ephedrine-rani-1, biotransformation
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Applied Catalysis A: General 219 (2001) 281–289
Transfer hydrogenolysis of aromatic alcohols using
Raney catalysts and 2-propanol
Benjamin H. Gross
1
, Robert C. Mebane
∗
, David L. Armstrong
Department of Chemistry, University of Tennessee at Chattanooga, Chattanooga, TN 37403–2598, USA
Received 9 February 2001; received in revised form 8 June 2001; accepted 10 June 2001
Abstract
Raney nickel in refluxing 2-propanol is an effective catalytic system for cleaving C–O bonds in aromatic alcohols by transfer
hydrogenolysis. Deoxygenation of alcohols substituted at the
-positions was accomplished. The reaction
appears not to be sensitive to substitution about the carbinol carbon. Aliphatic alcohols do not undergo hydrogenolysis with
this system. Some dehydromethylation is found in the hydrogenolysis of primary alcohols. With extended reaction times,
ring reduction accompanies hydrogenolysis of alcohols containing more than one aromatic ring. Raney cobalt is shown to
catalyze hydrogen transfer from 2-propanol. Raney cobalt in refluxing 2-propanol is an effective system for deoxygenating
-,
-,
-,
-, and
ε
-substituted alcohols only. Although Raney cobalt is less reactive than Raney nickel in transfer hydrogenolysis, it exhibits
greater selectivity as illustrated by the lack of ring reduction in alcohols containing more than one aromatic ring. © 2001 Elsevier
Science B.V. All rights reserved.
Keywords:
Raney nickel; Raney cobalt; Catalytic transfer hydrogenolysis; Hydrogen donor; Deoxygenation of aromatic alcohols
1. Introduction
of hydrogen from a variety of hydrogen donors [3,4].
2-Propanol is a useful donor because of its simplic-
ity, ready availability, and ease of use. Although the
literature is somewhat sparse, Raney nickel catalyzed
transfer hydrogenations utilizing 2-propanol have
been reported for the reduction of olefins [6], ketones
[6–8], phenols [6], aromatic nitro compounds [9–11],
and certain aromatic hydrocarbons [6,12].
Our own interest in this area was piqued by the
observation
Raney nickel is widely recognized as a versatile
catalyst for effecting reductive transformations of or-
ganic compounds [1,2]. Less well known and utilized
is Raney nickel’s ability to catalyze reductions us-
ing hydrogen donors instead of molecular hydrogen
[3,4]. Known as catalytic transfer hydrogenation, this
remarkable reaction was first described 50 years ago
by Kleiderer and Kornfeld [5] in their study on the
Raney nickel catalyzed transfer of hydrogen from
cholesterol to cyclohexanone. Since the first report,
Raney nickel has been shown to catalyze the transfer
of
Andrews
and
Pillai
[6]
that
ben-
zyl alcohol, benzhydrol and
-tetralol can undergo
hydrogenolysis with Raney nickel in refluxing
2-propanol. Catalytic hydrogenolysis of benzyl alco-
hols with molecular hydrogen has long been known
[13]. Indeed, catalytic hydrogenolysis of C–O bonds
∗
Corresponding author. Tel.:
+
1-423-755-4709;
to an aromatic ring in derivatives of benzyl alco-
hols has made the benzyl group a useful protecting
group in multistep synthesis [14,15]. Interestingly, so
fax:
+
1-423-755-5234.
E-mail address:
robert-mebane@utc.edu (R.C. Mebane).
1
Co-corresponding author.
0926-860X/01/$ – see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0926-860X(01)00700-1
282
B.H. Gross et al. / Applied Catalysis A: General 219 (2001) 281–289
Grace Company, Chattanooga Davison. The Raney
®
2800 nickel has a BET surface area of 82 m
2
/g and a
particle size range of 45–90 mm [22]. Raney
®
2700
cobalt has a BET surface area of 12 m
2
/g and a parti-
cle size range of 20–50 mm [22]. The Raney catalysts
were washed prior to use with distilled water (six
times) and 2-propanol (three times) and stored in
2-propanol.
CAUTION
: Raney nickel is a pyrophoric solid
when dry and may ignite spontaneously in air.
far as we know, the hydrogenolysis of alcohols under
hydrogen transfer conditions utilizing Raney nickel
and 2-propanol has not been systematically studied.
