Microwave-assisted synthesis of pyrazoles - a mini-review

Year 2025, Volume: 4 Issue: 1, 42 - 54, 30.04.2025

Abdüllatif Karakaya

https://doi.org/10.55971/EJLS.1605180

Abstract

Heterocyclic compounds including pyrazole have a serious area in the field of medicinal chemistry and modern drug development studies. Pyrazole is a five-membered ring system containing two adjacent nitrogen atoms. Pyrazole attracts great attention due to its wide biological activity scale and potential in the development of new drug molecules. Traditional methods have been used in the general synthesis methods of pyrazole for a long time, but since these methods can be performed within certain limits, it is necessary to benefit from new and sustainable methodologies. In this review, the use and benefits of microwave (MW)-assisted techniques under the general title of green chemistry will be emphasized. The use of MW techniques stands out with its advantages such as increasing the efficiency of synthesis, obtaining selective products and preventing environmental pollution. The area of use of the MW method in pyrazole synthesis, synthesis mechanisms, organic synthesis methods and benefits are examined in this study. The MW method used in the synthesis of the pyrazole ring, which stands out with its bioactive diversity, will be encountered much more in the coming years.

Keywords

pyrazole , microwave , green chemistry

References

• Majumder A, Gupta R, Jain A. Microwave-assisted synthesis of nitrogen-containing heterocycles. Green Chem Lett Rev. (2013); 6(2): 151–82. https://doi.org/10.1080/17518253.2012.733032
• Balaban AT, Oniciu DC, Katritzky AR. Aromaticity as a cornerstone of heterocyclic chemistry. Chem Rev. (2004); 104(5): 2777–812. https://doi.org/10.1021/cr0306790
• Sheldon RA. Catalysis: The key to waste minimization. In: Journal of Chemical Technology and Biotechnology., John Wiley & Sons Ltd. (1997); 381–8. https://doi.org/fm7wx6
• Alam MA. Pyrazole: an emerging privileged scaffold in drug discovery. Vol. 15, Future Medicinal Chemistry. Newlands Press Ltd. (2023); 2011–23. https://doi.org/10.4155/fmc-2023-0207
• Henary M, Kananda C, Rotolo L, Savino B, Owens EA, Cravotto G. Benefits and applications of microwave-assisted synthesis of nitrogen containing heterocycles in medicinal chemistry. Vol. 10, RSC Advances. Royal Society of Chemistry. (2020); 14170: 97. https://doi.org/10.1039/D0RA01378A
• Ansari A, Ali A, Asif M, others. Biologically active pyrazole derivatives. New J of Chem. (2017); 41(1): 16–41.
• Anastas PT, Beach ES. Green chemistry: the emergence of a transformative framework. Green Chem Lett Rev. (2007); 1(1): 9–24. https://doi.org/10.1080/17518250701882441
• Tucker JL. Green chemistry, a pharmaceutical perspective. Org Process Res Dev. (2006); 10(2): 315–9. https://doi.org/10.1021/op050227k
• Villar H, Frings M, Bolm C. Ring closing enyne metathesis: A powerful tool for the synthesis of heterocycles. Chem Soc Rev. (2007); 36(1): 55–66.
• Anastas PT, Beach ES. Green chemistry: the emergence of a transformative framework. Green Chem Lett Rev. (2007); 1(1): 9–24. https://doi.org/10.1080/17518250701882441
