PhenoFluor

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.

• References and Notes

• 1 O‘Hagan D. Chem. Soc. Rev. 2008; 37: 308
• 2 Kirsch P. Modern Fluoroorganic Chemistry. Wiley-VCH; Weinheim: 2004
• 3 Park BK, Kitteringham NR, O‘Neill PM. Annu. Rev. Pharmacol. Toxicol. 2001; 41: 443
• 4 Professor Dr. Tobias Ritter, co-founder and chief scientific advisor of SciFluor in cooperation with SciFluor Life Sciences LLC in Cambridge, MA, USA.
• 5 PhenoFluor^TM is commercially available at Sigma Aldrich
• 6 Tang P, Wang W, Ritter T. J. Am. Chem. Soc. 2011; 133: 11482
• 7 Sladojevich F, Arlow SI, Tang P, Ritter T. J. Am. Chem. Soc. 2013; 135: 2470