130 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 130±131$
Indium-mediated Reaction in Aqueous Media.
Synthesis of Phenacyl Sul®des by Reactions of
ꢀ-Bromoketones with Sodium Alkyl Thiosulfates$
Zhuangping Zhan, Yongmin Zhang* and Zhenghai Ma
Department of Chemistry, Hangzhou University, Hangzhou, 310028, P.R. China
Phenacyl sul®des are synthesized in moderate to good yields via reaction of ꢀ-haloketones with sodium alkyl thiosulfates
promoted by indium metal in aqueous media.
Metal-mediated reactions in aqueous media have recently
found considerable application in organic synthesis.1 Such
organometallic-type reactions in aqueous media have many
advantages. The most general worth in changing organo-
metallic reactions from strictly anhydrous organic solvents
to aqueous media is the ease of reaction in obviating
the need for in¯ammable anhydrous organic solvents and
troublesome inert atomospheres. For some reactions, for
example, alkylations of carbonyl groups in carbohydrates,
it is a great advantage that the substrates do not need ®rst
to be converted as they would be when using organic
solvents.2
conditions. However the type of reaction promoted by
indium seems to have been somewhat limited. The most
useful is the coupling of allylic halides with carbonyl
compounds in aqueous media to give the corresponding
homoallylic alcohols.
Here we report a novel reaction of a-haloketones with
sodium alkyl thiosulfates promoted by indium metal in
aqueous media.
The choice of metal in organometallic reactions in
aqueous media is however limited,2 the most commonly
used metals being zinc, tin and indium. Bismuth±zinc or
BiCl3±Al, BiCl3±Zn and BiCl3±Fe systems are also eective
for the allylation of carbonyl compounds and benzotriazole
intermediates.3
Compared to the use of zinc and tin where acid catalysis,
heat or sonication are often required, reactions with indium
usually possess the advantage of not needing any promoter,
and therefore indium-mediated organometallic reactions in
aqueous media have recently found considerable application
in organic synthesis. They have been used in the allylation
and propargylation of carbonyl compounds,2,4 the allylation
of the carbonyl group in b-oxoesters (which is extremely
dicult using organometallic reagents such as allylic mag-
nesium bromide and organolithium compounds because of
the acidity of the hydrogen on the carbon inbetween the
two carbonyl groups),5 bis-allylation of 1,3-dibromopropene
with carbonyl compounds at the same carbon,6 reductive
coupling of aldimines,7 etc.
In our experiments, we observed that no disul®des were
obtained. Thus we suggest that the reaction does not pro-
ceed via electron transfer from indium to the alkyl thio-
sulfate but involves an enolate intermediate, although we
have not enough proof to clarify this. Unlike other reactions
induced by indium, the present reaction is very slow at
room temperature and must be conducted at 60±65 8C.
Sul®des are a class of useful synthetic intermediates,
and many methods have been reported for their prep-
aration.12±15 Very recently, our group have reported that an
organosamarium reagent reacts with disul®des to aord
allyl sul®des.16 However the reaction must be conducted in
strictly anhydrous solvent and under an inert atmosphere.
In contrast, the present method circumvents these problems,
the reaction being carried out in aqueous tetrahydrofuran
solution and in the air. In view of the ready availability
of the starting materials, the simplicity of the synthetic
procedures, the mild reaction conditions and the moderate-
to-good yields of products, we consider that the present
procedure provides a novel practical route to phenacyl
sul®des.
Recently, we have reported that allylic and propargyl
bromides react with diorganyl diselenides in aqueous media
promoted by indium to give allylic and propargyl
selenides.8 This method oers some distinct advantages,
such as use of aqueous media and of mild and neutral
Table 1 Conditions, products, yields and mps
Reaction
time (t/h)
Yield
(%)a
Mp (T/8C)
(Lit.)
Entry
X
R
Product
a
b
c
d
e
f
H
H
H
H
H
H
Br
Br
PhCH2
C16H33
C12H25
C10H21
C8H17
C7H15
PhCH2
C12H25
18
15
15
15
15
15
18
15
PhCOCH2SCH2Ph
PhCOCH2SC16H33
PhCOCH2SC12H25
PhCOCH2SC10H21
PhCOCH2SC8H17
80
83
87
82
81
80
78
81
86±88(89)9
40±41
32±34(34±35)10
oil11
oil
oil
158±159
104±106
PhCOCH2SC7H15
p-BrC6H4COCH2SCH2Ph
p-BrC6H4COCH2SC12H25
g
h
aYields of isolated phenacyl sul®des based on RSSO3Na.
Experimental
*To receive any correspondence (e-mail: zgd@public.hz.zj.cn).
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
Typical Procedure.ÐIn a 50 mL round-bottomed ¯ask ®tted with
a re¯ux condenser were placed indium (1 mmol) in the form of
small grains cut from a bar of indium metal, sodium alkyl thio-
Zhan, Zhuangping
