[9e] The high versatility of the Au catalyst is due in part to
its low reactant affinity,[10] which has notably permitted the ac-
tivation of a wide range of functional groups or raw materials.
We were pleased to find that Au/TiO2 delivered a notable con-
version of 1 under the mild conditions probed (Table 1,
entry 1). Importantly, the reaction proceeded smoothly and ran
to completion within 15 h at 608C.[11] Benzamide (2) was the
only product formed in a yield greater than 97% (entry 2).
Prompted by this result, we examined a series of catalysts with
Au on other mineral supports, such as Fe2O3, Al2O3, SiO2, CeO2,
HAP, and activated carbon. These catalysts, however, were not
found to be particularly active, although in all cases the de-
sired amide could be produced exclusively (entries 3–8). In ad-
dition, the hydration did not take place when using TiO2 or the
catalyst precursor HAuCl4, nor with other Au compounds in-
cluding Au(PPh3)3Cl, Au2O3, bulk Au0 powder (mean particle
An ideal protocol to overcome these limitations is the use of
heterogeneous catalysts. Indeed, heterogeneous catalysis
offers many advantages, such as easy handling, stability, easy
recovery, and reusability. Despite these merits, only a handful
of heterogeneous systems were found to be effective for the
selective hydration of nitriles,[6] including Raney copper,[6a]
ruthenium hydroxide loaded on alumina [i.e., Ru(OH)x/Al2O3],[6c]
hydroxylapatite-supported silver nanoclusters [Ag/HAP, where
HAP is Ca10(PO4)6(OH)2][6e] and CeO2.[6g] Unfortunately, these cat-
alysts commonly require an inconvenient inert atmosphere for
their successful use, which has greatly restricted the utility of
these procedures. Furthermore, most of these heterogeneous
hydrations still suffered from harsh conditions (generally, T>
1408C), and low efficiency as well as limited substrate scope.
From both green and synthetic points of view, it is imperative
to develop advanced reusable catalyst systems that can offer
a simple, general, and more efficient hydration of nitriles, pref-
[a] Dr. Y.-M. Liu, L. He, M.-M. Wang, Prof. Dr. Y. Cao, Prof. Dr. H.-Y. He,
Prof. K.-N. Fan
Department of Chemistry
Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials
Fudan University
Handan Road 220, Shanghai 200433 (PR China)
Fax: (+86)21-65643774
Supporting Information for this article is available on the WWW under
ChemSusChem 2012, 5, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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