Synthesis of novel 2H-chromene-3-carboxylate isoxazole/isoxazoline derivatives via 1,3-dipolar cycloaddition reaction (NOAC)

Article abstract of DOI:10.1134/S1070363217020293

Synthesis of novel (3-phenylisoxazol-5-yl)methyl-2H-chromene-3-carboxylates (7a–7d) and (3-phenyl-4,5-dihydroisoxazol-5-yl)methyl-2H-chromene-3-carboxylates (8a–8p) by 1,3-dipolar cycloaddition, and nitrile oxide and alkyne cycloaddition (NOAC) is presented. The products are characterised by IR, ¹H and ¹³C NMR, and ESI-MS data.

Full text of DOI:10.1134/S1070363217020293

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 2, pp. 331–339. © Pleiades Publishing, Ltd., 2017.
Synthesis of Novel 2H-Chromene-3-carboxylate
Isoxazole/Isoxazoline Derivatives
via 1,3-Dipolar Cycloaddition Reaction (NOAC)1
B. Srinivas and G. L. D. Krupadanam*
Natural Products Lab, Department of Chemistry, Osmania University, Hyderabad, Telangana, 500007 India
*e-mail: davidkrupadanam624@gmail.com
Received September 6, 2016
Abstract—Synthesis of novel (3-phenylisoxazol-5-yl)methyl-2H-chromene-3-carboxylates (7a–7d) and (3-
phenyl-4,5-dihydroisoxazol-5-yl)methyl-2H-chromene-3-carboxylates (8a–8p) by 1,3-dipolar cycloaddition,
and nitrile oxide and alkyne cycloaddition (NOAC) is presented. The products are characterised by IR, 1H and
13C NMR, and ESI-MS data.
Keywords: 2H-chromene, 1,3-dipolar cycloadditions, 3,5-disubstitutedisoxazoles, isoxazolines
DOI: 10.1134/S1070363217020293
2H-Chromene derivatives are synthesized mostly
from salicylaldehydes [1]. Those exhibited a broad
range of pharmacological and biological [2–8] prope-
rties. The main representative of this class of com-
pounds is biologically active 2H-chromene-3-carbo-
xylic acid, isoxazole and isoxazoline derivatives
synthesized by 1,3-dipolar cycloaddition of nitrile
oxides to alkynes and alkenes [9]. Nitrile oxides are
generated usually from their aldoximes using different
oxidants like NaOCl, NBS, NCS, t-BuOI, and t-BuOCl
[10]. Many isoxazole derivatives are biologically
active compounds [11–15] and pharmaceuticals
[16–20]. Combining two and more bioactive moieties
in one molecule has been used as an efficient strategy
for designing new drugs [21]. The above information
initiated our study of synthesis of novel (3-phenyliso-
xazol-5-yl)methyl-2H-chromene-3-carboxylates (7a–
7d) and (3-phenyl-4,5-dihyroisoxazol-5-yl)methyl-2H-
chromene-3-carboxylates (8a–8p) regioselectively based
on 2H-chromene-3-carboxylic acids (2a, 2b).
solid 2H-chromene-3-carboxylic acids 2a, 2b with
high yields (Scheme 1).
Prop-2-yn-1-yl-2H-chromene-3-carboxylates 3a, 3b
and allyl 2H-chromene-3-carboxylates 4a, 4b were
synthesized independently from 2H-chromene-3-car-
boxylic acids 2a, 2b, propargyl bromide and allyl
bromide in the presence of K2CO3 as a base with
catalytic amounts of NaI with high yields (Scheme 2).
Scheme 1. Synthesis of 2H-chromene-3-carboxylic acids
(2a, 2b).
R1
O
CN
1a, 1b
(2) HCl, H2O,
(1) 10 % NaOH,
0−5°C, PH-1
H2O, 3 h,100°C
RESULTS AND DISCUSSION
R1
Synthesis of substituted 2H-chromene-3-cyanides
1a, 1b from substituted salisylaldehydes and
acrylonitrile was performed using the Baylis–Hillman
reaction [1]. Hydrolysis of 2H-chromene-3-cyanides
1a, 1b upon refluxing with NaOH solution (10%) gave
O
OH
O
2a, 2b
1 The text was submitted by the authors in English.
R1 = H (1a, 2a), OCH3 (1b, 2b).
331

332
SRINIVAS, KRUPADANAM
Scheme 2. Synthesis of prop-2-yn-1-yl-2H-chromene-3-carboxylates (3a, 3b) and allyl-2H-chromene-3-carboxylates (4a, 4b).
R1
R1
R1
O
O
O
2
1
O
OH
O
2a, 2b
3a, 3b
O
O
O
4a, 4b
(1) Propargyl bromide, K2CO3, acetone, reflux, 1–3 h; (2) allyl bromide, K2CO3, acetone, reflux, 1–3h. R1 = H (2a, 3a, 4a),
OCH3 (2b, 3b, 4b).
Scheme 3. Synthesis of substituted benzaldehyde oximes (6a–6i).
OH
R2
N
R2
O
.
R3
R4
R3
R4
NH2OH HCl, NaOAc
H
H
EtOH, H2O, reflux,1 h
R6
R6
R5
R5
5a−5i
6a−6i
R2 = R3 = R4 = R5 = R6 = H (6a), R2 = R4 = R6 = OCH3, R3 = R5 = H (6b), R2 = R3 = R5 = R6 = H, R4 = OCH3 (6c), R2 = R5 =
R6 = H, R3 = R4 OCH3 (6d), R2 = R6 = H, R3 = R4 = R5 = OCH3 (6e), R2 = R3 = R5 = R6 = H, R4 = CH3 (6f), R2 = R3 = R5 =
R6 = H, R4 = Cl (6g), R2 = R3 = R5 = R6 = H, R4 = OCH2Ph (6h), R2 = R3 = R5 = R6 = H, R4 = OPh (6i).
Synthesis of substituted benzaldehyde oximes 6a–
6i from substituted benzaldehydes 5a–5i was reported
earlier [22]. A mixture of a 5a–5i, hydroxylamine
hydrochloride and sodium acetate in ethanol was
refluxed for 1h to give the products 6a–6i in high
yields (80–96%) (Scheme 3).
EXPERIMENTAL
All reagents and solvents were purchased from
commercial sources and used without further
purification. Melting points were determined in open
capillaries on an electrical melting point apparatus. IR
spectra were recorded on a Shimadzu FT-IR-8400
Regioselective synthesis of substituted (3-phenyliso-
xazol-5-yl)methyl-2H-chromene-3-carboxylates 7a–7d
was carried out from substituted phenyl nitrile oxides
and prop-2-yn-1-yl-2H-chromen-3-carboxylates 3a, 3b
using 1,3-dipolar cycloaddition reaction. Only the sole
products 7a–7d were formed because of steric crowding
of chromene and electronic factors. Substituted phenyl
nitrile oxides were generated in situ from the cor-
responding benzaldehyde oximes (6d, 6e, 6g, 6i) in the
presence of NaOCl as an oxidant and triethylamine as
a base (Scheme 4). No side products 9a–9d were detected.
