Synthesis and Some Reactions of Pyrazole-3-carboxylic acid Having Trifluoromethyl Unit

Yıl 2019, Cilt: 9 Sayı: 4, 645 - 654, 15.10.2019

Elif Hacıalioğlu Volkan Taşdemir Hasan Genç İsrafil Tozlu

https://doi.org/10.17714/gumusfenbil.528165

Cited By: 1

Öz

4-benzoyl-5-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carboxylic
acid 2 was obtained from 4-benzoyl-5-phenyl-2,3-furandione 1 and (4-(trifluoromethyl)phenyl) benzaldehyde-phenyl hydrazone 1a. Obtained new pyrazole carboxylic
acid derivative was converted into acid chloride form. Reaction of new
derivatives between acid chloride and some of nucleophiles were progressed. The
esters (4a-c) were obtained using
Schotten Baumann method with the corresponding alcohols and acid chloride (3). Pyrazolopiridazinone derivatives (8, 9,
10) were obtained as a result of
cyclization reactions between pyrazole carboxylic acid and various hydrazines.
Additionally, reactions between an acide
chloride 3 and certain amines and
ureas were carried out to yield amides (5a,
5b-f) and carbo-urea (6a-c) derivatives. The nitrile compound
(7) was also synthesized from the
amine compound via the removal of water with the use of SOCl₂
and DMF. All synthesized molecules were subjected to antibacterial
activity to see their potential as unknown reagent. 6-nitro-3,4-diphenyl-2-(4-(trifluoromethyl)phenyl)-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-one
(10) showed antibacterial activity
against only the Gram-positive bacteria, Bacillus cereus and Micrococcus luteus, with a
MIC value of 32 and 128 µg/mL, respectively. This finding revealed that
functional group is important for antibacterial activity. Compound 10 having a
nitro group inhibited growing of bacteria more than positive control,
streptomycin in two different types of bacteria. This might be a good clue for
further investigation about antibacterial agents.

Anahtar Kelimeler

Cyclic oxalyl compounds, Cyclization, Fluoride, Pyrazole

Triflorometil Grubuna Sahip Pirazol-3-karboksilik Asit Sentezi ve Bazı Tepkimeleri

Öz

4-Benzoil-5-fenil-2,3-furandion 1 ve (4-(triflorometil)fenil)
benzaldehit-fenil hidrazonun 1a
reaksiyonundan 4-benzoil-5-fenil-1-(4-(triflorometil)fenil)-1H-karboksilik
asit 2 elde edildi. Elde edilen yeni
pirazol karboksilik asit (2) türevi,
asit klorürüne dönüştürüldü ve çeşitli nükleofillerle asit klorür arasında yeni
türevlerin reaksiyonları gerçekleştirildi. Esterler (4a-c), ilgili alkoller ve asit klorür (3) ile Schotten Baumann metodu kullanılarak elde
edildi.  Pirazolopiridazinon türevleri (8, 9,
10), pirazol karboksilik asit ve
çeşitli hidrazinler arasındaki halkalanma reaksiyonları sonucunda elde edildi. Ek
olarak, amidleri (5a, 5b-5f) ve karbon-üre türevlerini (6a-c) elde etmek için asit klorür ile
çeşitli aminler ve ürelerle reaksiyonlar gerçekleştirildi. Nitril bileşiği (7), SOCl₂ ve DMF kullanılarak amin
bileşiğinden suyun uzaklaştırılması ile elde edildi. Sentezlenen
tüm moleküller, potansiyel aktivitelerinden dolayı antimikrobiyal aktiviteye
tabi tutuldu. Moleküllerden 6-nitro-3,4-difenil-2-(4-(triflorometil)fenil)-2,6-dihidro-7H-pirazolo[3,4-d]piridazin-7-on
bileşiğinin (10) sadece Gram-pozitif
bakterilere karşı antibakteriyal aktivite gösterdi. Bacillus cereus ve Micrococcus
luteus, A MIC değerleri 32 ve 128 µg/mL aktif olduğu bulundu. Yapısında
nitro grubu bulunduran ve aktivite gösteren 10 nolu molekülden dolayı
fonksiyonel grubun aktivite üzerinde önemli bir etkisi olduğu söylenebilir.
Ayrıca 10 nolu molekülün pozitif kontrol olan streptomycin antibiyotiğinden daha
etkili bir zon oluşturduğu da gözlendi. Bu durumda etkisini gösterdiği
bakteriler için ileri çalışmalar konusunda iyi bir antibiyotik adayı olabilir.

