Efficient and Practical Arene Hydrogenation by Heterogeneous Catalysts under Mild Conditions

Article abstract of DOI:10.1002/chem.200900361

An efficient and practical arene hydrogenation procedure based on the use of heterogeneous platinum group catalysts has been developed. Rh/C is the most effective catalyst for the hydrogenation of the aromatic ring, which can be conducted in iPrOH under neutral conditions and at ordinary to medium H ₂ pressures (<10 atm). A variety of arenes such as alkylbenzenes, benzoic acids, pyridines, furans, are hydrogenated to the corresponding cyclohexyl and heterocyclic compounds in good to excellet yields. The use of Ru/C, less expensive than Rh/C, affords an effective and practical method for the hydrogenation of arenes including phenols. Both catalysts can be reused several times after simple filtration without any significant loss of catalytic activity.

Full text of DOI:10.1002/chem.200900361

FULL PAPER
DOI: 10.1002/chem.200900361
Efficient and Practical Arene Hydrogenation by Heterogeneous Catalysts
under Mild Conditions
Tomohiro Maegawa, Akira Akashi, Kiichiro Yaguchi, Yohei Iwasaki,
Masahiro Shigetsura, Yasunari Monguchi, and Hironao Sajiki*[a]
Abstract: An efficient and practical
arene hydrogenation procedure based
on the use of heterogeneous platinum
group catalysts has been developed.
Rh/C is the most effective catalyst for
the hydrogenation of the aromatic ring,
which can be conducted in iPrOH
under neutral conditions and at ordina-
ry to medium H2 pressures (<10 atm).
A variety of arenes such as alkylben-
zenes, benzoic acids, pyridines, furans,
are hydrogenated to the corresponding
cyclohexyl and heterocyclic compounds
in good to excellent yields. The use of
Ru/C, less expensive than Rh/C, af-
fords an effective and practical method
for the hydrogenation of arenes includ-
ing phenols. Both catalysts can be
reused several times after simple filtra-
tion without any significant loss of cat-
alytic activity.
Keywords: arenes · heterogeneous
catalysis · hydrogenation · rhodium ·
ruthenium
Introduction
of cyclohexane rings from arenes are classified into two
types of reactions:
The cyclohexane moiety is an important structure in diverse
organic compounds, such as natural products and functional
materials including pharmaceuticals. The modification of cy-
clohexane rings is rather more difficult than that of aromatic
rings, so the reduction of aromatic rings is a useful and im-
portant technique for obtaining a variety of cyclohexane de-
rivatives. In addition, the reduction of aromatic rings in the
structures of functional polymers, such as polycarbonates
and epoxy resins, is effective for induction of yellowing re-
sistance qualities, because the precursor aromatic rings can
effectively absorb light energy, causing yellow discoloration
of the polymers. Existing methods for aromatic ring reduc-
tion, however, require excess amounts of reagents and harsh
reaction conditions because of the stabilization of the aro-
matic ring by resonance hybridization (151 kJmolÀ1 or
36 kcalmolÀ1). Previously reported methods for construction
1) Reduction with a greater than stoichiometric amount of
a reducing agent, such as LiAlH4, a borane derivative,[1]
or a dissolving metal (Birch reduction).[2] These reagents
are moisture-sensitive and the reactions should be con-
ducted under anhydrous and strongly reducing and basic
conditions; some co-existing functional groups, such as
esters and ketones, would not be tolerated under these
conditions. Furthermore, these reactions produce large
amount of metal waste from the reducing agents.
2) Hydrogenation with a transition-metal catalyst.[3,4] Cata-
lytic hydrogenation is a simple, convenient, and sustaina-
ble method. Although some homogeneous catalysts do
efficiently promote arene hydrogenation,[5] residual
metal in the products makes industrial application diffi-
cult. On the other hand, the hydrogenation of arenes
through the use of heterogeneous metals (Ni, Rh, Ru, Pt,
and Pd)[4] has some advantages, such as easy handling,
less metal contamination in the products, and reuse of
the catalysts, which would make it suitable for industrial
production. However, conventional methods using heter-
ogeneous catalysts have required high pressures
(>10 atm) and temperatures and/or strongly acidic or
basic conditions. Only two mild hydrogenation methods,
using active Rh nanoparticles, have been reported,[6] and
only a few widely applicable hydrogenation methods for
aromatic nuclei are reported.[4,7] Therefore, a simple,
[a] Dr. T. Maegawa, A. Akashi, K. Yaguchi, Y. Iwasaki, M. Shigetsura,
Dr. Y. Monguchi, Prof. Dr. H. Sajiki
Laboratory of Organic Chemistry, Department of Organic
and Medicinal Chemistry, Gifu Pharmaceutical University
5-6-1 Mitahora-higashi Gifu 502-8585 (Japan)
Fax : (+81)58-237-5979
E-mail: sajiki@gifu-pu.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200900361.
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Table 1. Optimization of the heterogeneous catalyst for arene hydroge-
nation in H2O.
practical, and wide-ranging hydrogenation method is de-
sirable.
We have recently developed facile and efficient methods
for deuteration of various organic compounds through the
use of Pd/C,[8] Pt/C,[9] Rh/C,[10] or Ru/C[11] in D2O in the
presence of H2 gas. During the course of our study of the
deuteration of phenylalanine, we found that hydrogenation
of the aromatic ring occurred under the stated conditions
(Scheme 1).
Entry
Catalyst
T [8C]
t [h]
Ratio 1/2[a]
1
2
3
4
5
6
7
Pt/C (5%)
Ru/C (5%)
Rh/C (5%)
Pd/C (5%)
Ir/C (5%)
Pt/C (5%)
Ru/C (5%)
Rh/C (5%)
Rh/C (10%)
80
80
80
80
80
60
60
60
60
24
24
24
24
24
3
3
3
3
3:97
0:100
0:100
80:20
76:24
47:53
56:44
2:98
8
9[a]
0:100
[a] Ratio was determined by 1H NMR. [b] Rh/C (10%, 10 wt%) was
used as a catalyst.
Scheme 1. Pt/C-catalyzed (5%) hydrogenation of the aromatic ring of
phenylalanine under the deuteration conditions.
Table 2. Hydrogenation of aromatic compounds in the presence of Rh/C
(10%) in H2O at 608C under ordinary H2 pressure.
Encouraged by this result, we speculated that this reaction
might be developable into an efficient and general method
for hydrogenation of aromatic nuclei by optimization of the
reaction conditions. We have consequently developed an ef-
ficient hydrogenation method for diverse arenes in the pres-
ence of Rh/C in either H2O or iPrOH under ordinary to
medium H2 pressures (<10 atm). Furthermore, a practical
and cost-effective method for hydrogenation of arenes, in-
cluding phenol derivatives, in the presence of Ru/C as an in-
expensive catalyst has also been achieved.
Entry
1
Substrate
t [h]
Ratio 3/4[a]
3
0:100
2
3
4
6
0:100
24
24
24:58:18[b]
48:52
Results and Discussion
5
24
45:55
Rh/C catalysis
[a] The ratio was determined by 1H NMR. [b] The ratio refers to diphe-
nylmethane/cyclohexylmethylbenzene/dicyclohexylmethane.
Rh/C-catalyzed hydrogenation of arenes under ordinary H2
pressure in H2O:[12] We first examined a variety of heteroge-
neous catalysts with n-heptylbenzene as
a
substrate
crease in H2 pressure up to 5 atm led to completion of the
hydrogenation (entries 5 and 6) and the nuclei hydrogena-
tion of both aromatic rings was completed within 2 h
(entry 6).
