Condensation of salicylaldehydes with ethyl 4,4,4-trichloro-3-oxobutanoate: A facile approach for the synthesis of substituted 2H-chromene-3-carboxylates

Article abstract of DOI:10.1016/j.tetlet.2015.01.114

A highly efficient and simple protocol has been developed for the preparation of ethyl 2-oxo-2H-chromene-3-carboxylates 3a-v by the condensation of salicylaldehydes 1a-v with ethyl 4,4,4-trichloro-3-oxobutanoate 2 for the first time. The reaction is proceeding via Knoevenagel pathway followed by a selective addition of the phenolic hydroxyl group to the carbonyl group adjacent to the CCl₃ group rather than ester carbonyl due to a strong electron withdrawing effect and produced coumarin derivative 3a with the elimination of CHCl₃.

Full text of DOI:10.1016/j.tetlet.2015.01.114

Accepted Manuscript
Condensation of salicylaldehydes with ethyl 4,4,4-trichloro-3-oxobutanoate: A
facile approach for the synthesis of substituted 2H-chromene-3-carboxylates
Mudulkar Sairam, Gannerla Saidachary, Bhimapaka China Raju
PII:
S0040-4039(15)00141-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.01.114
TETL 45784
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
28 November 2014
12 January 2015
15 January 2015
Please cite this article as: Sairam, M., Saidachary, G., Raju, B.C., Condensation of salicylaldehydes with ethyl 4,4,4-
trichloro-3-oxobutanoate: A facile approach for the synthesis of substituted 2H-chromene-3-carboxylates,
Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.01.114
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Graphical Abstract
Condensation of salicylaldehydes with
ethyl 4,4,4-trichloro-3-oxobutanoate: A facile approach
for the synthesis of substituted 2H-chromene-3-carboxylates
Leave this area blank for abstract info.
Mudulkar Sairam, Gannerla Saidachary, Bhimapaka China Raju*

1
Tetrahedron Letters
journal homepage: www.els evier.com
Condensation of salicylaldehydes with ethyl 4,4,4-trichloro-3-oxobutanoate: A
facile approach for the synthesis of substituted 2H-chromene-3-carboxylates
Mudulkar Sairam, Gannerla Saidachary, Bhimapaka China Raju*
Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, India
ARTICLE INFO
ABSTRACT
Highly efficient and simple protocol has been developed for the preparation of ethyl 2-oxo-2H-
chromene-3-carboxylates 3a-v by the condensation of salicylaldehydes 1a-v with ethyl 4,4,4-
trichloro-3-oxobutanoate 2 for the first time. The reaction is proceeding via Knoevenagel
pathway followed by selective addition of phenolic hydroxyl group to the carbonyl group
adjacent to the CCl3 group rather than ester carbonyl due to strong electron withdrawing effect
and produced coumarin derivative 3a with the elimination of CHCl3.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
2H-Chromene-3-carboxylates
Knoevenagel condensation
Salicylaldehydes
2009 Elsevier Ltd. All rights reserved.
Ethyl 4,4,4-trichloro-3-oxobutanoate
coumarins (Scheme 1, a),7a-b however, ethyl 4,4,4-trifluoro-3-
oxobutanoate produced ethyl 2-hydroxy-2-2-(trifluoromethyl)-
2H-chromene-3-carboxylate (Scheme 1, b).7c
Synthesis of coumarin heterocycles1 continues to be an active
area of research. Knoevenagel, Pechmann, Perkin, Reformatsky
and Wittig reactions are widely used methods for synthesis of
coumarins.2 Knoevenagel condensation3 is the straightforward
method and the process consists of the condensation of 2-
hydroxy benzaldehydes (salicylaldehydes) with active methylene
compounds to produce 3-substituted coumarins. These
derivatives exist in many natural products4 namely warfarin,
phenprocoumon, coumatetralyl, bromadiolone, coumestrol etc.
(Fig. 1) and displayed variety of biological activities such as
antibiotics, antibacterial, antitumor, antiviral, anticoagulants,
antipsoriasis, and anti-HIV.5 In addition, coumarins have also
been commercially exploited due to their physicochemical
behavior such as optical brighteners and laser dyes.6 Therefore,
the development of synthetic methodologies for these
heterocycles are very much important.
Scheme 1. Synthetic approaches for 2H-chromenes.
