A new class of SN2 reactions catalyzed by protic solvents: Facile fluorination for isotopic labeling of diagnostic molecules.
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.
Kim
Dong Wook
DW
Department of Chemistry, Inha University, 253 Yonghyundong Namgu, Inchon 402-751, Korea.
Ahn
Doo-Sik
DS
Oh
Young-Ho
YH
Lee
Sungyul
S
Kil
Hee Seup
HS
Oh
Seung Jun
SJ
Lee
Sang Ju
SJ
Kim
Jae Seung
JS
Ryu
Jin Sook
JS
Moon
Dae Hyuk
DH
Chi
Dae Yoon
DY
D000438:Alcohols / Q000737:chemistry; D000478:Alkylation; D002384:Catalysis; D005461:Fluorine / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry; D008698:Mesylates / Q000737:chemistry; D015394:Molecular Structure; D012997:Solvents
D000438:Alcohols; D005462:Fluorine Radioisotopes; D008698:Mesylates; D012997:Solvents; D005461:Fluorine