Unique and convenient use of Raney nickel for the reduction of aryl bromides, benzyl alcohols, benzyl ethers, and benzylamines in an acidic medium

Article abstract of DOI:10.1246/bcsj.77.1405

A simple and convenient method for laboratory-scale reduction using Raney nickel is described. The reaction was achieved by the inclusion of sulfuric acid to a mixture of a substrate and Raney nickel. Using this method, several aryl bromides, benzyl alcohols, benzyl ethers, and benzylamines were cleaved at the carbon-bromine bond or at the benzylic position to afford corresponding hydrogenated products in good yields without the use of compressed hydrogen gas and without requiring any special apparatus.

Full text of DOI:10.1246/bcsj.77.1405

Short Articles
Bull. Chem. Soc. Jpn., 77, 1405–1406 (2004) 1405
reduction in which a number of unsaturated organic com-
pounds, such as ketones, aldehydes, Schiff’s bases, nitriles,
and nitro compounds were readily converted into correspond-
Unique and Convenient Use of Raney
Nickel for the Reduction of Aryl
Bromides, Benzyl Alcohols, Benzyl
Ethers, and Benzylamines in an
Acidic Medium
2
ing hydrogenated products in good yields. In the second appli-
cation, several types of ketones, aldehydes, and olefinic com-
pounds were reduced using Ra/Ni in the presence of sulfuric
acid to afford corresponding alcohols or alkanes in excellent
3
yields. In the case of ketones that have their carbonyl group di-
rectly to an aromatic nucleus, reduction using an excess amount
of Ra/Ni resulted in corresponding hydrocarbons. Herein, the
latter Ra/Ni–sulfuric acid method was applied for the reduction
of several aryl bromides, benzyl alcohols, benzyl ethers, and
benzylamines. It is well known that organic compounds that
bear a benzyl group attached to an oxygen, nitrogen, or halogen
tend to cleave at the benzylic position during hydrogenation
Ã
Yuji Nagata, Masanori Satoh, Satoru Sueda,
Mitsuhiro Okimoto, Yukio Takahashi,
and Tsunaki Yamashina
4
Department of Applied and Environmental Chemistry,
Kitami Institute of Technology, Koen-cho 165, Kitami,
Hokkaido 090-8507
via catalytic reduction or during a chemical reaction with so-
5
dium and mercury. Since Ra/Ni is soluble even in a weak acid,
such as acetic acid, catalytic reduction using Ra/Ni is typically
carried out under neutral or weakly basic conditions. To the
best of our knowledge, there have been no reports that describe
reductive cleavage utilizing hydrogen that is generated from
Ra/Ni, itself, under strong acidic conditions. The results of
the reduction of several aryl bromides, benzyl alcohols, benzyl
ethers, and benzylamines are given in Table 1. The optimal re-
