Easy and rapid method for disulfide syntheses using nanophase-manganese (VII) oxide coated clay

Article abstract of DOI:10.1080/10426500903147175

Disulfide bond formation by the oxidation of several thiol compounds using nanophase manganese (VII) oxide coated clay (NM7O coated clay) in chlorinated, nonchlorinated (toluene), and polar solvents (water) is described. During the process, nitro and methoxy groups remain unaffected. The NM7O coated clay is easily prepared, stable, and inexpensive to manufacture. Furthermore, this and other studies prove that NM7O coated clay properties, i.e., mineralogy, chemical, and reactivity, are different from KMnO4. This rapid and facile synthesis coupled with the use of the recyclable NM7O coated clay catalyst will save energy due to low temperature and rapid reaction times, as well as minimal disposal problems, thus decreasing production costs.

Full text of DOI:10.1080/10426500903147175

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Easy and Rapid Method for Disulfide
Syntheses Using Nanophase-Manganese
(VII) Oxide Coated Clay
Sudershan R. Gondi a , David Y. Son b , Edward R. Biehl b & Rajan K.
Vempati a b
a ChK Group, Inc., Plano, Texas, USA
b Southern Methodist University, Dallas, Texas, USA
Published online: 28 Dec 2009.
To cite this article: Sudershan R. Gondi , David Y. Son , Edward R. Biehl & Rajan K. Vempati (2009)
Easy and Rapid Method for Disulfide Syntheses Using Nanophase-Manganese (VII) Oxide Coated Clay,
Phosphorus, Sulfur, and Silicon and the Related Elements, 185:1, 34-39
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Phosphorus, Sulfur, and Silicon, 185:34–39, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903147175
EASY AND RAPID METHOD FOR DISULFIDE SYNTHESES
USING NANOPHASE-MANGANESE (VII) OXIDE COATED
CLAY
Sudershan R. Gondi,1 David Y. Son,2 Edward R. Biehl,2
and Rajan K. Vempati1,2
1ChK Group, Inc., Plano, Texas, USA
2Southern Methodist University, Dallas, Texas, USA
Disulfide bond formation by the oxidation of several thiol compounds using nanophase
manganese (VII) oxide coated clay (NM7O coated clay) in chlorinated, nonchlorinated
(toluene), and polar solvents (water) is described. During the process, nitro and methoxy
groups remain unaffected. The NM7O coated clay is easily prepared, stable, and inexpensive
to manufacture. Furthermore, this and other studies prove that NM7O coated clay properties,
i.e., mineralogy, chemical, and reactivity, are different from KMnO4. This rapid and facile
synthesis coupled with the use of the recyclable NM7O coated clay catalyst will save energy
due to low temperature and rapid reaction times, as well as minimal disposal problems, thus
decreasing production costs.
Keywords Catalyst; coupling; easy and rapid synthesis energy; stable
INTRODUCTION
Disulfide bond formation is important in peptide synthesis,1 protein stabilization,2
and in bioactive molecules.3 Thiols are the main precursors to disulfides, but they are highly
susceptible to air oxidation. Therefore, in multistep syntheses, the protection of thiols as
acetates or esters and their subsequent transformation into -SS-linkages is often necessary.
There are a few methods for the cleavage of thiol acetates under abnormal conditions,
such as longer reaction time (12 days), argon atmosphere, and photolysis.4 Recently, two
improved methods have been reported: one requires activation by stannates,5 while the other
uses a metallic reagent6 with a longer reaction time. The last decade has witnessed two major
changes in chemical manufacturing: 1) a large interest in “green” chemistry syntheses in
which toxic reagents, catalysts, and solvents have been replaced by nontoxic counterparts,
and 2) energy efficient processes to decrease CO2 footprint. This has been achieved by
the use of environmentally friendly solid-supported catalysts7 and/or in combination with
microwave irradiation.8 This modification not only increases the reaction rate, but affords
Received 18 May 2009; accepted 26 June 2009.
S.R.G. would like to acknowledge Prodev, Inc., for partial funding on this project. Furthermore, the authors
would like to thank Mr. Xiang Hua and Mrs. Jyothi Lekla for their assistance on the project.
Address correspondence to Dr. Edward R. Biehl, Chemistry, Southern Methodist University, 3215 Daniel
Ave., Dallas, TX 75275, USA. E-mail: ebiehl@smu.edu
34

