Catalytic oxidation of thiols to disulfides with vanadyl acetylacetonate (VO(ACAC)2)

Article abstract of DOI:10.1081/SCC-100104058

Catalytic amounts of VO(acac)₂ coupled with t-butylhydroperoxide chemoselectively oxidizes thiols to disulfides under mild reaction conditions and is generally useful for a wide variety of thiols.

Full text of DOI:10.1081/SCC-100104058

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CATALYTIC OXIDATION OF
THIOLS TO DISULFIDES WITH
VANADYL ACETYLACETONATE
(VO(ACAC)2)*
Sadagopan Raghavan a , A. Rajender a , Suju C.
Joseph a & Mohd. Abdul Rasheed a
a Organic Division I, Indian Institute of Chemical
Technology, Hyderabad, 500 007, India
Version of record first published: 02 Aug 2010.
To cite this article: Sadagopan Raghavan, A. Rajender, Suju C. Joseph & Mohd.
Abdul Rasheed (2001): CATALYTIC OXIDATION OF THIOLS TO DISULFIDES WITH
VANADYL ACETYLACETONATE (VO(ACAC)2)* , Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:10, 1477-1480
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SYNTHETIC COMMUNICATIONS, 31(10), 1477–1480 (2001)
CATALYTIC OXIDATION OF THIOLS TO
DISULFIDES WITH VANADYL
ACETYLACETONATE (VO(ACAC)2)*
Sadagopan Raghavan,y A.Rajender, Suju C.Joseph,
and Mohd.Abdul Rasheed
Organic Division I, Indian Institute of Chemical
Technology, Hyderabad 500 007, India
ABSTRACT
Catalytic amounts of VO(acac)2 coupled with t-butyl-
hydroperoxide chemoselectively oxidizes thiols to disulfides
under mild reaction conditions and is generally useful for a
wide variety of thiols.
Disulfides are important compounds from both synthetic and biologi-
cal viewpoints.1–3 Industrially, they find wide application as vulcanizing
agents4 for rubber and elastomers, imparting them excellent tensile strength.
The transformation of thiols to disulfides has been studied employing
various oxidants.5,6 The reported reagents suffer from one or more of the
following disadvantages: availability of the reagent; preparation of the
reagent; toxicity; high cost; and cumbersome work-up procedures.
Only recently has the catalytic coupling of thiols been the subject of some
investigation.7,8
*IICT communication No. 4400.
yCorresponding author.
1477
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

1478
RAGHAVAN ET AL.
Herein, we report on the use of catalytic quantities of VO(acac)2
coupled with t-butyl hydroperoxide to regenerate the oxidant, to bring
about the transformation of thiols to disulfides (Table 1). Primary, second-
ary alkyl thiols and aryl alkyl thiols undergo facile oxidation to the corre-
sponding disulfides. Of particular significance is that no oxidation of the
amino group is observed, a group that is not compatible with many oxidiz-
ing agents. Initially, the reaction was performed using 5 mole % of
VO(acac)2 and one equivalent of t-butyl hydroperoxide in dichloromethane
between À15ꢀC and room temperature. Using thiophenol as the substrate
and varying the amounts of VO(acac)2, it was found that only 0.5 mole %
Table 1. Catalytic Oxidation of Thiolsa,b
M.p of
disulfide (ꢀC)
Yield
Found Reported (%)Thiol
M.p of
disulfide (ꢀC)
Yield
Thiol
Found Reported (%)
144–145 143–14412
60–61
47–48
61–629
45–469
92
90
87
83
56–57 55–5713
71–72 71–7214
152–153 153–15411
Liq.9
70–71
42–43
72–7414
79–80
70–7110
43–4411
88
92
90
85
85
80
80
85
82
79–8010
69–70
70.515
125–128 124–12911 87
Viscous liq.9
Viscous liq.16
80
aReactions were carried out on 1 mmol scale.
bSatisfactory spectral data were obtained for all the disulfides.

THIOLS TO DISULFIDES
1479
was sufficient for the transformation. The reaction proceeded even in the
absence of VO(acac)2, albeit slowly, requiring about 16 h for the total
conversion.
TYPICAL EXPERIMENTAL PROCEDURE
To a solution of thiol (1 mmol)in dry dichloromethane (1 mL)at
À15ꢀC was added vanadyl acetylacetonate (0.5 mol%)and t-butylhydro-
peroxide (1 mmol). The reaction mixture was stirred for a period of 2 h, also
gradually allowing it to attain room temperature when TLC examination
revealed completion. The reaction mixture was then diluted with ether and
washed with water, 0.2 N NaOH, water, and brine. The organic layer was
dried over sodium sulfate and evaporated in vacuo to afford the crude
product, which was purified by column chromatography on silica gel
using 19:1 hexane:ethylacetate to afford the pure disulfide.
In conclusion, the catalytic method reported herein is general, simple,
and efficient for coupling thiols. The easy procedure, simple work-up, avail-
ability of the reagent, short reaction times, and excellent yields of the pro-
ducts will make this method a useful addition to available methodologies.
ACKNOWLEDGMENTS
S.R. is thankful to Dr. J.S. Yadav, Head, Org. Div. I and
Dr. K.V. Raghavan, Director, I.I.C.T, for their constant support and
encouragement. A.R, S.C.J., and M.A.R. are thankful to CSIR, New Delhi,
for a fellowship.
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Received in the UK January 7, 2000