Our research focused on feasible reactions of carbonyl
compounds/salicylaldehydes with 3-oxobutanoates bearing
chloro or trifluoro substituents. In this context, we studied the
reactivity of carbonyl compounds with ethyl 4,4,4-trifluoro-3-
oxobutanoate to provide a series of (E)-α,β-unsaturated esters and
ketones.8 Next, we studied the reactivity of various
salicylaldehydes with ethyl 4-chloro-3-oxobutanoate to provide
2,2,3-trisubstituted 2H-chromenes (Scheme 1, c),9a interim these
derivatives were successfully converted to useful heterocyclic
compounds.9b-e Ethyl 4,4,4-trichloro-3-oxobutanoate is an
Condensation of salicylaldehydes with ethyl 3-oxobutanoate,
ethyl 3-oxo-3-phenylpropanoate, diethyl malonate, diethyl 3-
oxopentanedioate produces the corresponding 3-substituted
-------------------------------------------------------------------------------
* Corresponding author: Fax: +914027160512. E-mail: chinaraju@iict.res.in

2
Tetrahedron
important β-ketoester utilized for the preparation of
A plausible mechanism for this reaction is shown in Scheme 3.
Initially, the active methylene group is reacting with carbonyl-C
atom of salicylaldehyde to yield the corresponding Knoevenagel
derivative A. Then, cyclization occurs by selective addition of
phenolic hydroxyl group to the carbonyl group adjacent to the
CCl3 group rather than ester carbonyl to give oxonium ion
intermediate B. This may be due to strong electron withdrawing
effect of CCl3. The unstable oxonium ion B readily converted to
coumarin derivative 3a with the elimination of CHCl3.
tetrahydropyrimidinones and pyrazoles.10 However, the reaction
of salicylaldehydes with ethyl 4,4,4-trichloro-3-oxobutanoate has
not been studied. In the course of our efforts in discovery and
identification of biologically active molecules, we found
coumarin derivatives as potent α-glucosidase/α-amylase as well
as DPPH/ABTS free radical scavenging inhibitors.11 Further, we
have reported coumarin based heterocyclic compounds as
anticancer agents.12 In this study, we report a facile method for
the synthesis of various 3-substituted coumarins by Knoevenagel
condensation of substituted salicylaldehydes with ethyl 4,4,4-
trichloro-3-oxobutanoate and the results are depicted below.
In an initial experiment, we conducted the reaction between
the salicylaldehyde (1a, 1.0 equiv) and ethyl 4,4,4-trichloro-3-
oxobutanoate (2, 1.0 equiv) with piperidine (30 mol%) in toluene
under reflux conditions. This afforded ethyl 2-oxo-2H-chromene-
3-carboxylate 3a in 90% isolated yield as colorless solid (Scheme
2, Table 1, entry 8).11 The coumarin derivative 3a was fully
characterized by using IR, 1H NMR, 13C NMR, HRMS
spectroscopy and compared with the authentic sample (see
experimental part, supporting information).
Scheme 3. Plausible mechanism
In order to evaluate the efficiency of this methodology,
various substituted salicylaldehydes having electron-donating
substituents at various positions on the benzene ring such as 5-
methyl (entry 1), 5-methoxy (entry 2), 3,5-ditertiarybutyl (entry
3), 4-hydroxy (entry 4), 2-hydroxy naphthaldehyde (entry 5) and
electron-withdrawing substituents such as 5-bromo (entry 6), 3,5-
dibromo (entry 7), 5-nitro (entry 8), 3,5-dinitro (entry 9) were
reacted with ethyl 4,4,4-trichloro-3-oxobutanoate 2 to provide
corresponding coumarins 3b-j (Table 2).
Scheme 2. Synthesis of ethyl 2-oxo-2H-chromene-3-carboxylate 3a.
The result encouraged us to optimize the reaction conditions,
the model reaction was investigated with various catalysts,
solvents and the results were tabulated in Table 1. The solvents
such as MeOH, EtOH, DCM, DMF, MeCN, THF, toluene and
ether in presence of piperidine was studied. We found that the
toluene was the solvent of choice in terms of yield and reaction
time for the formation of product 3a, hence toluene was chosen
as the solvent for further reactions. Further, the reaction was
studied with different bases such as PPh3, 1,4-
diazabicyclo[2,2,2]octane (DABCO), 4-(dimethylamino)pyridine
(DMAP), N(C2H5)3, pyridine, 1H-imidazole, EtN(iPr)2, 2,6-
lutidine, NaOMe in MeOH, KOH in ethanol and K2CO3 in DMF
were examined. Lutidine and KOH produced 3a in moderate
yields.
