B.L. Li et al. / Journal of Fluorine Chemistry 144 (2012) 45–50
49
simple. The catalyst system could be reused directly without
obvious decrease in the catalytic activity, pH and the product yield
during 12 times of recycle use. However, under the same
conditions, the use of phenylhydrazine as a substrate led to 25%
yield after 2 times of recycle use, and the pH of the reaction system
declined to 6.0 (Table 2) because of the liberation of ammonia
during the formation of the indole compound.
Based on the above results, the generality of the reaction in the
catalyst system was investigated for the synthesis of various indole
products. As shown in Table 3, the catalyst system exhibited very
high activities for Fischer indole synthesis. The desired indole
compounds were obtained in 90% to 96% yields by the reactions of
aryhydrazine hydrochlorides with cyclic ketones within 15 min at
100 8C (entries 1–5). Under the similar reaction conditions,
aliphatic aldehyde and ketones as well as aryl ketone (propio-
phenone) gave the corresponding indoles in 86–96% yields (entries
6–9). Reactions of aryhydrazine hydrochlorides having election-
withdrawing groups completed within 20 min at 100 8C to provide
the corresponding indoles in 86% to 95% yields (entries 10–17).
H3PO4, or CF3SO3H was added slowly to the aqueous solution of the
zwitterions. The mixture was stirred for 6 h at reflux and then dried
under a vacuum to obtain the final products of the desired novel
SO3H-functionalized ILs bearing two alkyl sulfonic acid groups. The
products were obtained in 92–95% yields and in high purities.
[(HSO3-p)2im][CF3SO3]: 1H NMR (500 MHz, D2O,
d ppm): 2.14–
2.19 (m, 4H), 2.76–2.79 (t, 4H, J = 7.5 Hz), 4.20–4.23 (t, 4H,
J = 7.5 Hz), 7.39–7.41 (d, 2H, J = 1.5 Hz), 8.70 (s, 1H). 13C NMR
(125 MHz, D2O,
d ppm): 20.9(2C), 28.1(2C), 49.0, 50.1(2C),
122.5(2C), and 135.3.
4.3. Representative procedure for the one-pot Fischer indole synthesis
Cyclohexanone (0.91 g, 10.0 mmol) was mixed with [(HSO3-
p)2im][CF3SO3] (0.5 mmol) in water (15 mL), and phenylhydrazine
hydrochloride (1.44 g, 10.0 mmol) was added. The mixture was
then stirred at 100 8C for about 15 min under microwave
irradiation. Reaction progress was monitored by GC–MS. After
completion, the reaction mixture was cooled to room temperature,
and 1,2,3,4-tetrahydrocarbazole was obtained by filtration. The
remaining mixture of [(HSO3-p)2im][CF3SO3]/H2O was reused
3. Conclusion
directly. 1H NMR (500 MHz, CDCl3,
d ppm): 1.86–1.93 (m, 4H),
In this paper, an environmental benign process for one-pot
microwave-assisted Fischer indole synthesis in a water medium
was established using novel SO3H-functionalized Brønsted acidic
ILs bearing two alkyl sulfonic acid groups of the imidazolium
cations and aryhydrazine hydrochlorides instead of aryhydrazines.
Thus, [(HSO3-p)2im][CF3SO3] exhibited the most efficient result for
transformation in water. The results reflect that the developed
methodology could offer significant improvements.
First, the entire process for the Fischer indoles was performed in
water without the need of organic solvents. Aryhydrazine
hydrochlorides are readily available, safe, low-toxic, and cheap
substrates that are more effective than phenylhydrazines. Second,
the reaction–separation–recycle process was quite convenient,
and the catalytic system of [(HSO3-p)2im][CF3SO3]/H2O could be
reused directly at least 12 times without a notable decrease in
catalytic activity. Third, the novel catalytic system effected by a
small amount of ILs (0.05 equivalent) could be successfully applied
to the Fischer indole synthesis using both single-carbonyl ketones
and cyclohexane-1,3-diones to afford good to excellent yields.
Further investigations involving the effectiveness of the benign
catalytic system for other reactions are currently underway.
2.70–2.74 (m, 4H), 7.05–7.12 (m, 2H), 7.27–7.29 (d, 1H, J = 7.5 Hz),
7.45–7.47 (d, 1H, J = 7.5 Hz), 7.67 (s, 1H). (Experimental proce-
dures, spectra and NMR data for the complexes see supporting
information)
4.4. UV–vis acidity evaluation
Tested ethanol solutions were prepared from dried ethanol, 3-
nitroanline and ILs, or 98% H2SO4, 85% H3PO4, 37% HCl and 99%
CF3SO3H. All the spectra were recorded on a SHIMADZU UV-
2401PC spectrophotometer at room temperature.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the
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