Oxidative coupling of thiols in solution and under solvent-free conditions

Article abstract of DOI:10.1070/MC2004v014n01ABEH001831

A mild and efficient method for the oxidative coupling of thiols by ammonium dichromate in the presence of silica chloride and wet SiO₂ in solution and under solvent free conditions is reported.

Full text of DOI:10.1070/MC2004v014n01ABEH001831

Mendeleev Commun., 2004, 14(1), 34–35
Oxidative coupling of thiols in solution and under solvent-free conditions
Farhad Shirini,*a Mohammad A. Zolfigolb and Mahroo Khaleghia
a Department of Chemistry, College of Science, Guilan University, Rasht, Iran. Fax: +98 131 322 0066; e-mail: shirini@guilan.ac.ir
b Department of Chemistry, College of Science, Bu-Ali Sina University, Hamadan, Iran. E-mail: zolfi@basu.ac.ir
DOI: 10.1070/MC2004v014n01ABEH001831
A mild and efficient method for the oxidative coupling of thiols by ammonium dichromate in the presence of silica chloride and
wet SiO2 in solution and under solvent free conditions is reported.
The selective oxidation of thiols to disulfides is of biological
i or ii
and synthetic interest.1 Thiols can be readily overoxidised so
2RSH
RSSR
that many studies have been carried out for their controlled
oxidation.2 Thus, a number of oxidising agents such as oxygen,3
barium permanganate,4 iodine–hydrogen iodide,5 aqueous HIO3,6
(NO3)3CeBrO3,7 sodium perborate,8 pyridinium chlorochromate,9
MnO2–HCl,10 Caro’s acid supported on silica gel11 and
CuNO3·3H2O12 have been used to oxidise thiols to disulfides.
However, a milder and more selective reagent is still in demand.
In continuation of our studies on silica chloride,13–15 we were
interested in using this reagent in combination with (NH4)2Cr2O7
and wet SiO2 for the oxidation of thiols to disulfides.
Here we report a mild, efficient and convenient method for
the oxidative coupling of thiols to disulfides in solution and
under solvent-free conditions. The oxidation of different thiols
by ammonium dichromate in the presence of silica chloride and
wet SiO2 was investigated in the absence of solvent (Scheme 1,
Table 1). In an easy procedure, a mixture of reactants was
stirred at 80 °C for an appropriate time (Table 1). The resulting
disulfides were isolated in good to high yields. The over-
oxidation of products was not observed with the use of this
method.†
Scheme 1 Reagents and conditions: i, (NH4)2Cr2O7/silica chloride/wet
SiO2, solvent free, 80 °C; ii, (NH4)2Cr2O7/silica chloride/wet SiO2, CH2Cl2,
reflux.
In order to compare the results with those obtained in solu-
tion, we tried to study the coupling reaction in dichloromethane.
Table 1 exhibits no appreciable difference between the results
obtained in solution and under neat condition.
Note that oxidation did not proceed with ammonium di-
chromate, silica chloride or wet SiO2 alone. These results could
be attributed to the probable in situ generation of H2CrO4 in a
low concentration at the surface of wet SiO2 by silica chloride
and ammonium dichromate.
To illustrate the efficiency of the proposed method, Table 2
compares our results with reported data on the relevant reagents.8,9
The method proposed can be used for the preparative syn-
thesis of disulfides from corresponding thiols.
This work was supported in part by the Guilan University
Research Council.
Table 1 Oxidative coupling of thiols by ammonium dichromate in the presence of silica chloride and wet SiO2.
Solvent-free oxidation Oxidation in solution
mp/°C or bp/°C
found (reported)
Entry Substrate
Product
Time/min
Yield (%)a
97
Time/min
5
Yield (%)a
92
N
N
1
2
3
3
5
—
SH
S
S
NH
NH
N
2
2
N
95
95
8
8
90
95
183–184 (182.5–183.5)16
SH
S
S
S
SH
3
—
N
N
2
N
N
4
15
2
90
90
20
7
85
90
—
HO
N
S
HO
N
SH
2
CO H
CO2H
SH
2
5
6
286–287 (289–290)16
S
S
2
1
1
1
90
92
90
5
7
5
92
90
86
59–60 (60)17
45–46 (45–46)18
71–72 (72)19
SH
2
7
8
9
Me
SH
Me
S
2
CH SH
2
CH S
2
2
1
92
5
90
127–129 (125–130)20
SH
S
2
aIsolated yield.
