Rosolic acid-catalyzed conversion of thiols to disulfides

Article abstract of DOI:10.1080/00397910802372590

Various aliphatic and aromatic thiols are converted to the corresponding disulphides by catalytic reaction of 4-[bis-(4-hydroxyphenyl)methylene]- cyclohexa-2,5-dienone in good yield. Copyright Taylor & Francis Group, LLC.

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Rosolic Acid–Catalyzed
Conversion of Thiols to
Disulfides
a
a
W. Marjit Singh & Jubaraj B. Baruah
a
Department of Chemistry , Indian Institute of
Technology , Guwahati, India
Published online: 22 Dec 2008.
To cite this article: W. Marjit Singh & Jubaraj B. Baruah (2008) Rosolic Acid–Catalyzed
Conversion of Thiols to Disulfides, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 39:2, 325-331, DOI:
10.1080/00397910802372590
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Synthetic Communications , 39: 325–331, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802372590
Rosolic Acid–Catalyzed Conversion
of Thiols to Disulfides
W. Marjit Singh and Jubaraj B. Baruah
Department of Chemistry, Indian Institute of Technology, Guwahati, India
Abstract: Various aliphatic and aromatic thiols are converted to the corresponding
disulphides by catalytic reaction of 4-[bis-(4-hydroxyphenyl)methylene]-cyclohexa-
2
,5-dienone in good yield.
Keywords: Catalyst, disulfides, redox dye, rosolic acid, thiols
INTRODUCTION
Many reagents have been developed for the synthesis of disulfides from
[
1–15]
thiols.
complicated by overoxidation of thiols to sulfoxides and sulfones.
The reactions often carried out with mild reagents such as S–S bond for-
However, synthesis of disulfides from thiols sometimes is
[
16–18]
[7]
mation reactions, are biologically important. Oxidative S–S coupling
reactions of thiols can also be done by oxidants such as flavins and cyto-
19]
chromes. The oxidative S–S bond formation is also important in cur-
ling of hair. For such a process, a biocompatible oxidant having dye
properties will be useful. The 4-[bis-(4-hydroxyphenyl)methylene] cyclo-
hexa-2,5-dienone conventionally known as rosolic acid is a quinonic
[
[
20]
[21]
dye that shows different color at different pH.
[
properties
It has also antifungal
In this article, the catalytic ability of
22]
[23]
and medical uses.
rosolic acid to oxidize thiols, leading to S–S bond formation in a very
mild reaction condition, is presented.
Received May 21, 2008.
Address correspondence to Jubaraj B. Baruah, Department of Chemistry,
Indian Institute of Technology, Guwahati 781039, India. E-mail: juba@iitg.
ernet.in
3
25

326
W. M. Singh and J. B. Baruah
EXPERIMENTAL
The reagent used were purchased from Aldrich Chemical Co. (USA) and
1
used without further purification. The H NMR spectra were recorded on
a Varian 400-MHz NMR spectrometer with tetramethylsilane as internal
standard. The mass spectra of the compounds were recorded on a Waters
liquid chromatography-mass spectrometer (LC-MS) by making matrix of
the samples in formic acid.
Typical Reaction Procedure
Rosolic acid (0.03 g, 0.1 mmol) was added to a solution of thiol (1 mmol)
in methanol or N,N-dimethylformamide (10 ml) at room temperature.
The solution decolorized initially and regained its red color after few min-
utes. The solution was stirred for 60 min and kept for crystallization. The
crystalline disulphides were obtained. The products were filtered, and the
1
compounds were characterized by recording their H NMR, IR, and LC-
MS data and comparing them with authentic samples. The disulphide
compounds prepared by this procedure and their yields are listed in
Table 1. Spectroscopic data of disulfide H and I (as in Table 1): For
ꢀ
1
H: Mp 268 C. H NMR (400 MHz, DMSO-d ): 8.57 (d, J ¼ 8.4 Hz,
6
ꢁ
1
2
3
1
H), 7.92 (d, J ¼ 8 Hz, 4H), 6.98 (t, J ¼ 7.6 Hz, 2H). IR (KBr, cm ):
437 (bw), 3094 (w), 2958 (w), 1681 (s), 1567 (s), 1498 (m), 1445 (s),
422 (s), 1334 (m), 1227 (s), 1191 (m), 1143 (m), 1008 (m), 827 (m), 757
ꢀ
1
(
s). LC-MS (m=e): 309 (m þ 1). For I: Mp 87 C, H NMR (400 MHz,
DMSO-d ): 12.89 (s, 2H), 8.04 (m, 4H), 7.24 (d, J ¼ 8.4 Hz, 2H). IR
6
ꢁ
1
(
(
KBr, cm ): 3585 (m), 3419 (w), 3117 (m), 2923 (w), 1625 (m), 1519
s), 1470 (s), 1386 (m), 1346 (s), 1174 (s), 1073 (m), 875 (m), 818 (m),
7
32 (m). LC-MS (m=e): 389 (m þ 1).
RESULTS AND DISCUSSION
The oxidation of aromatic and aliphatic thiols with a catalytic amount
(10 mol %) rosolic acid at room temperature under aerobic conditions
gives corresponding disulfides as shown in Scheme 1.
This oxidation reaction is simple and applicable to varieties of
aromatic and aliphatic thiols. These reactions can be carried out either
in methanol or N,N-dimethylformamide. The reaction of p-thiocresol
was optimized by changing the concentration of the catalyst. It was found
that with 10 mol% of rosolic acid the reaction gives good yield, and the
yield of the product is not affected by up to 50 mol% of rosolic acid.

