Alumina: An Efficient and Reusable Catalyst for the Oxidative Coupling of Thiols with DMSO

Article abstract of DOI:10.1039/a802772b

An inexpensive combination of common laboratory reagents, dimethyl sulfoxide (DMSO) and Chromatographic neutral alumina, gives an efficient, selective, and high-yielding oxidation of aromatic, aliphatic and alicyclic thiols to the corresponding disulfides in excellent yields under relatively mild conditions.

Full text of DOI:10.1039/a802772b

View Article Online / Journal Homepage / Table of Contents for this issue
472 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 472±473$
Alumina: an Efficient and Reusable Catalyst for the
Oxidative Coupling of Thiols with DMSO$
Masao Hirano,* Sigetaka Yakabe, Hiroyuki Monobe and
Takashi Morimoto
Department of Applied Chemistry, Faculty of Technology, Tokyo University of Agriculture
and Technology (TUAT), Koganei, Tokyo 184-8588, Japan
An inexpensive combination of common laboratory reagents, dimethyl sulfoxide (DMSO) and chromatographic neutral
alumina, gives an efficient, selective, and high-yielding oxidation of aromatic, aliphatic and alicyclic thiols to the
corresponding disulfides in excellent yields under relatively mild conditions.
In recent attempts to develop new synthetic reactions using
reagents insoluble in aprotic solvents, we have been fasci-
nated with
a remarkable catalysis of chromatographic
alumina enabling selective oxidations of a number of func-
tional groups1 and electrophilic chlorination of aromatic
ethers2 to occur under mild conditions. This ®nding together
with our continued interest in the chemistry of sulfur
compounds1,3 prompted us to investigate the oxidation
of thiols to disul®des4 with DMSO in combination with
alumina as the solid catalyst. Conventional DMSO% oxi-
dations of thiols are in general slow and, in certain cases,
gave the disul®des only in moderate yields.6 Consequently,
it is desirable to provide an e€ective, but simple method of
accelerating the reaction and/or enhancing disul®de yields in
order to make the DMSO oxidation practically attractive.
Oxidation of thiols 1 was carried out simply by eciently
stirring a heterogeneous mixture of 1 and chromatographic
neutral alumina in DMSO at 40±70 8C. An unpleasant
odour of concomitantly formed dimethyl sul®de (DMS)
at the work-up stage is observed, however, this indicates
successful oxidation. DMSO is not an easy solvent to
remove by distillation because of its high boiling point
(189 8C), but its reasonable solubility in water allowed its
easy removal by aqueous washing of the reaction mixture.
Accordingly, disul®des 2 can be readily worked-up without
diculty. Benzenethiol 1a, for example, cleanly a€orded
94% of diphenyl disul®de 2a after 30 min reaction at 40 8C
if alumina was added (entry 1); otherwise, the reaction
gave only 11% of 2a and 89% of 1a remained unreacted
even after 1 h, clearly indicating that the alumina catalysed
the reaction. A multigram scale reaction of 1a resulted
in successful formation of 2a (see Experimental). Oxidations
of aromatic thiols 1b±j can also be easily achieved, irrespec-
tive of the electronic properties of substituents and their
Scheme 1 i, Alumina, 40±70 8C
positions on the benzene ring. It is well known that the
ease with which thiols are oxidised with DMSO is strongly
dependent on their acidity (pKa) and, since aliphatic thiols
are less acidic, they are much less reactive than aryl
thiols.6b,c In fact, comparative studies using typical aryl
and aliphatic thiols (1a, k, o: pKa=6±7, 10.5 and 14, respec-
tively)6b showed that their conversions under the conditions
given in entry 1 are 100, 56, and 18%, respectively.
Aliphatic and alicyclic thiols, however, can be favorably
oxidised under selected conditions, a€ording disul®des in
excellent yields.
Earlier work closely related to the present oxidation, viz.
air oxidation using basic alumina as solid catalyst7 and
oxidation with DMSO,6 have elegantly postulated the roles
of alumina and DMSO in those reactions. These methods,
however, inconveniently required long periods of time and/
or high temperature to e€ect the reactions. Thus, there have
been a number of kinetic6e,8a and preparative8b investi-
gations into promoted DMSO oxidations using acids and
bases,6e or halogen compounds8a,b as catalysts. For example,
Oae and coworkers have reported that I2-catalysed DMSO
oxidation at ambient temperature for 5 h gives aliphatic
Table 1 Oxidative coupling of thiols with DMSO and aluminaa
Entry
t/h
T/8C
Disulfide (%)b
Entry
t/h
T/8C
Disulfide (%)b
1
2
3c
4
5
6
7
8
9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
40
40
40
40
40
40
50
40
40
2a (94)
2b (95)
2c (96)
2d (94)
2e (94)
2f (98)
2g (92)
2h (93)
2i (98)
10
11
12
13
14
15
16
17
18d
0.5
0.75
2.5
2.5
2.5
2.5
2.5
2.5
2.5
40
70
70
70
70
70
70
70
70
2j (92)
2k (98)
21 (97)
2m (95)
2n (96)
2o (quant.)
2p (99)
2q (91)
2r (quant.)
aThiol 1 (1 mmol), predried neutral alumina (1.5 g), DMSO (5 ml). bIsolated yield of disulfide 2 based
on the starting 1. cAlumina (2 g). dAlumina (2.5 g).
and aromatic disul®des in essentially quantitative yield.8b
*To receive any correspondence.
Although elevated temperature (40±70 8C) was required to
e€ect the present reaction, reaction periods were shorter
than those of Oae's procedure.8b Moreover, it can be
emphasized that the alumina is convenient, safe to handle
and, after calcination, the recovered alumina can be used
$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).
%Useful information on chemical and physical properties of DMSO
is available; ref. 5.

