686 JOURNAL OF CHEMICAL RESEARCH 2015
293 (12.3) (M+). Anal. calcd for C18H15NO3: C, 73.71; H, 5.15; N, 4.78;
found: C, 73.79; H, 5.04; N, 4.70%.
H2O/THF (50:50, V/V) at room temperature affords the desired
isoxazoles in reasonable yields. The Cu/AC/r-GO nanohybrid
proved to be a stable, non-hygroscopic, easy to prepare,
inexpensive, and environmentally benign heterogeneous nano-
catalyst that can be recycled for several reaction runs without
significant loss in its reactivity. The presence of amine groups on
the surface of the catalyst provides a ligand-free and leaching-
free catalyst which will be highly useful and economical for
industrial applications.
3-(3-Bromophenyl)-5-phenylisoxazole (3c): White solid; yield:
90%; m.p. 30–31°C (lit.18 30–32 °C); IR (νmax): 3100, 1596, 1471 cm–1;
1H NMR (CDCl3) δ 6.72 (s, 1H, C(4)-H of isoxazole), 6.85–6.89 (m,
1H, aryl), 7.41–7.48 (m, 2H, aryl), 7.48–7.53 (m, 4H, aryl), 7.92–7.99
(m, 2H, aryl); 13C NMR (CDCl3) δ 98.5, 123.1, 124.8, 125.1, 126.9,
128.7, 129.2, 130.7, 130.9, 131.5, 133.6, 160.6, 172.0; MS (EI) m/z (%):
299 (9.8) (M+). Anal. calcd for C15H10BrNO: 60.02; H, 3.36; Br, 26.62;
N, 4.67; found: 60.15; H, 3.47; Br, 26.69; N, 4.73%.
3,5-Diphenylisoxazole (3d): White solid; yield: 94%; m.p.
140–141 °C (lit.7 139–140 °C).; IR (νmax): 3050, 1594, 1456 cm–1;
1H NMR (CDCl3) δ 6.75 (s, 1H, C(4)-H of isoxazole), 7.45–7.52 (m,
6H, aryl), 7.89-7.95 (m, 4H, aryl); 13C NMR (CDCl3) δ 98.1, 120.3,
121.8, 125.9, 127.0, 129.3, 129.8, 130.1, 131.4, 162.8, 170.8; MS (EI)
m/z (%): 221 (6.9) (M+). Anal. calcd for C15H11NO: C, 81.43; H, 5.01; N,
6.33; found: C, 81.56; H, 5.14; N, 6.47%.
3-Phenyl-5-(pyridin-3-yl)isoxazole (3e): White solid, yield: 92%;
m.p. 143–144 °C (lit.24 143–144 °C); IR (νmax): 3112, 1598, 1463 cm–1;
1H NMR (CDCl3) δ 6.83 (s, 1H, C(4)-H of isoxazole), 7.34–7.40 (m,
4H, aryl), 7.61–7.69 (m, 2H, aryl), 8.03 (s, 1H, aryl), 8.27 (d, J = 8.0 Hz,
2H); 13C NMR (CDCl3) δ 97.1, 122.5, 124.7, 127.0, 128.9, 129.4, 131.2,
133.8, 145.9, 152.0, 164.1, 169.3; MS (EI) m/z (%): 222 (14.8) (M+).
Anal. calcd for C14H10N2O: C, 75.66; H, 4.54; N, 12.60; found: C, 75.74;
H, 4.62; N, 12.69%.
Experimental
All chemical reagents were purchased from either Fluka or Merck.
Solvents were purified by standard procedures, and stored over 3Å
molecular sieves. Reactions were followed by TLC using SILG/UV
254 silica-gel plates. Column chromatography was performed on silica
gel 60 (0.063–0.200 mm, 70–230 mesh; ASTM). Melting points were
measured using an Electrothermal IA 9000 melting point apparatus
in open capillary tubes and are uncorrected. IR spectra were obtained
using a Shimadzu FT-IR-8300 spectrophotometer. H and 13C NMR
1
spectrum was recorded on Bruker Avance-DPX-250 spectrometer
operating at 250/62.5 MHz, respectively. Chemical shifts are given
in δ relative to TMS as an internal standard, coupling constants J are
1
given in Hz. Abbreviations used for H NMR signals are: s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. GC-MS
was performed on a Shimadzu GC/MS-QP 1000-EX apparatus (m/z;
rel.%). Elemental analyses were performed on a PerkinElmer 240-B
micro-analyser. Halogen atoms in compounds were analysed using
the oxygen-flask combustion method (Schoniger application) and
subsequent potentiometric titration by a 835 Titrando Metrohm Titro
processor instrument and ion chromatography analysis using a Dionex
IC system.