The optimized reaction conditions were found to be appli-
cable to a variety of aromatic compounds, with the corre-
(Table 1). Pt/C, Ru/C, and Rh/C all proved to be effective
catalysts for arene hydrogenation in H2O (Table 1, en-
tries 1–3), whereas Pd/C and Ir/C showed relatively poor
catalyst activities (entries 4 and 5). Further investigation of
the catalyst activity at 608C indicated that Rh/C (10%) is a
most suitable catalyst for the hydrogenation of aromatic
nuclei (entry 9).
Table 3. Effect of temperature and H2 pressure.
To examine the applicability of different substrates, we
conducted some reactions with a selection of aromatic com-
pounds under the conditions described above. Although al-
kylbenzenes were completely hydrogenated (Table 2, en-
tries 1 and 2), the reactions of other substrates, such as di-
phenylmethane (3a), were incomplete under the same con-
ditions (entries 3–5).
We then investigated the effects of reaction temperature
and H2 pressure with diphenylmethane (3a) as a substrate
(Table 3). At 808C the reaction was very effective for the
hydrogenation of both nuclei (entry 3), whereas further
heating caused a drop in the product ratio (entry 4). An in-
Entry
T [8C]
H2 pressure [atm]
t [h]
Ratio 3a/4a/4b[a]
1
2
3
4
RT
60
80
90
80
80
1
1
1
1
3
5
24
24
24
24
15
2
38:45:17
24:58:18
1:42:57
30:64:6
0:2:98
5[b]
6[b]
0:0:100
[a] The ratio was determined by 1H NMR. [b] The reaction was per-
formed in a sealed tube.
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Efficient and Practical Arene Hydrogenation
FULL PAPER
Table 5. Effect of solvent.
sponding cyclohexane derivatives being obtained in good to
high yields (Table 4). The hydrogenations of alkylbenzene
and diphenylmethane, as well as of biphenyl, stabilized by a
stronger resonance hybridization, were complete within a
few hours (entries 1–4). Electron-deficient aromatic rings
were also hydrogenated (entries 5 and 6). Furthermore, het-
eroaromatic compounds were also reduced to the corre-
sponding saturated heterocyclic compounds without any
problems (entries 8–10). It is noteworthy that acetanilide
and nicotinamide underwent the hydrogenation without
their amide groups being affected (entries 7 and 10).
Entry
Solvent
Ratio 3a/4a/4b[a]
1
H2O
38:45:17
2:47:51
1:35:64
81:15:4
29:48:23
45:45:10
44:43:13
7:51:42
2
3
4
cyclohexane
AcOEt
THF
5
6
CH3OH
EtOH
7
8
9
10
nBuOH
tBuOH
iPrOH
dodecan-1-ol
1
0:26:74
52:30:18
Table 4. Arene hydrogenation in H2O in the presence of Rh/C (10%)
under H2 (5 atm) at 808C.
[a] The ratio was determined by H NMR.
Entry Substrate 3
t [h] Product 4
Yield [%][a]
96
fective solvent for the arene hydrogenation and re-examined
its scope and limitations in detail.
1[b]
3
Firstly, the reaction temperature in iPrOH under H2
(1 atm) was investigated (Table 6). Complete hydrogenation
of diphenylmethane was achieved when the reaction was
performed at 608C (entry 3), and the reaction was complete
within 12 h rather than the standard 24 h (entry 7). Conse-
quently, we employed 608C as the optimal temperature in
iPrOH.
2
2
73[c]
3
4
5
2
86
93
95
3
2.5
Table 6. Effect of the reaction temperature in iPrOH under ordinary H2
pressure.
6
6
91 (55:45)[d]
Entry
T [8C]
Ratio 3a/4a/4b[a]
7
8
9
3
90
90
96
1
2
3
4
5
6
RT
50
60
70
80
90
60
70
1
0:26:74
0:8:92
0:0:100
0:5:95
2:72:26
58:38:4
0:0:100
0:17:83
0.5
2
7[b]
8[b]
10
1.5
97
[a] The ratio was determined by H NMR. [b] For 12 h.
[a] Isolated yield. [b] H2 (1 atm). [c] The low yield is due to the volatile
nature of the product. [d] The ratio of cis/trans isomers is indicated in the
parentheses.
We next conducted the hydrogenation of various arene
derivatives in iPrOH (Table 7). Diverse arenes including
heterocycles were hydrogenated under ordinary H2 pressure
at 608C for 24 h to give the corresponding cyclohexane de-
rivatives (entries 1–4, 8–10), as was also the case even for
the highly electron-deficient isophthalic and terephthalic
acids (entries 6 and 7). However, the hydrogenation of
phthalic acid was incomplete (entry 5) because of reduced
catalyst activity of the Rh/C (10%) due to the formation of
a Rh-chelate with the ortho-carboxylic acid pair in the
phthalic acid. The arene hydrogenation of phenylalanine
was also incomplete, with 70% of the starting material re-
maining unchanged under the stated reaction conditions
(entry 11); the amino moiety may act as a catalyst poison.
The use of iPrOH for the hydrogenation: Although the use
of H2O as a solvent provides an environmentally friendly
method in terms of cost and toxicity, the poor solubilities of
organic compounds in H2O would be expected to suppress
the reactions. The use of an appropriate organic solvent
might therefore be helpful for efficient reaction progress
under milder conditions.
Surprisingly, a significant enhancement of the reaction
rate at RT was observed when iPrOH was used as a solvent
(Table 5, entry 9). We then employed iPrOH as the most ef-
Chem. Eur. J. 2009, 15, 6953 – 6963
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H. Sajiki et al.
Table 7. Arene hydrogenation under ordinary H2 pressure in iPrOH in
the presence of Rh/C (10%) at 608C.
(entries 4 and 5). Additionally, fluorene and 2-naphthol,
polycyclic arenes, were also reduced to the corresponding
poly-alicyclic products (entries 6 and 7). The hydrogenation
of heteroaromatic compounds also proceeded easily under
these conditions (entries 8 and 9); in particular, the hydroge-
nation of pyrrole-2-carboxylic acid gave racemic proline in
good yield (entry 8). Many monomers of functional poly-
mers possess aromatic rings as partial structures, and satu-
rated monomers might function as modifiers of the original
polymers to provide novel characteristic features. The hy-
drogenation of 4’-hydroxy-biphenylcarboxylic acid, a liquid-
crystal material, was complete in 20 h, giving the corre-
sponding bis-cyclohexane derivative (entry 10). It is note-
Entry Substrate 3
Product 4
Yield [%][a]
96
1
2
3
97
91
4
5
6
99 (67:33)[b]
incomplete
93 (60:40)[b]
Table 8. Arene hydrogenation in iPrOH under H2 (5 atm) at 608C.
Entry Substrate 3
t [h] Product 4
Yield [%][a]
95
7
8
93 (83:17)[b]
95
1
4
2
3
4
3
7
2
97
96 (85:15)[b]
46[c,d]
9
91
90
10
11
5
5
100[d]
AHCTUNGTRENNUNG
(70:30)[c]
6
7
8
9
80[d]
90[d]
95
12
97
10
8
[a] Isolated yield. [b] The ratio of cis/trans isomers is indicated in the pa-
rentheses. [c] The parentheses indicate the ratio of 3:4 from H NMR.
1
9
7
9
90
Indeed, N-acetylphenylalanine was completely hydrogenat-
ed (97% yield) under the same reaction conditions
(entry 12).
10
91[d]
Effect of H2 pressure (5 atm): Increasing the H2 pressure
was effective for the progress of the reactions, with their
rates being much improved (Table 8). The reactions of N-
acetylphenylalanine and its ethyl ester were completed
within 4 and 3 h under 5 atm H2 pressure (entries 1 and 2).
