Effect of solvent and hydrogen during selective hydrogenation

Article abstract of DOI:10.1016/S0040-4039(01)01787-7

Described is the solvent effect for the chemoselective hydrogenation of alkenes having a benzyloxy group (Bn-O-) using a hydrogenation system employing atomic hydrogen permeating through a Pd sheet electrode.

Full text of DOI:10.1016/S0040-4039(01)01787-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8323–8327
Effect of solvent and hydrogen during selective hydrogenation
a,
a
a
a
a
a
Shojiro Maki, * Yasuhiro Harada, Ryo Matsui, Makiko Okawa, Takashi Hirano, Haruki Niwa,
b
b
b
c
c
Megumi Koizumi, Yoshinori Nishiki, Tsuneto Furuta, Hiroshi Inoue and Chiaki Iwakura
a
Department of Applied Physics and Chemistry, The University of Electro-Communications, Chofu, Tokyo 182-8585, Japan
b
Permelec Electrode Ltd. Endo, Fujisawa, Kanagawa 252-0816, Japan
c
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
Received 7 August 2001; revised 10 September 2001; accepted 21 September 2001
Abstract—Described is the solvent effect for the chemoselective hydrogenation of alkenes having a benzyloxy group (Bn-O-) using
a hydrogenation system employing atomic hydrogen permeating through a Pd sheet electrode. © 2001 Elsevier Science Ltd. All
rights reserved.
1
1
. Introduction
mined by comparison with the H NMR data of
authentic samples that were synthesized by an alterna-
tive method.
The hydrogenation of alkenes having a benzyloxy
group without hydrogenolysis is quite difficult under
conventional conditions. In order to achieve the selec-
6
In benzene, the benzyl ester 1 was hydrogenated for 4
h using the hydrogenation system to give the selective
hydrogenation product 2 in 45% yield (Table 1). After
1
2
tive hydrogenation without hydrogenolysis, the
3
7
hydrogenation system employing atomic hydrogen per-
meating through a Pd sheet electrode has been devised.
Although this system was able to achieve selective
reduction in benzene as the solvent, hydrogenolysis
took place in MeOH. This result implies that solvent
influences surface condition of the Pd sheet, which is
used as a catalyst. Therefore, the effect of the aprotic
solvent was investigated for twodifferent types of alke-
nes as substrates including the benzyl ether or benzyl
ester site.
4
19 h, the benzyl ester 1 completely disappeared and
product 2 was produced in quantitative yield. Although
product 2 was subjected to reduction under the same
5
8
conditions for 24 h, the hydrogenolysis products 3 and
9
4
and any by-product were not detected at all. A
2. Experimental
The hydrogenation system is shown in Fig. 1. The
substrate was circulated using a roller pump at the rate
3
−1
of 2.4 cm min in solvent (reaction concentration of
.0 mM) at room temperature. During the reaction,
atomic hydrogen was provided by the electrolysis of
7
−
2
water (galvanostatic electrolysis, 10 mA cm ) in
another cell. For comparison, the reaction time was
−
1
standardized at 4 h (21 F mol ). After the reaction, the
reactant was simply concentrated, and then the residue
1
was weighed and analyzed by H NMR without purifi-
cation. The ratio and structure of products were deter-
*
0
Corresponding author.
Figure 1.
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01787-7

8
324
S. Maki et al. / Tetrahedron Letters 42 (2001) 8323–8327
Table 1.
Solvent
Time (h)
4
2 (%)
3 (%)
4 (%)
1 (%)
Benzene
45
100
29
0
0
0
0
100
0
0
70
0
100
0
84
0
100
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
55
0
71
0
100
33
9
88
0
57
6
22
0
89
0
0
1
9
4
0
4
4
5
4
5
4
0
4
5
4
0
4
Acetone
2
Petroleum ether
0
1
,4-Dioxane
67
21
12
0
43
10
78
0
1
3
2
1
5
Isopropyl ether
Toluene
Ethyl acetate
Dichloromethane
Methanol
11
0
0
100
100
5
methanol solution gave the product 3 after 4 h in
quantitative yield. Because the solubility of 1 was quite
low in petroleum ether, the reaction did not take place
at all. Toluene has a similar reactivity with benzene and
lower toxicity, therefore, toluene was utilized as the
reaction solvent instead of benzene. Accordingly, selec-
tive hydrogenation was expected in toluene, however,
the product 3 was produced before completing the
start, the product 3 was generated due to the succeeding
reaction after 4 h.
11
Results of the benzyl ether 5 reaction as a substrate
are summarized in Table 2. In benzene, a high hydro-
genation selectivity was observed to afford the product
4
6 in quantitative yield. For confirming the clear dis-
tinction between the hydrogenation and the
hydrogenolysis, 6 was subjected to hydrogenation by
the hydrogenation system for 24 h. As a result, no
10
hydrogenation. In other solvents, though the selective
hydrogenation took place within about 4 h from the
Table 2.
Solvent
Time (h)
4
6 (%)
7 (%)
5 (%)
Benzene
50
100
20
0
17
99
67
47
48
50
22
0
0
0
0
100
0
1
Trace
24
8
8
66
100
50
0
80
0
83
0
33
29
44
42
11
0
30
4
30
4
35
4
4
4
4
4
4
Acetone
Petroleum ether
1
,4-Dioxane
Isopropyl ether
Toluene
Ethyl acetate
Dichloromethane
Methanol

