Enhanced reactivity of silver- and gold-catalysed hydrogenations using silver(I) salts

Article abstract of DOI:10.1016/j.tetlet.2010.07.143

A novel application of silver(I) salt promoters in silver- and gold-catalysed hydrogenations was applied to the chemoselective reduction of halonitrobenzenes resulting in excellent conversions and selectivities. This reactivity, coupled with the low cost of silver relative to more expensive precious metal counterparts, demonstrates this catalytic system as an attractive alternative for challenging chemoselective transformations.

Full text of DOI:10.1016/j.tetlet.2010.07.143

Tetrahedron Letters 51 (2010) 5181–5184
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Enhanced reactivity of silver- and gold-catalysed hydrogenations using
silver(I) salts
Robert Crook , John Deering , Steven J. Fussell , Alan M. Happe , Seán Mulvihill b
a
a
a,*
a
a
Chemical Research & Development, Pfizer, Sandwich Laboratories, Sandwich CT13 9NJ, UK
School of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, UK
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel application of silver(I) salt promoters in silver- and gold-catalysed hydrogenations was applied to
the chemoselective reduction of halonitrobenzenes resulting in excellent conversions and selectivities.
This reactivity, coupled with the low cost of silver relative to more expensive precious metal counter-
parts, demonstrates this catalytic system as an attractive alternative for challenging chemoselective
transformations.
Received 18 June 2010
Revised 13 July 2010
Accepted 23 July 2010
Available online 3 August 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1
. Introduction
hydrogenation of a
,b-unsaturated aldehydes13 have provided new
and exciting possibilities for gold-catalysed hydrogenation reac-
tions. Although excellent progress has been made in this field
one drawback is the high temperatures and pressures required to
achieve high conversions.
This Letter describes the design of a chemoselective hydrogena-
tion of synthetically useful substrates using a novel combination of
a silver on alumina catalyst, or a range of gold catalysts, coupled
with a silver(I) salt promoter. This key combination of catalyst
and additive is shown to facilitate low temperature and pressure
hydrogenation reactions amenable to large scale manufacture
using an inexpensive metal and support.
Silver, gold and copper form a group in the periodic table tradi-
tionally known as the coinage metals. Silver and gold are relatively
inert metals allowing for many of the applications we associate
with them today. Their uses have ranged from jewellery and coins
to electrical conductors. Silver is also used in mirrors and until re-
cently, in photographic films and plates. However, with the advent
of digital cameras the enormous reduction in the use of silver
halide-based films has seen the price of silver decrease and remain
low in comparison to other precious metals (Table 1).
It was not until the mid 20th century that silver was first
identified as a metal for catalytic reactions, with the oxidation of
The reduction of chloronitrobenzenes to their respective chloro-
anilines is an important transformation in the production of phar-
1
2
carbon monoxide and the decomposition of formic acid. Since
then, its application as a catalyst has been widely reported as illus-
1
4
maceutical and agricultural products. Iron in acidic reaction
3
4
15
trated by the oxidation of methanol, the epoxidation of ethylene,
media is routinely used in academia and small scale process re-
and more recently, as a potential alternative to the more expensive
platinum used in catalytic converters for diesel engines.
search; however, disposal issues associated with the iron residues
render the process undesirable for larger scale manufacturing.
Alternative methodologies have also been reported using a range
5
The use of gold in catalysis was initially reported in the early
1
6
17
1
970s when Bond described the hydrogenation of olefins over sup-
of precious metals including platinum, palladium and more re-
6
18
ported gold catalysts. Hutchings and Haruta et al. continued to
cently gold, as catalysts for the hydrogenation of chloronitro-
make breakthroughs with their work around polyvinyl chloride
benzenes. Although progress has been made, chemoselectivity
can still be a problem with the hydrodehalogenated side product
often observed (Fig. 1).
7
(
PVC) manufacture and the use of gold nano-particles in carbon
8
monoxide oxidation, respectively.
The first report of using silver to catalyse hydrogenation reac-
tions was described by Nagase et al.9 However, it was not until
Table 1
Comparison of metal prices
the work by Claus, investigating the reduction of
a,b-unsaturated
1
0
11
$/Troy ounce a
aldehydes, and Qui, with the reduction of chloronitrobenzenes,
that the chemoselective properties of supported silver catalysts
were first illustrated. The use of gold catalysts for chemoselective
reductions of aromatic nitro compounds12 and the highly selective
Metal
Gold
Silver
Platinum
Palladium
1119
18
1668
490
a
*
Corresponding author.
Metal prices provided by http://www.metalmar-
kets.org.uk/ 2nd April 2010.
E-mail address: steven.fussell@pfizer.com (S.J. Fussell).
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.143

