Synthesis of novel pyrano[3,2-c]quinoline-2,5-diones using an acidic ionic liquid catalyst

Article abstract of DOI:10.1016/j.tetlet.2013.06.050

The synthesis of novel 4-substituted-3,4-dihydro-6H-pyrano[3,2-c]quinoline- 2,5-diones was accomplished efficiently via a three-component reaction between 4-hydroxyquinoline-2-one, Meldrum's acid, and an alkyl or arylaldehyde under catalysis by [Bmim]HSO₄. The ionic liquid catalyst offers the advantage of realizing the synthesis of the title products at ambient temperature and widens the scope of the reactants to include aliphatic aldehydes with respect to the catalysts already applied for similar syntheses.

Full text of DOI:10.1016/j.tetlet.2013.06.050

Accepted Manuscript
Synthesis of novel pyrano[3,2-c]quinoline-2,5-diones using an acidic ionic liq‐
uid catalyst
Kurosh Rad-Moghadam, Seyyedeh Cobra Azimi, Esmayeel Abbaspour-
Gilandeh
PII:
S0040-4039(13)01017-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.06.050
TETL 43103
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
21 December 2012
24 May 2013
12 June 2013
Please cite this article as: Rad-Moghadam, K., Azimi, S.C., Abbaspour-Gilandeh, E., Synthesis of novel pyrano[3,2-
c]quinoline-2,5-diones using an acidic ionic liquid catalyst, Tetrahedron Letters (2013), doi: http://dx.doi.org/
10.1016/j.tetlet.2013.06.050
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Graphical Abstract
Leave this area blank for abstract info.
Synthesis of novel pyrano[3,2-c]quinoline-2,5-
diones using an acidic ionic liquid catalyst
Kurosh Rad-Moghadam,* Seyyedeh Cobra Azimi, Esmayeel Abbaspour-Gilandeh
O
OH
O
O
O
[Bmim]HSO4
r.t.
R
R-CHO
O
O
N
O
H
N
H
O
1
2
3
4a-l

Tetrahedron Letters
2
TETRAHEDRON
LETTERS
Pergamon
Synthesis of novel pyrano[3,2-c]quinoline-2,5-diones using an
acidic ionic liquid catalyst
Kurosh Rad-Moghadam, Seyyedeh Cobra Azimi, Esmayeel Abbaspour-Gilandeh
Chemistry Department, University of Guilan, P.O.Box, 41335-19141, Rasht, Iran
Abstract— The synthesis of novel 4-substituted-3,4-dihydro-6H-pyrano[3,2-c]quinoline-2,5-diones was accomplished efficiently via a
three-component reaction between 4-hydroxyquinoline-2-one, Meldrum’s acid and an alkyl or arylaldehyde under catalysis by
[Bmim]HSO4. The ionic liquid catalyst offers the advantage of realizing the synthesis of the title products at ambient temperature and
widens the scope of the reactants to include aliphatic aldehydes with respect to the catalysts already applied for similar syntheses. © 2013
Elsevier Science. All rights reserved.
Keywords: 4-Hydroxy-2-quinolone, Ionic liquid, Meldrum’s acid, Reusable catalyst, Multicomponent reaction
The first multicomponent reaction (MCR) was reported by Strecker in 1850 for the synthesis of amino acids.1,2 Since then,
multi-component reactions (MCRs) have developed into a field of very active research, and have become an integral part of
modern synthetic organic chemistry due to their valued features such as convergence, productivity, simplicity, and generally
high yields.3 Because of these advantages, MCRs are usually considered for the development of environmentally benign
synthetic methods. Hence they are important from a green chemistry point-of-view. 4,5
Ionic liquids are becoming an increasingly rich area of study. They are referred to as a new generation of solvents having
excellent properties capable of being tailored, to a large extent, by altering the anionic or cationic components. Owing to their
dual organic and ionic nature, ionic liquids have the ability to interact with solutes in terms of both electrostatic and
dispersive forces. This imparts to them the ability to dissolve both organic and inorganic reactants as well as to stabilize polar
reacting species including those occurring at transition states. As a consequence of their interactions with reacting molecules,
remarkable rate enhancements and improvements in the selectivities of the reactions are sometimes obtained. The structural
variation of ionic liquids allows their properties to be fine-tuned for specific tasks, or for easy separation from the products.
———
 Corresponding author; Fax +98 131 3220066
E-mail: radmm@guilan.ac.ir