1
spectrophotometer in KBr pellets. H and 13C NMR
spectra were measured on
a
Bruker-DPX-400
spectrometer in DMSO-d6 and CDCl3 using TMS as
the standard. ESI-MS spectra were measured on a
LCMS 2010 VG mass spectrometer.
1
2H-Chromene-3-carboxylic acids (2a). H NMR
spectrum, δ, ppm: 4.9 d (J = 1.2 Hz, 2H, OCH2), 6.8 d
(J = 8.0 Hz, 1H, H8), 6.95 t.d (J = 7.2, 7.6, 0.8, 1.2 Hz,
1H, H6), 7.26 t.d (J = 8.0, 7.6, 1.6, 1.2 Hz, 1H, H7),
7.32 d.d (J = 7.6, 1.6 Hz, 1H, H5), 7.45 s (1H, H4),
12.86 (COOH). 13C NMR spectrum, δ, ppm: 64.18
(C2), 116.27 (C8), 120.72 (C4a), 121.5 (C6), 121.89
(C5), 129.25 (C7), 132.53 (C3), 135.90 (C4), 155.42
(C8a), 169.2 (COOH).
Synthesis of substituted (3-phenyl-4,5-dihydroiso-
xazol-5-yl)methyl-2H-chromene-3-carboxylates 8a–8p
from allyl 2H-chromene-3-carboxylates 4a, 4b pro-
ceeded regioselectively with substituted phenyl nitrile
oxides via 1, 3-dipolar cycloaddition reaction that led
to the corresponding solid products with high yields.
No side products 10a–10p were detected (Scheme 5).
Synthesis of prop-2-yn-1-yl-2H-chromene-3-
carboxylates (3a, 3b). To a stirred mixture of 2H-
chromene-3-carboxylic acids 2a, 2b (1 g, 0.0056 mol),
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SYNTHESIS OF NOVEL 2H-CHROMENE-3-CARBOXYLATE
333
Scheme 4. Regioselective synthesis of substituted (3-phenylisoxazol-5-yl)methyl-2H-chromene-3-carboxylates (7a–7d).
R1
R2
R3
R3
O
N
R4
R5
O
R2
O
R4
N
O
R6
HO
R5
R1
R6
6d, 6e, 6g, 6i
H
7a−7d
O
+
NaOCl, DCM, NEt3,
room temperature
O
R1
O
O
O
3a, 3b
N
O
R2
R3
O
R6
R5
R4
9a−9d
Not formed
R1 = R2 = R3 = R5 = R6 = H, R4 = OPh (7a), R1 = R3 = R4 = OCH3, R2 = R5 = R6 = H (7b), R1 = R3 = R4 = R5 = OCH3, R2 =
R6 = H (7c), R1 = OCH3, R2 = R3 = R5 = R6 = H, R4 = Cl (7d).
Scheme 5. Regioselective synthesis of substituted (3-phenyl-4,5-dihydroisoxazol-5-yl)methyl-2H-chromene-3-carboxylates
(8a–8p).
R3
R1
R4
R5
R2
R2
R3
O
N
O
N
O
R4
HO
R1
R6
H
O
O
R6
R5
6a−6h
8a−8p
O
NaOCl, DCM, NEt3,
room temperature
R1
+
O
O
4a, 4b
O
N
O
R2
R3
O
R6
R5
R4
10a−10p
Not formed
R1 = R2 = R3 = R4 = R5 = R6 = H (8a), R1 = R3 = R5 = H, R2 = R4 = R6 = OCH3 (8b), R1 = R2 = R3 = R5 = R6 = H, R4 = OCH3
(8c), R1 = R2 = R5 = R6 = H, R3 = R4 = OCH3 (8d), R1 = R2 = R6 = H, R3 = R4 = R5 = OCH3 (8e), R1 = R2 = R3 = R5 = R6 = H,
R4 = CH3 (8f), R1 = R2 = R3 = R5 = R6 = H, R4 = Cl (8g), R1 = R2 = R3 = R5 = R6 = H, R4 = OCH2Ph (8h), R1 = OCH3, R2 =
R3 = R4 = R5 = R6 = H (8i), R1 = R2 = R4 = R6 = OCH3, R3 = R5 = H (8j), R1 = R4 = OCH3, R2 = R3 = R5 = R6 = H (8k), R1 =
R3 = R4 = OCH3, R2 = R5= H (8l), R1 = R3 = R4 = R5 = OCH3, R2 = R6 = H (8m), R1 = OCH3, R2 = R3 = R5 = R6 = H, R4 = CH3
(8n), R1 = OCH3, R2 = R3 = R5 = R6 = H, R4 = Cl (8o), R1 = OCH3, R2 = R3 = R5 = R6 = H, R4 = OCH2Ph (8p).
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334
SRINIVAS, KRUPADANAM
anhydrous K2CO3 (1.54 g, 0.0112 mol) and catalytic
amount of NaI in 50 mL of anhydrous acetone was
added propargyl bromide (1.28 mL, 0.0170 mol)
within 15 min, followed by refluxing for 3–4 h. The
reaction was monitored by TLC. Upon completion of
the process the solvent was evaporated under reduced
pressure. The reaction mixture was washed with
hexane for removal of excess propargyl bromide, the
residual mixture was poured into 100 mL of ice-water
upon stirring, and extracted with EtOAc. The organic
layer was separated, washed with brine, dried with
Na2SO4, and concentrated under reduced pressure. The
products 3a, 3b were purified by column chromato-
graphy.
the organic layer separated, washed with brine, dried
with Na2SO4, and concentrated under reduced pressure.
A raw product 4a, 4b was purified by column chromato-
graphy.
Allyl 2H-chromene-3-carboxylate (4a). Colourless
1
oil, yield 76%. H NMR spectrum, δ, ppm: 4.71 d.t
(J = 5.7, 1.4 Hz, 2H, H1ʹ), 5.00 d (J = 1.4 Hz, 2H, H2),
5.27–5.30 (ABq, J = 10.29, 1.25 Hz, 1H, H3ʹb), 5.35–
5.39 (ABq, J = 17.06, 1.5 Hz, 1H, H3ʹa), 5.92–6.04 m
(1H, H2ʹ), 6.84 d (J = 8.2 Hz, 1H, H6), 6.89–6.94 m
(1H, H8), 7.12–7.15 m (1H, H7), 7.23 d.d.d (J = 8.1,
7.5, 1.7 Hz, 1H, H5), 7.46 br.d (J = 0.7 Hz, 1H, H4).
13C NMR spectrum, δ, ppm: 64.45 (C1ʹ), 65.43 (C2),
116.17 (C8), 118.51 (C4ʹa), 120.90 (C3ʹ), 121.81 (C6),
122.32 (C5), 128.98 (C7), 132.02-132.03 (C2ʹ), 132.04–
132.05 (C3), 133.90 (C4), 155.19 (C8ʹa), 164.28 (C3ʹa).
Prop-2-yn-1-yl-2H-chromene-3-carboxylate (3a).
