Copper oxide catalyzed domino process for the synthesis of substituted 2H-pyran-2-ones and polyhydroxy coumarin derivatives

Article abstract of DOI:10.1016/j.tet.2014.07.032

An efficient method for the synthesis of substituted 2H-pyran-2-ones and polyhydroxy coumarin derivatives has been developed via CuO-catalyzed C-C bond formation followed by intramolecular cyclization reaction by reacting electron-deficient alkynes with 1

Full text of DOI:10.1016/j.tet.2014.07.032

Tetrahedron 70 (2014) 7016e7021
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper oxide catalyzed domino process for the synthesis of
substituted 2H-pyran-2-ones and polyhydroxy coumarin derivatives
*
Utpal Kayal, Rajiv Karmakar, Dipanwita Banerjee, Gourhari Maiti
Department of Chemistry, Jadavpur University, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 April 2014
Received in revised form 23 June 2014
Accepted 8 July 2014
Available online 1 August 2014
An efficient method for the synthesis of substituted 2H-pyran-2-ones and polyhydroxy coumarin de-
rivatives has been developed via CuO-catalyzed CeC bond formation followed by intramolecular cycli-
zation reaction by reacting electron-deficient alkynes with 1,3-diketones and polyhydroxy benzenes,
respectively. The domino reaction proceeded smoothly by using commercially available catalysts under
reflux in toluene with very good yield.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Dialkyl acetylenedicarboxylate
Cyclohexane-1,3-dione
Polyhydroxy phenol
CuO catalyst
Pyrone derivatives
Coumarin derivatives
1. Introduction
using 1,3-dicarbonyl compounds and electron-deficient acetylene
derivatives in the presence of various reagents such as NaH,12a
It is well established that small heterocyclic molecules are
predominant building blocks for biologically active compounds and
designed medicinal agents in medicinal chemistry.1 Transition
metal-catalyzed reactions are among the most powerful tools in
modern organic synthesis for carbonecarbon bond formation.2 The
main stream of research in the area of transition metal catalysis
focused on metals such as Pd, Pt, Rh, Ir and Au. However, some of
these metals are potentially toxic and others are very expensive.
Therefore, utilization of nontoxic or less toxic and inexpensive
transition metal catalysts for the development of sustainable and
environmentally benign CeC and Ceheteroatom bond formation
processes is one of the fundamental goals in organic synthesis.
2H-Pyran-2-ones and coumarin scaffolds are key structural
motifs found in a large number of biologically important natural
products isolated from the diverse array of plant and marine
sources.3 2H-Pyran-2-ones and their analogues have been used as
valuable intermediates in modern organic synthesis due to the
existence of the suitable functional groups4 of natural products.
They also possess a wide range of pharmacological activities5 and
act as growth-regulating,6,7 antitumour,8,9 antimicrobial and anti-
fungal agents.10,11 Therefore, many synthetic methods for the syn-
thesis of functionalized 2H-pyran-2-ones have been established
Ph3P,12b ReBr(CO)5,12c silica gel,12d NaOH,12e PdCl2(PPh3)2eEt3N,12f
etc. in various reaction conditions. Very recently, Cao et al. re-
ported the DABCO catalyzed synthesis of 2H-pyran-2-ones.13
Coumarin derivatives are known to possess a wide range of bi-
ological activities including anticancer,14 anti-HIV,15 anti-acetyl-
cholinesterase,16 antifungal,17 antioxidant,18 antihelmintic,19
anticoagulant,20 antibacterial21 and antiviral22 activities. More-
over, other coumarins are of much interest as a result of their
toxicity,23 carcinogenicity24 and interesting photo physical prop-
erties.25 The majority of the naturally occurring coumarins are
highly oxygenated compounds such as 5,7-dihydroxycoumarin,
a natural coumarin first isolated in 1982.
Due to the versatile activities of coumarin derivatives, various
methods are known for the synthesis of substituted coumarins in
the literature26 using Pechmann, Perkin, Knoevenagel, Claisen,
Reformatsky condensation and Wittig reactions. Besides, the
combination of palladium catalysts and formic acid27 provides
a new atom economy synthesis of coumarins through the simple
addition of phenols with alkynoate esters. Yavari et al.28a reported
the synthesis of 4-carboxymethylcoumarins based on the aromatic
electrophilic substitution reaction between the conjugate base of
substituted phenols and a vinyltriphenylphosphonium salt gener-
ated from triphenylphosphine and electron-deficient alkynes.
