Synthesis of 2-methylchromone-8-acetic acids and 2-methyl-chromone-8-carboxylic acids

Article abstract of DOI:10.1081/SCC-100104068

2-Hydroxy-3-allylacetophenones on Claisen condensation with EtOAc/Na gave intermediate diketone, followed by cyclization in AcOH/HCl gave 8-ally1/-1-propenylchromones, which on ozonolysis gave 8-acetaldehydes or 8-carboxaldehydes. The above aldehydes on oxidation with KMnO4 furnished corresponding 8-acetic acids and 8-carboxylic acids.

Full text of DOI:10.1081/SCC-100104068

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SYNTHESIS OF 2-
METHYLCHROMONE-8-
ACETIC ACIDS AND 2-
METHYLCHROMONE-8-
CARBOXYLIC ACIDS
S. G. Jagadeesh a , G. L. David Krupadanam b & G.
Srimannarayana c
a Department of Organic Chemistry , IISc ,
Bangalore, 12, India
b Department of Chemistry , Osmania University ,
Hyderabad, 500 007, India
c Department of Organic Chemistry , IISc ,
Bangalore, 12, India
Published online: 02 Aug 2010.
To cite this article: S. G. Jagadeesh , G. L. David Krupadanam & G.
Srimannarayana (2001) SYNTHESIS OF 2-METHYLCHROMONE-8-ACETIC ACIDS
AND 2-METHYLCHROMONE-8-CARBOXYLIC ACIDS, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:10, 1547-1557, DOI: 10.1081/SCC-100104068
To link to this article: http://dx.doi.org/10.1081/SCC-100104068
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SYNTHETIC COMMUNICATIONS, 31(10), 1547–1557 (2001)
SYNTHESIS OF 2-METHYLCHROMONE-
8-ACETIC ACIDS AND 2-METHYL-
CHROMONE-8-CARBOXYLIC ACIDS
S. G. Jagadeesh,* G. L. David Krupadanam,
and G. Srimannarayana*,{
Department of Chemistry, Osmania University,
Hyderabad-500 007, India
ABSTRACT
2-Hydroxy-3-allylacetophenones on Claisen condensation
with EtOAc/Na gave intermediate diketone, followed by
cyclization in AcOH/HCl gave 8-allyl/-1-propenylchromones,
which on ozonolysis gave 8-acetaldehydes or 8-carbox-
aldehydes. The above aldehydes on oxidation with KMnO4
furnished corresponding 8-acetic acids and 8-carboxylic acids.
8-Substituted flavones are reported to have severaltypes of pharma-
cological activities. 3-Methylflavone-8-carboxylic acid derivatives have
coronary vasodilatory activity. These are also used for relaxation of con-
vulsion of smooth muscle of the lower urinary tract. The salt of
2-piperidinoethyl-3-methylflavone-8-carboxylate, named flavoxate hydro-
chloride, has been used as an excellent diuretic and effective remedial
*Present address: Department of Organic Chemistry, IISc, Bangalore-12, India.
E-mail: sgjaga@orgchem.iisc.ernet.in
{Corresponding author.
1547
Copyright & 2001 by MarcelDekker, Inc.
www.dekker.com

1548
JAGADEESH, KRUPADANAM, AND SRIMANNARAYANA
agent for treating Pollakiuria anosognosia.1 Recently, flavone-8-acetic acid
has been identified as a drug in the treatment of cancer named mito flaxone.2
8-Allyl-6-methoxy-2-styrylchromone is reported as an antitumor lead struc-
ture. It inhibits the growth of implanted colon-38 tumors in mice.3 From our
laboratory, Reddy et al.4 reported the synthesis of some analogs of 8-allyl-2-
styrylchromones. Recently, Kapoor et al.5 reported the synthesis of chro-
mone-8-ylalkanoic acids and assessed their in vitro antileshaminal activity
on Leishmania donovam strain UR-6.