Furthermore, hydrogen transfer from 2-propanol with
Raney cobalt has not been reported. Thus, as part of
our continuing work on transfer hydrogenations with
Raney catalysts and 2-propanol, we wish to describe
how Raney nickel in refluxing 2-propanol efficiently
deoxygenates aromatic alcohols under neutral con-
ditions. In addition we wish to report that Raney
cobalt does catalyze the transfer of hydrogen from
2-propanol and that the decreased reactivity of this
catalyst is warranted in the hydrogenolysis of benzyl
alcohols to suppress certain side reductions which can
be encountered with Raney nickel. The mild condi-
tions employed in these reactions offer considerable
advantages over the conventional method of catalytic
hydrogenolysis as neither hydrogen containment nor
a pressure vessel is required.
2.1. General procedure for Raney nickel catalyzed
hydrogenolysis of aromatic alcohols
The alcohol (2 g) was added to a mixture of Raney
nickel (5 g) in 2-propanol (30 ml). While open to
the atmosphere, the reaction mixture was vigor-
ously stirred and refluxed (water-cooled condenser
attached to flask) for the times indicated for the
individual alcohols listed in Tables 1–3. Aliquots
were removed at 0.25 h intervals and analyzed by
GC–MS. The yields reported in Tables 1–3 represent
percentage conversion of the starting alcohol to re-
duced product as determined by peak areas and are
the average of at least two reactions. Isolation of the
reduced product involved decanting the 2-propanol
solution, washing the Raney nickel with 2-propanol
(3
2. Experimental
1,2-Diphenylethanol (66.5–67.5
◦
C, lit. mp 67
◦
C
[16]) and 1-(2-fluorenyl)ethanol (mp 138–139
◦
C,
lit. mp 139–140
◦
C [17]) were prepared by sodium
borohydride reduction of 1,2-diphenylethanone and
2-acetylfluorene, respectively. The remaining alcohols
used in this study were available from commercial
suppliers and were used as obtained unless impuri-
ties were detected by GC analysis in which case the
alcohols were purified by distillation or recrystal-
lization. All alcohols used in this study were found
by GC analysis to have a purity in excess of 98%.
Progress of the hydrogenolysis reactions was moni-
tored by GC–MS using a fused silica capillary col-
umn (methyl 50% phenyl silicone, 25 m
10 ml), filtering the combined 2-propanol layers
through celite, and evaporation of the 2-propanol and
acetone.
×
2.2. General procedure for Raney cobalt catalyzed
hydrogenolysis of aromatic alcohols
This procedure was identical to that described above
for Raney nickel except that 4 g of Raney cobalt were
used in the reductions.
×
0
.
25 mm
i.d.,
m film thickness). With the exception
of those that follow, the products were identified
by comparison of retention times and fragmenta-
tion patterns with authentic samples. 2-Ethylfluorene
[18], 5,6,7,8-tetrahydro-2-ethylnaphthalene [19], 1,2,
3,4-tetrahydro-2-ethylnaphthalene [19], 5,6,7,8-tetra-
hydro-1-ethylnaphthalene [19], 1-cyclohexyl-2-phen-
ylethane [20], and
ci
s-hexahydrofluoren-9-one [21]
were found to have physical or spectral properties
identical to published reports. Raney
®
0.25
3. Results and discussion
All of the aromatic alcohols used in this study
with the exception of 1,2-diphenylethanol and
1-(2-fluorenyl)ethanol were available from commer-
cial suppliers. 1,2-Diphenylethanol and 1-(2-fluorenyl)
ethanol were conveniently prepared by sodium boro-
hydride reduction of 1,2-diphenylethanone and 2-
acetylfluorene, respectively (see Section 2). Tables 1–3
2800 nickel
and Raney
®
2700 cobalt were obtained from W.R.
