One-pot synthesis of 4-hydroxy-3-phenyl-2h-pyrano[3,2-b]benzofuran-2-one derivatives

Article abstract of DOI:10.1080/00397910802585886

Novel 4-hydroxy-3-phenyl-2H-pyrano[3,2-b]benzofuran-2-ones (15a-d), were synthesized in a one-step procedure by the reaction of substituted benzofuran-3-ones 12a-d and (chlorocarbonyl)phenyl ketene. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802585886

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One-Pot Synthesis of 4-
Hydroxy-3-phenyl-2H-
pyrano[3,2-b]benzofuran-2-one
Derivatives
Alireza Foroumadi a b , Sara Zamanian c , Alireza
Samzadeh-Kermani d & Abbas Shafiee a
a Department of Medicinal Chemistry , Faculty of
Pharmacy and Pharmaceutical Sciences Research
Center, Tehran University of Medical Sciences ,
Tehran, Iran
b Kerman Neuroscience Research Center , Kerman
University of Medical Sciences , Kerman, Iran
c Faculty of Sciences , Tehran University , Tehran,
Iran
d Faculty of Sciences , Tarbiat Modarress University ,
Tehran, Iran
Published online: 15 Apr 2009.
To cite this article: Alireza Foroumadi , Sara Zamanian , Alireza Samzadeh-Kermani
& Abbas Shafiee (2009) One-Pot Synthesis of 4-Hydroxy-3-phenyl-2H-pyrano[3,2-
b]benzofuran-2-one Derivatives, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:10, 1722-1728
To link to this article: http://dx.doi.org/10.1080/00397910802585886

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Synthetic Communications1, 39: 1722–1728, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802585886
One-Pot Synthesis of 4-Hydroxy-3-phenyl-2H-
pyrano[3,2-b]benzofuran-2-one Derivatives
Alireza Foroumadi,1,2 Sara Zamanian,3 Alireza Samzadeh-Kermani,4
and Abbas Shafiee1
1Department of Medicinal Chemistry, Faculty of Pharmacy and
Pharmaceutical Sciences Research Center, Tehran University of
Medical Sciences, Tehran, Iran
2Kerman Neuroscience Research Center, Kerman University of
Medical Sciences, Kerman, Iran
3Faculty of Sciences, Tehran University, Tehran, Iran
4Faculty of Sciences, Tarbiat Modarress University, Tehran, Iran
Abstract: Novel 4-hydroxy-3-phenyl-2H-pyrano[3,2-b]benzofuran-2-ones (15a–d),
were synthesized in a one-step procedure by the reaction of substituted
benzofuran-3-ones 12a–d and (chlorocarbonyl)phenyl ketene.
Keywords: Benzofuran-2-ones, (chlorocarbonyl)phenyl ketene, 2-pyrone
INTRODUCTION
The 2H-pyran-2-one (2-pyrone) ring system is a six-membered unsatu-
rated lactone (1, Fig. 1) that is found in a number of natural products
exhibiting a wide spectrum of biological activity.[1] Several 6-substi-
tuted-3-methyl-2-pyrones, called gibepyrones, were identified in culture
media of Gibberella fujikuroi, some of which showed antimicrobial
activity.[2] a-Pyrones bearing an olefinic side chain in conjunction with
a 6-alkyl substitution (2, Fig. 1), were isolated from fungal fermentation
media, and some of them showed androgen-like activity.[3]
Received August 16, 2008.
Address correspondence to Abbas Shafiee, Department of Medicinal Chemis-
try, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran
University of Medical Sciences, Tehran 14174, Iran. E-mail: ashafiee@ams.ac.ir
1722

