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Regioselective formation of 1,2,4-triazoles by the reaction of amidrazones in the presence of diethyl azodicarboxylate and catalyzed by triethylamine

  • Ashraf A. Aly
  • Alaa A. Hassan
  • Nasr K. Mohamed
  • Mohamed Ramadan
  • Alan B. Brown
  • Amal S. Abd El-Aal
  • Stefan Bräse
  • Martin Nieger
Original Article
  • 88 Downloads

Abstract

A general method for the synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed from reaction of amidrazones with ethyl azodicarboxylate and triethylamine (Mitsunobu reagent) in EtOH. This highly regioselective one-pot process provides rapid access to highly diverse triazoles. The reaction was explained, based on Mitsunobu reagent oxidizing ethanol to acetaldehyde, which would then react with amidrazones to give the substituted 3-methyltriazoles. A [2 + 3] cycloaddition reaction between two oxidized forms of amidrazones produced the second type of triazoles. X-ray structure analyses proved the structure of each type of product.

Graphical abstract

Keywords

Amidrazones Mitsunobu reagent Regioselective 1,2,4-Triazoles 

Notes

Acknowledgements

The authors thank 3-MET Society, Karlsruhe Institute of Technology, Karlsruhe, Germany, for financial support to Prof Ashraf A. Aly enabling him to carry out analyses in the aforesaid Institute. Purchase of the NMR spectrometer at Florida Institute of Technology was assisted by the US National Science Foundation (CHE 03-42251).

Supplementary material

11030_2018_9868_MOESM1_ESM.docx (152 kb)
Supplementary material 1 (DOCX 152 kb)

