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A synthesis of N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines from nitrile imines and Erlenmeyer thioazlactones

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Abstract

Erlenmeyer thioazlactones are reacted with hydrazonoyl chlorides in the presence of Et3N to afford functionalized N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines in excellent yields. This strategy is based on a domino double 1,3-dipolar cycloaddition reaction of nitrile imines to Erlenmeyer thioazlactones, followed by the elimination of carbon monoxide and phenylmethanthiol from the initially formed cycloadducts. This method provides fast access to a variety of structurally diverse N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines. The structure of a typical product was established by X-ray crystallography.

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References

  1. Viegas-Junior C, Danuello A, da Silva Bolzani V, Barreiro EJ, Fraga CAM (2007) Molecular hybridization: a useful tool in the design of new drug prototypes. Curr Med Chem 14:1829–1852. https://doi.org/10.2174/092986707781058805

    Article  CAS  PubMed  Google Scholar 

  2. Flick AC, Ding HX, Leverett CA, Kyne RE Jr, Liu KKC, Fink SJ, O’Donnell CJ (2017) Synthetic approaches to the new drugs approved during 2015. J Med Chem 60:6480–6515. https://doi.org/10.1021/acs.jmedchem.7b00010

    Article  CAS  PubMed  Google Scholar 

  3. Karrouchi K, Radi S, Ramli Y, Taoufik J, Mabkhot Y, Al-aizari F (2018) Synthesis and pharmacological activities of pyrazole derivatives: a review. Molecules 23:134. https://doi.org/10.3390/molecules23010134

    Article  CAS  PubMed Central  Google Scholar 

  4. Ansari A, Ali A, Asif M, Shamsuzzaman (2017) Biologically active pyrazole derivatives. New J Chem 41:16–41. https://doi.org/10.1039/C6NJ03181A

    Article  CAS  Google Scholar 

  5. Kramer CS (2016) Pyrazoles. In: Brase S (ed) Privileged scaffolds in medicinal chemistry: design, synthesis, evaluation, Chap 5. Royal Society of Chemistry (RSC), Cambridge, pp 115–131

    Google Scholar 

  6. Nissen SE, Yeomans ND, Solomon DH, Luscher TF, Libby P, Husni ME, Graham DY, Borer JS, Wisniewski LM, Wolski KE, Wang Q, Menon V, Ruschitzka F, Gaffney M, Beckerman B, Berger MF, Bao W, Lincoff AMN (2016) Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. Engl J Med 375:2519–2529. https://doi.org/10.1056/NEJMoa1611593

    Article  CAS  Google Scholar 

  7. Abd El Razik HA, Badr MH, Atta AH, Mouneir SM, Abu-Serie MM (2017) Benzodioxole-pyrazole hybrids as anti-inflammatory and analgesic agents with COX-1,2/5-LOX inhibition and antioxidant potential. Arch Pharm 350:1700026. https://doi.org/10.1002/ardp.201700026

    Article  CAS  Google Scholar 

  8. Elimairi I, Sami A, Baur DA, Elimairi A, Minisandram A (2017) Effect of novalgin, ibuprofen and therapeutic jaw exercises on patients with facial arthromyalgia. Int J Oral Maxillofac Surg 46:343. https://doi.org/10.1016/j.ijom.2017.02.1156

    Article  Google Scholar 

  9. Olguín J, Brooker S (2011) Spin crossover active iron (II) complexes of selected pyrazole-pyridine/pyrazine ligands. Coord Chem Rev 255:203–240. https://doi.org/10.1016/j.ccr.2010.08.002

    Article  CAS  Google Scholar 

  10. Perez J, Riera L (2009) Pyrazole complexes and supramolecular chemistry. Eur J Inorg Chem 2009:4913–4925. https://doi.org/10.1002/ejic.200900694

    Article  CAS  Google Scholar 

  11. Cavero E, Uriel S, Romero P, Serrano JL, Giménez R (2007) Tetrahedral zinc complexes with liquid crystalline and luminescent properties: interplay between nonconventional molecular shapes and supramolecular mesomorphic order. J Am Chem Soc 129:11608–11618. https://doi.org/10.1021/ja073639c

    Article  CAS  PubMed  Google Scholar 

  12. Navarro JA, Lippert B (2001) Simple 1:1 and 1:2 complexes of metal ions with heterocycles as building blocks for discrete molecular as well as polymeric assemblies. Coord Chem Rev 222:219–250. https://doi.org/10.1016/S0010-8545(01)00390-3

