A mild and facile method for complete hydrogenation of aromatic nuclei in water

Article abstract of DOI:10.1055/s-2006-939719

A mild and complete hydrogenation of aromatic rings catalyzed by heterogeneous 10% Rh/C proceeds at 80 °C in water under 5 atm of H ₂ pressure. This method is applicable to the hydrogenation of various carbon and heteroaromatic compounds such as alkylbenzenes, biphenyls, pyridines and furans. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-939719

1
440
LETTER
A Mild and Facile Method for Complete Hydrogenation of Aromatic Nuclei in
Water
C
T
omplete
H
ydr
o
m
Aromatic
N
uclei in
o
W
ater hiro Maegawa, Akira Akashi, Hironao Sajiki*
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Gifu 502-8585, Japan
Fax +81(58)2375979; E-mail: sajiki@gifu-pu.ac.jp
Received 22 February 2006
CO2H
CO2H
CO2H
NH2
5
% Pt/C, H2O
Abstract: A mild and complete hydrogenation of aromatic rings
catalyzed by heterogeneous 10% Rh/C proceeds at 80 °C in water
+
NH2
80 °C, H2
NH2
(1 atm)
under 5 atm of H pressure. This method is applicable to the hydro-
81:19
2
24 h
genation of various carbon and heteroaromatic compounds such as
alkylbenzenes, biphenyls, pyridines and furans.
Scheme 1 5% Pt/C-catalyzed hydrogenation of the benzene nuclei
of phenylalanine in H
Key words: hydrogenation, aromatic ring, heterogeneous catalyst,
O
2
rhodium, water
hydrogenation of the benzene nuclei of phenylalanine
under milder reaction conditions at 80 °C (Scheme 1).
The complete reduction of aromatic rings is important for
the synthesis of cyclohexane derivatives including the in- To develop a general and efficient method of the arene hy-
termediates for the chemicals and pharmaceuticals, which drogenation, the reaction conditions were optimized using
are usually difficult to synthesize by a direct cyclization.1 n-heptylbenzene as a substrate in the presence of various
A variety of methods for the reduction of aromatic rings heterogeneous catalysts in H
O. As shown in Table 1, Rh/
2
2
including metal hydride reaction, dissolving metal reduc- C and Ru/C as well as Pt/C were also effective for the
3
1,4
tion, and transition-metal-catalyzed hydrogenation
hydrogenation of the benzene nuclei of n-heptylbenzene
were reported although many of them require drastic con- (Table 1, entries 3–5). In order to clarify the difference of
ditions such as acidic or basic condition, elevated temper- the catalyst activity among them, the reaction was per-
ature and/or high pressure. Since metal hydride reduction formed under milder conditions (60 °C, 3 h). The Rh/C
using borane derivatives, LiAlH and so on or dissolving catalyst indicated the most effective catalyst activity
4
metal reductions such as Birch reduction require a mois- toward the arene hydrogenation in H
ture sensitive reagent in an anhydrous organic solvent, the and 9).
reaction procedures are considerably tedious. On the other
O (Table 1, entries 8
2
hand, catalytic hydrogenation is a simple and facile
Table 1 Optimization of the Heterogeneous Catalyst in Arene
method. Especially, heterogeneous catalysts including
platinum group metals such as Ni, Ru, Rh, Pd, and so on
Hydrogenation in H O
2
4
catalyst (20 wt%)
H2 (1 atm), H2O
are quite favorable catalysts for hydrogenation, because
it is easy to recover and recycle them from the reaction
mixture and the metal contamination to the products can
be avoided. On the other hand, conventional catalytic hy-
drogenation of aromatic nuclei regularly requires forcing
conditions and the choice of appropriate metals is neces-
sary in each substrate. Recently, an improved method
performed at room temperature under ordinary H2
pressure using Rh nanoparticles has been reported while
the reaction should be carried out in an organic solvent
1
2
Entry
Catalyst
Temp (°C) Time (h)
Ratio (1:2)
80:20
76:24
3:97
1
2
3
4
5
6
7
8
5% Pd/C
5% Ir/C
80
80
80
80
80
60
60
60
60
24
24
24
24
24
3
5% Pt/C
5% Ru/C
5% Rh/C
5% Pt/C
5% Ru/C
5% Rh/C
10% Rh/C
0:100
0:100
47:53
56:44
2:98
5
such as hexane.
During our study of selective deuteration methods cata-
6
7
lyzed by Pd/C and Pt/C, we observed a trace amount of
the benzene nuclei reduction of phenylalanine under the
3
H–D exchange conditions using 10% Pd/C in D O at
2
6
c
1
10 °C. By virtue of further investigation, it became
3
apparent that the use of 5% Pt/C in H O promoted the
2
9a
3
0:100
a
1
0 wt% of 10% Rh/C was used as a catalyst.
