Palladium-catalyzed simple and efficient hydrogenative cleavage of azo compounds using recyclable polymer-supported formate

Article abstract of DOI:10.1139/v05-071

Palladium-catalyzed room temperature transfer hydrogenation of azo compounds using recyclable polymer-supported formate as the hydrogen donor produces corresponding amine(s) in excellent yields (88%-98%). This method was found to be highly facile with selectivity over a number of other functional groups such as halogen, alkene, nitrile, carbonyl, amide, methoxy, and hydroxyl.

Full text of DOI:10.1139/v05-071

517
RAPID COMMUNICATION / COMMUNICATION RAPIDE
Palladium-catalyzed simple and efficient
hydrogenative cleavage of azo compounds using
recyclable polymer-supported formate
Keelara Abiraj, Gejjalagere R. Srinivasa, and D. Channe Gowda
Abstract: Palladium-catalyzed room temperature transfer hydrogenation of azo compounds using recyclable polymer-
supported formate as the hydrogen donor produces corresponding amine(s) in excellent yields (88%–98%). This method
was found to be highly facile with selectivity over a number of other functional groups such as halogen, alkene, nitrile,
carbonyl, amide, methoxy, and hydroxyl.
Key words: azo compounds, catalytic transfer hydrogenation, polymer-supported formate, 10% Pd-C, amines.
Résumé : L’hydrogénation par transfert, catalysée par le palladium de composés azo, et réalisée à la température am-
biante en faisant appel à du formiate déposé sur un polymère recyclable comme donneur d’hydrogène, conduit à la for-
mation des amines correspondantes avec d’excellents rendements (88 %–98 %). On a trouvé que cette méthode d’une
extrême facilité présente une sélectivité par rapport à d’autres groupes fonctionnels, tels les halogènes, alcènes, nitriles,
carbonyles, amides et groupes méthoxy et hydroxyles.
Mots clés : composés azo, hydrogénation par transfert catalytique, formiate déposé sur un polymère, 10 % Pd-C, amines.
[Traduit par la Rédaction] Abiraj et al. 520
Polymer-supported reagents, catalysts, and scavengers are
now ubiquitous throughout the fields of combinatorial chem-
istry, organic synthesis, and catalysis (1, 2). The use of
polymer-supported reagents couples the advantages of solu-
tion phase chemistry (ease of monitoring the progress of the
reaction by using chromatographic and spectroscopic tech-
niques) with those of solid phase methods (use of excess re-
agents and easy isolation and purification of products). The
utility and power of such reagents has been exquisitely dem-
onstrated by the groups of Ley and others in synthesizing
several complex natural products by multi-step sequences re-
quiring many different kinds of heterogenized reagents, which
can be removed by simple filtration (1–3). In view of the
rapid development in the field of polymer-supported chemis-
try over the last few years, there is a pressing need for the
proper exploitation of functionalized polymer-supported re-
agents in organic synthesis.
pounds, limitations include the use of harsh conditions and
(or) costly reagents (4). In comparison with all other reduc-
tion processes, catalytic transfer hydrogenation (CTH) em-
ploying hydrogen donors, e.g., ammonium formate, is safer,
cost-effective, highly selective, rapid, and environmentally
friendly (5). Various CTH systems such as cyclohexene –
5% Pd on asbestos (6a), ammonium formate – 10% Pd-C
(6b), ammonium formate – zinc (6c), ammonium formate –
magnesium (6d), hydrazinium monoformate – zinc (6e), and
ammonium chloride – zinc (6f) have been developed for the
reduction of azo compounds to the corresponding amine(s).
However, ammonium-formate-aided CTH systems are the
most versatile and widely employed. Though efficient, these
ammonium formate CTH reactions are often troublesome
since ammonium formate can sublime and block the reaction
apparatus. Also, the reaction leads to the release of ammonia
and could create significant problems when performed on a
large scale. Moreover, the use of formate salts as hydrogen
donors poses complications during isolation and purification
of water-soluble products. Recently, potassium formate has
been used as a hydrogen donor in various transfer hydroge-
nation reactions (7a–7c). However, alkali metal formate
salts are not recommended for CTH reactions as these hy-
drogen donors reduce the catalyst activity.
Reduction of azo compounds to the corresponding
amine(s) is a synthetically important transformation, both in
the laboratory and in industry. Although there are a good
number of methods available for the reduction of azo com-
Received 7 October 2004. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 22 April 2005.
Desai and Danks (8a) and Basu et al. (8b) performed the
transfer hydrogenation of alkenes using polymer-supported
formate as the hydrogen donor in the presence of Wilkinson’s
catalyst or Pd(OAc)2. However, it has been observed that
controlling the reduction rates is difficult with these active
K. Abiraj, G.R. Srinivasa, and D.C. Gowda.1 Department
of Studies in Chemistry, University of Mysore,
Manasagangotri, Mysore-570 006, Karnataka, India.
1Corresponding author (e-mail: dcgowda@yahoo.com).
Can. J. Chem. 83: 517–520 (2005)
doi: 10.1139/V05-071
© 2005 NRC Canada