5
182
R. Crook et al. / Tetrahedron Letters 51 (2010) 5181–5184
NO2
NH2
2 3
investigated in conjunction with the Ag/Al O catalyst for the
hydrogenation of p-CNB. The results are summarised in Table 2.
Whilst excellent selectivity was achieved in all cases with the 5%
Desired product
Ag/Al
showed a greater dependence on the additive used. Several metal
salts were beneficial with Zn(OAc) and Cu(OAc) showing some
2 3
O catalyst, conversion into the desired chloroaniline
X
X
2
2
promise, but silver salts clearly had the most beneficial effect.
In order to achieve both high chemoselectivity and conversion,
the presence of a silver cation and a basic anion was shown to be
1
2
2 3 2 3
important. AgOAc and Ag CO in combination with 5% Ag/Al O
yielded >99% of the chloroaniline at 100 °C and at a hydrogen pres-
sure of 250 psi. Further investigations showed that the AgOAc and
Ag
2 3
CO additives were both effective at a reduced pressure of
NO2
NH2
100 psi, but with a much slower reaction rate. However, at these
lower pressures, the AgOAc additive out-performed Ag
ing in high conversion and selectivity after 21 h.
2 3
CO result-
X = Cl, Br, I
Throughout the studies no hydrodechlorination of p-CNB or the
chloroaniline was observed in any of the reactions. Furthermore, p-
chloroaniline was not reduced to the undesired aniline when sub-
3
4
jected to the Ag/Al
00 °C.
Next, we attempted to apply the reaction conditions to a range
2 3
O and AgOAc system for 40 h at 250 psi and
Figure 1. Possible side reactions during the reduction of halonitroaromatics.
1
We started our investigation by comparing the effect of catalyst
on the hydrogenation of para-chloronitrobenezene (p-CNB). A tra-
ditional palladium catalyst, 5% Pd/C 58 was examined in tandem
2 3
with 5% Ag/Al O [both supplied by Johnson Matthey (J.M.)]. When
the palladium catalyst was used complete conversion into the ani-
line 4 was observed even at a low pressure of 40 psi. Gratifyingly,
of functionalised halonitrobenzenes. Table 3 illustrates that all the
halo-substituted nitrobenzenes were reduced selectively into the
corresponding halo-substituted anilines with the exception of
iodonitrobenzene where significant deiodination was observed.
In general, in situ yields of >95% could be achieved at a tempera-
ture of 100 °C at 150 psi for the chloro and fluoronitrobenzenes.
It was noted that the position of the halide had very little effect
on the hydrogenation process. However, the electronic effect of
the halogen did appear to have an important influence on the rate
of hydrogenation as illustrated in Table 3.
The conversion data illustrates that the rate of hydrogenation
decreases moving down group VII of the periodic table. Fluoroni-
trobenzene can be reduced selectively within 1 h whereas reduc-
tion of the corresponding iodonitrobenzene was incomplete after
30 h at the same temperature and pressure.
when the 5% Ag/Al
achieved but with only 15% conversion into the desired p-chloro-