action conditions listed in the table were determined separately
for each substrate.
Received December 4, 2003; E-mail: oki@chem.kitami-it.ac.jp
A simple and convenient method for laboratory-scale
reduction using Raney nickel is described. The reaction was
achieved by the inclusion of sulfuric acid to a mixture of a
substrate and Raney nickel. Using this method, several aryl
bromides, benzyl alcohols, benzyl ethers, and benzylamines
were cleaved at the carbon–bromine bond or at the benzylic
position to afford corresponding hydrogenated products in
good yields without the use of compressed hydrogen gas
and without requiring any special apparatus.
Although the reduction of aryl bromides (Entries 1 and 2) af-
forded the corresponding aromatic hydrocarbons in good
yields, the reduction of octyl bromide failed to proceed under
these conditions, even in the presence of excess Ra/Ni (En-
try 3). In the cases of 1-phenylethanol and 1-phenylpentanol,
the hydroxymethylene group was reduced to a methylene
ꢀ
group, even at low temperatures (10 C; Entries 5 and 6); in
contrast, the reduction of benzhydrol required elevated temper-
Raney nickel (Ra/Ni) has been widely used for the catalytic
1
ꢀ
reduction of a variety of organic compounds. Accordingly, we
atures (50 C; Entry 7). Although benzyl octyl ether was read-
have reported on two unique applications of Ra/Ni for the prep-
arative-scale reduction of organic compounds. In the first appli-
cation, Ra/Ni was employed as a cathode material for electro-
ily hydrogenated using less than an equimolar amount of Ra/Ni
(Entry 9), octyl 1-phenylethyl ether required a large excess of
Ra/Ni and MeOH to advance the reaction (Entry 11). Further-
Table 1. Reduction of Aryl Bromides, Benzyl Alcohols, Benzyl Ethers, and Benzylamines
Entry
Substratea)
Mol. ratiob)
Solvent/mL
H2O MeOH
Temp.
ꢀ
Product
Naphthalene
PhCH2Ph
n-C8H18
Yieldc)
%
C
1
2
3
4
5
6
7
8
9
1-Bromonaphthalene
4-PhCH2C6H4–Br
n-C8H17–Br
PhCH(OH)CH3
PhCH(OH)CH3
PhCH(OH)–n-C4H9
PhCH(OH)Ph
PhCH2–O–Ph
PhCH2–O–n-C8H17
PhCH2–O–CH(CH3)–n-C6H13
PhCH(CH3)–O–n-C8H17
PhCH2–NHPh
1.5
2.5
3.0
0.6
1.2
1.2
1.2
2.0
0.8
1.0
4.0
1.2
1.2
1.2
30
10
5
30
70
50
0
0
0
20
40
50
10
10
10
50
40
30
30
50
40
40
40
93
90
(9)
(51)
81
92
89
92
94
93
91
92
85
84
50
50
50
50
30
20
20
5
PhC2H5
PhC2H5
Ph-n-C5H11
PhCH2Ph
PhOH
n-C8H17OH
n-C6H13CH(CH3)OH
n-C8H17OH
PhNH2
0
70
50
50
95
30
30
30
10
11
12
13
14
30
30
30
PhCH2–N(n-C4H9)2
PhCH2–N(CH3)Ph
(n-C4H9)2NH
PhNHCH3
a) Substrate: 25 mmol. b) Ra/Ni (molar amount)/Substrate (mol). c) Isolated yields based on substrates. Value in parenthesis was
determind by GLC analysis.
Published on the web July 9, 2004; DOI 10.1246/bcsj.77.1405