3
Tetrahedron Letters
The emergence of catalytic ionic liquids composed of functional components has revealed their potential uses beyond that of
being simply green recyclable solvents of low vapor pressure.6,7
The 4-oxyquinolin-2-one framework constitutes the main part of numerous natural products possessing distinct properties of
general interest. This structural motif is broadly represented by pyranoquinolinone alkaloids manifesting diverse biological
activities including antibacterial, antifungal, anti-algal, anti-inflammatory, and antimalarial properties, as well as inhibition of
calcium signaling, platelet aggregation, and nitric oxide production.8-15 Furthermore, many of these alkaloids exhibit cancer
cell growth inhibitory activity and are investigated as potential anticancer agents.16 These valued properties have inspired
chemists to mimic such natural designs in developing derived analogues of alkaloids, for example, huajiaosimuline, veprisine
and flindersine, which all contian the key pyrano[3,2-c]quinolin-2-one pharmacophoric motif (Scheme 1).17-22
Scheme 1: Examples of bioactive pyrano[3,2-c]quinoline alkaloids.
With this background in mind, and in line with our interest in the synthesis of pyran-annulated compounds and also in
performing reactions with the aid of ionic liquids,23-30 we wanted to extend our recent method27 to the synthesis of new
pyrano[3,2-c]quinoline-2,5-dione derivatives. In this regard, the reaction of 4-hydroxyquinolin-2-one (1) with Meldrum’s
acid (2) and 4-methylbenzaldehyde (3a) was selected as a model system in the expectation of synthesizing the desired
pyrano[3,2-c]quinoline-2,5-dione 4a. Initial examinations of this trial reaction at ambient temperature in several media
including the ionic liquid N,N,N,N-tetramethylguanidinium triflate (TMGTf), which we previously used for the synthesis of
analogues of pyrano[3,2-c]pyran compounds,27 and likewise in aqueous or ethanolic solutions of L-proline,23 have not
resulted in satisfactory yields of the product 4a (Table 1). Further exploration revealed that increasing the reaction
temperature up to 80 °C had a moderate impact on improving the yield and the rate of this reaction. Under these conditions,
however, aliphatic aldehydes did not give the corresponding 4-alkyl products at all. Following this observation, we reasoned
that 4-hydroxyquinolin-2-one was not sufficiently nucleophilic, like 4-hydroxy-2H-pyran-2-one,27 to enter into reaction with
the other two components and required assistance by activating the electrophilic reactants. This was found to be the case
when the model reaction was carried out in the acidic ionic liquid, [Bmim]HSO4.32 The catalytic activity of this ionic liquid
seemed to be a consequence of its ionic and acidic characters. Valuable evidence in support of this premise was the

Tetrahedron Letters
4
observation that a dramatic improvement in the catalytic activity of [Bmim]BF4 was obtained by addition of p-
toluenesulfonic acid (50 mol% ), wherein the model reactions were catalyzed efficiently at room temperature. In contrast, the
reactions were only moderately successful above 80 °C in a 5 M ethanolic solution of p-toluenesulfonic acid.
Table 1. Optimization of the reaction conditions. a
O
OH
CHO
O
O
O
O
O
N
O
H
N
O
Me
H
Me
1
2
3
4a
Entry
Conditions
Time (min)
Yield of 4 (%)
Et3N,b EtOH, 80 °C
p-TSA, EtOH, r.t.
180
150
150
150
150
150
120
100
180
180
150
80
trace
45
63
43
78
73
70
75
1
2
3
4
5
6
7
8
9
p-TSA, EtOH, 80 °C
L-Proline,c EtOH, r.t.
L-Proline, EtOH, 80 °C
L-Proline, H2O/EtOH, 80 °C
TMGTf, r.t.
TMGTf, 80 °C
[Bmim][BF4], r.t.
[Bmim][BF4], 80 °C
p-TSA,d [Bmim][BF4], r.t.
[Bmim]HSO4, r.t.
--------
trace
82
10
11
12
85
a Reaction conditions: 4-hydroxyquinoline-2-one (1) (1 mmol), Meldrum’s acid (2) (1 mmol), 4-methylbenzaldehyde (3) (1 mmol).
b 10 mol%. c 50 mol%. d 50 mol%.
The generality and substituent scope of this new method was investigated by employing several aromatic and aliphatic
aldehydes. As shown in Table 2, the reaction was compatible with an array of aryl aldehydes bearing either electron-
withdrawing or electron-donating groups as well as sterically demanding substituents. To the best of our knowledge, this is
the first report on the synthesis of 4-substituted-3,4-dihydro-6H-pyrano[3,2-c]quinoline-2,5-diones at ambient temperature.
Both aromatic and aliphatic aldehydes underwent a smooth reaction with 4-hydroxyquinoline-2-one and Meldrum’s acid in
this ionic liquid to give fairly high yields of the products 4a-l at ambient temperature.
Table 2. Reaction of 4-hydroxyquinoline-2-one (1) with Meldrum’s acid (2) and various aldehydes (3).