B.H. Gross et al. / Applied Catalysis A: General 219 (2001) 281–289
283
Table 1
Raney nickel and Raney cobalt catalyzed transfer hydrogenolysis of benzylic alcohols with 2-propanol (one aromatic ring)
Entry
Substrate
Raney catalyst
Time (h)
Product(s)
Yield (%)
1
Benzyl alcohol
Ni
1.0
Toluene
87
Benzene
7
Benzaldehyde
4
Co
3.0
Toluene
95
2
4-Isopropylbenzyl alcohol
Ni
0.25
4-Isopropyltoluene
90
Isopropylbenzene
10
8
a
Co
24
4-Isopropyltoluene
3
4-Methoxybenzyl alcohol
Ni
0.25
4-Methoxytoluene
88
Methoxybenzene
9
Toluene
2
35
a
Co
24
4-Methoxytoluene
4
1-Phenylethanol
Ni
0.25
Ethylbenzene
96
Co
3.0
Ethylbenzene
100
5
1-(
p
-Tolyl)ethanol
Ni
0.50
4-Ethyltoluene
99
Co
24
4-Ethyltoluene
96
6
1-(4-Methoxyphenyl)ethanol
Ni
0.25
4-Methoxyethylbenzene
94
Ethylbenzene
6
6.0
4-Methoxyethylbenzene
46
Ethylbenzene
54
Co
24
4-Methoxyethylbenzene
92
7
1-Phenyl-1-butanol
Ni
0.25
Butylbenzene
98
Co
1.0
Butylbenzene
100
8
1-Phenyl-1-pentanol
Ni
0.25
Pentylbenzene
100
Co
2.0
Pentylbenzene
100
9
2,2-Dimethyl-1-phenyl-1-propanol
Ni
4.0
2,2-Dimethyl-1-phenylpropane
100
9
a
Co
24
2,2-Dimethyl-1-phenylpropane
10
Ethyl mandelate
Ni
1.0
Ethyl phenylacetate
100
Co
8.0
Ethyl phenylacetate
98
11
2-Phenyl-2-propanol
Ni
0.25
Isopropylbenzene
100
Co
3.5
Isopropylbenzene
99
12
1-Phenyl-1-cyclohexanol
Ni
0.25
Cyclohexylbenzene
100
Co
7.0
Cyclohexylbenzene
99
a
Remainder is starting material.
summarize the 31 aromatic alcohols investigated in
this study. The experimental procedure for the transfer
hydrogenolysis reaction is simple and straightforward.
To illustrate, the alcohol is stirred magnetically with
a suspension Raney catalyst in refluxing 2-propanol
while open to the atmosphere. The substrate to cat-
alyst ratio was 2:5 by weight for Raney nickel and
2:4 by weight for Raney cobalt. The catalyst loading
for Raney nickel is comparable to that used by others
reporting on hydrogen transfer reactions [11,12,23].
As described later, we find that the catalytic activity
of the Raney catalysts is retained after repeated use.
The progress of the reactions was conveniently moni-
tored by GC–MS. The reduced products were readily
isolated after filtration through celite to remove the
Raney catalyst followed by solvent removal. Products
were identified whenever possible by comparison
of retention times and fragmentation patterns with
authentic samples or by comparison with published
physical and spectral data (see Section 2).
284
B.H. Gross et al. / Applied Catalysis A: General 219 (2001) 281–289
Table 2
Raney nickel and Raney cobalt catalyzed transfer hydrogenolysis of benzylic alcohols with 2-propanol (two or more aromatic rings)
Entry
Substrate
Raney catalyst
Time (h)
Product(s)
Yield (%)
1
1,2-Diphenylethanol
Ni
1.0
Bibenzyl
97
5.0
1-Cyclohexyl-2-phenylethane
99
Co
1.5
Bibenzyl
100
2
Benzhydrol
Ni
0.25
Diphenylmethane
91
Cyclohexylphenylmethane
4
10
Cyclohexylphenylmethane
96
Co
1.0
Diphenylmethane
100
3
Triphenylmethanol
Ni
0.25
Triphenylmethane
96
Diphenylcyclohexylmethane
4
24
Triphenylmethane
65
Diphenylcyclohexylmethane
33
80
a
Co
24
Triphenylmethane
4
9-Hydroxyfluorene
Ni
1.0
Fluorene
33
Hexahydro-9-fluorenone
67
Complex mixture
b
24
Co
0.75
Fluorene
100
5
Dibenzosuberenol
Ni
0.50
Dibenzosuberane
100
Co
1.0
Dibenzosuberene
93
6
1-(2-Fluorenyl)ethanol
Ni
1.0
2-Ethylfluorene
95
4.0
2-Ethylfluorene
64
Ring reduced products
c
36
Co
2.0
2-Ethylfluorene
100
7
1-(1-Naphthyl)ethanol
Ni
4.0
5,6,7,8-Tetrahydro-1-ethylnaphthalene
84
1,2,3,4-Tetrahydro-1-ethylnaphthalene
16
Co
0.75
1-Ethylnaphthalene
100
8
1-(2-Naphthyl)ethanol
Ni
4.0
5,6,7,8-Tetrahydro-2-ethylnaphthalene
82
1,2,3,4-Tetrahydro-2-ethylnaphthalene
14
Co
0.50
2-Ethylnaphthalene
100
84
d
9
1-(4-Biphenylyl)ethanol
Ni
0.50
4-Ethylbiphenyl
Ring reduced products
e
24
Co
5.0
4-Ethylbiphenyl
98
a
Remainder is starting material.
b
GC–MS suggests mostly hexahydrofluorene.
c
GC–MS suggests a 1:1 mixture of 2-ethyl- and 7-ethyl-2,3,4,4
,9,9
-hexahydrofluorene.
d
GC–MS suggests that remainder is 1-(4-cyclohexylphenyl)ethanol.
e
GC–MS and
1
H NMR suggests a nearly 1:1 mixture of 1-cyclohexyl-4-ethylbenzene and
trans
-1-ethyl-4-phenylcyclohexane.
