Bull. Chem. Soc. Jpn. Vol. 81, No. 1 (2008)
Ó 2008 The Chemical Society of Japan
161
Table 1. Oxidation of Thiols into Disulfides Using 2
General Procedure for the Synthesis of Disulfides from
Thiols. In a typical reaction, a solution of N-tert-butyl-N-chloro-
cyanamide23 (1.0 g, 7.54 mmol) and sodium bromide (1 equiv) in
acetone (20 mL) was stirred for 2 min at room temperature, and
then the thiol (2 equiv) was added to the reaction mixture. The
color of reaction became yellow or brown, which disappears
immediately, indicating the completion of the reaction. Gas chro-
matographic analysis of the reaction mixture showed complete
conversion of the thiols to disulfides. tert-Butylcyanamide formed
as a side product due to the dechlorination of the reagent. The
reaction mixture was filtered and diluted with dichloromethane
(20 mL). The combined layer was washed with water (2 ꢃ 20
mL) and dried over anhydrous Na2SO4. Evaporation of the solvent
on a rotary evaporator gave a mixture of disulfides and tert-butyl-
cyanamide (bp 114–115 ꢂC/14 mmHg). Pure disulfides were ob-
tained either by distillation under vacuum (in case of liquid prod-
ucts) or recrystallization in DCM/Pet. ether (40–60 ꢂC) (in case of
solid products). All the products were compared with authentic
samples and gave satisfactory IR and NMR data. Some of repre-
sentative spectra data of the disulfides are included here.
Entry
Thiols
C2H5SH
(CH3)2CHSH
C4H9SH
C5H11SH
Disulfides
C2H5S–SC2H5
(CH3)2CHS–SCH(CH3)2
C4H9S–SC4H9
C5H11S–SC5H11
YieldaÞ/%
1
2
3
4
5
95
94
96
93
92
HOCH2CH2SH HOCH2CH2S–SCH2CH2OH
SH
S
S
S
6
7
90
96
98
93
95
S
SH
S
S
S
8
SH
SH
S
Cl
Cl
Cl
9
SH
SH
S
S
S
10
S
11
12
95
92
Dibutyl Disulfide:19b Bp 228–232 ꢂC, IR (KBr) 2959, 2927,
O2N
S
NO2
SH
O2N
S
2874, 1465, 1411, 1380, 1270, 1217, 1133, 1090, 911 cmꢁ1
.
1H NMR (CDCl3) ꢀ 0.87–0.97 (m, 6H), 1.31–1.52 (m, 4H), 1.55–
1.73 (m, 4H), 2.65 (t, 4H, J ¼ 7 Hz). 13C NMR (CDCl3) ꢀ 13.92,
21.62, 31.25, 38.96.
COOH
S
COOH
SH
S
13
14
90
94
Di-tert-butyl Disulfide:5b Bp 199–202 ꢂC, IR (KBr) 2960,
2922, 2895, 2864, 1455, 1388, 1360, 1217, 1160, 1H NMR
(CDCl3) 1.31 (s, 9H), 13C NMR (CDCl3) 30.44, 45.97.
Dicyclohexyl Disulfide:19b Bp 163–164 ꢂC, IR (KBr) 2925,
HOOC
S
S
SH
1
2850, 1449, 1261, 998 cmꢁ1. H NMR (CDCl3) ꢀ 1.14–1.34 (m,
N
N
O
N
O
10H), 1.52–1.62 (m, 2H), 1.73–1.81 (m, 4H), 1.96–2.03 (m, 4H),
2.61–2.69 (m, 2H). 13C NMR (CDCl3) ꢀ 25.64, 26.00, 32.80,
49.93.
S
SH
SH
S
S
15
16
92
95
65
O
S
S
Diphenyl Disulfide:16 Mp 59–60 ꢂC, IR (KBr) 3071, 1575,
O
O
O
1
1472, 741, 687 cmꢁ1. H NMR (DMSO-d6) ꢀ 7.27–7.30 (m, 2H),
7.34–7.41 (m, 4H), 7.51–7.54 (m, 4H). 13C NMR (DMSO-d6) ꢀ
127.17, 127.57, 129.46, 135.75.
17bÞ HS(CH2)4SH
18bÞ HS(CH2)5SH
S
p-Tolyl Disulfide: Mp 43–44 ꢂC, IR (KBr) 3021, 2972, 2917,
2864, 1890, 1633, 1564, 1594, 1488, 1448. 1H NMR (CDCl3) ꢀ
2.28 (s, 6H), 7.05–7.60 (m, 8H). 13C NMR (CDCl3) ꢀ 21.55,
128.51, 129.70, 135.42, 137.37.
S
S
72
a) Yields refer to isolated products. b) Reaction was carried out
in excess of acetone (dilution effect).
Dibenzyl Disulfide:19b Mp 69–72 ꢂC, IR (KBr) 3051, 3030,
1
1494, 1453, 758, 696 cmꢁ1. H NMR (DMSO-d6) ꢀ 3.71 (s, 4H),
7.24–7.29 (m, 4H), 7.30–7.37 (m, 6H). 13C NMR (DMSO-d6) ꢀ
41.61, 127.27, 128.39, 129.36, 137.27.
In summary, we demonstrated that N-tert-butyl-N-chloro-
cyanamide is a highly efficient and inexpensive reagent for
the oxidation of aliphatic/aromatic/heterocyclic thiols to the
corresponding disulfides. This reagent oxidizes thiols into the
disulfides under very mild conditions in almost quantitative
yields and irrespective of the presence of other functional
groups attached to thiols. In addition, it was found that cyclic
disulfides could be synthesized from dithiols in good yield. We
consider that this method is a useful addition to the array of
procedures for the oxidation of thiols into disulfides.
Di-p-nitrophenyl Disulfide:16 Mp 178–180, ꢂC, IR (KBr)
3032, 2931, 1610, 1535, 1349, 860. 1H NMR (CDCl3) ꢀ 7.64–8.19
(m, 8H). 13C NMR (CDCl3) ꢀ 124.49, 126.30, 144.16, 146.98.
1,2-Dithiane:5b Mp 33–34 ꢂC, IR (KBr) 2924, 2846, 1432,
1407, 1323, 1302, 1279, 1225, 1131, 1H NMR (CDCl3) ꢀ 1.71–
2.00 (4H, m), 2.62–2.90 (4H, m), 13C NMR (CDCl3) ꢀ 27.80,
33.35.
References
Experimental
1
a) S. Oae, Organic Sulfur Chemistry: Structure and Mech-
General. Melting points were determined with capillary and
1
anism, CRC: Boca Raton, FL, 1991, Vol. 1. b) R. J. Cremlyn, An
Introduction to Organosulfur Chemistry, John Wiley & Sons, New
York, 1996. c) A. Ogawa, Y. Nishiyama, N. Kambe, S. Murai, N.
´
David, L. Martin, H. Meudal, B.-P. Roques, M.-C. Fournie-
were uncorrected. H NMR and 13C NMR spectra were recorded
on a Bruker (400 and 100 MHz respectively) spectrometer (chem-
ical shifts in ꢀ, ppm) against TMS as internal standard; IR spectra
as KBr pellet on a Perkin-Elmer model BXII FT-IR spectropho-
tometer (ꢁ, cmꢁ1).