Facile synthesis of 9-acetyl-pyrano[2,3-f]isoflavones

Article abstract of DOI:10.14233/ajchem.2013.14117

The Baylis-Hillman reaction of 7-hydroxy-8-formyl isoflavones (1a-f) react with methyl ketone in presence of l,4-diazobicyclo[2.2.2]octane with nitrogen atmosphere to give 9-acetyl-pyrano[2,3-f]isoflavones (3a-f) in good yields.

Full text of DOI:10.14233/ajchem.2013.14117

Asian Journal of Chemistry; Vol. 25, No. 9 (2013), 4833-4835
http://dx.doi.org/10.14233/ajchem.2013.14117
Facile Synthesis of 9-Acetyl-pyrano[2,3-F]isoflavones
*
R. CHENNA KRISHNA REDDY, G. MADHUSUDANA RAO, M. THIRUPAL REDDY and Y.V. RAMI REDDY
Department of Chemistry, Sri Venkateswara University, Tirupati-517 502, India
*Corresponding author: Tel: +91 877 2289303; E-mail: dryvrsvu@gmail.com
(Received: 27 May 2012;
Accepted: 8 March 2013)
AJC-13083
The Baylis-Hillman reaction of 7-hydroxy-8-formyl isoflavones (1a-f) react with methyl ketone in presence of l,4-diazobicyclo[2.2.2]octane
with nitrogen atmosphere to give 9-acetyl-pyrano[2,3-f]isoflavones (3a-f) in good yields.
Key Words: 7-Hydroxy8-formyl isoflavones, l,4-diazobicyclo[2.2.2]octane, Baylis-Hillman reaction, Methyl vinyl ketone.
CHO
HO
O
O
INTRODUCTION
R1
HO
O
O
Hexamine
AcOH
R1
R2
R3
Natural and synthetic heterocyclic compounds play an
important role in both drug discovery and chemical biology.
The heterocyclic compounds compounds are mainly of the
classes of alkaloids, chromones, flavones, isoflavones etc. The
natural heterocyclics are plant secondary metabolites, which
protect the plant from attack by pathogens, fungi, bacteria and
insects1-5. Several synthetic analogs of these heterocyclics show
different bioactivity6-8. More than 50 % of the drug used in the
modern medicine is either derived from synthetic or natural
heterocyclic systems.
R2
R3
1a-f
2a-f
O
DABCO
CHCl3/N2
1,2,3 a = R1 = H
b = R1 = H
c = R1 = Cl
R2 = H R3=H
R2=H R3 = OCH3
R2 = H R3= Cl
5 days
4
COCH3
d = R1 =OCH3 R2 = H R3=OCH3
e = R1 = H
f = R1 = H
R2 = Cl R3= H
R2 = H R3=Br
O
O
R1
R2
With a view to synthesize new heterocyclic ring fused
isoflavones we studied the Duff's reaction of 8-formyl-7-
hydroxyisoflavones and isoflavones9,10. Literature shows that
Baylis Hillmann reaction of 2-hydroxy benzaldehyde proceed
via acrylo intermediate to gives rise to either three substituted
2-H isoflavones. Selective formation of 2-hydroxy benzaldehyde
depends on solvent and structural features of substrate.
R3
3a-f
Scheme-I
NR3
O
CH3
HO
O
H
C
O
O
N
R1
1a
N
O
R2
R3
EXPERIMENTAL
CH3
5
Melting points were determined on a Polmon instrument
(model No. MP 96). IR spectra were recorded on FT-IR Perkin-
1
Elmer 1605 spectrometer and H NMR (200 MHz) and 13C
O
CH3
NMR (50.3 MHz) were recorded on aVarianGemini 200 spec-
trometer using TMS as internal standard (chemical shifts are
expresed in ppm). UV spectra were obtained on a Shimadzu
UV-visible spectrophotometer (model UV-1601). Mass spectra
were recorded on a VG micromass70-70H instrument.