3.1. Raney nickel reductions
For the alcohols 1-phenyl-1-cyclohexanol, 1-phenyl-1-
pentanol, and dibenzosuberenol the isolated yields of
the hydrogenolysis products were 91, 80 and 94%,
respectively.
As evidenced by the reaction times reported in
Table 1, secondary and tertiary benzyl alcohols con-
taining a single aromatic ring (entries 4–12) un-
dergo rapid hydrogenolysis with Raney nickel and
2-propanol to give alkylbenzenes in excellent yields.
Aromatic alcohols are readily deoxygenated by
transfer hydrogenolysis with Raney nickel and
refluxing 2-propanol as seen in Tables 1–3. The
hydrogenolysis reaction is generally complete in a
matter of a few minutes to a few hours. The yields
reported in Tables 1–3 represent percentage con-
version of starting alcohol as determined by GC.
B.H. Gross et al. / Applied Catalysis A: General 219 (2001) 281–289
285
Table 3
Raney nickel and Raney cobalt catalyzed transfer hydrogenolysis of non-benzylic aromatic alcohols with 2-propanol
Entry
Substrate
Raney catalyst
Time (h)
Product(s)
Yield (%)
1
2-Phenylethanol
Ni
3.0
Ethylbenzene
80
Toluene
17
17
a
Co
24
Ethylbenzene
2
1-Phenyl-2-propanol
Ni
0.50
Propylbenzene
100
34
a
Co
24
Propylbenzene
3
1-Phenyl-2-butanol
Ni
0.50
Butylbenzene
100
17
a
Co
8.0
Butylbenzene
41
a
24
Butylbenzene
4
2-Methyl-1-phenyl-2-propanol
Ni
0.75
Isobutylbenzene
98
2
a
<
Co
24
Isobutylbenzene
5
3-Phenyl-1-propanol
Ni
2.0
Propylbenzene
80
Ethylbenzene
20
Co
24
No reaction
6
4-Phenyl-2-butanol
Ni
3.0
Butylbenzene
98
Co
24
No reaction
7
2-Methyl-4-phenyl-2-butanol
Ni
0.75
Isopentylbenzene
100
Co
24
No reaction
8
4-Phenyl-1-butanol
Ni
10
Butylbenzene
67
Propylbenzene
33
Co
No reaction
95
b
9
5-Phenyl-2-pentanol
Ni
7.0
Pentylbenzene
Co
24
No reaction
10
5-Phenyl-1-pentanol
Ni
6.0
Pentylbenzene
81
Butylbenzene
19
Co
24
No reaction
a
Remainder is starting material.
b
The MS of the remainder is consistent with 5-cyclohexyl-2-pentanol.
Hydrogenolysis of both the hydroxyl group and the
methoxy group occurs in the Raney nickel catalyzed
reaction of 1-(4-methoxyphenyl)ethanol (Table 1, en-
try 3). Loss of the hydroxyl group is much faster
than the hydrogenolysis of the methoxy group. Thus,
15 min into the reaction all of the starting alcohol is
consumed and 4-methoxyethylbenzene, the expected
product of alcohol hydrogenolysis, is the major prod-
uct (88%). If the reaction is allowed to proceed for
a longer time, then hydrogenolysis of the methoxy
group to give ethylbenzene becomes significant.
In addition to the expected hydrogenolysis prod-
ucts, the three primary benzyl alcohols used in this
study (Table 1, entries 1–3) give to a small extent
deoxygenated products containing one less carbon.
Andrews and Pillai [6] observed a similar result in
their Raney nickel study with benzyl alcohol. This
dehydromethylation reaction of primary alcohols with
nickel catalyst is not without precedence. For ex-
ample, dehydromethylation of primary alcohols has
been observed with Ni/Al
2
O
3
catalyst [24] and with
Raney nickel in refluxing toluene [23,25]. The most
likely origin of this dehydromethylation side reaction
involves the reversible nickel catalyzed oxidation of
the primary alcohol to an aldehyde followed by a
decarbonylation step which is well known [26].
As seen in Table 2, benzyl alcohols containing
more than one aromatic ring undergo hydrogenol-
ysis with Raney nickel in refluxing 2-propanol. In
addition, prolonged reaction times can lead to ring
reduction by transfer hydrogenation. To illustrate, hy-
drogenolysis of 1,2-diphenylethanol (Table 2, entry
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