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Insights into Large-Scale Synthesis of Benfotiamine
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    Insights into Large-Scale Synthesis of Benfotiamine
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    • Anamaria Hanganu
      Anamaria Hanganu
      Research Centre of Applied Organic Chemistry, University of Bucharest, 90 Panduri Street, RO-050663 Bucharest, Romania
      “C. D. Nenitzescu” Institute of Organic and Supramolecular Chemistry of the Romanian Academy, 202B Spl. Independentei, 060023 Bucharest, Romania
    • Maxim Maximov
      Maxim Maximov
      SC Microsin SRL, Pericle Papahagi Street 51–63, 032364 Bucharest, Romania
      Department of Science and Engineering of Oxide Materials and Nanomaterials, Politehnica University of Bucharest, Gh Polizu Street 1–7, 011061 Bucharest, Romania
    • Oana-Cristina Maximov
      Oana-Cristina Maximov
      SC Microsin SRL, Pericle Papahagi Street 51–63, 032364 Bucharest, Romania
    • Codruta C. Popescu
      Codruta C. Popescu
      Research Centre of Applied Organic Chemistry, University of Bucharest, 90 Panduri Street, RO-050663 Bucharest, Romania
      Department of Inorganic and Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 90 Panduri Street, RO-050663 Bucharest, Romania
    • Nicoleta Sandu
      Nicoleta Sandu
      Research Centre of Applied Organic Chemistry, University of Bucharest, 90 Panduri Street, RO-050663 Bucharest, Romania
    • Mihaela Florea
      Mihaela Florea
      Research Centre of Applied Organic Chemistry, University of Bucharest, 90 Panduri Street, RO-050663 Bucharest, Romania
      National Institute of Material Physics, 405A Atomistilor Street, 077125 Magurele, Romania
    • Anca G. Mirea
      Anca G. Mirea
      National Institute of Material Physics, 405A Atomistilor Street, 077125 Magurele, Romania
    • Cristian Gârbea
      Cristian Gârbea
      SC Microsin SRL, Pericle Papahagi Street 51–63, 032364 Bucharest, Romania
    • Mihaela Matache*
      Mihaela Matache
      Research Centre of Applied Organic Chemistry, University of Bucharest, 90 Panduri Street, RO-050663 Bucharest, Romania
      Department of Inorganic and Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 90 Panduri Street, RO-050663 Bucharest, Romania
      *Email: [email protected]
    • Daniel P. Funeriu*
      Daniel P. Funeriu
      Research Centre of Applied Organic Chemistry, University of Bucharest, 90 Panduri Street, RO-050663 Bucharest, Romania
      *Email: [email protected]
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    Organic Process Research & Development

    Cite this: Org. Process Res. Dev. 2024, 28, 11, 4069–4078
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    https://doi.org/10.1021/acs.oprd.4c00351
    Published October 14, 2024
    Copyright © 2024 American Chemical Society

    Abstract

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    There has been increased interest in the synthesis of benfotiamine during the past few years, most likely as a direct consequence of growing market demand. It has much higher bioavailability than thiamine (vitamin B1) and therefore is more suitable for therapeutic purposes, especially in oral form. We report herein our research in an academic-private R&D project in which we investigate all aspects of the process on small and large scales. The procedure involves two labor-intensive steps, starting from thiami3ne chloride hydrochloride with the key intermediate thiamine monophosphate phosphate (TMP─the phosphate ester of thiamine monophosphate). We obtained the crystalline form of benfotiamine directly from the synthesis in the crystalline form required on the market, as proven by XRD powder spectroscopy, IR, and RAMAN.

    Copyright © 2024 American Chemical Society

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    Organic Process Research & Development

    Cite this: Org. Process Res. Dev. 2024, 28, 11, 4069–4078
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.oprd.4c00351
    Published October 14, 2024
    Copyright © 2024 American Chemical Society

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