    Article  CAS  Google Scholar 

  13. Hu Y, Li CY, Wang XM, Yang YH, Zhu HL (2014) 1,3,4-Thiadiazole: synthesis, reactions, and applications in medicinal, agricultural, and materials chemistry. Chem Rev 114:5572–5610. https://doi.org/10.1021/cr400131u

    Article  CAS  PubMed  Google Scholar 

  14. Serban G, Stanasel O, Serban E, Bota S (2018) 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug Des Dev Ther 12:1545–1566. https://doi.org/10.2147/DDDT.S155958

    Article  CAS  Google Scholar 

  15. Jain AK, Sharma S, Vaidya A, Ravichandran V, Agrawal RK (2013) 1,3,4-Thiadiazole and its derivatives: a review on recent progress in biological activities. Chem Biol Drug Des 81:557–576. https://doi.org/10.1111/cbdd.12125

    Article  CAS  PubMed  Google Scholar 

  16. Alegaon SG, Hirpara MB, Alagawadi KR, Hullatti KK, Kashniyal K (2014) Synthesis of novel pyrazole–thiadiazole hybrid as potential potent and selective cyclooxygenase-2 (COX-2) inhibitors. Bioorg Med Chem Lett 24:5324–5329. https://doi.org/10.1016/j.bmcl.2014.08.062

    Article  CAS  PubMed  Google Scholar 

  17. Bekhit AA, Ashour HM, Ghany YSA, Bekhit AEDA, Baraka A (2008) Synthesis and biological evaluation of some thiazolyl and thiadiazolyl derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents. Eur J Med Chem 43:456–463. https://doi.org/10.1016/j.ejmech.2007.03.030

    Article  CAS  PubMed  Google Scholar 

  18. Kasımoğulları R, Bülbül M, Arslan BS, Gökçe B (2010) Synthesis, characterization and antiglaucoma activity of some novel pyrazole derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide. Eur J Med Chem 45:4769–4773. https://doi.org/10.1016/j.ejmech.2010.07.041

    Article  CAS  PubMed  Google Scholar 

  19. Abdel-Wahab BF, Abdel-Aziz HA, Ahmed EM (2009) Synthesis and antimicrobial evaluation of some 1,3-thiazole, 1,3,4-thiadiazole, 1,2,4-triazole, and 1,2,4-triazolo [3,4-b][1,3,4]-thiadiazine derivatives including a 5-(benzofuran-2-yl)-1-phenylpyrazole moiety. Monatsh Chem 140:601–605. https://doi.org/10.1007/s00706-008-0099-x

    Article  CAS  Google Scholar 

  20. Giustiniano M, Mercalli V, Amato J, Novellino E, Tron GC (2015) Exploiting the electrophilic and nucleophilic dual role of nitrile imines: one-pot, three-component synthesis of furo[2,3-d]pyridazin-4(5H)-ones. Org Lett 17:3964–3967. https://doi.org/10.1021/acs.orglett.5b01798

    Article  CAS  PubMed  Google Scholar 

  21. Guo CX, Zhang WZ, Zhang N, Lu XB (2017) 1,3-Dipolar cycloaddition of nitrile imine with carbon dioxide: access to 1,3,4-oxadiazole-2 (3 H)-ones. J Org Chem 82:7637–7642. https://doi.org/10.1021/acs.joc.7b00963

    Article  CAS  PubMed  Google Scholar 

  22. Wang LY, Tsai HJ, Lin HY, Kaneko K, Cheng FY, Shih HS, Wong FF, Huang JJ (2014) One-flask synthesis of 1,3,5-trisubstituted 1,2,4-triazoles from nitriles and hydrazonoyl chlorides via 1,3-dipolar cycloaddition. RSC Adv 4:14215–14220. https://doi.org/10.1039/C4RA00113C

    Article  CAS  Google Scholar 

  23. Huisgen R, Seidel M, Wallbillich G, Knupfer H (1962) Diphenyl-nitrilimin und seine 1.3-dipolaren additionen an alkene und alkine. Tetrahedron 17:3–29. https://doi.org/10.1016/S0040-4020(01)99001-5

    Article  CAS  Google Scholar 

  24. Guo CX, Zhang WZ, Zhang N, Lu XB (2017) 1,3-Dipolar cycloaddition of nitrile imine with carbon dioxide: access to 1,3,4-oxadiazole-2 (3 H)-ones. J Org Chem 82:7637–7642. https://doi.org/10.1021/acs.joc.7b00963