References

  1. 1.
    Curtis ADM, Jennings N (2008) 1,2,4-triazoles. Compr Heterocycl Chem III 5:159–209.  https://doi.org/10.1016/B978-008044992-0.00502-2 Google Scholar
  2. 2.
    Zhou C-H, Wang Y (2012) Recent researches in triazole compounds as medicinal drugs. Curr Med Chem 19:239–280.  https://doi.org/10.2174/092986712803414213 CrossRefPubMedGoogle Scholar
  3. 3.
    Shalini K, Kumar N, Drabu S, Sharma PK (2011) Advances in synthetic approach to and antifungal activity of triazoles. Beilstein J Org Chem 7:668–677.  https://doi.org/10.3762/bjoc.7.79 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Turan-Zitouni G, Kaplancikli ZA, Yildiz MT, Chevallet P, Kaya D (2005) Synthesis and antimicrobial activity of 4-phenyl/cyclohexyl-5-(1-phenoxyethyl)-3-[N-(2-thiazolyl)acetamido]thio-4H-1,2,4-triazole derivatives. Eur J Med Chem 40:607–613.  https://doi.org/10.1016/j.ejmech.2005.01.007 CrossRefPubMedGoogle Scholar
  5. 5.
    Walczak K, Gondela A, Suwinski J (2004) Synthesis and anti-tuberculosis activity of N-aryl-C- nitroazoles. Eur J Med Chem 39:849–853.  https://doi.org/10.1016/j.ejmech.2004.06.014 CrossRefPubMedGoogle Scholar
  6. 6.
    Holla BS, Poojary KN, Rao BS, Shivananda MK (2002) New bis-aminomercaptotriazoles and bis- triazolothiadiazoles as possible anticancer agents. Eur J Med Chem 37:511–517.  https://doi.org/10.1016/S0223-5234(02)01358-2 CrossRefPubMedGoogle Scholar
  7. 7.
    Almasirad A, Tabatabai SA, Faizi M, Kebriaeezadeh A, Mehrabi N, Dalvandi A, Shafiee A (2004) Synthesis and anticonvulsant activity of new 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4- oxadiazoles and 1,2,4-triazoles. Bioorg Med Chem Lett 14:6057–6059.  https://doi.org/10.1016/j.bmcl.2004.09.072 CrossRefPubMedGoogle Scholar
  8. 8.
    Mhasalkar MY, Shah MH, Nikam ST, Ananthanarayanan KG, Deliwala CV (1970) 4-Alkyl-5-aryl-4H-1,2,4-triazole-3-thiols as hypoglycemic agents. J Med Chem 13:672–674.  https://doi.org/10.1021/jm00298a021 CrossRefPubMedGoogle Scholar
  9. 9.
    Amir M, Shikha K (2004) Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of some new 2-[(2,6-dichloroanilino)phenyl]acetic acid derivatives. Eur J Med Chem 39:535–545.  https://doi.org/10.1016/j.ejmech.2004.02.008 CrossRefPubMedGoogle Scholar
  10. 10.
    Mitsunobu O, Yamada Y (1967) Preparation of esters of carboxylic and phosphoric acid via quaternary phosphonium salts. Bull Chem Soc Jpn 40:2380–2382.  https://doi.org/10.1246/bcsj.40.2380 CrossRefGoogle Scholar
  11. 11.
    Mitsunobu O (1981) The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products. Synthesis 1981:1–28.  https://doi.org/10.1055/s-1981-29317 CrossRefGoogle Scholar
  12. 12.
    Aly AA, Ramadan M, Abd El-Aziz M, Bräse S, Brown AB, Fathy HM, Nieger M (2017) Regioselective synthesis of 5-aminopyrazoles from reactions of amidrazones with activated nitriles: NMR investigation and x-ray structural analysis. Chem Pap 71:1409–1417.  https://doi.org/10.1007/s11696-017-0131-x CrossRefGoogle Scholar
  13. 13.
    Aly AA, Ramadan M, Abd El-Aziz M, Bräse S, Brown AB, Fathy HM (2017) Selectivity of amidrazones towards activated nitriles—synthesis of new pyrazoles and NMR investigation. Arkivoc.  https://doi.org/10.24820/ark.5550190.p009.877 Google Scholar
  14. 14.
    Aly AA, Hassan AA, Bräse S, Gomaa MA-M, Nemr FM (2017) Reaction of amidrazones with diaminomaleonitrile: synthesis of 4-amino-5-iminopyrazoles. J Heterocycl Chem 54:480–483.  https://doi.org/10.1002/jhet.2607 CrossRefGoogle Scholar
  15. 15.