White solid, yield 80%, mp 48–50°C. IR spectrum, ν,
cm–1: 1725 (C=O), 2150 (C≡C). 1H NMR spectrum, δ,
ppm: 2.53 t (J = 2.5 Hz, 1H, H3ʹ), 4.82 d (J = 2.5 Hz,
2H, H2), 5.04 d (J = 1.3 Hz, 2H, H1ʹ), 6.85 d (J = 8.2
Hz, 1H, H8), 6.93 t.d (J =7.5, 1.1 Hz, 1H, H6), 7.14 d.d
(J = 7.5, 1.6 Hz, 1H, H7), 7.22–7.26 m (1H, H5), 7.50 s
(1H, H4). 13C NMR spectrum, δ, ppm: 52.44 (C1ʹ),
64.28 (C2), 75.18 (C3ʹ), 77.54 (C2ʹ), 116.42 (C8),
120.76 (C4ʹa), 121.50 (C6), 121.68 (C5), 129.34 (C7),
132.67 (C3), 134.76 (C4), 155.28 (C8ʹa), 163.70 (C3ʹa).
Allyl 8-methoxy-2H-chromene-3-carboxylate (4b).
1H NMR spectrum, δ, ppm: 3.78 s (3H, H9), 4.63 d.t
(J = 5.6, 1.3 Hz, 2H, H1ʹ), 4.98 d (J = 1.3 Hz, 2H, H2),
5.19 (ABq, J = 10.29, 1.25 Hz, 1H, H3ʹb), 5.24–5.32
(ABq, J = 17.37, 1.25 Hz, 1H, H3ʹa), 5.84–5.94 m (1H,
H2ʹ), 6.69 d.d (J = 4.9, 4.1 Hz, 1H, H7), 6.78 d (J =
1.1 Hz, 1H, H6), 6.80 s (1H, H4), 7.37 d (J = 1.1 Hz,
1H, H5). 13C NMR spectrum, δ, ppm: 55.04 (C9), 63.69
(C1ʹ), 64.36 (C2), 113.52 (C7), 117.42 (C4ʹa), 119.92
(C3ʹ), 120.45 (C5), 120.51 (C6), 121.40 (C2ʹ), 130.98
(C3), 132.76 (C4), 143.03 (C8ʹa), 146.88 (C8), 163.08
(C3ʹa).
Prop-2-yn-1-yl 8-methoxy-2H-chromene-3-carbo-
xylate (3b). Yellow solid, yield 78%, mp 80–82°C. IR
1
spectrum, ν, cm–1: 1725 (C=O), 2160 (C≡C). H NMR
spectrum, δ, ppm: 2.53 t (J = 2.4 Hz, 1H, H3ʹ), 3.87 s
(3H, H9ʹ), 4.82 d (J = 2.5 Hz, 2H, H2), 5.06 d (J =
1.4 Hz, 2H, H1ʹ), 6.79 d.d (J = 5.7, 3.4 Hz, 1H, H7),
6.88 d (J = 2.2 Hz, 1H, H5), 6.89 s (1H, H4), 7.49 t (J =
1.3 Hz, 1H, H6). 13C NMR spectrum, δ, ppm: 52.24
(C1ʹ), 56.10 (C9ʹ), 64.57 (C2), 75.19 (C3ʹ), 77.53 (C2ʹ),
114.81 (C7), 121.06 (C4ʹa), 121.42 (C5), 121.55 (C6),
121.63 (C3), 134.69 (C4), 144.20 (C8ʹa), 147.96 (C8),
163.59 (C3ʹa). ESI-MS: m/z 282.1 [M + K]+, 284.1[M +
K + 2]+ .
Synthesis of substituted (3-phenylisoxazol-5-yl)
methyl-2H-chromene-3-carboxylates (7a–7d). To a
stirred solution of a compound 3a, b (100 mg, 0.46 mmol)
in 5 mL of dichloromethane were add trimethylamine
(0.064 mL, 0.46 mmol) and 2 mL of aqueous NaOCl
(9–12%) at. A substituted benzaldehyde oxime 6d, 6e,
6g, 6i (0.46 mmol) was added slowly within 30 min.
The reaction mixture was stirred at room temperature
for 6–8 h. Upon completion of the process, the reaction
mixture was dissolved in 10 mL of DCM and 20 mL of
water were added. The organic layer was separated,
dried over anhydrous Na2SO4 and concentrated under
reduced pressure. The raw products were purified by
column chromatography (silica gel 60–120, EtOAc/
hexane).
Synthesis of allyl 2H-chromene-3-carboxylates
(4a, 4b). To a stirred solution of 2H-chromene-3-
carboxylic acid 2a, 2b (1 g, 0.0056 mol) were added
anhydrous K2CO3 (1.54 g, 0.0112 mol), catalytic
amount of NaI in 50 mL of anhydrous acetone, and
allyl bromide (1.44 mL, 0.0170 mol) within 15 min
followed by refluxing for 1–3 h. The reaction was
monitored by TLC. Upon completion of the reaction,
the solvent was removed under reduced pressure, then
reaction mixture was poured into 100 mL of ice-water
upon stirring. The mixture was extracted with EtOAc,
[3-(4-Phenoxyphenyl)isoxazol-5-yl]methyl-2H-
chromene-3-carboxylate (7a). Light brown solid,
yield 80%, mp 106–108°C. IR spectrum, ν, cm–1: 1705
(C=O), 1639 (C=N). 1H NMR spectrum, δ, ppm: 4.80 s
(2H, H2ʹ), 5.11 s (2H, H5ʹa), 6.50 s (1H, H4), 7.04 d (J =
8.8 Hz, 2H, H5ʹ,8ʹ), 7.32–7.36 m (2H, H6ʹ,7ʹ), 7.37–7.47
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SYNTHESIS OF NOVEL 2H-CHROMENE-3-CARBOXYLATE
335
m (7H, H3″,5″,2‴,3‴,4‴,5‴,6‴), 7.73 d (J = 8.8 Hz, 3H, H4ʹ,2″,6″).
13C NMR spectrum, δ, ppm: 56.6 7 (C5ʹa), 70.11 (C2ʹ),
99.77 (C4), 114.53–114.70 (C8ʹ), 115.29 (C4ʹa), 121.69
(C3″,5″), 127.45 (C2‴,6‴), 127.49–127.53 (C6ʹ), 128.03–
128.08 (C4‴), 128.11 (C1″), 128.19–128.22 (C2″,6″),
128.25 (C5ʹ,3‴,5‴), 128.65 (C7ʹ), 128.69–128.74 (C3ʹ),
136.59 (C4ʹ), 160.26 (C8ʹa,4″,1‴), 162.06 (C5), 166.62–
166.37 (C3), 171.55 (C3ʹa). ESI-MS: m/z 425.0[M + H]+,
454.1[M + H + N2]+.
and 2 mL of aqueous NaOCl (9–12%). That was followed
by addition of a benzaldehyde oxime 6a–6h
(0.46 mmol) in portions within 30 min. The reaction
mixture was stirred for 6–8 h. Upon completion of the
process (TLC) the reaction mixture was dissolved in
10 mL of DCM and 20 mL of water and separated. The
organic layer was dried by Na2SO4, concentrate under
reduced pressure, and purified by column chromato-
graphy (silica gel 60–120 mesh, EtOAc/hexane).
