Sixth International Electronic Conference on Synthetic Organic Chemistry (ECSOC-6),
1-30 September
[E008]
The Atypical Condensations of 4-Oxo-4H-Benzopyran-3Carbaldehydes with Derivatives Coumarin-3-acetic- and
Coumarin-4-acetic Acids by Microwave Irradiation and
Classical Methods
B. Bartosova1, M. Lacova 1, A. Gaplovsky 2, J. Chovancova1,
N. Pronayova3 , P. Simunek4 and D. Loos1
1Department
of Organic Chemistry, 2Institute of Chemistry and Faculty of Natural
Sciences, Comenius University, SK-842 15 Bratislava, Slovakia, Tel. +421 7 60296338,
Fax +421 7 65429064
3Central Laboratories, Faculty of Chemical Technology, Slovak University of
Technology, SK 812 37 Bratislava, Slovak Republic,
4Technical University, Pardubice, Czech Republic
Abstract: The synthesis and spectroscopic characterization of new
coumarine derivatives: 3-(2-oxo-2H-chromen-4-yl)-2-oxo-2H, 5H-pyrano[3,2-c]chromen-5-yl esters of ethanoic acid, their reaction with
nucleophiles and rearrangement in acetic acid.
O
CH2
OCOCH3
O
O
O
O
O
O
O
O
O
O
CH3
O
O
O
O
O
O
CH3
CH3
Keywords: 3-Formylchromones, Coumarines, Condensation,
Nucleophilic reaction, Rearrangement,
Introduction
Thanks to their photochemical1,biological2 and pharmaceutical3 activity
of chromone and coumarine derivatives are the subject of the
considerable interest of research - workers. 3-Formylchromones occupy
a unique position from some reasons. They are carrying a significant
biological activity2, they have comfortable preparation by VilsmeierHaack reaction 4 they are attractive intermediates for preparation of
new heterocycles5,6. For preparation of products 4, 5, 6 we used
microwave irradiation7.
Results and discussion
3-Formylchromones reacted with 3-coumarin- or 4-coumarin- acetic
acids in acetanhydride at 90 - 100 ºC giving :
4a 3-(2-oxo-2H-chromen-4-yl)-2-oxo-2H,5H-pyrano[3,2-c]chromen-5-yl
acetate
4b 3-(2-oxo-2H-chromen-3-yl)-2-oxo-2H,5H-pyrano[3,2-c]chromen-5-yl
acetate
Reactions were carried out with the presence of CH3COOK as catalyst.
Products 4a and 4b were obtained as yellow solid in 80-86 % yields in
very high purity after 1-2 hrs. The reaction were carried out in acetic
anhydride in the presence of potasium acetate also under microwave
irradiation conditions. Products of 4a and 4b were obtained after ten
minutes irradiation in a microwave oven at 400 W. The yields and
purity of products were comparable by both experimental conditions.
The subsequent nucleophile reaction (alcoholysis) of compounds 4a and
4b producted ethers:
5a Alkyloxy-3-(-2-oxo-2H-chromen-4-yl)-5H-pyrano[3,2-c] chromen-2ones)
5b Alkyloxy-3-(2-oxo-2H-chromén-3--yl)-5H-pyrano[3,2-c]chromen-2ones)
in the presence of catalytic amount of p-toluensolfonic acid with various
alcohols at 60-100 ºC. Yields were about 80 %.
It was found that prepared all compounds 4 and 5 underwent a
rearrengment by treatment with acetic acid at 60-80 ºC vithout another
part of reaction medium and yielded compounds:
6a 3-(2-oxo-2H-chromen-4-yl)-3,10a-dihydro-pyrano[2,3-b] chromene2,5-diones
6b 3-(2-oxo-2H-chromen-3-yl)-3,10a-dihydro-pyrano[2,3-b] chromene2,5-diones (Scheme 1).
Conclusion
All used reaction in this contribution were going at very smooth
conditions and rendered pure products with high yields. All prepared
compounds have a very high intensity of fluorescence emission after
irradiation of UV light. The results showed that the effect of microwave
irradiation on the studied reactions was the shortening of the reaction
time and a smooth increase in the yields. The structure of products was
the same with those from reaction by classical conditions7,8.