Others28bef have utilized the above mentioned triphenylphosphine
methods for the synthesis of such type of compounds. Many of the
* Corresponding author. E-mail addresses: ghmaiti123@yahoo.co.in, gmaitiju@
gmail.com (G. Maiti).
http://dx.doi.org/10.1016/j.tet.2014.07.032
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

U. Kayal et al. / Tetrahedron 70 (2014) 7016e7021
7017
procedures suffer from harsh reaction conditions, use of stoichio-
metric amounts of reagents, reaction in highly basic condition, of-
ten under high reaction temperature and longer reaction time, poor
yields, etc. Hence, the development of an efficient synthesis of
functionalized pyrones and coumarin derivatives has been the fo-
cus of many researches for decades and continues to be an active
and rewarding area of research. Recently, Liu et al.29 reported
a facile and efficient method to synthesize polysubstituted furans
involving tin(II) and copper(I) reagents by addition/oxidative cy-
clization of alkynoates and 1,3-dicarbonyl compounds using DDQ
as the oxidant.
conversion and the yield of the product. But, beyond 5.0 mol %
there was no significant improvement of the rate as well as the
yield of the product. It is well established that Cu(II) or Cu(I) has
the ability to polarize the carbonecarbon triple bonds making
them more susceptible to nucleophilic attack. Moreover, in re-
cent times there had been a trend to explore the catalytic
properties of CuO.31 Encouraged by the initial results, both cyclic
and acyclic 1,3-diketones and alkyl but-2-ynedioate were sub-
jected to the reaction conditions and the results are summarized
in Table 2.
2. Results and discussion
Table 2
Synthesis of 2H-pyran-2-onesa
As part of our continued interest towards the development of
novel methodologies for the synthesis of heterocycles,30 a new
synthetic route to 4-carbomethoxy pyranones and coumarin de-
rivatives has been explored. Herein, we report a novel synthetic
route to 2H-pyran-2-ones and polyhydroxy coumarin derivatives
from electron-deficient alkynes by reacting with 1,3-diketones and
polyhydroxy benzenes, respectively, in the presence of copper
catalyst (CuO) in very good to excellent yield (Scheme 1).
Entry
1.
Substrate
Reagent
Product
Time (h)
3
Yieldb (%)
81
2.
3.
4.
5.
3
3
3
3
82
80
83
79
Scheme 1. Synthesis of 2H-pyran-2-ones and coumarin derivatives.
2a
2b
2a
Then, for optimization of the reaction conditions, DMAD (2a)
was treated with cyclohexane-1,3-dione (1c) using various cata-
lystesolvent combinations under reflux conditions with varied
reaction time as summarized in Table 1.
Table 1
Optimization of the reaction conditiona
6.
7.
8.
9.
2b
2a
2b
2a
2b
3
3
3
3
3
81
83
84
85
85
Entry
Catalyst
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
FeCl3
FeCl3
InCl3
InCl3
CuO
CuO
CuCl
HCl
PTSA
Yb(OTf)3
Yb(OTf)3
I2
I2
d
CH3CN
Toluene
CH3CN
Toluene
Toluene
CH3CN
Toluene
EtOH
12
12
12
12
3
43
58
51
62
79
49
65
8
8
12
12
12
12
12
12
12
3
c
9
EtOH
10
11
12
13
14
CH3CN
Toluene
EtOH
CH3CN
Toluene
5
8
44
40
12
a
Reaction conditions: cyclohexane-1,3-dione (1.0 mmol), dialkyl acetylenedi-
carboxylate (1.2 mmol), catalyst (0.05 mmol), solvent (1.3 mL).
b
Refers to pure and isolated yield.
Desired product not formed.
c
10.
From Table 1, it is evident that copper oxide (CuO)etoluene
was found to be the most effective catalystesolvent combination
under reflux both in terms of yield and reaction time. It was
observed that 5.0 mol % of the catalyst resulted the maximum
a
Reaction conditions: 1,3-dicarbonyl compounds (1 mmol), dialkyl but-2-
ynedioate (1.2 mmol), CuO (0.05 mmol), toluene (1.2 mL), 110 ꢀC, under atmo-
spheric pressure.
b
Pure and isolated yield after column chromatography.

7018
U. Kayal et al. / Tetrahedron 70 (2014) 7016e7021
Table 4
The promising results encouraged us to extend the scope of the
Synthesis of alkyl 2,5-dioxo-2,5-dihydropyrano[3,2-c]chromene-4-carboxylate de-
reaction with polyhydroxy benzene in place of 1,3-dicarbonyl
compounds to get the polyhydroxy coumarin derivatives under
similar reaction conditions. Thus, various polyhydroxy benzenes
were treated with electron-deficient alkynes in the presence of CuO
(5.0 mol %) in boiling toluene to afford the coumarin derivatives as
the sole product and the results are summarized in Table 3.
rivatives by using 4-hydroxy coumarin as the substratea
Entry
4-Hydroxy
coumarin
Dialkyl
but-2-ynoate
Product(s)
Time
(h)
Yieldb
(%)
Table 3
Synthesis of hydroxy coumarin derivatives by using polyhydroxy benzene as the
substratea
1
2.5
2.5
96
95
Entry Polyhydroxy
benzene
Dialkyl
but-2ynoate
Product(s)
Time Yieldb
(h)
(%)
2
1
2
3
4
67
a
Reaction condition: 4-hydroxy coumarin (1 mmol), dialkyl but-2-ynedioate
(1.2 mmol), CuO (0.05 mmol), toluene (1.2 mL), 110 ꢀC, atmospheric pressure.
b
Pure and isolated yield after column chromatography.
