Puccetti, Francesco; Lukin, Stipe; Užarević, Krunoslav; Colacino, Evelina; Halasz, Ivan; Bolm, Carsten; Hernández, José G. (2022) Mechanistic Insights on the Mechanosynthesis of Phenytoin, a WHO Essential Medicine. Chemistry : a European journal, 28 (13). ISSN 0947-6539
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Abstract
In recent years, mechanochemistry has enriched the toolbox of synthetic chemists, enabling faster and more sustainable access to new materials and existing products, including active pharmaceutical ingredients (APIs). However, molecular-level understanding of most mechanochemical reactions remains limited, delaying the implementation of mechanochemistry in industrial applications. Herein, we have applied in situ monitoring by Raman spectroscopy to the mechanosynthesis of phenytoin, a World Health Organization (WHO) Essential Medicine, enabling the observation, isolation, and characterization of key molecular-migration intermediates involved in the single-step transformation of benzil, urea, and KOH into phenytoin. This work contributes to the elucidation of a reaction mechanism that has been subjected to a number of interpretations over time and paints a clear picture of how mechanosynthesis can be applied and optimized for the preparation of added-value molecules.
| Item Type: | Article |
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| Uncontrolled Keywords: | ball milling ; in situ monitoring ; mechanochemistry ; phenytoin ; rearrangements |
| Subjects: | NATURAL SCIENCES > Chemistry |
| Divisions: | Division of Physical Chemistry |
| Depositing User: | Stipe Lukin |
| Date Deposited: | 13 May 2022 11:16 |
| URI: | http://fulir.irb.hr/id/eprint/7375 |
| DOI: | 10.1002/chem.202104409 |
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