O
CH3
H
H
OH
R3N
O
O
R1
H
O
O
O
R1
R2
R3
R2
O
7
6
R3
General procedure for the synthesis of 9-acetyl-pyrano[2,3-
f]isoflavones (3a-f)
-H2O
9-Acetyl-pyrano[2,3-f]isoflavone (3a)11,12: 7-Hydroxy-
8-formylisoflavone (3.1 g, 10 mmol), methyl vinyl ketone (4)
3a
Scheme-II

4834 Reddy et al.
Asian J. Chem.
(0.5 mL), l,4-diazobicyclo[2.2.2]octane (DABCO) (0.5 g, 4.54
mmol) in chloroform (50 mL), was stirred at room temperature
under N2 atmosphere in for 60 h. The chloroform was removed
by distillation and the product was purified by column chroma-
tography eluting with petroleum ether:ethylacetate (9:1) to give
9-acetyl-pyrano[2,3-f]isoflavone (3a), (2.3 g) 50-75 % yield.
3a (Scheme-I) was recrystallized from chloroform m.p. 206
ºC. IR (KBr, νmax, cm-1): Isoflavone carbonyl 1626 (C=O), 1654
(COCH3). UV (MeOH): 219 nm (log ε 5.1). 227 nm (log ε
δ 195.58 (9-C=O), 175.40 (C-4), 159.79 (C-2), 159.72
(C-6a), 159.79 (C-4'), 153.45 (C-2), 151.46 (C-l0b), 130.13
(C-6'), 129.65 (C-9), 126.37 (C-10), 125.37 (C-5), 114.81
(C-l0a), 123.45 (C-3), 118.90 (C-4a), 114.06 (C-6), 114.06
(C-l'), 109.18 (C-3'), 109.17 (C-5'), 64.91 (C-8), 55.36
(OCH3×2), 25.21 (9-CH3). EIMS: M+ m/z 378 (100 %).
9-Acetyl-pyrano[2,3-f]-3'-chloroisoflavone (3e):
Recrystallized from chloroform m.p. 185 ºC. IR (KBr, νmax
,
cm-1): Isoflavone carbonyl 1636 (C=O), 1654 (COCH3). UV
1
1
(MeOH): 210 nm (log ε 4.4), 224 nm (log ε 4.3). H NMR
4.7). H NMR (300 MHz) (CDCl3): δ 8.19 (d, J = 9.0 Hz,
H-5), 8.0 (s, H-2), 7.77 (bs, 10-H), 7.55 (m, 2H, H-2',6'), 7.42
(m, 3H, H-3', 4', 5'), 6.92 (d, J = 9.0 Hz, H-6), 5.15 (d, J = 1.0
Hz, OCH2-8), 2.50 (s, 9-COCH3). 13C NMR (75.5 MHz)
(CDCl3): δ 195.38 (9-C=O), 174.97 (C-4), 159.65 (C-6a),
153.32 (C-l0b), 151.93 (C-2), 131.30 (C-9), 130.25 (C-l'),
129.62 (C-4'), 128.49 (C-3',5'), 128.35(C-10), 114.85 (C-10a),
126.21 (C-5), 128.87 (C-2',6'), 125.77 (C-3), 118.8 (C-4a),
109.15 (C-6), 64.97 (C-8), 25.33 (9-CH3). EI MS: M+ m/z
318 (100), 317 (22), 303 (16), 275 (74 %).
(300 MHz) (CDCl3): δ 8.20 (d, J = 9.0 Hz, H-5), 8.01 (s, H-
2), 7.78 (bs, 10-H), 7.57 (m, H-2'), 7.40 (m, 3H, H-4',5',6'),
6.95 (d, J = 9.0 Hz, H-6), 5.17 (bs, OCH2-8), 2.50 (s, 9-
COCH3). 13C NMR (75.5 MHz) (CDCl3): δ 195.30 (9-C=O),
174.20 (C-4), 159.33 (C-6a), 153.54 (C-10b), 153.46 (C-2),
135.24 (C-3'). 135.12 (C-4'), 132.86 (C-l'), 130.19 (C-9),
129.85 (C-10), 129.73 (C-5'), 128.87 (C-2'), 128.87 (C-6'),
125.90 (C-5), 123.49 (C-3), 115.08 (C-10a), 118.66 (C-4a),
109.26 (C-6), 64.91 (C-8), 25.08 (9-CH3). EI MS: M+ m/z
352 (100 %).