Table 2. Preparation of coumarins 3b-j
Table 1. Optimization of reaction conditions for the synthesis of
ethyl 2-oxo-2H-chromene-3-carboxylate 3a.
Entry
Catalyst
Quantity
(equiv.)
0.3
Solvent
Time
(h)
5
Yieldc
(%)
80
40
55
60
58
35
60
90
90
--
1
2
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
PPh3
EtOH b
a
0.3
0.3
DCM
DMF a
18
6
3
4
0.3
0.3
CH3CN a
THF b
36
12
18
5
5
6
0.3
0.3
Ether a
7
MeOH b
Toluene b
Toluene b
Toluene b
Toluene b
Toluene b
Toluene b
Toluene b
Toluene b
Toluene b
Toluene b
MeOH b
EtOH b
8
0.3
1.0
4
9
4
10
11
12
13
14
15
16
17
18
19
20
0.3
0.3
6
DABCO
DMAP
9
25
35
10
--
0.3
0.3
0.3
0.3
18
15
12
12
12
12
12
12
24
N(C2H5)3
Pyridine
Imidazole
EtN(iPr)2
2,6-Lutidine
NaOMe
20
30
40
15
40
30
0.3
0.3
1.0
1.0
1.0
KOH
K2CO3
DMF b
a Room temperature, b Reflux, c Isolated yields.
aIsolated yields.

3
Electron donating groups such as methyl and methoxy
salicylaldehydes (1b-c) provided coumarins (3b-c) in very good
yields; however, the ditertiarybutyl substitution, and hydroxy
present on salicylaldehyde (1d-e) produced corresponding
coumarins (3d-e) in moderate to good yield due to steric
hindrance of tertiarybutyl and mesomeric effect. The 2-hydroxy-
1-naphthaldehyde (1f) was produced coumarin (3f) in low yield
due to resonance effect. The electron withdrawing groups present
on salicylaldehydes such as 3,5-dibromo salicyladehyde (1h)
provided corresponding coumarin (3h) in very good yield when
compared to 5-bromo salicyladehyde (1g). The 5-
nitrosalicylaldehyde (1i) provided corresponding coumarin (3i) in
good yield when compared to 3,5-dinitrosalicylaldehyde (1j) due
to intramolecular hydrogen bonding. Next, methoxy (1k),
benzyloxy (1l), allyloxy (1m), prenyloxy (1n) 2,2-
dimethoxyethoxy (1o) salicylaldehydes were prepared by the
reaction of 2,4-dihydroxybenzaldehyde 1e with corresponding
alkyl halides (Scheme 4). Thus prepared salicylaldehydes 1k-o
upon condensation with 2 provided corresponding coumarins 3k-
o in good yields.
2,4-Dihydroxybenzaldehyde 1e was reacted with 2-
methylbut-3-ene-2-ol in presence of BF3.O(C2H5)2 in dry 1,4-
dioxane
carbaldehyde 1r.
afforded
7-hydroxy-2,2-dimethylchroman-6-
Condensation of 1r with 2 provided ethyl
11d
8,8-dimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromene-3-
carboxylate 3r (Scheme 7).
Scheme 7. Preparation of coumarin 3r
Suzuki coupling11a of 5-bromosalicylaldehyde 1g with
phenylboronic acid, 4-chlorophenylboronic acid and pyrimidin-5-
ylboronic acid in the presence of Pd(PPh3)4 provided 4-
hydroxybiphenyl-3-carbaldehyde
hydroxybiphenyl-3-carbaldehyde
(1s),
and
4'-chloro-4-
2-hydroxy-5-
(1t)
(pyrimidin-5-yl)benzaldehyde (1u). Condensation of 1s-u with 2
provided corresponding coumarins 3s-u (Scheme 8).
