Skip to main content

Advertisement

SpringerLink
Log in

A three-component cyclocondensation reaction for the synthesis of new triazolo[1,5-a]pyrimidine scaffolds using 3-aminotriazole, aldehydes and ketene N,S-acetal

  • Original Article
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

This study describes the use of 3-aminotriazole, different aldehydes and N-methyl-1-(methylthio)-2-nitroethenamine as a ketene N,S-acetal in a three-component condensation for the synthesis of a novel library of triazolo[1,5-a]pyrimidine scaffolds. The presence of trichloroacetic acid as a Brønsted–Lowry acidic promoter in acetonitrile or water solvent and room temperature condition resulting novel triazolo[1,5-a]pyrimidine systems named N-methyl-6-nitro-5-aryl-3,5-dihydro-[1, 2, 4]triazolo[1,5-a]pyrimidine-7-amine. The structure of products and direction of the N-cyclization could be confirmed using spectral data. The effect of various solvents on the progress of process was investigated in the paper. The presence of five nitrogen heteroatoms, the use of various aldehydes affording a range of skeletally distinct triazolo[1,5-a]pyrimidine-based heterocycles, the potency to create numerous hydrogen bonds in the product structure, and direction of cyclization are attractive features of this reaction.

Graphic abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Scheme 2
Scheme 3

Similar content being viewed by others

References

  1. Holla BS, Mahalinga M, Karthikeyan MS, Poojary B, Akberali PM, Kumari NS (2005) Synthesis, characterization and antimicrobial activity of some substituted 1,2,3-triazoles. Eur J Med Chem 40:1173–1178

    Article  CAS  Google Scholar 

  2. Gujjar R, Marwaha A, El Mazouni F, White J, White KL, Creason S, Charman S (2009) Identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice. J Med Chem 52:1864–1872

    Article  CAS  Google Scholar 

  3. Sheremet EA, Tomanov RI, Trukhin EV, Berestovitskaya VM (2004) Synthesis of 4-aryl-5-nitro-1,2,3-triazoles. Russ J Org Chem 40:594–595

    Article  CAS  Google Scholar 

  4. Banu KM, Dinakar A, Ananthanarayanan C (1999) Synthesis, characterization, antimicrobial studies and pharmacological screening of some substituted 1,2,3-triazoles. Indian J Pharm Sci 61:202

    CAS  Google Scholar 

  5. Guan LP, Jin QH, Tian GR, Chai KY, Quan ZS (2007) Synthesis of some quinoline-2 (1H)-one and 1,2,4-triazolo[4,3-a]quinoline derivatives as potent anticonvulsants. J Pharm Pharm Sci 10:254–262

    CAS  PubMed  Google Scholar 

  6. Hafez H, Abbas HA, El-Gazzar AR (2008) Synthesis and evaluation of analgesic, anti-inflammatory and ulcerogenic activities of some triazolo-and 2-pyrazolyl-pyrido[2,3-d]-pyrimidines. Acta Pharm 58:359–378

    Article  CAS  Google Scholar 

  7. Passannanti A, Diana P, Barraja P, Mingoia F, Lauria A, Cirrincione G (1998) Pyrrolo[2, 3-d][1,2,3]triazoles as potential antineoplastic agents. Heterocycles 6:1229–1235

    Google Scholar 

  8. Manfredini S, Vicentini CB, Manfrini M, Bianchi N, Rutigliano C, Mischiati C, Gambari R (2000) Pyrazolo-triazoles as light activable dna cleaving agents. Bioorg Med Chem 8:2343–2346

    Article  CAS  Google Scholar 

  9. Johns BA, Weatherhead JG, Allen SH, Thompson JB, Garvey EP, Foster SA, Miller WH (2009) The use of oxadiazole and triazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 1: establishing the pharmacophore. Bioorg Med Chem Lett 19:1802–1806