Phthalic acid could also be hydrogenated under H2 (5 atm)
to afford the two cyclohexene-1,2-dicarboxylic acid isomers
(entry 3), whereas under ordinary pressure the reaction had
not gone to completion (Table 7, entry 5). The arene hydro-
genations of sterically hindered substrates, such as 1,2,4,5-
tetramethylbenzene and 1,3,5-tri-tert-butylbenzene, were
also successful, with the reactions being complete within 5 h
11
12
10
24
93
incomplete
[a] Isolated yield. [b] The ratio of cis/trans isomers is indicated in the pa-
rentheses. [c] The low yield is due to the volatile nature of the product.
[d] It is hard to determine the cis/trans isomers.
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Efficient and Practical Arene Hydrogenation
FULL PAPER
Table 10. Reuse of Rh/C.
worthy that the partial reduction of binaphthol proceeded
and racemic 5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-bi-2-naphthol
(entry 11), the optically active isomers of which are used as
chiral ligands, was obtained as the sole product. Unfortu-
nately, estradiol, which possesses a highly rigid steroid skele-
ton, was not completely hydrogenated (entry 12).
Entry
t [h]
Ratio 3a/4a/4b[a]
Yield [%]
1
2
3
4
5
4
4
5
5
7
0:0:100
0:0:100
0:0:100
0:0:100
0:0:100
90
78
87
72
74
Effect of H2 pressure (10 atm): Consequently, we decided to
apply a higher H2 pressure. As a result, the arene hydroge-
nation even of estradiol, with its robust and stable skeleton,
was complete within 6 h under 10 atm of H2 (Table 9,
1
[a] The ratio was determined by H NMR.
Ru/C catalysis
Table 9. Arene hydrogenation in iPrOH under H2 (10 atm) at 608C.
The application of Ru/C to arene hydrogenation: During
the course of our study of the Rh/C-catalyzed mild and
easily applicable hydrogenation of arenes, we investigated
the hydrogenation of bisphenol A, because hydrogenated bi-
sphenol A is a useful component of functional polymers that
resist yellow discoloration caused by light absorption by the
aromatic rings of epoxy or polycarbonate polymers prepared
from bisphenol A. In addition, bisphenol A is also suspected
to be an endocrine disrupter, whereas its hydrogenated
counterpart is not. The Rh/C-catalyzed hydrogenation of bis-
phenol A in iPrOH was complete after 7 h under H2 (5 atm)
at 608C. We also found that the Ru/C-catalyzed hydroge-
nation of bisphenol A was also complete after 12 h under
H2 (10 atm), giving totally hydrogenated bisphenol A
(Scheme 2). Although Rh/C is highly effective as an arene
hydrogenation catalyst, Rh is quite an expensive rare metal
in relation to other platinum group metals such as Ru and
Pd. Other platinum metals can also function as catalysts for
arene hydrogenation, although their catalyst efficiencies are
only applicable to certain substrates.[4] Therefore, the devel-
opment of a general method for hydrogenation of aromatic
nuclei based on Ru/C catalysis under medium H2 pressure
(<10 atm) would provide a useful and practical procedure
for the synthesis of cyclohexane derivatives, in particular for
industrial application.
Entry Substrate 3
t
Product 4
Yield
[%][a]
[h]
1
2
6
91[b]
20
88[b]
3
4
20
19
68[b]
79[b]
[a] Isolated yield. [b] It is hard to determine the cis/trans isomers.
entry 1). 1-Naphthol was also hydrogenated under 10 atm of
H2, although under 5 atm of H2 the reaction had been in-
complete, unlike that of 2-naphthol (entry 2; see also
Table 8, entry 7). Furthermore, polycyclic compounds, such
as p-quaterphenyl, underwent hydrogenation to give the cor-
responding alicyclic compounds in high yields (entry 3). 4-
Aminocyclohexanecarboxylic acid, which is a useful com-
pound as an intermediate for pharmaceuticals and agro-
chemicals, was easily obtained from 4-aminobenzoic acid by
arene reduction (entry 4).
Scheme 2. Hydrogenation of bisphenol A.
Initially, we once more optimized the reaction tempera-
ture and H2 pressure with diphenylmethane as a substrate.
Ru/C-catalyzed hydrogenation of diphenylmethane was
found to proceed efficiently under H2 (5 atm) at 608C
(Table 11, entry 7) although higher H2 pressure was required
than in the Rh/C-catalyzed reaction (see Table 6, entry 3).
We then studied the Ru/C-catalyzed hydrogenation of var-
ious arenes under the optimized conditions as noted above
(Table 12). A variety of arenes, such as alkylbenzenes (en-
Reuse of Rh/C: With the aim of extension to an environ-
mentally benign and more practical method, we examined
the reuse of Rh/C with diphenylmethane as a substrate. As
shown in Table 10, Rh/C could be reused five times without
any reactivation, although a gradual extension of the reac-
tion time was necessary.
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6957

H. Sajiki et al.
Table 11. Effect of temperature and H2 pressure in the Ru/C-catalyzed
hydrogenation.
responding hydrogenated product (Scheme 3), although no
reaction was observed in iPrOH (in which terephthalic acid
disodium salt does not dissolve.
Entry
T [8C]
H2 pressure [atm]
Ratio 3a/4a/4b[a]
1
2
3
4
5
6
7
8
RT
RT
60
80
60
80
60
80
1
1
1
1
3
3
5
5
1
88:9:3
48:40:12
10:65:25
92:5:3
0:28:72
0:9:91
0:0:100
0:0:100
[a] The ratio was determined by H NMR.
Scheme 3. Hdrogenation of terephthalic acid and its disodium salt in the
presence of Ru/C.
Table 12. Arene hydrogenation in H2O in the presence of Ru/C (10%)
under H2 (5 atm) at 808C.
Application to the hydrogenation of phenols: Cyclohexanols
are important and useful structural elements of many com-
pounds, such as pharmaceuticals and functional materials.
Three types of representative synthetic methods for produc-
ing the cyclohexanol moiety have been reported. Firstly, the
oxidation of cyclohexane derivatives is one of the most
useful methods for direct production of cyclohexanols,[13] al-
though mixtures of cyclohexanol and cyclohexanone deriva-
tives have been obtained due to partial over-oxidation. The
second method is the reduction of cyclohexanones to cyclo-
hexanols.[14] The utility of this method is dependent on the
availabilities of the cyclohexanones, and it is rather difficult
to obtain a wide variety of cyclohexanone derivatives. Third-
ly, the reduction of phenols is a powerful and simple method
for the syntheses of cyclohexanols, but conventional meth-
ods have problems similar to those of arene hydrogenation.
In addition, it is known that the hydrogenation of phenols
by the Rh catalyst may cause hydroxy group elimination.[4]
We therefore decided to explore the Ru/C-catalyzed hydro-
genation of phenols under optimized conditions [Ru/C
(10 wt%) at 608C under H2 (5 atm) in iPrOH]. Phenol and
alkyl-substituted phenols were completely hydrogenated to
the corresponding cyclohexanol derivatives within 4–12 h in
good to excellent yields (Table 13), and an olefin moiety
was also hydrogenated under the same conditions (entry 6).
Substituted cyclohexanols were obtained as cis/trans mix-
tures. The sterically hindered 2,6-dimethylphenol was also
hydrogenated under the same conditions without any need
for a prolonged reaction time (entry 8).
Entry
1[b]
Substrate 3
t [h]
Product 4
Yield [%][a]
92
24
2
4
60[c]
3
4
5
4
92
94
87
4
24
6
7
24
12
90
89
[a] Isolated yield. [b] H2 (1 atm). [c] The low yield is due to the volatile
nature of the product.
tries 1–3), biphenyl (entry 4), and benzoic acid (entry 5), as
well as acetanilide (entry 6) and an alkyl-substituted furan
(entry 7), were smoothly hydrogenated in good to high
yields within several hours.
