RT Journal Article
T1 Regioselective N-2 Alkylation of Tetrazoles with Phenacyl Halides under Mechanochemical Conditions and Its Application to a Solid-State Synthesis of the Antiepileptic Drug Cenobamate
A1 Bepirszcz, Kamila
A1 Mazzetta, Anna Maria
A1 Gómez-Carpintero Jiménez, Jorge
A1 Sánchez Cebrián, Juan Domingo
A1 González Matilla, Juan Francisco
A1 Menéndez Ramos, José Carlos
AB Tetrazole derivatives are very important compounds in medicinal chemistry, and their preparation typically requires multistep sequences. Therefore, the regioselective N-alkylation of tetrazoles is a highly significant synthetic objective. We have explored the alkylation of tetrazoles with phenacyl halides under mechanochemical conditions to enhance the selectivity for N-2 regioisomers. The yield and regioisomeric ratio were found to depend on the nature of the grinding auxiliary, which can be explained by the ion pair formation. This methodology enabled the fully mechanochemical synthesis of the antiepileptic drug cenobamate, representing a substantial improvement over existing methods from a sustainability perspective.
PB ACS Publications
SN 2168-0485
SN 2168-0485
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/134634
UL https://hdl.handle.net/20.500.14352/134634
LA eng
NO Bepirszcz K, Mazzetta AM, Gómez-Carpintero J, et al. Regioselective N-2 Alkylation of Tetrazoles with Phenacyl Halides under Mechanochemical Conditions and Its Application to a Solid-State Synthesis of the Antiepileptic Drug Cenobamate. ACS Sustainable Chem Eng 2025;13:7332–41. https://doi.org/10.1021/acssuschemeng.4c09608
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 28 abr 2026