• Daştan A, Kulkarni A, Török B. Environmentally benign synthesis of heterocyclic compounds by combined microwave-assisted heterogeneous catalytic approaches. Green chemistry. (2012); 14(1): 17–37. https://doi.org/10.1039/C1GC15837F
• De La Hoz A, Díaz-Ortiz Á, Moreno A, Sanchéz-Migallón A, Prieto P, Carrillo R, et al. Microwave-Assisted Reactions in Heterocyclic Compounds with Applications in Medicinal and Supramolecular Chemistry. CCHTS. (2007); 7: 877-902. https://doi.org/10.2174/138620707783220347
• Paul S, Nanda P, Gupta R, Loupy A. Zinc mediated friedel-crafts acylation in solvent-free conditions under microwave irradiation. Synthesis (Stuttg). 2003; (18): 2877–81. https://doi.org/10.1055/s-2003-42485
• Hoz A dl, Diaz-Ortiz A, Moreno A, Sanchez-Migallon A, Prieto P, Carrillo JR, et al. Microwave-assisted reactions in heterocyclic compounds with applications in medicinal and supramolecular chemistry. CCHTS. (2007); 10(10): 877–902. https://doi.org/10.2174/138620707783220347
• Larhed M, Hallberg A. Microwave-assisted high-speed chemistry: a new technique in drug discovery. Drug Discov Today. (2001); 6(8): 406–16. https://doi.org/10.1016/S1359-6446(01)01735-4
• Will H, Scholz P, Ondruschka B. Heterogene gasphasenkatalyse im mikrowellenfeld. Chemie Ingenieur Technik. (2002); 74(8): 1057–67. https://doi.org/10.1002/1522-2640(20020815)74:8<1057::AID CITE1057>3.0.CO;2-3
• Langa F, De La Cruz P, Espldora E, Garca JJ, Pérez MC, la Hoz A. Fullerene chemistry under microwave irradiation. Carbon N Y. (2000); 38(11–12): 1641–6. https://doi.org/10.1016/S0008-6223(99)00284-5
• de la Hoz A, Diaz-Ortis A, Moreno A, Langa F. Cycloadditions under microwave irradiation conditions: Methods and applications. European J Org Chem. (2000); (22): 3659–73. https://doi.org/fdcvcm
• Elander N, Jones JR, Lu SY, Stone-Elander S. Microwave-enhanced radiochemistry. Chem Soc Rev. (2000); 29(4): 239–49. https://doi.org/10.1002/9783527619559.ch18
• Kappe CO, Stadler A, Dallinger D. Microwaves in organic and medicinal chemistry. John Wiley & Sons. (2012); 52:26-37.
• Polshettiwar V, Varma RS. Microwave-assisted organic synthesis and transformations using benign reaction media. Acc Chem Res. (2008); 41(5): 629–39. https://doi.org/10.1021/ar700238s
• Polshettiwar V, Varma RS. Aqueous microwave chemistry: a clean and green synthetic tool for rapid drug discovery. Chem Soc Rev. (2008); 37(8): 1546–57. https://doi.org/10.1039/b716534j
• Cao X, Sun Z, Cao Y, Wang R, Cai T, Chu W, et al. Design, synthesis, and structure–activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility. J Med Chem. . (2014); 57(9): 3687–706. dx.doi.org/10.1021/jm4016284
• Salem MS, Sakr SI, El-Senousy WM, Madkour HMF. Synthesis, antibacterial, and antiviral evaluation of new heterocycles containing the pyridine moiety. Arch Pharm (Weinheim). (2013); 346(10): 766–73. https://doi.org/10.1002/ardp.201300183
• El-Sawy ER, Ebaid MS, Abo-Salem HM, Al-Sehemi AG, Mandour AH. Synthesis, anti-inflammatory, analgesic and anticonvulsant activities of some new 4, 6-dimethoxy-5-(heterocycles) benzofuran starting from naturally occurring visnagin. Arabian Journal of Chemistry. (2014); 7(6): 914–23. https://doi.org/10.1016/j.arabjc.2012.12.041
• Mabkhot YN, Barakat A, Al-Majid AM, Alshahrani S, Yousuf S, Choudhary MI. Synthesis, reactions and biological activity of some new bis-heterocyclic ring compounds containing sulphur atom. Chem Cent J. (2013); 7: 1–9.
