Reductive cleavage of azo compounds catalyzed by commercial zinc dust using ammonium formate or formic acid

Article abstract of DOI:10.1016/S0040-4039(01)02370-X

Azo compounds, both symmetric and unsymmetric, are cleaved to amine(s) by using commercial zinc dust and ammonium formate or formic acid in methanol, tetrahydrofuran or dioxane at room temperature. The reductive cleavage occurs without hydrogenolysis or hydrogenation of reducible moieties, such as -OH, -CH₃, -OCH₃, -COOH, -COCH₃, halogen, etc. The cleavage is very fast, clean, cost effective and high-yielding if compared with earlier methods, such as those using cyclohexene/5% Pd on asbestos, cyclohexene/10% Pd-C or hydrazine/10% Pd-C or Raney nickel.

Full text of DOI:10.1016/S0040-4039(01)02370-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1329–1331
Reductive cleavage of azo compounds catalyzed by commercial
zinc dust using ammonium formate or formic acid
Shankare Gowda, K. Abiraj and D. Channe Gowda*
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, Karnataka 570 006, India
Received 25 October 2001; revised 4 December 2001; accepted 13 December 2001
Abstract—Azo compounds, both symmetric and unsymmetric, are cleaved to amine(s) by using commercial zinc dust and
ammonium formate or formic acid in methanol, tetrahydrofuran or dioxane at room temperature. The reductive cleavage occurs
without hydrogenolysis or hydrogenation of reducible moieties, such as -OH, -CH , -OCH , -COOH, -COCH , halogen, etc. The
3
3
3
cleavage is very fast, clean, cost effective and high-yielding if compared with earlier methods, such as those using cyclohexene/5%
Pd on asbestos, cyclohexene/10% PdꢀC or hydrazine/10% PdꢀC or Raney nickel. © 2002 Elsevier Science Ltd. All rights reserved.
Metal-mediated reactions have a wide scope in organic
synthesis because of their simple work-up and selectiv-
ity. For example, the utility of zinc for the synthesis
require reaction times as long as 23–48 h at reflux and
expensive catalysts, such as 10% PdꢀC, 5% Pd on
asbestos and Raney Ni. Raney Ni catalyst is flammable
in the presence of air and presents considerable hazards
during handling. If the azo compounds contain
reducible or hydrogenolysable groups, such as a halo-
1
–6
of b,g-unsaturated ketones and homoallylic alcohols by
7,8
the reaction of an acid chloride with allyl bromide
has been demonstrated. Furthermore, zinc-mediated
9
10
amide bond formation, Friedel–Crafts acylation and
gen or a nitrile, then systems like 10% PdꢀC/
1
1
21
carbamate formation have also been demonstrated.
HCOONH
4
and 10% PdꢀC/triethyl ammonium
2
2
formate reduce the nitrile group to a methyl group
and remove the halogen from aromatic rings. More-
over, poor yields are reported during the reduction of
azo compounds to amines due to the formation of
intermediate hydrazo compounds.
1
2–14
The application of ammonium formate
acid
and formic
1
2,13
in the field of catalytic transfer hydrogenation
for the reduction of a variety of organic compounds
and the synthesis of peptides has been reviewed. The
application of catalytic transfer hydrogenation for
reduction and reductive cleavage of organic compounds
and in peptide synthesis is mainly centered on the use
of expensive catalysts, such as PdꢀC, RuꢀCa,
We wish to report a rapid, selective and simple cleavage
of substituted azo compounds to the corresponding
amino derivative(s) by using low-cost commercial zinc
dust and ammonium formate or formic acid at room
temperature in methanol, tetrahydrofuran or dioxane
(Scheme 1). This new system cleaved with ease a wide
variety of azo compounds to the corresponding
1
2–14
PdꢀCaCO , RuꢀC and Raney Ni.
Some systems,
3
like hydrazine/Raney Ni, have been developed for the
reduction of azo compounds to hydrazo compounds
and for reductive cleavage to amines.
15–17
17–20
These systems
Zn/HCO2NH4 or HCO2H
MeOH, r.t.
N
N
NH2 + H2N
X
Y
X
Y
X or Y = -H, halogen, -OH, -OCH , -COOH, -CH , -COCH , etc.
3
3
3
Scheme 1.
Keywords: ammonium formate; azo compounds; catalytic transfer hydrogenation; formic acid; reductive cleavage; zinc dust.
*
Corresponding author. Tel.: (home) 091-0821-344348, (office) 091-0821-515525, ext. 48; fax: 091-0821-421263/518835; e-mail:
dcgowda@yahoo.com
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02370-X