5
Tetrahedron Letters
O
O
OH
O
O
R
R-CHO
O
O
N
H
O
N
H
O
1
2
3
4a-l
Entry
R
Product
Yield (%) a,b
[Bmim]HSO4/ r.t.
Yield (%) a,c
TMGTf/ 80 °C
Yield (%) a,d
L-Proline, EtOH/ 80 °C
78
1
2
4-MeC6H4
4-ClC6H4
4-MeOC6H4
4-FC6H4
3-BrC6H4
C6H4
4a
4b
4c
4d
4e
4f
85
75
89
83
83
87
87
90
80
80
76
74
74
78
73
80
75
3
4
76
73
5
75
79
6
78
80
7
2,4-Cl2C6H3
Et
4g
4h
4i
79
83
8
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
9
n-Pr
10
11
12
n-hexyl
n-octyl
4j
4k
n-nonyl
4l
a Isolated yields. b reaction time = 80 min. c reaction time = 120 min d reaction time = 150 min.
As yet, we have not determined the mechanism of this reaction, but a plausible route is proposed in Scheme 2. The synthesis
is likely initiated by [Bmim]HSO4, which promotes a Knoevenagel condensation between Meldrum’s acid (2) and the
aldehyde (3) resulting in formation of intermediate 5. This intermediate subsequently undergoes a Michael-type addition with
4-hydroxyquinoline-2-one (1) to deliver the adduct 6. Cyclization of 6 via a translactonization reaction leads to liberation of
an acetone molecule leaving product 7 bearing a carboxyl group at the 3-position. Spontaneous decarboxylation of 7 gives the
4-aryl-product 4. The initial condensation during the three-component reaction appears to be influenced by the different pKa
values of the two dicarbonyl substrates such that the Knoevenagel condensation of Meldrum’s acid predominates due to its
stronger acidity. This consideration was in fact confirmed by isolation of intermediate 5. Contrary to our initial expectation,
the intermediate 7 derived from the aromatic and aliphatic aldehydes could not be isolated before undergoing a facile in situ
decarboxylation, even at room temperature. The rapid decarboxylation of these intermediates may be occuring through
catalysis by the acidic medium. A concomitant loss of acetone and CO2 from the intermediate 6 is also concievable in an
alternative pathway which generates the reactive intermediate ketene 8.31 The ketene 8 undergoes an intramolecular
cyclization to give the product 4. Similar applications of other 1,3-dicarbonyls such as ethyl acetoacetate, dimedone,

Tetrahedron Letters
6
cyclopentadione and acetylacetone instead of Meldrum's acid under [Bmim]HSO4 catalysis did not lead to formation of
products 4. This finding lends some credit to the proposal of ketene 8 intermediacy.
N
Bu
N
Bu
N
N
O
R
O
H
H
O
O
H S O-
O
5
O
O
H S O-
O
O
O
O
O
O
O
R
H
H
2
3
1
O
N
H
N
Bu
N
O
O
R
O
O
O
H S O-
O
O
O
O
CO2H
O
H
CO2
O
R
R
N
H
O
N
H
O
N
H
O
Acetone
6
7
4
Or alternatively
O
O
O
O
O
O
O
H
C
O
H
H
O
R
R
R
N
H
O
N
H
O
N
H
O
Acetone
+
CO2
6
8
4
Scheme 2. A plausible mechanism for the synthesis of products 4a-l.
The [Bmim]HSO4 ionic liquid could be recovered from the aqueous extracts of the reaction mixtures by evaporation of the
water under reduced pressure. It was found to retain almost all its initial activity after recovery when reused in the successive
cycles (Table 3).
Table 3: The effect of [Bmim]HSO4 recycling on the yield of 4-(4-methylphenyl)-3,4-dihydro-6H-pyrano[3,2-c]quinoline-2,5-dione 4a.

