1279558-75-6Relevant academic research and scientific papers
Selective C-F Functionalization of Unactivated Trifluoromethylarenes
Vogt, David B.,Seath, Ciaran P.,Wang, Hengbin,Jui, Nathan T.
, p. 13203 - 13211 (2019/09/03)
Fluorinated organic molecules are pervasive within the pharmaceutical and agrochemical industries due to the range of structural and physicochemical properties that fluorine imparts. Currently, the most abundant methods for the synthesis of the aryl-CF2 functionality have relied on the deoxyfluorination of ketones and aldehydes using expensive and poorly atom economical reagents. Here, we report a general method for the synthesis of aryl-CF2R and aryl-CF2H compounds through activation of the corresponding trifluoromethyl arene precursors. This strategy is enabled by an endergonic electron transfer event that provides access to arene radical anions that lie outside of the catalyst reduction potential. Fragmentation of these reactive intermediates delivers difluorobenzylic radicals that can be intercepted by abundant alkene feedstocks or a hydrogen atom to provide a diverse array of difluoalkylaromatics.
Mechanistic approach of the difference in non-enzymatic hydrolysis rate between the L and D enantiomers of no-carrier added 2-[18F] fluoromethyl-phenylalanine
Kersemans, Ken,Mertens, John,De Proft, Frank,Geerlings, Paul
, p. 80 - 85 (2011/10/30)
No-carrier added (n.c.a.) 2-[18F]fluoromethyl-l-phenylalanine was found to be very sensitive to hydrolysis in aqueous solutions. This problem was solved partially by the addition of calcium ions (0.04M), increasing the shelf-life to at least 6h. In this paper the defluorination reaction was studied in detail to elucidate its mechanism. Therefore, L and D enantiomers of 2-[18F]FMP and 4-[18F]FMP were synthesized, as well as 2-[18F]fluoromethyl-phenethylamine and 4-[18F] fluoromethyl-phenethylamine, both decarboxylated 'mimetic' molecules of the amino acid analogues. Radiosynthesis, using a customized Scintomics automatic synthesis hotboxthree module, resulted in a high overall yield and a radiochemical purity of >99%. The defluorination rates of all compounds were studied by HPLC. The L enantiomer of n.c.a 2-[18F]FMP defluorinated seven times faster than the D enantiomer and 2-[18F]fluoromethyl- phenethylamine. Both enantiomers of 4-[18F]FMP and 4-[ 18F]fluoromethyl-phenethylamine were stable. From these data, the reaction mechanism, involving two distinct intramolecular interactions, was derived. First, the interaction between the amine and the benzylic fluorine weakens the carbon-fluorine bond. Secondly, the formation of a second hydrogen bridge between the carboxyl group and one of the benzylic hydrogen atoms renders the fluorine atom even more susceptible to hydrolysis. The latter interaction induces an additional chiral center. The probability of its formation differs considerably between L and D enantiomers of n.c.a. 2-[18F]FMP, which explains the difference in hydrolysis rate. Copyright
Mechanistic approach of the difference in hydrolysis rate between the 2- and 4-isomers of no-carrier-added [18F]fluoromethyl-L-phenylalanine
Kersemans, Ken,Mertens, John,De Proft, Frank,Geerlings, Paul
, p. 220 - 223 (2012/05/20)
No-carrier-added (n.c.a.) 2-[18F]fluoromethyl-l-phenylalanine (2-[18F]FMP) was found to be very sensitive to hydrolysis in aqueous solutions. In this paper, the defluorination reaction was studied in detail to elucidate its mechanism
