Vol. 25, No. 7 (2013)
An Efficient Method for the Synthesis of Isoxazolines 3589
were performed using a scientific microwave oven (catalyst
electromagnetic System) with a power of 800 W specially
designed for organic synthesis. Thin-layer chromatography
was performed on precoated plates SiO2 (silica gel 60, F 254,
Merck) to monitor progress of the reaction and purity of the
compounds. Silica gel [60-120 mesh size), Merck] was used
for column chromatography. IR spectra of compounds were
recorded on Schimadzu IR 48 Spectrophotometer.All the NMR
spectra were recorded on BrukerAvance III, 400 MHz spectro-
meter with CDCl3/DMSO as solvent. Mass spectra were
recorded on 410 Prostar Binary LC with 500 MS IT PDA
detectors.
formed. The resulting products were purified by column
chromatography (chloroform/acetone 16:1 as eluant) to gave
1
a desired products (IIA-IIH). Melting point, IR and H NMR
spectra of compound IIC was found to be identical with the
one described in literature24 (Table-1)
5-(1H-Indol-3-yl)-3-(phenyl)-4,5-dihydroisoxazoline
(IIA, C17H14N2O): Yield: 89.92 %; m.p.: 160-162 ºC; reaction
time: 11 min; 1H NMR (400 MHz, CDCl3) 6.02-6.07 (dd, 1H),
3.55-3.62 (dd, 1H), 3.69-3.70 (dd, 1H), 7.09-7.76 (m, 10H),
8.175 (brs, 1H) ppm; IR (KBr, νmax, cm-1): 3335 (N-H), 1615
(C=C), 1572 (C=N); MS: m/z with +ve mode: 263.2 (M+.),
264.3 (M+1).
5-(1H-indol-3-yl)-3-(4-chlorophenyl)-4,5-dihydroiso-
xazoline (IIB, C17H13N2OCl): Yield: 84.34 %; m.p.: 176-
1
177 ºC; reaction time: 8 min; H NMR (400 MHz, CDCl3)
O
Ar
6.03-6.08 (dd, 1H), 3.27-3.59 (dd, 1H), 3.52-3.59 (dd, 1H),
7.10-7.68 (m, 9H), 8.15 (brs, 1H) ppm; IR (KBr, νmax, cm-1):
3410 (N-H), 1616 (C=C), 1588 (C=N); MS: m/z with +ve
mode: 297.1 (M+.), 298.2 (M+1).
CHO
O
NaOH, EtOH, r. t.
+
N
Ar
CH3
N
5-(1H-Indol-3-yl)-3-(4-methylphenyl)-4,5-dihydroiso-
xazoline (IIC, C18H16N2O):Yield: 83.27 %; m.p.: 165-166 ºC;
reaction time:- 10 min; 1H NMR (400 MHz, CDCl3) 2.39 (s,
3H), 5.99-6.04 (dd, 1H), 3.53-3.60 (dd, 1H), 3.68-3.74 (dd,
H
ICA - ICH
H
NH2OH.HCl, Basic Alumina
MW
1H), 7.09-7.64 (m, 9H), 8.15 (brs, 1H) ppm; IR (KBr, ν
,
max
Ar
cm-1): 3424 (N-H), 1610 (C=C), 1635 (C=N); MS: m/z with
+ve mode: 277.2 (M+.), 278.1 (M+1).
N
O
Ar = Aryl, Hetaryl, Naphthyl
5-(1H-indol-3-yl)-3-(2-pyridyl)-4,5-dihydroisoxazoline
(IID, C16H13N3O): Yield: 78.82 %; m.p.: 196-197 ºC; reaction
time: 14 min; 1H NMR (400 MHz, CDCl3) 6.01-6.98 (dd, 1H),
3.63-3.69 (dd, 1H), 3.79-3.87 (dd, 1H), 6.98-8.94 (m, 9H),
11.17 (brs, 1H) ppm; IR (KBr, νmax, cm-1): 3210 (N-H), 1594
(C=C), 1616 (C=N); MS: m/z with +ve mode: 265.12 (M+.),
266.2 (M+1).
