An efficient and convenient method for preparation of disulfides from thiols using air as oxidant catalyzed by Co-Salophen

Article abstract of DOI:10.1016/j.cclet.2011.06.007

Disulfides have been synthesized by oxidation of thiols using air as oxidant catalyzed by Co-Salophen with high yields, mild and neutral conditions, and easy procedures of the catalyst. The products were confirmed by ¹H NMR and IR.

Full text of DOI:10.1016/j.cclet.2011.06.007

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 1403–1406
www.elsevier.com/locate/cclet
An efficient and convenient method for preparation of disulfides
from thiols using air as oxidant catalyzed by Co-Salophen
Pin Ji Chai a, Yong Shu Li b, Cheng Xia Tan a,
*
a College of Chemical Engineering and Materials Sciences, Zhejiang University of Technology, Hangzhou 310014, China
b College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China
Received 19 April 2011
Available online 29 July 2011
Abstract
Disulfides have been synthesized by oxidation of thiols using air as oxidant catalyzed by Co-Salophen with high yields, mild and
1
neutral conditions, and easy procedures of the catalyst. The products were confirmed by H NMR and IR.
# 2011 Cheng Xia Tan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Disulfides; Air; Co-Salophen; Oxidant; Catalyst
Disulfides are important intermediates for chemical transformations [1]. They are mostly prepared from the
oxidation of thiols. Hydrogen peroxide is the most commonly used oxidant [2]. There are numerous other
methods reported for the preparation of disulfides, such as the oxidation of sodium alkyl thiosulfate by hydrogen
peroxide [3], reductive coupling of sulfonyl chlorides with piperidinium tetrathiotungstate [4] as well as with
sodium cyanoborohydride [5]. Although they are efficient synthesis of disulfides, their use is usually in the
laboratory and cannot be applied in industry because these reagents are expensive, provide low yields, or are not
environmentally friendly. Recently the oxidation of thiols to disulfides promoted by activated carbon-air system
was reported [6].
There has been considerable interest in the synthesis and catalytic activity of Schiff-M (M = metal ion) complexes
[7] in past decade because they mimic enzymatic systems. And Cobalt (II) is the good catalyst widespread used in
methoxycarbonylation of olefins [8], dimerization of propylene [9] and so on. Cobalt (II)–Schiff base complexes have
received attention for a long time, being good catalysts for oxidation with dioxygen. Co-Salophen (N,N0-
bis(salicylaldehyde)-1,2-phenylenediimino cobalt (II)) (Fig. 1) is one kind of Schiff-M complex, which is a
tetradentate ligand having a stable structure with two oxygen and two nitrogen atoms, and is analogous to
metalloporphyrins of cytochrome P450 in structure and catalytic activity. Its catalytic and oxygen-carrying function
has widely been recognized [10]. Herein, we report an efficient and convenient preparation of disulfides from thiols
using air catalyzed by Co-Salophen (Scheme 1).
* Corresponding author.
E-mail address: tanchengxia@zjut.edu.cn (C.X. Tan).
1001-8417/$ – see front matter # 2011 Cheng Xia Tan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.06.007

