Introduction
Thanks to their biological activity, chromone derivatives are the subject of the considerable pharmaceutical and chemical interest. 3-Formylchromones occupy a unique position from three reasons .They are carrying a significant biological activity [1,2], they have comfortable preparation by Vilsmeier-Haack reaction in very good yields [3] and they are attractive intermediates.
This work is in connection with our program of the synthesis, theoretical , spectral and antimycobacterial study of 3-formylchromone derivatives [4 -10].
Results and Discussion
We developed the optimal method of synthesis of 3-formylchromone 5a -
5e with condensed 2-oxopyrane ring. The synthetic strategy of
3-formylchromones has to be based on building of 2-benzopyrone skeleton. The
key step in the synthesis was the preparation of a suitable acetyl derivatives
4a-4e from which requested 3-formyl- chromones were obtained by
Vilsmeier-Haack formylation in 80 - 90 % yields. The synthesis of 5a -
5e is depicted in scheme. Acetylderivative 4d produced only aldehyde
5d, in any case could not to be prepared isomer 5d1.
.
The infrared spectra were registered in nujol suspension . The stretching
vibration of the carbonyl groups of the aldehydes 5 were observed as
intensive bands in three very well distinguishable regions. Bands in 1637 -
1655 cm-1 belonging to v(CO) of -pyrone ring, v(CO) aldehyde
groups were found in the region at 1693 - 1904 cm-1, v(CO) -pyrone
ring can be observed in the region at 1724 - 1760 cm-1
The 1H NMR spectra of prepared compounds confirmed
their structure. The signals of protons have displayed chemical shifts and
multiplicities corresponding to their surroundings.1H -NMR -spectra
of the prepared compounds are shown in experimental part.
Conclusion
The semiempirical AM1 molecular orbital calculations have been used to the
study of optimal geometries. The information about conformational properties
and the substituent effects on electronic structure of prepared aldehydes 5
were obtained.
. From calculation results were found a significant effect of
-pyrone-carbonyl group at formyl group. The activity was recorded on both
characteristics of the formyl bond. The polarization was magnified and
multiplicity was diminished . Owing to -pyrone-carbonyl group effect there
were found remarkable changes in increasing of positive charge at formyl carbon
( 0.241), proton acidity (0.170) and negative charge of oxygen (- 0.309). On
the other hand effect of formyl group on structure -pyrone ring was by much
less effective. There were observation slightly increasing of polarization and
smooth lowering of bond order ( 1.682) at double bond C-2 - C-3.
The little effect of benzene ring was noticed at formyl- and -pyrone
carbonyl groups and at mutual bond of both rings. The substituents caused also
only slight changes on the study systems.
The calculation of the dependence of the total energy values on the
formyl group rotation have shown an advantage of the both planar
arrangements . S-cis conformer was prefered. The deviation of formyl groups
from planar structure in s-cis conformer was nearly to 0.5and s-trans
conformer deviated about 10. The difference of total energy of both conformers
was in the range 22 - 26 kJmol-1.
Experimental
1HNMR spectra were measured on spectrometers Tesla BS 487
(80 MHz) and Bruker AM 300 (300,13 MHz) in solution of DMSO-d6, using HDMSO as
internal standard. The infrared spectra were recorded on Specord IR 75
spectrometer in paraffine oil. Melting points were determined on a Kofler
block. The reaction course was monitored by thin-layer chromatography (ethyl
ethanoate + cyclohexane).
The purity and structures of the prepared compounds were monitored by IR,
1HNMR spectroscopy as well as their elemental analyses
The synthesis of acetophenones 4a - 4e are described in
[11-13].
Synthesis of 3-formylchromones 5
General procedure
POCl3 (0,49 mol) was added droppwise to dimethylformamide
(DMF) (121 ml) with stirring at 30-35 C, after the addition, the mixture was
stirred at 50C for 1 h. Then the solution of 2-hydroxy- acetophenone
derivatives 4 (0.12 mol) in least amount of DMF was added droppwise
with stirring to the above mixture. After that the mixture was stirred at
45-55oC for 2 hours, kept over the night at room temperature and
slowly poured over mixture ice and water( 200 g).Product was stirred for 6
hours, then filtered off and recrystallized from ethanole
The following compounds were prepared by general pocedure:
8-Methyl-4,6-dioxo-4H,6H-pyrano[3,2-g]chromone-3-carbaldehyde
(5a)
M.p. 310 - 312 deg.C.
