S.S. Bhella et al. / Tetrahedron 65 (2009) 5928–5935
5933
stand at room temperature for overnight. Then, solvent was evap-
orated under vacuum to obtain the viscous yellow oil, which was
crystallized in chloroform–ether (1:2) to obtain nitrone as light
yellow powder (yield 90%). The nitrone was dried under vacuum
and stored under refrigeration.
(C]O), 150.4 (q), 136.7 (C7a0), 129.6 (C3a0), 126.2 (C20), 123.5 (2CH),
122.3 (2CH), 119.9 (C60), 119.4 (C40), 116.7 (C50), 115.2 (CH), 112.4
(C70) 111.3 (C30), 68.7 (C5), 66.7 (C3), 56.3 (C4), 52.3 (OCH3) ppm.
Mass (ESI): 345.0 (MþNa)þ. Anal. Calcd for C19H18N2O3 requires C
70.79, H 5.63, N 8.69, and found C 70.76, H 5.60, N 8.72.
4.2.1. C-(3-Indolyl)-N-phenylnitrone (19)
4.3.3. anti-3-(1H-Indol-3-yl)-2-phenyl-isoxazolidine-4-
carbonitrile (22)
Yellow powder (ether–chloroform, 2:1), mp 92–94 ꢁC. Yield
(90%). IR (KBr): 1631, 1612, 1575, 1519, 1444, 1242, 1124 cmꢀ1
.
1H
Light brown viscous oil. Yield (334 mg, 91%). IR (CHCl3): 3411,
NMR (CDCl3, 300 MHz):
d
11.61 (br s, 1H, NH), 9.27 (s, 1H, C3b–H),
2238, 1596, 1488, 1456, 1419, 1217, 750 cmꢀ1 1H NMR (CDCl3,
.
8.42 (s,1H, C2–H), 7.89 (unresolved dd,1H, Jw6.8 Hz, C4–H), 7.72 (d,
1H, J¼6.9 Hz, C7–H), 7.55–7.43 (m, 3H, arom.–Hs & C6–H), 7.25–7.14
300 MHz):
d
8.16 (br s, 1H, NH), 7.80 (d, 1H, J¼7.8 Hz, C40–H), 7.72 (d,
1H, J¼7.8 Hz, C70–H), 7.27–7.03 (m, 5H, arom.–Hs & C60–H, C20–H),
7.02–6.96 (m, 3H, arom.–Hs & C50–Hs), 5.01 (d, 1H, J¼5.7 Hz, C3–H),
4.48 (dd, 1H, J¼10.4 Hz & 8.1 Hz, C5-Ha), 4.35 (dd, 1H, J¼10.4 Hz &
5.7 Hz), 3.68 (unresolved ddd, 1H, Jw8.0 Hz & 5.7 Hz, C4-H). 13C
(m, 4H, arom.–Hs & C5-H) ppm. 13C NMR (CDCl3, 75 MHz):
d 150.9
(q), 136.4 (C7a), 128.5 (C3a), 127.6 (C3b), 125.1 (C2), 124.3 (2CH),
122.6 (2CH), 121.7 (C6), 120.4 (C4), 119.6 (C5), 115.1 (CH), 112.3 (C7),
107.8 (C3) ppm. Mass (ESI): 236.8 (Mþ), 259.8 (MþNa)þ. Anal. Calcd
for C15H12N2O requires C 76.25, H 5.12, N 11.86, and found C 76.29, H
5.09, N 11.84.
NMR (CDCl3, 75 MHz):
d
153.5 (q), 135.6 (C7a0), 128.9 (C3a0), 125.3
(C20), 122.7 (2CH), 122.3 (2CH), 120.9 (C60), 119.7 (C40), 118.9 (C50),
117.8 (CN), 115.4 (CH), 112.7 (C70), 71.5 (C3), 66.4 (C5), 44.7 (C4).
Mass (ESI): 289.1 (Mþ), 312.1 (MþNa)þ. Anal. Calcd for C18H15N3O
requires C 74.72, H 5.23, N 14.52, and found C 74.76, H 5.20, N 14.55.