3-(2,6-Dichlorophenyl)-5-phenyl-isoxazole (3f): Colourless liquid;
1
yield: 83%; IR (νmax): 3085, 1563, 1462, 764 cm-1; H NMR (CDCl3)
δ 6.85 (s, 1H, C(4)-H of isoxazole), 7.38–7.43 (m, 1H, aryl), 7.47–7.52
(m, 5H, aryl), 7.91–7.98 (m, 2H, aryl); 13C NMR (CDCl3) δ 99.8, 126.0,
127.5, 128.9, 129.1, 129.9, 130.8, 132.1, 136.4, 162.7, 171.2; MS (EI) m/z
(%): 289 (11.9) (M+). Anal. calcd for C15H9Cl2NO: C, 62.09; H, 3.13;
Cl, 24.44; N, 4.83; found: C, 62.17; H, 3.21; Cl, 24.49; N, 4.96%.
2-(3-(4-Chlorophenyl)isoxazol-5-yl)propan-2-ol (3g): White solid;
yield 91%; m.p. 97–98 °C; IR (νmax): 3400, 3048, 2976, 1598, 1461,
Synthesis of 3,5-disubstituted isoxazoles using Cu/AC/r-GO nanohybrid;
general procedure
1
784 cm–1; H NMR (CDCl3) δ 1.73 (s, 6H, 2CH3), 2.81 (s, 1H, OH),
In a round-bottom flask (50 mL), a mixture of Cu/AC/r-GO
nanohybrid (0.4 g, 0.008 mol %), appropriate hydroximyl chloride
(0.01 mol), alkyne (0.012 mol), and NaHCO3 (0.012 mol) were stirred
in H2O/THF (50:50, V/V) for the appropriate times (Table 2). After
completion of the reaction, the reaction mixture was vacuum-filtered
using a sintered-glass funnel and the residue was washed with acetone
(2 × 10 mL). The filtrate was then evaporated under vacuum to remove
the solvent. The remaining foam was dissolved in CHCl3 (100 mL) and
subsequently washed with water (2 × 100 mL). Afterwards, the organic
layer was dried over anhydrous sodium sulfate and evaporated. The
crude product was purified by short column chromatography on silica
gel eluting with n-hexane:EtOAc.
6.68 (s, 1H, C(4)-H of isoxazole),7.25 (d, J = 7.9 Hz, 2H, aryl), 7.67 (d,
J = 7.9 Hz, 2H, aryl); 13C NMR (CDCl3) δ 31.5, 70.4, 98.1, 126.0, 128.4,
+
130.8, 137.2, 162.7, 175.1; MS (EI) m/z (%): 237 (13.7) (M ). Anal.
calcd for C12H12ClNO2: C, 60.64; H, 5.09; Cl, 14.92; N, 5.89; found: C,
60.51; H, 5.17; Cl, 15.03; N, 5.96%.
5-((4-Methoxyphenoxy)methyl)-3-(4-nitrophenyl)isoxazole (3h):
White solid; yield: 95%; m.p. 139–140 °C (lit.7 138–140 °C); IR (νmax):
3071, 2943, 1590, 1563, 1480, 1348, 1216 cm–1; 1H NMR (CDCl3)
δ 3.47 (s, 3H, OCH3), 5.29 (s, 2H, OCH2), 6.83 (s, 1H, C(4)-H of
isoxazole), 6.75 (d, J = 8.0 Hz, 2H, aryl), 6.89 (d, J = 8.0 Hz, 2H, aryl),
7.80 (d, J = 8.1 Hz, 2H, aryl), 8.01 (d, J = 8.1 Hz, 2H, aryl); 13C NMR
(CDCl3) δ 53.1, 64.5, 97.6, 117.9, 119.0, 126.2, 129.7, 136.1, 148.5,
152.0, 156.9, 163.4, 171.8; MS (EI) m/z (%): 326 (15.6) (M+). Anal.
calcd for C17H14N2O5: C, 62.57; H, 4.32; N, 8.59; found: C, 62.65; H,
4.39; N, 8.72%.
