American Chemical Society
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A New Class of SN2 Reactions Catalyzed by Protic Solvents:  Facile Fluorination for Isotopic Labeling of Diagnostic Molecules

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journal contribution
posted on 2006-12-20, 00:00 authored by Dong Wook Kim, Doo-Sik Ahn, Young-Ho Oh, Sungyul Lee, Hee Seup Kil, Seung Jun Oh, Sang Ju Lee, Jae Seung Kim, Jin Sook Ryu, Dae Hyuk Moon, Dae Yoon Chi
Aprotic solvents are usually preferred for the SN2 reactions, because nucleophilicity and hence SN2 reactivity are severely retarded by the influence of the partial positive charge of protic solvents. In this work, we introduce a remarkable effect of using tertiary alcohols as a reaction medium for nucleophilic fluorination with alkali metal fluorides. In this novel synthetic method, the nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts (such as alkenes, alcohols, or ethers) compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with [18F]fluorine (t1/2 = 110 min) for positron emission tomographic (PET) imaging, and it is illustrated by the synthesis of four [18F]fluoride-radiolabeled molecular imaging probes[18F]FDG, [18F]FLT, [18F]FP-CIT, and [18F]FMISOin high yield and purity and in shorter times compared to conventional syntheses.