Sixth International Electronic Conference on Synthetic Organic Chemistry (ecsoc-6), 1-30 September




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Sixth International Electronic Conference on Synthetic Organic Chemistry (ECSOC-6), 1-30 September

[E008]

The Atypical Condensations of 4-Oxo-4H-Benzopyran-3-Carbaldehydes 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.



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 Vilsmeier-Haack 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-2-ones)

5b Alkyloxy-3-(2-oxo-2H-chromén-3--yl)-5H-pyrano[3,2-c]chromen-2-ones)

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] chromene-2,5-diones

6b 3-(2-oxo-2H-chromen-3-yl)-3,10a-dihydro-pyrano[2,3-b] chromene-2,5-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.


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-4-acetic 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-Oxo- 2H,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


1H-NMR-spectral data:

CDCl3, 300 MHz: 2.07 (s, 3H, H-12), 2.37 (s, 3H, H-10), 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, 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)-2-Oxo-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

1H-NMR-spectral data:

DCl3 300 MHz : 2.07 (s, 3H, H-12), 2.38 (s, 3H, H-11(10)), 2.41 (s, 3H, H-10(11)), 6.49 (s, 1H, H-6), 7.07 (d, 1H, 3J1,2 = 8.4 Hz, H-1), 7.17 (s, 1H, H-9), 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)-2-Oxo-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
1H-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,5H-Pyrano[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



1H-NMR-spectral data:

Mixture of CDCl3,DMSO 300 MHz : 1.98 (s, 3H, H-23 ), 6.40 (s, 1H, H-12), 7.07 (d, 1H, H-1), 7.12 (t, 1H, H-3), 7.35 (d,d, 2H, 3J 17,19 = 8.1 Hz, H-17,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 ,




1H-NMR-spectral data:

CDCl3, 300 MHz : 2.46 (s, 3H, H-10), 3.59 (s, 3H, H-12), 5.98 (s, 1H, H-11), 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

E
lemental analysis
: wi (calc.) 71.57%(C), 4.47 %(H)


wi (found) 71.69 %(C), 4.32 %(H)
1H-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).

13C-NMR-spectra:

DMSO, 300MHz : 14.616 (C-14), 20.626 (C-24), 63.459 (C-13), 96.06 (C-9), 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)
1H-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)

1H-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, 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).

13C-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 (C-10), 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)


1H-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, H-17,19), 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)-3,10a-dihydropyrano[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)

1H-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)-3,10a-dihydropyrano[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)


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.; El-Shaaer 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.


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