[3-(3,4-Dimethoxyphenyl)isoxazol-5-yl]methyl-8-
methoxy-2H-chromene-3-carboxylate (7b). White
solid, yield 78%, mp 134–136°C. IR spectrum, ν, cm–1:
1720 (C=O), 1656 (C=N). 1H NMR spectrum, δ, ppm:
3.88 s (3H, H9ʹ), 3.94 d (J = 8.4 Hz, 6H, H3″a,4″a), 5.30 s
(2H, H2ʹ), 5.36 s (2H, H5ʹa), 6.62 s (1H, H4), 6.83–6.77
m (1H, H7ʹ), 6.90 d.d (J = 7.0, 4.2 Hz, 3H, H6″,5″), 6.94
s (1H, H2″), 7.30 d.d (J = 8.3, 1.9 Hz, 1H, H6ʹ), 7.42 d
(J = 1.8 Hz, 1H, H5ʹ), 7.52 s (1H, H4ʹ). 13C NMR
spectrum, δ, ppm: 56.16 (C3″a), 56.54 (C9ʹ), 56.34 (C4″a),
60.93 (C5ʹa), 64.54 (C2ʹ), 102.45 (C4), 104.26 (C2″),
115.06 (C5″), 121.13 (C7ʹ), 121.32 (C4ʹa), 121.37 (C5ʹ,6″),
121.65 (C6ʹ), 123.99 (C1″), 135.19 (C3ʹ), 140.07 (C4ʹ),
144.32 (C8ʹa), 148.04 (C3″, 4″), 153.69 (C8ʹ), 162.54
(C5), 163.68 (C3), 167.04 (C3ʹa). ESI-MS: m/z 424.1
[M + H]+, 425.1[M + H + 1]+.
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl-2H-
chromene-3-carboxylate (8a). White solid, yield
85%, mp 104–106°C. IR spectrum, ν, cm–1: 1704 (C=O),
1636 (C=N). 1H NMR spectrum, δ, ppm: 3.22 d.d (J =
16.7, 6.6 Hz, 1H, H4), 3.52 d.d (J = 16.7, 10.9 Hz, 1H,
H4), 4.33 d.d (J = 11.9, 5.3 Hz, 1H, H5ʹa), 4.43 d.d (J =
11.9, 3.9 Hz, 1H, H5ʹa), 4.95 t (J = 1.2 Hz, 2H, H2ʹ),
5.01–5.11 m (1H, H5), 6.82 d (J =8.1 Hz, 1H, H6ʹ),
6.88 t.d (J = 7.5, 0.9 Hz, 1H, 8ʹ), 6.98 d.d (J = 7.5,
1.5 Hz, 1H, H7ʹ), 7.21 t.d (J = 8.1, 1.6 Hz, 1H, H5ʹ),
7.38 s (1H, H4ʹ), 7.40–7.44 m (3H, H3″,4″,5″), 7.67–7.74
m (2H, H2″,6″). 13C NMR spectrum, δ, ppm: 37.29 (C4),
64.28 (C2ʹ), 65.54 (C5), 78.15 (C5ʹa), 116.15 (C8ʹ), 120.73
(C4ʹa), 121.62 (C6ʹ), 121.78 (C2″,6″), 126.74 (C5ʹ), 128.85
(C3″,5″), 129.04 (C7ʹ), 129.14 (C4″), 130.36 (C3ʹ), 132.19
(C4ʹ), 134.55 (C1″), 155.22 (C3), 156.22 (C8ʹa), 164.23
(C3ʹa). ESI-MS: m/z 336.1[M + H]+, 337 [M + H + 1]+.
[3-(3,4,5-Trimethoxyphenyl)isoxazol-5-yl]methyl-
8-methoxy-2H-chromene-3-carboxylate (7c). White
solid, yield 70%, mp 126–128°C. IR spectrum, ν, cm–1:
1718 (C=O), 1645 (C=N). 1H NMR spectrum, δ, ppm:
3.89 s (3H, H9ʹ), 3.90 s (3H, H4″a), 3.93 s (6H, H3″a,5″a),
5.06 d.d (J = 19.4, 1.3 Hz, 2H, H2ʹ), 5.37 s (2H, H5ʹa),
6.63 s (1H, H4), 6.80 d.d (J = 6.1, 3.0 Hz, 1H, H6ʹ),
6.90 d (J =3.0 Hz, 1H, H7ʹ), 6.91 s (1H, H4ʹ), 7.03 s
(2H, H2″,6″), 7.53 d (J = 1.1 Hz, 1H, H5ʹ). ESI-MS: m/z
454.0[M + H]+.
[3-(2,4,6-Trimethoxyphenyl)-4,5-dihydroisoxazol-
5-yl]methyl-2H-chromene-3-carboxylate (8b). Light
grey solid, yield 70%, mp 104–106°C. IR spectrum, ν,
cm–1: 1696–1735 (C=O), 1596 (C=N). 1H NMR
spectrum, δ, ppm: 3.10 d.d (J = 17.0, 6.6 Hz, 1H, H4),
3.45–3.36 m (1H, H4), 3.78 s (6H, H2″a,6″a), 3.83 s (3H,
H4″a), 3.91 m (1H, H5), 4.29–4.43 m (2H, H5ʹa), 5.01 s
(2H, H2ʹ), 6.14 s (2H, H3″,5″), 6.83 d (J = 8.1 Hz, 1H,
H8ʹ), 6.92 d.d (J = 13.3, 6.3 Hz, 1H, H6ʹ), 7.14 d.d (J =
24.0, 7.3 Hz, 1H, H7ʹ), 7.23 d.d (J = 11.0, 4.5 Hz, 1H,
H5ʹ), 7.50 s (1H, H4ʹ). 13C NMR spectrum, δ, ppm:
40.57 (C4), 55.42 (C2″a,6″a), 55.94 (C4″a), 64.34 (C2ʹ),
64.38 (C5ʹa), 65.43 (C5), 91.64 (C3″,5″), 100.01 (C1″ ),
116.14 (C8ʹ), 120.88 (C4ʹa), 121.79 (C6ʹ), 122.01 (C5ʹ),
129.07 (C7ʹ), 13 2.10 (C3ʹ), 134.30 (C4ʹ), 152.18 (C3),
155.23 (C8ʹa), 159.53 (C2″a,6″a), 162.48 (C4″), 164.39
(C3ʹa). ESI-MS: m/z 426.1 [M + H]+, 427.1 [M + H + 1]+.