Conversion of Thiols to Disulfides
327
a
Table 1. Oxidation of thiols by rosolic acid
Sl. No.
Thiol
Disulfides
Isolated yield (%)
95
1
.
.
2
96
3
4
.
.
95
92
5
.
94
6
.
95
(
Continued )

328
W. M. Singh and J. B. Baruah
Table 1. Continued
Sl. No. Thiol
Disulfides
Isolated yield (%)
84
7.
b
8.
90
b
9.
95
b
10.
70
a
All the reactions were performed at room temperature for 1 h.
b
For entries 8–10 N,N-dimethylformamide was used as the solvent.
But, beyond 50 mol% of rosolic acid, the yield of disulphide decreases.
The results on oxidation of different thiols by catalytic reaction of rosolic
acid are listed in Table 1. The dehydrogenative coupling method by
[
7]
azide-based compounds is known in the literature ; however, in our
method we have not observed corresponding quinol derivative of rosolic
acid at the end of the reaction. Interestingly addition of thiol to 1,4-ben-
[
25]
zoquinone leads to corresponding sulphenyl derivative, and depending

Conversion of Thiols to Disulfides
329
Scheme 1. Catalytic conversion of thiols to disulfides.
on the reaction condition in the case of the reaction of thiophenols with
1
obtained.
,4-napthoquinone, C–S bonded 1,4-naphthalenediol derivatives can be
[
26]
On the basis of these observations, a reaction mechanism is pro-
posed. The proposed mechanism of the reaction (Scheme 2) involves an
initial nucleophilic attack of thiol on electron-deficient central carbon
of rosolic acid to form a C–S bonded compound. In quinone methides
such sp2-carbons are known to easily generate cations in the presence
[
23]
of an acid.
can easily form a C–S bond.
It is also a well-known fact that quinonic compounds
The next step of this reaction is the for-
[25,26]
mation of an SR radical, which dimerizes and forms the corresponding
disulphide, and the reconversion of the intermediate C–S bonded
compound to rosolic acid takes place. Alternatively, one may involve
the aerial oxidation of the C–S bonded compound to give the product;
however, we have observed that this catalytic oxidation can take place
in the absence of oxygen; this supports the reaction paths in Scheme 2.
In conclusion, we have described a mild and efficient catalytic
method for disulfide formation from thiols.
Scheme 2. Proposed mechanism for catalytic coupling of thiols.

330
W. M. Singh and J. B. Baruah
ACKNOWLEDGMENTS
Authors thank the Council of Scientific and Industrial Research,
New Delhi, India, for financial assistance.
REFERENCES
1
2
3
. Lenardao, E. J.; Lara, R. G.; Silva, M. S.; Jacob, R. G.; Perin, G. Clean and
fast oxidative transformation of thiols to disulphides under solvent-free
conditions. Tetrahedron 2007, 48, 7668–7670.
. Joshi, A. V.; Bhusare, S.; Baidossi, M.; Qafisheh, N.; Sasson, Y. Oxidative
coupling of thiols to disulfides using a solid anhydrous potassium phosphate
catalyst. Tetrahedron Lett. 2005, 46, 3583–3585.
. Khazaei, A.; Zolfigol, M. A.; Rostami, A. 1,3-Dibromo-5,5-dimethylhydan-
toin [DBDMH] as efficient and selective agent for the oxidation of thiols
to disulfides in solution or under solvent-free conditions. Synthesis 2004,
2959–2961.
4. Delaude, L.; Laszlo, P. A novel oxidizing reagent based on potassium ferrate.
J. Org. Chem. 1996, 61, 6360–6370.
5
. Peskin, A. V.; Winterbourn, C. C. Kinetics of the reactions of hypochlorous
acid and amino acid chloramines with thiols, methionine, and ascorbate. Free
Radical Bio. Med. 2001, 30, 572–579.
6
. Shaabani, A.; Tavasoli-Rad, F.; Lee, D. G. Potassium permanganate oxida-
tion of organic compounds. Synth. Commun. 2005, 35, 571–580.
. Christoforou, A.; Nicolaou, G.; Elemes, Y. N-Phenyltriazolinedione as an
efficient, selective, and reusable reagent for the oxidation of thiols to disul-
fides. Tetrahedron. Lett. 2006, 47, 9211–9213.
7
8
9
. Misra, A. K.; Agnihotri, G. Nitric acid–mediated oxidative transformation of
thiols to disulfides. Synth. Commun. 2004, 34, 1079–1085.
. Alam, A.; Takaguchi, Y.; Tsuboi, S. A simple, extremely fast, and high-
yielding oxidation of thiols to disulfides. Synth. Commun. 2005, 35,
1329–1333.
1
1
1
1
0. You, Y.; Ahsan, K.; Detty, M. R. Mechanistic studies of the tellurium(II)=
tellurium(IV) redox cycle in thiol peroxidase–like reactions of diorganotellur-
ides in methanol. J. Am. Chem. Soc. 2003, 125, 4918–4927.
1. Shah, S. T. A.; Khan, K. M.; Fecker, M.; Voelter, W. A novel method for the
syntheses of symmetrical disulfides using CsF-Celite as a solid base. Tetrahe-
dron Lett. 2003, 44, 6789–6791.
2. Hirano, M.; Yakabe, S.; Fukami, M.; Morimoto, T. An environmentally
friendly oxidation of thiols to disulfides by calcium hypochlorite and mon-
tmorillonite K10 in hexane. Synth. Commun. 1997, 27, 2783–2788.
3. Salehi, P.; Farrokhi, A.; Gholizadeh, M. Oxidative coupling of thiols by
pyridinium chlorochromate in solution and solvent free conditions. Synth
Commun. 2001, 31, 2777–2781.