• Abd El-Salam NM, Mostafa MS, Ahmed GA, Alothman OY. Synthesis and Antimicrobial Activities of Some New Heterocyclic Compounds Based on 6-Chloropyridazine-3 (2H)-thione. J Chem. (2013); 2013(1),890617: 1-8 https://doi.org/10.1155/2013/890617.
• Alkahtani HM, Almehizia AA, Al-Omar MA, Obaidullah AJ, Zen AA, Hassan AS, et al. In vitro evaluation and bioinformatics analysis of schiff bases bearing pyrazole scaffold as bioactive agents: antioxidant, anti-diabetic, anti-alzheimer, and anti-arthritic. Molecules. (2023); 28(20): 7125. https://doi.org/10.3390/molecules28207125
• Hossain M, Nanda AK. A review on heterocyclic: Synthesis and their application in medicinal chemistry of imidazole moiety. Science (1979). (2018); 6(5): 83–94. https://doi.org/10.11648/j.sjc.20180605.12
• Sharma M, Sandhu N, Saraswat V. Microwave assisted facile one pot synthesis of novel pyrazole derivative for multi-analyte detection (Fe3+ and Zn2+) and its solvatochromic studies. J Mol Struct. (2024); 1318: 139-183. https://doi.org/10.1016/j.molstruc.2024.139183
• Karrouchi K, Radi S, Ramli Y, Taoufik J, Mabkhot YN, Al-Aizari FA, et al. Synthesis and pharmacological activities of Pyrazole derivatives: A review. Molecules. (2018); 23(1): 134. https://doi.org/10.3390/molecules23010134
• Alcazar J, Diels G, Schoentjes B. Applications of the combination of microwave and parallel synthesis in medicinal chemistry. Comb Chem High Throughput Screen. (2007); 10(10): 918–32. https://doi.org/10.2174/138620707783220383
• Leadbeater NE. Microwave heating as a tool for sustainable chemistry. CRC press. (2010); 1: 290. https://doi.org/10.1201/9781439812709
• Dallinger D, Lehmann H, Moseley JD, Stadler A, Kappe CO. Scale-up of microwave-assisted reactions in a multimode bench-top reactor. Org Process Res Dev. (2011); 15(4): 841–54. https://doi.org/10.1021/op200090k
• Ju Y, Varma RS. Aqueous N-heterocyclization of primary amines and hydrazines with dihalides: Microwave-assisted syntheses of N-azacycloalkanes, isoindole, pyrazole, pyrazolidine, and phthalazine derivatives. Journal of Organic Chemistry. (2006); 71(1): 135–41. https://doi.org/10.1021/jo051878h
• Humphries PS, Finefield JM. Microwave-assisted synthesis utilizing supported reagents: A rapid and versatile synthesis of 1,5-diarylpyrazoles. Tetrahedron Lett. (2006); 47(14): 2443–6. https://doi.org/10.1016/j.tetlet.2006.01.100
• Corradi A, Leonelli C, Rizzuti A, Rosa R, Veronesi P, Grandi R, et al. New “Green” Approaches to the Synthesis of Pyrazole Derivatives. Molecules. (2007); 12: 1482–95. https://doi.org/10.3390/12071482
• Sauzem PD, Machado P, Rubin MA, da S. Sant’Anna G, Faber HB, de Souza AH, et al. Design and microwave-assisted synthesis of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles: Novel agents with analgesic and anti-inflammatory properties. Eur J Med Chem. (2008); 43(6): 1237–47. https://doi.org/10.1016/j.ejmech.2007.07.018
• Polshettiwar V, Varma RS. Nano-organocatalyst: magnetically retrievable ferrite-anchored glutathione for microwave-assisted Paal-Knorr reaction, aza-Michael addition, and pyrazole synthesis. Tetrahedron. (2010); 66(5): 1091–7. https://doi.org/10.1016/j.tet.2009.11.015