[3-(4-Chlorophenyl)isoxazol-5-yl]methyl 8-methoxy-
2H-chromene-3-carboxylate (7d). Light green solid,
yield 75%, mp 106–108°C. IR spectrum, ν, cm–1: 1707
(C=O), 1641 (C=N). 1H NMR spectrum, δ, ppm: 3.88 s
(3H, H9ʹ), 5.07 s (2H, H2ʹ), 5.37 s (2H, H5ʹa), 6.64 s
(1H, H4), 6.79 d.d (J = 6.1, 2.7 Hz, 1H, H7ʹ), 6.92–6.88
m (2H, H5ʹ,6ʹ), 7.44 d (J = 8.4 Hz, 2H, H3″,5″), 7.52 s
(1H, H4ʹ), 7.75 d (J = 8.4 Hz, 2H, H2″,6″). ESI-MS: m/z
398.0[M + H]+, 400.1 [M + H + 2]+.
[3-(4-Methoxyphenyl)-4,5-dihydroisoxazol-5-yl]-
methyl-2H-chromene-3-carboxylate (8c). Light grey
solid, yield 75%, mp 118–120°C. IR spectrum, ν, cm–1:
1699 (C=O), 1604 (C=N). 1H NMR spectrum, δ, ppm:
3.18 d.d (J = 16. 6, 6.5 Hz, 1H, H4), 3.49 d.d (J = 16.5,
10.8 Hz, 1H, H4), 3.84 s (3H, H4″a), 4.31 d.d (J = 11.8,
Synthesis of substituted (3-phenyl-4,5-dihydroiso-
xazol-5-yl)methyl-2H-chromene-3-carboxylates (8a–
8p). To a stirred solution of a compound 4a, 4b
(100 mg, 0.46 mmol) in 5 mL of dichloromethane
were added trimethylamine (0.064 mL, 0.46 mmol)
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5.4 Hz, 1H, H5ʹa), 4.41 d.d (J = 11.8, 3.7 Hz, 1H, H5ʹa),
4.95 s (2H, H2ʹ), 4.97–5.05 m (1H, H5), 6.82 d (J =
8.1 Hz, 1H, H4″), 6.88 d (J = 7.4 Hz, 1H, H3″), 6.90–
6.95 m (2H, H6ʹ,8ʹ), 7.00 d (J = 6.8 Hz, 1H, H7ʹ), 7.21 t
(J = 7.2 Hz, 1H, H5ʹ), 7.38 s (1H, H4ʹ), 7.63 d (J =
[3-(p-Tolyl)-4,5-dihydroisoxazol-5-yl)methyl-2H-
chromene-3-carboxylate (8f). White solid, yield 73%,
mp 104–106°C. IR spectrum, ν, cm–1: 1712 (C=O),
1
1647 (C=N). H NMR spectrum, δ, ppm: 2.39 s (3H,
H4″a), 3.20 d.d (J = 16.7, 6.5 Hz, 1H, H4), 3.51 d.d (J =
16.6, 10.9 Hz, 1H, H4), 4.31 d.d (J = 11.9, 5.4 Hz, 1H,
H5ʹa), 4.42 d.d (J = 11.9, 3.8 Hz, 1H, H5ʹa), 4.95–4.96
br.s (2H, H2ʹ), 5.00–5.10 m (1H, H5), 6.82 d (J =
8.1 Hz, 1H, H6ʹ), 6.89 t.d (J = 7.5, 0.8 Hz, 1H, H8ʹ),
6.98 d.d (J = 7.5, 1.5 Hz, 1H, H7ʹ), 7.20 d (J = 1.6 Hz,
1H, H5ʹ), 7.24 d (J = 7.9 Hz, 2H, H3″,5″), 7.37 s (1H,
H4ʹ), 7.59 d (J = 8.1 Hz, 2H, H2ʹʹ,6″). 13C NMR spectrum,
δ, ppm: 21.45 (C4″a), 37.40 (C4), 64.29 (C2ʹ), 65.60 (C5),
77.96 (5ʹa), 116.14 (C8ʹ), 120.74 (C4ʹa), 121. 65 (C6ʹ),
121.76 (C2″,6″), 126.32 (C1″), 126.6 9 (C5ʹ), 129.04
(C7ʹ), 129.54 (C3″,5″), 132.16 (C3ʹ), 134.52 (C4ʹ), 140.63
(C4″), 155.22 (C3), 156.17 (C8ʹa), 164.23 (C3ʹa). ESI-
MS: m/z 350.1 [M + H]+, 351.1 [M + H + 1]+, 372.1
[M + Na]+.
13
8.7 Hz, 2H, H2″,6″). C NMR spectrum, δ, ppm: 37.53
(C4), 55. 38 (C4ʹʹa), 64.29 (C2ʹ), 65.61 (C5ʹa), 77.86 (C5),
114.26 (C3″,5″,8ʹ), 116.14 (C4ʹa), 120.74 (C6ʹ), 121.67
(C1″), 121.77 (C5ʹ), 128.28 (C2″,6″), 129.04 (C7ʹ), 132.17
(C3ʹ), 134.50 (C4ʹ), 155.21 (C3), 155.79 (C8ʹa), 161.25
(C4″), 164.24 (C3ʹa). ESI-MS: m/z 366.1[M + H]+, 367
[M + H + 1]+.
[3-(3,4-Dimethoxyphenyl)-4,5-dihydroisoxazol-5-
yl]methyl-2H-chromene-3carboxylate (8d). White
solid, yield 75%, mp 110–112°C. IR spectrum, ν, cm–1:
1694–1738 (C=O), 1603 (C=N). 1H NMR spectrum, δ,
ppm: 3.19 d.d (J = 16.6, 6.5 Hz, 1H, H4), 3.50 d.d (J =
16.5, 10.8 Hz, 1H, H4), 3.91 s (3H, H4″a), 3.92 s (3H,
H3″a), 4.32 d.d (J = 11.8, 5.3 Hz, 1H, H5ʹa), 4.42 d.d
(J = 11.8, 3.9 Hz, 1H, H5ʹa), 4.96 t (J = 1.5 Hz, 2H,
H2ʹ), 5.03 t.d.d (J = 7.8, 5.9, 3.2 Hz, 1H, H5), 6.82 d
(J = 8.2 Hz, 1H, H5″), 6.85–6.88 m (1H, H6ʹ), 6.90 d.d
(J = 7.4, 1.0 Hz, 1H, H8ʹ), 7.00 d.d (J = 7.5, 1.6 Hz,
1H, H7ʹ), 7.06 d.d (J = 8.3, 2.0 Hz, 1H, H2″), 7.19–7.24
m (1H, H6″), 7.39 s (1H, H5ʹ), 7.41 d (J =1.9 Hz, 1H,
[3-(4-Chlorophenyl)-4,5-dihydroisoxazol-5-yl]-
methyl-2H-chromene-3-carboxylate (8g). White solid,
yield 80%, mp 110–112°C. IR spectrum, ν, cm–1: 1708
1
(C=O), 1639 (C=N). H NMR spectrum, δ, ppm: 3.19
d.d (J = 16.7, 6.7 Hz, 1H, H4), 3.50 d.d (J = 16.7, 10.9 Hz,
1H, H4), 4.33 d.d (J = 11.9, 5.4 Hz, 1H, H5ʹa), 4.43 d.d
(J = 11.9, 3.8 Hz, 1H, H5ʹa), 4.95 t (J = 1.5 Hz, 1H,
H2ʹ), 5.02–5.17 m (1H, H5), 6.83 d (J = 8.2 Hz, 1H,
H8ʹ), 6.91 t.d (J = 7.5, 1.0 Hz, 1H, H6ʹ), 7.00 d.d (J =
7.5, 1.6 Hz, 1H, H7ʹ), 7.20–7.26 m (1H, H5ʹ), 7.39 t (J =
2.5 Hz, 1H, H4ʹ), 7.41 d (J = 1.9 Hz, 1H, H3″,5″), 7.61–
7.65 m (2H, H2″,6″). 13C NMR spectrum, δ, ppm: 37.12
(C4), 64.26 (C2ʹ), 65.40 (C5ʹa), 78.45 (C5), 116.19 (C8ʹ),
120.69 (C4ʹa), 121.55 (C2″,6″), 121.84 (C5ʹ), 127.65
(C6″), 127.95 (C7ʹ), 129.02 (C3″,5″), 129.14 (C3ʹ), 132.26
(C4ʹ), 134.62 (C4″), 136.36 (C3), 155.26 (C8ʹa), 164.18
(C3ʹa). ESI-MS: m/z 370.0 [M + H]+, 372.0 [M + H + 2]+.