We now report a new and facile synthesis of 2-methylchromone-8-
acetic/carboxylic acids. Claisen condensation of 2-hydroxy-3-allylacetophe-
none (1a)6 with ethylacetate in the presence of puvlerized sodium gave
diketone (2a), which was not isolated. On cyclization with HCl in AcOH
medium and purification by chromatography, 2-methyl-8-allylchromone
(3a) was obtained (70%) (Scheme). On ozonolysis7,8 at ꢀ70ꢁC, 3a yielded
2-methylchromone-8-acetaldehyde (5a, 66%). 5a was oxidized with KMnO4
under neutralconditions to give 2-methycl hromone-8-acetic acid ( 6a, 48%).
Scheme.
Similarly, 5-methyl-3-allyl-2-hydroxyacetophenone (1b) via 4-(3-allyl-
2-hydroxy-5-methylphenyl)-2,4-butadione (2b) 2,6-dimethyl-8-allylchro-
mone (3b), on oxidation with ozone gave aldehyde (5b), which was further
oxidized with KMnO4 to 2,6-dimethylchromone-8-acetic acid (6b).
However, under similar Claisen condensation conditions, 5-chloro-3-
allyl-2-hydroxy-acetophenone (1c)4 gave an inseparable 1:1 mixture of
6-chloro-2-methyl-8-allyl-chromone and 6-chloro-2-methyl-8-(1-propenyl)
chromone (3c and 4c) (1H NMR). The formation of this mixture is due to
isomerization of the allylic double bond under strong basic conditions of the
Claisen condensation. The mixture was ozonized at ꢀ70ꢁC to yield two

ACETIC AND CARBOXYLIC ACIDS
1549
compounds, which were separated by chromatography, 6-chloro-2-methyl-
chromone-8-acetaldehyde (5c) and 6-chloro-2-methylchromone-8-carbox-
aldehyde (7c). Aldehyde (5c) was oxidized with KMnO4 under neutral
conditions to give the acid (6c), and aldehyde 7c was oxidized with
KMnO4 under neutralconditions to give the acid 8c.
Similarly 6-bromo-2-hydroxy-3-allylacetophenone 1d, on Clasien con-
densation, gave an inseparable 1:1 mixture of 6-bromo-2-methyl-8-allyl-
chromone (3d) and 6-bromo-2-methyl-8- (1-propenyl) chromone (4d).The
mixture was ozonized at –70ꢁC to yield two compounds, 6-bromo-2-methyl-
chromone-8-acetaldehyde (5d) and 6-bromo-2-methylchromone-8-carbox-
aldehyde (7d). Aldehyde 5d was oxidized with KMnO4 under neutral
conditions to give the acid 6d, and aldehyde 7d was oxidized with
KMnO4 under neutralconditions to give the acid 8d.
EXPERIMENTAL
Melting points were taken in open capillary tubes in sulfuric acid bath
and are uncorrected. FT-IR (KBr) spectra were obtained on a Perkin-Elmer
1605 spectrometer. 1H NMR and 13C NMR of all compounds were taken in
CDCl3 and 8c and 8d in DMSO-d6 on Varian Gemini 200 and 50.3 MHz,
with TMS as internalstandard (chemicalshifts in ꢀ ppm). EI mass spectra
were obtained on a modified Hitachi RMU-6L instrument. Ozonizer,
model-T-816 (Welesbech product, Line Son JOSC, California) was used.
Synthesis of 2-Methylchromone-8-acetic Acid (6a)
Synthesis of 2-methyl-8-allylchromone (3a)
A mixture of 2-hydroxy-3-allylacetophenone (1a)6 (8.0 g, 46 mmol)
and ethylacetate (200 mL) was refluxed in the presence of puvlerized
Na (3.0 g) for 3 h. Excess Na was decomposed with methanol(50 mL), the
mixture concentrated under vacuum, and then poured onto crushed ice. The
mixture was neutralized with dil AcOH (10%), the solid was filtered, washed
with chilled water, and dried in air to yield diketone 2a as a cream-yellow
powder. The solution of crude 2a in acetic acid (70 mL) and concentrated
HCl(20 mL) was refluxed for 1.5 h, then poured into ice water. The mixture
was filtered and purified by chromatography (silica gel, 200 g, 60–120 mesh)
by elution with pet-ether þ chloroform (8:2, v/v), 25 fractions each fraction
150 mL were collected. Fractions 5–23 concentrated and recrystallized from
chloroform to give 3a as light yellowish needles (7.0 g, 76%) m.p. 123ꢁC.

