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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

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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.

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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).

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Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Minia University, El-Minia, 61519, Egypt

    Ashraf A. Aly, Alaa A. Hassan, Nasr K. Mohamed & Amal S. Abd El-Aal

  2. Organic Pharmacy Department, Faculty of Pharmacy, Al-Azhar Branch of Assiut University, Assiut, Egypt

    Mohamed Ramadan

  3. Chemistry Department, Florida Institute of Technology, Melbourne, FL, 32901, USA

    Alan B. Brown

  4. Institute of Organic Chemistry, Karlsruhe Institute of Technology, 76131, Karlsruhe, Germany

    Stefan Bräse

  5. Department of Chemistry, University of Helsinki, PO Box 55, A. I. Virtasen aukio 1, 00014, Helsinki, Finland

    Martin Nieger

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  1. Ashraf A. Aly
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Correspondence to Ashraf A. Aly.

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Aly, A.A., Hassan, A.A., Mohamed, N.K. et al. Regioselective formation of 1,2,4-triazoles by the reaction of amidrazones in the presence of diethyl azodicarboxylate and catalyzed by triethylamine. Mol Divers 23, 195–203 (2019). https://doi.org/10.1007/s11030-018-9868-6

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