O
1
R
O
O
2
CHO
R
O
O
O
CH 2COOH
CH 2COOH
(CH3CO)2O
O
(CH3CO)2O
OCOCH3
1
O
OCOCH3
1
R
R
O
O
O
O
O
O
O
H+
4a
O
1
1
R
R
+
H
R2
O
O
3
O
O
ROH
ROH
O
O
H+
+
H +
O
2
O
R
O
O
O
O
1
O
R
3
H+
R
4b
H
O
6a
6b
1
+
O
O
R
3
R
O
O
O
O
O
O
5a
O
O
R2
5b
R1 = H, 6-CH3 , 6-Cl, 6- NO2, R2 = 6-CH3, 7-CH3, 7-OH,
R3 = CH3OH CH3CH2OH, CH2=CHCH2OH
( Scheme 1 )
Experimental part
General
Products were confirmed by elemental analyses and NMR spectra. The
melting points were determined on a Kofler block . 1H and 13C NMR
spectra were measured on a 300 MHz spectrometer VARIAN GEMINI
200 in deuterated CHCl3.
All microwave assisted reactions were carried out in a Lavis - 1000
multi Quant microwave oven. The apparatus was adapted for
laboratory applications with magnetic stirring and external reflux
condenser.
Synthesis of compounds 4a and 4b
Microwave irradiation method
A mixture of 6-R-3-formylchromones ( 2.26 mmol), R2-coumarin-4acetic acids ( or coumarin-3-acetic acid) ( 2.26 mmol), freshly fused
potassium acetate ( 0.2mmol) was solved in anhydrous acetic anhydride
(4 cm2) and stirred and irradiated in a microwave oven for 10 minutes
at 400W. The solid was filtered off washed by diethylether.
Classical synthetic method
A mixture of the same composition as in above method was heated at 90
- 100 ºC for 2 hrs. Isolation products was accomplished as above
described.
Analytical Data for: 3-(6-Methyl-2-Oxo-2H-Chromen-4-yl)-2-Oxo2H,5H-Pyrano[3,2-c]Chromen-5-yl Acetate.
For : C24H16O7(M = 416.3), Melting point is 244-247 C
elemental analysis: wi (calc.) 69.23% C, 3.87 % H
wi ( found) 69.36 % C, 3.82 % H
1
O
2
OCOCH3
3
5
4
6
O
O
H3C
10
1
12
11
H-NMR-spectral data:
O
O
9
7
8
CDCl3, 300 MHz: 2.07 (s, 3H, H-12), 2.37 (s, 3H, H-10), 6.09 (s, 1H, H11), 6.47 (s, 1H, H-6), 7.12 (dd, 1H, 3J1,2 = 8.1 Hz, 4J1,3 = 0.9 Hz, H-1),
7.16-7.21 (m, 2H, H-3 + H-9), 7.28 (d, 1H, 3J7,8 = 8.4 Hz, H-7), 7.36 (dd,
1H, 3J8,7 = 8.4 Hz, 4J8,9 = 1.8 Hz, H-9), 7.46-7.52 (m, 2H, H-2), 7.48 (s, 1H,
H-5), 7.91 (dd, 1H, 3J4,3 = 8 Hz, 4J4,2 = 1.8 Hz, H-4).
Analytical Data for: 9-Methyl- 3-(6-Methyl-2-Oxo-2H-Chromen-4-yl)-2Oxo-2H,5H-Pyrano[3,2-c]Chromen-5-yl Acetate.
For: C25H18O7 (M = 430.4), Melting point is 202-204 C ,
elemental analysis: wi (calc.) 70.59% C, 3.77 % H
wi ( found) 70.38 % C, 3.62 % H
1
H-NMR-spectral data:
DCl3 300 MHz : 2.07 (s, 3H, H-12), 2.38 (s, 3H, H-11(10)), 2.41 (s, 3H, H10(11)), 6.49 (s, 1H, H-6), 7.07 (d, 1H, 3J1,2 = 8.4 Hz, H-1), 7.17 (s, 1H, H9), 7.28 (d, 1H, 3J7,8 = 8.4 Hz, H-7), 7.32-7.39 (m, 3H, H-3 + H-5 + H-8),
7.58 (s, 1H, H-4), 7.77 (d, 4J3,2 = 1.8 Hz, H-2).
Analytical Data for: 9-Methyl- 3-(7-Methyl-2-Oxo-2H-Chromen-4-yl)-2Oxo-2H,5H-Pyrano[3,2-c]Chromen-5-yl Acetate.
