Clean and efficient hydrogenative cleavage of azo compounds using polymer-supported formate and zinc

Article abstract of DOI:10.1081/SCC-200054755

Azo compounds, both symmetric and asymmetric, were chemoselectively reduced to the corresponding amine(s) using recyclable polymer-supported formate as a hydrogen donor in the presence of zinc at room temperature. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200054755

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Clean and Efficient
Hydrogenative Cleavage
of Azo Compounds Using
Polymer‐Supported Formate
and Zinc
a
a
a
G. R. Srinivasa , K. Abiraj & D. Channe Gowda
a
Department of Studies in Chemistry , University of
Mysore , Mysore, Karnataka, India
Published online: 16 Aug 2006.
To cite this article: G. R. Srinivasa , K. Abiraj & D. Channe Gowda (2005) Clean
and Efficient Hydrogenative Cleavage of Azo Compounds Using Polymer‐Supported
Formate and Zinc, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 35:9, 1161-1165, DOI: 10.1081/
SCC-200054755
To link to this article: http://dx.doi.org/10.1081/SCC-200054755
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Synthetic Communications , 35: 1161–1165, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200054755
Clean and Efficient Hydrogenative Cleavage
of Azo Compounds Using
Polymer-Supported Formate and Zinc
G. R. Srinivasa, K. Abiraj, and D. Channe Gowda
Department of Studies in Chemistry, University of Mysore,
Mysore, Karnataka, India
Abstract: Azo compounds, both symmetric and asymmetric, were chemoselectively
reduced to the corresponding amine(s) using recyclable polymer-supported formate
as a hydrogen donor in the presence of zinc at room temperature.
Keywords: Amines, azo compounds, hydrogenative cleavage, polymer-supported
formate, zinc
INTRODUCTION
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
[1]
compounds, catalytic transfer hydrogenation (CTH) has many distinctive
[2]
advantages. The combination of reagents such as cyclohexene/5% Pd on
[
3a]
[3b]
[3c]
asbestos,
ammonium formate/magnesium,
ammonium formate/10% Pd-C,
[
ammonium formate/zinc,
[3e]
3d]
hydrazinium monoformate/zinc, and
have been developed for the reduction of azo
[
3f]
ammonium chloride/zinc
compounds to the corresponding amine(s). Ammonium formate is efficient
for reduction, the sublimation and isolation of water-soluble products pose
Received in India December 14, 2004
Address correspondence to D. Channe Gowda, Department of Studies in Chemistry,
University of Mysore, Manasagangotri, Mysore 570 006, Karnataka, India. Fax: 091-
0
821-2421263/2518835. E-mail: dcgowda@yahoo.com

1162
G. R. Srinivasa, K. Abiraj, and D. C. Gowda
Scheme 1.
[4]
disadvantages with this reagent. The use of polymer-supported reagents for
this transformation would be an ideal choice to circumvent these problems. For
example, the polymer-supported formate has been developed and utilized for
transfer hydrogenation of alkenes in the presence of Wilkinson’s catalyst or
[5]
Pd(OAc)2. We have investigated the polymer-supported formate and zinc
as a versatile combination to cleave the azo derivatives into the corresponding
amine(s). Our investigations revealed that the use of polymer-supported
formate in conjunction with zinc is highly efficient for the facile reduction
of substituted azo compounds to the corresponding amine(s) (Scheme 1).
The scope of this new system is illustrated in Table 1, where we examined
series of azocompounds, both symmetric and asymmetric, with avarietyof sub-
stituents. All the products were characterized by comparison of their TLC,
1
melting points, IR spectra, and H-NMR spectra with authentic samples. The
reactions are rapid (10–20 min) and high yielding (86–96%). The present
system selectively reduced azo compounds to the corresponding amine(s)
[
2a,2b]
[2a,2c]
without interfering with halogen
[
(Table 1, entries 2–4), alkene
[2a,7]
2a,6]
(
Table 1, entry 5), nitrile
(Table 1, entry 6), and carbonyl
(Table 1,
entries 7 and 8) groups. Other functional groups, such as amide, methoxy,
acid, and hydroxyl groups, are also compatible with the present system. The
polymer-supported formate was regenerated and eight successive recycle
runs were performed without any decrease in the reaction yield.
In conclusion, a highly facile, polymer-supported formate/zinc system
was developed for the smooth hydrogenative cleavage 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 CTH technique. The advantages include safe reaction medium, high selec-
tivity, rapidity, ease of operation, and simple recovery of the hydrogen donor.
In addition, this approach is very helpful for the reduction of symmetric azo
compounds to obtain the corresponding amines in pure form with no workup.
EXPERIMENTAL
For this study, the polymer-supported formate was prepared by washing
aminomethyl polystyrene (2 mmol/g) with an excess of 50% solution of