4.3. General procedure for the reaction of C-(3-indolyl)-N-
phenylnitrone (19) with various dipolarophiles (20a–f)
under monomode microwave irradiation
4.3.4. anti-3-(1H-Indol-3-yl)-2-phenyl-isoxazolidine-4-carboxylic
acid amide (23)
In the 150 ml round bottom flask, added the C-(3-indolyl)-
N-phenylnitrone (19, 1.28 mmol) and dipolarophiles (20a–f,
1.0 equiv). Then, the flask containing the contents, fitted with
a condenser was placed in the cavity of the microwave reactor. After
closing the cavity of the reactor with the cavity lid, the contents
were irradiated (150 W, 100 ꢁC) for 5 min (1 min hold time and
4 min running time) till all the nitrone was consumed (TLC). In case
of dipolarophiles (20c & 20f), they were first dissolved in dry
benzene (1 ml) to get suspension, which was then allowed to react
with nitrone (19). After completion of the reaction, the residues
were loaded onto silica gel column (60–120 mesh, column packed
in hexane); elution of column using hexane–chloroform (gradient)
afforded 21–26. The reported yields based on isolated pure prod-
ucts and relative proportions determined in the mixtures by 1H
NMR spectroscopy.
Colourless solid (hexane–chloroform, 2:1), mp 152–154 ꢁC.
Yield (358 mg, 92%). IR (KBr): 3432, 3047, 1685, 1581, 1496, 1474,
1214, 1150 cmꢀ1 1H NMR (CDCl3, 300 MHz):
. d 8.12 (br s, 1H, NH),
7.82 (d, 1H, J¼7.2 Hz, C40–H), 7.74 (d, 1H, J¼7.8 Hz, C70–H), 7.27–7.11
(m, 4H arom.–Hs & C60, C50–Hs, C20–H), 7.08 (dd, 2H, J¼7.8 Hz &
2.9 Hz, arom.–Hs), 6.93 (t, 1H, J¼7.2 Hz, arom.–H), 6.60 and 5.54 (br
s, 1H each, –NH2) 5.42 (d, 1H, J¼5.6 Hz, C3–H), 4.53 (unresolved dd,
1H, Jw8.1 Hz, C5–Ha), 4.38 (dd,1H, J¼11.2 Hz & 5.9 Hz, C5–Hb), 3.78
(unresolved ddd, 1H, Jw8.3 Hz & 5.4 Hz, C4–H) ppm. 13C NMR
(CDCl3, 75 MHz):
d
176.8 (–CONH2), 151.4 (q), 136.6 (C7a0), 128.6
(C3a0), 125.9 (C20), 124.5 (2CH), 122.3 (2CH), 120.7 (C60), 119.4 (C40),
116.7 (C50), 115.2 (CH), 112.4 (C70) 111.3 (C30), 68.7 (C5), 66.7 (C3),
56.3 (C4). Mass (ESI): 307.0 (Mþ), 330.1 (MþNa)þ. Anal. Calcd for
C18H17N3O2 requires C 70.34, H 5.58, N 13.67, and found C 70.38, H
5.56, N 13.64.
4.3.1. syn-3-(1H-Indol-3-yl)-2-phenyl-isoxazolidine-4-carboxylic
acid methyl ester (21a)
4.3.5. anti-3-(1H-Indol-3-yl)-4-methyl-2-phenyl-isoxazolidine-4-
carboxylic acid methyl ester (24)
Brownish viscous oil. Yield (327 mg, 80%). IR (CHCl3): 3382,
Yellow viscous oil. Yield (370 mg, 87%). IR (CHCl3): 3409, 2950,
2980, 1731, 1599, 1521, 1426, 1216 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
d
1733, 1596, 1488, 1456, 1201, 748 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
d
8.34 (br s, 1H, NH), 7.78 (d, 1H, J¼6.6 Hz, C40–H), 7.69 (d, 1H,
8.20 (br s, 1H, NH), 7.79 (d, 1H, J¼7.8 Hz, C40–H), 7.40 (d, 2H,
