Synthesis, Cyclization and Nucleophilic Substitution Reactions of Substituted Pyrazole Carboxylic Acid

Abstract

Substituted pyrazole carboxylic acid 2a-b derivatives, obtained from 2,3-furandione 1 and benzaldehyde hydrazone 11a-b was converted via reactions of its acid chloride 3a-b. The corresponding ester 6a-b, urea 7a-b, and amide derivatives 4a-b, 8a-b were obtained from the reaction of the acyl chloride of the pyrazole carboxylic acid with various alcohols, urea, and amines. Additionally, the corresponding nitrile derivatives 5 were obtained by extracting water from the amide derivatives (SOCl2 / DMF). Furthermore, cyclization reactions of substituted pyrazole carboxylic acid derivatives using hydrazine were investigated 9 and reaction of 2b decarboxylation product 10.

Keywords

• cyclization
• decarboxylation
• pyrazole carboxylic acid
• pyrazole

Sübstitüe Pirazol Karboksilik Asit Sentezi, Siklizasyonu ve Nükleofilik Yer Değiştirme Reaksiyonları

Abstract

Substitüe pirazol karboksilik asit 2a-b türevleri 2,3-furandion 1 ve benzaldehit hidrazon 11a-b elde edildi. Pirazol karboksilik asit türevleri asit klorürlerine 3a-b dönüştürüldü. Pirazol karboksilik asitin asit klorürü çeşitli alkoller, üre ve aminlerle reaksiyonundan karşılık gelen ester 6a-b, üre 7a-b ve amid 4a-b, 8a-b türevleri elde edildi. Ek olarak, amid türevlerinden (SOCl2/DMF) ile su çekilerek karşılık gelen nitril türevleri 5 elde edildi. Ayrıca pirazol karboksilik asit türevlerinin hidrazin ile siklizasyon reaksiyonlarından 9 ve dekarboksilasyonu sonucu 10 türevlerinin eldesi reaksiyonları araştırılmıştır.

Keywords

• Siklizasyon
• dekarboksilasyon
• pirazol karboksilit asit
• pirazol

References

1. Akçamur Y, Penn G, Ziegler E, Sterk H, Kollenz G, Peters K, Peters E.M, 1986. Reactions of Cyclic Oxalyl Compounds. Reaction of 4-benzoyl-5-phenyl-furan-2,3-dione with Phenylhydrazones and Phenylhydrazıne. Monatsh Chemistry, 117, 231-245.
2. Akçamur Y, Şener A, Ipekoglu A.M, Kollenz G, 1997. Functionalization and Cyclization Reactions of 4-Benzoyl-1,5-diphenyl- 1H-pyrazole-3-carboxylic Acid. Journal Heterocyclic Chemistry, 34, 221-224.
3. Baird M.S, 2003. Thermally Induced Cyclopropene−Carbene Rearrangements: An Overview. Chemical Reviews, 103(4):1271-1294.
4. Banks R.E, Smart S.E, Tatlow J.C, 1994. Organofluorine Chemistry.Principles and Commercial Applications: New York, Plenum: 52-200.
5. Bildirici İ, Şener A, Atalan E, Battal A, 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(5):327-340.
6. Frizzo C. P, Villetti M.A, Tier A.Z, Gindri I.M, Buriol L, Rosa F.A, Claramunt R.M, Sanz D, Martins M.A.P, 2013. Structural and thermodynamic properties of new pyrazolo[3,4-d]pyridazinones. Thermochimicaacta. 574, 63-72.
7. Genç H, 2009. Reaction of 4-Ethoxycarbonyl-5-phenyl-2,3-dihydro-2,3-furandione with Some Hydrazine Nucleophiles. Asian Journal of Chemistry, 21(1):299-303.
8. Genç H, Tan M, Gümüş S, Mengeş N, Bildirici İ, Şener A, 2010. Studies on the different reaction pathways between 3-Acetyl-5-benzoyl-6- methyl-2-phenyl-4H-pyran-4-one and alkylamines. Bulletin of Korean Chemical Society, 31(9):2633-2636.

