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


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


Amidrazones Mitsunobu reagent Regioselective 1,2,4-Triazoles 



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)


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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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