Green route for the synthesis of 3-substituted indoles using [bmim]HSO4 as non-halogenated…
the other hand, the yields of obtained products were good-
to-excellent without formation of any side products such as
bis(indolyl) methanes that are normally obtained under acids
condition. In each case, the reaction media is clean and this
one-pot, three-component procedure revealed some improve-
ments and advantages over existing methods. However, a
signifcant fraction of this present work is the application
of [bmim][HSO4] as non-halogenated ILs, which are not
only commercially available, but also greener and non-toxic
candidate for the synthesis of 3-substituted indoles rather
than the halogenated ILs. The other features of this new
method are simple isolation and purifcation of the prod-
ucts, reusable catalyst and synthesis of three new derivative
were obtained on a Bruker DRX-300 MHz NMR instrument.
Mass spectra were taken on an Agilent 5973 Network Mass
Selective Detector instrument.
General procedure for the preparation
of 3‑substituted indoles
To a mixture of the aldehyde (1 mmol), malononitrile or
ethyl cyanoacetate (1 mmol), indole (1 mmol) in 5.0 cm3
ethanol was added [bmim]HSO4) (20 mol%). The reaction
mixture was stirred and heated under refux condition for
1–1.5 h and the reaction progress was monitored by TLC.
After completion of the reaction, the reaction mixture was
cooled to room temperature. The precipitate was fltered
of and recrystallized from ethanol to aford the desired
compound.
malononitrile as a relatively acidic compound with pKA of
11 is ionized to malononitrile anion 5. Then ionic liquid acti-
vated-aldehyde 1 react with malononitrile anion 5 in Knoev-
enagel condensation reaction to aford arylidene compound
6. Michael reaction indole 2 with 6 give intermediate 7 fol-
lowing H-shift to obtain 3-substituted indole 4 (Scheme 3).
To compare the merits of this catalytic method with
those of previously reported ones, results of the formation
of 4e were compiled in the presence of a variety of acidic
catalysts. From the results given in Table 5, the advantages
of our method are evident, regarding the catalyst amounts,
which are very important in the chemical industry especially
when they are combined with easy separation, short reaction
time and high yield accompanied by the synthesis of some
new compounds 4f, 4g, and 4h (Table 1), shows that our
studies.
The synthesis of compounds 4e was also used to assess
the reusability of the [bmim]HSO4 catalyst. After separation
of the product, the moderate liquor containing a solution of
[bmim][HSO4] in ethanol was evaporated. Then, the residue
was solved in 15 cm3 water and 15 cm3 dichloromethane was
added and the catalyst was extracted by separatory funnel.
Aqueous layer containing IL was evaporated and IL was
obtained after drying on oven for 3 h and used in the synthe-
sis of 4e for some runs. The catalyst could be reused at least
four times without appreciable loss of efciency, yield of 4e
(run no.): 95% (1), 88% (2), 88% (3), 83% (4).
2‑[(Furan‑2‑yl)(1H‑indol‑3‑yl)methyl]malononitrile (4f,
C16H11N3O) To 0.096 g furfural (1.0 mmol), 0.066 g malon-
onitrile (1.0 mmol), and 0.117 g indole (1.0 mmol) dissolved
in 5.0 cm3 EtOH and 0.047 g [bmim]HSO4) (0.2 mmol) was
added. The mixture was refuxed for 75 min, cooled, and fl-
tered. Recrystallization from ethanol aforded 0.214 g (82%)
1
4f. White solid; m.p.: 98–100 °C; H NMR (300 MHz,
Conclusion
CDCl3): δ = 4.42 (d, J = 6.8 Hz, 1H), 4.88 (d, J = 6.7 Hz,
1H), 6.07 (d, J=3.5 Hz, 1H), 6.86 (dd, J=3.5 Hz, 1.8 Hz,
1H), 7.13 (t, J=7.4 Hz, 1H), 7.20–7.28 (m, 2H), 743–7.52
(m, 3H), 8.34 (s, 1H) ppm; 13C NMR (75 MHz, CDCl3):
δ = 28.3, 41.4, 107.6, 111.1, 111.9, 112.9, 113.4, 113.8,
119.9 ppm; IR (KBr): v = 3414, 2840, 2225, 1605, 1582,
1458 cm−1.
In summary, [bmim]HSO4 has been used for the frst time
as an efective ionic liquid for the synthesis of polysubsti-
tuted pyrroles through one-pot, three-components reaction
of indole, aldehydes, and malononitrile. Mild reaction con-
ditions, wide substrate scope, excellent functional group
tolerance, good overall yields, use of an inexpensive, not
halogenated IL, and environmentally benign catalyst are the
key advantages of the present method.
2‑[(E)‑1‑(1H‑Indol‑3‑yl)‑3‑phenylallyl]malononitrile
(4g, C20H15N3) To 0.132 g cinnamaldehyde (1.0 mmol),
0.066 g malononitrile (1.0 mmol), and 0.117 g indole
(1.0 mmol) dissolved in 5.0 cm3 EtOH and 0.047 g [bmim]
HSO4) (0.2 mmol) was added. The mixture was refuxed for
67 min, cooled, and fltered. Recrystallization from ethanol
aforded 0.213 g (72%) 4g. Yellow solid; m.p.: 110–112 °C;
1H NMR (300 MHz, CDCl3): δ=4.14 (d, J=6.8 Hz, 1H),
4.51 (d, J = 6.8 Hz, 1H), 6.36 (dd, J= 15.42 Hz, 7.53 Hz,
2H), 7.17–7.50 (m, 10H), 8.36 (s, 1H) ppm; 13C NMR
Experimental
Melting points were measured using the capillary tube
method with an electro thermal 9200 apparatus. IR spectra
were recorded on Perkin Elmer FT-IR spectrometer scanning
between 4000 and 400 cm−1. 1H NMR and 13C NMR spectra
1 3
Shekarchi, Maral