Effect of solubility: The Ru/C-catalyzed hydrogenation of
terephthalic acid was incomplete even under 10 atm H2
pressure, so we assumed that the solubility of terephthalic
acid was affecting the reaction progress. Terephthalic acid is
nearly insoluble both in iPrOH and in H2O, which might be
the cause of the low reactivity of the Ru/C-catalyzed hydro-
genation, although the reaction efficiency of the Rh/C-cata-
lyzed arene hydrogenation had been only slightly affected
because of the high catalyst activity. With the H2O-soluble
terephthalic acid disodium salt as a substrate, the hydroge-
nation indeed proceeded completely in H2O to give the cor-
In cases of phenols possessing other oxygen functions
such as ester groups or additional hydroxy groups, or pos-
sessing additional aromatic rings, the reactions did not go to
completion under the same conditions, because the lone
pairs of these oxygen-containing functional groups or the p
electron systems of the other aromatic rings were able to co-
ordinate strongly to the Ru metal and to decrease the cata-
lyst activities, acting as a certain type of catalyst poison. We
then examined the reaction temperature effect under 5 atm
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Efficient and Practical Arene Hydrogenation
Table 13. Ru/C-catalyzed hydrogenation of phenols.
FULL PAPER
Table 14. Hydrogenation of phenols at 908C under H2 (5 atm).
Entry Substrate
Product
t [h] Yield [%][a]
(cis/trans)[b]
Entry Substrate
Product
t
Yield
[h] [%][a]
(cis/
trans)[b]
1
2
4
7
92
72 (17)[c]
(58:23)
79 (62:38)
1
2
24
13
3
4
5
7
75 (57:43)
79 (43:57)
98 (53:47)
96
(80:20)
12
6
77
(61:39)
3
4
24
24
75
(67:33)
6
7
8
12
7
98 (65:35)
100 (83:17)
94[c]
98
(17:83)
5
6
24
21 74
8
1
[a] Isolated yield. [b] cis/trans ratio was determined by H NMR. [c] The reac-
tion was incomplete and the yield of the recovered starting material is indi-
cated in parentheses.
1
[a] Isolated yield. [b] cis/trans ratio was determined by H NMR. [c] It is hard
to determine the ratio of the stereoisomers.
H2 pressure. The hydrogenation of such substrates proceed-
ed at 908C to give the corresponding cyclohexanols
(Table 14, entries 2–6) except in the case of catechol
(entry 1).
Table 15. Hydrogenation of phenols at 1208C under H2 (10 atm).
The hydrogenation of catechol was not complete even
after 24 h at 908C, because of the strong coordination be-
tween the 1,2-diol functionality and Ru metal (entry 1). It is
noteworthy that the 4-phenylphenol, which has stronger res-
onance stabilization, underwent hydrogenation in high yield
to give the trans cyclohexanol derivative as the major prod-
uct (entry 5).
To develop the applicability of this synthetic method for
cyclohexanol derivatives, we conducted reactions under
10 atm of H2 at 1208C for those phenolic substrates, such as
catechol, that had been resistant to the milder conditions.
Fortunately, catechol was completely hydrogenated within
8 h (Table 15, entry 1). The hydrogenation of benzene-1,3,5-
triol proceeded with accompanying dehydroxylation to give
cyclohexene-1,3-diol in 77% yield as a cis/trans mixture
(entry 2). 4,4’-Dihydroxybiphenyl and 3-hydroxypyridine,
which can act as relatively strong catalyst poisons, were hy-
drogenated to give the corresponding 4,4’-bicyclohexyl and
piperidin-3-ol in 97% and 94% yields, respectively (en-
tries 3 and 4). Furthermore, the hydrogenation of estrone,
with its rigid structure, also proceeded smoothly both at the
aromatic ring and at the ketone functionality (entry 5).
Entry Substrate
Product
t
Yield
[h] [%][a]
(cis/
trans)[b]
89
(59:41)
1
2
8
77
(65:35)
24
97
(67:33)
3
4
12
4
94
5
24 100[c]
1
[a] Isolated yield. [b] cis/trans ratio was determined by H NMR. [c] It is hard
to determine the ratio of the stereoisomers.
Chem. Eur. J. 2009, 15, 6953 – 6963
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6959

H. Sajiki et al.
(100), 67 (18), 55 (68); HRMS (EI): m/z calcd for C13H26: 182.20345 [M]+
; found: 182.20444. The 1H NMR spectrum of the product was identical
with that of an authentic sample from Tokyo Chemical Industry Co., Ltd.
Reuse of Ru/C: Finally, we examined the reuse of the Ru/
catalyst for the hydrogenation of diphenylmethane
(Table 16). The reaction proceeded in high yield each time,
although the reaction time had to be extended for each
reuse.
C
tert-Butylcyclohexane (Table 2, entry 2; Table 4, entry 2; Table 12,
entry 2): 1H NMR (CDCl3): d=1.76–1.63 (m, 5H), 1.21–0.83 ppm (m,
15H); 13C NMR (CDCl3): d=48.4, 32.6, 27.8, 27.7, 27.5, 27.3, 26.8 ppm;
MS (EI): m/z (%): 140 [M]+ (8), 125 (13), 83 (25), 69 (25), 56 (100). The
1H NMR spectrum of the product was identical with that of an authentic
sample from Tokyo Chemical Industry Co., Ltd.
Table 16. Reuse of Ru/C.
Cyclohexylmethylbenzene (5; Table 2, entry 3; Table 3, entries 1–5):[15]
This compound was obtained together with dicyclohexylmethane by the
hydrogenation of diphenylmethane (3a). The 1H NMR spectrum of the
product was identical with that in the literature.[15]
Entry
t [h]
Ratio 3a/4a/4b[a]
Yield [%]
Dicyclohexylmethane (6; Table 2, entry 3; Table 4, entry 3; Table 7,
entry 1; Table 12, entry 3):[16] 1H NMR (CDCl3): d=1.68–1.60 (m, 10H),
1.34–1.12 (m, 8H), 1.02 (t, J=7.0 Hz, 2H), 0.87–0.77 ppm (m, 4H);
13C NMR (CDCl3): d=45.7, 34.4, 33.8, 26.8, 26.6 ppm; MS (EI): m/z (%):
180 [M]+ (53), 97 (37), 83 (100), 67 (34), 55 (71); HRMS (EI): m/z calcd
for C13H24: 180.18780 [M]+; found: 180.18865. The 1H NMR spectrum of
the product was identical with that in the literature.[16]
1
2
3
4
5
1
2
3
3
0:0:100
0:0:100
0:0:100
0:0:100
0:0:100
93
92
95
94
92
4.5
1
[a] Confirmed by H NMR.
Cyclohexanecarboxylic acid (Table 2, entry 4; Table 7, entry 3; Table 12,
entry 5): 1H NMR (CDCl3): d=2.32 (m, 1H), 1.91–1.14 ppm (m, 10H);
13C NMR (CDCl3): d=43.0, 28.8, 25.8, 25.4 ppm; MS (EI): m/z (%): 128
[M]+ (51), 99 (21), 83 (69), 73 (64), 55 (100); HRMS (EI): m/z calcd for
C7H12O2 [M]+: 128.08373; found: 128.08336. The 1H NMR spectrum of
the product was identical with that of an authentic sample from Nacalai
Tesque Co., Ltd.
Conclusions
In conclusion, we have developed an efficient and practical
hydrogenation method under mild conditions, both with the
heterogeneous Rh/C catalyst and also with Ru/C as a cheap-
er and in some cases more practical heterogeneous catalyst.
The method is effective and applicable for the hydrogena-
tion of a wide variety of arenes, including phenols. The use
of recoverable catalysts and iPrOH and the employment of
mild reaction conditions should lead to a practical and envi-
ronmentally friendly strategy for the synthesis of cyclohex-
ane derivatives.