IIA - IIH
N
H
Scheme-I: Synthetic route for the synthesis of target compounds (IIA-IIH)
5-(1H-indol-3-yl)-3-(4-fluorophenyl)-4,5-dihydroiso-
xazoline (IIE, C18H17N2OF): Yield: 74.62 %; m.p.: 205-207
ºC; reaction time: 14 min; 1H NMR (400 MHz, CDCl3) 6.03-
6.05 (dd, 1H), 3.53-3.59 (dd, 1H), 3.67-3.74 (dd, 1H), 6.09-
7.67 (m, 9H), 8.154 (brs, 1H) ppm; IR (KBr, νmax, cm-1): 3256
(N-H), 1608 (C=C), 1583 (C=N); MS: m/z with +ve mode:
297.32 (M+.), 298.21 (M+1).
TABLE-1
PHYSICO-CHEMICAL PROPERTIES OF SYNTHESIZED
ISOXAZOLINES VIA SCHEME-I
Compound Ar
Yield (%)a
89.92
84.34
83.57
78.82
74.62
81.27
80.24
86.62
m.p. (ºC) [L. m.p.]
160-162
IIA
IIB
IIC
IID
IIE
IIF
IIG
IIH
Phenyl
4-Chlorophenyl
4-Methylphenyl
2-Pyridyl
176-177
165-166 [167]25
196-197
5-(1H-indol-3-yl)-3-(4-methoxyphenyl)-4,5-dihydro-
isoxazoline (IIF, C18H16N2O2 ): Yield: 84.57 %; m.p.: 170-
1
173 ºC; reaction time: 15 min; H NMR (400 MHz, CDCl3)
4-Fluorophenyl
4-Methoxyphenyl
2-Naphthyl
205-207
170-173
204-206
4-Nitrophenyl
192-195
3.79 (s, 3H), 5.92-6.01 (dd, 1H), 3.59-3.61 (dd, 1H), 3.63-
3.78 (dd, 1H), 7.11-7.61 (m, 9H), 8.16 (brs, 1H) ppm; IR (KBr,
ν
max, cm-1): 3251 (N-H), 1607 (C=C), 1612 (C=N); MS: m/z
Synthesis of 5-(1H-Indol-3-yl)-3-(substituted aryl)-4,
5-dihydroisoxazoline derivatives (IIA-IIH): A mixture of
1-(1H-indol-3-yl)-3-(substituted aryl)-prop-1-en-3-ones
(1 mmol) and hydroxylamine hydrochloride (2 mmol) in EtOH
was added basic alumina (20 g) in 100 mL beaker. The reaction
mixture was thoroughly stirred and dried in air. The reactants
loaded on basic alumina were placed in an alumina bath23 and
were irradiated in the scientific microwave oven intermittently
at 30 s interval for specified time at 455 watt. Reaction progress
was monitored by TLC. Reaction mixture was cooled to room
temperature after completion of reaction and the product was
extracted into organic solvent and was kept in air after partial
evaporation of solvent fine crystals of isoxazolines were
with +ve mode: 293.3 (M+.).
5-(1H-indol-3-yl)-3-(2-naphthyl)-4,5-dihydro-
isoxazoline (IIG, C15H13N3O): Yield: 80.24 %; m.p.: 204-206
ºC; reaction time: 10 min;1H NMR (400 MHz, CDCl3) 6.02-
6.07 (dd, 1H), 3.55-3.62 (dd, 1H), 3.68-3.71 (dd, 1H), 7.02-
7.78 (m, 12H), 8.17 (brs, 1H) ppm; IR (KBr, νmax, cm-1): 3253
(N-H), 1618 (C=C), 1582 (C=N); MS: m/z with +ve mode:
313.21 (M+.).
5-(1H-indol-3-yl)-3-(4-nitrophenyl)-4,5-dihydro-
isoxazoline (IIH, C17H13N3O3):Yield: 86.62 %; m.p.: 192-195
ºC; reaction time: 14 mins; 1H NMR (400 MHz, CDCl3) 6.03-
6.06 (dd, 1H), 3.52-3.59 (dd, 1H), 3.67-3.74 (dd, 1H), 6.08-