9. Genç H, Taşdemir V, Tozlu İ, Öğün E, 2019. Synthesis of Novel Tetra-Substituted Pyrazole Derivatives from 2,3-Furandione. Letters in Organic Chemistry, 16(11):891-897.
10. Hagmann W. K, 2008. The Many Roles for Fluorine in Medicinal Chemistry. Journal of Medicinal Chemistry, 51(15):4359-4369.
11. Harper D. B, O'Hagan D, Murphy C. B, 2003. Fluorinated Natural Products: Occurrence and Biosynthesis. Natural Production of Organohalogen Compounds; Handbook of Environmental Chemistry: Berlin, Heidelberg, Springer, 141.
12. Joule J. A, Mills K, 2010. Heterocyclic Chemistry, Blackwell. Oxford. 1-150.
13. Kamal A, Visweswarasastry K. N, Chandrasekhar D, Mani G.S, Adiyala P.R, Nanubolu J.B, Singarapu K.K, Andmaurya R.A, 2015. One-Pot, Three-Component Approach to the Synthesis of 3,4,5-Trisubstituted Pyrazoles. The Journal of Organic Chemistry, 80(9):4325-4335.
14. Kappe C. O, Terpetschnig E, Penn G, Kollenz G, Peters K, Peter E. M, 1995. Substituent effect on the site of nucleophilic attack at 1H-pyrrole-2,3-diones. Liebigs Annalen der Chemie, 3, 537-543.
15. Korkusuz E, Yıldırım İ, 2011. On the Reactions of Furan-2,3-diones with Oxindole (=1,3-Dihydro-2H-indol-2-one) and Lawesson Reagent. Synthesis of New 1,3-Dihydro-2H-indol-2-ones, Bis-furanones, and Bis-pyrrolones. Helvetica, 94(5):801-810.
16. Mahajan R.N, Havaldar F.H, Fernandes P.S, 1991. Syntheses and biological activity of heterocycles derived from 3-methoxy-1-phenyl-1H-pyrazole-5-carboxylate. Indian Chemical Society, 68, 245-246.
17. Matyus P, 1998. 3(2H)-Pyrıdazınones-Some Recent Aspects Of Synthetıc And Medicinal Chemistry. J. Heterocyclic Chemistry, 35,1075.
18. Shawali A.S, 1977. Synthesis and tautomeric structure of some 2H-pyrazolo[3,4-d]pyridazines. Journal of Heterocyclic Chemistry, 14, 375-381.
19. Şener A, Kasımoğulları R, Şener M. K, Bildirici İ, Akçamur Y, 2002. Studies on the reactions of cyclicoxalyl compounds with hydrazines or hydrazones II [1]:Synthesis and reactions of 4-benzoyl-1-(3-nitrophenyl)-5- phenyl-1H-pyrazole-3-carboxylic acid. Journal of Heterocyclic Chemistry, 39(1):869-875.
20. Şener A, Genc H, Tozlu I, Sener M. K, 2004. Studies on the Reactions of 4-Ethoxycarbonyl-5-phenyl-2,3-dihydro-2,3- furandione with Some NH Nucleophiles. Turkis Journal of Chemistry, 28(5):659-665.
21. Şener A, Kasimogullari R, Sener M.K, Genç H, 2004. Studies on reactions of cyclic oxalyl compounds with hydrazines or hydrazones. 2. Synthesis and reactions of 4-benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid. Chemistry of Heterocyclic Compounds, 40(8):1039-1046.
22. Şener A, Tozlu İ, Genç H, Bildirici İ, Arısoy K, 2007. Synthesis and some reactions of 4-(ethoxycarbonyl)-1,5-diphenyl-1H-pyrazole-3-carboxylic acid. Journal of Heterocyclic Chemistry, 44(5):1077-1081.
23. Şener A, Eskinoba S, Bildirici İ, Genç H, Kasımoğulları R, 2007. A study on chemical behaviors of some 4-pyrones synthesized by one-step reactions towards various amines. Journal of Heterocyclic Chemistry, 44, 337-341.
24. Şener A, Mengeş N, Akkurt M, Karaca S, Büyükgüngör, O, 2008. Efficient synthesis of some oxalacetic acid and pyruvic acid derivatives from the reactions of 2, 3-furandiones with 2-phenylindole. Tetrahedron Letters, 49(17):2828-2831.
25. Şener A, Bildirici İ, Genç H, Mengeş N, Eskinoba S, 2008. One Step Synthesis of Some 2,5,6-Trisubstituted-1,3-Dioxin-4-ones. Turkish Journal of Chemistry, 32(1):19-24.
26. Yılırım I, Saripinar E, Güzel Y, Patat S, Akçamur Y, 1995. Theoretical investigations on the mechanism of interaction of 4-formyl furan-2,3-dion and urea. Journal of Molecular Structure: THEOCHEM, 334(2):165-171.
27. Yıldırım İ, Kandemirli F, Korkusuz E, 2005. Experimental And Theoretical Studies On The Functionalization Reaction Of 4- Benzoyl -1,5- Diphenyl-1h-Pyrazole-3- Carboxylic Acid And Chloride With 2,3- Diaminopyridine. Molecules. 10(3):559-571.
28. Taslimi P, Türkan F, Cetin A, Burhan H, Karaman M, Bildirici I, Gulçin İ, Şen F, 2019. Pyrazole[3,4-d]pyridazine derivatives: Molecular docking and explore of acetylcholinesterase and carbonic anhydrase enzymes inhibitors as anticholinergics potentials. Biyoorganic Chemistry, 92,103213.
29. Tewari A. K, Mishra A, 2001. Synthesis and anti-inflammatory activities of N4, N5-disubstituted-3-methyl-1H-pyrazolo[3,4-c]Pyridazines. Bioorganic and Medicinal Chemistry, 9(3):715-718.
30. Tozlu I, Hacıalioğlu E, Taşdemir V, Genç H, 2019. Synthesis and Some Reactions of Pyrazole-3-carboxylic acid Having Trifluoromethyl Unit. Gümüşhane Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 9(4):645-654.