Scheme 8. Preparation of coumarins 3s-u
Next, 2,4-dihydroxybenzaldehyde 1e was reacted with 2-
bromo-1,1-dimethoxyethane in the presence of NaHCO3, KI in
Scheme 4. Preparation of coumarins 3k-o
anhydrous
DMF
yielded
4-(2,2-dimethoxyethoxy)-2-
Further, various salicylaldehydes were prepared and utilized
for the preparation of coumarin derivatives (Scheme 5-9). Ethyl
8-allyl-2-oxo-2H-chromene-3-carboxylate 3p was prepared from
3-allyl-2-hydroxybenzaldehyde 1p as per scheme-5. Alkylation
of salicylaldehyde 1a with 3-bromoprop-1-ene in the presence of
K2CO3 provided 2-allyloxybenzaldehyde 1aa. Claisen
rearrangement13 of 2-allyloxybenzaldehyde at >200 0C furnished
1p. Condensation of 1p with 2 provided 3p.
hydroxybenzaldehyde 1o. Cyclization of salicylaldehyde 1o in
presence of acidic Amberlyst-15 in toluene under reflux
conditions provided 6-hydroxybenzofuran-5-carbaldehyde14a (1v,
50%) and 4-hydroxybenzofuran-5-carbaldehyde14b (1w, 10%,
Scheme 9). These carbaldehydes 1v-w were separated by column
chromatography. Knoevenagel condensation of 1v with 2 under
optimized conditions afforded ethyl 7-oxo-7H-furo [3,2-
g]chromene-6-carboxylate 3v (Scheme 9).
Scheme 5. Preparation of coumarin 3p
Preparation of ethyl 8-allyl-7-hydroxy-2-oxo-2H-chromene-3-
carboxylate 3q has been achieved from 3-allyl-2,4-
dihydroxybenzaldehyde 1q (Scheme-6). Alkylation of 2,4-
dihydroxybenzaldehyde with 3-bromoprop-1-ene in the presence
of NaHCO3 with KI in CH3CN provided corresponding 4-
(allyloxy)-2-hydroxybenzaldehyde. Claisen rearrangement13 of 4-
(allyloxy)-2-hydroxybenzaldehyde at >200 0C provided
corresponding salicylaldehyde 1q. Condensation of 1q with 2
provided 3q (Scheme 6).
Scheme 9. Synthesis of coumarin 3v
In conclusion, we developed a facile method for the synthesis
of substituted 2H-chromene-3-carboxylates by the condensation
of substituted salicylaldehydes with ethyl 4,4,4-trichloro-3-
oxobutanoate for the first time. The results were summarized in
Table 1 indicate the scope and generality of the reaction with
respect to the examples described therein. Ethyl 4,4,4-trichloro-3-
oxobutanoate is an important β-ketoester and we are investigating
the various reactions to prepare biologically important
heterocyclic compounds. Heterocyclic compounds are important
especially in pharmaceutical and medicinal chemistry; the present
protocol can be extended for the synthesis of biologically
important heterocyclic compounds.
Acknowledgments
The authors thank Dr. M. Lakshmi Kantam, Director and Dr. S.
Chandrasekhar, Head, Natural Products Chemistry Division,
CSIR-IICT for their constant encouragement and support. M.S.
thanks UGC and G.S thank CSIR, New Delhi for financial
Scheme 6. Preparation of coumarin 3q

4
Tetrahedron
12. Kumar, J. A.; Saidachary, G.; Mallesham, G.; Sridhar, B.; Jain, N.;
Kalivendi, S. V.; Rao, V. J.; Raju, B. C. Eur. J. Med. Chem. 2013, 65,
389-402.
support. B. China Raju acknowledges SERB-DST, New Delhi
for financial support (SB/EMEQ-301/2013).
13. Majumdar, K. C.; Nandi, R. K. Tetrahedron 2013, 69, 6921-6957.
14. (a) Queval, B. Eur. J. Med. Chem. 1974, 8, 335-339. (b) Zou, Y.;
Lobera, M.; Snider, B. B. J. Org. Chem. 2005, 70, 1761-1770.
Supplementary Material
Supplementary data associated with this article can be found,
in the online version, at
15. Typical procedure for the preparation of 3a-v: Piperidine (21 mg, 30
mol%) was added slowly to a stirred solution of salicylaldehyde 1a (100
mg, 1 equiv) and ethyl 4,4,4-trichloro-3-oxobutanoate 2 (192 mg, 1
equiv) in toluene (2 mL) at room temperature. The reaction mixture
was refluxed for 4 h. After completion of the reaction (TLC), the crude
product was subjected to column chromatography purification using
silica gel (60:120) provided coumarin 3a as colorless solid. Yield: 90%,
m.p. 90-92 0C. 1H NMR (300 MHz, CDCl3): δ 1.42 (t, 3H, J = 7.2 Hz,
CH3), 4.4 (q, 2H, J = 7.2 Hz, OCH2), 7.32-7.36 (m, 2H, aromatic), 7.61-
7.69 (m, 2H, aromatic), 8.51 (s, 1H, aromatic) ppm. 13C NMR (75 MHz,
CDCl3): δ 14.08, 61.82, 116.56, 117.70, 118.06, 124.72, 129.40, 134.23,
148.49, 154.97, 156.60, 162.86 ppm. IR (KBr): 2926, 1700, 1648, 1606,
1451, 1266, 1175, 1121 cm-1. ESI-MS: m/z 219 [M+H]+; 241 [M+Na]+.
