PAPER
2513
Trimethylchlorosilane (TMSCl) and Cyanuric Chloride (CC) Catalyzed
Efficient Oxidative Coupling of Thiols with Dimethylsulfoxide
Efficient
Oxidati
a
b
T
hiols ak Karimi,* Hassan Hazarkhani, Daryoush Zareyee
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), P. O. Box 45195-159, Gava Zang, Zanjan, Iran
Fax +98(241)4249023; E-mail: karimi@iasbs.ac.ir
Received 26 June 2002; revised 26 August 2002
Method A, Method B or Method C
Abstract: Different types of thiols were rapidly and efficiently con-
verted to disulfides using DMSO in the presence of catalytic
amounts of either trimethylchlorosilane (TMSCl) or cyanuric
chloride (CC).
R
SH
RS SR
CH2Cl2, r.t.
Method A = DMSO (3.0 equiv), TMSCl (0.1 equiv)
Method B = DMSO (1.5 equiv), CC (0.4 equiv)
Method C = DMSO (3.0 equiv), CC (0.1 equiv)
Key words: thiols, disulfides, oxidative coupling
Cl
N
Cl
TMSCl = (CH3)3SiCl
CC
=
N
N
Oxidative conversion of thiols to disulfides is of impor-
tance from both the biological1 and synthetic point of
view,2 as shown by a plethora of procedures and methods
that have been devised for this transformation.2,3 The re-
ported reagents suffer from one or more of the following
disadvantages such as availability of reagent, toxicity,
high cost, or laborious work-up procedures. Very recently
the catalytic coupling of thiols were the subject of some
investigations.4 Among these, it was shown that DMSO in
combination with a variety of co-reagents can be used for
this purpose.5 However, many of these protocols suffer
from drawbacks such as long reaction times, use of excess
of DMSO (usually as solvent) and, in certain cases, mod-
erate to low yield of the desired disulfides. Thus, the de-
velopment of new improved protocol for a high yielding
oxidative coupling of thiols to disulfides using inexpen-
sive reagents such as DMSO is still required. Application
of DMSO in organic transformations is of interest because
of its stability, ease of handling, non-corrosiveness, its
safe nature and inexpensiveness. However, the major lim-
itation of the use of DMSO is its low oxidizing power.
This problem can be circumvented by prior treatment of
DMSO with a variety of oxophilic co-reagents as shown
by the pioneering work of Swern et. al.6 Along this line,
herein, we wish to disclose that DMSO in the presence of
10 mol% of trimethylchlorosilane (TMSCl), oxidizes thi-
ols to corresponding disulfides (Scheme 1, Table 1).
Cl
Scheme 1
Table 1 collects the results attained in the oxidation of
typical aromatic (Method A, entries 1, 4, 6, 8, 13), aliphat-
ic (Method A, entries 10, 16, 19, 21) and alicyclic thiols
(Method A, entry 23) together with the optimized reaction
conditions. Inspection of these data clearly shows the ef-
ficiency of the presented method for oxidative coupling of
thiols to their disulfide in substantially good to excellent
yields. The reactions are clean and the work-up of the re-
action products is easy.
On the other hand it was known from the pioneering work
of Senier that cyanuric chloride could function as a highly
oxophilic reagent for the conversion of carboxylic acids
into their acid chlorides.7 Subsequent to this observation,
the use of CC as a chemical reagent has been previously
reported for converting carboxylic acids into chlorides,
esters, amides, peptides, macrolactones,8,9 mild and selec-
tive reduction of carboxylic acids,10 synthesis of -diazo
ketones,11 deoxygenation of sulfoxides,12 synthesis of -
lactams,13 converting alcohols into alkyl chlorides,14 and
DMSO-mediated Swern oxidation of alcohols.15 These
observations encouraged us to test the ability of cyanuric
chloride for catalyzing the oxidative coupling of thiols to
the corresponding disulfides in presence of DMSO. A va-
riety of structurally diverse thiols undergo facile coupling
to the corresponding disulfides when treated with CC
(0.1 0.4 equiv) and DMSO (1.5 equiv) at room tempera-
ture (Table 1, Method B and C). It is worth mentioning
that shorter reaction times were achieved when the reac-
tion was carried out in the presence of stoichiometric
amounts of CC (Table 1, Method B, entries 2, 11, 14, 17,
25). The efficiency of the method in comparison with the
TMSCl/DMSO protocol can be clearly understood in the
term of quantitative coupling of sodium dimethyl- and di-
ethyldithio carbamate (Table 1, entries 27 30).
We first examined the oxidation of thiophenol as a model
substrate in the presence of a fivefold excess of DMSO
and a stoichiometric amount of TMSCl in CH2Cl2 as sol-
vent (10 mL). The reaction was completed within 10 min-
utes at room temperature and the corresponding
diphenyldisulfide was isolated in excellent yield (95%).
However, in continuation of this study, we found that the
reaction also proceeded well in the presence of a catalytic
amount of TMSCl and a lower excess of DMSO (3 equiv).
Synthesis 2002, No. 17, Print: 02 12 2002.
Art Id.1437-210X,E;2002,0,17,2513,2516,ftx,en;Z09802SS.pdf.
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