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G.S. Suresh Kumar et al. / Journal of Molecular Structure 1047 (2013) 109–120
compounds have become an interesting target for synthetic chem-
ists. The syntheses of BIMs have been reviewed by Shiri et al. [4].
One pot syntheses of phenoxyalkyl esters of 3,30-bis(indo-
lyl)methane using formylphenoxyaliphatic acids and indole/
substituted–indoles in alcohol using potash alum as catalyst and
their biological activity have recently been reported by us [3].
Due to the vast application possibility of phenoxyalkyl esters of
3,30-BIMs, we are fascinated to develop newer synthetic methods
and study their molecular properties using DFT method. To the
best of our knowledge, there are no reports regarding the use of
potassium titanyl oxalate as a catalyst for the solvent-free synthe-
ses of 3,30-BIMs, although other titanium based catalysts have been
known in a variety of organic reactions [5] and syntheses of BIMs
[6]. Herein we report efficient, solvent-free syntheses of pheno-
xyalkyl esters of 3,30-BIMs catalyzed by potassium titanyl oxalate,
[K2TiO(C2O4)2ꢁ2H2O] at relatively milder conditions. The molecular
properties like geometry, molecular electrostatic potential, total
energy, EHOMO, ELUMO, dipole moment, ionization potential, electron
affinity, electronegativity, chemical potential, absolute hardness,
softness, nucleophilicity etc. of these molecules are discussed
based on DFT method.
30%), 423.2 ([M-H]+, 100%), 309.1 ([M–Indole]+, 8.0%), 308.1 ([M–
H–Indole]+, 42%), Anal. Calcd. for C27H24N2O3: C, 76.39; H, 5.70;
N, 6.60%, Found: C, 76.28; H, 5.69; N, 6.63%.
Ethyl 2-[4-{bis(1H-indol-3-yl)methyl}phenoxy] propionate (3b).
Pale pink solid, mp = 164–166 °C, FT-IR (KBr): 3419, 3368,
1720 cmꢂ1 1H NMR (300 MHz, CDCl3): 1.24 (t, J = 14.1 Hz, 3H),
,
2.74 (t, J = 12.9 Hz, 2H), 4.12–4.20 (m, 4H), 5.80 (s, 1H), 6.53 (s,
2H), 6.77 (d, J = 8.7 Hz, 2H), 6.89 (d, J = 7.8 Hz, 2H), 7.11–7.18 (m,
4H), 7.31 (d, J = 8.7 Hz, 2H), 7.36 (d, J = 7.8 Hz, 2H), 7.81(s, 2H),
13C NMR (75 MHz, CDCl3): 14.1, 34.7, 39.3, 60.7, 63.4, 111.0,
114.3, 119.1, 119.8, 119.9, 121.8, 123.5, 127.0, 129.6, 136.5,
136.7, 156.8, 171.2, ESI-MS: m/z 438.2(M+, 30%), 437.2 ([M–H]+,
100%), 323.1 ([M–Indole]+, 8.0%), 322.1 ([M–H–Indole]+, 40%), Anal.
Calcd. for C28H26N2O3: C, 76.69; H, 5.98; N 6.39%. Found: C, 76.73;
H, 6.03; N, 6.46%.
Ethyl 2-[4-{bis(1H-indol-3-yl)methyl}-2-methoxyphenoxy] acetate
(3c). Pale pink solid, mp = 153–155 °C, FT-IR (KBr): 3385,
1743 cmꢂ1 1H NMR (300 MHz, CDCl3): 1.23 (t, J = 12.3 Hz, 3H),
,
3.65 (s, 3H), 4.21 (q, J = 12.3 Hz, 2H), 4.60 (s, 2H), 5.77 (s, 1H), 6.45
(s, 2H), 6.61 (d, J = 8.1 Hz, 2H), 6.70 (d, J = 7.5 Hz, 2H) 6.88 (s, 1H),
6.97 (t, J = 7.5 Hz, 2H), 7.12 (t, J = 7.5 Hz, 2H), 7.26 (d, J = 8.1 Hz,
2H), 7.34 (d, J = 7.5 Hz, 2H), 7.89(s, 2H), 13C NMR (75 MHz, CDCl3):
14.1, 39.7, 55.7, 61.2, 66.5, 111.1, 112.8, 113.8, 119.0, 119.4, 120.4,
121.7, 123.6, 126.9, 136.6, 138.5, 145.4, 149.2, 169.3, ESI-MS:m/z
453.2 (M+, 50%), 454.2 ([M–H]+, 10%), 339.2 ([M–Indole]+, 4.0%),
338.2 ([M–H–Indole]+, 20%), Anal. Calcd. for C28H26N2O4: C, 73.99,
H 5.77, N 6.16%. Found: C, 74.03; H, 5.81; N, 6.21%.