aniline 2 (100 °C, 300 psi H ). Thus, our next aim was to develop
2 3
O catalyst was used, a selective reduction was
2
milder reaction conditions for the reduction of halonitrobenzenes
whilst increasing the conversion during the hydrogenation. To
achieve this goal, we investigated the possibility of enhancing
the reactivity with an additive.
Akao et al. identified Rh/C doped with additives, such as
Fe(OAc)
2
and Ni(NO
3
)
2
Á6H
2
O, as excellent promoters for accelerat-
ing the reduction of a range of functionalised nitrobenzenes
Table 4 shows that a combination of AgOAc and Al O alone can
2
3
1
9
including 4-chloronitrobenzene under hydrogenation conditions.
This approach appeared attractive and so a range of additives was
also catalyse the selective hydrogenation of p-CNB to chloroaniline
in yields of up to 39% with no hydrodehalogenation.
Interestingly, in all reactions containing AgOAc a thin silver film
was observed. The silver film indicates the formation of silver par-
ticles from AgOAc during the hydrogenation process and this could
be, in part, responsible for the enhanced conversion observed on
addition of silver(I) salts to the reactions. The formation of these
silver particles could provide an alternative catalytic site for the
reaction to take place. However, Table 4 also suggests that it is only
Table 2
Selective hydrogenation of p-CNB with JM 5% Ag/Al
2
O
3
catalyst
5
% Ag/Al O (10 wt%)
2 3
NO2
Additive (1 eq)
NH2
MeOH, H2
2 3
when all three components are combined, Ag catalyst, Al O and
AgOAc, that high yields are observed at the temperatures and pres-
sures stated.
We also studied the effect of additives on the gold-catalysed
hydrogenations. Hence, the same selection of additives was inves-
2 3
tigated in conjunction with a 5% Au/Al O catalyst provided by
Johnson Matthey. Table 5 lists the excellent selectivities obtained
in all reactions with no hydrodehalogenation products observed.
Once more the choice of additive had an important effect on the
conversion. Without an additive the reaction was very slow under
the conditions studied, but enhanced reaction rates were achieved
2 3
using silver salts. With Ag CO and AgOAc the reaction was com-
plete within 6 h at 100 °C and 250 psi. This evidence supports the
importance of both a silver cation and a basic anion.
Cl
Cl
2
1
50 psi
00 C
o
Additive
None
CF
Na
NaOAc
CaCO
AgBF
Ni(NO
Fe(OAc)
Zn(OAc)
Cu(OAc)
Ag
Ag
Ag
AgOAc
AgOAc
Time (h)
Conversiona (%)
20
20
20
20
20
20
20
20
20
20
20
15
6
3
SO
3
Ag
2
CO
3
10
11
16
18
18
20
35
51
54
29
99
90
99
3
4
3
)
2
Á6H
2
O
2
2
2
2
2
2
O
CO
CO
b
3
3
23
6
21b
6
To obtain a greater understanding of the factors influencing the
hydrogenation process this investigation was continued with
the exploration of a diverse range of gold-supported catalysts. The
hydrogenation of p-CNB was again used as the test reaction at
100 °C and 150 psi. The results shown in Table 6 illustrate that
a
No hydrodehalogenation observed.
Reactions performed at 100 psi.
b