    Article  CAS  Google Scholar 

  10. Duran A, Dogan HN, Rollas S (2002) Synthesis and preliminary anticancer activity of new 1,4-dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-5H-1,2,4-triazoline-5-thiones. Farmaco 57:559–564

    Article  CAS  Google Scholar 

  11. Beasley SC, Cooper N, Gowers L, Gregory JP, Haughan AF, Hellewell PG, Naylor R (1998) Synthesis and evaluation of a novel series of phosphodiesterase IV inhibitors. A potential treatment for asthma. Bioorg Med Chem Lett 8:2629–2634

    Article  CAS  Google Scholar 

  12. De Clercq ERIK (1997) In search of a selective antiviral chemotherapy. Clin Microbiol Rev 10:674–693

    Article  Google Scholar 

  13. Weide T, Saldanha SA, Minond D, Spicer TP, Fotsing JR, Spaargaren M, Fokin VV (2010) NH-1,2,3-triazole inhibitors of the VIM-2 metallo-β-lactamase. ACS Med Chem Lett 1:150–154

    Article  CAS  Google Scholar 

  14. Chai B, Qian X, Cao S, Liu H, Song G (2003) Synthesis and insecticidal activity of 1,2,4-triazole derivatives. Arkivoc 2:141–145

    Article  Google Scholar 

  15. Keri RS, Patil SA, Budagumpi S, Nagaraja BM (2015) Triazole: a promising antitubercular agent. Chem Biol Drug Des 86:410–423

    Article  CAS  Google Scholar 

  16. Sharma V, Shrivastava B, Bhatia R, Bachwani M, Khandelwal R, Ameta J (2011) Exploring potential of 1,2,4-triazole: a brief review. Pharmacologyonline 1:1192–1222

    Google Scholar 

  17. Katritzky AR, Qi M, Feng D, Zhang G, Griffith MC, Watson K (1999) Synthesis of 1,2,4-triazole-functionalized solid support and its use in the solid-phase synthesis of trisubstituted 1,2,4-triazoles. Org Lett 1:1189–1191

    Article  CAS  Google Scholar 

  18. Murlykina MV, Morozova AD, Zviagin IM, Sakhno YI, Desenko SM, Chebanov VA (2018) Aminoazole-based diversity-oriented synthesis of heterocycles. Front Chem 6:1–43

    Article  Google Scholar 

  19. Yu J, Shi F, Gong LZ (2011) Brønsted-acid-catalyzed asymmetric multicomponent reactions for the facile synthesis of highly enantioenriched structurally diverse nitrogenous heterocycles. Acc Chem Res 44:1156–1171

    Article  CAS  Google Scholar 

  20. Hassan S, Mueller TJ (2015) Multicomponent syntheses based upon copper-catalyzed alkyne-azide cycloaddition. Adv Synth Catal 357:617–666

    Article  CAS  Google Scholar 

  21. Zhu QN, Zhang YC, Xu MM, Sun XX, Yang X, Shi F (2016) Enantioselective construction of tetrahydroquinolin-5-one-based spirooxindole scaffold via an organocatalytic asymmetric multicomponent [3 + 3] cyclization. J Org Chem 81:7898–7907

    Article  CAS  Google Scholar 

  22. Guo J, Miao H, Zhao Y, Bai X, Zhu Y, Wang Q, Bu Z (2019) An unexpected multi-component one-pot cascade reaction to access furanobenzodihydropyran-fused polycyclic heterocycles. Chem Commun 55:5207–5210

    Article  CAS  Google Scholar 

  23. Karami B, Farahi M, Banaki Z (2015) A novel one-pot method for highly regioselective synthesis of triazoloapyrimidinedicarboxylates using silica sodium carbonate. Synlett 26:1804–1807

    Article  CAS  Google Scholar 

  24. Sedash YV, Gorobets NY, Chebanov VA, Konovalova IS, Shishkin OV, Desenko SM (2012) Dotting the i’s in three-component Biginelli-like condensations using 3-amino-1,2,4-triazole as a 1,3-binucleophile. RSC Adv 2:6719–6728