1
330
S. Gowda et al. / Tetrahedron Letters 43 (2002) 1329–1331
amine(s). Many primary and secondary functional
groups, such as halogens, -CH3, -OH, -COOH,
cal azo compounds, clearly indicated that no hydrazo
compounds were formed during the reductive cleavage
of the azo compounds.
-
COCH , -OCH , etc., are tolerated.
3 3
The cleavage of an azo compound in the presence of
zinc dust and ammonium formate or formic acid was
complete within 3–10 min. The course of the reaction
was monitored by thin layer chromatography (TLC)
and IR spectra. The work-up and isolation of the
products were easy. Thus, all compounds reduced (a
few examples are listed in Table 1) by this system were
obtained in good yields (90–95%). Products were char-
acterized by comparison of their melting points, TLC
and IR spectra with authentic samples. The disappear-
ance of a strong absorption band between 1630 and
Furthermore, the ammonium formate or formic acid/
zinc system is more effective than either cyclohexene/
18
19
5
%
Pd on asbestos,
cyclohexene/10% PdꢀC ,
20
20
hydrazine/10% PdꢀC or hydrazine/Raney Ni. Most
of the reactions are complete in less than 5 min at room
temperature, as monitored by TLC by the disappear-
ance of the starting materials and concomitant forma-
tion of the product(s). In addition, the methods
mentioned earlier require long reaction times, e.g. 16–
4
8 h, and high temperatures.
−
1
1
575 cm due to the -NꢁN- stretching and the appear-
Thus, the cleavage of azo compounds can be accom-
plished at room temperature in a short time with com-
mercial zinc dust instead of expensive platinum or
palladium, etc., without affecting the reduction of any
reducible or hydrogenolysable substituents. The yields
are virtually quantitative and the products were analyt-
ically pure. This procedure will therefore be of general
use, especially in cases where rapid, mild and selective
reduction or cleavage is required. Further investigations
of other useful applications related to the deblocking of
protecting groups in peptide synthesis are in progress.
ance of a strong absorption band between 3500 and
3
−
1
300 cm due to the -NH group clearly showed that
2
the azo compounds had been cleaved into their con-
stituent amine(s). Furthermore there was no absorption
−
1
between 2290 and 2440 cm , which clearly indicated
the absence of the -NHꢀNH- group. A control experi-
ment carried out using an azo compound with ammo-
nium formate or formic acid but without zinc dust
failed to yield the desired product. The appearance of
one spot in the TLC, in the case of symmetrical azo
compounds, and two spots, in the case of unsymmetri-
Table 1. Reductive cleavage of azo compounds catalyzed by commercial zinc dust using ammonium formate or formic acid
Zn/HCO2NH4 or HCO2H
N
N
NH2 + H2N
MeOH, r.t.
X
Y
X
Y
Substrate
Product
Substrate
Y
Product
Duration (min)
Yield (%)a
Melting point (°C)
X
X
Y
Found
Literature
23
-
H
-H
-H
2-CH3
3-CH3
2-Br
3-OCH3
-H
4-N(CH3)2
4-N(CH3)2
4-N(CH3)2
4-NH , 3-CH
3-COCH3
4-Cl
-H
3
6
5
7
7
10
8
13
15
12
9
95
94
95
93
112c
114
144
125
116
b
23
2
3
2
3
-CH3
-CH3
-Br
2%-CH3
3%-CH3
2%-Br
3%-OCH3
4%-COOH
-H
2-CH3
3-CH3
2-Br
3-OCH3
4-COOH
-H
142
126
115
82
b
23
b
23
c
23
-OCH3
94
80
c
23
23
23
-H
95, 80
95, 95
92, 55
91, 88
92, 93
90
91
93, 95
89
113 , 188
114, 186
c
24
4
4
4
4
3
4
4
2
1
-N(CH3)2
-N(CH3)2
-N(CH3)2
-NH , 3-CH3
-COCH3
-Cl
-NH2
-OH
52, 113
52, n.d.
53, 146
65, 144
99
71
140, 113
172
188
53, 114
d
e
24
4%-SO Na
4-SO Na
53,
–
3
3
2
4
23
23
2%-COOH
2%-CH3
3%-COCH3
4%-Cl
-H
2%-OH
2-COOH
2-CH3
3-COCH3
4-Cl
-H
2-OH
53, 145
b
23
64, 144
2
2
3
2
3
101
70
2
3
8
5
7
16
2
3
4-NH2
2-OH
1-Aminonaphthalene
141, 11423
2
3
174
190
2
3
,1%-Azonaphthalene
85
In the case of unsymmetrical azo compounds, the first-mentioned data refer to the left-hand fragment azo compound and the next-mentioned data
refer to the right-hand fragment of the reductively cleaved azo compound.
a
Isolated yields are based on a single experiment and the yields were not optimized.
Melting point of benzoyl derivative.
Melting point of acetyl derivative.
The low yield is due to its water-soluble nature, TLC analysis indicates 95–98% cleavage.
b
c
d
e
n.d. Not determined.

S. Gowda et al. / Tetrahedron Letters 43 (2002) 1329–1331
1331
Experimental
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ammonium formate (2 g) or formic acid (3 mL) was
stirred under a nitrogen atmosphere at room tempera-
ture. After the completion of the reaction (monitored
by TLC or by the disappearance of the starting material
color), the reaction mixture was filtered through a
Celite pad and washed with solvent. When ammonium
formate was used, the combined filtrate and washings
were concentrated under vacuum. The residue was
taken into 15 mL chloroform or ether, washed twice
with 15 mL saturated brine solution and finally washed
with water. The organic layer was dried over anhydrous
magnesium sulfate and the solvent was removed using a
rotary evaporator. For further purification/separation
of products, the residue was purified either by prepara-
tive TLC or by column chromatography. When formic
acid was used, the filtrate and washings were neutral-
ized with ammonia then evaporated under vacuum and
worked up, as mentioned above. After chromato-
graphic separation/purification, the IR spectra and
melting points were compared with authentic samples.
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