Tribromoisocyanuric acid (TBCA) and oxone-MX systems as oxidizing agents: Oxidative coupling of thiols to their corresponding disulfides under mild and heterogeneous conditions

Article abstract of DOI:10.1002/jccs.200700159

Tribromoisocyanuric acid (TBCA) and Oxone-MX systems were used as effective oxidizing agents for the oxidation of thiols to their corresponding disulfides under mild conditions at room temperature with good to excellent yields.

Full text of DOI:10.1002/jccs.200700159

Journal of the Chinese Chemical Society, 2007, 54, 1115-1118
1115
Communication
Tribromoisocyanuric Acid (TBCA) and OxoneÒ-MX Systems as Oxidizing
Agents: Oxidative Coupling of Thiols to their Corresponding Disulfides
under Mild and Heterogeneous Conditions
Mohammad Ali Zolfigol,a* Khodabakhsh Niknam,b Mojtaba Bagherzadeh,c
Arash Ghorbani-Choghamarani,d Nadiya Koukabi,a Maryam Hajjamia and Eskandar Kolvaria
aFaculty of Chemistry, Bu-Ali Sina University, Hamedan, P.O. Box 6517838683, Iran
bDepartment of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
cDepartment of Chemistry, Sharif University of Technology, P.O. Box 11395-9516, Tehran, Iran
dDepartment of Chemistry, Faculty of Science, Ilam University, Ilam, Iran
Tribromoisocyanuric acid (TBCA) and OxoneÒ-MX systems were used as effective oxidizing agents
for the oxidation of thiols to their corresponding disulfides under mild conditions at room temperature
with good to excellent yields.
Keywords: Tribromoisocyanuric acid (TBCA); OxoneÒ; Sodium chloride; Potassium chloride;
Potassium bromide; Oxidation of thiols; Disulfides; Oxidative coupling of thiols;
Heterogeneous conditions; Wet SiO2.
The vital role of thiols and disulfides in living sys-
tems has focused on their interconversion reactions. Oxida-
tive conversion of thiols to disulfides is of importance from
both biological and synthetic points of view, as shown by a
plethora of procedures and methods that have been devised
for this transformation.1 Morover thiols can be conve-
niently protected as disulfides and regenerated by cleavage
of the S-S bond.2 Oxidative coupling of thiols to disulfides
have been reported via nitrosothiol intermediates in the
presence of NO+ sources such as: alkyl nitrites, nitrosyl
salts, dinitrogen trioxide, dinitrogen tetroxide, trichloro-
nitromethane, oxalic acid dihydrate, inorganic acidic salts,
silica sulfuric acid, silica chloride/NaNO2, metal nitrate
and ionic complex of [NO+.18-crown-6.H(NO3)2].3-12 Thiols
are susceptible to over oxidation and hence there are other
reported reagents on their controlled oxidation such as
HMDS/DMSO,1a TMSCl/CC,1b I2/acetonitrile,13a Ti(IV)/
NaI,13b NaClO/montmorillonite K10,14 gamma-PCC or
gamma-PCC-SiO2,15 (n-BuPPh3)2Cr2O7,16 trinitratoceri-
um(IV) bromate,17 (PhCH2PPh3)HSO5,18 tripropylammo-
nium chlorochromate,19 Dowex 1-x8/dichromate20 and (n-
Bu4N)2S2O8.21 Consequently, aerobic oxidation of thiols to
disulfides in the presence of potassium phosphate,2 Co(II)
phthalocyanines,22a Cs-F-Cellite22b and basic mineral sup-
port,22c has been also studied. However, there is a need for a
simple, inexpensive and safe system for this purpose. To
the best our knowledge OxoneÒ is an inexpensive, wa-
ter-soluble, and stable oxidizing reagent that is commer-
cially available, but this reagent is insoluble in organic
solvents. Hajipour et al. recently reported a new derivative
of OxoneÒ, namely benzyltriphenylphosphonium peroxy-
monosulfate [i.e. PhCH2PPh3)HSO5] so that it is quite solu-
ble in organic solvents such as CH2Cl2, CHCl3, acetone,
etc.18 Although this reagent can convert thiols to disulfides,
it has an organic cationic counterpart which is not suitable
for green chemistry. OxoneÒ, which contains potassium
peroxymonosulfate, KHSO5, as the oxidizing species, is
commercially available as the triple salt 2KHSO5.KHSO4.
K2SO4. There are more than one hundred reports in the lit-
erature where OxoneÒ is used as an oxidizing source for or-
ganic substrates.23 Also it has been used as a solid acid and
has preceded acid catalyzed reactions such as the other
solid acids i.e. hetropoly acids,24 silica sulfuric acid and sil-
ica cloride,25 Nafion-H26 and metal hydrogensulfates.27
Recently Mattos et al. reported a new method for the
preparation of tribromoisocyanuric acid (TBCA), so that
* Corresponding author. Fax: 0098-811-8272404 and 8257407; E-mail: zolfi@basu.ac.ir, mzolfigol@yahoo.com