Recycling the catalyst
After completion of the reaction, the catalyst was vacuum-filtered
from the reaction mixture using a sintered glass funnel followed
by successive washing with distilled water (20 mL) and anhydrous
acetone (20 mL). The catalyst was then kept in a vacuum oven at 80 °C
for 1 h and stored in a sealed vessel in a refrigerator.
1-(4-((3-(Furan-2-yl)isoxazol-5-yl)methoxy)phenyl)ethanone (3i):
White solid; yield: 84%; m.p. 136–137 °C (lit.7 135–136 °C); IR (νmax):
1
3100, 2951, 1715, 1561, 1479, 1228 cm–1; H NMR (CDCl3) δ 2.78 (s,
N,N-Dimethyl-4-(5-phenylisoxazol-3-yl)benzenamine (3a): White solid;
yield 84%; m.p. 126–128 °C; IR (νmax): 3105, 2973, 1596, 1483 cm–1;
1H NMR (CDCl3) δ 2.97 (s, 6H, 2CH3), 6.02 (s, 1H, C(4)-H of isoxazole),
6.98 (d, J = 8.5 Hz, 2H, aryl), 7.39 (d, J = 8.5 Hz, 2H, aryl), 7.68–7.73 (m,
2H, aryl), 7.81–7.86 (m, 3H, aryl); 13C NMR (CDCl3) δ 44.6, 99.1, 120.3,
124.5, 125.9, 127.5, 128.1, 129.9, 131.2, 141.5, 169.8, 171.1; MS (EI) m/z
(%): 264 (10.5) (M +). Anal. calcd for C17H16N2O: C, 77.25; H, 6.10; N,
10.60; found: C, 77.38; H, 6.17; N, 10.52%.
Ethyl 4-(5-phenylisoxazol-3-yl)benzoate (3b): White solid; yield
92%; m.p. 139–141 °C; IR (νmax): 3072, 2973, 1742, 1590, 1483 cm–1;
1H NMR (CDCl3) δ 1.38 (t, J = 7.6 Hz, 3H, CH3), 4.26 (q, J = 7.6 Hz,
2H,CH2), 6.42 (s, 1H, C(4)-H of isoxazole), 7.21–7.26 (m, 3H, aryl),
7.50–7.54 (m, 2H, aryl), 7.69 (d, J = 8.1 Hz, 2H, aryl), 7.90 (d, J = 8.1
Hz, 2H, aryl); 13C NMR (CDCl3) δ 13.5, 64.2, 97.9, 126.2, 127.0, 127.8,
129.0, 130.4, 131.0, 132.1, 133.7, 163.5, 167.8, 179.9; MS (EI) m/z (%):
3H, CH3), 5.29 (s, 2H, OCH2), 6.58 (s, 1H, C(4)-H of isoxazole), 6.90
(d, J = 2.5 Hz, 1H, C(3)-H of furan), 7.15 (d, J = 8.3 Hz, 2H, aryl), 7.62
(t, J = 2.5 Hz, 1H, C(4)-H of furan), 7.83 (d, J = 2.5 Hz, 1H, C(5)-H of
furan), 7.98 (d, J = 8.3 Hz, 2H, aryl); 13C NMR (CDCl3) δ 23.0, 62.7,
99.2, 108.9, 115.8, 116.3, 131.7, 132.5, 142.9, 143.7, 154.8, 162.5, 168.0,
184.5; MS (EI) m/z (%): 283 (12.6) (M +). Anal. calcd for C16H13NO4:
C, 67.84; H, 4.63; N, 4.94; found: C, 67.92; H, 4.70; N, 5.08 %.
1,3-Dimethyl-7-((3-phenylisoxazol-5-yl)methyl)-1H-purine-
2,6(3H,7H)-dione (3j): White solid; yield: 86%; m.p. 123–124 °C
(lit.19 123 °C); IR (νmax): 3075, 2938, 1725, 1708, 1697, 1556, 1462 cm–1;
1H NMR (CDCl3) δ (s, 3H, N3-CH3), 3.59 (s, 3H, N1-CH3), 5.69 (s,
2H, NCH2), 6.75 (s, 1H, C(4)-H of isoxazole), 7.44–7.46 (m, 3H, aryl),
7.75–7.79 (m, 3H, aryl, C(8)-H of theophylline); 13C NMR (CDCl3) δ
28.0, 31.2, 41.1, 102.4, 106.2, 126.8, 128.2, 128.9, 130.3, 141.2, 148.8,
151.5, 155.2, 162.8, 165.7; MS (EI) m/z (%): 337 (7.4) (M +). Anal. calcd