4
2
65
79
proposed mechanism has been depicted in Fig. 1. The Michael ad-
dition of the enol/enolate of the 1,3-diketone to the Cu-complexed
alkyne ester followed by the lactonization yielded the desired
product. The intermediate A was isolated by the decomposition of
the reaction mixture before completion of the reaction. The in-
termediate A was subjected to further reaction under similar con-
ditions to afford the desired product.
4
5
6
7
2
77
63
62
73
2.5
2.5
2.5
Fig. 1. Plausible reaction mechanism.
To investigate the catalytic reactivity, it was observed that CuO
behaves like a heterogeneous catalyst and it can be recovered from
the reaction mixture by simple filtration, washed with toluene and
dried for further use. In repeated experiments, cyclohexane-1,3-
done was treated with the recovered catalyst under similar re-
action condition. In four such runs, the conversions were 100%, 90%,
70%, 30%, respectively, which shows that the activity of the catalyst
gradually decreasing and the reaction rates were also slower.
8
2.5
70
a
Reaction condition: polyhydroxy benzene (1 mmol), dialkyl but-2-ynedioate
(1.2 mmol), CuO (0.05 mmol), toluene (1.2 mL), 110 ꢀC, under atmospheric pressure.
b
Pure and isolated yield after column chromatography.
It is noteworthy that 1-(2,4,6-trihydroxyphenyl)ethanone, un-
der identical reaction conditions produced densely functionalized
coumarin derivatives, which can be further elaborated to get the
complex molecular framework with coumarin scaffold (Table 3,
entries 5 and 6). However, 1,3-dihydroxy benzene (resorcinol)
ended up with the formation of a mixture of two isomeric com-
pounds (Table 3, entries 7 and 8). The scope of the reaction was
further extended by using 4-hydroxy coumarin as the substrate in
place of 1,3-dicarbonyl compound under similar reaction condi-
tions to produce coumarinopyrone derivatives in excellent yield
and the results are summarized in Table 4.
3. Conclusions
In conclusion, we have developed a facile and efficient method
for the syntheses of polysubstituted pyran-2-ones and coumarins
via CuO-catalyzed electrophilic addition followed by cyclization of
alkynoates and 1,3-dicarbonyl compounds in refluxing toluene.
This methodology provides an easy access to build up the library of
polysubstituted pyranone and coumarin derivatives, two different
categories of biologically important compounds by using a single
catalyst. The major advantages of this protocol are (i) ready acces-
sibility of starting materials, (ii) cheap and relatively environmen-
tally benign copper(II) catalyst, (iii) mild reaction conditions and
(iv) ease of isolation of product with very good yields.
A series of controlled experiments were performed to un-
derstand the probable mechanism of the transformation and the

U. Kayal et al. / Tetrahedron 70 (2014) 7016e7021
7019
4. Experimental
4.1. General
4.32 (q, J¼7.2 Hz, 2H), 3.81 (s, 3H), 1.33 (t, J¼7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3)
d
166.7, 164.7, 164.1, 159.7, 146þ.0, 113.6, 109.2, 62.6,
52.6, 19.3, 13.9; HRMS calcd for C11H12O6 240.0634, found
240.0631; IR (KBr):
n
¼1755,1732,1632,1556,1439,1402,1387,1261,
All reactions were carried out under the atmospheric pressure as
well as in an open air using flame-dried reaction vessels. Unless
otherwise noted, all commercially available compounds were used
as purchased without further purification. 1H NMR spectra were
recorded as solutions in DMSO-d6 and CDCl3. Chemical shifts are
1176, 1086, 1036, 1014, 870, 777 cmꢂ1
.