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Can. J. Chem. Vol. 83, 2005
Scheme 1.
Table 1. Hydrogenative cleavage of azo compounds using polymer-supported formate and 10% Pd-C.
Melting point (°C)
Entry
R
R′
Time (h)
Yield (%)a
Found
Literature
1
2
3
4
5
H
4-Cl
2-Br
4-I
H
4′-Cl
2′-Br
4′-I
4′-CH2=CH2
2.0
2.5
3.0
2.5
4.0
98b
96
112–114
71
98–100
63–65
210–212d
114 (11a)
70 (11a)
99 (11a)
63 (11a)
213–214 (11a)
94b
95
4-CH2=CH2
94c
6
4-CH2-CN
4′-CH2-CN
5.0
90
47–49
45–48 (11a)
7
8
4-CHO
4-COCH3
4′-CHO
3.5
5.0
93
94
72–74
105
72 (11a)
106 (11b)
4′-COCH3
9
2-CH3
2′-CH3
4′-CONH2
4′-OCH3
3.0
4.5
4.0
96e
142–144
114–115
57–59
144 (11a)
114 (11a)
57 (11a)
10
11
4-CONH2
4-OCH3
95
94b
12
13
14
2-OH
4-COOH
4-NH2, 3-CH3
2′-OH
4′-COOH
2′-CH3
3.5
4.0
5.0
95
173–175
187
63–65, 144
174 (11a)
188 (11a)
64 (11a), 144 (11a)
96
88, 92e
15
4-NH2
H
5.0
88, 90b
145, 112–114
145–147 (11b), 114 (11a)
aYields of isolated products.
bIsolated as the acetyl derivative.
cThe spectra were compared to those of a commercial sample.
dBoiling point.
eIsolated as the benzoyl derivative.
homogeneous catalysts. On the other hand, the use of hetero-
geneous catalysts offers several advantages over homoge-
neous systems such as easy recovery and recycling of the
catalyst, high selectivity, easy product isolation, and
minimization of undesired toxic wastes. In this context, we
probed the reduction of azo compounds employing polymer-
supported formate as a hydrogen donor in the presence of
10% palladium on carbon as the heterogeneous catalyst. Our
investigations revealed that the use of polymer-supported
formate in conjunction with 10% Pd-C is highly efficient for
the facile reduction of substituted azo compounds to the cor-
responding amine(s) (Scheme 1).
3300 cm–1 ascribed for the NH2 group and no absorption
bands were noticed for the substrate azo compound (between
1630–1575 cm–1) and intermediate hydrazo compound
(2290–2440 cm–1) clearly indicating the complete conver-
sion of azo compounds to their corresponding amino deri-
vate(s). Further, the appearance of a broad singlet between
δ 4.5 and 6.5 owing to the NH2 protons in the 1H NMR spec-
tra confirmed the products evidently. The reactions are, on
the whole, reasonably fast and high yielding (88%–98%). It
is worthwhile to note that our system selectively reduced
azo compounds to the corresponding amines in the presence
of other sensitive functional groups such as halogen (5a, 5b)
(Table 1, entries 2–4), alkene (5a, 5f) (Table 1, entry 5),
nitrile (5a, 5b) (Table 1, entry 6), and carbonyl (5a, 9) (Ta-
ble 1, entries 7 and 8), which are susceptible to reduction
under transfer hydrogenation conditions. In addition, many
other functional groups such as amide, methoxy, acid, and
hydroxyl are also compatible with the present system.
In the case of symmetrically substituted azo compounds,
A wide range of structurally varied azo compounds, both
symmetric and unsymmetric, underwent reduction by this
procedure to furnish the corresponding amine(s). The results
are summarized in Table 1. All the products were character-
1
ized by comparison of their TLC, melting points, IR and H
NMR spectra with authentic samples. The IR spectra of all
the products showed a sharp doublet between 3500 and
© 2005 NRC Canada