1116 J. Chin. Chem. Soc., Vol. 54, No. 5, 2007
Zolfigol et al.
Table 1. Oxidation of thioles (1) to their corresponding disulfides (2) with a combination of
Oxoneâ/NaCl (I), Oxone®/KCl (II), Oxoneâ/KBr (III)a,b,c and tribromocyanuric acid
(TBCA)d (IV) in dicholoromethane at room temperature
Substrate
Product
Time (Min)
Yield (%)e
Entry
R
1
2
I
II
III
IV
I
II
III
IV
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
Ph
2a
2b
2c
2d
2e
2f
20
75
40
50
25
30
-
10
10
20
25
20
10
10
25
93 97
45 50
88
73
92
78
4-FC6H4
4-ClC6H4
PhCH2
90 120
15 25
210 420
445 90
94 97 Sluggish 91
25
90
50
95 96
60 30
98 97
60 58
93 86
99
15
98
48
95
92
65
92
62
89
n-C8H17
Cyclohexyl
CH2CH2OH
C2H4COOH
1g
1h
2g
2h
60 120 120
120 45 70
a Oxoneâ/MX/Substrate: for entries of 1a-1e (1.15/1.15/1 mmol), 1f-1i: (1.3/1.3/1 mmol), for
each one mmol of thiols 0.2 g of wet SiO2 (50% w/w) was used. b Oxidation reactions with
Oxoneâ/KI (V) system were sluggish. c Oxidation reaction did not occur in the absence of metal
halide. d TBCA/Substrate: 0.33 mmol for each one mmol of thiols. e Isolated yields.
the described methodology proved to be simpler and con-
siderably less expensive than the preparation proposed by
Gottardi.28 Tribromoisocyanuric acid is used for the regio-
selective bromination of activated aromatic rings29 and
regioselective cobromination of alkenes.28
tion and evaporation of the solvent.32,33 The results and re-
action conditions are given in Table 1. Among potassium
halide KI was not suitable for this transformation, and the
oxidation reaction with OxoneÒ-KI is sluggish. These re-
agent systems are effective sources for the in situ genera-
tion of halonium species34 because an oxidation reaction
did not occur in the absence of metal halide only by using
OxoneÒ.
In continuation of our studies on using heterogeneous
oxidizing agents in organic transformation,30 we have
found that TBCA or OxoneÒ reagents have been used by
others as excellent systems for different purposes28,31 espe-
cially when OxoneÒ is combined with sodium or potassium
halides. Therefore, herein we wish to report a simple, cheap
and convenient method for the effective conversion of
thiols (1) to their corresponding disulfides (2) by using
tribromoisocyanuric acid (TBCA), and OxoneÒ-MX (MX
In conclusion, a practical and efficient oxidation of
thiols has been achieved. We suggest that these systems
could be used for the oxidation of a wide variety of thiols
under mild and heterogeneous conditions.
ACKNOWLEDGMENT
Scheme I
Financial support for this work by the Center of Excel-
lence in Development of Chemical Methods (CEDCM) of
Bu-Ali Sina University, Hamadan, Iran, is gratefully ac-
knowledged.
= NaCl, KCl, KBr) under mild and heterogeneous condi-
tions (Scheme I).
Received May 22, 2006.
Good types of thiols were subjected to oxidation in
the presence of TBCA and OxoneÒ-MX (MX = NaCl, KCl,
KBr) and wet SiO2 (50%, w/w) in dichloromethane at room
temperature and proceeded with good to excellent yields
(Scheme I). After completion of the reaction the resulting
reaction mixture was filtered off on anhydrous Na2SO4.
The resultant disulfides (2) were obtained by simple filtra-
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reagents and needed reactions times indicated in the Table).
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disappearance of the starting materials 1 on TLC, reaction
mixture was filtered off. The residue was washed with
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2a-IR (Nujul): 3080, 1575, 1472, 738 cm-1; H NMR (90
1
MHz, acetone-d6), d (ppm): 7.4-7.2 (m, 10H). 2b-IR (KBr):
1
3061, 1589, 1486, 1229, 824 cm-1; H NMR (CDCl3), d
(ppm): 7.4 (m, 4H), 6.99 (m, 4H). 2c-IR (Nujul): 3100, 1461,
1377, 1092, 814 cm-1; 1H NMR (DMSO-d6), d (ppm): 7.5 (m,
1
8H). 2d-IR (Nujul): 3061, 1494, 1453, 695 cm-1; H NMR
(CDCl3), d (ppm): 3.68 (s, 4H), 7.2 (s, 10H). 2f-IR (Nujul):
2933, 1450, 1125 cm-1; 1H NMR (CDCl3), d (ppm): 1.3-2.0
(m, 20H), 2.9-3.3 (m, 2H). 2g-IR (KBr): 3349, 2925, 1398,
1
1045 cm-1; H NMR (CDCl3), d (ppm): 4.2 (s, 2H), 3.5 (t,
2H), 2.5 (t, 2H). 2h-IR (Nujul): 3000-3500, 2925, 1697,
1399 cm-1; 1H NMR (Acetone-d6), d (ppm): 2.7 (t, 2H), 2.9 (t,
2H), 11 (b, 2H).
34. Khazaei, A.; Zolfigol, M. A.; Rostami, A. Synthesis 2004,
2959.