    Aly AA, Hassan AA, Gomaa MA-M, Bräse S, Nemr FM (2017) Reaction of amidrazones with phthaloyl chloride—synthesis of 1,2,4-triazolium salts (part I). J Heterocycl Chem 54:775–779.  https://doi.org/10.1002/jhet.2643 CrossRefGoogle Scholar
  16. 16.
    Aly AA, Gomaa MAM, NourEl- Din AM, Fahmi MS (2006) Amidrazones in the synthesis of 1H-1,2,4-triazoles. Z Naturforsch 61b:1239–1242.  https://doi.org/10.1515/znb-2006-1009 CrossRefGoogle Scholar
  17. 17.
    Aly AA, Brown AB, Shawky AM (2017) One-pot reaction of amidrazones, phthaloyl chloride, and triethyl amine: synthesis of (1′,2′,4′-triazole)-2-benzoic acid. J Heterocycl Chem 54:2375–2379.  https://doi.org/10.1002/jhet.2829 CrossRefGoogle Scholar
  18. 18.
    Aly AA, Shaker RM (2005) 5-Benzyl-1H-tetrazoles from the reaction of 1-aryl-5-methyl-1H-tetrazoles with 1,2-dehydrobenzene. Tetrahedron Lett 46:2679–2682.  https://doi.org/10.1016/j.tetlet.2005.02.072 CrossRefGoogle Scholar
  19. 19.
    Aly AA, Ramadan M, Abd Al-Aziz M, Fathy HM, Bräse S, Brown AB, Nieger M (2016) Reaction of amidrazones with 2,3-diphenylcyclopropenone: synthesis of 3-(aryl)-2,5,6-triphenylpyrimidin-4(3H)-ones. J Chem Res 40:637–639.  https://doi.org/10.3184/174751916x14743924 CrossRefGoogle Scholar
  20. 20.
    Aly AA, Ramadan M, Morsy NM, Elkanzi NAA (2017) Inclusion of carbonyl groups of benzo[b]thiophene-2,5-dione into amidrazones: synthesis of 1,2,4-triazine-5,6-diones. J Heterocycl Chem 54:2067–2070.  https://doi.org/10.1002/jhet.2805 CrossRefGoogle Scholar
  21. 21.
    Aly AA, Gomaa MAM, NourEl-Din AM, Fahmy MS (2007) Reactions of amidrazones with 1,4-quinones. Arkivoc 16:41–50.  https://doi.org/10.3998/ark.5550190.0008.g04 Google Scholar
  22. 22.
    Aly AA, NourEl-Din AM, Gomaa MA-M, Fahmy MS (2008) Rapid and facile synthesis of 4-aryl-5-imino-3-phenyl-1H-naphtho[2,3-f]-1,2,4-triazepine-6,11-diones via the reaction of amidrazones with dicyanonaphthoquinone. Z Naturforschung 63B:223–228.  https://doi.org/10.1515/znb-2008-0217 CrossRefGoogle Scholar
  23. 23.
    Aly AA, Ishak EA, Ramadan M, Elkanzi NAA, El-Reedy AAM (2017) Amidrazones and 2-acetylcyclopentanone in the synthesis of cyclopenta[e][1,3,4]oxadiazepines. J Heterocycl Chem 54:1652–1655.  https://doi.org/10.1002/jhet.2727 CrossRefGoogle Scholar
  24. 24.
    Nájera C, Sansano JM, Yus M (2015) 1,3-Dipolar cycloadditions of azomethine imines. Org Biomol Chem 13:8596–8636.  https://doi.org/10.1039/C5OB01086A CrossRefPubMedGoogle Scholar
  25. 25.
    Yoneda F, Suzuki K, Nitta Y (1966) A new hydrogen-abstracting reaction with diethyl azodicarboxylate. J Am Chem Soc 88:2328–2829.  https://doi.org/10.1021/ja00962a05 CrossRefGoogle Scholar
  26. 26.
    Hayashi M, Shibuya M, Iwabuchi Y (2011) Oxidation of alcohols to carbonyl compounds with diisopropyl azodicarboxylate catalyzed by nitroxyl radicals. J Org Chem 77:3005–3009.  https://doi.org/10.1021/jo300088b CrossRefGoogle Scholar
  27. 27.
    Cao HT, Grée R (2009) DEAD-(cat)ZnBr2, an efficient system for the oxidation of alcohols to carbonyl compounds. Tetrahedron Lett 50:1493–1494.  https://doi.org/10.1016/j.tetlet.2009.01.080 CrossRefGoogle Scholar
  28. 28.
    Shi M, Zhao G-L (2004) Aza-Baylis–Hillman reactions of diisopropyl azodicarboxylate or diethyl azodicarboxylate with acrylates and acrylonitrile. Tetrahedron 60:2083–2089.  https://doi.org/10.1016/j.tet.2003.12.059 CrossRefGoogle Scholar
  29. 29.
    Tsunoda T, Otsuka J, Yamamiya Y, Ito S (1994) N,N,N′,N′-Tetramethylazodicarboxamide (TMAD), a new versatile reagent for Mitsunobu reaction. Its application to synthesis of secondary amines. Chem Lett 23:539–542.  https://doi.org/10.1246/cl.1994.539 CrossRefGoogle Scholar