Employing the similar procedure as mentioned for 3a,
compounds 3b-f were obtained from 1b-f as solids in 50-75 %
yield.
9-Acetyl-pyrano[2,3-f]-4-bromoisoflavone (3f): Recrys-
tallized from chloroform m.p. 211 ºC. IR (KBr, νmax, cm-1):
Isoflavone carbonyl 1624 (C=O), 1667 (COCH3). UV
9-Acetyl-pyrano[2,3-f]-4 '-methoxyisoflavone (3b):
1
Recrystallized from chloroform m.p. 189 ºC. IR (KBr, νmax
,
(MeOH): 254 nm (log ε 4.6), 229 nm (log ε 4.4). H NMR
cm-1): Isoflavone carbonyl 1628 (C=O), 1654 (COCH3). UV
(300 MHz) (CDCl3): δ 8.02 (d, J = 9.0 Hz, H-5), 7.95 (s, H-2),
7.70 (bs, 10-H), 7.55 (d, J = 9.0Hz, H-2',6'), 7.40 (d, J = 9.0
Hz, H-3',5'), 6.95 (d, J = 9.0 Hz, H-6), 5.15 (d, J = 1.0 Hz,
OCH2-8), 2.45 (s, 9-COCH3). 13C NMR (75.5 MHz) (CDCl3):
δ 195.35 (9-C=O), 174.70 (C-4), 159.82 (C-6a), 153.34 (C-
10b), 151.84 (C-2), 131.65 (C-2',6'), 130.40 (C-3',5'), 130.24
(C-9), 130.17 (C-1'), 129.76 (C-10), 114.98 (C-10a), 125.94
(C-5), 124.77 (C-3), 118.73 (C-4a), 109.12 (C-6), 122.62 (C-
4'), 64.91 (C-8), 25.09 (9-CH3). El MS: M+ m/z 397(100 %).
1
(MeOH): 227 nm (log ε 4.6), 319 nm (log ε 4.2). H NMR
(300 MHz) (CDCl3): δ 8.17 (d, J = 9.0Hz, H-5), 7.95 (s,H-2),
7.75 (bs,10-H): 7.45 (d, J = 8.7Hz, 2H, H-2',6'), 6.95 (d, J =
8.7Hz, 2H, H-3'5'), 6.90 (d, J = 9.0 Hz. H-6), 5.13 (d, J = 1.0
Hz, OCH2-8), 3.83 (4'-OCH3), 2.48 (s, 9-COCH=). 13C NMR
(75.5 MHz) (CDCl3): δ 195.34 (9-C=O), 175.52 (C-4), 159.83
(C-6a), 159.52 (C-4'), 153.26 (C-l0b), 151.30 (C-2), 130.21
(C-9), 129.99 (C-2',6'), 129.51 (C-10), 126.24 (C-5), 125.30
(C-3), 123.48 (C-1'), 118.78 (C-4a), 114.70 (C-10a), 113.95
(C-3',5'), 109.04 (C-6), 64.89 (C-8), 55.36 (4'-OCH3), 25.27
(9-CH). El MS: M+ m/z 348 (380 %).
RESULTS AND DISCUSSION
Synthesis of 9-acetyl-pyrano[2,3-f] isoflavones (3a-f)13-15
:
9-Acetyl-pyrano[2,3-f]-2'.4'-dichloroisoflavone (3c):
7-Hydroxy-8-formylisoflavones (2a-f) on reaction with methyl
vinyl ketone (4) in the presence catalytic amount of 1,4-
diazobicyclo[2.2.2]octane (DABCO), in chloroform under N2
(Baylis-Hillman reaction) gave 9-acetyl-pyrano[2,3-f]
isoflavones, (9-acetyl-4H,8H-pyrano[2,3-f]chromen-4-ones)
(3a-f) (Scheme-I).
