Simple Oxidation of Thiols with Sodium lodate under Solid-Solution Biphasic Conditions

Article abstract of DOI:10.1039/a804667k

A variety of aromatic, aliphatic, and alicyclic thiols were readily oxidised with a combination of sodium iodate and Chromatographic neutral alumina in hexane to afford the corresponding disulfides in excellent yields under mild and neutral conditions.

Full text of DOI:10.1039/a804667k

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816 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 816±817$
Simple Oxidation of Thiols with Sodium Iodate
under Solid±Solution Biphasic Conditions$
Masao Hirano,* Sigetaka Yakabe, Ken-ichiro Ando and
Takashi Morimoto
Department of Applied Chemistry, Faculty of Technology, Tokyo University of Agriculture and
Technology (TUAT), Koganei, Tokyo, 184-8588, Japan
A variety of aromatic, aliphatic, and alicyclic thiols were readily oxidised with a combination of sodium iodate and
chromatographic neutral alumina in hexane to afford the corresponding disulfides in excellent yields under mild and
neutral conditions.
Much e€ort has been invested in realising selective
oxidations of organic compounds.1 The majority of con-
ventional methods require the use of large amounts of
heavy metal salts (Cr6‡, Pb4‡, Hg2‡, Tl3‡, Se4‡ etc.) to
e€ect the reactions, and therefore su€er frequently from the
disposal problem of quantities of toxic wastes and a lack of
economical applicability. When recent environmental and
economical constraints2 are taken into consideration, these
processes may no longer be attractive as synthetic methods.
Improved procedures are based either on the combined use
of a metal salt as the catalyst and a clean reagent as the
terminal oxidant or on the replacement of a stoichiometric
oxidant with a safer reagent, thus reducing or eliminating
toxic chemicals at source. In the latter context, it may be of
considerable interest to use inorganic oxohalogen acid
derivatives, since the reagents are inexpensive and safe to
handle,% and the oxidant residues are in general environ-
mentally compatible and can easily be removed from the
®nal reaction mixtures.
Contrary to extensive investigation into periodate-based
reactions,4 sodium iodate (NaIO3, 1) appears to be less
attractive as a laboratory oxidizing agent. Earlier reactions
using 1, of which we are aware, are those on the oxidative
alkoxylation of 1,2-naphthoquinone,5a oxidation of di-
hydroxyarenes to quinones5b and of a number of functional
groups5c under aqueous conditions. Consequently, those
methods are unavoidably accompanied by laborious work-
ups of products and production of large volume aqueous
e‚uents. The latest work5c indeed included the oxidation
of thiols at elevated temperature, but examined only
two substrates, viz. 2e and 2k (see Scheme 1), and thus
lacked generality; moreover, the yields of the disul®des
were not indicated. Our previous observation that 1 in
absolute methanol gives a facile oxidation of catechol to
4,5-dimethoxy-o-benzoquinone6 might suggest that 1 can
favorably be used in a dry medium. Consequently, we have
tested the synthetic potential of 1 for the oxidation of
thiols7 in an aprotic solvent, since the new procedure could
eliminate experimental problems inherent to this type of
reagent.
An attempted reaction carried out by simply stirring a
mixture of 1 and a thiol 2 in hexane, however, was sluggish
and failed to give the disul®de 3 in a synthetically useful
yield within a reasonable period of time. GLC analysis
of the reaction mixture of benzenethiol 2a, for example,
showed that only 34% of diphenyl disul®de 3a was obtained
from a 1 h reaction at 20 8C and 66% of 2a remained
unreacted. Prolonged reaction achieved 100% conversion
(ca. 3 h; 2a 100%), but test runs at elevated temperatures
(40 8C and under gentle re¯ux) resulted in decreased
conversions (44 and 27%, respectively), and therefore
NaIO3 in hexane is unattractive for the present purpose.
It might be expected that the oxidation could conveniently
be performed under mild conditions within a shorter reac-
tion period by making use of the catalytic e€ect of solid
supports.8 Thus, 2a was then treated with 1 in the presence
of untreated (commercial) and predried alumina for 30 min
at 20 8C, but these reactions achieved only 20 and 18% con-
versions, respectively. On the other hand, use of alumina
preloaded with an optimum amount of water (moist
alumina) achieved 100% conversion. Filtration, followed
by removal of the solvent gave a quantitative yield of
3a with satisfactory purity (entry 1 in Table 1). Another
control experiment performed under hexane±water biphasic
conditions without adding alumina gave 3a in only 55%
yield, clearly indicating that moist alumina catalyses the
reaction. It should be noted that the set-up of the moist
alumina-based reaction and the work-up of the product
are straightforward, and the reaction can be accomplished
under much milder conditions than those of the earlier
procedure.5c In addition, from environmental and econom-
ical points of view, use of hexane as the solvent should be
favorable.
NaIO3,
Moist alumina,
Hexane
±
2 R SH
± ± ±
4R S S R
20 8C, 0.5±2 h
2
3
2,3
R
2,3
R
2,3
R
a
b
c
d
e
f
Ph
g
h
i
j
k
l
2-ClC6H4
3-ClC6H4
4-ClC6H4
4-O2NC6H4
PhCH2
C6H13
m
n
o
p
q
r
C8H17
4-MeOC6H4
2-MeC6H4
3-MeC6H4
4-MeC6H4
4-BrC6H4
C10H21
C12H25
C14H29
c-C5H9
c-C6H11
The NaIO3/moist alumina system can successfully be
used for the oxidation of substituted benzenethiols 2b±j,
regardless of the electronic properties of the substituents
(entries 2, 5, 6, 9, and 10) and their positions on the benzene
ring (entries 3±5 and 7±9). Aralkyl thiol 2k, aliphatic thiols
bearing medium to long alkyl chains 2l±p, and alicyclic
thiols 2q,r also underwent smooth oxidation, a€ording the
corresponding disul®des in nearly quantitative yields from
1±2 h reactions.
Oxidative coupling of 2 to 3 has been a subject of
extensive research7 and many reagent systems are currently
available, but some limitations and/or diculties in
their performance have been pointed out.9 The simple,
Scheme 1
*To receive any correspondence. Fax: ‡81-423-88-7033
$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).
%Some safety assessments of sodium iodate have recently been
made.3

