ChemComm
Cite this: Chem. Commun., 2011, 47, 6981–6983
COMMUNICATION
Preparation of secondary and tertiary amines from nitroarenes and
alcoholsw
Chun-Chin Lee and Shiuh-Tzung Liu*
Received 21st March 2011, Accepted 26th April 2011
DOI: 10.1039/c1cc11609f
Various secondary amines were obtained selectively from the
reaction of nitroarenes with primary alcohols in the presence of
ruthenium(II) complexes having phosphine-amine ligands as the
catalyst. Secondary amines could be further alkylated with a
primary alcohol using the same catalyst, but different conditions.
However, secondary amines, potential key intermediates in
this cascade reaction, were not obtained in this synthesis. To
generalize this methodology we report here the preparation of
secondary amines from nitroarenes and alcohols catalyzed by
a phosphine-amine ruthenium(II) complex. The secondary
amine derivatives can be transferred into tertiary amines by
using the same catalyst under a modified condition.
Direct synthesis of useful molecules from simple starting
materials in one-pot tandem reactions is an important issue
in chemistry owing to several inherent advantages such as
simplifying separation steps, reducing the use of reagents, and
increasing yields. In order to meet the environmental concern,
the development of new catalytic systems for tandem reactions
has received much attention.1
At the start of our studies we investigated the reaction of
nitrobenzene with benzyl alcohol as a model system (eqn (1)).
In a typical experiment, a mixture of nitrobenzene (0.3 mmol),
benzyl alcohol (1.8 mmol), potassium tert-butoxide and
1 mol% of the ruthenium catalyst (based on nitro compound)
was heated at 110 1C for 24 h. Excess amount of alcohol was
used not only as the reactant but also as the solvent. A catalyst
screening of the model reaction (Table 1) revealed that various
ruthenium(II) complexes triggered the oxidation of benzyl
alcohol and reduction of nitroarenes smoothly, but the ligands
have a significant impact on the selectivity of amine versus
imine products. In all instances, the secondary amine
(N-benzylaniline), not 31-amine, was obtained as the major
product, suggesting that the secondary amine did not further
react with the carbonyl compound under these reaction
conditions. The best result was obtained when ruthenium
complex 2 was used as a catalyst, giving the desired amine in
97% yield, whereas all other complexes gave fair results. The
use of excess of benzyl alcohol is necessary in order to achieve
the higher yield. However, only a trace amount of amine
product, N-benzylideneaniline, was obtained by using the
stoichiometric amount of benzyl alcohol toward nitrobenzene
even carrying out the reaction under a hydrogen atmosphere
(entry 3).
In this regard, transition metal catalyzed N-alkylation of
amines with alcohols by borrowing-hydrogen strategy is one
of the typical examples.2,3 In this approach, the alcohol is
initially oxidized to the corresponding carbonyl compound
accompanied with the generation of metal-hydride. Subsequently,
the carbonyl compound reacts with amines to form imines,
which are then reduced to amines by the pre-generated
hydrides. Furthermore, the use of nitroarenes as the nitrogen
source in the one-pot tandem amination is even more challenging
due to the difficulty of selective reduction of nitro groups.4
Several catalytic systems for the one-pot reductive aminations
of aldehydes with nitroarenes have been recently developed,
including the following: pyridinium dichromate/Wilkinson’s
catalyst in sol–gel matrices,5 H2/Pd/C,6 palladium nanoparticles,7
9
H2/Au/Fe2O3,8 and Au–Pd/Al2O3. A tandem process for the
preparation of imines from nitroarenes with alcohols can
be achieved by using an Ir–Pd bimetallic complex as the
catalyst.10
Both nitroarenes and alcohols are cheap and readily available
organic compounds, and the direct amination of nitroarenes
with alcohols would be a more sustainable fashion. Indeed, Li
and co-workers demonstrated the possibility for the preparation
of N,N-dialkylanilines with the use of a NHC–ruthenium
complex as the catalyst (NHC = N-heterocyclic carbene).11
ð1Þ
The scope of the reaction with respect to nitrobenzene
derivatives and alcohols was investigated (Table 2). Under
the optimized reaction conditions, various substituted nitro-
arenes reacted with benzyl alcohol to yield the corresponding
amines in good yields except p-fluoronitrobenzene (entry 5)
and o-bromonitrobenzene (entry 11). Obviously, the strong
electron-withdrawing substituent and steric bulkiness on the
Department of Chemistry, National Taiwan University, Taipei 106,
Taiwan. E-mail: stliu@ntu.edu.tw; Fax: +886 22363 6359;
Tel: +886 23366 1661
w Electronic supplementary information (ESI) available: Experimental
details and characterization of compounds. See DOI: 10.1039/
c1cc11609f
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6981–6983 6981
Lee, Chun-Chin