HRMS (ESI): m/z calcd for C12H10O4 [M + H]+ 219.0651: found;
219.0660. 3j) Ethyl 6,8-dinitro-2-oxo-2H-chromene-3-carboxylate: Red
color solid. Yield: 41%, m.p. 116-118 0C. 1H NMR (300 MHz, CDCl3):
δ 1.43 (t, 3H, J = 7.2 Hz, CH3), 4.45 (q, 2H, J = 7.2 Hz, OCH2), 8.64 (s,
1H, aromatic), 8.79 (d, 1H, J = 2.6 Hz, aromatic), 9.05 (d, 1H, J = 2.6
Hz, aromatic) ppm. 13C NMR (75 MHz, CDCl3): δ 14.13, 63.06, 120.29,
121.58, 124.07, 128.70, 142.66, 145.91, 150.84, 152.24, 156.13, 161.20
ppm. IR (KBr): 3089, 2949, 2856, 1780, 1709, 1624, 1541, 1347, 1095,
References and notes
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3.
4.
-1
1013 cm . ESI-MS: m/z 309 [M+H]+; 331 [M+Na]+. 3m) Ethyl 7-
(allyloxy)-2-oxo-2H-chromene-3-carboxylate: Pale yellow solid. Yield:
61%, m.p. 96-98 0C. 1H NMR (300 MHz, CDCl3): δ 1.4 (t, 3H, J = 7.1
Hz, CH3), 4.4 (q, 2H, J = 7.1 Hz, OCH2), 4.63 (d, 2H, J = 5.0 Hz,
OCH2), 5.37 (d, 1H, J = 10.7 Hz, CH), 5.45 (d, 1H, J = 17.4 Hz, CH),
5.99-6.09 (m, 1H, CH), 6.83 (s, 1H, aromatic), 6.91 (dd, 1H, J = 1.8, 8.5
Hz, aromatic), 7.50 (d, 1H, J = 8.7 Hz, aromatic), 8.51 (s, 1H, aromatic)
ppm. 13C NMR (75 MHz, CDCl3): δ 14.25, 61.68, 69.47, 101.16,
111.67, 114.09, 118.88, 130.67, 131.66, 139.23, 148.92, 157.12, 157.41,
163.39, 164.02 ppm. IR (KBr): 2924, 2853, 1755, 1617, 1430, 1293,
1215, 1126 cm-1. ESI-MS: m/z 275 [M+H]+; 297 [M+Na]+. HRMS
(ESI): m/z calcd for C15H14O5 [M+H]+; 275.0914; found; 275.0917. 3n)
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Ethyl
7-(3-methylbut-2-enyloxy)-2-oxo-2H-chromene-3-carboxylate:
Pale yellow solid. Yield: 58%, m.p. 90-92 0C. 1H NMR (300 MHz,
CDCl3): δ 1.41 (t, 3H, J = 6.8 Hz, CH3), 1.79 (s, 3H, CH3), 1.83 (s, 3H,
CH3), 4.41 (q, 2H, J = 7.6 Hz, OCH2), 4.63 (d, 2H, J = 6.1 Hz, OCH2),
5.43-5.55 (m, 1H, CH), 6.83 (s, 1H, CH), 6.91 (d, 1H, J = 8.3 Hz CH),
7.51 (d, 1H, aromatic), 8.52 (s, 1H, aromatic) ppm. 13C NMR (75 MHz,
CDCl3): δ 14.26, 18.30, 25.80, 61.67, 65.71, 101.00, 111.48, 114.24,
118.19, 130.61, 139.72, 148.99, 157.23, 157.51, 159.97, 163.47, 164.46
ppm. IR (KBr): 2958, 2924, 2854, 1761, 1704, 1614, 1382, 1223, 1182,
1115 cm-1. ESI-MS: m/z 303 [M+H]+: 325 [M+Na]+. HRMS (ESI): m/z
calcd for C17H18O5 [M + H]+: 303.1227; found; 303.1229. 3o) Ethyl 7-
6.
