Angewandte
Chemie
DOI: 10.1002/anie.201205792
Iron Nanocatalysis
In Situ Generated Iron Oxide Nanocrystals as Efficient and Selective
Catalysts for the Reduction of Nitroarenes using a Continuous Flow
Method**
David Cantillo, Mostafa Baghbanzadeh, and C. Oliver Kappe*
Functionalized anilines are industrially important intermedi-
ates in the preparation of pharmaceuticals, agrochemicals,
dyes, and pigments. The most commonly used method for the
synthesis of anilines is the reduction of aromatic nitro
pensive nanocatalysts that can be easily separated and
[12,13]
recovered after the reaction.
Nanosized materials feature
unique properties as catalysts: the high surface-to-volume
ratio of nanoparticles compared to a bulk material generally
results in an extremely high catalytic activity and often
[
1]
compounds. While traditional non-catalytic reduction pro-
cesses (that is using Fe/HCl) generate large amounts of
undesirable waste; catalytic hydrogenation using heteroge-
neous transition-metal catalysts is a well-established tech-
nique and often the method of choice for the reduction of
[
12]
improved selectivity.
Herein, we present a novel method in nanocatalysis
applied to the selective reduction of nitroarenes to anilines in
a continuous-flow format. In a solution containing the
nitroarene, Fe O nanocrystals were generated in situ from
[
2,3]
nitroarenes to anilines.
the presence of other common functional groups can occur,
often requiring the use of carefully selected and expensive
However, selectivity problems in
3
4
[4]
an inexpensive Fe precursor using hydrazine hydrate as the
reducing agent at elevated temperatures. Upon formation, the
highly reactive nanocrystals then selectively catalyze the
reduction of the nitro group with hydrazine with unparalleled
efficiency. Importantly, the originally colloidal nanocatalyst
remains in solution during the time required for nitro group
[
3]
precious metal catalysts (for example, Pd, Pt, or Ru).
Therefore, significant efforts have been made to develop
more efficient and sustainable methods to achieve the
selective reduction of nitroarenes to anilines. Apart from
the use of hydrogen, several other stoichiometric reducing
reduction. The Fe O4 nanocrystals subsequently start to
3
[
5]
[6]
[7]
agents such as ammonium salts, silanes, boranes, sodium
aggregate forming a precipitate that is easily removable
using a simple magnet. This unique process combines the
benefits of homogeneous and heterogeneous nanocatalysts,
and is particularly valuable for continuous manufacturing
applications because the initial homogeneous reaction mix-
ture can be easily processed in a safe and scalable way using
continuous-flow technology.
[8]
[9]
[10]
borohydride, formic acid, and hydrazine,
have been
used in combination with a number of different metal
[
5–10]
catalysts.
Hydrazine, specifically the less hazardous hy-
drazine hydrate (N H ·H O), is a particularly good reagent
2
4
2
because it generates only N2 as a side product and is
comparatively safe to handle.
In the past few years, interest in the use of iron-based
catalysts in organic synthesis has increased dramatically.
First, we evaluated the generation of iron oxide (that is,
magnetite, Fe O ) nanoparticles by treatment of various Fe
[11]
3
4
Iron is an abundant, eco-friendly, relatively nontoxic, and
inexpensive element, and thus the development of catalysts
based on this metal is highly desirable. Several Fe-catalyzed
procedures for the hydrazine-mediated reduction of nitro-
precursors with hydrazine hydrate, essentially following
[
14]
known procedures. All experiments were performed using
small-scale microwave batch heating at elevated temper-
atures, thus rapidly generating the desired nanoparticles,
ensuring short reaction times for the nitroarene reductions,
and a high throughput for use in the continuous-flow method.
A typical reaction mixture (see Table 1) consisted of a solution
[
10a–g]
arenes have been reported.
In the general context of
nanocatalysis, magnetic nanomaterials, in particular iron
oxide nanoparticles, have become very attractive as inex-
of tris(acetylacenato)iron(III) (Fe(acac) ), nitrobenzene, and
3
hydrazine in methanol at 1508C in a sealed vessel with
microwave irradiation, the formation of solid magnetic
particles during the irradiation process could be readily
observed after a few minutes with the aid of a built-in camera
(see Supporting Information, Figure S1). The magnetic par-
ticles could be unambiguously identified as single-phase cubic
[
*] Dr. D. Cantillo, Dr. M. Baghbanzadeh, Prof. Dr. C. O. Kappe
Christian Doppler Laboratory for Microwave Chemistry (CDLMC)
and Institute of Chemistry, Karl-Franzens-University Graz
Heinrichstrasse 28, 8010 Graz (Austria)
E-mail: oliver.kappe@uni-graz.at
Homepage: http://www.maos.net
[
**] This work was supported by a grant from the Christian Doppler
Research Society (CDG). D.C. thanks the Ministerio de Ciencia
e Innovaciꢀn of Spain for a scholarship. We also thank W. Gçssler,
W. Haas, and S. Mitsche for ICP-MS, TEM, and XRD analyses,
respectively, and B. Gutmann for assistance with the continuous-
flow experimentation.
Fe O4 by their X-ray powder diffraction (XRD) patterns
3
(Figure S2), while high-resolution transmission electron mi-
croscopy (HRTEM) micrographs obtained from a sample of
stabilized colloidal Fe O nanocrystals revealed the size of the
3
4
crystals to be 6 Æ 2 nm (Figure S3).
The efficiency of the Fe O nanocrystals generated in situ
3
4
for the reduction of nitroarenes was first studied using
nitrobenzene as model substrate (Figures S4,S5). Experi-
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!