Conversion of Thiols to Disulfides
331
1
4. Demir, A. S.; Igdir, A. C.; Mahasneh, A. S. Novel conversion of thiols into
disulfides, via S-nitrosothiol intermediates using trichloronitromethane.
Tetrahedron 1999, 55, 12399–12404.
1
5. Weber, W. G.; McLeary, J. B.; Sanderson D. Facile preparation of bis(thio-
carbonyl)didulphides via elimination. Tetrahedron Lett. 2006, 47, 4771–4774.
6. Freeman, F.; Angeletakis, C. N. Formation of disulfoxides, sulfinic
anhydrides, and sulfines during the m-chloroperoxybenzoic acid oxidation
of symmetrical S-alkyl alkanethiosulfinates. J. Am. Chem. Soc. 1983, 105,
1
4039–4049.
1
7. Iranpoor, N.; Mohajer, D.; Rezaeifard, A.-R. Rapid and highly chemoselec-
tive biomimetic oxidation of organosulfur compounds with tetra-
butylammonium peroxymonosulfate in the presence of manganese
meso-tetraphenylporphyrin and imidazole. Tetrahedron Lett. 2004, 45,
3811–3815.
1
8. Lazzaro, F.; Crucianelli, M.; De Angelis, F.; Neri, V.; Saladino, R. Novel
oxidative side-chain transformation of amino acids and peptides by methyl-
trioxorhenium=H O system. Tetrahedron Lett. 2004, 45, 9237–9240.
2
2
1
2
2
9. Jocelyn, D. C. Biochemistry of the Thiol Group; Academic Press: New York,
1992.
0. Lehninger, A. L.; Nelson, D. L.; Cox, M. M. Principles of Biochemistry, 2nd
ed. CBS Publishers and Distributors: New Delhi, India, 1993.
1. Lee, J. W.; Lee, J.-S.; Chang, Y-T. Colorimetric identification of carbohy-
drates by a pH indicator=pH change inducer ensemble. Angew. Chem., Int.
Ed. Eng. 2006, 45, 6485–6487.
2
2. Maeda, K.; Oya, H.; Yamada, K.; Yamamoto, J.; Nakashima, M.; Sekiya, A.
The effect of potassium on ouabain toxicity in reserpinized guinea pigs.
Nagoya J. Med. Sci. 1971, 33, 241–245.
2
3. LeRoy, B. R. Colorimetric analysis of the saliva with the clinical significance.
New York Med. J. 1909, 87, 448–450.
2
4. Arques, A.; Amat, A. M.; Santos-Juanes, L.; Vercher, R. F.; Marin, M. L.;
Miranda, M. 2,4,6-Triphenylthiapyrylium cation as homogeneous solar
photocatalyst. Catal. Today 2007, 129, 37–42.
2
5. Singh, M. W.; Karmakar, A.; Barooah, N.; Baruah, J. B. Variations in pro-
duct in reactions of naphthoquinone with primary amines. Beil. J. Org.
Chem. 2007, 3, 10.
2
6. Stasevych, M. V.; Plotnikov, M. Y.; Platonov, M. O.; Sabat, S. I.;
Musyanovych, R. Y.; Novikov, V. P. Sulfur-containing derivatives of 1,4-
naphthoquinone, part 2: Sulfenyl derivative synthesis. Heteroatom Chem.
2005, 16, 587–598.