For: C25H18O7 (M = 430.4), Melting point is 206-208 C ,
elemental analysis: wi (calcd.) 70.59% C, 3.77 % H
wi ( found) 70.29 % C, 3.54 % H
1
H-NMR-spectral data:
CDCl3 300 MHz : 2.06 (s, 3H, H-12), 2.41 (s, 3H, H-11 (10)), 2.46 (s, 3H,
H-10 (11)), 6.44 (s, 1H, H-6), 7.05-7.10 (m, 2H, H-1 + H-8), 7.20 (s, 1H,
H-7), 7.29 (d, 1H, 3J9,8 = 8.1 Hz, H-9), 7.32-7.35 (m, 2H, H-2 + H-5), 7.57
(s, 1H, H-4), 7.76 (d, 1H, 4J3,2 = 1.8 Hz, H-3).
Analytical Data for: 3-(2-Oxo-2H-Chromen-3-yl)-2-Oxo-2H,5HPyrano[3,2-c]Chromen-5-yl Acetate (4b)
For : C23H14O7 (M = 402.4), Melting point is 278-280 C ,
elemental analysis: wi (calcd.) 68.59% C, 3.50 % H
wi (found) 68.46% C, 3.54 % H
1
2
22 23
6 O 12 OCOCH3
11
3
4
5
10
7
O 8
O
13
9
21
O
O 14
20
15
19
16
17
18
1
H-NMR-spectral data:
Mixture of CDCl3,DMSO 300 MHz : 1.98 (s, 3H, H-23 ), 6.40 (s, 1H, H12), 7.07 (d, 1H, H-1), 7.12 (t, 1H, H-3), 7.35 (d,d, 2H, 3J 17,19 = 8.1 Hz, H17,H-19), 7,40 (t,1H, H-2 ), 7,59(t,1H, H-18), 7,66(d,1H, H-16), 7.80 (t,
1H, H-4), 8,23(s,1H,H-10), 8,55(s.1H,H-14)
Synthesis of compounds 5a and 5b
The synthesis is very simple, compounds 4a or 4b are stirring after
reflux in alcoholic solution. After 2 hrs yellow heated solid products
were filtered off. The products are very pure. The products were
obtained in 85 % yield after 10 minutes irradiated in microwave oven at
400W
Analytical Data for: 5-methoxy- 3-(7-Methyl-2-Oxo-2H-Chromen-4-yl)Pyrano[3,5H- 2-c]Chromen-2-on (5a)
For : C23H16O6(M = 388.3), Melting point is 214-215 C ,
12
1
O
2
O CH3
11
3
5
4
6
O
O
O
O
9
7
8
CH3
10
1
H-NMR-spectral data:
CDCl3, 300 MHz : 2.46 (s, 3H, H-10), 3.59 (s, 3H, H-12), 5.98 (s, 1H, H11), 6.43 (s, 1H, H-6), 7.08 (dd, 1H, 4J(8,7) = 1.2 Hz, 3J(8,9) = 8.1 Hz, H-8),
7.13-7.22 (m, 2H, H-1 + H-3), 7.19 (s, 1H, H-7), 7.30 (d, 1H, 3J(9,8) = 8.4
Hz, H-9), 7.46-7.52 (m, 2H, H-2), 7.47 (s, 1H, H-5), 7.91 (dd, 1H, 4J(4,2) =
1.8 Hz, 3J(4,3) = 7.8 Hz, H-4).
Analytical Data for: 5-Ethoxy- 3-(7-Methyl-2-Oxo-2H-Chromen-4-yl)5H-Pyrano[3,2-c]Chromen-2-on
For C24H18O6, M=402.4, Melting point: 231–233 oC
Elemental analysis: wi (calc.) 71.57%(C), 4.47 %(H)
wi (found) 71.69 %(C), 4.32 %(H)
H3 C
14
O
13
O
9
8
10
O
17
19
O
6
4
O
11
O
16
18
5
2
7
12
15
3
1
21
20
23
22
CH3
24
1
H-NMR spectral data:
CDCl3, 300MHz : 1.24 (t, 3H, 3J13,12 = 7.2 Hz, H-13), 2.45 (s, 3H, H-10),
3.74-3.84 (m, 1H, 2J12,12 = 9.8 Hz, 3J12,13 = 6.9 Hz, H-12), 3.97-4.07 (m,
1H, 2J12,12 = 9.6 Hz, 3J12,13 = 7.2 Hz, H-12), 6.08 (s, 1H, H-11), 6.43 (s, 1H,
H-6), 7.07 (dd, 1H, 3J8,9 = 8.1 Hz, 4J8,7 = 1.5 Hz, H-8), 7.12 (dd, 1H, 3J1,2 =
8.1 Hz, 4J1,3 = 0.9 Hz, H-1), 7.15-7.21 (m, 2H, H-3), 7.19 (s, 1H, H-7), 7.31
(d, 1H, 3J9,8 = 8.1 Hz, H-9), 7.45-7.51 (m, 2H, H-2), 7.47 (s,1H, H-5), 7.90
(dd, 3J4,3 = 7.8 Hz, 4J4,2 = 1.8 Hz, H-4).