7
Tetrahedron Letters
O
O
OH
CHO
O
O
O
O
N
H
O
N
O
Me
H
Me
1
2
3
4a
Run
Yield (%)
1
2
3
85
84
84
Reaction conditions: 4-hydroxyquinoline-2-one (1), Meldrum’s acid (2), 4-methylbenzaldehyde (3a) (1 mmol of each one), [Bmim]HSO4 (0.5 mL), at r.t.
The NMR spectral data as well as elemental analyses of all the products were consistent with their structures. For example,
the 1H NMR spectrum of 4a displayed an AMX spin system for the CH2CH protons (at δ= 2.91, 3.47 and 4.48). A relatively
strong coupling between a vicinal pair of protons of this system (3J= 7.8 Hz) can be attributed to their somewhat axial
orientation in the molecule, and consequently to restricted inversion of the dihydropyranoquinoline ring in which the aryl
substituent resides at the equatorial position. The 13C NMR spectra of compounds 4a-l displayed the expected signals at
apropriate chemical shifts corresponding to the resonances of all the carbon atoms.
In conclusion, we have developed a very simple and efficient method for the synthesis of pyrano[3,2-c]quinoline-2,5-diones
by a straightforward, one-pot, three-component condensation of 4-hydroxyquinoline-2-one, Meldrum’s acid and an
aromatic/aliphatic aldehyde at room temperature in [Bmim]HSO4. In sharp contrast with previously reported methods used
for similar syntheses, the present method affords the products at ambient temperature and importantly realizes the application
of aliphatic aldehydes for the synthesis of 4-alkylpyrano[3,2-c]quinoline-2,5-diones. The operational simplicity of the
procedure, short reaction times, convenient work-up, and reusability of the ionic liquid make this method attractive.
Acknowledgement
We gratefully acknowledge the financial support of this work by the Research Council of the University of Guilan.
References and notes
1. Strecker, A.; Liebigs Ann. Chem. 1850, 75, 27-45.
2. Lei, M.; Ma, L.; Hu, L. Monatsh. Chem. 2010, 141, 1005-1008.
3. Tan, J. N.; Lia, M.; Gu, Y. Green Chem. 2010, 12, 908-914.

