New entry to 9-acetyl/formyl-substituted 2H,8H-pyrano[2,3-f]chromen-2-ones through Baylis-Hillman reaction

Article abstract of DOI:10.1080/00397910802139346

A new facile route to 9-acetyl/formyl-substituted 2H,8H-pyrano[2,3-f] chromen-2-ones is described. The Baylis-Hillman reaction involving the condensation of methyl vinyl ketone/acrolein with 7-hydroxy-2-oxo-2H-chromen-8- carbaldehydes in the presence of diazabicyclo[2.2.2]octane (DABCO) under N2 atmosphere at room temperature furnished the desired compounds in good yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802139346

Synthetic Communications1, 38: 2459–2464, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802139346
New Entry to 9-Acetyl/Formyl-Substituted
2H,8H-Pyrano[2,3-f]Chromen-2-ones through
Baylis–Hillman Reaction
A. Raghotham, T. Lavanya, and P. Pratap Reddy
Department of Chemistry, Osmania University, Hyderabad, India
Abstract: A new facile route to 9-acetyl=formyl-substituted 2H,8H-pyrano[2,3-
f]chromen-2-ones is described. The Baylis–Hillman reaction involving the
condensation of methyl vinyl ketone=acrolein with 7-hydroxy-2-oxo-2H-
chromen-8-carbaldehydes in the presence of diazabicyclo[2.2.2]octane (DABCO)
under N2 atmosphere at room temperature furnished the desired compounds in
good yields.
Keywords: Acrolein; DABCO; Methyl vinyl ketone
INTRODUCTION
Naturally occurring 2H-chromen-2-ones have several biomedical applica-
tions such as platelet aggregation, enzyme inhibition, cytotoxic activity,
and antiviral, antibacterial, antifungal activities.[1–10] Dicoumarol,[11]
which has anticoagulant activity, antibiotics novobiocin and chlorobio-
cin,[12,13] and Calonides A and B,[14] which inhibit HIV-1 replication in
vitro, represent some of the bioactive substituted 2H-chromen-2-ones.
In view of this diverse bioactivity, we have planned the synthesis of
new 2H-chromen-2-ones with a pyran ring fused at the 7,8-position
employing the Baylis–Hillman protocol.
The Baylis–Hillman reaction[15–17] is an efficient carbon–carbon bond-
forming reaction and provides convenient access to several benzannulated
Received August 26, 2007
Address correspondence to P. Pratap Reddy (current address), Research &
Development, Integrated Product Development, Dr. Reddy’s Laboratories Ltd.
Survey No. 42, 45 and 46, Bachupally, Qutubullapur, Ranga Reddy District,
Hyderabad 500 055, India. E-mail: prataprp@reddys.com
2459

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A. Raghotham, T. Lavanya, and P. P. Reddy
heterocyclic molecules. Various 2H-1-chromenes were prepared[18–20] by
Key and coworkers using Baylis–Hillman adducts, obtained from the reac-
tion of salicylaldehyde with activated alkenes.
In our present study, we have chosen 7-hydroxy-2-oxo-2H-chromen-
8-carboxaldehydes (1a–d) as starting compounds to access the desired
new 2H,8H-pyrano[2,3-f]chromen-2-one derivatives.
RESULTS AND DISCUSSION
7-Hydroxy-2-oxo-2H-chromen-8-carbaldehydes (1a–d), on reaction with
methyl vinyl ketone in the presence of a catalytic amount of 1, 4-diazabi-
cyclo [2.2.2] octane (DABCO) in chloroform under N2 atmosphere at
room temperature for 48 h, followed by column chromatography purifi-
cation, yielded a crystalline compound characterized as 9-acetyl-4-
methyl-2H,8H-pyrano[2,3-f] chromen-2-one (2a). IR spectrum of 2a
showed carbonyl absorptions at 1677 cmꢀ1 and 1721 cmꢀ1. In the
1HNMR (CDCl3) spectrum, the 8-OCH2 protons of the new pyran ring
appeared at d 5.06 (J ¼ 1.5 Hz), and an H-10 signal appeared as a singlet
at d 7.82. A signal corresponding to methyl protons of 9-COCH3
appeared at d 2.45. Formation of a new fused pyran ring at the 7,8-
position of the chromenone is evident from these signals. In the 13CNMR
(CDCl3) spectrum of 2a, the signal due to the acetyl carbonyl carbon
resonated at d 195.9, and that of 8-OCH2appeared at d 64.8. The signals
of olefinic carbons C9 and C10 appeared at d 130.3 and 127.7, respect-
ively. The other carbon signal assignments are d 160.2 (C-2), 158.2
(C-6a), 152.2 (C-10b), 151 (C-4), 126.6 (C-5), 114.1 (C-4a), 112.8 (C-3),
112.2 (C-6), 109.2 (C-10a), 25.3 (carbonyl CH3), and 18.8 (C-4, CH3).
EI mass spectrum is characterized by the presence of M þ 1 peak at
m=z 280. Similar reaction conditions were used for the preparation of
other 9-acetyl-2H,8H-pyrano[2,3-f] chromen-2-ones (2b–d) (Scheme 1).
Reaction of 2H-chromen-2-ones 1a–d with acrolein in the presence of
DABCO under a nitrogen atmosphere afforded 9-formyl-2H,8H-
pyrano[2,3-f]chromen-2-ones (2e–h) (Scheme 1).
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
The purity of all the compounds was checked by thin-layer chromato-
graphy (TLC) on silica-gel-coated plates. IR spectra were recorded in
KBr pellets, 1HNMR spectra were recorded on a Varian 200-MHz instru-
ment with TMS as internal standard, and chemical shifts are expressed in
d ppm. Mass spectra were measured on MS 30 and MS 9 (AEI) at 70 eV.