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J. CHEM. RESEARCH (S), 1998 817
Table 1 Oxidative coupling of thiols 2 to disulfides 3 with NaIO3 and aluminaa
Entry No.
t/h
Disulfide (%)b
Entry No.
t/h
Disulfide (%)b
1
2
3
4
5
6
7
8
9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
3a (quant.)
3b (98)
3c (99)
3d (94)
3e (95)
3f (95)
3g (99)
3h (92)
3i (99)
10
11
12
13
14
15
16
17
18
0.5
1
1
3j (98)
3k (quant.)
3l (96)
3m (99)
3n (quant.)
3o (quant.)
3p (quant.)
3q (97)
1
1.5
1.5
1.5
1.5
2
3r (98)
aUnder argon, at 20 8C; 1mmol of thiol 2, 2 mmol of NaIO3, 1g of freshly prepared moist alumina, and
10 ml of hexane were used in every run. bIsolated yield of disulfide 3 based on the starting material 2.
inexpensive procedure demonstrated here gives a rapid,
We thank Dr Masahiro Natsume for the provision of
GC±MS facilities at TUAT.
mild, clean oxidation of a wide range of thiols, and
therefore could be a method of choice for the synthesis of
symmetrical disul®des.
Received, 18th June 1998; Accepted, 1st September 1998
Paper E/8/04667K
Experimental
General.Ð1H NMR spectra were recorded with a JEOL PMX-60
(60 MHz) spectrometer for solutions in CDCl3 using Me4Si as an
internal standard. Analytical GLC was performed on a Shimadzu
References
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GC-4CM instrument, equipped with
diameter glass column packed with 3% Silicone OV-17 on Uniport
HP and interfaced with Shimadzu Chromatopac C-R6A
a
FID via
a
2 m 5 mm
a
integrator, with temperature programming. Melting points were
determined on a Yanagimoto MP-S3 melting point apparatus and
are uncorrected. thiols 2a±r and reagent grade NaIO3 powder
(Kanto Chemical, Japan) were used as received from commercial
sources. Moist alumina (H2O content, 17 wt%) was prepared by
adding deionised water (0.2 g) in portions to oven-dried (500 8C,
1 h) chromatographic neutral alumina (ICN Biomedical, Alumina
N, Super I; 1 g), followed by vigorous shaking of the mixture after
every addition for a few min until a free-¯owing powder was
obtained.
Oxidation Procedure.ÐA 30 ml two-necked round-bottomed
¯ask, equipped with a Te¯on-coated stirrer bar, a re¯ux condenser,
and a gas-inlet tubing connected to a dry argon-®lled balloon, was
arranged in order to conduct the reaction under a dry and inert
atmosphere by linking the top of the condenser to a liquid paran
trap via ¯exible silicone-rubber tubing. A general procedure is
described for the oxidation of benzenethiol 2a. Thus, the ¯ask was
charged with 2a (0.100 g, 1 mmol), NaIO3 (0.4 g, 2 mmol), freshly
prepared moist alumina (1 g), and hexane (10 ml). After ¯ushing
the ¯ask with argon, the resultant heterogeneous mixture was
maintained at 20 8C while ecient stirring was continued in order
to ensure a smooth reaction and to attain reproducible results.
After 30 min, the whole material was transferred onto a sintered
glass funnel and the ®lter cake was washed thoroughly with
portions of dry diethyl ether (total 50 ml). Rotary evaporation of
the solvent left pure (1H NMR, GC, and TLC) diphenyl disul®de
3a in quantitative yield (0.109 g, mp 57±58 8C; reported mp10
58±60 8C).
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Oxidations of the other thiols 2b±r were carried out as above,
reaction periods of which were determined on the basis of reactivity
of the thiols and yield of disul®des 3b±r. In cases where coloured
(pale to deep yellow depending on substrates) products were
obtained, a single chromatography on a silica gel column (Merck
silica gel 60, hexane) discharged the colour and gave disul®des with
satisfactory purities (>98%).