• Abdel-Aziz HA, El-Zahabi HSA, Dawood KM. Microwave-assisted synthesis and in-vitro anti-tumor activity of 1,3,4-triaryl-5-N-arylpyrazole-carboxamides. Eur J Med Chem. (2010); 45(6): 2427–32. https://doi.org/10.1016/j.ejmech.2010.02.026
• Antre R V., Cendilkumar A, Goli D, Andhale GS, Oswal RJ. Microwave assisted synthesis of novel pyrazolone derivatives attached to a pyrimidine moiety and evaluation of their anti-inflammatory, analgesic and antipyretic activities. Saudi Pharmaceutical Journal. (2011); 19(4): 233–43. https://doi.org/10.1016/j.jsps.2011.05.006
• Sahu PK, Sahu PK, Gupta SK, Thavaselvam D, Agarwal DD. Synthesis and evaluation of antimicrobial activity of 4H-pyrimido[2,1-b] benzothiazole, pyrazole and benzylidene derivatives of curcumin. Eur J Med Chem. (2012); 54: 366–78. https://doi.org/10.1016/j.ejmech.2012.05.020
• Alam MM, Marella A, Akhtar M, Husain A, Yar MS, Shaquiquzzaman M, et al. Microwave assisted one pot synthesis of some pyrazole derivatives as a safer anti-inflammatory and analgesic agents. Acta Pol Pharm. (2013); 70(3): 435–41.
• Selvam TP, Kumar PV, Saravanan G, Prakash CR (2014). Microwave-assisted synthesis, characterization and biological activity of novel pyrazole derivatives. Journal of Saudi Chemical Society., 18(6),1015–21.
• Bagley MC, Baashen M, Chuckowree I, Dwyer JE, Kipling D, Davis T. Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in werner syndrome cells. Pharmaceuticals. (2015); 8(2): 257–76. https://doi.org/10.3390/ph8020257
• Farmani HR, Mosslemin MH, Sadeghi B. Microwave-assisted green synthesis of 4,5-dihydro-1H-pyrazole-1-carbothioamides in water. Mol Divers. (2018); 22(3): 743–9. https://doi.org/10.1007/s11030-018-9814-7
• Mótyán G, Gopisetty MK, Kiss-Faludy RE, Kulmány Á, Zupkó I, Frank É, et al. Anti-cancer activity of novel dihydrotestosterone-derived ring a-condensed pyrazoles on androgen non-responsive prostate cancer cell lines. Int J Mol Sci. (2019); 20(9): 2170. https://doi.org/10.3390/ijms20092170
• Goulart TB, Neves AM, Soares MSP, Stefanello FM, Campos PT, Moura S, et al. Design, synthesis, and structure of alkyl 1H-pyrazolecarboxylates from a raspberry ketone methyl ether. Chem Heterocycl Compd (N Y). (2020); 56(10): 1314–20. https://doi.org/10.1007/s10593-020-02816-z
• Masaret GS. Synthesis of new Spiropyrazole derivatives under microwave irradiation and docking study for inhibition the microbes and COVID-19. J Mol Struct. (2022); 1269. https://doi.org/10.1016/j.molstruc.2022.133581
• Anwer KE, Sayed GH, Essa BM, Selim AA. Green synthesis of highly functionalized heterocyclic bearing pyrazole moiety for cancer-targeted chemo/radioisotope therapy. BMC Chem. (2023); 17(1). https://doi.org/10.1186/s13065-023-01053-7
• Kumar KS, Robert AR, Rao AV, Thainana SK, Harikrishna S, Maddila S. A rapid, efficient microwave-assisted synthesis of novel bis-pyrazole analogues using non-toxic and cost-effective catalyst under green solvent medium. CDC. (2024); 54. https://doi.org/10.1016/j.cdc.2024.101165
• Sharma M, Sandhu N, Saraswat V. Microwave assisted facile one pot synthesis of novel pyrazole derivative for multi-analyte detection (Fe3+ and Zn2+) and its solvatochromic studies. J Mol Struct. (2024); 1318. https://doi.org/10.1016/j.molstruc.2024.139183