1550
JAGADEESH, KRUPADANAM, AND SRIMANNARAYANA
1
IR 1648 (C ¼ O) cmꢀ1, H NMR ꢀ 2.4 (s, 3H, CH3) 3.6 (d, J ¼ 7, 2H,
H-1’) 5.1 (m, 2H, H-3’) 6.0 (m, 1H, H-2’) 6.1 (s, 1H, H-3) 7.4 (t, 1H,
H-6) 7.6 (dd, J ¼ 8,2, 1H, H-7) 8.0 (dd, J ¼ 8,2, 1H, H-5). Mass m/z
at (Mþ) 200. Analysis C13H12O2, calc.; C, 77.98; H, 6.04. Found C,
77.96; H, 6.08%.
Synthesis of 2-methylchromone-8-acetaldehyde (5a)
Through a solution of 2-methyl-8-allylchromone (3a) (3.0 g, 15 mmol)
in dry dichloromethane (100 mL) at ꢀ70ꢁC, ozone gas was bubbled
for 1.5 h. The reaction mixture was quenched with dimethylsulfide
(DMS) (1.0 g, 16.2 mmol). Dichloromethane was distilled off. The
mixture was poured into ice-cold water and extracted with chloroform.
On concentration, a gummy mass was obtained, which was purified
by chromatography (silica gel, 100 g, 60–120 mesh) elution with
chloroform. Twenty fractions, each 100 mL, were collected. Fractions
4–17 concentrated and recrystallized from chloroform to give 5a as
light cream crystals (2.0 g, 66%), m.p. 137ꢁC. IR 1729 (CHO) 1638
(C ¼ O) cmꢀ1
,
1H NMR ꢀ 2.40 (s, 3H, CH3) 4.05 (s, 2H, H-1’)
6.10 (s, 1H, H-3) 7.70 (t, 1H, H-6) 8.10 (dd, J ¼ 8,2, 1H, H-7)
8.30 (dd, J ¼ 8,2, 1H, H-5) 9.71 (s, CHO) ppm. Mass m/z at (Mþ)
202. Analysis C12H10O3, calc.; C, 71.26; H, 4.99. Found C, 71.29; H, 4.50%.
Synthesis of 2-methylchromone-8-acetic acid (6a)
The mixture of 2-methylchromone-8-acetaldehyde (5a) (1.5 g,
7.5 mmol), MgSO4 (1.56 g, 13 mmol) and dry acetone (40 mL) and
KMnO4 (1.0 g, 7 mmol) was stirred for 3 h. Acetone was distilled off
and the mixture was dissolved in water, filtered, the filtrate was
washed with chloroform, and then acidified with dil HCl (10%) to pH 2.0.
A colorless solid separated, which was filtered, and recrystallized
from methanolto yiedl 2-methychl romone-8-acetic acid (
6a), (0.75 g,
48%), m.p. 248ꢁC. IR 3470 (OH) 1632 (C ¼ O) cmꢀ1, UV (MeOH)
230 nm (log e 4.47) 310 (3.82). 1H NMR ꢀ 2.4 (s, 3H, CH3) 4.0
(s, 2H, H-1’) 6.1 (s, 1H, H-3) 7.5 (t, 1H, H-6) 7.8 (dd, J ¼ 8,2,
1H, H-7,) 8.6 (dd, J ¼ 8,2, 1H, H-5) 11.5 (s, OH) ppm. Mass m/z
at (Mþ) 218. Analysis C12H10O4, calc.; C, 66.04; H, 4.62. Found C,
66.04; H, 4.64%.

ACETIC AND CARBOXYLIC ACIDS
1551
Synthesis of 2,6-Dimethylchromone-8-acetic Acid (6b)
2-Hydroxy-3-allyl-5-methylacetophenone (1b)
2-Hydroxy-3-allyl-5-methylacetophenone (1b) was prepared by follow-
ing the procedure in ref (4) with 87% yield b.p. 157ꢁC. 1H NMR ꢀ 2.5 (3H, s,
CH3) 2.6 (3H, s, COCH3) 3.4 (2H, d, J ¼ 7, H-1’) 5.2 (2H, m, H-3’) 5.9, (1H,
m, H-2’) 7.3 (1H, d, J ¼ 2.5, H-4) 7.6 (1H, d, J ¼ 2.5, H-6) 12.5 (1H, s, OH)
ppm. Mass m/z at (Mþ) 276. Analysis C12H14O2, calc.; C, 75.78; H, 7.42.