2. Experimental section
Melting points were measured in open capillary tubes and are
uncorrected. The 1H NMR and 13C NMR spectra were recorded on
a Bruker (Avance) 300 MHz NMR instrument using TMS as internal
standard and CDCl3 as solvent. Infrared spectra were recorded on a
JASCO FT-IR Model 410 spectrophotometer (in KBr pellet). Band
positions are reported in reciprocal centimeters (cmꢂ1). Silica
gel-G plates (Merck) were used for TLC analysis with a mixture
of n-hexane and ethyl acetate as eluent. The electrospray mass
spectra were recorded on a THERMO Finnigan LCQ Advantage
Ethyl 2-[4-{bis(1H-indol-3-yl)methyl}-2-methoxyphenoxy] propi-
onate (3d). Pale pink solid, mp = 142–144 °C, FT-IR (KBr): 3414;
3370; 1739 cmꢂ1 1H NMR (300 MHz, CDCl3): 1.22 (t, J = 12.6 Hz,
.
3H), 2.78 (t, J = 13.2 Hz, 2H), 3.66 (s, 3H), 4.12 (q, J = 12.6 Hz, 2H),
4.23 (t, J = 13.2 Hz, 2H), 5.78 (s, 1H), 6.51 (s, 2H), 6.75 (d,
J = 7.5 Hz, 1H), 6.89 (s, 1H), 6.97 (d, J = 7.5 Hz, 1H), 7.12 (t,
J = 7.8 Hz, 2H), 7.26 (t, J = 8.1 Hz, 2H), 7.36 (d, J = 7.8 Hz, 2H), 7.87
(d, J = 8.1 Hz, 2H), 13C NMR (75 MHz, CDCl3): 14.1, 34.6, 39.7,
55.8, 60.6, 64.7, 111.0, 112.9, 113.8, 119.0, 119.6, 119.8, 120.7,
121.7, 123.6, 126.9, 136.6,137.7, 146.2, 149.2, 171.2, ESI-MS: m/z
468.0 (M+, 32%), 467.3 ([M–H]+, 100%), 353.1 ([M–Indole]+, 4.0%),
352.1 ([M–H–Indole]+, 30%), Anal. Calcd. for C29H28N2O4: C,
74.34; H, 6.02; N, 5.98%. Found: C, 74.39; H, 5.98; N, 5.93%,
Ethyl 2-[2-{bis(1H-indol-3-yl)methyl}phenoxy] acetate (3e). Pale
max ion trap mass spectrometer. Samples (10 lL) (dissolved in sol-
vent such as methanol/acetonitrile/water) were introduced into
the ESI source through Finnigan surveyor autosampler. Elemental
analyses were performed on a Perkin Elmer 2400 Series II Elemen-
tal CHNS analyzer. Phenoxyaliphatic acids [7] and their corre-
sponding esters [8] were synthesised as per the reported method.
2.1. General synthesis of phenoxyalkyl esters of BIMs
pink solid, mp = 176–178 °C, FT-IR (KBr): 3401, 1749 cmꢂ1 1H
,
NMR (300 MHz, CDCl3): 1.22 (t, J = 12.9 Hz, 3H), 4.18 (q,
J = 12.9 Hz, 3H), 4.58 (s, 2H), 6.43 (s, 1H), 6.55 (s, 2H), 6.78–6.87
(m, 3H), 6.98 (t, J = 7.8 Hz, 2H), 7.11–7.17 (m, 4H), 7.34 (d,
J = 8.1 Hz, 2H), 7.44 (d, J = 7.8 Hz, 2H), 7.84 (s, 2H), 13C NMR
(75 MHz, CDCl3): 14.0, 32.5, 61.0, 66.2, 110.8, 112.0, 119.0,119.4,
120.1, 121.5, 121.7, 123.5, 127.0, 127.2, 130.0, 133.2, 136.8,
155.8, 169.1, ESI-MS: m/z 424.2 (M+, 8%), 423.2 ([M–H]+, 32%),
309.2 ([M–Indole]+, 22%), 308.2 ([M–H–Indole]+, 100%), Anal.