Piperidin-3-ol (Table 2, entry 5; Table 4, entry 9; Table 8, entry 9;
Table 15, entry 4): 1H NMR (CD3OD): d=3.56 (m, 1H), 2.99 (dd, J=
12.1, 3.4 Hz, 1H), 2.80 (dt, J=12.6, 4.1 Hz, 1H), 2.49 (m, 1H), 2.39 (dd,
J=12.3, 8.5 Hz, 1H), 1.93 (m, 1H), 1.74 (m, 1H), 1.51–1.33 ppm (m,
2H); 13C NMR (CD3OD): d=67.7, 53.9, 46.4, 34.2, 25.2 ppm; MS (EI):
m/z (%): 101 [M]+ (30), 57 (42), 44 (100); HRMS (EI): m/z calcd for
C5H11NO: 101.08407 [M]+; found: 101.08329. The 1H NMR spectrum of
the product was identical with that of an authentic sample from Tokyo
Chemical Industry Co., Ltd.
Bicyclohexyl (Table 4, entry 4; Table 7, entry 2; Table 12, entry 4):
1H NMR (CDCl3): d=1.73–1.60 (m, 10H), 1.20–0.90 ppm (m, 12H);
13C NMR (CDCl3): d=43.5, 30.2, 26.9 ppm; MS (EI): m/z (%): 166 [M]+
Experimental Section
(36), 82 (100), 67 (40), 55 (45); HRMS (EI): m/z calcd for C12H12
:
1
166.17215 [M]+; found: 166.17129. The H NMR spectrum of the product
was identical with that of an authentic sample from Tokyo Chemical In-
dustry Co., Ltd.
Arene hydrogenation in H2O (Tables 1–4):
A mixture of substrate
(1.0 mmol) and Rh/C (10%; Rh on activated carbon, N.E. Chemcat;
10 wt% of substrate) in H2O (1 mL) in a sealed tube was stirred at 808C
under H2 pressure (5 atm) for the given time. Reaction completion was
generally indicated by a constant H2 pressure after a gradual decrease.
After cooling to room temperature, the reaction mixture was diluted with
ether (20 mL) and then filtered through a membrane filter (Millipore,
Millex-LH, 0.45 mm). The filtrate was partitioned between ether (20 mL)
and water (20 mL) and the aqueous layer was extracted with ether. The
combined ethereal organic layers were washed with brine and dried over
anhydrous MgSO4. After removal of the drying agent by simple filtration,
the filtrate was concentrated in vacuo to give the corresponding hydro-
genated product.
Cyclohexane-1,3-dicarboxylic acid (cis and trans mixture; Table 4,
entry 6; Table 7, entry 6; Table 12, entry 6): 1H NMR (CD3OD): d=5.44
(brs, 2H), 2.67–1.25 ppm (m, 10H); 13C NMR (CD3OD): d=179.4, 179.3,
43.7, 40.4, 32.6, 30.7, 29.9, 29.1, 26.1, 23.4 ppm; MS (FAB+, Gly): m/z
(%): 173 [M+H]+ (5), 155 (6); HRMS (FAB+, Gly): m/z calcd for
C8H13O4: 173.0814 [M+H]+; found: 173.0806. The 1H NMR spectrum of
the product was identical with that of an authentic sample from Tokyo
Chemical Industry Co., Ltd.
N-Cyclohexylacetamide (Table 4, entry 7; Table 7, entry 8; Table 12,
entry 6):[17] 1H NMR (CDCl3): d=6.06 (brs,1H), 3.73 (m, 1H), 1.97 (s,
3H), 1.90 (m, 2H), 1.73 (m, 2H), 1.62 (m, 1H), 1.33 (m, 2H), 1.22–
1.14 ppm (m, 3H); 13C NMR (CDCl3): d=169.1, 47.9, 32.7, 25.2, 24.9,
22.9. ppm; MS (EI): m/z (%): 100 [M]+ (7), 141 (50), 98 (24), 70 (11), 60
(100); HRMS (FAB+, Gly): m/z calcd for C8H15NO: 141.11537 [M+H]+;
found: 141.11555. The 1H NMR spectrum of the product was identical
with that in the literature.[17]
Arene hydrogenation in iPrOH (Tables 6–16): A mixture of substrate
(1.0 mmol) and catalyst (Rh or Ru on activated carbon, N.E. Chemcat;
10 wt% of substrate) in iPrOH (1 mL) in a sealed tube was stirred at the
given temperature and pressure. Reaction completion was indicated by a
constant H2 pressure after a gradual decrease. After cooling to room tem-
perature, the reaction mixture was diluted with CH3OH (20 mL) and the
catalyst was removed by filtration through a membrane filter (Millipore,
Millex-LH, 0.45 mm). The filtrate was concentrated in vacuo to give the
corresponding hydrogenated product.
2-Pentyltetrahydrofuran (Table 4, entry 8; Table 7, entry 10; Table 12,
entry 7): 1H NMR (CDCl3): d=3.74 (m, 1H), 3.66 (m, 1H), 3.58 (m,
1H), 1.84 (m, 1H), 1.74 (m, 2H), 1.45 (m, 1H), 1.36–1.18 (m, 8H),
0.78 ppm (t, J=6.8 Hz, 3H); 13C NMR (CDCl3): d=80.0, 68.1, 36.3, 32.6,
32.0, 26.7, 26.3, 23.2, 14.5 ppm; MS (FAB+, Gly): m/z: 143 [M+H]+
(4%); HRMS (FAB+, Gly): m/z calcd for C9H19O: 143.1436 [M+H]+;
found: 143.1441.
n-Heptylcyclohexane (2; Table 2, entry 1; Table 4, entry 1; Table 12,
entry 1): 1H NMR (CDCl3): d=1.70–1.32 (m, 5H), 1.26–1.09 (m, 16H),
0.90–0.81 ppm (m, 5H); 13C NMR (CDCl3): d=37.8, 37.7, 32.1, 30.1, 29.5,
27.0, 26.9, 26.6, 22.8, 14.1 ppm; MS (EI): m/z (%): 182 [M]+ (34), 83
6960
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ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 6953 – 6963

Efficient and Practical Arene Hydrogenation
FULL PAPER
Piperidine-3-carboxamide (Table 4, entry 10; Table 7, entry 9): 1H NMR
(CD3OD): d=2.95 (dd, J=12.2 Hz, 4.4 Hz, 1H), 2.84 (m, 1H), 2.59 (m,
1H), 2.47 (m, 1H), 2.27 (m, 1H), 1.82 (m, 1H), 1.64–1.36 ppm (m, 3H);
13C NMR (CD3OD): d=180.6, 47.6, 45.2, 29.8, 26.9 ppm; MS (FAB+,
Gly): m/z: 129 [M+H]+ (4%); HRMS (FAB+, Gly): m/z calcd for
Decahydronaphthalen-2-ol (mixture of isomers; Table 8, entry 7):[19]
1H NMR (CDCl3): d=4.14 (m, 0.01H), 3.81 (brs, 0.33H), 3.58 (m,
0.65H), 2.12 (brs, 1H), 1.87–0.86 ppm (m, 16H); 13C NMR (CDCl3): d=
66.6, 50.0, 35.2, 34.8, 34.5, 31.6, 30.2, 26.6, 25.7, 24.7, 20.9 ppm; MS (EI):
m/z (%): 136 [MÀ18]+ (100), 121 (38), 107 (26), 94 (58), 67 (30), 55 (26).
1
1
C6H13N2O: 129.10280 [M+H]+; found: 129.10331. The H NMR spectrum
The H NMR spectrum of the product was identical with that in the liter-
ature.[19]
of the product was identical to that of an authentic sample from Aldrich
Co., Ltd.