Anahtar Kelimeler

Siklik okzalil bileşikleri, Halkalanma, Florür, Pirazol

Kaynakça

• Adnan, A.B., Ashour, H.M.A., Ghany, Y.S.A., Bekhit, A.E.D.A. and Baraka, A., 2008. Synthesis and biological evaluation of some thiazolyl and thiadiazolyl derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents. European Journal of Medicinal Chemistry, 43, 456-463.
• Abunada., N.M., Hassaneen, H.M., Nadia, G.K. and Miqdad, A.O., 2008. Synthesis and Antimicrobial Activity of Some New Pyrazole, Fused Pyrazolo[3,4-d]-pyrimidine and Pyrazolo[4,3-e][1,2,4]- triazolo[1,5-c]pyrimidine Derivatives. Molecules, 13, 1501-1517.
• Akbas, E. and Berber, I., 2005. Antibacterial and antifungal activities of new pyrazolo [3, 4-d] pyridazin derivatives, European Journal of Medicinal Chemistry, 40, 401-405.
• Akçamur, Y., Şener, A., İpekoglu, A.M. and Kollenz, G., 1997., Functionalization and cyclization reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic acid, Journal of Heterocyclic Chemistry, 34, 221-224.
• Baasner, B., Hagemann, H. and Tatlow, J.C., 2000. Houben-Weyl Organofluorine Compounds: Thieme: Stuttgart, Germany,. 740 p.
• Badawey, E.S.A.M. and El-Ashmawey, I.M., 1998. Nonsteroidal antiinflammatory agents - Part 1: Antiinflammatory, analgesic and antipyretic activity of some new 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-ones. European Journal of Medicinal Chemistry, 33, 349-361.
• Banks, R.E., Smart, S.E and Tatlow, J.C., 1994. Organofluorine Chemistry.Principles and Commercial Applications: New York, Plenum Press., 52-200.
• Bauer, A.W., Kirby., W.M.M., Sheris, J.C. and Turck, M., 1966. Antibiotic susceptibility testing by a standardized single disk method, American Journal of Clinical Pathology, 45, 493-496.
• Bildirici, İ., Şener, A., Atalan, E., Battal, A. and Genç, H., 2009. Synthesis and Antibacterial Activity of 4-benzoyl-1-(4-carboxy-phenyl)-5-phenyl-1H-pyrazole-3-carboxylic Acid and Derivatives, Medicinal Chemistry Research, 18, 327-340.
• Çetin, A., Bildirici, İ., 2018. A study on synthesis and antimicrobial activity of 4-acyl-pyrazoles. Journal of Saudi Chemical Society, 22, 279-296.
• Chambers, R.D., 2004. Fluorine in Organic Chemistry: Oxford, Blackwell Publishing, Oxford, 406p.
• Genç, H., Tasdemir, V., Tozlu, I. and Ögün, E., 2019. Synthesis of Novel Tetra-Substituted Pyrazole Derivatives from 2,3- Furandione, Letters in Organic Chemistry, doi: 10.2174/1570178616666190314150302
• Hagmann, W.K., 2008. The Many Roles for Fluorine in Medicinal Chemistry, Journal of Medicinal Chemistry, 51, 4359-4369.
• Harper, D.B., O'Hagan, D. and Murphy, C.B., 2003. Fluorinated Natural Products: Occurrence and Biosynthesis. Natural Production of Organohalogen Compounds; Handbook of Environmental Chemistry: Berlin, Heidelberg, Springer, 141p.
• Jorgensen, J.H. and Ferraro M.J., 2009. Antimicrobial susceptibility testing: a review of general principles and contemporary practices, Clinical Infectious Diseases 49, 1749-1755.