3 : 1 ratio.
13
H4ʹ). C NMR spectrum, δ, ppm: 37.43 (C4), 55.97 d
(2C, C3″a,4″a), 64.29 (C2ʹ), 65.56 (C5ʹa), 78.03 (C5),
108.76 (C5″), 110.62 (C8ʹ), 116.16 (C2ʹʹ), 120.39 (C4ʹa),
120.73 (C6ʹ), 121.64 (C6″), 121.80 (C1″), 121.92 (C5ʹ),
129.00 (C7ʹ), 132. 20 (C3ʹ), 134.55 (C4ʹ), 149.28 (C3″),
151.08 (C4″), 155.21 (C3), 155.98 (C8ʹa), 164.24 (C3ʹa).
ESI-MS: m/z 396.1 [M + H]+, 397.1 [M + H+1]+.
[3-(3,4,5-Trimethoxyphenyl)-4,5-dihydroisoxazol-
5-yl]methyl-2H-chromene-3-carboxylate (8e). White
solid, yield 70%, mp 100–102°C. IR spectrum, ν, cm–1:
1695–1736 (C=O), 1602 (C=N). 1H NMR spectrum, δ,
ppm: 3.20 d.d (J = 16.6, 6.5 Hz, 1H, H4), 3.51 d.d (J =
16.5, 10.8 Hz, 1H, H4), 3.88 s (9H, H3″a,4″a,5″a), 4.33 d.d
(J = 11.9, 5.2 Hz, 1H, H5ʹa), 4.44 d.d (J = 11.9, 3.9 Hz,
1H, H5ʹa), 4.96 d (J = 1.0 Hz, 2H, H2ʹ), 5.01–5.10 m
(1H, H5), 6.82 d (J = 8.1 Hz, 1H, H6ʹ), 6.88 d.d (J =
7.5, 1.0 Hz, 1H, H8ʹ), 6.92 s (2H, H2″,6″), 7.00 d.d (J =
7.5, 1.6 Hz, 1H, H7ʹ), 7.20–7.25 m (1H, H5ʹ), 7.39 s
(1H, H4ʹ). 13C NMR spectrum, δ, ppm: 37.40 (C4),
56.31 (C3″a,5″a), 60.95 (C4″a), 64.28 (C2ʹ), 65.49 (C5ʹa),
78.30 (C5), 104.15 (C2″,6″), 116.18 (C8ʹ), 120.71 (C4ʹa),
121.59 (C6ʹ), 121.83 (C1″), 124.53 (C5ʹ), 128.98 (C7ʹ),
132.25 (C3ʹ), 134.60 (C4ʹ), 140.12 (C4″), 153.43 (C5″, 3″),
155.21 (C3), 156.08 (C8ʹa), 164.20 (C3ʹa). ESI-MS: m/z
426.1 [M + H]+, 427.1 [M + H + 1]+.
[3-(4-Benzyloxyphenyl)-4,5-dihydroisoxazol-5-
yl]methyl-2H-chromene-3-carboxylate (8h). White
solid, yield 70%, mp 128–130°C. IR spectrum, ν, cm–1:
1721 (C=O), 1651 (C=O). 1H NMR spectrum, δ, ppm:
3.17 d.d (J = 16.6, 6.5 Hz, 1H, H4), 3.48 d.d (J = 16.6,
10.8 Hz, 1H, H4), 4.31 d.d (J = 11.8, 5.4 Hz, 1H, H5ʹa),
4.40 d.d (J = 11.8, 3.9 Hz, 1H, H5ʹa ), 4.95 s (2H, H2ʹ),
5.01 m (1H, H5), 5.10 s (2H, H-1‴a), 6.82 d (J = 8.1 Hz,
1H, H8ʹ), 6.86–6.90 m (1H, H6ʹ), 6.96–7.04 m (3H,
H3‴,4‴,5‴), 7.21 t.d (J = 8.1, 1.6 Hz, 1H, H7ʹ), 7.31–7.45
m (6H, H4ʹ,5ʹ,2‴,6‴,3″,5″), 7.63 d (J = 8. 8 Hz, 2H, H2″,6″).
13C NMR spectrum, δ, ppm: 37.53 (C4), 64.31 (C2ʹ),
65.57 (C1‴a), 70.12 (C5ʹa), 77.89 (C5), 115.18 (C8ʹ),
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116.16 (C3″,5″), 120.76 (C4ʹa), 121.68 (C6ʹ), 121.77
(C2‴,6‴), 121.95 (C1″), 127.44 (C4‴), 128.16 (C5ʹ), 128.30
(C2″,6″), 128.67 (C7ʹ), 129.04 (C3‴,5‴), 132.16 (C3ʹ),
134.52 (C4ʹ), 136.46 (C1‴), 155.25 (C3), 155.72 (C8ʹa),
160.43 (C4″), 164.24 (C3ʹa). ESI-MS: m/z 442.1 [M +
H]+, 443.1 [M + H + 1]+.
ppm: 37.53 (C4), 55.37 (C4″a), 56.12 (C9ʹ), 64.59 (C2ʹ),
65.58 (C5ʹa), 77.84 (C5), 114.26 (C3″,5″), 114.76 (C7ʹ),
121.04 (C4ʹa), 121.43 (C5ʹ), 121.47 (C6ʹ), 121. 67 (C1″),
121.78 (C2″,6″), 128.27 (C3ʹ), 134.49 (C4ʹ), 144.17 (C8ʹa),
147.93 (C8ʹ), 155.75 (C3), 161.25 (C4″), 164.17 (C3ʹa).
ESI-MS: m/z 396.1 [M + H]+, 397.1 [M + H + 1]+.
