Catalytic activation of hydrazine hydrate by gold nanoparticles: Chemoselective reduction of nitro compounds into amines

Article abstract of DOI:10.1016/j.catcom.2013.02.024

Supported gold nanoparticles (< 1 mol%) catalyze for the first time the activation of NH₂NH₂ as a transfer hydrogenation agent. Aryl and alkyl nitro compounds are cleanly and selectively reduced into the corresponding amines in the presence of 4 equivalents of hydrazine. The reaction tolerates other potentially reducible functionalities such as carboxylate, carbonyl, cyano or halides which remain intact.

Full text of DOI:10.1016/j.catcom.2013.02.024

Catalytic Activation of Hydrazine Hydrate by Gold Nanoparticles: Chemose-
lective Reduction of Nitro Compounds into Amines
Petros L. Gkizis, Manolis Stratakis, Ioannis N. Lykakis
PII:
DOI:
Reference:
S1566-7367(13)00076-9
doi: 10.1016/j.catcom.2013.02.024
CATCOM 3424
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
14 January 2013
26 February 2013
27 February 2013
Please cite this article as: Petros L. Gkizis, Manolis Stratakis, Ioannis N. Lykakis,
Catalytic Activation of Hydrazine Hydrate by Gold Nanoparticles: Chemoselective
Reduction of Nitro Compounds into Amines, Catalysis Communications (2013), doi:
1
0.1016/j.catcom.2013.02.024
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Catalytic Activation of Hydrazine Hydrate by Gold
Nanoparticles: Chemoselective Reduction of Nitro
Compounds into Amines
1
2
1,
Petros L. Gkizis, Manolis Stratakis, and Ioannis N. Lykakis *
1Department of Chemistry, Aristotle University of Thessaloniki, University Campus 54124,Thessaloniki,
Greece
2Department of Chemistry, University of Crete, Voutes 71003 Iraklion, Greece
*Corresponding author: Tel: +30-2310-997871, Fax: +30-2310-997679, E-mail: lykakis@chem.auth.gr
Abstract: Supported gold nanoparticles (<1 mol%) catalyze for the first time the
activation of NH NH as a transfer hydrogenation agent. Aryl and alkyl nitro
2
2
compounds are cleanly and selectively reduced into the corresponding amines in the
presence of 4 equivalents of hydrazine. The reaction tolerates other potentially reducible
functionalities such as carboxylate, carbonyl, cyano or halides which remain intact.
1
. Introduction
Reduction of the nitro group into an amine is an important process, as the amine
functionality appears in several biologically active natural products, dyes, and ligands
for transition-metal catalyzed reactions. Since the amino group serves as a site for
further derivatization, amines are also important intermediates for the production
ofpharmaceutical substances, photographic materials, agrochemicals, polymers, and
rubber materials [1]. Perhaps, the most popular methodology to accomplish the nitro to

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amine transformation is the transition metal-catalyzed hydrogenation [2], which
however often suffers from low chemoselectivity if additional reducible functionalities
are present. In recent years, significant progress has been achieved in the field of nitro
aromatic compounds reduction under catalysis by supported gold nanoparticles (Au
NPs) [3-5]. The direct hydrogenation catalyzed by Au/TiO [6-8], and other supported
2
Au NPs catalysts [9-13] is highly chemoselective in favour of the nitro group, yet it
requires rather harsh conditions in terms of temperature and pressure. Efficient Au-
catalyzed transfer hydrogenation processes utilizing CO/H O [14], and HCOONH [15],
2
4
as reducing agents were recently reported. Although reduction of nitro aromatics
especially p-nitrophenol) by NaBH [16-20] or t-BuNH -BH [21] under catalysis by
(
4
2
3
several monometallic or dimetallic Au NPs are known, the processes are of limited
synthetic value as the reducing agents should be used in substantial molar excess
relative to the substrates. In addition, a photochemical Au NPs-catalyzed transfer
hydrogenation of nitroarenes into azoarenes by ethanol was presented [22].
Following our recent interest for novel applications of supported Au NPs as
heterogeneous catalysts in organic transformations [23-26], we focused on the
exploration of utilizing hydrazine hydrate as a transfer hydrogenation reagent for nitro
compounds, a hitherto unknown transformation under Au-catalysis conditions.
Hydrazine has been already used as a reductant of aromatic and heteroaromatic nitro
compounds in the presence of several metals (e.g. Rh, Fe, Ni, Co, Cu, Zn) [27-34].
Herein, we report the first gold-catalyzed chemoselective reduction of aryl and alkyl
nitro compounds into the corresponding anilines and alkyl amines by activation of
hydrazine as a hydrogen donor molecule.
2
. Experimental Methods

