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Improved Method for the Total Synthesis of Azaperone and Investigation of Its Electrochemical Behavior in Aqueous Solution

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Chemical Research in Chinese Universities Aims and scope

Abstract

Azaperone, with anti-anxiety and anti-aggressive activities used in veterinary medicine, is a member of the butyrophenone class. It is ordinarily utilized for a wide range of indications, such as sedation, obstetrics, and anesthesia. In this research, an improved synthetic route is presented for azaperone using a phase-transfer catalyst(PTC). In general, it was synthesized as a dopamine antagonist in four steps. The bis(2-chloroethyl) amine intermediate is easily obtained after the conversion of the alcohol groups into the chloride leaving group using thionyl chloride(95% yields). The alkylation of commercially available 2-amino pyridine in the presence of PTC was then carried out, giving 1-(pyridin-2-yl) piperazine with 75% yield. 1-(Pyridin-2-yl) piperazine was finally alkylated using 4-chloro-1-(4-fluorophenyl) butan-1-one to achieve azaperone with 60% yield. The butyrophenone intermediate was obtained via the Friedel-Crafts reaction of fluorobenzene with 4-chlorobutyryl chloride in the presence of AlCl3. High efficiency, gentle reaction conditions, and fast and simple procedure are the advantages of this method. Also, the electrochemical oxidation behaviour of azaperone was investigated using cyclic and differential pulse voltammetry techniques. Cyclic voltammetric studies indicated an irreversible process for azaperone electro-oxidation with a peak potential of 0.78 V in a phosphate buffer solution(pH=7.0) vs. Ag/AgCl(saturated KCl) electrode. The value of the peak current vs. the azaperone concentration was enhanced linearly in the range of 10–70 µmol/L, and the detection limit was found to be 3.33 µmol/L.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, University of Imam Hossein, Tehran, Iran

    Mohammad Javad Taghizadeh

  2. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Maryam Saleh Mohammadnia

  3. Electrochemical Sensors Research Laboratory, Department of Chemistry, Faculty of Science, Shahid Rajaee Teacher Training University, Lavizan, P. O. Box 1678815811, Tehran, Iran

    Masoumeh Ghalkhani

  4. Young Researchers and Elites Club, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Esmail Sohouli

Authors
  1. Mohammad Javad Taghizadeh
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  2. Maryam Saleh Mohammadnia
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  3. Masoumeh Ghalkhani
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  4. Esmail Sohouli
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Correspondence to Esmail Sohouli.

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40242_2021_1061_MOESM1_ESM.pdf

Improved Method for the Total Synthesis of Azaperone and Investigation of its Electrochemical Behavior in Aqueous Solution

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Taghizadeh, M.J., Mohammadnia, M.S., Ghalkhani, M. et al. Improved Method for the Total Synthesis of Azaperone and Investigation of Its Electrochemical Behavior in Aqueous Solution. Chem. Res. Chin. Univ. 38, 546–551 (2022). https://doi.org/10.1007/s40242-021-1061-2

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  • DOI: https://doi.org/10.1007/s40242-021-1061-2

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