LETTER
485
Raney Nickel: An Effective Reagent for Reductive Dehalogenation of Organic
Halides
A. F. Barrero,* E. J. Alvarez-Manzaneda,* R. Chahboun, R. Meneses, J. L. Romera
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain
Fax +34 58 24 33 18; E-mail: afbarre@goliat.ugr.es; eamr@goliat.ugr.es.
Received 25 January 2001
have described that NiCl ·2H O-Li-DTBB (cat.) reduces
organic halides in high yields.
2
2
1
Abstract: Raney Nickel is an effective reagent to achieve the
chemoselective reductive dehalogenation of organic halides. Fluo-
1
rides and vinyl halides are unreactive under the used experimental During our research into the use of Raney nickel as a
conditions.
chemoselective reductor we found that activated Raney
Key words: reduction, halides, chemoselectivity
nickel is an effective reagent in the reduction of organic
halides. Some representative examples are summarized in
the table, which shows that benzyl halides (5a-8a) and
-
halocarbonyl and related compounds (1a-3a, 9a-11a)
The present authors have previously reported the effec-
tiveness of Raney nickel to accomplish the chemoselec-
tive reduction of aldehydes in the presence of ketones and
are easily reduced after treating with Raney nickel in tet-
rahydrofuran at room temperature for 45 min-2 h. The
treatment of a solution of bromolactone 4a in tetrahydro-
furan with Raney nickel at room temperature for 5 min
yielded lactone 4b in 80%; the carbon-carbon double
bond was also reduced when the reaction was allowed to
proceed for longer times (1 h), and the lactone 4c was ob-
tained in 90%. Alkyl iodides (12a-15a) react under the
same reaction conditions after 1-6 h. Alkyl bromides
the reduction of conjugated olefins in
unsaturated
carbonyl compounds, which also contain isolated carbon-
1
,2
carbon double bonds. Our recent studies have revealed
that this reagent may also be very effective in carrying out
the chemoselective reduction of organic halides.
The replacement of halogen by hydrogen has attracted
great interest among organic chemists, stimulating con-
siderable investigation, and a number of methods have
(
2
16a-22a) exhibit lower reactivity. Alkyl chlorides (23a-
6a) were reduced under refluxing tetrahydrofuran, in the
3
been reported hitherto. A variety of reducing agents are
presence of an excess of Raney nickel (double the quanti-
ty used for the other halides); under these conditions the
carbonyl group of 25a was also reduced. Reductive deha-
logenation of chloride 23a was carried out at room tem-
perature after 1.5 h; under these conditions, the quinoline
ring was also reduced.
now available, and many of them are successfully applied
to practical organic synthesis. Metallic zinc in acetic acid
has been efficiently used for reductive dehalogenation.4
The use of metal hydrides has also been found effective.
Thus, lithium aluminum hydride reduces alkyl halides to
5
the corresponding hydrocarbons, with good yields. Sodi-
Allyl halides exhibited a different behavior which will be
reported in a forthcoming paper.
nitro, ester or carboxylic groups, which remain unaltered.6 In summary, a new synthetic application of Raney nickel
Stannanes have been used extensively to replace halogen has been developed. This reagent reduces organic halides
by hydrogen. Tri-n-butyltin hydride is able to reductively with high chemoselectivity; it has some advantages over
um borohydride in aprotic polar solvents reduces primary,
secondary, tertiary and benzyl halides, in the presence of
7
replace iodides and bromides at room temperature, and other methods, such as easy manipulation and mild condi-
chlorides under more extreme conditions; fluorides are tions. The order of reactivity is benzyl = -halocarbonyl >
not reactive. This reagent exhibits high chemoselectivity iodides > bromides > chlorides. Fluorides and vinyl ha-
and is compatible with a variety of other functional lides do not react.
groups. A drawback of this reagent is its toxicity.
Catalytic hydrogenation has also been used to achieve the
reductive dehalogenation of organic halides, the reaction
rate being dependent on the structural feature and the
halogen involved. For example, alkyl iodides and alkyl
Typical experimental procedure
1
.5 g of a slurry of commercial aqueous Raney nickel (Fluka, cat.
no. 83440)* was added to a solution of halide (150 mg) in THF
10 mL) and the mixture was further vigorously stirred at room tem-
perature or under reflux (except for chlorides, which were refluxed
(
bromides are converted into the corresponding hydrocar-
8
bons by hydrogenation over palladium on carbon. Will- in the presence of double amount of Raney nickel) for the especified
iams et al. reported that the Raney nickel catalyst is time. The mixture was diluted with ether and filtered through silica
gel, and the solvent was evaporated to yield the reduced compound.
readily deactivated by the halide during hydrogenation
and, therefore, massive amounts of the catalyst are usually * The Raney nickel was weighed as an aqueous slurry after remov-
9
,10
required in order to improve yields. Recently, Yus et al. ing four fifth of water.
Synlett 2001 No. 4, 485–488 ISSN 0936-5214 © Thieme Stuttgart · New York