  30. 30.
    Tsunoda T, Kawamura Y, Uemoto K, Ito S (1998) Mitsunobu type C-N bond formation with 4,7-dimethyl-3,5,7-hexahydro-1,2,4,7-tetrazocin-3,8-dione (DHTD), a new cyclic azodicarboxamide. Heterocycles 47:177–179.  https://doi.org/10.3987/com-97-s(n)78 CrossRefGoogle Scholar
  31. 31.
    Sakamoto I, Kaku H, Tsunoda T (2003) Preparation of (cyanomethylene)trimethylphosphorane as a new Mitsunobu-type reagent. Chem Pharm Bull 51:474–476.  https://doi.org/10.1248/cpb.51.474 CrossRefPubMedGoogle Scholar
  32. 32.
    Hughes DL (2004) The Mitsunobu reaction. Org React (NY) 42:335–656.  https://doi.org/10.1002/0471264180.or042.02 Google Scholar
  33. 33.
    Jenkins ID, Mitsunobu O (2001) Triphenylphosphine-diethyl azodicarboxylate. In: Paquette LA (ed) Electronic encyclopedia of reagents for organic synthesis. Wiley, New York.  https://doi.org/10.1002/047084289x.rt372 Google Scholar
  34. 34.
    Müller D, Beckert R, Görls H (2001) Bis-amidines as useful building blocks for heterofulvenes and -fulvalenes. Synthesis 2001:601–606.  https://doi.org/10.1055/s-2001-12366 CrossRefGoogle Scholar
  35. 35.
    Siddaiah V, Basha GM, Srinuvasarao R, Yadav SK (2011) HClO4-SiO2: an efficient reusable catalyst for the synthesis of 3,4,5-trisubstituted 1,2,4-triazoles under solvent-free conditions. Catal Lett 141:1511–1520.  https://doi.org/10.1007/s10562-011-0665-4 CrossRefGoogle Scholar
  36. 36.
    Mangarao N, Mahaboob Basha G, Ramu T, Srinuvasarao R, Prasanthi S, Siddaiah V (2014) Brønsted acid-catalyzed simple and efficient synthesis of 1,2,4-triazoles and 1,2,4-oxadiazoles using 2,2,2-trichloroethyl imidates in PEG. Tetrahedron Lett 55:177–179.  https://doi.org/10.1016/j.tetlet.2013.10.147 CrossRefGoogle Scholar
  37. 37.
    Ito S, Tanaka Y, Kakehi A, Miyazawa H (1977) The reaction of N-(phenylsulfonyl)-benzohydrazonoyl chloride with N-substituted benzamidines, with benzimidates, and with 2-aminopyridines. Bull Chem Soc Jpn 50:2969–2972.  https://doi.org/10.1246/bcsj.50.2969 CrossRefGoogle Scholar
  38. 38.
    Nakka M, Tadikonda R, Nakka S, Vidavalur S (2016) Synthesis of 1,2,4-triazoles, N-fused 1,2,4-triazoles and 1,2,4-oxadiazoles via molybdenum hexacarbonyl-mediated carbonylation of aryl iodides. Adv Synth Catal 358:520–525.  https://doi.org/10.1002/adsc.201500703 CrossRefGoogle Scholar
  39. 39.
    Sheldrick GM (2015) SHELXT—integrated space-group and crystal-structure determination. Acta Crystallogr A 71:3–8.  https://doi.org/10.1107/S2053273314026370 CrossRefGoogle Scholar
  40. 40.
    Sheldrick GM (2015) Crystal structure refinement with SHELXL. Acta Crystallogr C 71:3.  https://doi.org/10.1107/S2053229614024218 CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Ashraf A. Aly
    • 1
  • Alaa A. Hassan
    • 1
  • Nasr K. Mohamed
    • 1
  • Mohamed Ramadan
    • 2
  • Alan B. Brown
    • 3
  • Amal S. Abd El-Aal
    • 1
  • Stefan Bräse
    • 4
  • Martin Nieger
    • 5
  1. 1.Chemistry Department, Faculty of ScienceMinia UniversityEl-MiniaEgypt
  2. 2.Organic Pharmacy Department, Faculty of PharmacyAl-Azhar Branch of Assiut UniversityAssiutEgypt
  3. 3.Chemistry DepartmentFlorida Institute of TechnologyMelbourneUSA
  4. 4.Institute of Organic ChemistryKarlsruhe Institute of TechnologyKarlsruheGermany
  5. 5.Department of ChemistryUniversity of HelsinkiHelsinkiFinland

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