Pyrano[3,2-b]benzofuran-2-one Derivatives
1723
Figure 1. Chemical structure of some synthetic 2-pyrones.
Some simple 6-alkyl-4-hydroxy-2-pyrones, for example 3 and 4 (Fig. 1),
as well as more complex 3,5-disubstituted-4-hydroxy-2-pyrone (e.g., fusa-
pyrone) have shown biological activity; the latter compound is a recent
example of a 4-hydroxy-2-pyrone with considerable antifungal activity.[4]
The synthesis of a large number of biologically active compounds
containing 2-pyrone has been reported.[5,6] In addition, the synthesis of
2H-pyran-2-ones substituted in the 4-, 5-, and 6-positions through the
reaction of enamines with excess ketene has been reported.[7] Recently,
a new alternative synthetic route to unsymetrically 5,6-disubstituted
2-pyrones has been developed based on the reaction of (Z)-2-en-4-ynoic
acid with iodine and NaHCO3 in acetonitrile.[8]
Substituted 4-methyl-2H-pyran-2-ones could be prepared from the
reaction of methylketones, N, N-dimethylacetamide dimethyl acetal,
and N-acetylglycines.[9]
There are also several synthetic methods for the preparation of fused
2H-pyran-2-ones. Benzothieno[2,3-c]pyran-3-ones (5, Fig. 1) and the iso-
meric [3,2-c]pyranes (6, Fig. 1) were also synthesized by the cyclization of
the corresponding keto acid.[10]
3-Substituted-5,6-fused 2H-pyranones 7 and 8 have been synthesized
by the reaction of 3-(dimethylamino)propenoates with a variety of O- and
C-nucleophiles including phenols and enoles (Scheme 1).[11]
Recently, the synthesis of 2,5-diphenyl-4-hydroxy-1,3-oxazin-6-one
(9) from the reaction of (chlorocarbonyl)phenyl ketene and benzamide
has been reported.[12] Some novel 5-acyl (or benzyl)-4-hydroxy-3-phenyl-
2-pyranone (10) have been synthesized by the reaction of (chlorocarbonyl)-
phenyl ketene (11) with 1,3-dicarbonyl compounds (Scheme 2).[13]

1724
A. Foroumadi et al.
Scheme 1. Synthesis of 5,6-fused 2H-pyranones.[11]
Herein, we report a new and efficient one-pot synthesis of
pyrano[3,2-b]benzofurans 15a–d.
CHEMISTRY
The reaction between (chlorocarbonyl)phenyl ketene (11) and substituted
benzofuran-3-ones (12a–d) provides 4-hydroxy-3-phenyl-2H-pyrano[3,2-
b]benzofuran-2-one derivatives (15a–d) in good yields (Scheme 3).
A plausible mechanism for the formation of 15a–d is illustrated in
Scheme 4. According to this mechanism, reaction of the enol form of
12 with (chlorocarbonyl)phenyl ketene 11 gives 13, which upon intramo-
lecular cyclization will produce target compounds 15 through the inter-
mediate 14 (Scheme 4).
Scheme 2. Synthesis of 9[11] and 10[12] from chlorocarbonyl phenyl ketene 11.

Pyrano[3,2-b]benzofuran-2-one Derivatives
1725
Scheme 3. One-pot synthesis of pyrano[3,2-b]benzofurans 15a–d.
In summary, we have developed a novel and expedient route to the
synthesis of 4-hydroxy-3-phenyl-4H-pyrano[3,2-b]benzofuran-3-ones
15a–d in good yields.
EXPERIMENTAL
Melting points were taken on a Kofler hot stage apparatus and are
uncorrected. 1H NMR and 13C NMR spectra were obtained with a Bruker
FT-500 spectrometer in chloroform-d1, and tetramethylsilane (TMS) was
used as an internal standard. Mass spectra were recorded with a Finnigan
Mat TSQ-70 spectrometer. Infrared (IR) spectra were acquired on a
Nicollet Magna 550-FT spectrometer. Elemental analyses were carried
Scheme 4. Plausible mechanism for the formation of pyrano[3,2-b]benzofurans
15a–d.