Pyrrole-2-carboxylic acid (Table 8, entry 8):[20] 1H NMR (D2O): d=4.10
(m, 1H), 3.25 (m, 2H), 2.21 (m, 1H), 1.92 ppm (m, 3H); 13C NMR
(D2O): d=174.7, 61.4, 46.2, 29.1, 23.9 ppm; MS (EI): m/z (%): 71
4-Isopropylcyclohexanecarboxylic acid (cis and trans mixture; Table 7,
1
À
entry 4): H NMR (CDCl3): d=2.62 (m, 0.66H, cis-CH CO2H), 2.23 (m,
1
[MÀCO2]+ (91), 70 (100), 44 (15), 41 (21). The H NMR spectrum of the
À
0.33H, trans-CH CO2H), 2.18–1.97 (m, 2H), 1.40–1.19 ppm (m, 4H);
product was identical with that in the literature.[20]
13C NMR (CDCl3): d=176.76, 175.52, 45.00, 42., 28, 29.20, 26.57, 25.57,
24.07 ppm; MS (EI): m/z (%): 170 [M]+ (31), 152 (10), 127 (38), 109
4-(4-Hydroxycyclohexyl)cyclohexanecarboxylic acid (mixture of isomers;
Table 8, entry 10): 1H NMR (CDCl3): d=4.00 (m, 0.74H), 3.53 (m,
0.26H), 2.61 (m, 0.71H), 2.23 (m, 0.29H, CHCO2H), 1.86–0.88 ppm (m,
2H); 13C NMR (CDCl3): d=24.1, 25.4, 35.5, 70.3 ppm; MS (EI): m/z
(%): 162 [MÀ18]+ (18), 149 (12), 127 (32), 109 (22), 81 (100), 67 (26), 55
(22); elemental analysis (%) calcd for C13H22O3: C 68.99, H 9.80; found:
C 68.63, H 9.98.
1
(38), 98 (8), 81
(100), 59 (23), 41 (16). The H NMR spectrum of the prod-
uct was identical with that of an authentic sample from Tokyo Chemical
Industry Co., Ltd.
Cyclohexane-1,4-dicarboxylic acid (cis and trans mixture; Table 7,
entry 7): 1H NMR ([D6]DMSO): d=12.09 (brs, 2H), 2.35–2.12 (m, 2H),
1.88 (m, 1H), 1.69–1.55 (m, 6H), 1.30 ppm (m, 1H); 13C NMR
([D6]DMSO): d=176.6, 176.3, 41.8, 41.8, 27.8, 25.7 ppm; MS (EI): m/z
(%): 154 [MÀ18]+ (16), 126 (68), 108 (52), 81 (100), 67 (28), 54 (23). The
1H NMR spectrum of the product was identical with that of an authentic
sample from Tokyo Chemical Industry Co., Ltd.
2-Amino-3-cyclohexylpropanoic acid (not isolated; Table 7, entry 11):[18]
1H NMR (D2O): d=3.64 (dd, J=8.5, 5.4 Hz, 1H), 1.69–0.79 ppm (m,
13H). The 1H NMR spectrum of the product was identical with that in
the literature.[18]
1-(2-Hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-5,6,7,8-tetrahydronaph-
thalen-2-ol (mixture of isomers; Table 8, entry 11): 1H NMR (CDCl3):
d=7.04 (d, J=6.0 Hz, 2H), 6.81 (d, J=6.0 Hz, 2H), 4.61 (brs, 2H), 2.73
(t, J=5.6 Hz, 4H), 2.31–2.25 (m, 2H), 2.18–2.12 (m, 2H), 1.74–1.65 ppm
(m, 8H); 13C NMR (CDCl3): d=151.3, 137.1, 130.9, 130.2, 118.9, 112.9,
29.2, 27.0, 22.9 ppm; MS (EI): m/z (%): 294 [M]+ (100), 276 (8), 248
(13), 237 (8), 147 (12), 126 (8), 84 (85), 47(11); HRMS (EI): m/z calcd
for C20H22O2: 294.16138 [M]+; found: 252.2803.
(8R,9R,13S,14R)-13-Methyl-hexadecahydro-1H-cyclopenta[a]phenan-
threne-3, 17-diol (hydrogenated estrone, mixture of isomers; Table 8,
entry 12; Table 9, entry 1; Table 15, entry 5): 1H NMR (CDCl3): d=3.76–
3.61 (m, 2H), 2.33–0.63 ppm (m, 26H); 13C NMR (CDCl3): d=81.5, 79.7,
66.8, 50.7, 48.4, 46.9, 45.6, 43.3, 41.5, 40.1, 38.5, 38.4, 36.7, 36.0, 34.5, 32.4,
32.1, 31.6, 31.5, 30.2, 26.6, 26.0, 25.9, 24.3, 23.1, 20.1, 16.8, 11.0 ppm; MS
(EI): m/z (%): 278 [M]+ (18), 260 (98), 242 (86), 216 (55), 201 (100); ele-
mental analysis (%) calcd for C18H30O2: C 77.65, H 10.86; found: C
76.82, H 10.77.
2-Acetylamino-3-cyclohexylpropanoic acid (Table 7, entry 12; Table 8,
entry 1): 1H NMR (CD3OD): d=4.39 (dd, J=10.2, 5.0 Hz, 1H), 1.93 (s,
3H), 1.75 (m, 1H), 1.68–1.58 (m, 5H), 1.52 (m, 1H), 1.33 (m, 1H), 1.25–
1.12 (m, 3H), 0.95 (m, 1H), 0.84 ppm (m, 1H); 13C NMR (CD3OD): d=
176.7, 173.9, 173.8, 52.0, 40.7, 35.9, 35.3, 33.7, 28.0, 27.8, 27.6, 22.9,
22.8 ppm; MS (FAB+, NBA): m/z: 214 [M+H]+ (17%); HRMS (FAB+,
NBA): m/z calcd for C11H20NO3: 214.1443 [M+H]+; found: 214.1447.
Ethyl 2-acetamido-3-cyclohexylpropanoate (Table 8, entry 2): 1H NMR
(CD3OD): d=4.43 (dd, J=9.8, 5.5 Hz, 1H), 4.14 (qd, J=7.1, 1.5 Hz,
2H), 1.97 (s, 3H), 1.78–1.51 (m, 7H), 1.37 (m, 1H), 1.26–1.12 (m, 3H),
1.25 (t, J=7.1 Hz, 3H), 0.98 (m, 1H), 0.90 ppm (m, 1H); 13C NMR
(CD3OD): d=174.2, 173.1, 173.0, 62.0, 51.6, 51.5, 40.1, 40.0, 35.3, 34.6,
33.3, 27.5, 27.3, 27.1, 22.4, 22.3, 14.5 ppm; MS (FAB+, NBA): m/z (%):
242 [M+H]+ (92), 168 (26), 126 (15); HRMS (FAB+, NBA): m/z calcd
for C13H24NO3: 242.1756 [M+H]+; found: 242.1751.
Decahydronaphthalen-1-ol (mixture of isomers; Table 9, entry 2):[20]
1H NMR (CDCl3): d=3.76 (m, 0.26H), 3.65 (m, 0.67H), 3.18 (m, 0.07H),
2.13–0.87 ppm (m, 17H); 13C NMR (CDCl3): d=73.3, 42.9, 41.0, 35.6,
31.7, 29.2, 26.3, 24.4, 24.2, 21.4, 18.8 ppm; MS (EI): m/z (%): 100
[MÀ18]+ (7), 136 (100), 121 (23), 107(22), 94(33), 81 (28), 67 (26), 55
1
(16). The H NMR spectrum of the product was identical with that in the
literature.[20]
Cyclohexane-1,2-dicarboxylic acid (cis and trans mixture; Table 8,
entry 3): 1H NMR ([D6]DMSO): d=12.08 (brs, 2H), 2.71 (m, 1.69H, cis-
1-Cyclohexyl-4-(4-cyclohexylcyclohexyl)cyclohexane (mixture of isomers;
Table 9, entry 3): 1H NMR (CDCl3): d=1.89–0.80 ppm (m, 42H);
13C NMR (CDCl3): d=43.4, 41.4, 41.1, 39.8, 39.3, 35.7, 30.9, 30.7, 30.6,
30.4, 30.2, 30.2, 26.9, 26.8, 26.7, 26.5, 26.0 ppm; MS (EI): m/z: 100
[MÀ18]+ (7%); elemental analysis (%) calcd for C24H42: C 87.19, H
12.81; found: C 86.93, H 13.06.
