Hydrogenation of azides over copper nanoparticle surface using ammonium formate in water

Article abstract of DOI:10.1021/jo200915h

Aryl azides undergo clean reduction by copper nanoparticles and ammonium formate in water. The surface hydrogen on copper nanoparticles is considered to be the active reducing species. A variety of functionalized aryl azides and aryl sulfonyl azides are reduced by this procedure to the corresponding amines with excellent chemoselectivity in high yields.

Full text of DOI:10.1021/jo200915h

NOTE
pubs.acs.org/joc
Hydrogenation of Azides over Copper Nanoparticle Surface Using
Ammonium Formate in Water
Sabir Ahammed, Amit Saha, and Brindaban C. Ranu*
Department of organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata-700032, India
S Supporting Information
b
ABSTRACT: Aryl azides undergo clean reduction by copper nanoparticles and
ammonium formate in water. The surface hydrogen on copper nanoparticles is
considered to be the active reducing species. A variety of functionalized aryl
azides and aryl sulfonyl azides are reduced by this procedure to the corresponding
amines with excellent chemoselectivity in high yields.
Scheme 1. Hydrogenation of Azides
he transition metal nanoparticles play an important role in
organic reactions because of their high surface to volume
T
ratio and larger number of active sites per unit area compared to
the parent metal.1 Hydrogenation over metals, particularly Pd
and Pt, is widely used for the reduction of a variety of function-
alities and is significantly influenced by the surface of the metal
catalyst.2 Recently, several reports appeared that demonstrated
efficient hydrogenation over the surface of Pd, Pt, and Ru
nanoparticles where these metals dissociate H2 and facilitate
the hydrogenation process.3 However, although these noble
metals are frequently employed, use of less expensive Cu
nanoparticles for hydrogenation is very limited.4 In general,
copper metal and copper salts are more acceptable to the
environment, and thus we became interested in finding new
applications of Cu nanoparticles for hydrogenation of useful
organo-functional groups with a particular attention to chemo-,
regio-, and stereoselectivity.
Organic azides are very versatile and useful synthons and have
wide applications in the synthesis of triazoles and other
heterocycles.5 The reduction of azides provides a very straight-
forward route to amines, which are an important class of
compounds and have potential uses in chemistry and biology,
such as synthesis of bioactive pharmaceuticals and natural
products.6 This protocol became more appealing because of
the easy accessibility of azides from the corresponding halides
and sulfonates.7 A large variety of reducing agents have been
employed for the conversion of azides to amines.5c,8 These
include a variety of hydride reducing agents,5c triphenyl
phosphine,8a metal-catalyzed hydrogenations,8b radical initiators,8c
Zn(BH4)2,8d Cl2InH,8e molybdenum xanthate/PhSiH3,8f etc.
Although these reagents are, in general, satisfactory, several of
them have limitations with regard to general applicability, cost
efficiency, and selectivity, and their success also varies from
substrate to substrate having other reducible functionalities.9 Thus,
an alternative, simple, and inexpensive reducing agent offering
moreeco-friendly reaction conditionsand efficiency is appreciated.
We report here a highly chemoselective reduction of aryl azides by
hydrogenation on Cu(0) nanoparticle surfaces using ammonium
formate in water (Scheme 1).
Table 1. Standardization of Reaction Conditions
entry solvent catalyst (Cu NPs) temp (°C) time (h) yield (%)
1
2
THF
DMF
dioxane
toluene
H2O
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
1 equiv
0.5 equiv
0.25 equiv
66
110
100
100
100
70
7
7
7
7
8
8
8
8
8
8
14
75
31
24
83
10
3
4
5
6
H2O
7
H2O
25
8
H2O
100
100
100
83
83
31
9
H2O
10
H2O
To standardize the reaction conditions, several experiments
were performed for a representative reaction of phenyl azide with
a varied amount of Cu nanoparticles with variation of solvent,
reaction temperature, and time. The results are shown in Table 1.
It was found that water at reflux for 8 h provides the best yield
with 50 mol % of Cu nanoparticles (with respect to azide).
Although the yield of product using DMF is comparable, those in
relatively nonpolar THF, dioxane, and toluene are far from
satisfactory. The reaction did not proceed at room temperature.
Received: May 7, 2011
Published: July 28, 2011
r
2011 American Chemical Society
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|