Found C, 75.76; H, 7.40%.
Synthesis of 2,6-dimethyl-8-allylchromone (3b)
A mixture of 2-hydroxy-3-allyl-5-methylacetophenone (1b) (8.0 g,
42 mmol) and ethyl acetate (200 mL) was refluxed in the presence of pulver-
ized Na (3.0 g) for 3 h. Excess Na was decomposed with methanol(50 mL);
the mixture was concentrated under vacuum and then poured onto crushed
ice. The mixture was neutralized with dil AcOH (10%), the solid was fil-
tered, washed with chilled water, and dried in air to yield diketone 2b as a
colorless powder. The solution of crude 2b in acetic acid (70 mL) and conc
HCl(20 mL) was refluxed for 1.5 h, then poured into ice water. The mixture
was filtered and purified by chromatography (silica gel, 200 g, 60–120 mesh)
by elution with pet-ether þ chloroform (7:3, v/v). Thirty fractions, each
fraction 100 mL, were collected. Fractions 7–24 concentrated and recrystal-
lized from chloroform to give 3b as brownish crystals (5.85 g, 65%) m.p.
98ꢁC. IR 1646 (C ¼ O) cmꢀ1, H NMR ꢀ 2.3 (s, 3H, CH3) 2.4 (s, 3H, CH3)
1
3.5 (d, J ¼ 7, 2H, H-1’) 5.1 (m, 2H, H-3’) 5.9 (m, 1H, H-2’) 6.1 (s, 1H, H-3)
7.2 (d, J ¼ 2, 1H, H-7) 7.7 (dd, J ¼ 8,2, 1H, H-5) ppm. Mass m/z at (Mþ) 214.
Analysis C14H14O2, calc.; C, 78.47; H, 6.59. Found C, 78.49; H, 6.57%.
Synthesis of 2,6-dimethylchromone-8-acetaldehyde (5b)
Through a solution of 2-methyl-8-allylchromone (3b) (3.0 g, 14 mmol)
in dry dichloromethane (100 mL) at ꢀ70ꢁC, ozone gas was bubbled for
1.5 h. The reaction mixture was quenched with dimethylsulfide (DMS)
(1.0 g, 16.2 mmol). Dichloromethane was distilled off. The mixture was
poured into ice-cold water and extracted with chloroform. On concentra-
tion, a gummy mass was obtained, which was purified by chromatography
(silica gel, 200 g, 60–120 mesh) elution with pet-ether þ chloroform, (1:1, v/v).
Twenty-three fractions, each 100 mL, were collected. Fractions 5–16

1552
JAGADEESH, KRUPADANAM, AND SRIMANNARAYANA
concentrated and recrystallized from chloroform to give 5b as a colorless
powder (1.8 g, 60%), m.p. 142ꢁC. IR 1718 (CHO) 1635 (C ¼ O) cmꢀ1
,
1H NMR ꢀ 2.2 (s, 3H, CH3) 2.4 (s, 3H, CH3) 4.0 (s, 2H, H-1’) 6.0 (s, 1H,
H-3) 7.7 (d, J ¼ 1.5, 1H, H-7) 8.3 (dd, J ¼ 8,2, 1H, H-5) 9.7 (s, CHO) ppm.
Mass m/z at (Mþ) 216. Analysis C13H12O3, calc.; C, 72.20; H, 5.60. Found
C, 72.18; H, 5.64%.
Synthesis of 2,6-dimethylchromone-8-acetic acid (6b)
The mixture of 2,6-dimethylchromone-8-acetaldehyde (5b) (1.3 g,
6 mmol), MgSO4 (1.44 g, 12 mmol), dry acetone (40 mL) and KMnO4
(0.9 g, 5.8 mmol) was stirred for 3 h. Acetone was distilled off and the
mixture was dissolved in water, filtered, the filtrate was washed with chloro-
form, and then acidified with dilHCl(10%) to pH 2.0. A soild separate,
which was filtered recrystallized from methanol to yield 2,6-dimethyl-
chromone-8-acetic acid (6b) as light cream crystals (0.62 g, 45%), m.p.