1404
P.J. Chai et al. / Chinese Chemical Letters 22 (2011) 1403–1406
N N
Co
O O
Fig. 1. Co-Salophen.
Co-Salophen
2RSH
RSSR
air, 60¡æ
Scheme 1. Synthesis of symmetrical disulfides.
1. Experimental
All materials were obtained from commercial source. Melting points were obtained with a capillary melting point
apparatus and are uncorrected. Infrared spectra were recorded on Nicolet Aviatar-370 infrared spectrophotometer in
KBr with absorptions in cmꢀ1. 1H NMR spectra (500 MHz) were determined on Varian 500 instrument using CDCl3 or
DMSO-d6 as the solvent with TMS as an internal standard.
1.1. General procedure for the preparation of Co-Salophen
Salicylide (0.02 mol) and o-phenylenediamine (0.01 mol) were solved in 40 mL EtOH stirring at 60 8C for 1 h.
Then filtrated, washed with EtOH, dried at 60 8C under vacuum to obtain short columnar yellow crystal Salophen
(2.99 g), yield 95%, mp 158–160 8C. Salophen (1.58 g, 5 mmol) and Co(OAc)2 (0.89 g, 5 mmol) were added under the
nitrogen protection, then injected 20 mL EtOH. The reaction was taken at 55–65 8C for 2 h; filtrated at reduced
pressure and washed with EtOH, dried at 60 8C under vacuum to obtain dull-red solid (1.70 g), yield 91.0%, mp
>300 8C. IR (KBr): 3437 cmꢀ1, 1607 cmꢀ1, 1561 cmꢀ1, 590 cmꢀ1, 420 cmꢀ1
.
The products were confirmed by IR. The band emerging at 3437 cmꢀ1 and 1607 cmꢀ1 in the FT-IR spectrum could
be assigned to the vibrations of n (O–H) and the characteristic imido (C N) band respectively. And bands at
1607 cmꢀ1 and 1520 cmꢀ1 due to n (C N) and n (C–O) vibrations, respectively, in the Schiff-base, which were shifted
relative to the free ligand (Schiff-base) (1607 cmꢀ1 and 1561 cmꢀ1). The more or less shifting of these bands indicated
that the cobalt ion was bonded to the ligand through the two N and O donor atoms as a tetradentate ONNO
functionality. The absorption bands near 590 cmꢀ1 and 420 cmꢀ1 further affirmed the coordination of Schiff-base to
cobalt ion through Co-O and Co-N bands.
1.2. General procedure for the preparation of disulfide
Thiols (0.6 mmol), ethanol (8 mL), Co-Salophen (0.006 mmol) were added in flask with a magnetic stirring bar,
bubbling air into the solution at 60 8C. The progress of the reaction was monitored by TLC. When the reaction
finished, the catalyst were filtered, then the products were separated by column chromatography.
The products were confirmed by 1H NMR and IR. Di(4-methylphenyl)disulfide (3a): 1H NMR (500 MHz, CDCl3):
d 7.35 (d, 4H, J = 8.0 Hz), 7.10 (d, 4H, J = 8.0 Hz), 2.31 (s, 6H); IR (KBr): 3019, 1488, 801, 479 cmꢀ1; Di-(2-
methylphenyl)disulfide (3b): 1H NMR (500 MHz, CDCl3): d 7.36 (m, 2H), 7.06–7.08 (m, 6H), 2.35 (s, 6H); IR (KBr):
2976, 1585, 1465, 1039, 737 cmꢀ1; Di(2-benzothiazyl)disulfide (3c): 1H NMR (500 MHz, DMSO-d6): d 8.01 (d, 2H,
J = 8.0 Hz), 7.85 (d, 2H, J = 8.0 Hz), 7.54 (d, 2H, J = 7.5 Hz), 7.43 (d, 2H, J = 7.0 Hz). IR (KBr): 2922, 669,
443 cmꢀ1; Diphenyldisulfide (3d): 1H NMR (500 MHz, CDCl3): d 7.50 (d, 4H, J = 8.5 Hz), 7.31 (dt, 4H, J = 7.5 Hz),
1
7.25 (dt, 2H, J = 7.0 Hz). IR (KBr): 3070, 685, 461 cmꢀ1; Di(2-bromophenyl)disulfide (3e): H NMR (500 MHz,
CDCl3): d 7.14–7.59 (m, 8H). IR (KBr): 1588, 1441, 1244, 1036, 740 cmꢀ1; Di(4-methoxyphenyl)disulfide (3f): 1H
NMR (500 MHz, CDCl3): d 7.48 (d, 4H, J = 8.0 Hz), 6.79 (d, 4H, J = 8.0 Hz), 3.86 (s, 6H); IR (KBr): 2837, 1578,

P.J. Chai et al. / Chinese Chemical Letters 22 (2011) 1403–1406
1405
Table 1
The effects of amount of catalyst, reaction time and temperature on yield.a
Entry
Catalyst/mmol
Time/h
Temp./8C
Yieldc/mol%
1
2
0.003
0.006
0.015
None
0.006b
0.006
0.006
0.006
0.006
0.006
0.006
0.006
0.006
3
60
60
60
60
60
60
60
60
60
60
20
40
80
56
96
96
Trace
11
35
65
85
96
96
24
75
80
3
3
3
4
3
5
3
6
0.5
1
7
8
2
9
3
10
11
12
13
4
3
3
3
a
All reactions were run with p-methylbenzenethiol (0.6 mmol), ethanol (8 mL).
Co(OAc)2.
b
c
Isolated yields based on p-methylbenzenethiol.
1473, 1270, 1238, 1059, 1036, 1021, 740 cmꢀ1; Di(4-chlorophenyl)disulfide (3g): 1H NMR (500 MHz, CDCl3): d 7.24
(d, 4H, J = 8.0 Hz), 7.45 (d, 4H, J = 8.0 Hz); IR (KBr): 1568, 1471, 1386, 1112, 1010, 815 cmꢀ1; Di(2-
chlorophenyl)disulfide (3h): 1H NMR (500 MHz, CDCl3): d 7.11–7.52 (m, 8H); IR (KBr): 1564, 1448, 1247, 1028,
746 cmꢀ1; Dibenzyldisulfide (3i): 1H NMR (500 MHz, CDCl3): d 7.02–7.28 (m, 10H), 2.45 (s, 4H); IR (KBr): 3020,
2900, 1595, 1490, 1445, 710, 690 cmꢀ1
.
2. Results and discussion
Using p-methylbenzenethiol as substrate the reaction was optimized by experimenting with various reaction
conditions (solvent, amount of catalyst, reaction time and temperature). Results are shown in Table 1. Among the
solvents tested, ethanol gave the best results. To examine the catalytic activity of Co-Salophen, we explore the
oxidation of thiol in the presence of 0.5%, 1.0%, 2.5%, no Co-Salophen and 1.0% Co(OAc)2. According to Table 1,
1.0% of Co-Salophen was enough and efficient for this reaction, and an excessive amount of the catalyst did not
increase the yields (Table 1, entries 1–3). It was found that the oxidation of thiol did not occur in the absence of Co-
Salophen (Table 1, entry 4) and Co(OAc)2 could not promote the reaction very well (Table 1, entry 5). It was
interesting in the yield of the oxidation at 80 8C (Table 1, entry 13) was lower than at 60 8C (Table 1, entry 9). It may be
that higher temperature results in reduction of the catalytic and oxygen-carrying activity (Table 1, compare entries 11–
13). Our results show that the optimum condition for the oxidation of p-methylbenzenethiol is with 1.0 mmol% of the
catalyst Co-Salophen, 3 h at 60 8C in ethanol.
Table 2
Aerobic oxidative coupling of thiols to disulfides catalyzed by Co-Salophen.a
Compound
Time/h
Yieldb/mol%
Mp/8C
Lit/mp/8C
3a
3b
3c
3d
3e
3f
3
3
3
3
3
3
3
3
4
96
95
94
95
92
96
94
96
90
47–48
36–37
177–178
59–60
97
48 [5]
37–38 [11]
177–179 [12]
59–60 [13]
97–98 [11]
120 [11]
118–119
70–71
86–87
70–71
3g
3h
3i
72 [5]
87–88 [11]
71 [14]
a
The reactions were carried out with 0.6 mmol of substrates with 1% Co-Salophen at 60 8C and bubbling of air into the solution.
Yields based on the thiols.
b