Abiraj et al.
519
Table 2. Recycling of polymer-supported
formate for the reduction of azobenzene.
pounds to obtain the corresponding amines in pure form
with no work-up.
Cycle
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
2.0
2.0
3.0
3.5
3.5
4.0
4.0
4.0
98
97
97
97
97
95
93
92
Experimental
Preparation of polymer-supported formate
The aminomethyl polystyrene (Advanced Chemtech, 1%
DVB cross-linked, 100–200 mesh, 2 mmol/g) was washed
with an excess of a 50% solution of formic acid in dichloro-
methane. The resulting polymer was washed thoroughly and
successively with dichloromethane and ether, and dried un-
der vacuum. The obtained resin was used as such for the re-
duction.
the separation of products from the reaction mixture is sim-
ple and involves, in most of the cases, direct removal of the
catalyst and resin by filtration and evaporation of the solvent
under vacuum. The crude product, so isolated, was of excel-
lent purity for most purposes. Hence, this procedure is highly
advantageous to obtain water-soluble aromatic amines in
high yields (Table 1, entries 2, 8, 11–13). Further, it is note-
worthy here that the polymer-supported formate was regen-
erated and could be reused for further hydrogenolysis
process. In total, 10 successive recycle runs were possible
before there was an appreciable decrease in the reaction
yield (Table 2).
To obtain optimum reduction conditions, a number of
trails with a range of solvents, which are commonly em-
ployed for CTH reactions, were carried out. Methanol is
found to be the best one as far as the solubility of substrate
and rate of reaction is concerned. To examine the effects of
catalyst loading, the reduction was attempted using different
ratios of catalyst and substrate. We observed the optimal ra-
tio of catalyst to substrate to be 1:4 by weight (approxi-
mately 0.05 mmol catalyst for 1 mmol of substrate). However,
the rate of reduction was significantly slower when smaller
amounts of catalyst were used. During the recycle runs, an-
other 0.025 mmol of catalyst was added after the fifth cycle
to increase the rate of reduction.
Determination of polymer-supported formate loading
The polymer-supported formate (1 g) was placed in a
manually operated solid phase vessel and washed thoroughly
with dil. HCl (0.05 N). The HCl washing containing formic
acid (released from the resin) was collected and diluted to
50 mL in a volumetric flask. An aliquot (10 mL) of this
solution was titrated potentiometrically against a standard
NaOH solution. The formate loading was calculated to be
1.92 mmol/g.
General procedure for the reduction of azo compounds
To a solution of the azo compound (1 mmol) in methanol
(15 mL) taken in a horizontal solid phase vessel, polymer-
supported formate (1 g) and 10% Pd-C (50 mg, 0.05 mmol)
were added. The suspension was shaken well2 for the speci-
fied time at room temperature (Table 1). After consumption
of the starting material, as monitored by TLC, the reaction
mixture was filtered and washed thoroughly with methanol.
The combined washings and filtrate were evaporated under
reduced pressure. The crude product was found to be analyt-
ically pure in most cases. Where necessary, the crude prod-
uct was taken into the organic layer and washed with
saturated sodium chloride. For recycling purposes, the resi-
due containing the polymer-supported formate and the cata-
lyst was washed thoroughly and successively with DMF,
dichloromethane, a 50% solution of formic acid in dichloro-
methane, dichloromethane, and ether. The activated resin
along with the catalyst were dried under vacuum and used as
obtained for further reduction reactions.
The reductive cleavage of azo compounds proceeds smoothly
despite the dual heterogeneity of catalyst and polymer sup-
port. The initial step in the reduction would be the formation
of palladium diformate by the reaction of palladium with the
formate released from the polymeric support (10a, 10b). The
palladium formate can then transfer two hydrogen atoms to
the azo compound. In addition to this essential feature, the
In the case of the reduction of unsymmetrically substi-
tuted azo compounds, the crude product was subjected either
to preparative TLC or to column chromatography to separate
two different constituent amines.
+
polymer-supported NH3 may also provide H+ to complete
the reduction process (10c).
In conclusion, a highly facile polymer-supported formate –
10% Pd-C system was developed for the smooth reduction
of azo compounds to the corresponding amine(s). The use of
polymer-supported formate combines the advantages of
polymer-supported chemistry with the flexibility of the CTH
technique. The advantages include a safe reaction medium,
high selectivity, rapidity, ease of operation, and simple re-
covery of the hydrogen donor. In addition, this approach is
highly helpful for the reduction of symmetric azo com-
Acknowledgements
We gratefully acknowledge financial support from the
University Grants Commission, New Delhi. We also ac-
knowledge the Council of Scientific and Industrial Research,
New Delhi for a research fellowship (to KA).
2 The reaction mixture was subjected to shaking using a manual shaker as the shaking of the polymer-supported formate instead of stirring in-
creases its life for recycling purposes.
© 2005 NRC Canada

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Can. J. Chem. Vol. 83, 2005
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