SYNLETT 2006, No. 9, pp 1440–1442
0
1.
0
6.
2
0
0
6
Advanced online publication: 26.04.2006
DOI: 10.1055/s-2006-939719; Art ID: U02106ST
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Complete Hydrogenation of Aromatic Nuclei in Water
1441
Next, we applied the selected reaction conditions (10% Table 3 Effect of Temperature and H Pressure
2
Rh/C, 60 °C) to the hydrogenation of some aromatic com-
pounds (Table 2). Simple alkylbenzenes were hydro-
genated to the corresponding cyclohexane derivatives
1
(
0% Rh/C
10 wt%)
+
H2O, H2, 24 h
(
Table 2, entries 1 and 2) although the hydrogenation of
1
2
3
the benzene nuclei of other substrates such as diphenyl-
methane did not complete even after 24 hours (Table 2,
entries 3–5). To establish the further optimized condi-
tions, we reinvestigated the reaction temperature and H2
pressure (Table 3).
Entry
Temp (°C)
Pressure H (atm)
Ratio (1:2:3)a
24:58:18
1:42:57
2
1
2
3
60
80
90
80
80
1
1
1
3
5
30:64:6
Table 2 Hydrogenation of Aromatic Compounds Using 10% Rh/C
4b,c
0:2:98
in H O at 60 °C under Ordinary H Pressure
2
2
10% Rh/C (10 wt%)
5b,d
0:0:100
R
R
H2 (1 atm), H2O, 60 °C
a
1
The ratio was determined by H NMR.
The reactions were performed in the sealed tube.
For 15 h.
For 2 h.
1
2
b
c
d
Entry
1
Substrate
Time (h)
3
Ratio (1:2)a
0:100
2
6
0:100
also easily hydrogenated to cyclohexanecarboxylic acid
with 95% yield (Table 4, entry 3). Hydrogenation of
biphenyl was completed within 3 hours regardless of its
large resonance energy (Table 4, entry 4). The present
method is also applicable to the hydrogenation of
heteroaromatic compounds such as furans and pyridines.
3
4
24
24
24:58:18b
48:52
CO H
2
2
-Amylfuran was readily hydrogenated to the correspond-
ing tetrahydrofuran derivative in 30 minutes in 90% yield
Table 4, entry 5). It should be noted that pyridine
5
OH
24
45:55
(
N
Table 4 Application to Various Aromatic Compoundsa
a
1
The ratio was determined by H NMR.
b
The ratio indicated diphenylmethane:cyclohexylmethylbenzene:
Entry Substrate
1
Time Product
h)
Yield
dicyclohexylmethane.
b
(
(%)
2
73c
Consequently, the slight elevation of the reaction tem-
perature up to 80 °C apparently improved the ratio of the
reduction products (Table 3, entry 2) while the additional
heating at 90 °C rather suppressed the hydrogenation
2
2
86
95
(
Table 3, entry 3), which may be caused by the decrease
3
CO H
2.5
CO H
2
2
of H gas solubility into water. Great enhancement of the
2
hydrogenation rate was observed with a rise in H pres-
2
sure. When the reaction was performed under 3 atm of H2
pressure, diphenylmethane was almost completely hydro-
genated to dicyclohexylmethane in 15 hours (Table 3,
4
5
6
3
93
90
96
0.5
2
entry 4). In addition, 5 atm of H pressure accelerated
2
O
N
O
the hydrogenation of diphenylmethane to complete within
OH
O
OH
2
hours (Table 3, entry 5). In the previous report, the
hydrogenation of diphenylmethane catalyzed by 5% Rh/C
in AcOH under 6.9 MPa (ca. 68 atm) gave a mixture of
partially hydrogenated products together with the desired
N
H
7
1.5
O
97
8
NH2
NH2
dicyclohexylmethane.
N
N
H
The scope of the arene hydrogenation was investigated
with diverse arenes including the heteroaromatic com-
a
All reactions were carried out at 80 °C under 5 atm H pressure using
2
pounds using 10% Rh/C in H O at 80 °C under 5 atm of
2
10% Rh/C (10% of the weight of the substrate) in H O (1 mL).
2
b
H pressure. Alkylbenzenes were hydrogenated to cyclo-
Isolated yield.
2
c
hexane derivatives in good yields (Table 4, entries 1 and
The low yield is due to the volatile nature of the product.
