Published on Web 04/12/2007
Gold Catalysts Open a New General Chemoselective Route to Synthesize
Oximes by Hydrogenation of r,â-Unsaturated Nitrocompounds with H2
Avelino Corma,* Pedro Serna, and Hermenegildo Garc´ıa
Instituto de Tecnolog´ıa Qu´ımica, UPV-CSIC, AV. los Naranjos, s/n, Valencia, Spain
Received January 19, 2007; E-mail: acorma@itq.upv.es
Table 1. Catalytic Results of the Hydrogenation of Several
R,â-Unsaturated Nitrocompounds
Oximes are highly valuable organic molecules considering their
numerous applications for polymers,1 fungicides,2 biochemicals,3
fragrances,4 or simply as latent protected forms of aldehydes and
ketones. Particularly, the manufacture of cyclohexanone oxime
represents a key step in the sequence of the Nylon 6 production,
so that the development of easy and clean procedures for obtaining
this oxime results in high interest. Traditionally, oximes are
synthesized by condensation of an aldehyde or a ketone with
hydroxylamine, but the use of this reagent is less desirable for large-
scale processes owing to its intrinsic toxicity and unstability. Other
functional group transformations, and particularly partial reduction
and isomerization of the nitro groups, require harsh reaction
conditions, and are characterized by poor selectivity. The hydro-
genation of R,â-unsaturated nitrocompounds to produce oximes is
not trivial (see Scheme 1) because of the presence of the easily
reducible double bond, as well as the possibility of undesired
secondary reactions in molecules with sensitive groups. Currently,
the only possibility in achieving certain selectivity of the oxime,
when reacting R,â-unsaturated nitrocompounds, was the use of
stoichiometric amounts of organic hydrogen donors5 (e.g., am-
monium formate, decaborane, formic acid, etc). However, the use
of these organic or inorganic reductants is not industrially sustain-
able from an environmental point of view, owing to the high E
factor6 value of such processes.
We have recently presented7 that gold catalysts can selectively
reduce nitro into amino groups when other easily reducible groups,
such as double bond and carbonyls, are present. It would be also
extremely valuable from the synthetic point of view if, using H2 as
reductant, gold could selectively hydrogenate R,â-unsaturated
nitrocompounds into the corresponding oximes. In fact, the nitro
to oxime transformation, combined with the Henry reaction, would
open a powerful synthetic route for complex molecules starting from
aldehydes or ketones under mild conditions. Indeed, the Henry
condensation of an aldehyde or ketone with a nitroalkane, followed
by dehydration of the resulting â-nitro alcohol, is the most versatile
method for preparation of nitroalkenes, and from it a whole array
of derivatives (R,â-unsaturated aldehydes or ketones, nitroalkanes,
amines, and nitrogenated compounds, etc).8
% metal
(mol)
T
P
time conversion selectivitya
substrate
catalysts
(
°
C) (bar) (h)
(%)
(%)
trans-â-nitrostyrene
Au/TiO2 0.64
90 10 2.00
90 10 0.03
90 10 0.03
90 15 3.00
90 15 1.75
90 15 0.25
98.8
99.2
99.0
99.1
73.4
81.9
94.5
98.7
99.1
95.4
98.5
97.9
99.6
69.8
67.1
97.1
38.1
66.3
91.1
42.5
85.3
91.5
85.7
88.6
95.7
0.0
Pd/C
Pt/C
0.32
0.34
trans-4-methoxy-â-
nitrostyrene
Au/TiO2 0.78
Pd/C
Pt/C
0.24
0.30
trans-4-bromo-â-
nitrostyrene
Au/TiO2 0.78 100 15 3.00
Pd/C
Pt/C
0.81 100 15 0.50
0.44 100 15 0.25
â,2-dinitrostyrene
Au/TiO2 0.93 110 15 3.0
Pd/C
Pt/C
0.67 110 15 0.25
0.52 110 15 0.25
0.5
1-Nitro-1-Cyclohexene Au/TiO2 0.27 110 15 0.5
90.9
70.6
52.6
Pd/C
Pt/C
0.42 110 15 0.03
0.23 110 15 0.03
a Cis/trans mixture of products, excepts for 1-nitro-1-cyclohexene.
First, the selectivity toward the oxime formation in the presence
of a conjugated double bond was examined by reacting the trans-
â-nitrostyrene (see Table 1). While the activity of Pd, and Pt
catalysts is higher than that of the Au catalyst, the yield to oxime
is notably poorer with the former metals because of the occurrence
of secondary reactions. Pd/C catalyst produces 28% of the corre-
sponding saturated nitro compound, showing that simultaneous
reduction of the nitro and the double bond occurs. Other secondary
reactions, such as the formation of N,N-bis(2-phenylethyl)amine
(19%) or the complete hydrogenation of the substrate to the
saturated amine compound (5%) were also observed. Pt/C provides
a slightly better selectivity to the oxime than Pd/C, although 5%
of the saturated nitro compound and an important amount of
N,N-bis(2-phenylethyl)amine (18%) are observed. Contrarily, the
Au/TiO2 system is very selective to the oxime, avoiding both the
hydrogenation of the double bond and the formation of other
products and giving selectivity above 97% to the oxime at levels
of conversion close to 99%. The byproducts observed were the nitro
saturated and the amino saturated compounds, always in amounts
below 3%.
When electron donating or withdrawing groups are present in
the aromatic ring of nitrostyrene, the chemoselectivity of gold
catalyst is still high. For instance (see Table 1), reaction with
substituted methoxy- and bromo-â-nitrostyrenes also gives higher
selectivity with the gold catalyst. We have not observed any
secondary reaction affecting the methoxy or the halogen group
(dehalogenation), under the selected reaction conditions, but the
presence of methoxy and Br groups obviously influences the rate
and selectivity for the production of the oxime on the different metal
catalysts. Thus, while the presence of a methoxy group improves
the selectivity with Pt/C, it is not still a sufficiently strong electron
donor to completely suppress the double bond hydrogenation by
In this work, we present a general chemoselective catalytic
process for the transformation of R,â-unsaturated nitrocompounds
into oximes, using H2 as reducing agent, and gold (Au/TiO2) as
catalyst. Gold, unlike other noble metal-based catalysts, such as
commercial Pd/C or Pt/C, shows a unique selectivity and quite
general use for converting substituted nitro compounds into the
corresponding oximes. The reaction is considerably greener than
any of the known alternatives and involves an easy work up (see
Supporting Information).
Table 1 shows the reaction conditions and catalytic results for
the hydrogenation with H2 of several substituted R,â-unsaturated
nitrocompounds, using 1.5 wt % Au/TiO2 and commercial 5 wt %
Pd/C (Fluka, 75992) and 5 wt % Pt/C catalysts (Fluka, 80982).
9
6358
J. AM. CHEM. SOC. 2007, 129, 6358-6359
10.1021/ja0704131 CCC: $37.00 © 2007 American Chemical Society
Corma, Avelino