1726
A. Foroumadi et al.
out with a Perkin-Elmer model 240-C apparatus. The results of elemental
analyses (C, H) were within ꢀ0.4% of the calculated values.
General Procedure for the Preparation of 4-Hydroxy-3-phenyl-4H-
pyrano[3,2-b]benzofuran-2-ones (15a–d)
(Chlorocarbonyl)phenyl ketene (0.18 g, 1 mmol) was added to substituted
benzofuran-3-one (12a–d) (1 mmol) in dry diethyl ether (10 ml) with stir-
ring at room temperature for 4 h. The solid product was collected and
recrystallized from ethanol in good yield.
Data
4-Hydroxy-3-phenyl-4H-pyrano[3,2-b]benzofuran-2-one (15a)
Yield: 65%; yellow crystals; mp 259–260ꢁC; IR (KBr): t 3446 (OH), 3092
(CꢂH aromatic), 1644 (C ¼ O); 1H NMR (CDCl3): d ¼ 7.22–7.70 (m, 9H,
aromatic); 13C NMR (CDCl3): d ¼ 162.7, 155.5, 153.7, 141.5, 132.69,
132.4, 130.8, 128.4, 127.6, 127.0, 124.4, 119.4, 117.7, 112.7, 103.1; MS:
m=z (%) ¼ 279 (Mþ þ 1, 11); 278 (Mþ, 52); 221 (40); 161 (20); 118
(100); 89 (45); 49 (65). Anal. calcd. for C17H10O4: C, 73.38; H, 3.62;
found: C, 73.63; H, 3.45.
4-Hydroxy-8-methoxy-3-phenyl-4H-pyrano[3,2-b]benzofuran-2-one
(15b)
Yield: 67%; orange crystals; mp 269–271ꢁC; IR (KBr): t 3371 (OH), 3010
(CꢂH aromatic), 1659 (C ¼ O), 1198 (CꢂO); 1H NMR (CDCl3): d ¼ 3.89
(s, 3H, OMe), 6.91–6.98 (m, 3H, aromatic), 7.40–7.49 (m, 5H, aromatic),
15.03 (s, 1H, OH); 13C NMR (CDCl3): d ¼ 162.9, 159.3, 156, 155.1, 142.6,
133.3, 130.7, 128.4, 127.5, 124.2, 116.1, 112.8, 110.1, 92.5, 55.1; MS: m=z
(%) ¼ 309 (Mþ þ 1, 18); 308 (Mþ, 100); 251 (15); 188 (20); 132 (12); 117
(25). Anal. calcd. for C18H12O5: C, 70.13; H, 3.92; found: C, 69.95;
H, 4.05.
4-Hydroxy-7-methoxy-3-phenyl-4H-pyrano[3,2-b]benzofuran-2-one
(15c)
Yield: 61%; pale yellow crystals; mp 285–287ꢁC; IR (KBr): t 3436
(OH), 3031 (CꢂH aromatic), 1623 (C ¼ O), 1234 (CꢂO); 1H NMR

Pyrano[3,2-b]benzofuran-2-one Derivatives
1727
(CDCl3): d ¼ 3.89 (s, 3H, OMe), 7.33 (d, J ¼ 2.5 Hz, 1H, H6-aromatic),
7.10 (dd, J1 ¼ 2.5 Hz, J2 ¼ 9.0 Hz, 1H, H8-aromatic), 7.80 (d, J ¼ 9.0 Hz,
1H, H9-aromatic), 7.44 (d, J ¼ 7.5 Hz, 2H, H2,6-phenyl), 7.38 (t,
J ¼ 7.5 Hz, 1H, H4-phenyl), 7.29 (t, J ¼ 7.5 Hz, 2H, H3,5-phenyl); 13C
NMR (CDCl3): d ¼ 162.6, 160.3, 155.5, 155.8, 142.3, 132.8, 131.6,
130.9, 127.6, 126.9, 119.8, 113.2, 111, 101.3, 96.6; MS: m=z (%) ¼ 309
(Mþ þ 1, 20); 308 (Mþ, 100); 251 (35); 191 (25); 134 (30); 119 (97); 88
(98); 63 (93). Anal. calcd. for C18H12O5: C, 70.13; H, 3.92; found: C,
69.91; H, 4.02.
4-Hydroxy-7,9-dimethoxy-3-phenyl-4H-pyrano[3,2-b]benzofuran-
2-one (15d)
Yield: 66%; pale green crystals; mp 250–252ꢁC; IR (KBr): t 3416 (OH),
1
3041 (CꢂH aromatic), 1659 (C ¼ O), 1214 (CꢂO); H NMR (CDCl3):
d ¼ 3.87 (s, 3H, OMe), 3.95 (s, 3H, OMe), 6.54 (d, J ¼ 2.1 Hz, 1H, H8-
aromatic), 6.86 (d, J ¼ 2.1 Hz, 1H, H6-aromatic), 7.50 (d, J ¼ 7.5 Hz,
2H, H2,6-phenyl), 7.30 (t, J ¼ 7.5 Hz, 1H, H4-phenyl), 7.17 (t, J ¼ 7.5 Hz,
2H, H3,5-phenyl); 13C NMR (CDCl3): d ¼ 163.2, 160.4, 159.1, 157, 142.9,
140.1, 131.7, 130.2, 128.5, 127.9, 124.1, 104.7, 96.8, 92.3, 54.5; MS: m=z
(%) ¼ 338 (Mþ, 96); 295 (10); 221 (60); 135 (55); 88 (100); 61 (98). Anal.
calcd. for C19H14O6: C, 67.45; H, 4.17; found: C, 67.66; H, 4.08.
ACKNOWLEDGMENTS
This work was financially supported by grants from Research Council of
Tehran University of Medical Sciences and INSF (Iran National Science
Foundation).
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