S. Maki et al. / Tetrahedron Letters 42 (2001) 8323–8327
8325
1
2
corresponding hydrogenolysis compound 7 and any
suggested that the atomic hydrogen and/or the condi-
tion of the Pd black-(S) surface causes the selectivity of
the hydrogenation, in addition to the solvent effect.
In order to confirm the effect of atomic hydrogen,
substrates 1 and 5 were hydrogenated under the
hydrogen gas using the Pd black-(S) as a catalyst. As
shown in Table 3, several different results were
obtained upon comparison with the corresponding
result when using the developed hydrogenation system.
by-product were obtained.
The hydrogen source of this hydrogenation system is
atomic hydrogen’ which is produced by the electrolysis
of water. Pd black that was deposited on the Pd sheet
surface, viz. Pd black-(S), was produced by the hydro-
gen reduction using the ‘atomic hydrogen’ being pro-
vided from the hydrogenation system. Therefore, it is
14
‘
13
Table 3.
Solvent
Time (h)
2 (%)
3 (%)
4 (%)
1 (%)
Benzene
4
8
100
100
100
45
40
36
7
33
78
8
0
0
0
55
0
12
40
67
18
92
100
24
100
0
0
0
0
0
3
20
0
0
0
0
0
0
2
4
4
4
8
4
4
4
4
4
4
1
Acetone
Petroleum ether
0
60
49
33
0
4
0
0
0
0
1
,4-Dioxane
Isopropyl ether
Toluene
Ethyl acetate
Dichloromethane
0
76
0
0
0
0
1
,2-Dimethoxyethane
Methanol
Table 4.
Solvent
Time (h)
6 (%)
7 (%)
5 (%)
Benzene
4
8
100
100
100
100
17
0
0
0
0
0
0
0
0
0
0
14
2
4
4
8
4
8
4
4
4
8
4
4
4
4
1
Acetone
0
83
Trace
17
35
24
0
0
0
83
12
11
100
Petroleum ether
B100
83
1
,4-Dioxane
51
76
B100
100
100
17
Isopropyl ether
Toluene
0
Trace
0
0
0
55
0
2
Ethyl acetate
Dichloromethane
33
89
0
1
,2-Dimethoxyethane
Methanol
0

8
326
S. Maki et al. / Tetrahedron Letters 42 (2001) 8323–8327
In benzene, the reaction time was improved and, need-
less to say, a high selectivity was observed. It was
remarkable that the petroleum ether and the 1,4-diox-
ane solution conditions gave product 4 that was pro-
duced by the reaction dominated by the hydrogenolysis.
In fact, the benzyl ester 1 was not converted into
product 4 by the hydrogenation system, thus, it was
implied that hydrogen source influences the reaction
selectivity.
toluene, the benzyl ether 5 was converted into product
6 in almost 100% yield within 4 h and after 24 h, 6 was
still stable under this condition without hydrogenolysis.
This result indicates that practical application including
mass production is possible. In other solvents, the
results were almost same using the hydrogenation
system.
The Pd black-(S) exhibited selective hydrogenation
15
activity for various substrates in 100% yields (Table
5). In all the substrates, no hydrogenolysis products
On the other hand, the results for the benzyl ether 5 are
summarized in Table 4. As a noteworthy point, in
16
and by-products were detected. In order to confirm
Table 5.
Pd black-(S)
(
4% w/w)
Substrate
Product
+
SM
benzene, rt
Entry
1
Substrate
Product
Time (h) Yield (%) SM (%)
MeO
MeO
OBn
MeO
MeO
OBn
4
4
100
100
0
0
2
MeO
OBn
OBn
MeO
OBn
4
0
100
49
2
24
51
MeO
MeO
4
8
100
0
MeO
MeO
MeO
MeO
OBn
OBn
OBn
4
63
37
3
4
OBn
OBn
24
100
0
MeO
MeO
OBn
OBn
MeO
4
24
76
0
COOEt MeO
MeO
COOEt
2
4
100
MeO
MeO
5
6
4
78
22
0
CHO
MeO
CHO
OBn
24
100
MeO
MeO
MeO
MeO
4
4
100
100
0
0
OBn
2
MeO
MeO
OBn
MeO
MeO
OBn
4
66
34
0
OBn
OBn
7
8
24
100
O
O
COOBn
COOBn
4
100
100
0
0
MeO
MeO
MeO
MeO
2
4
COOBn
COOBn
4
4
69
31
0
9
2
100
N
N
Bn
Bn