À
À
CH CO2H), 2.40 (m, 0.31H, trans-CH CO2H), 1.92–1.91 (m, 2H), 1.73–
1.70 (m, 2H), 1.24–0.90 ppm (m, 4H); 13C NMR ([D6]DMSO): d=182.9,
182.3, 43.3, 42.9, 39.9, 32.7, 31.4, 28.9, 28.7, 26.6, 26.4, 20.0, 19.7 ppm; MS
(EI): m/z (%): 154 [MÀ18]+ (20), 126 (72), 108 (36), 81 (100), 66 (55), 41
(46). The 1H NMR spectrum of the product was identical with that of an
authentic sample from Wako Pure Chemical Product.
4-Aminocyclohexanecarboxylic acid (cis and trans mixture; Table 9,
entry 4): 1H NMR (D2O): d=3.03 (m, 1H), 2.28–1.10 ppm (m, 13H);
13C NMR (CDCl3): d=199.2, 198.0, 64.5, 63.7, 61.3, 59.7, 56.0, 44.4, 44.3,
42.3, 42.0, 40.3, 40.1, 39.5 ppm; MS (EI): m/z (%): 100 [M]+ (7), 145 (16),
1,2,4,5-Tetramethylcyclohexane (mixture of isomers; Table 8, entry 4):
1H NMR (CDCl3): d=1.75–1.64 (m, 4H), 1.43–1.26 (m, 4H), 0.86 ppm
(d, J=7.1 Hz, 12H); 13C NMR (CDCl3): d=43.3, 39.6, 38.0, 36.6, 36.1,
35.2, 34.1, 33.6, 32.3, 20.2, 19.9, 17.8, 12.2 ppm; MS (EI): m/z (%): 140
[M]+ (32), 125 (57), 98 (21), 83 (31), 69 (100), 55 (54); HRMS (EI): m/z
calcd for C10H20 [M]+ 140.1565; found: 140.1560.
1
129 (12), 83 (15), 58 (100), 45 (38). The H NMR spectrum of the product
was identical with that of an authentic sample from Aldrich Co., Ltd.
Cyclohexanol (Table 13, entry 1):[21] 1H NMR (CDCl3): d=3.62 (m, 1H),
1.99–1.82 (m, 2H), 1.80–1.62 (m, 2H), 1.53 (m, 1H), 1.32–1.18 ppm (m,
5H); 13C NMR (CDCl3): d=70.3, 35.5, 25.4, 24.1 ppm; MS (EI): m/z
1,3,5-Tri-tert-butylcyclohexane (mixture of isomers; Table 8, entry 5):
1H NMR (CDCl3): d=2.08–0.52 ppm (m, 36H); 13C NMR (CDCl3): d=
48.5, 32.8, 28.1, 27.8 ppm; MS (EI): m/z (%): 252 [M]+ (14), 196 (23), 139
(29), 125 (19), 111 (12), 83 (20), 69 (18), 57 (100); HRMS (EI): m/z calcd
for C18H36: 252.2817 [M]+; found: 252.2803.
1
(%): 100 [M]+ (7), 82 (89), 57 (100). The H NMR spectrum of the prod-
uct was identical with that in the literature.[21]
2-Methylcyclohexanol (cis and trans mixture; Table 13, entry 2):
1H NMR (CDCl3): d=3.78 (m, 0.62H, cis-CHOH), 3.12 (m, 1H), 1.94
(m, 1H), 1.75–1.24 (m, 8H), 1.91–0.93 ppm (m, 3H); 13C NMR (CDCl3):
d=76.4, 71.1, 40.2, 35.8, 35.4, 33.6, 32.4, 28.7, 25.4, 25.2, 24.4, 20.6, 18.5,
16.9 ppm; MS (EI): m/z (%): 114 [M]+ (9), 96 (52), 81 (55), 57 (100).
The 1H NMR spectrum of the product was identical with that of an au-
thentic sample from Tokyo Chemical Industry Co., Ltd.
1
Dodecahydro-1H-fluorene (Table 8, entry 6): H NMR (CDCl3): d=2.08–
1.05 ppm (m, 22H); 13C NMR (CDCl3): d=43.0, 37.3, 35.3, 29.2, 24.4,
24.2, 22.1 ppm; MS (EI): m/z: 178 [M]+ (44), 135 (7), 121 (18), 97 (100),
67 (60), 55(24); HRMS (EI): m/z calcd for C18H36: 178.17215 [M]+;
found: 178.17115.
Chem. Eur. J. 2009, 15, 6953 – 6963
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6961

H. Sajiki et al.
3-Methylcyclohexanol (cis and trans mixture; Table 13, entry 3):[22]
1H NMR (CDCl3): d=4.05 (m, 0.43H, trans-CHOH,), 3.55 (m, 0.57H,
cis-CHOH), 1.96–0.74 ppm (m, 12H); 13C NMR (CDCl3): d=70.7, 66.8,
44.6, 41.5, 35.4, 31.4, 26.5, 24.1, 22.3, 21.9, 20.0 ppm; MS (EI): m/z (%):
96 (9), 81 (76), 71 (100), 57 (35). The 1H NMR spectrum of the product
was identical with that in the literature.[22]
(2), 98 (57), 83 (42), 80 (27), 70 (37), 54 (100). The 1H NMR spectrum of
the product was identical with that of an authentic sample from Tokyo
Chemical Industry Co., Ltd.
4-Cyclohexylcyclohexanol (cis and trans mixture; Table 14, entry 5):
1
À
H NMR (CDCl3): d=3.96 (m, 0.17H, cis-CH OH), 3.49 (m, 0.83H,
trans-CH OH), 2.00–0.93 ppm (m, 20H); 13C NMR (CDCl3): d=71.4,
À
4-Methylcyclohexanol (cis and trans mixture; Table 13, entry 4):[23]
1H NMR (CDCl3): d=3.94 (m, 0.47H, cis-CHOH), 3.53 (m, 0.53H, trans-
CHOH), 1.93 (m, 1H), 1.71–1.68 (m, 2H), 1.34–1.20 (m, 2.5H), 1.01–
0.87 ppm (m, 4.5H); 13C NMR (CDCl3): d=70.8, 66.8, 35.5, 33.3, 32.1,
31.7, 31.0, 28.9, 21.9, 21.5 ppm; MS (EI): m/z (%): 114 [M]+ (26), 96
67.1, 42.9, 42.5, 36.0, 32.9, 30.5, 30.4, 28.2, 26.9, 23.9 ppm; MS (EI): m/z
(%): 182 [M]+ (2), 164 (100), 82 (82). The 1H NMR spectrum of the
product was identical with that of an authentic sample from Tokyo
Chemical Industry Co., Ltd.
2, 2-Bis(4’-hydroxycyclohexyl)propane (mixture of isomers; Table 14,
entry 6): 1H NMR (CD3OD): d=3.50 (m, 0.83H), 2.05–1.90 (m, 4H),
1.62–1.79 (m, 4H), 1.29–1.02 (m, 10H), 0.74 ppm (s, 6H); 13C NMR
(CD3OD): d=71.8, 44.7, 37.5, 36.9, 26.2, 21.1 ppm; elemental analysis
(%) calcd for C15H28O2: C 74.95, H 11.74; found: C 74.40, H 11.75.
