Revealing the Mechanism of Alcohol Side Product Formation in Crown Ether-Mediated Nucleophilic Fluorination Using Acetonitrile as Solvent.

ABSTRACT: Nucleophilic fluorination of primary alkyl halides using KF salt and catalyzed and mediated by crown ether and bulky alcohols is an established method for monofluorination of organic compounds. However, in the presence of a small concentration of water molecules in the organic solvent, alcohol side products are formed. This is an intriguing finding because water molecules are unreactive toward the S_N2 reaction. Further, the formation of a hydroxide ion via deprotonation of water by the fluoride ion faces the problem of very different pK _a values in acetonitrile solution, which were calculated to be 19.5 for HF and 41.9 for H₂O. This work explores the mechanism behind this side reaction via theoretical calculations and experiments. We found that the d

SUBMITTER: Avila EP 

PROVIDER: S-EPMC12311644 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature