Introduction
Fluorine has been demonstrated to have a dramatic impact on the physiochemical properties
of organic compounds.[1]
[2] These effects can often lead to altered solubility and influence drug metabolism[3] making it an interesting substituent for pharmaceutical studies and drug design.
The introduction of fluorine can be accomplished by deoxyfluorination. Although there
are many commercially available fluorinating agents, there is still a lack of reagents
for the manipulation of more complex molecules. A new nucleophilic deoxyfluorination
reagent, 1,3-bis-(2,6-diisopropylphenyl)-2,2-difluoro-2,3-dihydro-1H-imidazole (PhenoFluor), has recently been developed by Ritter and co-workers.[4] It is air stable and can be stored in anhydrous toluene for about two months without
detectable decomposition. The reagent is commercially available[5] (CAS: 1314657-40-3) as a crystalline, nonexplosive solid. Furthermore, an exotherm
of only 0.15 kcal
.
g–1 was observed by differential scanning calorimetry (DSC) at PhenoFluor’s decomposition
temperature of 213 °C. PhenoFluor can be used in different solvents such as toluene,
dioxane and dichloromethane (MeCN is not suitable). The only drawback is its high
molar mass of 427 g
.
mol–1 making it impractical in large-scale reactions. It can be synthesized in four steps
from glyoxal and 2,6-di-tert-butylaniline.
Scheme 1 Preparation of PhenoFluor.