13
C-NMR-spectra:
DMSO, 300MHz : 14.616 (C-14), 20.626 (C-24), 63.459 (C-13), 96.06 (C9), 159.238 (C-11), 120.195 (C-12), 158.05 (C-19), 149.035 (C-10), 117.25
(C-8), 132.864 (C-7), 142.873 (C-15), 107.245, 107.363, 114.226, 115.088,
116.336, 120.195, 122.247, 123.549, 125.029, 126.260, 128.690, 138.457
(C-Ar).
Analytical Data for: 5-Allyloxy- 3-(7-Methyl-2-Oxo-2H-Chromen-4-yl)5H-Pyrano[3,2-c]Chromen-2-on
For C25H18O6, M=414.4, Melting point: 209–211 oC
Elemental analysis: wi (calc.) 72.39 % (C), wi4.34 % (H)
wi (found) 7 % (C), 4.49 % (H)
1
H-NMR-spectral data:
CDCl3, 300 MHz : 2.46 (s, 3H, H-10), 4.26-4.42 (m, 2H, H-12), 5.27 (m,
1H, H-15), 5.33 (m, 1H, H-14), 5.90 (m, 1H, H-13), 6.12 (s, 1H, H-11),
6.43 (s, 1H, H-6), 7.08 (dd, 1H, 3J8,9 = 7.8 Hz, 4J8,7 = 1.2 Hz, H-8), 7.13
(dd, 1H, 3J1,2 = 8.1 Hz, 4J1,3 = 0.9 Hz, H-1), 7.17-7.22 (m, 2H, H-3 ), 7.19
(s, 1H, H-7),7.31 (d, 1H, 3J9,8 = 8.1 Hz, H-9), 7.46-7.52 (m, 2H, H-2), 7.47
(s, 1H, H-5), 7.91 (dd, 1H, 3J4,2 = 7.8 Hz, 4J4,2 = 1.5 Hz, H-4).
Analytical Data for: 5-Ethoxy- 3-(6-Methyl-2-Oxo-2H-Chromen-4-yl)5H-Pyrano[3,2-c]Chromen-2-on
For C24H18O6, M=402.4, Melting point: 238–239 oC
Elemental analysis: wi (calc.) 71.57%(C), 4.47 % wi(H)
wi (found) 71,56 %(C), 4,49 %(H)
H3C
14
O
13
O
9
8
17
19
O
7
O
12
15
11
O
16
18
21
20
23
22
CH3
24
5
2
10
O
3
1
6
4
1
H-NMR-spectral data:
CDCl3, 300 MHz : 1.24 (t, 3H, 3J13,12 = 6.9 Hz, H-13), 2.37 (s, 3H, H-10),
3.74-3.85 (m, 1H, 2J12,12 = 9.6 Hz, 3J12,13 = 7.2 Hz, H-12), 3.98-4.09 (m,
1H, 2J12,12 = 9.9 Hz, 3J12,13 = 7.2 Hz, H-12), 6.09 (s, 1H, H-11), 6.47 (s, 1H,
H-6), 7.12 (dd, 1H, 3J1,2 = 8.1 Hz, 4J1,3 = 0.9 Hz, H-1), 7.16-7.21 (m, 2H,
H-3 + H-9), 7.28 (d, 1H, 3J7,8 = 8.4 Hz, H-7), 7.36 (dd, 1H, 3J8,7 = 8.4 Hz,
4
J8,9 = 1.8 Hz, H-9), 7.46-7.52 (m, 2H, H-2), 7.48 (s, 1H, H-5), 7.91 (dd,
1H, 3J4,3 = 8 Hz, 4J4,2 = 1.8 Hz, H-4).
13
C-NMR-spectral data:
DMSO, 300MHz : 14.79 (C-14), 19.996 (C-2), 63.63 (C-13), 96.147 (C-9),
116.215 (C-8), 126,342 (C-12), 133.019 (C-7), 142.949 (C-15), 151.16 (C10), 158.255 (C-19), 159.386 (C-11), 107.397, 113.524, 114.397, 116.215,
116.378, 117.395, 117.44, 120.419, 122.342, 122.399, 132.932, 149.293,
152.526 (C-Ar).