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2
.1. General procedure of nitro compounds reduction by hydrazine catalyzed by
Au/TiO2
To a sealed tube containing the nitro compound (0.6 mmol) and 2 mL ethanol
were added 2.6-6.0 mmol of NH NH (see Table 2) and Au/TiO (100 mg, 1 wt% in
2
2
2
o
[
Au], 0.8 mol%). The reaction was heated at 60 C for an appropriate time (see Table 2)
under an inert atmosphere. The reaction was monitored by TLC, and after completion,
the slurry was filtered under pressure through a short pad of celite and silica gel to
withhold the supported catalyst with the aid of ethanol or methanol (~5 mL). The filtrate
was evaporated under vacuum to afford the corresponding amines in pure form. The
1
13
spectroscopic data ( H NMR, C NMR) of amines 1a-20a are in agreement with those
previously reported [28, 30, 31], while the majority of them are commercially available
substances. The screened catalysts Au/TiO , Au/Al O , and Au/ZnO (~1 wt% in Au) are
2
2
3
commercially available (Strem Chemicals), and have an average gold crystallite size of
2-3 nm.
~
2
.2. Recycling studies in the Au/TiO catalyzed reduction of p-nitroanisole by hydrazine
2
Reaction conditions: 0.3 mmol of p-nitroanisole (1), 0.8 mol% of Au/TiO , 1.2
2
o
mmol of hydrazine (in each cycle), 1 mL ethanol, 60 min at 60 C. After each catalytic
run, the catalyst (Au/TiO ) was isolated by filtration, washed with ethanol, and dried
2
under ambient conditions.
3
. Results and Discussion
3
.1. Conditions evaluation in the catalytic reduction of p-nitroanisole (1)
To optimize the reaction conditions, the reduction of p-nitroanisole (1) by
different hydrazo compounds, solvents and supported gold catalysts was initially
investigated (Table 1). Au/TiO (0.8 mol%), 4.0 equiv of NH NH hydrate and EtOH as
2
2
2
the solvent of choice, provide the fast (1 h) quantitative and selective reduction of 1 into

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the corresponding aniline 1a (Table 1, entry 7). Lower amounts of hydrazine (1 or 2
equivalents) lead to incomplete reduction, however in the presence of 3 equivalents of
NH NH prolonged reaction time is required. Au/Al O and Au/ZnO (Table 1, entries
2
2
2
3
1
2 and 13) are less efficient as compared to Au/TiO . No by-products such as azoxy-,
2
azo- or 1,2-diarylhydrazine were seen during the progress of the reaction [35]. The
reaction is feasible with structurally analogous reagents such MeNHNH and 4-
2
NO PhNHNH (Table 1, entries 9 and 11), yet, prolonged reaction times are required. In
2
2
the case of PhNHNHPh, no reduction was seen (Table 1, entry 10), as it was readily
oxidized into azobenzene. In the absence of gold catalysts, p-nitroanisole (1) was
completely unreactive [36] (Table 1, entry 12). Furthermore, Au/TiO can be reused
2
four times without significant loss of catalytic activity (see Supporting Information).
3
.2. Reduction of nitro compounds into amines with hydrazine catalyzed by Au/TiO2
Regarding the scope and limitations of this reductive methodology, a series of
nitroarenes (2-18) and nitroalkanes (19-20) were examined (Table 2). For all
nitroarenes, the corresponding substituted anilines were formed in excellent yields, with
product selectivity >95%. Inert atmosphere conditions are preferable, as under an open
air, minor amounts of azoxyarenes are occasionally seen via a Au NPs-catalyzed
aerobic oxidation of the produced substituted anilines [35].
Chloro and bromo-substituted nitroarenes (7-8) were reduced without
undergoing any dehalogenation. In addition, carbonyl, carboxylate, and cyano
functionalities in nitroarenes 9-14 remain intact, indicative of a highly chemoselective
process. In case of 4-nitro acetophenone (9) reduction, the corresponding aryl amine
(9a) was isolated as the only product (Table 2, entry 8). On the other hand, a mixture of
hydrazone 10a (E/Z=5/1) was isolated when 4-nitro benzaldehyde (10) was reduced
under the same catalytic conditions (Table 2, entry 9). Under slightly acidic conditions

