2,5 -Diazachalcones. I. Preparation, structure, and antibacterial effects of some substituted 2^5'-diazachalcones

Transcription

1 2,5 -Diazachalcones. I. Preparation, structure, and antiacterial effects of some sustituted 2^5'-diazachalcones a D. DOŘÁČKOA, a J. ZÁMOCKÁ, a J. HEGER, A. NAGY, and a. HARTELOÁ Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Komenský University, 884 Bratislava ь Scientific-Research Institute, Faculty of Pharmacy, Komenský University, 884 Bratislava Received 14 June 1978 Accepted for pulication 10 Septemer 1979 Ten hitherto unknown 2;5'-diazachalcones variously sustituted at the isocyclic residue have een prepared y means of a modified ClaisenSchmidt condensation of methylpyrazinyl ketone with aromatic aldehydes. The structure of the sustances was verified y i.r. and 'H-n.m.r. spectral data. The sustances show antiacterial effects towards Staphylococcus aureus, Bacillus sutilis, and Escherichia coli. Видоизмененной конденсцией по КлейзенуШмидту метилпирзинилкетон с некоторыми ромтическими льдегидми было приготовленных десять новых 2;5'-дизхлконов с рзными зместителями н изоциклическом осттке. Их структур был подтвержден интерпретцией ИК и ^Н-ЯМР спектров. Приготовленные соединения окзлись ктивными по отношению к Staphylococcus aureus, Bacillus sutilis и Escherichia coli. The present paper descries a new group of chalcones that contain two nitrogen atoms in one heterocycle. Azachalcones known so far, on account of the presence of the conjugated CH = CHHC = О system, show various iological effects, e.g. antiacterial [15], cardiovascular [6, 7], cytostatic [8, 9], etc. The effect of sustituents (OH, OCH 3, OC2H5) on the aromatic ring of 2',5'-diazachalcones upon antiacterial effects has een studied. The new sustances have een synthesized y a modified, diethylamine-catalyzed ClaisenSchmidt condensation of methylpyrazinyl ketone with aromatic aldehydes. The modification was applied ecause the original procedure [10, 11] was unsuccessful Chem. zvesti 34 (2) (1980) 263

2 D. DOŘÁČKOÁ, J. ZÁMOCKÁ, J. HEGER, A. NAGY,. HARTELOÁ Experimental The prepared sustances were crystallized from asolute ethanol. For yields, elemental analyses, and melting points see Tale 1. The i.r. spectra ( cm" 1 ) were recorded using a doule-eam UR-20 spectrophotometer (Zeiss, Jena) and applying KBr ( mg of the sample/800 mg KBr) or Nujol techniques. The instrument was calirated against a polystyrene foil. The 'H-n.m.r. spectra were otained at 80 Hz. The measurements were run on solutions in DMSO-d 6 (internal standard hexamethyldisiloxane) with a Tesla BS 487 В spectrometer. The recorded chemical shifts were then calculated for tetramethylsilane. For i.r. and 'H-n.m.r. spectral data see Tale 2. The antiacterial effects were tested y the method of incent using 1% solutions of the sustances in 1,2-dimethoxyethane and standard microial strains: Staphylococcus aureus OXFORD, Bacillus sutilis, and Escherichia coli. 2;5'-Diazachalcones (1-Х) A mixture of methylpyrazinyl ketone (0.01 mol), the respective aldehyde (0.01 mol), and diethylamine (0.01 mol) in pyridine (4.4 ml) was oiled for 1 h. The mixture was cooled and poured onto ice, the ph eing adjusted to 34 y the addition of a few drops of acetic acid. The mixture, from which a portion of the product precipitated immediately, was stored overnight in a refrigerator, the crystalline material was collected y filtration and recrystallized several times. Results and discussion Since the condensation of methylpyrazinyl ketone with aromatic aldehydes y means of the original ClaisenSchmidt procedure [10, 11] was unsuccessful the method was modified in that higher temperature (100 C) and longer reaction times were applied, and during the isolation of products the ph was adjusted to 34. This caused a favourale shift of the reaction equilirium resulting in a sustantial increase (y 40%) of the yields of the desired products. Also, diethylamine was used as the catalyst. The asicity of this amine is sufficient to assure smooth reaction without the formation of y-products. The otained 2;5'-diazachalcones are crystalline, coloured from light-yellow to orange, water insolule sustances. The structure of the prepared compounds was confirmed y i.r. and ^-n.m.r. spectra, the interpretation of which was ased on pulished data oserved for geometrically isomeric chalcones and azachalcones, mainly their hydroxy derivatives [12], while 2-hydroxychalcone was used as a reference sustance. It follows from the literature [13] that a and at cm" 1 in the i.r. spectra is diagnostic of the presence of a trans azachalcone isomer. In the spectra of 2;5'-diazachalcones studied herein the characteristic and was shifted to cm -1 and was split in some cases. The and reflects off-plane deforma- 264 Chan, zvesti 34 (2) (1980).