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl-8-
methoxy-2H-chromene-3-carboxylate (8i). Light
grey solid, yield 85%, mp 120–122°C. IR spectrum, ν,
cm–1: 1702 (C=O), 1639 (C=N). 1H NMR spectrum, δ,
ppm: 3.22 d.d (J = 16.3, 5.9 Hz, 1H, H4), 3.58–3.43 m
(1H, H4), 3.86 s (3H, H9ʹ), 4.34 d (J = 4.3 Hz, 1H, H5ʹ),
4.43 d (J = 9.2 Hz, 1H, H5ʹa), 5.02 s (3H, H5, H2ʹ), 6.63
d (J = 5.3 Hz, 1H, H7ʹ), 6.86 m (2H, H5ʹ,6ʹ), 7.40 m (4H,
[3-(3,4-Dimethoxyphenyl)-4,5-dihydroisoxazol-
5-yl]methyl-8-methoxy-2H-chromene-3-carboxylate
(8l). Light grey solid, yield 70%, mp 140–145°C. IR
spectrum, ν, cm–1: 1740 (C=O), 1694 (C=N). 1H NMR
spectrum, δ, ppm: 3.20 d.d (J = 16.6, 6.5 Hz, 1H, H4),
3.50 d.d (J = 16.5, 10.8 Hz, 1H, H4), 3.87 s (3H, H9ʹ),
3.92 d (J = 2.1 Hz, 6H, H3″a,4″a), 4.33 d.d (J = 11.8,
5.3 Hz, 1H, H5ʹa), 4.43 d.d (J = 11.8, 3.8 Hz, 1H, H5ʹa),
5.02 s (3H, H2ʹ, H5), 6.65 d.d (J = 6.6, 2.0 Hz, 1H, H5″),
6.82–6.94 m (2H, H5ʹ,6ʹ,7ʹ), 7.06 d.d (J = 8.2, 1.6 Hz,
1H, H4ʹ), 7.36–7.46 m (2H, H2″,6″), 13C NMR spectrum,
δ, ppm: 37.41 (C4), 55.96 (C4″), 55.98 (C3″), 56.09
(C9ʹ), 64.58 (C2ʹ), 65.54 (C5ʹa), 78.01 (C5), 108.70 (C5″),
110.60 (C7ʹ), 114.70 (C2″), 120.40 (C4ʹa), 120.98 (C5ʹ),
121.39 (C6″), 121.51 (C6ʹ), 121.74 (C1″), 121.89 (C3ʹ),
134.53 (C4ʹ), 144.11 (C8ʹa), 147.91 (C3″), 149.25 (C4″),
151.05 (C8ʹ), 155.97 (C3), 164.18 (C3ʹa). ESI-MS: m/z
426.1 [M + H]+, 427.1 [M + H + 1]+, 448.1 [M + Na]+.
13
H4ʹ, H3″,4″,5″), 7.69 m (2H, H2″,6″). C NMR spectrum,
δ, ppm: 37.27 (C4), 56.12 (C9ʹ), 64.58 (C2ʹ), 65.53 (C5ʹa),
78.14 (C5), 114.79 (C7ʹ), 121.04 (C4ʹa), 121.41 (C5ʹ),
121.49 (C6ʹ), 121.74 (C2″,6″), 126.73 (C3″,5″), 128.84
(C4″), 129.13 (C3ʹ), 130.34 (C4ʹ), 134.52 (C1″), 144.17
(C8ʹa), 147.93 (C8ʹ), 156.21 (C3), 164.15 (C3ʹa). ESI-
MS: m/z 366.1 [M + H]+, 367.1 [M + H+1]+.
[3-(2,4,6-Trimethoxyphenyl)-4,5-dihydroisoxazol-
5-yl]methyl-8-methoxy-2H-chromene-3-carboxylate
(8j). Yellow solid, yield 75%, mp 126–128°C. IR spec-
trum, ν, cm–1: 1704 (C=O), 1599 (C=N). 1H NMR spec-
trum, δ, ppm: 3.10 d.d (J = 17.0, 6.5 Hz, 1H, H4), 3.39
d.d (J = 17.0, 10.8 Hz, 1H, H4), 3.78 s (6H, H2″a,6″a),
3.83 s (3H, H4″a), 3.88 s (3H, H9ʹ), 4.37 d (J = 4.9 Hz,
2H, H5ʹa), 4.93–5.03 m (1H, H5), 5.07 s (2H, H2ʹ), 6.14
s (2H, H3″,5″), 6.76 d.d (J = 6.0, 2.9 Hz, 1H, H7ʹ), 6.86–
6.91 m (2H, H5ʹ,6ʹ), 7.50 s (1H, H4ʹ). 13C NMR spec-
trum, δ, ppm: 40.70 (C3), 55.43 (C2″a,4″a,6″a), 55.95
(C9ʹ), 56.12 (C2ʹ), 64.70 (C5ʹa), 65.49 (C5), 77.19 (C5ʹa),
90.74 (C3″, C5″), 99.95–100.10 (C1″), 114.64 (C7ʹ),
121.04 (C4ʹa), 121.50 (C5ʹ), 121.58 (C6ʹ), 122.09 (C3ʹ),
134.33 (C4ʹ), 144.16 (C8ʹa), 147.95 (C8ʹ), 152.40 (C3),
159.53 (C2″,6″), 162. 46 (C4″), 164.40 (C3ʹa). ESI-MS:
m/z 456.2 [M + H]+, 457.2 [M + H + 1]+.
[3-(3,4,5-Trimethoxyphenyl)-4,5-dihydroisoxazol-
5-yl]methyl-8-methoxy-2H-chromene-3-carboxylate
(8m). White solid, yield 70%, mp 130–132°C. IR spec-
trum, ν, cm–1: 1704–1738 (C=O), 1573–1601 (C=N).
1H NMR spectrum, δ, ppm: 3.21 d.d (J = 16.6, 6.6 Hz,
1H, H4), 3.51 d.d (J = 16.5, 10.9 Hz, 1H, H4), 3.87 s
(3H, H9ʹ), 3.89 s (9H, H3″a,4″a,5″a), 4.33 d.d (J = 11.9,
5.1 Hz, 1H, H5ʹa), 4.44 d.d (J = 11.7, 3.6 Hz, 1H, H5ʹa),
5.03 s (2H, H2ʹ), 5.07 m (1H, H5), 6.65 d.d (J = 6.8,
2.0 Hz, 1H, H7ʹ), 6.87 t (J = 4.3 Hz, 2H, H5ʹ,6ʹ), 6.92 s
(2H, 2″, 6″), 7.38 s (1H, H4ʹ). 13C NMR spectrum, δ,
ppm: 37.37 (C4), 56.10 (C9ʹ), 56.32 (C3″a,5″a), 60.94 (C4″
a), 64.58 (C2ʹ), 65.46 (C5ʹa), 78.28 (C5), 104.16 (C2″,6″),
114.78 (C7ʹ), 120.96 (C4ʹa), 121.39 (C5ʹ), 121.53 (C6ʹ),
121.72 (C1″), 124.52 (C3ʹ), 134.58 (C4ʹ), 140.14 (C4″),
144.15 (C8ʹa), 147.95 (C3″,5″), 153.44 (C8ʹ), 156.03 (C3),
164.14 (C3ʹa). ESI-MS: m/z 456.2 [M + H]+, 457.1
[M + H + 1]+.