230ꢁC. IR 3445 (OH) 1637 (C ¼ O) cmꢀ1, UV (MeOH) 236 nm (loge 4.43)
313 (3.64). 1H NMR ꢀ 2.2 (s, 3H, CH3) 2.4 (s, 3H, CH3) 4.0 (s, 2H, H-1’) 6.0
(s, 1H, H-3) 7.8 (d, J ¼ 1.5, 1H, H-7) 8.3 (dd, J ¼ 8,2, 1H, H-5) 11.6 (s, OH)
ppm. Mass m/z at (Mþ) 232. Analysis C13H12O4, calc.; C, 67.22; H, 5.21.
Found C, 67.24; H, 5.19%.
Synthesis of 6-Chloro-2-methylchromone-8-acetic Acid (6c)
and 6-Chloro-2-methylchromone-8-carboxylic Acid (8c)
Synthesis of 6-chloro-2-methyl-8-allylchromone (3c) and
6-chloro-2-methyl-8-(1-propenyl)chromone (4c)
A mixture of 2-hydroxy-3-allyl-5-chloroacetophenone (1c)4 (8.0 g,
38 mmol), ethyl acetate (200 mL), and Na (3.0 g) was refluxed for 3 h.
Then excess Na was decomposed with methanol(50 mL), the mixture con-
centrated under vacuum and then poured onto crushed ice. The mixture was
neutralized with dil AcOH (10%), the solid was filtered, washed with chilled
water, and dried in air to yield diketone 2c as a light orange powder. The
solution of crude 2c in acetic acid (70 mL) and conc HCl(20 mL) was
refluxed for 1.5 h, then poured into ice water. The mixture was filtered
and purified by crystallization from methanol to give as yellowish crystals
(7.0 g, 79%) m.p. 116ꢁC. IR 1647 (C ¼ O) cmꢀ1, H NMR indicated the
1
product to be a 1:1 mixture of two compounds, 6-chloro-2-methyl-8-allyl-
chromone (3c), ꢀ 2.4 (s, 3H, CH3) 3.6 (d, J ¼ 7, 2H, H-1’) 5.1 (m, 2H, H-3’)

ACETIC AND CARBOXYLIC ACIDS
1553
6.0 (m, 1H, H-2’) 6.1 (s, 1H, H-3) 7.6 (d, J ¼ 2, 1H, H-7) 8.0 (d, J ¼ 2, 1H, H-
5), 6-chloro-2-methyl-8-(1-propenyl)chromone (4c) ꢀ 2.0 (m, 3H, H-3’) 2.4
(s, 3H, CH3) 6.1 (s, 1H, H-3) 6.4 (m, 1H, H-2’) 6.8 (d, J ¼ 16,1H, H-1’) 7.4
(d, J ¼ 2, 1H, H-7) 8.0 (d, J ¼ 2, 1H, H-5) ppm. Mass m/z at (Mþ) 234.
Analysis C13H11O2Cl, calc.; C, 66.65; H, 4.74. Found C, 66.62; H, 4.75%.
The mixture could not be purified by chromatography.
Synthesis of 6-chloro-2-methylchromone-8-acetaldehyde (5c) and
6-chloro-2-methylchromone-8-carboxaldehyde (7c)
Through a solution of the mixture 6-chloro-2-methyl-8-allylchromone
(3c) and 6-chloro-2-methyl-8-(1-propenyl)chromone (4c) (6.0 g, 67 mmol) in
dry dichloromethane (150 mL) at ꢀ70ꢁC, ozone gas was bubbled for 1.5 h.