View Article Online
J. CHEM. RESEARCH (S), 1998 473
gave pure (1H NMR, GC and TLC) diphenyl disul®de 2a in 94%
yield (0.103 g, mp 60±61 8C; reported mp9 62±63 8C). The recovered
alumina was calcined at 500 8C for 3 h with shaking at 30 min inter-
vals and was able to be used for repeat runs.
Gram scale synthetic reaction carried out with DMSO (30 ml), 1a
(50 mmol, 5.5 g) and alumina (7 g) in a 100 ml round bottom three
necked ¯ask, ®tted with the same equipments as those employed in
small scale experiments, at 40 8C for 1 h gave 5.18 g of 2a (95%).
Table 2 Recycling of alumina in the oxidation of benzenethiol
1a with DMSOa
Run
2ab (%)
1
94
2
93
3
94
4
93
5
94
6
89
7
90
8
91
aAt 40 8C, for 0.5 h; 1a (1 mmol), predried neutral alumina
(1.5 g), DMSO (5 ml). bAverage GLC yield of diphenyl disulfide
2a from several experiments based on the starting 1a; biphenyl
was used as an internal standard.
We thank Messrs. Nobuteru Uraoka and Mitsunori Goto
and Miss Keiko Kimura for their skill in carrying out
preliminary experiments at TUAT.
for several repeat oxidations without serious decrease in
activity (Table 2). These advantages might make the
present system a useful modi®cation of conventional DMSO
oxidations.
Received, 14th April 1998; Accepted, 11th May 1998
Paper E/8/02772B
In conclusion, a reusable catalyst, alumina, aided DMSO
oxidation of a broad range of thiols, providing a practical
(inexpensive, simple, fast, high-yielding) procedure for
disul®de synthesis.
References
1 (a) M. Hirano, S. Yakabe, J. H. Clark and T. Morimoto,
J. Chem. Soc., Perkin Trans. 1, 1996, 2693; (b) M. Hirano,
S. Yakabe, S. Itoh, J. H. Clark and T. Morimoto, Synthesis,
1997, 1161 and references cited therein.
2 M. Hirano, S. Yakabe, H. Monobe, J. H. Clark and T. Morimoto,
J. Chem. Soc., Perkin Trans. 1, 1997, 3081; Synth. Commun.,
1997, 27, 3749.
3 M. Hirano, S. Yakabe, H. Chikamori, J. H. Clark and
T. Morimoto, J. Chem. Res. (S), 1998, 310; M. Hirano, K. Ukawa,
S. Yakabe, J. H. Clark and T. Morimoto, Synthesis, 1997, 858.
4 G. Capozzi and G. Modena, in The Chemistry of the Thiol Group,
ed. S. Patai, John Wiley & Sons, London, 1974, ch. 17; J. March,
Advanced Organic Chemistry, Wiley, New York, 1992, 4th edn.,
pp. 1204±1205; M. Hudlicky, Oxidations in Organic Chemistry,
Am. Chem. Soc., Washington, DC, 1990, pp. 250±252.
5 T. T. Tidwell, Org. React., 1990, 39, 297; W. W. Epstein and