1
406 Bull. Chem. Soc. Jpn., 77, No. 7 (2004)
Ó 2004 The Chemical Society of Japan
more, our results show that the amount of Ra/Ni has a signifi-
cant effect on the yields of the products. For example, in the
case of 1-phenylethanol, reducing the molar ratio of Ra/Ni
from 1.2 to 0.6 resulted in a decreased yield of ethylbenzene
from 81 to 51% (Entries 4 and 5) with unreacted substrate. It
is interesting to note that, when dissolved completely by the ad-
dition of sulfuric acid, the evolved hydrogen gas from the Ra/
Ni was approximately 1.5 times by volume as compared to that
from an equal weight of ordinary nickel powder. As a note, in
all cases the hydrogenation product of the aromatic moiety was
not detected.
was cooled to room temperature, and then subsequently warmed
ꢀ
in a water bath (70 C) with occasional shaking for 30 min. The
resulting Ra/Ni (approximately 2.15 g, 37 mmol) was washed
with water (3 Â 50 mL), and was used immediately.
Typical Procedures for the Reduction. In a 100- or 200-mL
three-necked round-bottomed flask equipped with a reflux con-
denser and a dropping funnel, the substrate (25 mmol) was dis-
solved in the solvents and in the presence of Ra/Ni, as listed in
Table 1. To the mixture, sulfuric acid was added dropwise using
a dropping funnel over a period of ca. 2 h (60% w/w H2SO4 aq
1
2 mL per each 37 mmol of Ra/Ni). During the course of the re-
action, the mixture was magnetically stirred to avoid the formation
of any lumps. Ra/Ni was almost completely dissolved upon the ad-
dition of sulfuric acid; however, any solid residues were removed
by filtration using suction. After saturating the filtrate with sodium
chloride, the oily layer was extracted with ether (3 Â 50 mL). The
combined ether extracts were washed with aqueous sodium hydro-
gencarbonate (3% w/w, 30 mL) and dried over anhydrous magne-
sium sulfate. Upon removal of the ether solvent, the resulting res-
idue was further purified by distillation under reduced pressure. In
the cases where the product was an amine, the filtrate was alkalified
before extraction by the addition of aqueous sodium hydroxide
(25% w/w), followed by an appropriate amount of saturated aque-
ous sodium chloride to avoid possible complications due to the for-
mation of colloidal nickel hydroxide under basic conditions.
Although the details of the reaction mechanism of this reduc-
tion remain unclear, it can be suggested that the reaction pro-
ceeds by consuming both the adsorbed hydrogen on the Ra/
Ni and the hydrogen generated by the reaction between Ra/
Ni and sulfuric acid. Presumably, the hydrogen is activated
on fresh nickel surfaces that are ceaselessly renewed during
the reaction. In the initial stages of the hydrogenation, most
of the substrates are adsorbed on the Ra/Ni surfaces. As the re-
action proceeds, the substrates gradually react with the hydro-
gen formed between Ra/Ni and sulfuric acid to produce the
corresponding hydrogenated products, along with the dissolu-
tion of Ra/Ni into nickel sulfate. In this reductive methodolo-
gy, it can be said that Ra/Ni plays an important role not only
as a catalyst, but also as the hydrogen source.
The advantages of this reduction method are that the reaction
can be carried out without use of extraneous hydrogen, and
does not require any counter-pressure apparatus, such as an au-
toclave at reaction temperatures lower than 50 C. Overall, hy-
drogenated products were obtained in high yields by relatively
simple handling procedures.
References
1
For examples, see: a) J. S. Pizey, ‘‘Synthetic Reagents,’’
Ellis Horwood (1974), Vol. 2, p. 175. b) W. H. Hartung and R.
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Vol. 7, p. 263. c) R. Schroter, ‘‘Newer Methods of Preparative
Organic Chemistry,’’ Interscience Pub. (1948), p. 61.
ꢀ
2
T. Chiba, M. Okimoto, and H. Nagai, Bull. Chem. Soc. Jpn.,
6, 719 (1983).
M. Okimoto, T. Chiba, and Y. Takata, Nippon Kagaku
Kaishi, 1985, 1671.
Experimental
5
All of the products were identified by comparing their physical
and spectral data with those of authentic samples. Benzyl ethers
and benzylamines were prepared according to typical Williamson
syntheses and alkylation of amines, respectively. Other reagents
were obtained from commercial suppliers, and were used without
further purifications.
Typical Procedures for the Development of Ra/Ni. To a sus-
pension of Raney nickel alloy (4.3 g; content of Ni, 50% w/w;
Wako Pure Chemical Industries, Ltd.) in distilled water (40 mL)
in a 200-mL round-bottomed flask was added sodium hydroxide
3
4
a) S. Nishimura, Yuki Gosei Kagaku Kyokaishi, 19, 499
6
7
(1961). b) S. Nishimura, Bull. Chem. Soc. Jpn., 32, 1155 (1959).
c) A. G. Anderson, Jr. and R. Lok, J. Org. Chem., 37, 3953 (1972).
5 W. R. Brasen and C. R. Hauser, Org. Synth., Coll. Vol. IV,
508 (1963).
6 M. Onaka, M. Kawai, and Y. Izumi, Bull. Chem. Soc. Jpn.,
59, 1761 (1986).
7 F. G. Willson and T. S. Wheeler, Org. Synth., Coll. Vol. I,
102 (1941).
(
6.5 g). After allowing to stand for several minutes, the mixture