[3-(4-Methoxyphenyl)-4,5-dihydroisoxazol-5-yl]-
methyl-8-methoxy-2H-chromene-3-carboxylate (8k).
White solid, yield 76%, mp 118–120°C. IR spectrum,
ν, cm–1: 1702–1739 (C=O), 1606 (C=N). 1H NMR spe-
ctrum, δ, ppm: 3.18 d.d (J = 16.6, 6.4 Hz, 1H, H4),
3.48 d.d (J = 16.5, 10.8 Hz, 1H, H4), 3.84 s (3H, H9ʹ),
3.86 s (3H, H4″a), 4.32 d.d (J = 11.7, 5.2 Hz, 1H, H5ʹa),
4.41 d.d (J = 11.7, 3.5 Hz, 1H, H5ʹa), 5.02 s (3H, H5,
H2ʹ), 6.65 d (J = 5.9 Hz, 1H, H7ʹ), 6.82–6.89 m (2H,
H5ʹ,6ʹ), 7.62 d (J = 8.5 Hz, 2H, H2″,6″), 7.38 s (1H, H4ʹ),
[3-(p-Tolyl)-4,5-dihydroisoxazol-5-yl]methyl-8-
methoxy-2H-chromene-3-carboxylate (8n). White
solid, yield 70%, mp 120–122°C. IR spectrum, ν, cm–1:
1739 (C=O), 1694 (C=N). 1H NMR spectrum, δ, ppm:
2.38 s (3H, H4″a), 3.20 d.d (J = 16.7, 6.6 Hz, 1H, H4),
3.50 d.d (J = 16. 6, 10.9 Hz, 1H, H4), 3.86 s (3H, H9ʹ),
4.32 d.d (J = 11.8, 5.3 Hz, 1H, H5ʹa), 4.42 d.d (J = 11.8,
13
6.93 d (J = 8.5 Hz, 2H, H3″,5″). C NMR spectrum, δ,
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338
SRINIVAS, KRUPADANAM
3.8 Hz, 1H, H5ʹa), 4.98–5.07 m (3H, H5,2ʹ), 6.63 d.d (J =
6.8, 1.7 Hz, 1H, H7ʹ), 6.85 q (J = 8.1 Hz, 2H, H5ʹ,6ʹ),
7.22 d (J = 7.9 Hz, 1H, H3″,5″), 7.37 s (1H, H4ʹ), 7.58 d
form of UGC-SRF and Head of Department of
Chemistry, Osmania University, Hyderabad, India for
providing laboratory facilities and CFRD, O.U,
Hyderabad, India for providing spectral data.
13
(J = 8.0 Hz, 2H, H2″,6″). C NMR spectrum, δ, ppm:
21.46 (C4″a), 37.38 (C4), 56.10 (C9ʹ), 64.58 (C2ʹ), 65.61
(C5ʹa), 77.94 (C5), 114.71 (C7), 121.04 (C8ʹa), 121.41
(C5ʹ), 121.47 (C6ʹ), 121.74 (C2″,6″), 126.28 (C1″), 126.68
(C3″,5″), 129.54 (C3ʹ), 134.51 (C4ʹ), 140.63 (C4″), 144.13
(C8ʹa), 147.90 (C8ʹ), 156.18 (C3), 164.18 (C3ʹa). ESI-
MS: m/z 380.1 [M + H]+, 381.1 [M + H + 1]+.
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[3-(4-Chlorophenyl)-4,5-dihydroisoxazol-5-yl]-
methyl-8-methoxy-2H-chromene-3-carboxylate (8o).
White solid, yield 75%, mp 130–134°C. IR spectrum,
ν, cm–1: 1712–1740 (C=O), 1579–1595 (C=N). 1H NMR
spectrum, δ, ppm: 3.19 d.d (J = 16.7, 6.7 Hz, 1H, H4),
3.49 d.d (J = 16. 7, 10.9 Hz, 1H, H4), 3.87 s (3H, H9ʹ),
4.34 d.d (J = 11.9, 5.2 Hz, 1H, H5ʹa), 4.43 d.d (J = 11.9,
3.8 Hz, 1H, H5ʹa), 5.01 s (1H, H2ʹ), 5.07 m (1H, H5),
6.65 d.d (J = 6.4, 2.3 Hz, 1H, H7ʹ), 6.88 t (J = 6.4 Hz,
1H, H6ʹ, 5ʹ), 7.36–7.43 m (3H, H4ʹ,3″,5″), 7.62 d (J =
13
8.5 Hz, 2H, H2″,6″). C NMR spectrum, δ, ppm: 37.09
(C4), 56.10 (C9ʹ), 64.55 (C2ʹ), 65.41 (C5ʹa), 78.43 (C5),
114.76 (C7ʹ), 120.99 (C4ʹa), 121.35 (C5ʹ), 121.56 (C6ʹ),
121.65 (C2″,6″), 127.62 (C1″), 127.95 (C3″,5″), 129.13
(C3ʹ), 134.60 (C4ʹ), 136.34 (C4″), 144.12 (C8ʹa), 147.92
(C8), 155.31 (C3), 164.12 (C3ʹa). ESI-MS: m/z 400.0
[M + H]+, 402.0 [M + H + 2]+. 3 : 1 ratio.
[3-(4-Benzyloxyphenyl)-4,5-dihydroisoxazol-5-
yl]methyl-8-methoxy-2H-chromene-3-carboxylate
(8p). White solid, yield 70%, mp 126–128°C. IR
spectrum, ν, cm–1: 1740 (C=O), 1694 (C=N). 1H NMR
spectrum, δ, ppm: 3.18 d.d (J = 16.6, 6.6 Hz, 1H, H4),
3.48 d.d (J = 16.6, 10.8 Hz, 1H, H4), 3.87 s (3H, H9ʹ),
4.32 d.d (J = 11.8, 5.4 Hz, 1H, H5ʹa), 4.40 d.t (J = 16.7,
8.3 Hz, 1H, H5ʹa), 4.96–5.07 m (3H, H5,2ʹ), 5.10 s (2H,
H1‴a), 6.66 d.d (J = 6.9, 1.9 Hz, 1H, H7ʹ), 6.82–6.90 m
(2H, H5ʹ,6ʹ), 7.00 d (J = 8.8 Hz, 2H, H3″,5″), 7.32–7.45 m
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13
(6H, H4ʹ,2‴,3‴,4‴,5‴,6‴), 7.63 d (J = 8.8 Hz, 1H, H2″,6″). C
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(C2ʹ), 65.58 (C1‴a), 70.10 (C5ʹa), 77.86 (C5), 114. 70
(C4″,5″), 115 .16 (C7), 121.05 (C4ʹa), 121.43 (C5ʹ),
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ACKNOWLEDGMENTS
One of the authors (B. Srinivas) is thankful to the
UGC-New Delhi, India for financial support in the
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SYNTHESIS OF NOVEL 2H-CHROMENE-3-CARBOXYLATE
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