3 i о. r Tale 1 Data for the prepared 2,'5'-diazachalcones > о z m Compound R 1 R 2 Formula M Calculated/found %C %H %N Yield % M.p. C / II III I I II III IX x 3-OQH 5 3-OQH5 3-OH 4-OH 3-OH 4-OH 3-OH 4-OH H H H 3-ОСНз 4-ОСНз 3-ОСНз O O 3 H 14 H 14 O 2 O 2 O 2 H 12 H 12 H I (decomp.)

4 ON ON Tale 2 Spectral characteristics of the prepared 2 5'-diazachalcones 'H-NMR<5,p.p. m. IR v, cm" 1 Compound CH A = CHfl- сн=сн- v(c = 0) ß /л., Hz У(С :-н) (»Л. v(c = C) s-trans s -cis / II III I I II III IX X }' }' )* sh 1644 sh 1644 sh 1654 sh 1654 sh 1647 sh 1644 sh 1654 sh 1673 (1698) 1672 (1697) (1668 sh) 1673 (1665 sh) D < О >' Я < > N О E x m > z o d doulet, sh shoulder, a in KBr, in Nujol.

5 2\5'-DIAZACHALCONES. I tion virations of the hydrogen atoms of the vinylene group [1416]. It follows that the prepared sustances are trans -isomers. From the point of view of conformation (s-cis and s-trans isomers) of chalcones and azachalcones diagnostically important region in their i.r. spectra is that at cm" 1 [17]. In the spectra of the sustances under investigation two intense ands were present at cm" 1. These were assigned to a,0-unsaturated ketone and characterized the vinylene and the keto group. The and at cm" 1 was that of C = C stretching virations and the one at was assigned to C = 0 virations in the s-cis and s-trans forms of azachalcone (Tale 2). The spectra otained y oth KBr and Nujol techniques showed that 2;5'-diazachalcones were the s-cis conformers; in some cases minor amounts of s-trans conformers were also detected, as a result of the presence of two nitrogen-containing heterocycle, instead of an isocycle, causing more pronounced energetical nonequivalency of the two possile conformers. The hydroxyl groups of the sustances were associated, linked via intermolecular hydrogen onds. The and at 1668 cm -1 present in the spectrum of 4-hydroxy-2',5'- diazachalcone showed a shoulder reflecting the С = О stretching viration of the s-cis conformer, proaly as a result of the formation of hydrogen onds. The olefinic hydrogen atoms present in the molecules of azachalcones are reflected in the ^-n.m.r. spectra as a typical AB system of protons. The ß-proton signal appears in the spectra of 2;5'-diazachalcones at a lower field than that of the a-proton (ôh B and <5H A ), due to the deshielding effect of the caronyl group. The oserved value of the coupling constants ( Hz) corresponds to the trans arrangements of the olefinic hydrogens [17]. Thus ^-n.m.r. spectra confirmed the interpretation of the i.r. spectra of the prepared sustances. All compounds studied showed effects against Staphylococcus aureus OXFORD and Escherichia coli. Only 2-hydroxy-3-methoxy-2;5'-diazachalcone showed activity against Bacillus sutilis. References 1. Annigeri, A. C. and Siddapa, S., Indian J. Chem. 1, 484 (1963). 2. Ďurinda, J., Sziics, L., Krasnec, Ľ., Heger, J., Springer,., Kolena, J., and Keleti, J., Acta Fac. Pharm. Bohemoslov. 12, 89 (1966). 3. Maruoka, M., Fishisaki, J., and Kyoraigawa, K., Japan (1965). 4. Geiger, W. S. and Conn, J. E., /. Amer. Chem. Soc. 67, 112 (1945). 5. Irikura, T. S., Sato, S. H., Ushiyama, K., Ito, A., Ono, H. L, and Matsui, Y. О., Japan (1971). 6. Koo, J., /. Pharm. Sei. 53, 1329 (1964). 7. Buu Hoi, N. P., Xuong, N. D., and Sy, M., Bull Soc. Chim. Fr. 1958, Donnelly, D., Geoghegam, R., O'Brien, C, Philin, E., and Wheeler, T. S., /. Med. Chem. 8, 872 (1965). Chem. zvesti 34 (2) (1980) 267

6 D. DOŘÁČKOÁ, J. ZÁMOCKÁ, J. HEGER, A. NAGY,. HARTELOÁ 9. Devitt, P. F., Timoney, A., and ickers, M. A., J. Org. Chem. 26, 4941 (1961). 10. Koo, J., /. Org. Chem. 26, 635, 1185 (1961). 11. Terentyev, A. P., Gracheva, P. A., Preorazhenskaya, N. N., and olkova, L. M., Zh. Oshch. Khim. 33, 4006 (1963). 12. Documentation of Molecular Spectroscopy, p Butterworths, London, Coleman, L. E., /. Org. Chem. 21, 1193 (1956). 14. Orlov,. D., Tsukerman, S.., and Lavnishin,. F., op. Stereokhim. 1, 89 (1971). 15. Dzurilla, M. and Kristián, P., Collect. Czech. Chem. Commun. 35, All (1970). 16. Sohár, P., Széll, P., and Dudas, Т., Acta Chim. (Budapest) 70, 355 (1971). 17. Tsukerman, S.., Surov, Ya. N., and Lavnishin,. F., Zh. Oshch. Khim. 38, 524 (1968). Translated y P. Kováč 268 Chem. zvesti 34 (2) (1980)