Article
Rahimizadeh et al.
amine products for secondary amine was obtained.
Reusability of catalyst was examined for 5 times un-
der the conditions on entry 20. It shows suitable yields after
each run (Entry 21 to 25).
MHz) spectrometers. All chemical shifts are reported as ppm and
were referenced to residual solvent signals. IR spectra were re-
corded on a Thermo Nicolet Avatar-370-FTIR spectrometer.
Mass spectra were recorded on Varian CH7A spectrometer.
General procedure for the synthesis of 3-aminoalkylated
indoles: A mixture of aldehyde (1 mmol), N-alkylaniline (2
mmol) and ferric hydrogensulfate (FHS) (10 mol %) was stirred at
45 oC for 3 min followed by addition of indole (1 mmol) and stir-
ring is continued till the completion of the reaction as indicated by
TLC (Table 2). The reaction mixture was diluted with diethyl
ether (10 mL) and filtrate to recover the catalyst and extracted
with (2 × 10 mL) HCl 5%. The organic phase washed with (2 × 10
mL) H2O. The organic phase was dried over Na2SO4, filtered, and
evaporated under reduced pressure. The resulting crude product
was purified by column chromatography (silica gel, hexane–
EtOAc, 3:1) to obtain analytically pure products. Some of the
products are known compounds. (Table 2) and were characterized
by comparison of their mp and spectral data with those of authen-
tic samples.
We used some catalysts such as FeCl3, FeCl2 and
Fe(NO3)3 but they had not results like Fe(HSO4)3, (Entry
26 to 28).
The scope and generality of this method is illustrated
in Table 2.
Different aldehydes, including aromatic aldehydes
with electron-donating and electron-withdrawing groups,
and different N-alkylanilines such as N-methyl- and N-eth-
ylanilines, afforded the desired products in good yields.
Electron-withdrawing groups on aldehyde react rapidly
and were good reagents in this reaction. N-methylaniline is
also better in comparison with N-ethylaniline because of
low steric effects. N-Alkylanilines were used in excess to
avoid the formation of bis(indolyl)alkanes. (Table 2)
A plausible mechanism was shown in Figure 1. Ac-
cordingly, after benzaldehyde activation with catalyst, an
iminium ion obtained from aldehyde and N-alkylaniline
which readily reacted with electron reach indole ring in 3
position. [Figure 1] The by-product is water and the cata-
lyst was regenerated after proton abstraction from indole
ring.
SPECTRA DATA
[(1H-Indol-3-yl)-(4-isopropyl-phenyl)-methyl]-methyl-
o
1
phenyl-amine (2): Dark brown solid; mp = 75-77 C H NMR
(100 MHz, CDCl3): d 7.90 (br s, 1 H), 6.90–7.45 (m, 7H), 6.40–
6.65 (d, J = 12.0 Hz, 2H), 5.50 (s, 1H), 2.70-3.05 (m, 1H), 2.80 (s,
3H), 1.15-1.40 (d, J = 12.0 Hz, 6H). IR (KBr): 3412, 2958, 2924,
1613, 1516, 1455, 741 cm–1. MS: m/z = 355 [M + H]+. Anal.
Calcd. for C25H26N2: C, 84.70; H, 7.39; N, 7.90. Found: C, 84.63;
H, 7.35; N, 7.93. [(1H-Indol-3-yl)-(4-chloro-phenyl)-methyl]-
Decreasing of reaction times, increasing of isolated
yields, low percent of bis indolylmethane formation as by-
product and solvent free conditions are the benefits of this
method by means of FHS as catalyst.29
o
1
ethyl-phenyl-amine (7): Brownish red solid; mp = 105 C H
NMR (100 MHz, CDCl3): d 8.00 (br s, 1H), 7.45–7.55 (m, 2H),
6.85–7.40 (m, 8H), 6.45–6.60 (d, J = 12.0 Hz, 2H), 5.60 (s, 1H),
3.15 (q, J = 17.0 Hz, 2H), 1.25 (t, J = 17.0 Hz, 3H). IR (KBr):
3412, 1613, 1516, 1488, 1455, 743 cm–1. MS: m/z = 361 [M + H]+.
Anal. Calcd. for C23H21ClN2: C, 76.55; H, 5.87; N, 7.76. Found:
C, 76.49; H, 5.85; N, 7.79. [(1H-Indol-3-yl)-(3-nitro-phenyl)-
methyl]-ethyl-phenyl-amine (8): Yellow solid; mp = 87-90 oC
1H NMR (100 MHz, CDCl3): d 8.10 (d, J = 8.0 Hz, 2H), 8.00 (br s,
1H), 7.45-7.55 (m, 2H), 6.85-7.40 (m, 8H), 6.45-6.60 (d, J = 12.0
Hz, 2H), 5.65 (s, 1H), 3.15 (q, J = 17.0 Hz, 2H), 1.20 (t, J = 17.0
Hz, 3H). IR (KBr): 3412, 1613, 1524, 1349, 743 cm–1. MS: m/z =
372 [M + H]+. Anal. Calcd. for C23H21N3O2: C, 74.37; H, 5.70; N,
11.31. Found: C, 74.32; H, 5.71; N, 11.36. [(1H-Indol-3-yl)-(4-
methoxy-phenyl)-methyl]-ethyl-phenyl-amine (9): Brown
solid; mp = 74 oC 1H NMR (100 MHz, CDCl3): d 8.00 (br s, 1H),
7.25–7.65 (m, 8H), 6.90–7.20 (m, 4H), 6.70–6.80 (d, J = 4.0 Hz,
2H), 5.45 (s, 1H), 3.90 (s, 3H), 3.00 (q, J = 17.0 Hz, 2H), 1.10 (t, J
EXPERIMENTAL
All solvents and reagents were purchased from Merck and
Fluka. NMR spectra were recorded on Bruker Aspect 3000 (100
Fig. 1. A plausible mechanism for this reaction.
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© 2014 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2014, 61, 000-000