Tetrahedron Letters
4. Kobayashi, S.; Chem. Soc. Rev. 1999, 28, 1-15.
8
5. Tejedor, D.; Gonzalez-Cruz, D.; Santos-Exposito, A.; Marrero-Tellado, J. J.; de Armas, P.; Garcıa-Tellado, F. Chem.
Eur. J. 2005, 11, 3502-3510.
6. Turner, E. A.; Pye, C. C.; Singer, R. D. J. Phys. Chem. A. 2003, 107, 2277-2288.
7. Chowdhury, S.; Mohan, R. S.; Scott, J. L. Tetrahedron 2007, 63, 2363-2389.
8. (a) Davion, T.; Joseph, B.; Merour, Y. Synlett 1998, 1051-1052. (b) Tietze, L. F.; Zhou, Y. F. Angew. Chem. Int. Ed.
1999, 38, 2045-2047.
9. Fujita, Y.; Oguri, H.; Oikawa. H. J. Antibiot., 2005, 58, 425-427.
10. Hanawa, F.; Fokialakis, N.; Skaltsounis, A. L. Planta Med. 2004, 70, 531-535.
11. Cantrell, C. L.; Schrader, K. K.; Mamonov, L. K.; Sitpaeva, G. T.; Kustova, T. S.; Dunbar, C.; Wedge, D. E. J. Agric.
Food Chem. 2005, 53, 7741-7748.
12. Chen, J. J.; Liao, P. H.; Huang, C. H.; Chen, S. Y.; I. S. J. Nat. Prod. 2007, 70, 1444-1448.
13. Koizumi, F.; Fukumitsu, N.; Zhao, J.; Chanklan, R.; Miyakawa, T.; Kawahara, S.; Iwamoto, S.; Suzuki, M.; Kakita,
S.; Rahayu, E. S.; Hosokawa, S.; Tatsuta, K.; Ichimura, M. J. Antibiot. 2007, 60, 455-458.
14. Chen, I. S.; Tsai, I. W.; Teng, C. M.; Chen, J. J.; Chang, Y. L.; Ko, F. N.; Lu, M. C.; Pezzuto, J. M. Phytochemistry
1997, 46, 525-529.
15. Ito, C.; Itoigawa, M.; Furukawa, A.; Hirano, T.; Murata, T.; Kaneda, N.; Hisada, Y.; Okuda, K.; Furukawa, H. J. Nat.
Prod. 2004, 67, 1800-1803.
16. Chen, I. S.; Wu, S. J.; Tsai, I. L.; Wu, T. S.; Pezzuto, J. M.; Lu, M. C.; Chai, H.; Suh, N.; Teng, C. M. J. Nat. Prod.
1994, 57, 1206-1211.
17. Xuesen, F.; Dong, F.; Yingying, Q.; Xinying, Z.; Jianji, W.; Philippe, M. L.; Graciela, A.; Robert, S.; Erik, D. C.
Bioorg. Med. Chem. Lett. 2010, 20, 809-813.
18. Kishore, N.; Mishra, B. B.; Tripathi, V.; Tiwari, V. K. Fitoterapia 2009, 80, 149-163.
19. Matteelli, A.; Carvalho, A. C.; Dooley, K. E.; Kritski, A. Future Microbiol. 2010, 5, 849-858.
20. Schiemann, K.; Finsinger, D.; Zenke, F.; Amendt, C.; Knochel, T.; Bruge, D.; Buchstaller, H.; Emde, U.; Stahle, W.;
Anzali, S. Bioorg. Med. Chem. Lett. 2010, 20, 1491-1495.
21. Kumar, A.; Srivastava, S.; Gupta, G.; Chaturvedi, V.; Sinha, S.; Srivastava, R. ACS Comb. Sci. 2011, 13, 65-71.
22. Itoh, K.; Hasegawa, M.; Tanaka, J.; Kanemasa, Sh. Org. Lett. 2005, 7, 979-981.
23. Yavari, I.; Sabbaghan, M.; Hossaini, Z. Synlett 2008, 1153-1154.

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Tetrahedron Letters
24. Khurana, J. M.; Kanika, V. Tetrahedron Lett. 2011, 52, 3666-3669.
25. Rad-Moghadam, K.; Sharifi-Kiasaraie, M. Tetrahedron 2009, 65, 8816-8820.
26. Rad-Moghadam, K.; Sharifi-Kiasaraie, M.; Taheri-Amlashi, H. Tetrahedron 2010, 66, 2316-2321.
27. Rad-Moghadam, K.; Sharifi-Kiasaraie, M.; Azimi, S. C. Tetrahedron 2012, 68, 6472-6476.
28. Rad-Moghadam, K.; Mohseni, M. Monatsh. Chem. 2004, 135, 817-821.
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31. Patel, B. H.; Mason, A. M.; Barrett, A. G. M. Org. Lett. 2011, 13, 5156-5159.
32. Typical procedure for the preparation of 4-(4-methylphenyl)-3,4-dihydro-6H-pyrano[3,2-c]quinoline-2,5-dione
(4a):
A mixture of 4-hydroxyquinoline-2-one (1) (0.161 g, 1 mmol), Meldrum's acid (2) (0.144 g, 1 mmol) and 4-
methylbenzaldehyde (0.119 g, 1 mmol) was added to a vial containing a magnetic stirring bar and the ionic liquid
([Bmim]HSO4, 0.5 mL). The mixture was sealed and stirred at r.t. until disappearance of the starting materials had
occurred (80 min). The residue was washed with cold H2O (3 × 7 mL) to extract the ionic liquid. The solid residue
was recrystallized from EtOH (95.5%) to give the pure product 4a (0.26 g, 85%). The ionic liquid was recovered
from the aqueous extracts by evaporation of H2O under reduced pressure and reused in the subsequent runs.
White powder; (0.260 g, 85%). Mp 330-332 oC. IR (KBr): 3184, 3006, 2955, 2903, 1779, 1657 (C=O), 1382, 1311,
1119, 1106 cm-1. 1H NMR (400.22 MHz, DMSO-d6): δH 2.25 (s, 3H, CH3), 2.91 (d, 1H, J 16.0 Hz, 3-HB), 3.47 (dd,
1H, 2J 16.0 and 3J 7.8 Hz, 3-HA), 4.48 (d, 1H, J 7.8 Hz, 4-H), 7.07 (d, 2H, J 8.0 Hz, 4-Aryl), 7.12 (d, 2H, J 8.0 Hz,
4-Aryl), 7.30 (t, 1H, J 7.8 Hz, 9-H), 7.40 (d, 1H, J 7.8 Hz, 7-H), 7.62 (t, 1H, J 7.8 Hz, 8-H), 7.83 (d, 1H, J 7.8 Hz,
10-H), 12.00 (s, 1H, NH), 13C NMR (100.63 MHz, DMSO-d6): δC 21.04 (CH3), 34.64 (C-3), 36.84 (C-4), 112.27,
112.81, 115.93, 122.11, 122.70, 126.96, 129.92, 131.81, 136.86, 138.28, 138.68, 154.92, 161.36, 166.80. MS (EI, 70
eV) m/z: 305 (M+, 100), 227 (97), 262 (91), 248 (28), 186 (23), 115 (21), 92 (28). Anal. Calcd. for C19H15NO3
(305.11): C, 74.74; H, 4.95; N, 4.59%. Found: C, 74.87; H, 4.83; N, 4.64%.
All the products were similarly characterized and their data are available in the supplementary file of this paper.