4.2.4. Methyl-2,5-dioxo-5,6,7,8-tetrahydro-2H-chromene-4-
carboxylate (3ca). White solid (201 mg, 0.79 mmol, 79%); mp
98e100 ꢀC; Rf (20% EtOAc/petroleum ether) 0.22; 1H NMR
expressed in parts per million (ppm,
d
) with reference to the re-
(300 MHz, CDCl3)
d
6.15 (s, 1H), 3.90 (s, 3H), 2.86 (t, J¼6.3 Hz, 2H),
sidual acetone in DMSO-d6 (
d
¼2.54 ppm) and chloroform in CDCl3
2.55 (t, J¼6.9 Hz, 2H), 2.13e2.19 (m, 2H); 13C NMR (75 MHz, CDCl3)
(
d
¼7.26 ppm) as an internal standard. All coupling constants are
d
192.4, 175.4, 165.8, 158.6,þ145.9, 112.3, 112.0, 53.1, 36.5, 28.4, 19.8;
absolute values and are expressed in hertz (Hz). The description of
HRMS calcd for C11H10O5 222.0528, found 222.0523; IR (KBr):
the signals in 1H NMR include: s¼singlet, br s¼broad singlet,
n
¼1756, 1738, 1672, 1553, 1444, 1402, 1272, 1195, 1155, 1062, 996,
d¼doublet, t¼triplet, m¼multiplet and dd¼doublet of doublets. 13
C
926, 871, 847, 762 cmꢂ1
.
NMR spectra were recorded in DMSO-d6 and CDCl3 solution with
complete proton decoupling. High-resolution mass spectra (HRMS)
were recorded with a Qtof Micro YA263 spectrometer. IR (infrared
spectroscopy) was recorded in an FT-IR spectrometer; the IR spectra
of solid compounds were recorded in KBr pallet. The reactions were
monitored routinely with pre-coated silica gel on aluminum plates
(Merck), which were analyzed with KMnO4 solution. Solvents, re-
agents and chemicals were purchased from Aldrich, Merck, SRL,
Spectrochem and toluene was distilled over sodium prior to use.
4.2.5. Ethyl-2,5-dioxo-5,6,7,8-tetrahydro-2H-chromene-4-
carboxylate (3cb). White solid (228 mg, 0.81 mmol, 81%); mp
69e71 ꢀC; Rf (20% EtOAc/petroleum ether) 0.22; 1H NMR
(300 MHz, CDCl3)
d
6.13 (s, 1H), 4.36 (q, J¼7.2 Hz, 2H), 2.85 (t,
J¼6.3 Hz, 2H), 2.54 (t, J¼6.6 Hz, 2H), 2.10e2.19 (m, 2H), 1.33 (t,
J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 192.3, 175.3, 165.3, 158.7,
146.2, 112.3, 112.0, 62.5, 36.5, 28.4, 19.8, 13.8; HRMS calcd for
þ
C
12H12O5 236.0685, found 236.0701; IR (KBr):
n
¼1755, 1738,
1682, 1622, 1556, 1408, 1371, 1327, 1265, 1194, 1165, 1134, 1094,
4.2. Representative experimental procedure for preparation
1030, 968, 918, 849 cmꢂ1
.
of diethyl 6-methyl-2-oxo-2H-pyran-4,5-dicarboxylate (3bb)
4.2.6. Methyl-7,7-dimethyl-2,5-dioxo-5,6,7,8-tetrahydro-2H-chro-
mene-4-carboxylate (3da). White solid (234 mg, 0.83 mmol, 83%);
mp 91e93 ꢀC; Rf (20% EtOAc/petroleum ether) 0.21; 1H NMR
To a magnetically stirred mixture of ethyl acetoacetate (130 mg,
1.0 mmol) and diethyl acetylenedicarboxylate (204 mg, 1.2 mmol) in
1.3 mL dry toluene in a 10 mL round bottom flask, CuO (4 mg,
0.05 mmol) as a catalyst was added and stirred for 3 h at 110 ꢀC
temperature. The progress of the reaction was monitored by TLC.
After completion of the reaction, the solvent was evaporated under
reduced pressure, and crude product was purified by column chro-
matography (using 60e120 mesh silica gel) eluting with 10% ethyl
acetate in petroleum ether to afford 3bb (249 mg, 0.83 mmol, 83%) as
a colourless liquid; Rf (20% EtOAc/petroleum ether) 0.25; 1H NMR
(300 MHz, CDCl3)
1.13 (s, 6H); 13C NMR (75 MHz, CDCl3)
145.7, 111.9, 111.4, 53.2, 50.6, 42.1, 32.5, 28.2; HRMS calcd for
13H14O5þ 250.0841, found 250.0837; IR (KBr):
¼1756, 1734, 1682,
1557, 1439, 1410, 1312, 1259, 1238, 1145, 1044, 1009, 972, 889,
860 cmꢂ1
d
6.16 (s,1H), 3.90 (s, 3H), 2.73 (s, 2H), 2.42 (s, 2H),
d
192.4, 174.0, 165.8, 159.0,
C
n
.
