Selective and simple phase transfer catalyzed synthesis of disulfides from thiols

Article abstract of DOI:10.1039/a903845k

Two novel methods of synthesis of disulfides from thiols or their Na salts in the phase transfer catalytic system CBr₄/18-crown-6/benzene or toluene are developed and the products isolated in 67-8.8% yields.

Full text of DOI:10.1039/a903845k

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624 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 624^625y
Selective and Simple Phase Transfer Catalyzed
Synthesis of Disulfides from Thiolsy
Edgars Abele, Ramona Abele and Edmunds Lukevics
Latvian Institute of Organic Synthesis, 21 Aizkraukles str., Riga, LV-1006, Latvia
Two novel methods of synthesis of disulfides from thiols or their Na salts in the phase transfer catalytic system
CBr4/18-crown-6/benzene or toluene are developed and the products isolated in 67^88% yields.
Synthesis of disul¢des from thiols is an important process
from both synthetic and biochemical points of view.1
The main type of these reactions is the oxidation of thiols
Experimental
GC analysis was performed on a Chrom-5 instrument equipped
with a £ame-ionization detector using a glass column packed with
5% OV-101/Chromosorb W-HP (80^100 mesh) (1.2 m  3 mm).
Thiols, carbon tetrabromide and 18-crown-6 were Fluka products.
Typical Procedure. Synthesis of 2. Method A.öFinely powdered
K2CO3 (1.66 g, 12 mmol) was added to a solution of 1a^f (4 mmol),
CBr4 (0.663 g, 2 mmol), 18-crown-6 (52 mg, 0.2 mmol) in benzene
(7 ml). The reaction mixture was stirred 5^7 h at room temperature
4
in the presence of molecular oxygen,2 DMSO,5;6 metal
oxide,7 metal ions,8 nitric oxide,9 sodium perborate,10
thallium(III) acetate,11 bromine,12 iodine,13 borohydride
exchange resin,14 calcium hypochlorite and silica gel,15
DMSO/alumina,16 and NaIO3/alumina,17 MnO2.18
Table 1 Synthesis of disulfides (2a^g) from thiols (1a^g)
Compound
R
Method
T/ 8C
t/h
Isolated yield(%)
Yield(%)
1a
1b
1c
1d
1d
1e
1f
ꢀCH3†2CH
CH3ꢀCH2†
Ph
PhCH2
PhCH2
2-pyridyl
2-pyrimidyl
8-quinolyl
A
A
A
A
B
A
A
B
20
20
20
20
110
80
6
6
6
7
3
6
5
3
83
79
78
83
88
67
80
68
823
8519
823
4
8911
8911
7510
8520
ö21
80
110
1g
(under re£ux for the thiols 1e,f) (GC and GC/MS control). Any solid
substance was ¢ltered o¡ and the ¢ltrate was evaporated under
reduced pressure. The residue was puri¢ed by column
chromatography using benzene as eluent for disul¢des 2a^d and ben-
zene/ethyl acetate (1 : 1) for 2e^f.
Method B.öNa-salt of thiols 1d,g (2.5 mmol) was added to the sol-
ution of CBr4 (0.41 g, 1.25 mmol) and 18-crown-6 (66 mg, 0.25 mmol)
in toluene (4 ml) and the reaction mixture was boiled under re£ux for
3 h. Any solid substance was ¢ltered o¡ and the ¢ltrate was evapor-
ated at reduced pressure. The residue was puri¢ed by column
chromatography on silica gel.
We have developed two novel and simple phase transfer
catalytic (PTC) methods for the synthesis of aliphatic, aro-
matic and heterocyclic disul¢des (2a^g) from the corre-
sponding thiols (1a^g) (see Experimental). Both methods
included oxidation of thiols (1a^f) by CBr4/solid
K2CO3/18-crown-6/benzene (method A, Scheme 1) or by
sodium thiolates (1d,g) by CBr4/18-crown-6/toluene
(method B) (Table 1). In all cases bromoform was formed.
This suggests that the reactions of dimerization proceed
via brominated thiols (RSBr), not detectable due to their
rapid decomposition.
Received, 13th May 1999; Accepted, 7th July 1999
Paper E/9/03845K
Method A
CBr4 (0.5 equiv.) / solid K2CO3
RSH
18-crown-6 / benzene
20 ˚C or reflux
1a–f
References
1
G. Capozzi and G. Modena, The Chemistry of Thiol Group in
Chemistry of Functional Groups, ed. S. Patai, Wiley, New
York, 1974, Part 1, pp. 785^839.
RSSR
2a–g
CBr4 (0.5 equiv.) / 18-crown-6
CHBr3
RSNa
1d,g
2
3
K.-T. Liu and Y. C. Tong, Synthesis, 1978, 669.
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toluene / reflux
Method B
4
5
6
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Scheme 1
The structure of the disul¢des was con¢rmed by data of
1H NMR and mass spectra.
Thus, two simple, convenient and general methods for the
synthesis of disul¢des, especially for heterocyclic ones,
which are di¤cult to obtain by other methods, have been
developed.
7
8
9
10 A. McKillop and D. Kuyuncu, Tetrahedron Lett., 1990, 31,
5007.
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y This is a Short Paper as de¢ned in the Instructions for Authors,
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