E. J. Lenarda˜o et al. / Tetrahedron Letters 48 (2007) 7668–7670
Table 1. Solvent-free synthesis of symmetrical disulfides 2a–i
7669
Entry
Thiol 1
Disulfide 2
Time (min)
Methoda (Yield, %)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
C6H5SH 1a
1a
(C6H5S)2 2a
2a
180
2
300
3.5
240
3
A (73)
B (93)
A (80)
B (95)
A (78)
B (90)
A (84)
B (96)
A (73)
B (86)
A (82)
B (97)
A (55)
B (72)
A (70)c
A (48)d
p-ClC6H4SH 1b
1b
(p-ClC6H4S)2 2b
2b
m-ClC6H4SH 1c
1c
(m-ClC6H4S)2 2c
2c
o-ClC6H4SH 1d
1d
(o-ClC6H4S)2 2d
2d
90
1.5
330
4
300
2
360
4
600
420
C6H5CH2SH 1e
1e
(C6H5CH2S)2 2e
2e
p-ClC6H4CH2SH 1f
1f
(p-ClC6H4CH2S)2 2f
2f
p-MeOC6H4SH 1g
1g
(p-MeOC6H4S)2 2g
2g
CH3(CH2)11SH 1h
HO(CH2)2SH 1i
[CH3(CH2)11S]2 2h
[HO(CH2)2S]2 2i
a Method A: The experiments were performed at room temperature. Method B: The experiments were performed under MW irradiation at 148 W.
b Yields of pure products isolated by column chromatography; the spectral data and mp were in perfect agreement with those reported in the
literature.2,3
c The reaction mixture was heated at 70 °C.
d The reaction mixture was heated at 50 °C.
2a was not significantly increased. Similarly, using
Al2O3/KF in the presence of benzene (5 mL), 2a was ob-
tained in 75% yield after stirring for 4 h at room temper-
ature. By using basic alumina without KF, the desired
product 2a was obtained only in 44% yield after stirring
at room temperature for 4.5 h. Aiming to reduce the
reaction time, the mixture was irradiated with micro-
waves (148 W/70 °C, Method B). Complete consump-
tion of thiol 1a was observed after irradiation for
2 min and 2a was obtained in 93% yield (Table 1,
entry 2). When the same protocol was performed at
reduced MW power (125 W/55 °C), the formation of
2a was observed in 81% yield after a longer reaction time
(60 min).
twice. This method consists in low consumption of
solvent, short reaction time, mild reaction conditions,
excellent yields, and simplicity, with non-aqueous
work-up. Besides, the reaction time was dramatically
reduced and the yields were increased by irradiation
with microwaves.
Acknowledgments
This project was funded by FAPERGS, CNPq and par-
tially by a grant from the ChemRAWN XIV Interna-
tional Green Chemistry Grants Program.
In order to check the possibility of intervention of spe-
cific (nonpurely thermal) microwave effects, the reaction
was also examined using a pre-heated oil-bath at the
same final temperature (70–75 °C), as measured at the
end of exposure to the MW-assisted synthesis. However,
it was observed that 2 h was required to obtain 2a in
yield (85%) similar to that obtained after 2 min under
MW.
References and notes
1. (a) Uemura, S. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7,
pp 757–787; (b) Oae, S. Organic Sulfur Chemistry: Structure
and Mechanism; CRC Press: Boca Raton, FL, 1991; (c)
Cremlyn, R. J. An Introduction to Organosulfur Chemistry;
Wiley & Sons: New York, 1996.
2. (a) Joshi, A. V.; Bhusare, S.; Baidossi, M.; Qafisheh, N.;
Sasson, Y. Tetrahedron Lett. 2005, 46, 3583; (b) Shaabani,
A.; Tavasoli-Rad, F.; Lee, D. G. Synth. Commun. 2005, 35,
571; (c) Ali, M. H.; McDermott, M. Tetrahedron Lett. 2002,
43, 6271; (d) Christoforou, A.; Nicolaou, G.; Elemes, Y.
Tetrahedron Lett. 2006, 47, 9211; (e) Raghavan, S.;
Rajender, A.; Joseph, S. C.; Rasheed, M. A. Synth.
Commun. 2001, 31, 1477; (f) Zhong, P.; Guo, M.-P. Synth.
Commun. 2001, 31, 1825; (g) Misra, A. K.; Agnihotri, G.
Synth. Commun. 2004, 34, 1079; (h) Alam, A.; Takaguchi,
Y.; Tsuboi, S. Synth. Commun. 2005, 35, 1329; (i) Liu, K.-
T.; Tong, Y.-C. Synthesis 1978, 669; (j) Shah, S. T. A.;
Khan, K. M.; Fecker, M.; Voelter, W. Tetrahedron Lett.
2003, 44, 6789; (k) Hirano, M.; Yakabe, S.; Fukami, M.;
Morimoto, T. Synth. Commun. 1997, 27, 2783.
Since the best conditions were established, the protocols
were extended to the oxidation of other aromatic thiols
with good results using Methods A and B (Scheme 1,
Table 1, entries 3–14). However, for the aliphatic thiols
1h–i, the respective products 2h–i could be obtained only
using conventional heating (entries 15 and 16). It was
also observed that the catalytic system can be re-used
for two cycles, just by washing it with ethyl acetate
and drying under vacuum. The recycled catalytic system
was successfully employed to both the methods, at room
temperature and under microwave irradiation.
In conclusion, several disulfides could be prepared di-
rectly under solvent-free conditions in the presence of
solid-supported basic catalysis, which can be re-used
3. (a) Salehi, P.; Farrokhi, A.; Gholizadeh, M. Synth. Com-
mun. 2001, 31, 2777; (b) Khazaei, A.; Zolfigol, M. A.;
Rostami, A. Synthesis 2004, 2959; (c) Leino, R.; Lo¨nnqvist,