    Article  CAS  Google Scholar 

  25. Chen Q, Jiang LL, Chen CN, Yang GF (2009) The first example of a regioselective Biginelli-like reaction based on 3-alkylthio-5-amino-1,2,4-triazole. J Heterocycl Chem 46:139–148

    Article  CAS  Google Scholar 

  26. Farghaly TA, Shawali SA, Abbas MH, Abdel-hafez AN (2015) A facile synthesis of new polyazaheterocycles via one-pot three-components condensation reaction and study of their reactions with nitrilimines. Curr Org Synth 12:95–101

    Article  CAS  Google Scholar 

  27. Shaabani A, Seyyedhamzeh M, Ganji N, Sangachin MH, Armaghan M (2015) One-pot four-component synthesis of highly substituted[1,2,4]triazolo[1,5-a]pyrimidines. Mol Divers 19:709–715

    Article  CAS  Google Scholar 

  28. Karami B, Farahi M, Banaki Z (2015) A new protocol for catalyst-free regioselective synthesis of 5,9-dihydropyrimido[5,4-e][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-diones. Synlett 26:741–744

    Article  CAS  Google Scholar 

  29. Murlykina MV, Sakhno YI, Desenko SM, Shishkina SV, Shishkin OV, Sysoiev DO, Van der Eycken EV (2015) Study of the chemoselectivity of multicomponent heterocyclizations involving 3-amino-1,2,4-triazole and pyruvic acids as key reagents, and biological activity of the reaction products. Eur J Org Chem 2015:4481–4492

    Article  CAS  Google Scholar 

  30. Komykhov SA, Bondarenko AA, Musatov VI, Diachkov MV, Gorobets NY, Desenko SM (2017) (5S,7R)-5-Aryl-7-methyl-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidin-7-ols as products of three-component condensation. Chem Heterocycl Compd 53:378–380

    Article  CAS  Google Scholar 

  31. Gladkov ES, Sirko SM, Musatov VI, Shishkina SV, Tkachenko IG, Komykhov SA, Desenko SM (2018) New spiro derivative of dihydro-1,2,3-triazolo[1,5-a]pyrimidine as a product of multicomponent reaction. Chem Heterocycl Compd 54:1139–1144

    Article  CAS  Google Scholar 

  32. Bayat M, Safari F, Nasri S, Hosseini FS (2019) A chemoselective synthesis and biological evaluation of novel benzo[g]thiazolo[3,2-a]quinolone derivatives. Monatsh Chem 150:703–710

    Article  CAS  Google Scholar 

  33. Bayat M, Nasri S (2018) Synthesis and dynamic 1H NMR study of pyrazolo substituted pyrrolo[2,3-d]pyrimidines via a regioselective heterocyclization. J Mol Struct 1154:366–372

    Article  CAS  Google Scholar 

  34. Ponra S, Majumdar KC (2016) Brønsted acid-promoted synthesis of common heterocycles and related bio-active and functional molecules. RSC Adv 6:37784–37922

    Article  CAS  Google Scholar 

  35. Hioe J, Šakić D, Vrček V, Zipse H (2015) The stability of nitrogen-centered radicals. Org Biomol Chem 13:157–169

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Financial support of this research from Imam Khomeini International University, Iran, is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin, Iran

    Solmaz Karami, Mohammad Bayat, Shima Nasri & Faezeh Mirzaei

Authors
  1. Solmaz Karami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Bayat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shima Nasri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Faezeh Mirzaei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Bayat.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 10769 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karami, S., Bayat, M., Nasri, S. et al. A three-component cyclocondensation reaction for the synthesis of new triazolo[1,5-a]pyrimidine scaffolds using 3-aminotriazole, aldehydes and ketene N,S-acetal. Mol Divers 25, 2053–2062 (2021). https://doi.org/10.1007/s11030-020-10096-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-020-10096-0

Keywords

Search

Navigation