S. Maki et al. / Tetrahedron Letters 42 (2001) 8323–8327
8327
HREIMS: found m/z 300.1367 (M ); calcd for C H O
4
+
the clear distinction between the hydrogenation and the
hydrogenolysis, every reactant was maintained under
reducing conditions for a sufficient time after the
hydrogenation was completed. As a result, neither the
corresponding hydrogenolysis product nor any by-
18
20
300.1362.
8. Compound 3: H NMR (270 MHz, CDCl
t, J=7.6 Hz), 2.91 (2H, t, J=7.6 Hz), 3.86 (3H, s), 3.87
1
): l 2.67 (2H,
3
13
(3H, s), 6.73–6.82 (3H, complex); C NMR (67.8 MHz,
CDCl ): l 30.24 (t), 35.79 (t), 55.81 (q), 55.91 (q), 111.35
(d), 111.66 (d), 120.08 (d), 132.76 (s), 147.58 (s), 148.92
products were obtained in all cases. A methanol
3
5
solution
immediately gave the corresponding
+
(
s), 178.54 (s); HREIMS: found m/z 210.0896 (M ); calcd
hydrogenolysis product in quantitative yield.
for C H O 210.0892.
11
14
4
1
9
. Compound 4: H NMR (270 MHz, CDCl ): l 3.93 (6H,
In conclusion, it is implied that a complex interaction
involving the substrate, solvent, surface of the catalyst
and hydrogen source affect the hydrogenation selectiv-
ity. The mechanism of selectivity including the surface
conditions of the catalyst is currently under
investigation.
3
s), 6.33 (1H, d, J=15.8 Hz), 6.88 (1H, d, J=8.2 Hz), 7.08
(
(
1H, d, J=1.7 Hz), 7.14 (1H, dd, J=8.2, 1.7 Hz), 7.73
13
1H, d, J=15.8 Hz); C NMR (67.8 MHz, CDCl ): l
3
5
1
1
5.85 (q), 55.94 (q), 109.68 (d), 110.97 (d), 114.95 (d),
23.07 (d), 127.01 (s), 146.82 (d), 149.19 (s), 151.43 (s),
72.44 (s); HREIMS: found m/z 208.0730 (M ); calcd for
+
C H O 208.0736.
11
12
4
1
1
0. When 1,4-dioxane was used as the reaction solvent, there
Acknowledgements
was a trace of 3 formed in several cases.
1
1. Compound 5: H NMR (270 MHz, CDCl ): l 1.30 (3H,
3
d, J=7.0 Hz), 3.83 (6H, s), 3.90–4.00 (1H, m), 5.00–5.08
This work financially supported by a Grant-in-Aid for
Scientific Research, No.12650848, from the Ministry of
Education, Science, Sports and Culture of Japan and
the Mitsubishi Chemical Corporation Fund.
(
2H, complex), 5.04 (2H, s), 5.96–6.09 (1H, m), 6.58 (1H,
13
s), 6.71 (1H, s), 7.32–7.46 (5H, complex); C NMR (67.8
MHz, CDCl ): l 19.59 (q), 35.20 (d), 56.12 (q), 56.56 (q),
3
7
1
1
2
1.80 (t), 99.84 (d), 111.58 (d), 112.82 (t), 126.33 (s),
27.33 (d), 127.82 (d), 128.50 (d), 137.46 (s), 142.94 (d),
43.48 (s), 147.58 (s), 149.79 (s); HREIMS: found m/z
References
+
98.1573 (M ); calcd for C H O 298.1569.
19
22
3
1
1
1
2. Compound 7: H NMR (270 MHz, CDCl ): l 0.87 (3H,
3
1. Newham, J. Chem. Rev. 1963, 63, 123.
t, J=7.5 Hz), 1.22 (3H, d, J=6.6 Hz), 1.60 (2H, quin,
J=7.5 Hz), 2.84 (1H, qt, J=7.5, 6.6 Hz), 3.81 (3H, s),
2. (a) Fletcher, H. G. Methods Carbohydr. Chem. II 1963,
1
4
66; (b) Bindra, J. S.; Grodski, A. J. Org. Chem. 1978,
3, 3240; (c) House, H. O. In Modern Synthetic Reac-
3
.83 (3H, s), 4.52 (1H, br. s, -OH), 6.41 (1H, s), 6.66 (1H,
13
s); C NMR (67.8 MHz, CDCl ): l 12.17 (q), 20.75 (q),
3
tions; Benjamin, W. A., Ed.; 1972; pp. 23–26.
30.12 (t), 33.82 (d), 55.92 (q), 56.76 (q), 100.86 (d), 110.94