The reaction mixture was quenched with dimethylsulfide (DMS) (1.62 g,
26 mmol). Dichloromethane was distilled off. The mixture was poured
into ice-cold water and extracted with chloroform. On concentration, a
colorless gummy mass was obtained, which was purified by chromatography
(silica gel, 150 g, 60–120 mesh) elution with pet-ether þ chloroform,
(1:1, v/v). Thirty-five fractions, each 150 mL, were collected. Fractions
5–16 concentrated and recrystallized from methanol to give aldehyde 5c
as colorless crystals (1.7 g, 56%), m.p.118ꢁC. IR 1725 (CHO) 1645
1
(C ¼ O) cmꢀ1, H NMR ꢀ 2.42 (s, 3H, CH3) 3.95(s, 2H, H-1’) 6.19 (s, 1H,
H-3) 7.49(d, J ¼ 2, 1H, H-7) 8.08 (d, J ¼ 2, 1H, H-5) 9.89 (s, CHO) ppm.
Mass m/z at (Mþ) 236. Analysis C12H9O3Cl, calc.; C, 61.04; H, 3.84. Found
C, 61.01; H, 3.86%.
Fractions 20–32 concentrated and recrystallized from methanol to give
7c as light cream crystals (1.0 g, 35%), m.p. 135ꢁC. IR 1695 (CHO) 1652
(C ¼ O) cmꢀ1, 1H NMR ꢀ 2.45 (s, 3H, CH3) 6.24 (s, 1H, H-3) 8.13 (d, J ¼ 2,
1H, H-7) 8.38 (d, J ¼ 2, 1H, H-5) 10.6 (s, CHO) ppm. Mass m/z at (Mþ) 222.
Analysis C11H7O3Cl, calc.; C, 59.39; H, 3.17. Found C, 59.39; H, 3.13%.
Synthesis of 6-chloro-2-methylchromone-8-acetic acid (6c)
The mixture of 6-chloro-2-methylchromone-8-acetaldehyde (5c) (1.0 g,
4.23 mmol), MgSO4 (0.63 g, 3.3 mmol), and dry acetone (40 mL) and
KMnO4 (0.6 g, 3.68 mmol) was stirred for 3 h. Acetone was distilled off and
the mixture was dissolved in water, filtered, the filtrate was washed with
chloroform, and then acidified with dil HCl (10%) to pH 2.0. A solid
separate, which was filtered, recrystallized from methanol to yield 6-chloro-
2-methylchromone-8-acetic acid (6c) as colorless crystals (0.45 g, 42%),

1554
JAGADEESH, KRUPADANAM, AND SRIMANNARAYANA
m.p.213ꢁC. IR 3437 (OH) 1628 (C ¼ O) cmꢀ1, UV (MeOH) 236 nm
1
(log e 4.36) 323 (3.75). H NMR ꢀ 2.47 (s, 3H, CH3) 3.98 (s, 2H, H-1’)
6.22 (s, 1H, H-3) 8.08 (bs, 1H, H-7) 8.50 (bs, 1H, H-5) 11.65 (s, OH) ppm.
Mass m/z at (Mþ) 236. Analysis C12H9O4Cl, calc.; C, 55.46; H, 2.96.
Found C, 55.42; H, 2.94%.
Synthesis of 6-chloro-2-methylchromone-8-carboxylic acid (8c)
The mixture of 6-chloro-2-methylchromone-8-carboxyaldehyde (7c)
(0.7 g, 3.15 mmol), MgSO4 (0.6 g, 5 mmol), and dry acetone (40 mL) and
KMnO4 (0.56 g, 3.6 mmol) was stirred for 3 h. Acetone was distilled off
and the mixture was dissolved in water, filtered, the filtrate was washed
with chloroform, and then acidified with dil HCl (10%) to pH 2.0. A solid
separate, which was filtered, recrystallized from methanol to yield 6-chloro-
2-methylchromone-8-carboxylic acid (8c) as colorless crystals (0.28 g, 38%),
m.p. 210ꢁC. IR 3384 (OH) 1645 (C ¼ O) cmꢀ1, 1H NMR ꢀ 2.48 (s, 3H, CH3)
4.05 (s, OH) 6.22 (s, 1H, H-3) 8.13 (d, J ¼ 2, 1H, H-7) 8.25 (d, J ¼ 2, 1H,
H-5) ppm. Mass m/z at (Mþ) 222. Analysis C11H2O4Cl, calc.; C, 55.37;
H, 2.90. Found C, 55.39; H, 2.94%.