2
), and electron-poor arenes such as benzoic acid were
Synlett 2006, No. 9, 1440–1442 © Thieme Stuttgart · New York

1
442
T. Maegawa et al.
LETTER
derivatives which are well-known to be a catalyst poison Acknowledgment
for platinum metal catalysts are successfully hydro-
We thank N.E. Chemcat Corporation for supplying 10% Rh/C used
in this report.
genated within 2 hours in excellent yields (Table 4, entries
and 7).
6
In conclusion, we have developed a facile and efficient
method for the hydrogenation of aromatic compounds
References and Notes
(1) Rylander, P. N. Catalytic Hydrogenation in Organic
Synthesis; Academic Press: New York, 1979, 175.
catalyzed by heterogeneous Rh/C in H O at 80 °C under
2
5
atm of H pressure. This method is mild and environ-
2
(
2) (a) Lyle, R. E.; Thomas, J. J. J. Org. Chem. 1965, 30, 1907.
mentally friendly since the reaction can be carried out in
(
b) Gribble, G. W.; Lord, P. D.; Skotnicki, J.; Dietz, S. E.;
Eaton, J. T.; Johnson, J. L. J. Am. Chem. Soc. 1974, 96,
812. (c) Yalpani, M.; Lunow, T.; Köster, R. Chem. Ber.
1989, 122, 687. (d) Yalpani, M. Chem. Ber. 1990, 123, 983.
H O under neutral conditions without using hydrocarbons
2
such as hexane, which is known as a good solvent in
the general hydrogenation. The method presented here
can be tolerated for a variety of aromatics including the
heteroaromatic compounds. Further application to other
aromatic compounds is now underway.
7
(3) (a) Benkeser, R. A.; Robinson, R. E.; Sauve, D. M.; Thomas,
O. H. J. Am. Chem. Soc. 1955, 77, 3230. (b) Marcinow, Z.;
Rabideau, P. W. J. Org. Chem. 1990, 55, 3812.
(
4) (a) Muetterties, E. L.; Bleeke, J. R. Acc. Chem. Res. 1979,
2, 324. (b) Rothwell, I. P. Chem. Commun. 1997, 1331.
c) Nishimura, S. Handbook of Heterogeneous Catalytic
1
(
Experimental Procedure
Caution! Rhodium on carbon can undergo a dust explosion. After
Hydrogenation for Organic Synthesis; Wiley-Interscience:
New York, 2001, 414.
9
use, the catalysts are likely to contain adsorbed hydrogen, which
may ignite when the catalyst dries. Use in a fume hood.
(5) Park, I. S.; Kwon, M. S.; Kim, N.; Lee, J. S.; Kang, K. Y.;
Park, J. Chem. Commun. 2005, 5667.
(
6) (a) Sajiki, H.; Hattori, K.; Aoki, F.; Yasunaga, K.; Hirota, K.
Synlett 2002, 1149. (b) Sajiki, H.; Aoki, F.; Esaki, H.;
Maegawa, T.; Hirota, K. Org. Lett. 2004, 6, 1485.
A mixture of substrate (1.0 mmol) and 10% Rh/C (N.E. Chemcat
Corporation; 10 wt% of substrate) in H O (1 mL) in a sealed tube
2
was hydrogenated up to 5 atm H pressure at 80 °C for the appropri-
2
(
c) Maegawa, T.; Akashi, A.; Esaki, H.; Aoki, F.; Sajiki, H.;
ate time. Reaction completion was generally indicated by standing
Hirota, K. Synlett 2005, 845. (d) Sajiki, H.; Esaki, H.; Aoki,
F.; Maegawa, T.; Hirota, K. Synlett 2005, 1385.
at the constant value of the H pressure after gradual decrease. After
2
cooling, the reaction mixture was diluted with Et O, then filtered us-
2
(
(
(
7) Sajiki, H.; Ito, N.; Esaki, H.; Maesawa, T.; Maegawa, T.;
Hirota, K. Tetrahedron Lett. 2005, 46, 6995.
ing a membrane filter (Millipore, Millex-LH, 0.45 mm). The filtrate
was partitioned between Et O and H O and the aqueous layer was
2
2
8) Rylander, P. N.; Steele, D. R. Engelhard Ind. Tech. Bull.
extracted with Et O. The combined etheral organic layers were
2
1965, 5, 113.
washed with brine and dried over anhyd MgSO . After removal of
4
9) Handbook of Reagents for Organic Synthesis, Oxidizing and
Reducing Agents; Burke, S. D.; Danheiser, R. L., Eds.; John
Wiley and Sons: Chichester, 1999, 339.
the drying agent by simple filtration, the filtrate was concentrated in
1
0
vacuo to give the corresponding hydrogenated product.
(
10) The products were identified by comparison with authentic
spectral data.
Synlett 2006, No. 9, 1440–1442 © Thieme Stuttgart · New York