310 J. CHEM. RESEARCH (S), 1998
Oxidation by Chemical Manganese Dioxide. Part 2.1
Simple and High-yielding Synthesis of Symmetrical
Disulfides via the Oxidative Coupling of Thiols$
J. Chem. Research (S),
1998, 310±311$
Masao Hirano,*a Sigetaka Yakabe,a Hideki Chikamori,a
James H. Clarkb and Takashi Morimotoa
aDepartment of Applied Chemistry, Faculty of Technology, Tokyo University of Agriculture
and Technology, Koganei, Tokyo 184-8588, Japan
bDepartment of Chemistry, University of York, Heslington, York YO1 5DD, UK
Aromatic, aliphatic, and alicyclic thiols readily underwent oxidative coupling with chemical manganese dioxide in hexane
to afford the corresponding disulfides in essentially quantitative yields under relatively mild conditions.
Thiols (R0SH, 1) and disul®des (RS0SR, 2) occur in
nature and the cysteine-cystine interconversion is a well
known important biological process in living organisms.2
Oxidative coupling of 1 to 2 using various laboratory
reagents3 has been achieved very easily under mild con-
ditions even with atmospheric air (plus alumina as the solid
base), for example.4 In view of economical, practical, and
recent environmental5 demands, however, use of expensive
or toxic oxidizing reagents, long reaction times, synthetically
unsatisfactory yields of 2 and/or production of large volume
euents in the conventional procedures may now make
them unattractive.6
In the preceding paper,1 we have reported the facile
oxidation of benzylic alcohols with a combination of chemi-
cal manganese dioxide (CMD)7 and molecular sieves (MS)
in hexane. Since S0H bonds in 1 are in general weaker
than O0H bonds in alcohols,8 we have tested the synthetic
value of the CMD/MS system for the oxidative dimerization
of various thiols to the disul®des (Scheme 1).
2a in 97% yield, but was experimentally unattractive. In
contrast, a repeat run with 1 mmol of CMD proceeded
smoothly, and 1a was consumed completely within 1 h, giv-
ing quantitative yield of 2a. Thus, the current procedure can
be favorably compared to earlier methods using AMD as
reported by Wallace9a [89% after 22 h reaction in xylene at
55 8C, [AMD]/[2a] 1 (mole ratio)] and by Papadopoulos et
al.9a [92% after 5±6 h reaction in re¯uxing CHCl3, [AMD]/
[2a] = 5 (weight ratio)] in terms of the yield of 2a and es-
pecially of the reaction period. In addition, from economical
and environmental points of view, hexane is a more attrac-
tive solvent than a halomethane or an aromatic solvent.
The oxidations of the benzenethiol series 1a±j were
accomplished readily to give the disul®des 2a±j in nearly
quantitative yields, regardless of electronic properties (1a, b,
e, f, i, and j) and the positions of substituents on the ben-
zene ring (1c±e and 1g±i), despite the facts that o-substitu-
ents exhibited strong steric hindrance in the oxidations of
benzylic alcohols with AMD10 and also with CMD.1 The
CMD/MS system was also useful for the oxidations of the
aralkyl thiol 1k, aliphatic thiols bearing medium to long
alkyl chains 1l±p, and alicyclic thiols 1q, r. It should be
noted that although the ease with which thiols are oxidized
by certain sulfoxides is strongly dependent on the acidities
of the thiols, viz. 1a>1kw1o,11 there is no signi®cant dier-
ence in the reactivities of these thiols under our experimental
conditions. In fact, the oxidation of an equimolar mixture
of 1a and 1o gave 2a (20% by GLC), 2o (22%), and the
unsymmetrical disul®de, Ph0S0S0C12H25 (57%), clearly
indicating that 1o has comparable reactivity to that of 1a
towards CMD.
Scheme 1
Summing up, the CMD/MS system in re¯uxing hexane
can be conveniently used for the oxidative coupling of thiols
and is applicable to a wide range of substrates.
Oxidative coupling of 1 was carried out simply by gently
re¯uxing a heterogeneous mixture of 1, CMD, and MS
in hexane under a dry and inert atmosphere. Stoichio-
metrically, it is likely that 1 mol of CMD can oxidize 2 mol
of 1 to give 1 mol of 2 and 1 mol of water, eqn. (1),
Experimental
General.ÐMolecular sieves 4A powder (Aldrich) was predried
in an oven (350 8C, 6 h). Thiols 1a±r and CMD (Wako) were used
as received. Hexane was rigourously dried, distilled and stored over
molecular sieves. Mps were determined on a Yanagimoto MP-S3
melting point apparatus and are uncorrected. Analytical gas chro-
matography was performed on a Shimadzu GC-4CM instrument
with a 2 m 5 mm diameter glass column packed with 3% OV-17
on Uniport HP and interfaced with a Shimadzu Chromatopac C-
R6A integrator, with temperature programming.
Oxidation Procedure.ÐThis was similar to that described pre-
viously1 and the reactions of 1a±r (1 mmol) were carried out with
CMD (1±2 mmol), predried MS (0.5 g) and hexane (10 ml), and
100% conversion was attained within 1 h in each experiment. In
addition, the successful synthesis of 2a (98%) on a multigram scale
was achieved by using 1a (40 mmol), CMD (44 mmol) and predried
MS (3 g) in hexane (50 ml) from 1 h reaction.
2RS H MnIVO2 4 RS SR MnIIO H2O ꢀ1
since the reduction of MnIVO2 to MnIIO is a two-electron
transfer process. The GLC analysis of a test run performed
with 1 mmol of benzenethiol 1a and 0.5 mmol of CMD
showed that the reaction was clean and uncomplicated by
the formation of by-products, but a considerable amount of
1a still remained (19%) and diphenyl disul®de 2a was
obtained only in 81% yield even after 3 h. Prolonged reac-
tion (ca. 5 h) enabled 100% conversion of 1a and produced
*To receive any correspondence.
$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).
One of us (J.H.C.) would like to thank the RAEng/
EPSRC for a Clean Technology Fellowship.
Hirano, Masao