Synthesis of 6-Bromo-2-methylchromone-8-acetic Acid (6d)
and 6-Bromo-2-methylchromone-8-carboxylic Acid (8d)
2-hydroxy-3-allyl-5-bromoacetophenone (1d)
2-Hydroxy-3-allyl-5-bromoacetophenone was prepared by following
the procedure in ref. (4) with 90% yield, b.p. 157ꢁC. H NMR ꢀ 2.52 (3H,
1
s, COCH3) 3.42 (2H, d, J ¼ 7, H-1’) 5.18 (2H, m, H-3’) 5.99 (1H, m, H-2’)
7.44 (d, J ¼ 2.0, H-4) 7.68 (1H, d, J ¼ 2.0, H-6) 12.57 (1H, s, OH) ppm. Mass
m/z at (Mþ) 254. Analysis C11H11O2Br, calc.; C, 51.79; H, 4.35. Found
C, 51.81; H, 4.33%.
Synthesis of 6-bromo-2-methyl-8-allylchromone (3d) and
6-bromo-2-methyl-8-(1-propenyl)chromone (4d)
A mixture of 2-hydroxy-3-allyl-5-bromoacetophenone (1d) (10 g,
40 mmol), ethyl acetate (200 mL), and Na (3.0 g) was refluxed for 3 h.
Then excess Na was decomposed with methanol(50 mL), the mixture was
concentrated under vacuum, and then poured onto crushed ice. The mixture
was neutralized with dil AcOH (10%), the solid was filtered, washed with
chilled water, and dried in air to yield diketone 2d as a brownish powder.

ACETIC AND CARBOXYLIC ACIDS
1555
The solution of crude 2d in acetic acid (70 mL) and conc HCl(22 mL) was
refluxed for 1.5 h, then poured into ice water. The mixture was filtered and
purified by crystallization from methanol to give an olive-gray powder
(9.5 g, 87%) m.p. 110ꢁC. IR 1649 (C ¼ O) cmꢀ1. H NMR indicated the
1
product to be a 1:1 mixture of two compounds, 6-bromo-2-methyl-8-allyl-
chromone (3d), ꢀ 2.4 (s, 3H, CH3) 3.6 (d, J ¼ 7, 2H, H-1’) 5.1 (m, 2H, H-3’)
6.0 (m, 1H, H-2’) 6.1 (s, 1H, H-3) 7.7 (d, J ¼ 2, 1H, H-7) 8.15 (d, J ¼ 2, 1H,
H-5), 6-bromo-2-methyl-8-(1-propenyl) chromone (4d) ꢀ 2.0 (m, 3H, H-3’)
2.4 (s, 3H, CH3) 6.1 (s, 1H, H-3) 6.4 (m, 1H, H-2’) 6.7 (d, J ¼ 16, 1H, H-1’)
7.5 (d, J ¼ 2, 1H, H-7) 8.1 (d, J ¼ 2, 1H, H-5) ppm. Mass m/z at (Mþ) 278.
Analysis C13H11O2Br, calc.; C, 56.12; H, 3.39. Found C, 56.14; H, 3.42%.
The mixture could not be purified by chromatography.
Synthesis of 6-bromo-2-methylchromone-8-acetaldehyde (5d) and
6-bromo-2-methylchromone-8-carboxaldehyde (7d)
Through a solution of the mixture 6-bromo-2-methyl-8-allylchromone
(3d) and 6-bromo-2-methyl-8-(1-propenyl)chromone (4d) (6.0 g, 22 mmol) in
dry dichloro methane (150 mL) at ꢀ70ꢁC, ozone gas was bubbled for 1.5 h.
The reaction mixture was quenched with dimethylsulfide (DMS) (1.5 g,
24 mmol). Dichloromethane was distilled off. The mixture was poured into
ice-cold water and extracted with chloroform. On concentration a colorless
gummy mass was obtained, which was purified by chromatography (silica
gel, 100 g, 60–120 mesh) elution with pet-ether þ ethylacetate, (1:1, v/v).