The Journal of Organic Chemistry
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Table 2. Reduction of Aromatic Azides by Cu Nanoparticles/
HCOONH4
Figure 1. TEM image of Cu nanoparticles.
Figure 2. Energy-dispersive X-ray spectra of Cu.
Thus, in a typical experimental procedure, a mixture of aryl
azide, Cu nanoparticles, and ammonium formate in water was
heated under reflux for a certain period of time (TLC). Standard
workup and purification by column chromatography provided
the pure product.
Copper nanoparticles were prepared from copper sulfate by
reaction with hydrazine hydrate in ethylene glycol.10 The particle
sizes are in the range of 6À8 nm as observed in transmission
electron microscopy (TEM) (Figure 1). The identity of the
particles as being of copper was established by energy-dispersive
X-ray spectroscopy (EDS) (Figure 2).
a Yields refer to those of purified products characterized by IR and 1H
and 13C NMR spectroscopic data. b The known compounds are
identified by comparison of their spectroscopic data with those reported.
presented in Table 2. Significantly, 4-, 3-, and 2-nitrophenyl
azides (Table 2, entries 4À6) underwent clean reaction, giving
the corresponding nitroanilines without any reduction of nitro
Several substituted aryl azides were reduced by this procedure
to produce the corresponding aromatic amines. The results are
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The Journal of Organic Chemistry
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group. These results indicate that reduction of azide functionality
is more facile than that of the nitro group by the copper nano-
particles/HCOONH4 reagent system.4 The nitro group at the
2-position did not pose any steric constraint (Table 2, entry 6).
The nitrile, ketocarbonyl, carboxylic ester, carboxylic acid, amide, O-
allyl, N-allyl, OMe, F, Cl, Br, and I remained unaffected in
the reduction of the corresponding azides bearing these function-
alities. The O-benzyl functional group is also compatible with this
procedure (Table 2, entry 17). 6-Azidoquinoline was reduced to
6-aminoquinoline, keeping the heterocyclic ring intact. 1,4-Diazo-
benzene was reduced to 4-azidoaniline with selective reduction of
one azido group. Significantly, use of excess (3 equiv) Cu nano-
particles and ammonium formate also reduced only one azido
group. Methyl sulfonyl azide and 4-methylphenyl sulfonyl azide
(Table 2, entries 21 and 22) also underwent clean reductions to the
corresponding amides by this procedure. Many conventional pro-
cedures involving hydride reducing agents, metals, and hydrogena-
tion failed to give such broad spectrum of selectivity.5c,8
Figure 3. Rate of progress of reduction with time.
In general, all of the reactions are clean and high yielding. The
azides are easily prepared following a reported procedure.7 The
reductions are not at all effective with Cu nanoparticles alone in
the absence of ammonium formate. On the other hand, the
reaction was also not initiated using ammonium formate alone in
the absence of Cu nanoparticles. A combination of Cu nanopar-
ticles and ammonium formate in water at 100 °C is essential for a
successful reaction. The rate of reduction based on the progress
of reaction with time (NMR) for a particular substrate is found to
be uniform (Figure 3).
Table 3. Comparison of Results of Reductions of Aromatic
Azides Using Metallic Cu Powder with Cu Nanoparticles
To establish the absolute necessity of Cu(0) nanoparticles for
this reduction, a comparison of results of a few representative
reactions with those by freshly prepared metallic Cu (prepared
by reaction of CuSO4 and Zn dust15) is presented in Table 3.
These results showed only a marginal activity of metallic Cu
powder, whereas much higher activity was observed using Cu
nanoparticles during the transfer hydrogenation process using
ammonium formate16 under the reaction conditions. To under-
stand the reaction pathway, we carried out the reaction in the
