COMMUNICATION
DOI: 10.1002/chem.201003095
Ruthenium-Catalyzed Nitro and Nitrile Compounds Coupling with Alcohols:
Alternative Route for N-Substituted Amine Synthesis
Xinjiang Cui,[a, b, c] Yan Zhang,[a] Feng Shi,*[a] and Youquan Deng[a]
Amines and their derivatives play critical roles as building
blocks, functional linkages, and key moieties in peptides,
polymers, and many natural products and pharmaceuticals.
In addition, a plenty of naturally and man-made bioactive
compounds, such as amino acids, nucleic acids, and enzymes,
contain N-substituted amines.[1] N-Substituted amines are
usually prepared by the alkylation of amines with halides.[2]
However, this method is problematic due to overalkyation,
the toxic nature of halides and related alkylating reagents,
and the generation of stoichiometric unwanted byproducts.
In many cases, N-substituted amines could also be synthe-
sized by hydroamination[3] and hydroaminomethylation[4] re-
actions. An environmental benign procedure to produce N-
substituted amines is the catalytic alkylation of amines with
alcohols.[5] Clearly, alcohols are readily available, nonexpen-
sive, and nontoxic, and water is the only byproduct theoreti-
cally. Thus, the reaction is environmentally friendly intrinsi-
cally. However, employing alcohols as alkylation reagents is
severely limited because of the poor electrophilicity of most
alcohols. The borrowing-hydrogen technology makes the use
of alcohol as alkylation reagent more facile. In this method,
the poorly electrophilic alcohol was converted into aldehyde
with the liberation of metal hydride. The aldehyde reacts
with amine to form imine with water as byproduct. The
imine was then reduced by the metal hydride to obtain the
final product. This interesting transformation has been stud-
ied extensively since the reports by Grigg[6] and Watanabe,[7]
and various transition-metal catalysts including ruthenium[8]
and iridium[9] complexes were studied subsequently.
borrowing hydrogen methods was restricted to the reaction
of amines with alcohols. It is still a challenge to find other
ways to achieve the amination of alcohols. It is known that
primary amines are normally produced by the hydrogena-
tion of nitrobenzenes and benzonitriles.[10] The transfer hy-
drogenation reaction of nitroarenes and nitriles[11] by alco-
hols has been long known in the literature, as has the con-
densation reaction of amines with alcohols .[5,8] However,
these reactions have not previously been performed in one
pot in the presence of a single catalytic system. It would be
an ideal reaction if substituted amines could be synthesized
in one step from nitro or nitrile compounds and alcohols. In
this way, the specific equipment, rigorous reaction condi-
tions, and complicated operations could be avoided. In one
word, a multistep reaction would be realized in one-pot.
Based on the continuous interest in the developing of
simple and economic method for the synthesis of N-
substituted secondary amine, we tried a new route to realize
the amination of alcohols to secondary amine from nitro or
nitrile compounds directly (Scheme 1).
Scheme 1. One-pot synthesis of N-substituted amines from nitro and ni-
trile compounds and alcohols.
Despite the importance of the N-substituted amines, to
date, the selective synthesis of N-substituted amines through
The reaction condition optimization was started with
[{RuACHTNUGRTNEUNG
(p-cymene)Cl2}2] as catalyst[12] with a variety of ligands
at 1308C (Scheme 2, Table 1). Clearly, under ligand-free
conditions, the nitrobenzene is totally converted into imine
and no alkylated amine was observed, entry 1. With the ad-
dition of typical nitrogen ligands, that is, bpy (bipyridine),
TMEDA (tetramethylethylenediamine), and phen (phenan-
throline), there is no evident improvement in the catalytic
activity (entries 2–4). The selectivity to N-alkylated product
was <10%. The employment of phosphine ligand, however,
promoted the reaction more efficiently. In the presence of
PPh3, 23% of amine could be obtained (entry 5). Interest-
ingly, the selectivity to N-benzyl-p-tolueneamine could be
promoted efficiently by using DPPE (1,2-bis(diphenylphos-
phino)ethane), DPPP (1,3-bis(diphenylphosphino)propane)
and DPPB (1,2-bis(diphenylphosphanyl)benzene) (en-
[a] X. Cui, Dr. Y. Zhang, Dr. F. Shi, Prof. Y. Deng
Centre for Green Chemistry and Catalysis
Lanzhou Institute of Chemical Physics, CAS
Middle Tian Shui Road, 18, Lanzhou (P.R. China)
Fax : (+86)931-8277088
[b] X. Cui
Graduate School of the Chinese Academy of Sciences
Beijing, 100049 (P.R. China)
[c] X. Cui
State Key Laboratory of Applied Organic Chemistry and
Department of Chemistry, Lanzhou University
Lanzhou, 730000 (P.R. China)
Supporting information for this article is available on the WWW
Chem. Eur. J. 2011, 17, 2587 – 2591
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2587