Thirty fractions, each 150 mL, were collected. Fractions 4–17 concentrated
and recrystallized from methanol to give aldehyde 5d as colorless crystals
(1.38 g, 46%), m.p. 129ꢁC. IR 1721 (CHO) 1648 (C ¼ O) cmꢀ1, H NMR
1
ꢀ 2.4 (s, 3H, CH3) 3.9(s, 2H, H-1’) 6.1 (s, 1H, H-3) 7.6 (d, J ¼ 2, 1H, H-7) 8.2
(d, J ¼ 2, 1H, H-5) 9.8 (s, CHO) ppm. Mass m/z at (Mþ) 280. Analysis
C12H9O3Br, calc.; C, 51.39; H, 3.26. Found C, 51.43; H, 3.24%.
Fractions 20–28 concentrated and recrystallized from methanol to give
7d as colorless crystals (1.5 g, 52%), m.p. 147ꢁC. IR 1699 (CHO) 1647
1
(C ¼ O) cmꢀ1, H NMR ꢀ 2.4 (s, 3H, CH3) 6.2 (s, 1H, H-3) 8.2 (d, J ¼ 2,
1H, H-7) 8.5 (d, J ¼ 2, 1H, H-5) 10.6 (s, CHO) ppm. Mass m/z at (Mþ) 266.
Analysis C11H7O3Br, calc.; C, 49.47; H, 2.64. Found C, 49.51; H, 2.58%.
Synthesis of 6-bromo-2-methylchromone-8-acetic acid (6d)
The mixture of 6-bromo-2-methylchromone-8-acetaldehyde (5d)
(1.0 g, 3.5 mmol), MgSO4 (0.64 g, 5.35 mmol), and dry acetone (40 mL)

1556
JAGADEESH, KRUPADANAM, AND SRIMANNARAYANA
and KMnO4 (0.6 g, 3.68 mmol) was stirred for 3 h. Acetone was distilled off
and the mixture was dissolved in water, filtered, the filtrate was washed with
chloroform, and then acidified with dil HCl (10%) to pH 2.0. A solid was
filtered and recrystallized from methanol to yield 6-bromo-2-methylchro-
mone-8-acetic acid (6d) as colorless crystals (0.55 g, 35%), m.p. 261ꢁC. IR
3449 (OH) 1632 (C ¼ O) cmꢀ1, UV (MeOH) 228 nm (log e 4.42) 307 (3.71).
1H NMR ꢀ 2.4 (s, 3H, CH3) 3.9 (s, 2H, H-1’) 6.2 (s, 1H, H-3) 7.7 (bs, 1H,
H-7) 8.4 (bs, 1H, H-5) 11.5 (s, OH) ppm. Mass m/z at (Mþ) 296. Analysis
C12H9O4Br, calc.; C, 49.63; H, 2.65. Found C, 49.61; H, 2.64%.
Synthesis of 6-bromo-2-methylchromone-8-carboxylic Acid (8d)
The mixture of 6-bromo-2-methylchromone-8-carboxaldehyde (7d)
(1.0 g, 3.75 mmol), MgSO4 (0.71 g, 6 mmol), and dry acetone (40 mL) and
KMnO4 (0.67 g, 4.3 mmol) was stirred for 3 h. Acetone was distilled off and
the mixture was dissolved in water, filtered, the filtrate was washed with
chloroform, and then acidified with dil HCl (10%) to pH 2.0. A solid was
filtered and recrystallized from methanol to yield 6-bromo-2-methyl-
chromone-8-acetic acid (8d) as colorless crystals (0.44 g, 42%), m.p.
225ꢁC. IR 3384 (OH) 1648 (C ¼ O) cmꢀ1, H NMR ꢀ 2.4 (s, 3H, CH3) 3.5
1
(s, OH) 6.2 (s, 1H, H-3) 8.2 (d, J ¼ 2, 1H, H-7) 8.3 (d, J ¼ 2, 1H, H-5) ppm.
Mass m/z at (Mþ) 282. Analysis C11H7O4Br, calc.; C, 46.67; H, 2.49. Found
C, 46.65; H, 2.47%.
ACKNOWLEDGMENTS
One of the authors (SGJ) thanks CSIR, New Delhi, for awarding SRF
and the Director, IICT, for provding spectra. The authors also thank UGC,
New Delhi, for financial assistance in the form of Special Assistance
Programme (SAP).
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Received in the USA August 9, 2000