3. (a) Iwakura, C.; Abe, T.; Inoue, H. J. Electrochem. Soc.
(
d), 123.89 (d), 143.29 (s) 146.73 (s), 147.52 (s); HREIMS:
1
996, 143, 71; (b) Inoue, H.; Abe, T.; Iwakura, C. J.
+
found m/z 210.1254 (M ); calcd for C H O 210.1256.
12
18
3
Chem. Soc., Chem. Commun. 1996, 55; (c) Yoshida, Y.;
Ogata, S.; Nakamatsu, S.; Shimamune, T.; Inoue, H.;
Iwakura, C. J. Electroanal. Chem. 1998, 444, 203–207; (d)
Inoue, H.; Yoshida, Y.; Ogata, S.; Shimamune, T.; Inoue,
H.; Iwakura, C. J. Electrochem. Soc. 1998, 145, 138–141.
. Maki, S.; Harada, Y.; Hirano, T.; Niwa, H.; Yoshida, Y.;
Ogata, S.; Nakamatsu, S.; Inoue, H.; Iwakura, C. Synth.
Commun. 2000, 30, 3575–3583.
3. For the palladinization, 6 M KOH solution was put in
the compartment having a Ni sheet anode and a Pd
cathode for the production of active hydrogen. A 1 M
HCl solution containing 28.0 mM PdCl was introduced
2
into the other compartment for the deposition of Pd
black. The palladinization was carried out by hydrogen
reduction using atomic hydrogen, which was produced by
4
−2
galvanostatic electrolysis at 10 mA cm , followed by
i
5
. Other protic solvents, for example EtOH and PrOH,
passage through the Pd sheet electrode. During the palla-
gave similar results with MeOH.
dinization, the PdCl solution was circulated at a flow
2
−1
1
6
. Compound 1: H NMR (270 MHz, CDCl ): l 3.90 (3H,
3
3
rate of 2.4 cm min using a roller pump (Furue Science,
RP-NE). For the hydrogenation reaction, the Pd black,
which was deposited on the Pd sheet, was washed with
degassed distilled water and then dried with Ar gas.
s), 3.91 (3H, s), 5.25 (2H, s) 6.36 (1H, d, J=15.8 Hz),
6
.86 (1H, d, J=8.5 Hz), 7.04 (1H, d, J=2.0 Hz), 7.10
(
(
1H, dd, J=8.5, 2.0 Hz), 7.31–7.44 (5H, complex), 7.67
13
1H, d, J=15.8 Hz); C NMR (67.8 MHz, CDCl ): l
3
14. The reaction was conducted under the same condition
used for the hydrogenation system except for the hydro-
gen source.
5
1
1
1
5.83 (q), 55.93 (q), 66.22 (t), 109.54 (d), 110.98 (d),
15.51 (d), 122.67 (d), 127.30 (s), 128.19 (d), 128.24 (d),
28.56 (d), 136.13 (s), 145.05 (d), 149.17 (s), 151.14 (s),
1
5. The structures of the substrates and the reaction products
+
66.98 (s); HREIMS: found m/z 298.1201 (M ); calcd for
were determined based on the various spectral data (IR,
1
13
C H O 298.1205.
Mass, H NMR, C NMR).
1
8
18
4
1
7
. Compound 2: H NMR (270 MHz, CDCl ): l 2.67 (2H,
16. All reactants were simply filtered and concentrated, then
3
t, J=7.2 Hz), 2.92 (2H, t, J=7.2 Hz), 3.83 (3H, s), 3.85
the generation rate and construction of the reaction
products were confirmed by measuring the H NMR
without any treatment, for example, isolating or purifying
the residue. Moreover, a further experiment was carried
out for all the reactions, and the reproducibility was
confirmed.
1
(
(
(
3H, s), 5.11 (2H, s), 6.70–6.79 (3H, complex), 7.28–7.39
13
5H, complex); C NMR (67.8 MHz, CDCl ): l 30.56
3
t), 36.12 (t), 55.76 (q), 55.88 (q), 66.23 (t), 111.28 (d),
1
1
11.63 (d), 120.10 (d), 128.15 (d), 128.19 (d), 128.51 (d),
33.01 (s), 135.90 (s), 147.48 (s), 148.87 (s), 172.73 (s);