4.2.7. Ethyl-7,7-dimethyl-2,5-dioxo-5,6,7,8-tetrahydro-2H-chro-
mene-4-carboxylate (3db). White solid (260 mg, 0.84 mmol, 84%);
mp 138e140 ꢀC; Rf (20% EtOAc/petroleum ether) 0.21; 1H NMR
(300MHz,CDCl3)
d
6.46(s,1H),4.32(q, J¼7.2Hz,2H),4.28(q, J¼7.2 Hz,
2H), 2.47 (s, 3H),1.36 (t, J¼7.2 Hz, 3H),1.29 (t, J¼7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3)
d
166.7, 164.3, 164.2, 159.8, 146.2, 113.6, 109.5, 62.6,
(300 MHz, CDCl3)
d
6.17 (s, 1H), 4.39 (q, J¼7.2 Hz, 2H), 2.74 (s, 2H),
þ
62.0, 19.3, 13.9 (ꢁ2); HRMS calcd for C12H14O6 254.0790, found
2.43 (s, 2H), 1.36 (t, J¼7.2 Hz, 3H), 1.15 (s, 6H); 13C NMR (75 MHz,
254.0798; IR (KBr):
n
¼1755, 1732, 1632, 1556, 1470, 1446, 1408, 1385,
CDCl3) d 192.3, 173.9, 165.4, 159.1, 146.1, 111.8, 111.5, 62.6, 50.7, 42.2,
þ
1263, 1180, 1082, 1036, 1016, 951, 876, 862, 777, 629 cmꢂ1
.
32.5, 28.2, 13.9; HRMS calcd for C14H16O5 264.0998, found
264.1002; IR (KBr):
¼1753,1737,1678, 1623, 1560, 1472,1426,1369,
1314, 1267, 1178, 1150, 1048, 1030, 890, 855, 777 cmꢂ1
n
4.2.1. 5-Ethyl 4-methyl 6-methyl-2-oxo-2H-pyran-4,5-dicarboxylate
.
(3ba). White semi solid (218 mg, 0.80 mmol, 80%); Rf (20% EtOAc/
petroleum ether) 0.25; 1H NMR (300 MHz, CDCl3)
d
6.44 (s, 1H),
4.2.8. Methyl-2,5-dioxo-7-phenyl-5,6,7,8-tetrahydro-2H-chromene-
4-carboxylate (3ea). White solid (281 mg, 0.85 mmol, 85%); mp
166e168 ꢀC. Rf (20% EtOAc/petroleum ether) 0.32; 1H NMR
4.27 (q, J¼7.2 Hz, 2H), 3.86 (s, 3H), 2.47 (s, 3H), 1.30 (t, J¼7.2 Hz, 3H);
13C NMR (75 MHz, CDCl3)
d
166.9, 164.7, 164.2, 159.7, 146.0, 113.6,
þ
109.3, 62.1, 53.1, 19.3, 13.9; HRMS calcd for C11H12O6 240.0634,
(500 MHz, CDCl3)
(d, J¼7.5 Hz, 2H), 6.22 (s, 1H), 3.94 (s, 1H), 3.51e3.57 (m, 1H),
d
7.39 (t, J¼7.5 Hz, 2H), 7.31 (t, J¼7.5 Hz, 1H), 7.25
found 240.0630; IR (KBr):
n
¼1751, 1732, 1630, 1554, 1439, 1402,
1267, 1173, 1082, 1036, 986, 860, 777, 758 cmꢂ1
.
3.07e3.15 (m, 2H), 2.75e2.89 (m, 2H); 13C NMR (125 MHz, CDCl3)
d
191.7, 174.5, 165.7, 158.8, 145.8, 140.8, 129.3, 127.9, 126.6, 112.4,
þ
4.2.2. Dimethyl-6-methyl-2-oxo-2H-pyran-4,5-dicarboxylate
(3aa). White solid (209 mg, 0.80 mmol, 81%); mp 48e50 ꢀC; Rf
(20% EtOAc/petroleum ether) 0.25; 1H NMR (300 MHz, CDCl3)
112.3, 53.3, 43.9, 38.2, 36.1; HRMS calcd for C17H14O5 298.0841,
found 298.0842; IR (KBr):
n
¼1738, 1673, 1630, 1552, 1437, 1403,
1267, 1151, 1133, 1052, 1022, 992, 925, 874, 843, 761, 704 cmꢂ1
.
d
6.46 (s, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 2.46 (s, 3H); 13C NMR
(75 MHz, CDCl3)
52.7, 19.3; HRMS calcd for C10H10O6þ 226.0477, found 226.0479; IR
(KBr):
¼1753, 1727, 1632, 1551, 1436, 1390, 1267, 1198, 1171, 1123,
1083, 1035, 985, 918, 854, 779, 759, 630 cmꢂ1
d
167.0, 164.7, 164.6, 159.7, 145.7, 113.8, 109.1, 53.2,
4.2.9. Ethyl-2,5-dioxo-7-phenyl-5,6,7,8-tetrahydro-2H-chromene-4-
carboxylate (3eb). Colourless semi solid (304 mg, 0.85 mmol, 85%);
Rf (20% EtOAc/petroleum ether) 0.32; 1H NMR (500 MHz, CDCl3)
n
.