F. W. Sweat, Chem. Rev., 1967, 67, 247.
6 (a) C. N. Yiannios and J. V. Karabinos, J. Org. Chem., 1963,
28, 3246; (b) T. J. Wallace, Chem. Ind. (London), 1964, 501;
(c) J. Am. Chem. Soc., 1964, 86, 2018; (d) T. J. Wallace and J. J.
Mahon, J. Am. Chem. Soc., 1964, 86, 4099; (e) J. Org. Chem.,
1965, 30, 1502; T. J. Wallace and H. A. Weiss, Chem. Ind.
(London), 1966, 1558.
Experimental
General.Ð1H NMR spectra were recorded with a JEOL PMX-60
(60 MHz) spectrometer for solutions in CDCl3 using TMS as an
internal standard. Analytical GLC was performed on a Shimadzu
GC-4CM instrument, equipped with FID via a 2 mm 5 mm diam-
eter glass column packed with 3% Silicone OV-17 on Uniport HP
and interfaced with a Shimadzu Chromatopac C-R6A integrator,
with temperature programming. Melting points were determined on
a Yanagimoto MP-S3 melting point apparatus and are uncorrected.
Thiols 2a±o and reagent grade DMSO were used as received from
commercial sources; the purities of thiols were checked by GLC
prior to use. Chromatographic neutral alumina (ICN Biomedical,
Alumina N, Super I) was predried in an oven at 500 8C for 1 h.
Oxidation Procedure.ÐA representative procedure was as follows:
a 30 ml two-necked round bottom ¯ask, equipped with a Te¯on-
coated stirrer bar and a re¯ux condenser, the top of which was
®tted with a CaCl2 drying tube, was charged with benzenethiol 1a
(0.110 g, 1 mmol), DMSO (5 ml), and predried alumina (1 g) and
was then immersed in a thermostatic oil-bath. The resultant hetero-
geneous mixture was maintained at 40 8C while ecient stirring was
continued for 30 min in order to ensure smooth reaction and to
attain reproducible results. The reaction mixture was cooled rapidly
to room temperature by external cooling and was then ®ltered
7 K. T. Liu and Y-C. Tong, Synthesis, 1978, 669.
through
a
sintered glass funnel. The ®lter cake was washed
8 (a) O. G. Lowe, J. Org. Chem., 1975, 40, 2096; (b) T. Aida,
T. Akasaka, N. Furukawa and S. Oae, Bull. Chem. Soc. Jpn.,
1976, 49, 1441.
9 Dictionary of Organic Compounds, Chapman and Hall, 6th edn,
1996.
thoroughly with portions of ether (total 50 ml), and the combined
solvent was washed with brine (20 ml  3) to remove DMSO and
dried (MgSO4). Filtration, removal of the ether on a rotary evapor-
ator, followed by chromatography on silica gel (hexane±AcOEt),