Table 1. Hydrogenative cleavage of azo compounds using polymer-supported formate and zinc
Melting point (8C)
0
a
Entry
R
R
Time (min)
Yield (%)
Found
Literature
b
[8a]
1
2
3
4
5
6
7
8
9
H
H
10
10
15
12
15
18
20
16
10
20
20
18
20
20
15
96
114
69–70
98–99
62–64
210–212
47–49
70–72
105
114
0
[8a]
4-Cl
2-Br
4-I
4 -Cl
96
70
0
b
[8a]
2 -Br
94
99
0
[8a]
4 -I
95
63
0
c
d
[8a]
4-CH
4-CH
2
55 CH
-CN
2
4 -CH
2
55 CH
-CN
2
92
213–214
0
[8a]
2
4 -CH
2
93
95
95
45–48
0
[8a]
4-CHO
4 -CHO
72
0
[8a]
[8a]
[8a]
4-COCH
3
4 -COCH
3
106
144
114
0
e
2-CH
4-CONH
3
2 -CH
3
96
143–144
113–114
0
1
1
1
1
1
1
0
1
2
3
4
5
2
4 -CONH
2
94
0
b
[8a]
4-OCH
2-OH
3
4 -OCH
3
93
57–59
57
0
[8a]
2 -OH
96
94
175
174
0
0
[8a]
4-COOH
4 -COOH
186–188
188
e
[9a]
64 , 144
[8a]
4-NH
4-NH
2
2
, 3-CH
3
2 -CH
H
3
86, 90
65–66, 143–145
145, 113–114
b
[8b]
[8a]
89, 92
145147,
114
a
b
c
Yields of isolated products.
Isolated as acetyl derivative.
The spectra were compared to those of a commercial sample.
d
Boiling point.
Isolated as benzoyl derivative.
e

1164
G. R. Srinivasa, K. Abiraj, and D. C. Gowda
formic acid in dichloromethane. The resulting polymer was washed
thoroughly and successively with dichloromethane and ether, and dried
under vacuum. The obtained resin was used as such for the reduction.
1
The H NMR spectra were recorded on an AMX-400 MHz spectrometer
using CDCl as the solvent and TMS as internal standard. IR spectra were
3
recorded on Shimadzu FTIR- 8300 spectrometer. The melting points
were determined by using a Thomas–Hoover melting point apparatus
and are uncorrected. Thin-layer chromatography was carried out on silica-
gel plates obtained from Whatman Inc. The substrates were either commercial
products and were used as purchased or were prepared according to literature
procedures. Aminomethyl polystyrene resin was purchased from Advanced
Chemtech (1% DVB cross-linked, 100–200 mesh, 2 mmol/g). Zinc dust
was purchased from E-Merck Ltd (India). All of the solvents used were
analytical grade or were purified according to standard procedures.
General Procedure for the Reduction of Azo Compounds
A suspension of azo compound (5 mmol), polymer-supported formate (1 g),
and zinc dust (5 mmol) in methanol (15 mL) taken in a horizontal solid-
phase vessel was shaken well for the specified time at room temperature
(Table 1). (The reaction mixture was subjected to shaking using a manual
shaker because the shaking of the polymer-supported formate instead of
stirring increases its life for recycling purposes.) After consumption of
the starting material, as monitored by TLC, the reaction mixture was filtered
and washed thoroughly with methanol. The combined filtrate was evaporated
under reduced pressure. The crude product was found to be analytically pure in
most cases. Where necessary, the crude product was taken into the organic
layer and washed with saturated sodium chloride.
In the case of reduction of asymmetrically substituted azo compounds, the
crude product was subjected either to preparative TLC or to column chromato-
graphy to separate two different constituent amines.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from the University Grants
Commission, New Delhi, India. We also acknowledge Council of Scientific
and Industrial Research, New Delhi, India, for a research fellowship (to K. A.).
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