R. Crook et al. / Tetrahedron Letters 51 (2010) 5181–5184
5183
Table 3
Table 5
Selective hydrogenation of
catalyst
a
range of halonitroaromatics with JM 5% Ag/Al
2
O
3
Selective hydrogenation of p-CNB with JM 5% Au/Al
2
O
3
catalyst
5
% Au/Al O (10 wt%)
2 3
5
% Ag/Al O (10 wt%)
2 3
Additive (1 eq)
NO2
NH2
NO2
AgOAc (1 eq)
NH2
X
X
MeOH, H2
250 psi
100 C
Cl
Cl
MeOH, H2
o
o
1
00 C
X= H, F, Cl, Br, I
Conversion (%) a
Additive
Time (h)
No additive
20
20
20
20
20
20
20
20
20
20
20
6
11
2
3
3
3
Substrate
Pressure Time Conversion %Hydrodehalogenation
Fe(OAc)
Ni(NO
Zn(OAc)2
CF SO Ag
2
(psi)
(h)
(%)
3 2
) Á6H
2
O
NO2
3
3
2
1
1
50
50
50
8
99
0
0
0
NaOAc
AgBF4
3
7
Cl
Cl
NO2
NO2
Cu(OAc)
CaCO
2
10
12
12
37
99
99
3
11
21
99
Na
Ag
2
CO
O
3
2
AgOAc
Ag CO
2
3
4
10a
a
No hydrodehalogenation observed.
Cl
NO2
Table 6
Cl
Cl
1
1
50
50
14.5
14
99
0
0
Comparison of catalyst supports for the hydrogenation of p-CNB after 20 h
Metal catalyst (10 wt%)
NO2
Additive (1 eq)
NO2
NH2
99
MeOH, H2
Cl
Cl
2
50 psi
o
1
00 C
NO2
1
1
50
50
0.5
24
100
0
0
Catalyst
Additive
Conversiona (%)
F
Br
I
Ag/Al
Ag/Al
2
O
O
3
3
None
AgOAc
None
AgOAc
None
AgOAc
None
AgOAc
None
AgOAc
10
100
11
77
6
63
22
52
13
2
2
NO2
2 3
Au/Al O
70
Au/Al O3
2
Au/SiO
Au/SiO
2
2
NO2
Au/TiO2
Au/TiO2
Au/C
42b
1
1
50
50
30
24
19
Au/C
NO2
a
No hydrodehalogenation observed.
100
n/a
a
Reaction carried out at 50 °C.
the solid support does have a large effect on the hydrogenation
process.
b
1
0% of nitrobenzene also formed.
It was found that a metallic oxide support was required to en-
hance reaction rates for the selective reduction of p-CNB. For
2
example, when the Au/SiO catalyst was doped with AgOAc, a
Table 4
10-fold increase in conversion was observed when compared to
the system without the additive. The corresponding reaction when
carbon was used as a support, resulted in retardation of the rate
when AgOAc was added, thus illustrating the importance of a me-
tal support for this reaction.
Selective hydrogenation of p-CNB
Metal catalyst (10 wt%)
additive (1 eq)
NO2
NH2
During this investigation, silver and gold catalysts have been
shown to be activated in the presence of a range of different addi-
tives and catalyse the hydrogenation of aromatic nitro compounds
in excellent yields and selectivity. The best system utilised silver
acetate and the procedure was optimised to more commercially
advantageous temperatures and pressures without compromising
chemical performance. The results described herein highlight the
potential of supported silver and gold catalysts activated by AgOAc
as excellent hydrogenation catalysts for selective synthesis of
haloanilines.
MeOH, H2
Cl
Cl
1
1
50 psi
00 C
o
Catalyst
Additive
Time (h)
Conversiona (%)
Ag/Al
None
None
None
2
O
3
AgOAc
AgOAc
6
20
20
17
99
3
4
Al
Al
2
O
O
3
2
3
and AgOAc
39
a
No hydrodehalogenation observed.

5
184
R. Crook et al. / Tetrahedron Letters 51 (2010) 5181–5184
2
. Typical experimental procedure for the Ag/Al
2
O
3
and AgOAc-
Koning for their scientific input, and Johnson Matthey for their
donation of a novel silver catalyst.
mediated hydrogenation of chloronitrobenzene
5
% Ag/Al O (10 wt%)
2 3
References and notes
NO2
AgOAc (1 eq)
MeOH,
NH2
1.
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o
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00 C
1
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HEL CAT18 autoclave. Using an Eppendorf pipette the reaction
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a
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2
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1.8 lm column.
Acknowledgements
2006, 10, 1178–1183.
The authors would like to thank Neal Sach, Charles Gordon,
Andrew Derrick, Julian Smith, Stephen Challenger and Pieter De