sulfenyldimesylamines,11 4-nitroarenesulfenanilides,12 sulfenyl-
sulfinamidines,13 sulfenyl thiocarbonates,14 sulfenyl thiocyan-
ates,15 thionitrites,16 thioimides,17 thiolsulfinates and thiolsul-
fonates,18 and thiophosphonium salts.19 Two popular examples
that illustrate these points are the thioimide17 and thiocarbonate14
methodologies. Both methods involve two-step procedures, and
both involve harsh reagents for the sulfenyl intermediate
preparation, Br2 or SO2Cl2 for the former and ClCOSCl for the
latter. Other procedures of practical use involve reaction of a
thiol with a sulfinylbenzimidazole,20 sequential oxidation of
thiols with barbituric acid derivatives,21 rhodium-catalyzed
exchange of a disulfide,22 an electrochemical approach via a
sulfenium cation,23 and use of DEAD24 in a sequential coupling
of two different thiols. In conjunction with a medicinal chemistry
project on garlic mimics as potentially new antimicrobial agents,
it became our objective to develop a one-pot procedure involving
an environmentally friendly oxidant that could be recycled in
order to furnish a procedure with “green” character. We were
inspired by the work of Abe25 from the 1970s which demon-
strated that N-chlorosuccinimide reacts with a thiol to form a
sulfenyl chloride, which on addition of triethylamine subse-
quently reacts with the byproduct succinimide to form an
N-sulfenylsuccinimide (Scheme 1).
Inexpensive, One-Pot Synthesis of Unsymmetrical
Disulfides Using 1-Chlorobenzotriazole
Roger Hunter,* Mino Caira, and Nashia Stellenboom
Department of Chemistry, UniVersity of Cape Town,
Rondebosch 7701, South Africa
ReceiVed March 31, 2006
A new synthesis of unsymmetrical disulfides is described.
The reaction of a thiol R1SH with 1-chlorobenzotriazole
(BtCl) at -78 °C in DCM affords a high-yielding conversion
to R1SBt without appreciable formation of the symmetrical
disulfide R1SSR1. R1SBt is then reacted with R2SH to form
the unsymmetrical disulfide in a one-pot sequence with green
character that avoids the use of toxic and harsh oxidizing
agents. The methodology has been developed for synthesis
of various types of disulfides.
From the point of view of unsymmetrical disulfide synthesis,
this sequence suffers from reaction of the reactive sulfenyl
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10.1021/jo060693n CCC: $33.50 © 2006 American Chemical Society
Published on Web 09/15/2006
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J. Org. Chem. 2006, 71, 8268-8271