DISULFIDE SYNTHESES USING NM7O COATED CLAY
35
Scheme 1
a simple workup and ease of manipulation of the reaction. Herein, we report a rapid
and convenient method for the oxidative coupling of thiols using a nanophase manganese
(VII) oxide coated clay (NM7O coated clay)9 catalyst as shown in Scheme 1. The NM7O
coated clay properties, i.e., mineralogical, chemical, and reactivity, are distinct and unique
from KMnO4.10 This method affords a rapid, low temperature method for the synthesis of
disulfides that avoids the use of activating reagents or excess chlorinated solvent.
RESULTS AND DISCUSSION
To determine the optimum reaction conditions and solvent for the above thiol-
coupling reactions shown in Scheme 1, we studied the conversion of benzenethiol (1a)
to diphenyl disulfide (2a) in various solvents, temperatures, and reaction times. The re-
sults, shown in Table I, show that nearly quantitative yields (∼98%) of 2a were obtained
when the reactions were carried out in chloroform (entry 3) at room temperature for 2 h
and in toluene (entry 1) at 40◦C. The other solvents listed, acetonitrile (entry 2) and
dichloromethane (entry 4), required longer reaction times (3 h and 6 h, respectively) and
gave significantly lower yields of 2a (66% and 87%, respectively). Thus we decided to
carry out subsequent reactions in toluene at 40◦C and chloroform at room temperature.
We next used these conditions to the conversion of a variety of thiols (1a–k) to the
corresponding disulfides (2a–k), and the results are listed in Table II. All products were
characterized by MS, NMR, melting point, and by comparison of their Rf values to those
of authentic samples.
As shown in Table II, most of the listed disulfides (2a, 2c, 2f, 2g, 2h, 2i, and 2k)
were obtained in essentially quantitative yields within 1–3 h when the reactions were run in
toluene or chloroform. Additionally, the reaction of the water-soluble butane-1-thiol (1a)
carried out in water at room temperature gave the corresponding disulfide 2b in 98% yield.
It is noteworthy that diallyic disulfide (2g) (entry 7) was obtained in 98% yield when the
reaction was run in toluene; however, in chloroform the yield of 2g was lowered to 65%.
Table I Thiophenol reaction conditions using NM7O coated clay
Entry
Substrate
Solvent
Toluene
Acetonitrile
Chloroform
Time
Temperature
% Yield
1
2
3
4
Thiophenol
Thiophenol
Thiophenol
Thiophenol
2 h
3 h
2 h
6 h
40◦C
rt
rt
rt
98
66
98
87
Dichloromethane
rt = room temperature.

36
S. R. GONDI ET AL.
Table II Syntheses of disulfide compounds using NM7O coated clay
Reaction
Condi-
tions
Yield
Product (%)
Entry No.
1
Thiol
Solvent Time
Ref.†
11
Toluene
CHCl3
2h
2h
40◦C
rt
2a
97
98
2
3
Water
2 h
1 h
rt
2b
2c
98
12
13
Toluene
CHCl3
40◦C
rt
97
99
4
5
Toluene
Toluene
2h
40◦C
40◦C
2d
2e
98
94
14
15
2 h
6
Toluene
CHCl3
2 h
40◦C
rt
2f
98
97
16
7
8
Toluene
CHCl3
3 h
2 h
40 ◦C
rt
2g
2h
99
65
17
18
Toluene
CHCl3
40◦C
rt
98
97
9
Toluene
CH3Cl
2 h
40◦C
rt
2i
2j
99
98
19
20
10
Toluene
3 h‡
40◦C
60
99
11
Toluene
CHCl3
2 h
40◦C
rt
2k
21
†References.
‡Reaction incomplete even with additionalNM70 (1:3) and longer reaction time (18 h).
rt = room temperature.