• Kappe, C.O. Terpetsching, E., Penn, G., Kollenz, G., Peters, K., Peters, E.M. and VonSchnering, H.G., 1995. Reactions of cyclic oxalyl compounds, 37. Substituent effects on the site of nucleophilic attack at 1H-pyrrole-2,3-diones. Liebigs Annalen der Chemie, 3, 537-543.
• Kollenz, G., Ziegler, E. Ott, W. and Igel, H., 1976. Synthesen von Heterocyclen, CC1 Reaktionen mit cyclischen Oxalylverbindungen, XVIII2 Zur Reaktion von 4-Benzoyl-5-phenyl-2,3-dihydrofuran-2,3-dion mit H-aktiven Nucleophilen., Z.Naturforsch, 31B, 1511-1514.
• Londershausen, M., 1996. Approaches to New Parasiticides. Pesticide Science, 48, 269-292.
• Menges, N. and Bildirici, İ., 2017. Synthesis and evaluation of aromaticity and tautomerization of pyrazolopyridazin(on)es. Journal of Chemical Sciences, 129, 741-752.
• Menozzi, G., Mosti, L. and Schenone, P., 1987. Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. VI. Synthesis of ethyl or methyl 1,5-disubstituted 1H-pyrazole-4-carboxylates. Journal of Heterocyclic Chemistry, 24, 1669-1675.
• Nepali, K., Lee, H.Y. and Liou, J.P., 2019. Nitro-Group-Containing Drugs. Journal of Medicinal Chemistry, 62, 2851-2893.
• Sarma, K.N. Subha, M.C.S and Rao, K.C., 2010. A facial synthesis and antimicrobial activity of some pyrazole derivatives carrying indole. European Journal of Chemistry, 7, 745-750.
• Scherowsky, G. and Franke, H., 1974. Thermolyse von 2-methoxy-2.3.5-triaryl-1.3.4-oxadiazolinen in gegenwart von abfangreagenzien, Tetrahedron Letter, 18, 1673-1676.
• Şener, A., Genc, H., Tozlu, I. and Şener, M.K., 2004. Studies on the Reactions of 4-Ethoxycarbonyl-5-phenyl-2,3-dihydro-2,3- furandione with Some NH Nucleophiles. Turkish Journal of Chemistry, 28, 659-665.
• Şener, A., Kasımogullari, R., Şener, M.K., Bildirici, I., Akçamur, Y., 2002. Studies on the reactions of cyclic oxalyl compounds with hydrazines or hydrazones: Synthesis and reactions of 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid. Journal of Heterocyclic Chemistry, 39, 869–875.
• Şener, A., Tozlu, İ., Genç, H., Bildirici, İ. and Arisoy, K., 2007. Synthesis and some reactions of 4-(ethoxycarbonyl)-1,5-diphenyl-1H-pyrazole-3-carboxylic acid. Journal of Heterocyclic Chemistry, 44, 1077-1081.
• Shawali, S., 1977. Synthesis and tautomeric structure of some 2H-pyrazolo[3,4-d]pyridazines. Journal of Heterocyclic Chemistry, 14, 375-381.
• Thomson, W.T., 1997. Agricultural chemicals-Book II. Herbicides: California, USA,Thomson Publications, 268p.
• Wayne, P., 2003. National Committee for Clinical Laboratory Standards: NCCLS Document M7-A6 6th edition, USA, 19-97.
• Yıldırım, İ., Sarıpınar, E, Güzel, Y., Patat, Ş. and Akçamur, Y., 1995. Theoretical investigations on the mechanism of interaction of 4-formyl furan-2, 3-dione and urea, Journal of Molecular Structure: THEOCHEM, 334, 165-171.