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Mendeleev Commun., 2004, 14(1), 34–35
3
4
K.-T. Liu and Y. C. Tong, Synthesis, 1978, 669.
H. Firouzabadi, E. Mottaghinejad and M. Seddighi, Synthesis, 1989,
378.
Table 2 Oxidation of thiophenol and benzylmercaptane with our method
(1), sodium perborate (2) and pyridinium chlorochromate (3).
5
6
7
T. Aida, T. Akasaka, N. Furukawa and S. Oae, Bull. Chem. Soc. Jpn.,
1976, 49, 1441.
F. Shirini, M. A. Zolfigol, M. M. Lakouraj and M. R. Azadbar, Russ. J.
Org. Chem., 2001, 37, 1340.
H. Tajik, F. Shirini, O. Farahkhah, M. M. Lakouraj and I. Mohammadpoor-
Baltork, Russ. J. Org. Chem., 2002, 38, 1384.
Yield (%) (t/min)
Substrate
1
2
3
PhSH
PhCH2SH
90 (1)
90 (1)
92 (120)
93 (120)
94 (114)
91 (108)
8
9
A. MaKcillop and D. Koyuncu, Tetrahedron Lett., 1990, 31, 5007.
H. Firouzabadi, N. Iranpoor, H. Parham, A. Sardarian and J. Toofan,
Synth. Commun., 1984, 14, 717.
References
1 (a) G. Capozzi and G. Modena, in The Chemistry of the Thiol Group,
ed. S. Patti, Wiley, New York, 1974, Part 2; (b) D. C. Jocelyn,
Biochemistry of the Thiol Group, Academic Press, New York, 1992.
2 S. Oae, D. Fukushima and H. Y. Kim, J. Chem. Soc., Chem. Commun.,
1977, 407.
10 A. Fabratti, F. Ghelfi, R. Grandi and U. M. Pagnoni, Synth. Commun.,
1994, 24, 2393.
11 B. Movassagh, M. M. Lakouraj and K. Ghodrati, Synth. Commun.,
1999, 29, 3597.
12 H. Firouzabadi, N. Iranpoor and M. R. Zolfigol, Synth. Commun.,
1998, 28, 1179.
13 H. Firouzabadi, N. Iranpoor, B. Karimi and H. Hazarkhani, Synlett,
2000, 263.
14 M. A. Zolfigol, F. Shirini and A. Ghorbani Chaghamarani, Synth.
Commun., 2002, 32, 1809.
15 F. Shirini, M. A. Zolfigol, M. Khaleghi and I. Mohammadpoor-Baltork,
Synth. Commun., 2003, 33, 1839.
16 L. Field and J. E. Lawson, J. Am. Chem.. Soc., 1958, 80, 838.
17 F. Ogura, H. Yamaguchi, T. Otsubo and H. Tanaka, Bull. Chem. Soc.
Jpn., 1982, 55, 641.
18 J. Drabowicz and M. Mikolajczyk, Synthesis, 1980, 32.
19 M. Huang and C. C. Chan, Synthesis, 1982, 1091.
20 V. I. Cohen, J. Org. Chem., 1977, 42, 2510.
†
General procedure for the oxidation of thiols in dichloromethane. A
suspension of a substrate (1 mmol), (NH4)2Cr2O7 (0.252 g, 1 mmol),
silica chloride (0.3 g) and wet SiO2 (50 wt%, 0.2 g) in dichloromethane
(3 ml) was heated for a specified time (Table 1) under reflux. The
progress of the reaction was monitored by TLC, and the mixture was
filtered upon completion. The residue was washed with CH2Cl2 (10 ml).
Then, anhydrous MgSO4 was added to the filtrate and filtered off after
10 min. Solvent evaporation followed by column chromatography on
silica gel gave corresponding disulfides in good to high yields.
General procedure for the oxidative coupling of thiols under solvent-
free conditions. A mixture of a substrate (1 mmol), (NH4)2Cr2O7 (0.252 g,
1 mmol), wet SiO2 (50 wt%, 0.2 g) and silica chloride (0.3 g) was heated
at 80 °C for a specified time (Table 1). The progress of the reaction was
monitored by TLC. The reaction mixture was triturated with CH2Cl2
(10 ml) and then filtered. Anhydrous MgSO4 was added to the filtrate
and filtered off after 10 min. Solvent evaporation followed by column
chromatography on silica gel gave the corresponding disulfides in good
to high yields.
Spectroscopic data for the products are as follows.
Table 1, entry 1: 1H NMR (60 MHz, DMSO) d: 8.01 (br., 2H), 7.70 (d,
4H), 7.26 (d, 4H). Found (%): C, 56.30; H, 3.36; N, 18.80, S, 21.51.
Calc. for C14H10N4S2 (%): C, 56.35; H, 3.38; N, 18.78; S, 21.49.
1
Table 1, entry 3: H NMR (60 MHz, DMSO) d: 8.50 (s, 2H), 8.30
(d, 2H), 7.70 (d, 2H), 7.00 (q, 4H). Found (%): C, 54.48; H, 3.67; N,
12.75; S, 29.15. Calc. for C10H8N2S2 (%): C, 54.51; H, 3.66; N, 12.72;
S, 29.11.
Table 1, entry 4: 1H NMR (60 MHz, DMSO) d: 8.20 (d, 2H), 9.00 (br.,
2H), 6.00 (d, 2H). Found (%): C, 42.80; H, 1.83; N, 12.51; S, 28.56.
Calc. for C8H4N2S2O2 (%): C, 42.85; H, 1.80; N, 12.49; S, 28.59.
Received: 14th July 2003; Com. 03/2157
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