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it readily hydrolyzes, however, the corresponding 4-amino aldehyde is unstable. In
addition, nitroalkanes (19, 20) were also reduced into the corresponding amines in good
yield, yet, excess of hydrazine (10 equiv) and prolonged reaction time [37] are required
(Table 2, entries 18 and 19).
3
.3. Proposed mechanistic scenario for the catalytic reduction of nitro compounds to
amines catalyzed by Au/TiO using hydrazine as hydrogen source.
2
Regarding the mechanism of reaction, we observed the following: a) For
nitroarenes bearing through resonance electron donating groups at the para-position
(e.g. 1, 4 and 5), no intermediate product(s) were seen during the progress of the
reduction; in other words, only reacting nitroarene and produced aniline were detected.
In all other cases, aryl hydroxylamines were observed as the only intermediates, being
the major constituent of the reaction mixture after the disappearance of the nitroarenes.
b) In the same context, for the cases where hydroxylamines are formed, they slowly
convert into anilines. Thus, the reduction of nitroarenes into hydroxylamines is faster
than the reduction of hydroxylamines into anilines. In the later cases, due to the
extended reaction times, more hydrazine is required since the reductant decomposes
under the reaction conditions in a competing pathway. c) Azoxyarenes may be seen as
minor by-products (10-20% relative yield) only when the reactions are run under open
air conditions, indicative that they derive from the Au NPs-catalyzed aerobic oxidation
of the produced anilines. Indeed, azoxybenzene (2d) and nitrosobenzene (2b) were
o
formed in ~60 % relative yield when aniline (2a) was heated at 60 C in ethanol in the
presence of Au/TiO (0.8 mol%) for 1 h under open air conditions. d) Azoxyarene (2d)
2
is less reactive against hydrazine in the presence of Au/TiO (1 mol%), and provides
2
after 20 h at reflux, 1,2-diphenylhydrazine (2f) in merely 15% relative yield. Under the
same catalytic reaction conditions, azobenzene (2e) cleanly transforms into 2f within a

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few minutes [38], while 2f is very slowly reduced into aniline (10% conversion after 24
h at reflux). e) Nitrosobenzene (2b) rapidly affords aniline with only 1.2 equiv of
hydrazine in the absence of the catalyst (Scheme 1).
Based on these observations we propose in general, that the condensation route
(formation of azoxyarenes as intermediates en route to anilines) does not take place.
More likely, there are two dissecting pathways following the direct route. For substrates
such as 1, 4 and 5, whose corresponding nitrosocompounds are stabilized through
resonance, nitrosoarenes may be formed as intermediates, which are rapidly reduced
into anilines by hydrazine (pathway I, Scheme 1). Nitroarenes that in principle form less
thermodynamically stable nitrosoarenes, do not follow the classical direct route
(
nitroarene  nitrosoarene  aryl hydroxylamine  aniline), but rather skip the
nitrosoarene intermediate, leading directly to aryl hydroxylamines (pathway II, Scheme
). A similar mechanistic profile has been also proposed by Corma and co-workers [7]
1
in the hydrogenation of nitroarenes catalyzed by Au/TiO . In general, it is possible that
2
the reduction occurs by gold-hydride species [3] that are formed via activation of
hydrazine by the Au NPs. Additional work is neccessary however, to clarify this
assumption. We rule out a Au-catalyzed hydrogenation [6] that in principle proceeds
very slowly. Hydrogen gas could have been formed via the Au-catalyzed decomposition
of hydrazine.
4
. Conclusions
In conclusion, we report for the first time that supported gold nanoparticles can
activate hydrazine hydrate as a reducing agent in the transfer hydrogenation of aryl and
alkyl nitro compounds into the corresponding amines. The reaction is highly
chemoselective if additional reducible functionalities are present. The current work

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extends the utility of a readily available catalyst (Au/TiO ) toward new applications in
2
catalysis and organic chemistry.
5
. Acknowledgment
COST action CM1201 is kindly acknowledgment. Two of the authors (I.N.L. and M.S.)
acknowledge the Academy of Athens for the Zervas-Hildegard award 2012.
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://
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Scheme captions list
Scheme 1. Proposed pathways for the gold-catalyzed reduction of nitroarenes into
anilines by hydrazine

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Table captions list
Table 1. Evaluation of supported Au catalysts, hydrazo compounds and solvents, in the
catalytic reduction of p-nitroanisole (1) into p-anisidine (1a)
Table 2. Chemoselective reduction of nitro compounds into amines by hydrazine
catalyzed by Au/TiO2

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Table 1. Evaluation of supported Au catalysts, hydrazo compounds and solvents, in the
catalytic reduction of p-nitroanisole (1) into p-anisidine (1a)
a
The screened catalysts (~1 wt% in Au) were commercially available, and have an average gold
crystallite size of ~2-3 nm.
b
p-Nitrophenol was used.
c
4
.0 equiv.
d
e
1
Relative yield of 1a as determined by H NMR.
Value in parenthesis corresponds to isolated yield.

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Table 2. Chemoselective reduction of nitro compounds into amines by hydrazine
catalyzed by Au/TiO2
(
Continued)

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a
Isolated yields. In all cases the product selectivity was >95%.
b
Isolated yield of the corresponding hydrazones.

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Graphical abstract
1
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8
6
4
2
0
0
0
0
0
1
2
3
4
Number of reuse

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Highlights
•
•
•
Supported gold nanoparticles catalyze for the first time the activation of hydrazine.
Hydrazine was used as a transfer hydrogenation agent.
Chemoselective reduction of aryl and alkyl nitro compounds into amines was
observed.
Catalyst was recycled several times without loss of its activity.
•