    Article  CAS  PubMed  Google Scholar 

  25. Liu H, Jia H, Wang B, Xiao Y, Guo H (2017) Synthesis of spirobidihydropyrazole through double 1,3-dipolar cycloaddition of nitrilimines with allenoates. Org Lett 19:4714–4717. https://doi.org/10.1021/acs.orglett.7b01961

    Article  CAS  PubMed  Google Scholar 

  26. Garve LK, Petzold M, Jones PG, Werz DB (2016) [3 + 3]-Cycloaddition of donor–acceptor cyclopropanes with nitrile imines generated in situ: access to tetrahydropyridazines. Org Lett 18:564–567. https://doi.org/10.1021/acs.orglett.5b03598

    Article  CAS  PubMed  Google Scholar 

  27. Alizadeh A, Moafi L, Zhu LG (2016) Highly regioselective synthesis of pyrazole derivatives using a 1,3-dipolar cycloaddition approach. Synlett 27:595–598. https://doi.org/10.1055/s-0035-1560905

    Article  CAS  Google Scholar 

  28. Gomha SM, Muhammad ZA, El-Reedy AA (2018) Intramolecular ring transformation of bis-oxadiazoles to bis-thiadiazoles and investigation of their anticancer activities. J Heterocycl Chem 55:2360–2367. https://doi.org/10.1002/jhet.3300

    Article  CAS  Google Scholar 

  29. Shawali AS (2014) 1,3,4-Thiadiazoles of pharmacological interest: recent trends in their synthesis via tandem 1,3-dipolar cycloaddition. J Adv Res 5:1–17. https://doi.org/10.1016/j.jare.2013.01.004

    Article  CAS  PubMed  Google Scholar 

  30. de Castro PP, Carpanez AG, Amarante GW (2016) Azlactone reaction developments. Chem Eur J 22:10294–10318. https://doi.org/10.1002/chem.201600071

    Article  CAS  PubMed  Google Scholar 

  31. Parhizkar G, Khosropour AR, Mohammadpoor-Baltork I, Parhizkar E, Amiri Rudbari H (2018) CsF-Catalyzed transannulation reaction of oxazolones: diastereoselective synthesis of diversified trans-N-(6-oxo-1,4,5,6-tetrahydropyrimidin-5-yl) benzamides with arylidene azlactones and amidines. ACS Comb Sci 20:358–365. https://doi.org/10.1021/acscombsci.8b00027

    Article  CAS  PubMed  Google Scholar 

  32. Ziyaei-Halimehjani A, Khoshdoun M (2016) Tandem esterification/1,4-addition-type Friedel–Crafts alkylation reactions of phenols/naphthols with olefinic thioazlactones: access to functionalized 1,2-dihydrobenzo [f] chromen-3-ones and 3,4-dihydrochromen-2-ones. J Org Chem 81:5699–5704. https://doi.org/10.1021/acs.joc.6b00740

    Article  CAS  PubMed  Google Scholar 

  33. Bernabé M, Cuevas O, Fernandez-Alvarez E (1977) A new synthesis of 1-amino-2-arylcyclopropanecarboxylic acids. Synthesis 1977:191–193. https://doi.org/10.1055/s-1977-24318

    Article  Google Scholar 

  34. Arenal I, Bernabé M, Cuevas O, Alvarez EF (1983) Reaction of 5 (4 h)-thiazolones with diazomethane. Tetrahedron 39:1387–1393. https://doi.org/10.1016/S0040-4020(01)91909-X

    Article  CAS  Google Scholar 

  35. Bernabe M, Cuevas O, Alvarez EF (1977) Romg expansion reaction in substituted thiazolones. Tetrahedron Lett 18:895–896. https://doi.org/10.1016/S0040-4039(01)92784-4

    Article  Google Scholar 

  36. Yavari I, Khalili G (2010) A diastereoselective synthesis of phosphorylated dihydro-1H-pyrazoles from dialkyl phosphites, acetylenic esters, and hydrazonoyl chlorides. Synlett 2010:1862–1864. https://doi.org/10.1055/s-0030-1258118

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the Research Council of Tarbiat Modares University for supporting this work.

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Authors and Affiliations

  1. Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran

    Issa Yavari, Zohreh Taheri & Sara Sheikhi

  2. Department of Inorganic Chemistry, Chemistry and Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran

    Samira Bahemmat & Mohammad R. Halvagar

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Yavari, I., Taheri, Z., Sheikhi, S. et al. A synthesis of N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines from nitrile imines and Erlenmeyer thioazlactones. Mol Divers 24, 727–735 (2020). https://doi.org/10.1007/s11030-019-09981-0

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