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Optimization of Omeprazole Synthesis: Physico‐Chemical Steering Towards Greener Processes
Author(s) -
Vojčić Nina,
Bregović Nikola,
Cindro Nikola,
Požar Josip,
Horvat Gordan,
Pičuljan Katarina,
Meštrović Ernest,
Tomišić Vladislav
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201700433
Subject(s) - omeprazole , solvation , methanol , solvent , chemistry , protonation , process engineering , biochemical engineering , combinatorial chemistry , computer science , organic chemistry , medicine , ion , engineering
This work presents an optimization of the synthetic procedure for production of Omeprazole, a highly important pharmaceutical. The physico‐chemical measurements of the protonation and solution processes regarding the Omeprazole precursors aided the conception of the optimization strategy based primarily on the modifications of the reaction media. To this end, the protonation ( K H ) and solvation properties (solubilities, solution enthalpies, and entropies) of the starting materials and the intermediate were determined in different methanol/water mixtures and pure methanol, allowing the selection of the solvent optimal for the Omeprazole synthesis. In addition, it was proven that the energetically demanding refluxing procedure, which is conventionally used in the first step of the Omeprazol synthesis, was unnecessary. Similar holds for the time‐consuming trituration employed in the step involving precipitation of the final product. It was shown that trituration period can be significantly reduced without affecting the purity of the product. Taking into account the above‐mentioned findings, the improved procedure (compared to the standard one) for Omeprazol preparation was proposed. It was based on a greener process demanding less organic solvent, exhibiting enhanced energy‐ and time‐efficiency, which could be implemented in the large scale production. The concept devised in this work could easily be extended to other systems ameliorating the synthetic procedures of valuable drugs, rendering higher profit and lowering ecological risks.