1406
P.J. Chai et al. / Chinese Chemical Letters 22 (2011) 1403–1406
O2
CoSalophen
H2O
CoSalophen OO
RSH
CoSalophen OOH
RSSR
RS
Fig. 2. Mechanism of oxidation of thiols to disulfides.
With optimized conditions in hand, we explored the scope of the reaction, including aromatic and alkyl thiols
(Table 2). To our delight, the catalytic oxidation occurred smoothly with excellent selectivity and yield. Co-Salophen
was recycled, reused four times, and the yields are 95%, 90%, 82% and 51% respectively. It was shown that recycled
Co-Salophen still had catalytic activity.
It is possible that different metal ions keeps appearing. The mechanism of oxidation of thiols to disulfides by Co-
Salophen may be as follow [15]: the thiols were oxidized into disulfides by the active oxygen with the help of
CoSalophen (II) (Fig. 2).
3. Conclusions
In summary, we have developed an experimentally simple Co-Salophen catalyzed aerobic oxidation of thiols into
disulfides using air as oxidant. This catalytic oxidation system is clean, selective and very effective. Further oxidation
reactions using this system are in progress in our laboratory.
References
[1] A. Ogawa, Y. Nishiyama, N. Kambe, et al. Tetrahedron Lett. 28 (1987) 3271.
[2] For reviews, see: G. Capozzi, G. Modena, in: S. Patai (Ed.), The Chemistry of the Thiol Group, part 2, Wiley, NY, 1974, pp 785–839.
[3] R.E. Stutz, R.L. Shriner, J. Am. Chem. Soc. 55 (1933) 1242.
[4] P. Dhar, R. Ranjan, S. Chandrasekaran, J. Org. Chem. 55 (1990) 3728.
[5] S. Kagabu, Org. Prep. Proced. Int. 21 (1989) 388.
[6] M. Hayashi, K. Okunaga, S. Nishida, et al. Tetrahedron Lett. 51 (2010) 6734.
[7] (a) D. Monti, P. Tagliatesta, G. Mancini, et al. Angew. Chem. Int. Ed. 37 (1998) 1131;
(b) E.R. Birnbaum, J.A. Labinger, J.E. Bercaw, et al. Inorg. Chim. Acta 270 (1998) 433.
[8] J.M. Yin, M. Guo, R. Wang, et al. Chin. Chem. Lett. 11 (2000) 223.
[9] S.Z. Wu, S.W. Lu., Chin. Chem. Lett. 14 (2003) 958.
[10] A.M. Daly, C.T. Dalton, M.F. Renehan, et al. Tetrahedron Lett. 40 (1999) 3617.
[11] G. Palumbo, M. Parrilli, O. Neri, et al. Tetrahedron Lett. 23 (1982) 2391.
[12] S.P. Sharma, Catal. Commun. 10 (2009) 905.
[13] J.I.G. Cadogan, S.V. Ley, G. Pattenden, et al., Dictionary of Organic Compounds, 6th ed., vols. 1–3, Chapman & Hall, 1996, 2-6 Boundary
Raw, London SE18HN, UK.
[14] B. Milligan, J.M. Swan, J. Chem. Soc. (1962) 683.
[15] (a) D. Chen, A.E. Martell, Inorg. Chem. 26 (1987) 1026;
(b) B. Ortiz, S.M. Park, Bull. Korean Chem. Soc. 21 (2000) 405.