J¼7.5 Hz, C70–H), 7.26 (s, 1H, C20–H), 7.16–7.04 (m, 6H, arom.–Hs &
C60, C50–Hs), 6.97 (t, 1H, J¼7.2 Hz, arom.–H), 5.46 (d, 1H, J¼8.1 Hz,
C3–H), 4.57 (unresolved dd, 1H, Jw7.9, C5–Ha), 4.41 (dd, 1H,
J¼10.8 Hz & 6.5 Hz, C5-Hb), 3.79 (unresolved ddd, 1H, Jw8.2 Hz &
5.9 Hz, C4-H), 3.09 (s, 3H, OCH3) ppm. 13C NMR (CDCl3, 75 MHz):
J¼8.1 Hz), 7.35–7.22 (m, 4H, arom.–Hs & C60, C50–Hs), 7.21 (d, 1H,
J¼2.3 Hz, C20–H), 6.99 (dd, 2H, J¼8.4 Hz & 3.2 Hz, arom.–Hs), 6.90 (t,
1H, J¼7.2 Hz, arom.–H), 5.43 (s, 1H, C3–H), 4.61 (d, 1H, J¼8.4 Hz, C5–
H), 3.97 (d, 1H, J¼8.4 Hz, C5–H), 3.73 (s, 3H, OCH3), 1.56 (s, 3H, C4–
CH3) ppm; 13C NMR (CDCl3, 75 MHz):
d 170.5 (C]O), 150.4 (q),
d
170.1 (C]O), 150.3 (q), 135.7 (C7a0), 128.9 (C3a0), 125.9 (C20), 123.9
135.5 (C7a0), 127.8 (C3a0), 124.9 (C20), 123.7 (2CH),122.1 (2CH),120.9
(C60), 119.5 (C40), 118.5 (C50), 115.3 (CH), 112.1 (C70), 111.3 (C30), 67.2
(C5), 64.6 (C3), 53.4 (C4), 51.9 (OCH3), 18.2 (CH3) ppm. Mass (ESI):
336.1 (Mþ), 359.0 (MþNa)þ. Anal. Calcd for C20H20N2O3 requires C
71.41, H 5.99, N 8.33, and found C 71.46, H 6.01, N 8.30.
(2CH), 122.5 (2CH), 121.9 (C60), 119.5 (C40), 118.5 (C50), 115.3 (CH),
112.1 (C70), 111.3 (C30), 67.2 (C5), 64.6 (C3), 51.8 (C4), 51.4
(OCH3) ppm. Mass (ESI): 345.0 (MþNa)þ. Anal. Calcd for
C19H18N2O3 requires C 70.79, H 5.63, N 8.69, and found C 70.81, H
5.65, N 8.67.
4.3.6. anti-3-(1H-Indol-3-yl)-5-methyl-2-phenyl-isoxazolidine-4-
carboxylic acid ethyl ester (25)
4.3.2. anti-3-(1H-Indol-3-yl)-2-phenyl-isoxazolidine-4-carboxylic
acid methyl ester (21b)
Yellow viscous oil. Yield (365 mg, 88%). IR (CHCl3): 3418, 2280,
Brownish viscous oil. Yield (53 mg, 13%). IR (CHCl3): 3411, 3012,
1732, 1598, 1488, 1429, 1217, 750 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
2952, 1731, 1598, 1521, 1489, 1428, 1215 cmꢀ1
.
1H NMR (CDCl3,
d
8.16 (br s, 1H, NH), 7.80 (d, 1H, J¼7.8 Hz, C40–H), 7.72 (d, 1H,
300 MHz):
d
8.13 (br s, 1H, NH), 7.82 (d, 1H, J¼7.8 Hz, C40–H), 7.72 (d,
J¼7.8 Hz, C70–H), 7.27–7.03 (m, 5H, arom. –Hs & C60–H, C20–H),
7.02–6.96 (m, 3H, arom. –Hs & C50–Hs), 5.22 (d, 1H, J¼5.9 Hz, C3–H),
4.38 (dq, 1H, J¼8.9 Hz & 5.9 Hz, C5–H), 4.17 (q, 2H, J¼7.2 Hz, OCH2),
3.08 (dd, 1H, J¼8.9 Hz & 6.7 Hz, C4–H), 1.51 (d, 3H, J¼5.9 Hz, C5–
CH3), 1.22 (t, 3H, J¼7.2 Hz, CH3) ppm. 13C NMR (CDCl3, 75 MHz):
1H, J¼7.8 Hz, C70–H), 7.27 (d, 1H, J¼2.5 Hz, C20–H), 7.26–7.13 (m, 4H
arom.–Hs & C60, C50–Hs), 7.05 (dd, 2H, J¼7.8 Hz & 2.9 Hz, arom.–Hs),
6.93 (t, 1H, J¼7.2 Hz, arom.–H), 5.28 (d, 1H, J¼5.4 Hz, C3–H), 4.44–
4.41 (m, 2H, C5–Hs), 3.71 (unresolved ddd, 1H, Jw7.9 Hz & 5.4 Hz,
C4–H), 3.67 (s, 3H, OCH3) ppm. 13C NMR (CDCl3, 75 MHz):
d
172.0
d
170.1 (C]O), 150.3 (q), 135.7 (C7a0), 128.9 (C3a0), 125.9 (C20), 123.9