d
7.38 (t, J¼7.5 Hz, 2H), 6.21 (s, 1H), 4.43 (q, J¼7.0 Hz, 2H), 3.51e3.57
(m,1H), 3.06e3.15 (m, 2H), 2.75e2.89 (m, 2H),1.38 (t, J¼7.0 Hz, 3H);
13C NMR (125 MHz, CDCl3)
191.6, 174.5, 165.4, 158.9, 146.2, 140.9,
129.2, 127.8, 126.6, 112.3, 62.7, 43.9, 38.2, 36.1, 14.0; HRMS calcd for
18H16O5þ 312.0998, found 312.0998; IR (KBr):
¼1734, 1675, 1639,
4.2.3. 4-Ethyl 5-methyl 6-methyl-2-oxo-2H-pyran-4,5-dicarboxylate
d
(3ab). Colourless liquid (243 mg, 0.82 mmol, 82%); Rf (20% EtOAc/
petroleum ether) 0.25; 1H NMR (300 MHz, CDCl3)
d
6.46 (s, 1H),
C
n

7020
U. Kayal et al. / Tetrahedron 70 (2014) 7016e7021
1552, 1430, 1403, 1257, 1131, 1130, 1052, 1022, 990, 925, 880, 813,
768 cmꢂ1
(br s, 1H), 8.34 (d, J¼8.4 Hz, 1H), 6.64e6.68 (m, 2H), 6.45 (s, 1H),
3.78 (s, 3H); 13C NMR (125 MHz, DMSO-d6)
168.0, 165.4, 163.4,
.
d
157.7, 13þ3.1, 130.0, 118.4, 112.1, 111.7, 98.4, 52.1; HRMS calcd for
1679, 1625, 1573, 1483, 1367, 1301, 1245, 1173, 883, 736 cmꢂ1
.
4.2.10. Methyl 8-hydroxy-2-oxo-2H-chromene-4-carboxylate
C
11H8O5 220.0372, found 220.0377; IR (KBr):
n
¼3457, 3035, 1761,
(5aa). White solid (169 mg, 0.67 mmol, 67%); mp 79e81 ꢀC; Rf
(20% EtOAc/petroleum ether) 0.30; 1H NMR (300 MHz, CDCl3)
d
7.25
(dd, J¼1.2, 6.0 Hz, 1H), 7.18e7.21 (m, 1H), 7.13e7.16 (m, 2H), 6.48 (s,
1H), 3.82 (s, 3H); 13C NMR (75 MHz, CDCl3)
163.5, 154.1, 145.2,
4.2.17. Methyl 5-hydroxy-2-oxo-2H-chromene-4-carboxylate
d
(6da). Yellow semi solid (116 mg, 0.46 mmol, 46%); Rf (20%
138.6, 13þ8.4, 125.9, 124.7, 117.4, 116.9, 106.1, 51.9; HRMS calcd for
EtOAc/petroleum ether) 0.72; 1H NMR (300 MHz, CDCl3)
d 11.84 (br
C
11H8O5 220.0372, found 220.0377; IR (KBr):
n
¼3471, 1762, 1680,
s, 1H), 7.36 (t, J¼8.4 Hz, 1H), 6.77 (s, 1H), 6.68 (d, J¼8.5 Hz, 1H), 6.59
1620, 1548, 1463, 1336, 1347, 1282, 1235, 1060, 874, 783 cmꢂ1
.
(d, J¼7.8 Hz, 1H), 3.96 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 169.8,
167.4,157.5,156.9,136.6,132.9,119.2,114.9,108.3,102.0, 53.9; HRMS
þ
4.2.11. Ethyl 8-hydroxy-2-oxo-2H-chromene-4-carboxylate
calcd for C11H8O5 220.0372, found 220.0377; IR (KBr):
n
¼3055,
(5ab). White semi solid (182 mg, 0.65 mmol, 65%); Rf (20%
1761, 1665, 1625, 1571, 1463, 1332, 1286, 1249, 1032, 883, 797 cmꢂ1
.
EtOAc/petroleum ether) 0.30; 1H NMR (300 MHz, CDCl3)
d 7.25 (d,
J¼8.7 Hz, 2H), 7.15e7.20 (m, 2H), 4.28 (q, J¼7.2 Hz, 2H), 1.35 (t,
4.2.18. Ethyl 7-hydroxy-2-oxo-2H-chromene-4-carboxylate
(5db). Red fluorescent solid (73 mg, 0.26 mmol, 26%); mp
158e160 ꢀC; Rf (20% EtOAc/petroleum ether) 0.33; 1H NMR
J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 163.1, 154.2, 145.0, 138.6,
138.4, 125.9, 124.7, 117.4, 116.9, 106.7, 60.9, 14.0; HRMS calcd for
þ
C
12H10O5 234.0528, found 234. 0527; IR (KBr):
n
¼3455, 1763,
(500 MHz, DMSO-d6)
d
10.93 (br s, 1H), 8.35 (d, J¼8.5 Hz, 1H),
1675, 1620, 1582, 1459, 1342, 1289, 1245, 1032, 883, 796 cmꢂ1
.