Table 1. Optimization of the reaction conditions. a
O
OH
CHO
O
O
O
O
O
N
O
H
N
H
O
Me
Me
1
2
3
4a
Entry
Conditions
Time (min)
Yield of 4 (%)
Et3N,b EtOH, 80 °C
p-TSA, EtOH, r.t.
180
150
150
150
150
150
120
100
180
180
150
80
trace
45
63
43
78
73
70
75
1
2
3
4
5
6
7
8
9
p-TSA, EtOH, 80 °C
L-Proline,c EtOH, r.t.
L-Proline, EtOH, 80 °C
L-Proline, H2O/EtOH, 80 °C
TMGTf, r.t.
TMGTf, 80 °C
[Bmim][BF4], r.t.
[Bmim][BF4], 80 °C
p-TSA,d [Bmim][BF4], r.t.
[Bmim]HSO4, r.t.
--------
trace
82
10
11
12
85
a Reaction conditions: 4-hydroxyquinoline-2-one (1) (1 mmol), Meldrum’s acid (2) (1 mmol), 4-methylbenzaldehyde (3) (1 mmol).
b 10 mol%. c 50 mol%. d 50 mol%.

Table 2. Reaction of 4-hydroxyquinoline-2-one (1) with Meldrum’s acid (2) and various aldehydes (3).
O
O
OH
O
O
R
R-CHO
3
O
O
N
H
O
N
H
O
1
2
4a-l
Entry
R
Product
Yield (%) a,b
[Bmim]HSO4/ r.t.
85
Yield (%) a,c
TMGTf/ 80 °C
Yield (%) a,d
L-Proline, EtOH/ 80 °C
78
1
2
4-MeC6H4
4-ClC6H4
4-MeOC6H4
4-FC6H4
3-BrC6H4
C6H4
4a
4b
4c
4d
4e
4f
75
89
83
83
87
87
90
80
80
76
74
74
78
73
80
75
3
4
76
73
5
75
79
6
78
80
7
2,4-Cl2C6H3
Et
4g
4h
4i
79
83
8
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
9
n-Pr
10
11
12
n-hexyl
n-octyl
4j
4k
4l
n-nonyl
a Isolated yields. b reaction time = 80 min. c reaction time = 120 min d reaction time = 150 min.
Table 3: The effect of [Bmim]HSO4 recycling on the yield of 4-(4-methylphenyl)-3,4-dihydro-6H-pyrano[3,2-c]quinoline-2,5-dione 4a.
O
OH
CHO
O
O
O
O
O
N
O
H
N
O
Me
H
Me
1
2
3
4a
Run
Yield (%)
1
2
3
85
84
84
Reaction conditions: 4-hydroxyquinoline-2-one (1), Meldrum’s acid (2), 4-methylbenzaldehyde (3a) (1 mmol of each one), [Bmim]HSO4 (0.5
mL), at r.t.