1H-NMR (DMSO): 10.12(1H,s,CHO), 8.86(1H,s,H-2), 8.18(1H,d,H-10),
7.67(1H,d,H-9), 6.53(1H,s,H-7)
Anal. calc. for C14H8O5 (256.2): C 65.62, H
3.13; found: C 65.33, H 3.12 .
6-Methyl-4,6-dioxo-4H,8H-pyrano[3,2-g]chromone-3-carbaldehyde
(5b)
M.p. 255 - 260 deg.C.
1H-NMR (DMSO): 10.12(1H,s,CHO),8.97(1H,s,H-2), 8.39(1H,s,H-5),
7.87(1H,s,H-10), 6.56(1H,s,H-7), 2.54(3H,s,CH )
Anal. calc. for C14H8O5 (256.2): C 65.62, H
3.13; found: C 65.48, H 3.01 .
10-Methyl-4,8-dioxo-4H,8H-pyrano[2,3-h]chromone-3-carbaldehyde
(5c)
M.p. 233 - 234 deg.C.
1H-NMR (DMSO): 10.14(1H,s,CHO), 9.02(1H,s,H-2), 8.31(1H,d,H-5),
7.58(1H,d,H-6), 6.57(1H,s,H-9), 2.74(3H,s,CH )
Anal. calc. for C14H8O5 (256.2): C 65.62, H
3.13; found: C 65.32, H 3.07 .
6-Methyl-5-hydroxy4,8-dioxo-4H,8H-pyrano[3,2-g]chromone-3-carbaldehyde
(5d)
M.p. 273 - 274 deg.C.
1H-NMR (DMSO) : 10.05(1H,s,CHO), 8.63(1H,s,h-2), 8.12(1H,s,H-10),
6.78(1H,s,H-7), 6.26(1H,s,OH), 2.54(3H,s,CH )
Anal. calc. for C14H8O6 (272.2): C 61.79, H
2.94; found: C 61.62, H 2.99 .
8-Methyl-9-hydroxy4,6-dioxo-4H,6H-pyrano[2,3-f]chromone-3-carbaldehyde
(5e)
M.p. 290 - 293 deg.C.
1H-NMR (DMSO) : 10.07(1H,s,CHO), 9.06(1H,s,H-2), 7.30(1H,s,H-10),
6.31(1H,s,H-7), 2.62(3H,s,CH )
Anal. calc. for C14H8O6 (272.2): C 61.79, H
2.94; found: C 61.77, H 2.92 .
References and Notes
1. Nohara A.; Umetani T.; Sanno Y. Tetrahedron 1974,30,
3553.
2. Brown R.C.; Harard R.; U.S. 4238, 606 (1980); Chem. Abstr. 94p, 156755
(1981).
3. Nohara A.; Umetani T.; Sanno Y. Tetrahedron Lett. 1973,
22, 1995-1998.
4. El-Shaaer, H.M.; Zahradník, P.; Lacova, M.; Matulova, M. Collect.
Czech. Chem. Commun, 1994, 59, 1673-1681.
5. El-Shaaer, H.M.; Perjessy, A.; Zahradnik, P.; Lacova, M.; Sustekova, Z.
Monatsh. Chem., 1993, 124, 539-548
6. Stankovicova, H.; Fabian W.M.F.; Lacova, M. Molecules, 1996,
1, 223-235
7. Lacova, M.; Stankovicova, H.; Odlerova, Z. Il Farmaco, 1995,
50, 885-888
8. El-Shaaer, H.M.; Lacova, M.; Odlerova, Z.., Furdik, M. Chem.Papers
1986, 40, 121.
9. Stankovicova, H.; Gasparova, R.; Lacova, M.; Chovancova, J. Collect.
Czech. Chem. Commun, 1994, 59, 1673-1681
10. Kralova, K.; Sersen, F.; Lacova, M.; Stankovicova, H. Biologia
Plantarum 1996, 38, 397-404
11. Russell, A.; Frye, J.R. Org. Synth.,Coll. Vol. III. 281, John Wiley
and Sons, New York 1967.
12. Desai, R.D.; Ekhlas, M. Proc Indian Acad SCi (A,
1938,567 , Chem. Abstr. 1939, 33, 3356 .
13. Sethna, S.M.; Shah, N.M.; Shah, R.C. J. Chem. Soc.1938,
228.
Comments
During 1-30 September 1997,
all comments on this poster should be sent by e-mail to ecsoc@listserv.arizona.edu
with A0032 as the message subject of your e-mail. After the conference,
please send all the comments and reprints requests to the author(s).