7.
Sharma, V. K.; Saharo, P. D.; Sharma, N.; Rastogi, R. C.; Ghoshal, S.
K.; Mohan, D. Spectrochim. Acta A. 2003, 59, 1161-1170.
(a) Sugino, T.; Tanaka, K. Chem. Lett. 2001, 110-111; (b) Chen, J.;
Zhang, Y. J. Chem. Res. 2001, 394-395; (c) Chizhov, D. L.;
Sosnovskikh, V. Y.; Pryadeina, M. V.; Burgart, Y. V.; Saloutin, V. I.;
Charushin, V. N. Synlett 2008, 281-285.
(2,2-dimethoxyethoxy)-2-oxo-2H-chromene-3-carboxylate:
Brownish
color solid. Yield: 51%, m.p. 98-100 0C. 1H NMR (300 MHz, CDCl3): δ
1.40 (t, 3H, J = 6.9 Hz, CH3), 3.48 (s, 6H, OCH3), 4.08 (d, 2H, J = 5.1
Hz, OCH2), 4.40 (q, 2H, J = 6.9 Hz, OCH2), 4.75 (t, 1H, J = 5.1 Hz,
CH), 6.84 (d, 1H, J = 2.3 Hz, CH), 6.93 (dd, 1H, J = 2.4 Hz, 8.7 Hz,
aromatic), 7.51 (d, 1H, J = 8.7 Hz, aromatic), 8.5 (s, 1H, aromatic) ppm.
13C NMR (75 MHz, CDCl3): δ 14.24, 54.39, 61.71, 68.09, 101.15,
101.67, 111.91, 113.78, 114.38, 130.72, 148.81, 157.02, 157.31, 163.33,
8.
9.
Raju, B. C.; Suman, P. Chem. Eur. J. 2010, 16, 11840-11842.
(a) Raju, B. C.; Saidachary, G.; Kumar, J. A.; Sridhar, B. Helv. Chim.
Acta. 2011, 94, 248-253. (b) Raju, B. C.; Saidachary, G.; Kumar, J. A.
Tetrahedron 2012, 68, 6289-6297. (c) Saidachary, G.; Veera Prasad, K.;
Divya, D.; Singh, A.; Ramesh, U.; Sridhar, B.; Raju. B. C. Eur. J. Med.
Chem. 2014, 76, 460-469; (d) Raju, B. C.; Prasad, K. V.; Saidachary,
G.; Sridhar, B. Org. Lett. 2014, 16, 420-423; (e) Saidachary, G.; Prasad,
K. V.; Sairam, M.; Raju, B. C. Tetrahedron Lett. 2014, 55, 4753-4757.
-1
163.8 ppm. IR (KBr): 2933, 1738, 1620, 1449, 1227, 1134, 1036 cm .
ESI-MS: m/z 323 [M+H]+; 345 [M+Na]+. HRMS-ESI: calcd for
C16H18O7 [M+ Na]+; 345.0945; found; 345.0931. 3q) Ethyl 8-allyl-7-
hydroxy-2-oxo-2H-chromene-3-carboxylate: Brownish color solid:
Yield: 70%, m.p. 190-192 0C. 1H NMR (300 MHz, CDCl3): δ 1.4 (t, 3H,
J = 7.2 Hz, CH3), 3.68 (d, 2H, J = 6.1 Hz, CH2), 4.4 (q, 2H, J = 7.2 Hz,
OCH2), 5.16-5.24 (m, 2H), 5.94-6.04 (m, 1H, CH), 6.35 (brs, 1H, OH),
6.88 (d, 1H, J = 8.5 Hz, aromatic), 7.41 (d, 1H, J = 8.5 Hz, aromatic),
8.50 (s, 1H, aromatic) ppm.13C NMR (75 MHz, CDCl3 + DMSO-d6): δ
13.45, 25.78, 60.28, 109.90, 111.16, 112.79, 114.38, 128.0, 130.17,
134.10, 148.81, 154.33, 156.56, 161.35, 162.46 ppm. IR (KBr): 3265,
2924, 1707, 1604, 1570, 1491, 1375, 1236, 1058 cm-1. ESI-MS: m/z 275
[M+H]+; 297 [M+Na]+: HRMS (ESI): m/z calcd for C15H14O5 [M + H]+;
275.0914; found; 275.0926. 3r) Ethyl 8,8-dimethyl-2-oxo-2,6,7,8-
tetrahydropyrano[3,2-g]chromene-3-carboxylate: Pale yellow solid.