6.65e6.68 (m, 2H), 6.44 (s, 1H), 4.25 (q, J¼7.0 Hz, 2H), 1.28 (t,
J¼7.0 Hz, 3H); 13C NMR (125 MHz, DMSO-d6)
d 168.5, 165.5, 163.9,
4.2.12. Methyl-5,7-dihydroxy-2-oxo-2H-chromene-4-carboxylate
(5ba). Yellow solid (212 mg, 0.79 mmol, 79%); mp 218e220 ꢀC; Rf
(20% EtOAc/petroleum ether) 0.48; 1H NMR (300 MHz, DMSO-d6)
158.3, 133.6, 130.5, 119.4, 112.6, 99.0, 61.5, 14.6; HRMS calcd for
C
12H10O5þ 234.0528, found 234. 0527. IR (KBr):
1693, 1649, 1485, 1368, 1327, 1267, 1155, 1092, 819, 764 cmꢂ1
n
¼3327,1795,1755,
.
d
11.27 (br s, 1H), 10.61 (br s, 1H), 6.52 (s, 1H), 6.14 (d, J¼1.5 Hz, 1H),
6.05 (d, J¼1.5 Hz, 1H), 3.76 (s, 3H); 13C NMR (75 MHz, DMSO-d6)
4.2.19. Ethyl 5-hydroxy-2-oxo-2H-chromene-4-carboxylate
d
168.4, 168.3, 164.4, 157.4,þ157.3, 128.0, 117.9, 101.0, 99.2, 91.5, 52.8;
(6db). Yellow semi solid (123 mg, 0.44 mmol, 44%); Rf (20%
HRMS calcd for C11H8O6 236.0321, found 236.0321; IR (KBr):
EtOAc/petroleum ether) 0.73; 1H NMR (300 MHz, CDCl3)
d 11.93 (br
n
¼3367, 2927, 1803, 1770, 1686, 1653, 1609, 1503, 1408, 1328, 1239,
s, 1H), 7.35 (t, J¼8.4 Hz, 1H), 6.77 (s, 1H), 6.68 (d, J¼8.4 Hz, 1H), 6.58
1155, 1038, 974 cmꢂ1
.
(d, J¼7.8 Hz, 1H), 4.40 (q, J¼7.2 Hz, 2H), 1.40 (t, J¼7.2 Hz, 3H); 13C
NMR (125 MHz, CDCl3)
115.0, 108.4, 102.1, 63.6, 14.1; HRMS calcd for C12H10O5 234.0528,
d
169.4,167.7,157.6, 157.0,136.7,132.8,120.0,
þ
4.2.13. Ethyl 5,7-dihydroxy-2-oxo-2H-chromene-4-carboxylate
(5bb). Yellow solid (228 mg, 0.77 mmol, 77%); mp 182e184 ꢀC; Rf
(20% EtOAc/petroleum ether) 0.50; 1H NMR (300 MHz, DMSO-d6)
found 234.0527; IR (KBr):
n
¼3425, 2992, 1783, 1678, 1620, 1572,
1464, 1380, 1282, 1240, 1221, 1021, 880, 795, 780 cmꢂ1
.
d
11.33 (br s, 1H), 10.64 (br s, 1H), 6.49 (s, 1H), 6.14 (d, J¼1.5 Hz, 1H),
6.05 (d, J¼1.5 Hz, 1H), 4.22 (q, J¼7.2 Hz, 2H), 1.25 (t, J¼7.2 Hz, 3H);
13C NMR (75 MHz, DMSO-d6)
168.4, 168.0, 164.6, 157.5, 157.4,
128.2, 117.8, 101.1, 99.2, 91.5, 62.0, 14.3; HRMS calcd for C12H10O6
250.0477, found 250.0479; IR (KBr):
¼3316, 1804, 1769, 1680, 1649,
1615, 1485, 1365, 1325, 1231, 1155, 1042, 818, 779 cmꢂ1
4.2.20. Methyl-2,5-dioxo-2,5-dihydropyrano[3,2-c]chromene-4-
carboxylate (8aa). Yellow solid (292 mg, 0.96 mmol, 96%); mp
213e215 ꢀC; Rf (20% EtOAc/petroleum ether) 0.31; 1H NMR
d
þ
n
(300 MHz, CDCl3)
d
8.09 (d, J¼7.8 Hz, 1H), 7.70e7.76 (m, 1H),
.