9-acetyl/formyl-2H,8H-pyrano[2,3-f]chromen-2-ones
2461
Scheme 1. Synthesis of 2H,8H-pyrano[2,3-f]chromen-2-one derivatives.
General Procedure for the Synthesis of 9-Acetyl-2H,8H-pyrano
[2,3-f]chromen-2-ones (2a–d)
To a solution of 7-hydroxy-2-oxo-2H-chromen-8-carbaldehyde derivatives
(1a–d, 0.001 mmol) in chloroform (5 mL), methyl vinyl ketone
(0.002 mmol) and DABCO (0.001 mmol) were added. The reaction mixture
was stirred at room temperature under nitrogen atmosphere for 48 h. The
solvent was evaporated and the solid residue was chromatographed over
silica gel (60–120 mesh), eluting with petroleum ether and ethyl acetate
(9:1), to provide the corresponding 9-acetyl-2H,8H-pyrano[2,3-f]chro-
men-2-ones 2a–d. They were recrystallized from chloroform.
Data
9-Acetyl-4-methyl-2H,8H-pyrano [2,3-f]chromen-2-one (2a)
ꢁ
1
Greenish white crystals; yield 80%; mp 220 C; HNMR (CDCl3) d 2.4 (s,
3H, CH3), 2.46 (s, 3H, COCH3), 5.06 (s, 2H, 8-CH2), 6.78 (d, 1H, H-6,
J ¼ 8.73 Hz), 7.6 (d, 1H, H-5, J ¼ 8.73 Hz), 7.82 (s, H-10). Anal. calcd for
C15H12O4: C, 70.21; H, 4.32; O, 24.72. Found C, 69.96; H, 4.08, and O, 24.53.
9-Acetyl-3-bromo-4-methyl-2H,8H-pyrano [2,3-f]chromen-2-one (2b)
Pale yellow crystals; yield 72%; mp 252ꢁC; IR (KBr) 1662 and 1727 cmꢀ1
1HNMR (CDCl3) d 2.4 (s, 3H, CH3), 2.6 (s, 3H, COCH3), 5.2 (s, 2H,
;