Recrystallized from chloroform m.p. 200 ºC. IR (KBr, νmax
,
cm-1): Isoflavone carbonyl 1629 (C=O), 1633 (COCH3). UV
1
(MeOH): 223 nm (log ε 4.7), 247 nm (log ε 4.6). H NMR
(300 MHz) (CDCl3): δ 8.19 (d, J = 9.0 Hz, H-5), 7.95 (s, H-2),
7.78 (bs, 10-H), 7.26-7.33 (m, 2H, H-5',H-6'). 6.95 (d. J = 9.0
Hz, H-6), 7.52 (bs. H-3'), 5.17 (d, J = 1.0 Hz, OCH2-8), 2.49
(s,9-C OCH3). 13C NMR (75.5 MHz) (CDCl3): δ 195.35
(9-C=O), 174.15 (C-4), 159.93 (C-6a), 153.45 (C-10b), 153.45
(C-2), 135.24 (C-2'), 135.12 (C-4'), 132.88 (C-l'), 130.18
(C-9), 129.73 (C-5'), 129.84 (C-10), 128.89 (C-6'), 127.11
(C-3'), 123.50 (C-3), 115.07 (C-10a), 118.65 (C-4a), 125.96
(C-5), 109.26 (C-6), 64.91 (C-8), 25.08 (9-CH3). EI MS: M+
m/z 387 (10 %).
In its IR spectrum of 9-acetyl-pyrano[2,3-f] isoflavone
(3a), the C=O appeared at 1626 cm-1 and the acetyl carbonyl
at 1654 cm-1. Its UV spectrum (3a) showed bands at 219 nm
(log ε 5.1), 227 nm (log ε 4.7). In the 1H NMR spectrum of 3a
recorded in (300 MHz) (CDCl3), the 8-OCH2 group of the
new ring system appeared as doublet at δ 5.15 (J = 1.0 Hz)
due to allylic coupling with H-10. H-10 appeared as broad
singlet at δ 7.77, while the 9-COCH3 appeared as a singlet at
2.50. These three signals, suggest that a new fused pyran ring
is formed at 7,8 position of the isoflavone. Other signals in
the 1H NMR are from the original isoflavone moiety. The H-2
appeared as a singlet at δ 8.00, H-5 appeared as a doublet at
8.19 (J = 9.0 Hz) and H-6 appeared as a doublet at δ 6.92 (J =
9.0 Hz). The other aromatic protons appeared as a multiplets
H-2',6' at δ 7.55, H-3',4',5' at δ 7.42. In the 13C NMR (75.5
MHz) (CDCl3) spectrum of 9-acetyl-pyrano[2,3-f]isoflavone
9-Acetyl-pyrano[2,3-f]-2 ',4'-dimethoxyisoflavone
(3d): Recrystallized from chloroform m.p. 188 ºC. IR (KBr,
νmax, cm-1): Isoflavone carbonyl 1624 (C=O), 1652 (COCH3).
UV (MeOH): 218 nm (log ε 4.4), 230 nm (log ε 3.6). 1H NMR
(300 MHz) (CDCl3): δ 8.21 (d, J = 9.0 Hz, H-5), 8.02 (s, H-2),
7.79 (bs.H-10), 6.92-7.26 (m, 3H, H-3',5',6'), 6.94 (d, J = 9.0
Hz, H-6), 5.16 (d, J = 1.0 Hz, OCH2-8), 3.94 (2'-OCH3), 3.92
(4'-OCH3), 2.50 (s,9-COCH3). 13C NMR (75.5 MHz) (CDCl3):

Vol. 25, No. 9 (2013)
Facile Synthesis of 9-Acetyl-pyrano[2,3-F]isoflavones 4835
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carbons C-9 and C-10 appeared at δ 131.30 and 128.35. The
other carbon signals assignments are 174.97 (C-4), 159.65
(C-6a), 153.32 (C-l0b), 151.93 (C-2), 130.25 (C-1'), 129.62
(C-4'), 128.87 (C-2',6'), 128.49 (C-3',5'), 125.77 (C-3), 118.88
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