Analytical Data for: 5-Ethoxy- 3-(6-Methyl-2-Oxo-2H-Chromen-3-yl)5H-Pyrano[3,2-c]Chromen-2-on(5b)
For C24H18O6, M=402.4, Melting point: 208–210 oC
Elemental analysis: wi (calc.) 73.82 % (C), 4.60 % (H)
wi (found) 73.76 % (C), 4.59 % (H)
1
2
22
23
6 O 12 OCH2CH3
11
Cl
4
5
10
7
O 8
O
13
9
21
O
O 14
20
15
19
16
17
1
18
H-NMR-spectral data:
CDCl3, 300 MHz : 1.22 (t, 3H, 3J22,23= 6.9 Hz, H-23), 3.89 (t, 2H, H-22),
6.19 (s, 1H, H-12), 7.03 (d, 1H, H-1), 7.36 (d, 1H, H-2), 7.35 (dd, 2H, H17,19), 7.57 (t, 1H, H-19), 7.62 (d, H-16), 7.85 (s, 1H, H-4), 8.39 (s, 1H,
H-10), 8.73 (s, 1H, H-14).
Synthesis of compounds 6a and 6b
Starting compounds for preparation of title products were all
compounds obtained under No 4 or 5. The compounds 4 or 5 are
stirring after reflux in acetic acid for 30 minutes at 60 ºC. Products were
filtered off after cooling. The products were obtained in 75 % yield. The
products were recrystalized from dry toluene. Compounds 6b are
rather insoluble in common solvent. Because of their poor solubility in
DMSO we could not measure their 1H-NMR-spectra by to now time.
Analytical Data for: 3-(7-Methyl-2-Oxo-2H-Chromen-4-yl)-3,10adihydropyrano[2,3-b]chromen-2,5-dion
For C22H14O6, M=374.4, Melting point: 214–215 oC
Elemental analysis: wi (calc.) 70.59 % (C), 5.77 % (H)
wi (found) 70.62 % (C), 3.54 % (H)
1
2
O 12 O
O 10
6
CH3
8
3
4
11
9
5
O
O
7
O
1
H-NMR-spektrum:
CDCl3, 300 MHz : 2.46 (s, 3H, H-11), 3.47 (d, 1H, 3J6,5 = 5.7 Hz, H-6),
6.43 (s, 1H, H-7), 6.47 (d, 1H 3J5,6 = 5.4 Hz, H-5), 7.08 (d, 1H, 3J9,10 = 7.5
Hz, H-9), 7.12 (d, 1H, 3J1,2 = 8.4 Hz, H-1), 7.16-7.22 (m, 2H, H-3 + H-8),
7.31 (d, 1H, 3J10,9 = 7.8 Hz, H-10), 7.49 (m, 1H, H-2), 7.53 (s, 1H, H-12),
7.91 (dd, 1H, 3J4,3 = 7.8 Hz, 4J4,2 = 1.2 Hz, H-4).
Analytical Data for: 3-(2-Oxo-2H-Chromen-3-yl)-3,10adihydropyrano[2,3-b]chromen-2,5-dion (6b)
For C21H12O6, M=360.3, Melting point: 303 - 305 oC
Elemental analysis: wi (calc.) 69.94 % (C), 3.33 % (H)
wi (found) 70.21 % (C), 3.05 % (H)
1
2
6 O 12 O
O
11
3
4
5
7
O
8
O
10 13
21
9
O
14
20
15
19
16
17
18
Acknowledgements: Financial support for this research by the Slovak Grant Agency is
gratefully acknowledged, Grant No. 1/8207/01
References
1. Gaplovsky, A.; Donovalova, J.; Lacova, M.; Mracnova, R.; ElShaaer H. M., Journal of Photochemistry and Photobiology- A:
Chemistry 2000, 136, 61.
2. Eicher, T.; Hauptmann, S., The Chemistry of Heterocycles, Georg
Thieme Verlag Stuttgard, New York ,1995.
3. Edwards, A.M.; Howell, J.B.L., Clinical and Experimental Allergy:
2000, 30, 756.
4. Nohara, A.; Ishiguto, T.; Sanno, Y., Tetrahedron 1974, 13, 1183.
5. Stankovicova,H.; Lacova, M.; Gaplovsky, A.; Chovancova J.;
Pronayova, N., Tetrahedron 2001, 57,3455.
6. Sabitha G., Aldrichimica Acta 1996,29,15
7. Lacova, M.; Gasparova, M.; Loos, D.; Liptay, T.; Pronayova, N.,
Molecules 2000, 5,167.
8. Galema, A.S., Chemical Society Rewiews,1997,26, 233.

Corresponding author