Calcd. for C27H24N2O3: C, 76.39; H, 5.70; N, 6.60%. Found: C,
76.45; H, 5.7; N, 6.55%.
A mixture of indole/2-methylindole (10 mmol, 2 equiv.), form-
ylphenoxyalkyl ester (5 mmol, 1 equiv.) and potassium titanyl oxa-
late (20 mol%) were mixed together and kept at 30/80 °C. The
progress of the reaction was monitored by TLC (ethyl acetate:n-
hexane 1:9 v/v). After the consumption of the starting materials,
the solid formed was scraped and extracted with ethyl acetate
(3 ꢃ 10 mL) and filtered through a cotton plug to remove the cata-
lyst. Then the combined organic layer was washed with a saturated
solution of sodium bisulfate followed by brine. The organic layer
was separated and filtered through a sodium sulfate bed. Then
the solvent was distilled off and the crude solid recrystallized from
hot ethanol. Wherever required, the purification was performed
by column chromatography (60–120 mesh silica gel, ethyl
acetate:hexane).
Ethyl 2-[2-{bis(1H-indol-3-yl)methyl}phenoxy] propionate (3f).
Pale pink solid, mp = 166–168 °C, FT-IR (KBr): 3419, 1700 cmꢂ1
,
1H NMR (300 MHz, CDCl3): 1.11 (t, J = 11.4 Hz, 3H), 2.65 (t,
J = 12.6 Hz, 2H), 3.92 (q, J = 11.4 Hz, 2H), 4.23 (t, J = 12.6 Hz, 2H),
6.27 (s, 1H), 6.66 (s, 2H), 6.81 (t, J = 7.5 Hz, 2H), 6.92–6.99 (m,
3H), 7.15–7.19 (m, 3H), 7.32 (d, J = 8.1 Hz, 2H), 7.39 (d, J = 7.8 Hz,
2H), 7.87 (s, 2H), 13C NMR (75 MHz, CDCl3): 13.9, 32.4, 34.7, 60.4,
64.1, 110.8, 111.9, 119.0, 119.4, 119.9, 120.8, 121.6, 123.4, 127.1,
127.2, 129.6, 132.9, 136.7, 155.8, 171.0, ESI-MS: m/z 438.2 (M+,
18%), 437.2 ([M–H]+, 54%), 323.0 ([M–Indole]+, 10%), 322.0 ([M–
H–Indole]+, 100%), Anal. Calcd. for C28H26N2O3: C, 76.69; H, 5.98;
N, 6.39%. Found: C, 76.78; H, 6.03; N, 6.43%.
The spectral data of phenoxyalkyl esters of BIMs (3a-n) are
summarized below: Ethyl 2-[4-{bis(1H-indol-3-yl)methyl}phenoxy]
acetate (3a). Pale pink solid, mp = 172–174 °C, FT-IR (KBr): 3397,
3344, 1747 cmꢂ1 1H NMR (300 MHz, CDCl3): 1.32 (t, J = 14.1 Hz,
,
3H), 4.29 (q, J = 14.1 Hz, 2H), 4.59 (s, 2H), 5.83 (s, 1H), 6.46 (s,
2H), 6.78 (d, J = 8.1 Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 7.16–7.30 (m,
6H), 7.40 (d, J = 8.1 Hz, 2H), 7.81 (s, 2H), 13C NMR (75 MHz, CDCl3):
14.0, 39.2, 61.3, 65.4, 111.0, 114.3, 119.0, 119.5, 119.8, 121.7, 123.6,
126.9, 129.6, 136.6, 137.4, 156.0, 169.2, ESI-MS: m/z 424.3 (M+,
Ethyl 2-[2-{bis(2-methyl-1H-indol-3-yl)methyl}-6-methoxyphen-
oxy] acetate (3g). Pink solid; mp = 170–172 °C, FT-IR (KBr): 3393,