2462
A. Raghotham, T. Lavanya, and P. P. Reddy
8-CH2), 6.8 (d, 1H, H-6, J ¼ 8.7 Hz), 7.6 (d, 1H, H-5, J ¼ 8.7 Hz), 7.8 (s,
H-10); EI-MS m=z (%) 337 (M þ 2). Anal. calcd. for C15H11BrO4: C,
53.68; H, 3.26; O, 19.2. Found C, 53.32; H, 3.12; O, 19.02.
9-Acetyl-4-phenyl-2H,8H-pyrano [2,3-f]chromen-2-one (2c)
Brown color crystals; yield 75%; mp 192 ꢁC; IR (KBr) 1656 and
;
1714 cmꢀ1 1HNMR (CDCl3) d 2.5 (s, 3H, COCH3), 5.3 (s, 2H, 8-
CH2), 6.2 (s, 1H, H-3), 6.7 (d, 1H, H-6, J ¼ 8.76 Hz), 7.4–7.6 (m, 5H,
Ar-H), 7.8 (d, 1H, H-5, J ¼ 8.76 Hz), 7.82 (s, H-10); EI-MS m=z (%)
342 (M þ 1). Anal. calcd. for C20H14O4: C, 75.20; H, 4.29; O, 20.2. Found
C, 75.01; H, 4.16; O, 19.86.
9-Acetyl-4-methyl-3-phenyl-2H,8H-pyrano [2,3-f]chromen-2-one (2d)
Brown color crystals; yield 69%; mp 231 ꢁC; IR (KBr) 1666 and
1
1713 cmꢀ1; HNMR (CDCl3) d 2.3 (s, 3H, CH3), 2.48 (s, 3H, COCH3),
5.21 (s, 2H, 8-CH2), 6.6 (d, 1H, H-6, J ¼ 8.72 Hz), 7.2–7.6 (m, 5H, Ar-
H), 7.82 (d, 1H, H-5, J ¼ 8.72 Hz), 7.86 (s, 1H, H-10); EI-MS m=z (%)
291 (M þ 1). Anal. calcd. for C21H16O4: C, 75.86; H, 4.78; O, 19.20.
Found C, 75.61; H, 4.66; O, 19.06.
General Procedure for the Preparation of 2e–h
To a solution of 7-hydroxy-2-oxo-2H-chromen-8-carbaldehyde (1a-d,
0.001 mmol) in chloroform (5 mL), acrolein (0.002 mmol), and DABCO
(0.001 mmol) were added. The reaction mixture was stirred at room
temperature under nitrogen atmosphere for 36 h. The chloroform was
stripped off and the solid residue was chromatographed over silica gel
(60–120 mesh) by eluting with petroleum ether and ethyl acetate (9:1)
to provide compounds 2e–h, which were crystallized from chloroform.
Data
4-Methyl-2-oxo-2H,8H-pyrano [2,3-f]chromen-9-carbaldehyde (2e)
Greenish white colored crystals, yield 83%, mp 232–234 ꢁC; IR (KBr)
1
1676 and 1724 cmꢀ1; HNMR (CDCl3) d 2.4 (s, 3H, CH3), 5.1 (s, 2H,
8-CH2), 6.1 (s, 1H, H-3), 6.8 (d, 1H, H-6, J ¼ 8.76 Hz), 7.5 (d, 1H, H-
5, J ¼ 8.76 Hz), 7.8 (s, 1H, H-10), 9.6 (s, 1H, CHO); 13CNMR (CDCl3)
189.5, 160.4, 152.8, 152.5, 149.2, 129.8, 126.6, 126.4, 124.2, 113.2,

9-acetyl/formyl-2H,8H-pyrano[2,3-f]chromen-2-ones
2463
112.6, 108, 64, 18.7; EI-MS m=z (%) 243 (M þ 1). Anal. calcd. for
C14H10O4: C, 69.38; H, 4.12; O, 26.40. Found C, 69.13; H, 3.95; O, 26.13.
3-Bromo-4-methyl-2-oxo-2H,8H-pyrano [2,3-f]chromen-9-
carbaldehyde (2f)
Pale yellow crystals; yield 74%; mp 211 ꢁC; IR (KBr) 1669 and
1
1716 cmꢀ1; HNMR (CDCl3) d 2.4 (s, 3H, CH3), 5.2 (s, 2H, 8-CH2),
6.8 (d, 1H, H-6, J ¼ 8.8 Hz), 7.6 (d, 1H, H-5, J ¼ 8.8 Hz), 7.8 (s, 1H,
H-10), 9.6 (s, 1H, CHO); EI-MS m=z (%) 321 (Mþ ). Anal. calcd. for
C14H9BrO4: C, 52.28; H, 2.76; O, 19.32. Found C, 52.03; H, 2.55; O,
19.13.
4-Phenyl-2-oxo-2H,8H-pyrano [2,3-f]chromen-9-carbaldehyde (2 g)
White crystals; yield 76%; mp 198 ꢁC; IR (KBr) 1662 and 1731 cmꢀ1
;
1HNMR (CDCl3) d 5.1 (s, 1H, 8-CH2), 6.2 (d, 1H, H-6, J ¼ 8.72 Hz),
7.42–7.6 (m, 5H, Ar-H), 7.9 (d, 1H, H-5, J ¼ 8.72 Hz), 7.98 (s, 1H, H-
10), 9.7 (s, 1H, CHO); EI-MS m=z (%) 305 (M þ 1). Anal. calcd. for
C19H12O4: C, 74.93; H, 3.96; O, 20.0. Found C, 75.71; H, 3.74; O, 19.86.
4-Methyl-3-phenyl-2-oxo-2H,8H-pyrano [2,3-f]chromen-9-
carbaldehyde (2 h)
ꢁ
Brown crystals; yield 68%; mp 216 C; IR (KBr) 1689 and 1731 cmꢀ1
;
1HNMR (CDCl3) d 2.4 (s, 3H, CH3), 5.2 (s, 2H, 8-CH2), 6.2 (d, 1H,
H-6, J ¼ 8.76 Hz), 7.42–7.6 (m, 5H, Ar-H), 7.92 (d, 1H, H-5,
J ¼ 8.76 Hz), 7.98 (s, 1H, H-10), 9.7 (s, 1H, CHO); EI-MS m=z (%)
318 (M þ 1). Anal. calcd. for C20H14O4: C, 75.39; H, 4.40; O, 20.60.
Found C, 75.16; H, 4.18; O, 20.36.
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