1
(100), 81 (85), 57 (78). The H NMR spectrum of the product was identi-
cal with that in the literature.[23]
4-tert-Butylcyclohexanol (cis and trans mixture; Table 13, entry 5):
1H NMR (CDCl3): d=4.03 (m, 0.53H, cis-CHOH), 3.51 (m, 0.47H, trans-
CHOH), 2.02–0.85 ppm (m, 18H); 13C NMR (CDCl3): d=71.1, 65.8, 48.0,
47.1, 36.0, 33.3, 32.5, 27.6, 27.4, 25.6, 20.9 ppm; MS (EI): m/z (%): 156
[M]+ (2), 138 (19), 123 (23), 99 (28), 81 (51), 57 (100). The 1H NMR
spectrum of the product was identical with that of an authentic sample
from Tokyo Chemical Industry Co., Ltd.
4,4’-Bicyclohexanol (cis and trans mixture; Table 15, entry 3): 1H NMR
À
(CD3OD): d=3.90–3.82 (m, 0.66H, cis-CH OH), 3.49–3.31 (m, 1.34H,
À
trans-CH OH), 2.00–1.90 (m, 2H), 1.85–1.60 (m, 4H), 1.55–1.35 (m,
4H), 1.21–1.04 ppm (m, 8H); 13C NMR (CD3OD): d=71.9, 71.8, 67.6,
43.5, 43.4, 42.9, 36.7, 33.7, 31.7, 29.7, 29.6, 28.1, 25.4, 25.3 ppm; MS (EI):
1
m/z (%): 180 [M]+ (8), 162 (69), 81 (100). The H NMR spectrum of the
1
2-Propylcyclohexanol (cis and trans mixture; Table 13, entry 6): H NMR
product was identical with that of an authentic sample from Tokyo
Chemical Industry Co., Ltd.
(CDCl3): d=3.86 (m, 0.65H, cis-CHOH), 3.20 (m, 0.35H, trans-CHOH),
1.96–1.08 (m, 13H), 1.00–0.89 ppm (m, 3H); 13C NMR (CDCl3): d=75.7,
70.4, 45.8, 41.9, 36.6, 35.4, 35.1, 34.0, 31.1, 27.5, 26.5, 26.2, 25.8, 21.5, 21.1,
20.6, 15.4, 15.3 ppm; MS (EI): m/z (%): 124 (27), 95 (46), 82 (100), 57
(69). The 1H NMR spectrum of the product was identical with that of an
authentic sample from Tokyo Chemical Industry Co., Ltd.
2-tert-Butylcyclohexanol (cis and trans mixture; Table 13, entry 7):[24]
1H NMR (CDCl3): d=4.25 (m, 0.83H, cis-CHOH), 3.47 (m, 0.17H, trans-
CHOH), 1.94–0.79 ppm (m, 18H); 13C NMR (CDCl3): d=73.4, 67.8, 53.6,
50.9, 37.8, 35.0, 32.5, 29.2, 28.5, 26.7, 26.1, 25.1, 21.1, 19.9 ppm; MS
(FAB+, NPOE): m/z (%): 156 [M]+ (7), 123 (55), 71 (79), 57 (100). The
1H NMR spectrum of the product was identical with that in the litera-
ture.[24]
Acknowledgements
This work was partially supported by the Nagase Science Technology De-
velopment Foundation. We thank N.E. Chemcat Co., Ltd., for their gift
of the catalysts.
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2,6-Dimethylcyclohexanol (mixture of isomers; Table 13, entry 8):
1H NMR (CDCl3): d=3.55 (m, 0.37H), 3.34 (m, 0.09H), 2.68 (t, J=
9.4 Hz, 0.23H), 1.67–1.22 (m, 8H), 0.98 ppm (m, 6H); 13C NMR (CDCl3):
d=82.1, 75.6, 39.8, 37.2, 34.2, 33.6, 33.1, 30.5, 27.3, 25.8, 25.5, 19.9, 18.7,
18.6, 18.0 ppm; MS (EI): m/z (%): 128 [M]+ (65), 110 (35), 95 (51), 81
(27), 71 (100). The 1H NMR spectrum of the product was identical with
that of an authentic sample from Tokyo Chemical Industry Co., Ltd.
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Cyclohexane-1,2-diol (cis and trans mixture; Table 14, entry 1; Table 15
entry 1): 1H NMR (CDCl3): d=3.75 (m, 0.59H, cis-CHOH), 3.32 (m,
0.41H, trans-CHOH), 1.92 (m, 1H), 1.74–1.53 (m, 4H), 1.30–1.24 ppm
(m, 3H); 13C NMR (CDCl3): d=75.2, 70.3, 32.56, 29.5, 24.0, 21.1,
24.0 ppm; MS (EI): m/z (%): 116 [M]+ (21), 98 (40), 70 (100), 57 (58).
[4] S. Nishimura, in Handbook of Heterogeneous Catalytic Hydrogena-
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Methyl 2-hydroxycyclohexanecarboxylate (cis and trans mixture;
Table 14, entry 2):[22] 1H NMR (CDCl3): d=4.14 (m, 0.65H, cis-CHOH),
3.76 (m, 0.35H, trans-CHOH), 3.71 (s, 3H), 3.15 (brs, 0.65H), 2.95 (brs,
0.35H), 2.48 (m, 0.65H, trans-CHCO2-), 2.25 (m, 0.35H, cis-CHCO2-),
2.01–1.76 (m, 5H), 1.48–1.26 ppm (m, 4H); 13C NMR (CDCl3): d=176.1,
175.6, 70.8, 66.7, 51.7, 51.2, 46.6, 33.7, 31.7, 28.0, 24.9, 24.7, 24.3, 23.8,
20.0 ppm; MS (EI): m/z (%): 140 [M]+ (8), 130 (41), 108 (15), 87 (100),
81 (34). The 1H NMR spectrum of the product was identical with that in
the literature.[22]
Cyclohexane-1,3-diol (cis and trans mixture; Table 14, entry 3; Table 15,
entry 2): 1H NMR (CDCl3): d=4.08 (m, 0.39H, trans-CHOH), 3.75 (m,
0.61H, cis-CHOH), 3.13 (brs, 1H), 2.05 (m, 1H), 1.87–1.27 ppm (m,
7H); 13C NMR (CDCl3): d=68.4, 66.7, 41.9, 33.8, 33.6, 18.8, 18.5 ppm;
1
MS (EI): m/z (%): 116 [M]+ (3), 98 (100), 80 (57), 70 (51). The H NMR
spectrum of the product was identical with that of an authentic sample
from Tokyo Chemical Industry Co., Ltd.
Cyclohexane-1,4-diol (cis and trans mixture; Table 14, entry 4): 1H NMR
([D6]DMSO): d=4.42 (m, 1.34H, cis-CHOH), 4.29 (m, 0.66H, trans-
CHOH), 3.52 (m, 0.33H), 3.35 (m, 0.67H), 1.79–1.68 (m, 2.5H), 1.61–
1.50 (m, 1.5H), 1.40 (m, 1H), 1.21–1.11 ppm (m, 2.5H); 13C NMR
([D6]DMSO): d=68.2, 65.9, 33.0, 30.3 ppm; MS (EI): m/z (%): 116 [M]+
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6962
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Chem. Eur. J. 2009, 15, 6953 – 6963

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FULL PAPER
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Received: February 10, 2009
Published online: June 9, 2009
Chem. Eur. J. 2009, 15, 6953 – 6963
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6963