DISULFIDE SYNTHESES USING NM7O COATED CLAY
37
Interestingly, both the electron-withdrawing 4-nitro group and electron-donating 4-
hydroxy group on the respective phenylthiols (entries 5 and 4) gave respective coupling
products 2e and 2d in 94% and 98% yields. However, despite the utility and simplicity of
these reactions, limitations were encountered. For example, ditrityl disulfide 2j (entry 10)
was obtained in 60% when the reaction was run for 3 h in toluene at 40◦C; attempts to
increase the yield of 2j by prolonged heating for 18 h failed. However, even though the
yield of ditrityl disulfide was low (60%), to the best of our knowledge, it is the highest yield
reported to date.
The kinetics and mechanism of the oxidation of a thiol to a disulfide by the one-
equivalent oxidants neptunium (VI) and cobalt (III) have been reported.22 The major features
of that proposed mechanism involve an initial 1-equiv oxidation of a thiol to a thiol radical in
the rate determining step (RDS). The resulting radical then is thought to react with another
thiol to give the stable disulfide radical, which presumably is converted to the disulfide. It
is possible that the nanophase Mn(VII)O used in our study behaves similarly. We, however,
have insufficient evidence for the role of Mn(VII)O in the process. Studies are underway,
and the results will be submitted in due course.
CONCLUSION
In summary, we have developed a convenient and practical alternative to disulfide
synthesis by coupling various types of thiol groups using NM7O coated clay. The lower
temperature and rapid syntheses of disulfides coupled with the use of recyclable NM7O
coated clay catalyst will save energy and decrease production costs. Furthermore, the
reaction appears to be surface-based and catalytic, since the NM7O coated clay can be
reused multiple times for making additional disulfide compounds. We are carrying out
mechanistic studies and will report the conclusions in due course.
EXPERIMENTAL
Thiophenol and trityl thiol were obtained from Acros and Aldrich, respectively. The
natural montmorilinite clay, Bentonite L-10, was purchased from Southern Clay Products,
Gonzalez, TX, USA. All other materials were reagent grade unless otherwise specified. 1H
and 13C NMR spectra were obtained on a 400-MHz Bruker Advance NMR spectrometer.
Melting points were collected on a TA Instruments DSC 2010 Differential Scanning
◦
Calorimeter using a heating rate of 10 C min−1 and nitrogen as a purge gas. Thin layer
chromatography was done on precoated silica gel 60f 254 (0.5 mm) glass plates. The
NM7O coated clay (Bentonite-L-10) was prepared by adding MnCl2 4H2O (720 g) to water
(500 mL), and stirring for 5 min to dissolve the salt to yield a solution (termed Solution A).
Then montmorillonite clay (2000 g) was added to water (8 L) and stirred for 30 min, or until
a uniform suspension was achieved (termed Suspension B). Solution A and Suspension B
were added and mixed in another vessel to make a beige-colored suspension of Mn(OH)2.
After 30 min of stirring, 1.5 L, 5.2 M NaOH (1.5 L) was added, and the resultant pH of
the suspension was 13. Subsequently, 1,4-phenylenediamine (PDA, 40 g) was added to
the suspension and stirred for 30 min. The PDA-added suspension was lowered to pH
7.8 by the addition of 6 N HCl, during which time the color of the suspension changed
from green to violet within 1 h. The violet color is the indication of NM7O coated clay.
The oxidation states were characterized and confirmed by cyclic voltametric techniques
and visible spectroscopy.10 The suspension contained 22% by weight NM7O coated clay