Yield: 57%, m.p. 154-156 0C. 1H NMR (300 MHz, CDCl3): δ 1.39 (s,
6H, CH3), 1.40 (t, 3H, J = 7.2 Hz, CH3), 1.87 (t, 2H, J = 6.7 Hz, CH2),
2.85 (t, 2H, J = 6.7 Hz, CH2), 4.39 (q, 2H, J = 7.2 Hz, OCH2), 6.72 (s,
1H, aromatic), 7.29 (s, 1H, aromatic), 8.45 (s, 1H, aromatic) ppm. 13C
NMR (75 MHz, CDCl3): δ 14.28, 21.80, 26.94, 32.22, 61.57, 76.60,
104.31, 111.31, 113.65, 119.28, 130.21, 148.98, 155.56, 157.47, 160.46,
10. (a) Martins, M. A. P.; Teixeira, M. V. M.; Cunico, W.; Scapin, E.;
Mayer, R.; Pereira, C. M. P.; Zanatta, N.; Bonacorso, H. G.; Peppe, C.;
Yuan, Y-F. Tetrahedron Lett. 2004, 45, 8991-8994; (b) Arban R.;
Bianchi, F.; Buson, A.; Cremonesi, S.; Di Fabio, R.; Gentile, G.;
Micheli, F.; Pasquarello, A.; Pozzan, A.; Tarsi, L.; Terreni, S.; Tonelli,
F. Bioorg. Med. Chem. Lett. 2010, 20, 5044-5049.
11. (a) Raju, B. C.; Tiwari, A. K.; Kumar, J. A.; Ali, A. Z.; Agawane, S.
B.; Saidachary, G.; Madhusudana, K. Bioorg. Med. Chem. 2010, 18,
358-365; (b) Kumar, J. A.; Tiwari, A. K.; Ali, A. Z.; Rao, R. R.; Raju,
B. C. J. Heterocycl.Chem. 2011, 48, 1251-1257; (c) Kumar, J. A.;
Tiwari, A. K.; Saidachary, G.; Kumar, D. A.; Ali, A. Z.; Sridhar, B.;
Raju, B. C. Medicinal Chemistry 2013, 9, 806-811. (d) Kumar, J. A.;
Tiwari, A. K.; Saidachary, G.; Kishor, C.; Kumar, D. A.; Ali, A. Z.;
Sridhar, B.; Addlagatta, A.; Raju, B. C. Med. Chem. Res. 2014, 23,
2821-2833.

5
163.69 ppm. IR (KBr): 3054, 2971, 2928, 1733, 1696, 1558, 1373,
1230, 1148, 1118, 1024 cm-1. ESI-MS: m/z 303 [M+H]+; 325 [M+Na]+.
HRMS (ESI): m/z calcd for C17H18O5 [M + H]+; 303.1227; found;
303.1239. 3v) Ethyl 7-oxo-7H-furo [3,2-g]chromene-6-carboxylate:
Pale yellow solid; Yield: 28%, m.p. 136-138 0C. 1H NMR (300 MHz,
CDCl3): δ 1.43 (t, 3H, J = 7.2 Hz, CH3), 4.44 (q, 2H, J = 7.2 Hz,
OCH2), 6.86-6.90 (brs, 1H, aromatic), 7.50 (s, 1H, aromatic), 7.74 (d,
1H, J = 2.3 Hz, aromatic), 7.83 (d, 1H, aromatic), 8.67 (s, 1H, aromatic)
ppm. 13C NMR: (75 MHz, CDCl3): δ 14.25, 61.89, 99.74, 106.44,
114.44, 116.09, 121.90, 125.48, 147.40, 149.56, 153.08, 156.94, 157.96,
163.29 ppm. IR (KBr): 2925, 2853, 1760, 1627, 1458, 1261, 1216, 1122
cm-1. ESI-MS: m/z 259 [M+H]+; 281 [M+Na]+. HRMS-ESI: m/z calcd
for C14H10O5 [M+H]+; 259.0601; found; 259.0598.