Communications
DOI: 10.1002/anie.201106612
Hydrogenation
Unprecedented Catalytic Hydrogenation of Urea Derivatives to
Amines and Methanol**
Ekambaram Balaraman, Yehoshoa Ben-David, and David Milstein*
Catalytic hydrogenation of polar bonds, in particular organic
carbonyl groups, has captured considerable attention, because
it provides environmentally benign approaches to syntheti-
Notably, alkyl and aryl urea compounds are readily
synthesized from reactions of amines with CO2 in the
presence of various catalysts, such as 1,8-diazabicyclo-
[1]
[6]
[7]
[8]
[9]
cally important building blocks, such as alcohols and amines.
[5.4.0]undec-7-ene,
[Bmim]OH
CsOH,
Cs CO ,
Au/polymers,
2
3
[
10]
[11]
The ease of hydrogenation of carbonyl groups, in which
hydride transfer to the carbonyl carbon is involved, generally
corresponds to the electrophilicity of this carbon. The lower
electrophilicity of the carbonyl group, as a result of resonance
effects involving alkoxy or amido groups, makes hydrogena-
or KOH/PEG1000,
and by using ionic
liquids, N-methylpyrrolidone, and supercritical carbon diox-
ide as solvents. Transition-metal-catalyzed synthesis of urea
[
12]
derivatives was also reported.
Recently, Zhao et al.
reported the synthesis of dialkyl urea derivatives from CO2
and amines in the absence of any catalysts, organic solvents, or
[2]
[3]
tions of esters, amides, and even more so, carbonic acid
derivatives, such as organic carbonates, carbamates and urea
derivatives, very difficult (Figure 1). The common trend in the
reactivity of polar carbonyl groups towards hydrogenation
[13]
other additives. In this context, mild hydrogenation of urea
derivatives to methanol is very attractive, as it would
represent a mild, two-step hydrogenation of CO to methanol,
2
reactions
is
RC(O)H > RC(O)R’ @ RC(O)OR’ >
which is of intense current interest with regard to hydrogen
[14,15]
RC(O)NR ’ @> ROC(O)OR’ > ROC(O)NR ’ >
storage and “methanol economy”.
Direct, heterogene-
2
2
ously catalyzed hydrogenation of CO to methanol requires
2
harsh conditions of temperature and pressure and suffers
from the formation of byproducts such as CO, hydrocarbons,
[16]
and higher alcohols, making this approach difficult. More-
over, the direct hydrogenation of urea derivatives to the
corresponding amines and methanol can also provide an
alternative approach for amine protection chemistry,
because amines can be protected as urea derivatives by
Figure 1. Resonance forms of urea derivatives.
[17]
[
3d]
R NC(O)N R’, urea derivatives being the most challeng-
2
2
ing. Indeed, as far as we know, catalytic hydrogenation of urea
derivatives has never been reported, be it under heteroge-
neous or homogeneous catalysis. In fact, alkyl urea com-
pounds have been used as solvents in catalytic hydrogenation
reactions. For example, rhodium-catalyzed hydrogenation of
carbon monoxide to ethylene glycol under very high pressure
treatment with nontoxic, abundant CO under mild condi-
tions.
2
We have developed several unique reactions catalyzed by
tridentate PNN and PNP Ru(II) pincer complexes based on
[2a,18–19]
[20]
pyridine
and acridine backbones. These complexes
show a new mode of metal–ligand cooperation based on
ligand aromatization–dearomatization, which has led to a
(
p(H ) = 200 bar) and at elevated temperature (2008C) using
2
[
21]
N,N,N’,N’-tetramethylurea (TMU) as an inert solvent was
number of bond activation processes.
[
4]
[3c]
reported. In addition, sugar-urea-salt melts were used as
Recently, hydrogenation of amides to
the corresponding alcohols and amines
by selective cleavage of the CÀN bond
“
green solvents” for Rh-catalyzed hydrogenation reactions
[5]
and found to be sustainable reaction media.
under homogeneous conditions, cata-
lyzed by the bipyridine-based pincer
complex 1 (Figure 2) was developed.
An analogous NHC complex is effective
in hydrogenation of nonactivated esters
to the corresponding alcohols under
[
*] Dr. E. Balaraman, Y. Ben-David, Prof. D. Milstein
Department of Organic Chemistry
The Weizmann Institute of Science, 76100 Rehovot (Israel)
E-mail: david.milstein@weizmann.ac.il
Homepage: http://www.weizmann.ac.il/Organic_Chemistry/mil-
stein.shtml
Figure 2. Bipyridyl-
based PNN Ru(II)
pincer complex 1.
[2f]
mild conditions.
Complex 1 effec-
tively catalyzes also the novel hydro-
[
**] This research was supported by the European Research Council
under the FP7 framework, (ERC number 246837), by the Israel
Science Foundation, by the MINERVA Foundation, and by the
Kimmel Center for Molecular Design. D.M. is the holder of the Israel
Matz Professorial Chair of Organic Chemistry.
genation of organic carbonates to alcohols, organic carba-
mates to methanol and amines, and alkyl formates to
methanol and alcohols, which are of current interest with
[22]
regard to mild stepwise CO hydrogenation to methanol.
2
Here we report the first example of catalytic hydro-
genation of urea derivatives. Selective formation of methanol
and the corresponding amines takes place by the double
cleavage of the robust CÀN bonds under mild, neutral
Supporting information, including the general procedure for the
catalytic hydrogenation reactions and spectroscopic data for
1
1702
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 11702 –11705