7.41e7.49 (m, 2H), 6.39 (s,1H), 4.0 (s, 3H); 13C NMR (125 MHz, CDCl3)
d
164.7, 162.9, 157.2, 157.0, 153.8, 146.8, 135.4, 1þ25.5, 124.0, 117.6,
4.2.14. Methyl-8-acetyl-5,7-dihydroxy-2-oxo-2H-chromene-4-
carboxylate (5ca). Yellow solid (195 mg, 0.63 mmol, 63%); mp
207e209 ꢀC; Rf (20% EtOAc/petroleum ether) 0.40; 1H NMR
113.3, 112.9, 101.0, 53.7; HRMS calcd for C14H8O6 272.0321, found
272.0320; IR (KBr):
n
¼1751,1732,1634,1607, 1549,1489, 1458, 1433,
1398, 1275, 1217, 1068, 1047, 1020, 908, 868, 833, 766 cmꢂ1
.
(500 MHz, CDCl3)
1H), 3.96 (s, 1H), 2.70 (s, 1H); 13C NMR (100 MHz, CDCl3)
170.3, 170.1, 166.8, 162.8, 160.3, 130.8, 116.8, 114.6, 101.8, 93.7, 54.2,
d
13.46 (s, 1H), 12.82 (s, 1H), 6.66 (s, 1H), 6.20 (s,
d
201.5,
4.2.21. Ethyl-2,5-dioxo-2,5-dihydropyrano[3,2-c]chromene-4-car-
boxylate (8ab). Yellow solid (315 mg, 0.95 mmol, 95%); mp
197e199 ꢀC; Rf (20% EtOAc/petroleum ether) 0.31; 1H NMR
þ
31.8; HRMS calcd for C13H10O7 278.0427, found 278.0429; IR
(KBr):
¼3070, 3011, 2684, 1801, 1684, 1647, 1616, 1574, 1541, 1522,
1489, 1448, 1362, 1338, 1292, 1240, 1049, 976, 964, 897, 827,
779 cmꢂ1
n
(300 MHz, CDCl3)
d
8.09 (dd, J¼1.2, 7.8 Hz, 1H), 7.69e7.75 (m, 1H),
7.40e7.46 (m, 2H), 6.38 (s, 1H), 4.47 (q, J¼7.2 Hz, 2H), 1.40 (t,
.
J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 164.1, 162.7, 157.2, 156.8,
153.6, 147.0, 135.2, 125.4, 123.9, 117.4, 113.1, 112.8, 100.9, 63.1, 13.9;
þ
4.2.15. Ethyl-8-acetyl-5,7-dihydroxy-2-oxo-2H-chromene-4-
carboxylate (5cb). Yellow solid (210 mg, 0.62 mmol, 62%); mp
206e208 ꢀC; Rf (20% EtOAc/petroleum ether) 0.40; 1H NMR
HRMS calcd for C15H10O6 286.0477, found 286.0470; IR (KBr):
n
¼1753, 1736, 1632, 1607, 1541, 1462, 1402, 1277, 1215, 1148, 1068,
1043, 1018, 906, 872, 835, 758 cmꢂ1
.
(300 MHz, CDCl3) d 13.45 (br s, 1H), 12.90 (br s, 1H), 6.66 (s,1H), 6.20
(s, 1H), 4.39 (q, J¼7.2 Hz, 2H), 2.73 (s, 3H), 1.40 (t, J¼7.2 Hz, 3H); 13
C
Acknowledgements
NMR (125 MHz, CDCl3)
d 201.5, 170.1, 169.8, 166.8, 162.8, 160.2,
130.6, 118.6, 117.5, 102.4, 101.7, 63.8, 31.8, 14.1; HRMS calcd for
U.K. (SRF), R.K. (SRF) and D.B. (JRF) thanks Council of Scientific
and Industrial Research, Government of India, New Delhi for
awarding their fellowships.
þ
C
14H12O7 292.0583, found 292.0589; IR (KBr):
n
¼3076, 2997,
2611, 1811, 1636, 1616, 1558, 1456, 1367, 1362, 1333, 1286, 1246,
1059, 1022, 962, 939, 879, 845, 764 cmꢂ1
.
Supplementary data
4.2.16. Methyl-7-hydroxy-2-oxo-2H-chromene-4-carboxylate
(5da). Red solid (68 mg, 0.27 mmol, 27%); mp 152e154 ꢀC; Rf (20%
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2014.07.032.
EtOAc/petroleum ether) 0.33; 1H NMR (300 MHz, DMSO-d6)
d 10.91

U. Kayal et al. / Tetrahedron 70 (2014) 7016e7021
7021
17. Sardari, S.; Mori, Y.; Horita, K.; Micetich, R. G.; Nishibe, S.; Daneshtalab, M. Bi-
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