38
S. R. GONDI ET AL.
with a Mn content of 7%. Unless otherwise indicated, the compounds were obtained
commercially and used without further purification.
In a typical experimental procedure, the thiol compounds were treated with excess
NM7O coated clay, i.e., 1:2 molar ratio of thiol compounds and Mn (based on its content in
NM7O coated clay) in chloroform at room temperature or in toluene at 40◦C in the presence
of air for 2 h. After completion of the reaction, the NM7O coated clay was filtered, and
the filtrate was concentrated using a rotary evaporator under reduced pressure. Thin layer
chromatography was done on precoated silica gel 60f 254 (0.5 mm) glass plates. Column
chromatography was used to yield the pure disulfide.
REFERENCES
1. M. Bodanszky, Principles of Peptide Synthesis (Springer-Verlag, Berlin, 1984), Chapter 4.
2. K. Fuwa, W. E. C. Wacker, R. Druyan, A. F. Bartholomay, and B. L. Vallee, Proc. Natl. Acad.
Sci. (USA), 46, 1298 (1960).
3. (a) J. R. Johnson, W. F. Bruce, and J. D. Dutcher, J. Am. Chem. Soc., 65, 2005 (1943); (b) P. A.
Miller, K. P. Milstrey, and P. W. Trown, Science, 159, 431 (1968).
4. (a) A. P. Breen, J. A. Murphy, C. W. Patterson, and N. F. Woosfer, Tetrahedron, 49, 10643 (1993);
(b) P. Dubs and R. Stussi, Helv. Chim. Acta, 61, 2351 (1978); (c) J. F. Grunwell, D. L. Foerst,
and M. J. Sanders, J. Org. Chem., 42, 1142 (1977).
5. T. Sato, J. Otera, and H. Nozaki, Tetrahedron Lett., 31, 3595 (1990).
6. H. M. Meshram, Tetrahedron Lett., 34, 2521 (1993).
7. (a) A. McKillop and D. W. Young, Synthesis, 401 and 481 (1979); (b) P. Laszlo, Preparative
Chemistry Using Supported Reagent (Academic Press, San Diego, 1987), pp. 2, 4; (c) H. M.
Meshram, G. S. Reddy, and J. S. Yadav, Tetrahedron Lett., 38, 8891 (1997); (d) H. M. Meshram,
G. S. Reddy, D. Srinivas, and J. S. Yadav, Synth. Commun., 28, 2593 (1998); (e) J. S. Yadav, H.
M. Meshram, G. S. Reddy, and G. Sumithra, Tetrahedron Lett., 39, 3043 (1998).
8. (a) R. S. Varma and H. M. Meshram, Tetrahedron Lett., 38, 5247 (1997); (b) R. S. Varma, R. K.
Saini, and H. M. Meshram, Tetrahedron Lett., 38, 6525 (1997); (c) R. S. Varma, R. K. Saini, and
R. Dahiya, Tetrahedron Lett., 38, 7823 (1997); (d) R. S. Varma and R. Saini, Tetrahedron Lett.,
38, 2623 (1997); (e) E. E. Reid, Organic Chemistry of Bivalent Sulphur Compounds (Chemical
Publishing Co., Inc., New York, 1960), vol. III; (f) P. Laszlo and A. Camelis, Aldrichimica Acta,
21, 97 (1988).
9. R. K. Vempati and D. Y. Son, Solid Support Stabilized Mn(III) and Mn(VII) and Method of
Preparation, U.S. Patent No. 6,953,763 B2, (2006)
10. R. K. Vempati, G. Bhat, and R. W. Wagner, Proceedings of the INTC ‘06, Houston, TX, USA,
Sept. 25–28, 2006.
11. (a) A. Herrera, J. Org. Chem., 69, 4545 (2004); (b) M. Furukawa, Synthesis, 165 (1975).
12. (a) A. R. Hajipour, J. Sulfur Chem., 27, 441 (2006); (b) A. Christoforou, Tetrahedron Lett., 47,
9211 (2006).
13. (a) L. V. Saloutina, Russ. J. Org. Chem., 42, 1307 (2006); (b) W. E. Fristad, Synth. Commun., 15,
1 (1985).
14. (a) R. S. Sengar, New J. Chem., 27, 1115 (2003); (b) A. Nakahashi, J. Poly. Sci. Part A: Poly.
Chem., 45, 3580 (2007).
15. (a) D. Suresh Kumar, J. Org. Chem., 72, 2106 (2007); (b) H. Boerzel, Inorg. Chem., 42, 1604
(2003).
16. (a) A. K. Misra, Synth. Commun., 34, 1079 (2004); (b) S. A. Okecha, Chem. & Ind. (London,
United Kingdom), 19, 788 (1980); (c) E. M. Gordon, J. Med. Chem., 31, 2199 (1988).
17. (a) O. Higuchi, J. Agri. Food. Chem., 51, 7208 (2003); (b) F. E. Chen, Synth. Commun., 32, 3487
(2002).

DISULFIDE SYNTHESES USING NM7O COATED CLAY
39
18. (a) N. Taniguchi, J. Org. Chem., 71, 7874 (2006); (b) S. Chorbadzhiev, J. Prakt. Chem. (Leipzig),
319, 1036 (1977).
19. (a) F. Freeman, Magn. Reson. Chem., 26, 813 (1988); (b) G. J. Derbesy, J. Org. Chem., 60, 1044
(1995); (c) R. Priefer, J. Am. Chem. Soc., 124, 5626 (2002); (d) F. J. Arnaiz, Polyhedron, 21,
1635 (2002); (e) S. M. Bonesi, Photochem. & Photobiol. Sci., 3, 489 (2004).
20. (a) J. C. Cochran, S. R. Friedman, and J. P. Frazier, J. Org. Chem., 61, 1533 (1996); (b) G.
Derbesy and D. N. Harpp, Tetrahedron Lett., 35, 5381 (1994); (c) R. Steudel, S. Foerster, and J.
Albertsen, Chem. Ber., 124, 2357 (1991); (d) M. Ostrowski, J. Jeske, P. G. Jones, and W. W. du
Mont, Chem. Ber., 126, 1355 (1993).
21. (a) D. Camp, Aus. J. Chem., 43, 161 (1990); (b) A. R. Hajipour, J. Sulfur Chem., 27, 441 (2006);
(c) A. R. Hajipour, J. Chem. Res., 286 (2004); (d) M. C. Caserio, Phosphorous, Sulfur, & Silicon,
23, 169 (1985).
22. M. Woods, J. Karbwang, J. S. Sullivan, and E. Deutsch, Inorg. Chem., 15, 1678 (1976).