presence of TEMPO (2,2,6,6-tetramethylpiperidine N-oxide)
and we did not find any effect of this radical quencher, indicating
a nonradical process. Like Pd hydride formation from Pd
nanoparticles,3a initially we considered the intermediacy of
CuH. However, the formation of CuH under the reaction
conditions in water is very unlikely. Moreover, our attempts to
trap CuH with ligands such as Ph3P did not succeed. The
reduction of azides requires only a catalytic amount of Cu
nanoparticles, although an optimum amount is necessary for a
successful reaction. Thus, we ruled out the formation of free
CuH. We observed a gradual change of pH (6.91 to 6.41) of the
reaction medium toward the acidic range with the progress of the
reaction (Table 4). Thus, it is more likely that Cu nanoparticles
dissociate the H2 molecule,3a generated from ammonium
formate,16 and adsorb hydrogen onto its surface. We suggest
that a Cu(0) nanoparticle, with its surface hydrogen, interacts
with the azide, forming a type of weak complex like A, which then
transfers hydride to azide, leaving a proton on the Cu surface that
eventually makes it acidic. To check whether the drop in pH is
due to liberation of acidic CO2 in the reaction process,17 we
performed another experiment using hydrogen gas in place of
ammonium formate and observed a similar pH change from 6.91
to 6.45, indicating this change of pH as an inherent characteristic
of the process. This transfer process is repeated to provide the
intermediate C via B, leading to the product, as outlined in
a Yields refer to those of purified products characterized by IR and 1H
and 13C NMR spectroscopic data.
Table 4. Measurement of pH during Reduction of 1-Azido-4-
nitrobenzenea
entry
time (h)
pH
1
2
3
4
5
0
2
4
6
8
6.91
6.83
6.60
6.56
6.41
a The reaction was performed at 100 °C, and the pH was measured at
room temperature after cooling the reaction mixture.
Scheme 2. This adsorbed surface hydrogen is moderately acti-
vated, and thus it facilitates the reduction of azides with high
selectivity.18 It may be assumed that the reactivity observed with
Cu nanoparticles may arise from the synergism of small Cu
nanoparticles to activate the H2.3d
The water deactivates the Cu nanoparticles after one reaction,
and the catalyst cannot be used further; however, when the
reaction is carried out in DMF under argon, the Cu nanoparticles
can be used for two more cycles although they are gradually
deactivated in contact with air and moisture during workup.
Nevertheless, we chose water as a reaction medium over DMF as
water is green and cost-effective.
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Scheme 2. Proposed Mechanism
’ ACKNOWLEDGMENT
We are pleased to acknowledge the financial support from
DST, New Delhi, in the form of the award J.C. Bose National
Fellowship to B.C.R. (Grant No. SR/S2/JCB-11/2008). S.A. and
A.S. thank CSIR, New Delhi, for their fellowships. We acknowl-
edge support of Nanoscience Project Unit at IACS, funded by
DST, New Delhi. We thank Dr. T.K. Paine of Inorganic
Chemistry Department of IACS for helpful discussions.
In conclusion, we have developed a new protocol for hydro-
genation utilizing hitherto unexplored adsorbed hydrogen on Cu
nanoparticle surfaces for the reduction of aryl azides to the
corresponding amines. To the best of our knowledge, we are not
aware of any report using Cu nanoparticles as a catalyst surface
for hydrogenation. The operational simplicity, excellent chemos-
electivity, high yields, use of water as reaction medium, cost
effectiveness of catalyst, and compatibility with a wide spectrum
of functional groups make this procedure more attractive. More
significantly, this demonstrates the potential of Cu nanoparticles
as a catalyst surface for hydrogenation and promotes further
investigation for reduction of useful functionalities.
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’ AUTHOR INFORMATION
Corresponding Author
*E-mail: ocbcr@iacs.res.in.
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