Modern Methods to Prepare Monofluoroaliphatic Compounds

Abstract

Organic fluorine chemistry has been important since the 1930s. The development of fluorine chemistry during World War II is well documented. Fluorine chemistry emerged in the 1950s because of three events: Large‐scale research designed to synthesize fluorine‐containing rockets was initiated. A fluorine atom at a specific site in a steroid molecule was found to enhance beneficial pharmacological effects New analytical techniques evolved (e.g., GC and NMR). There are eight reactions important for preparation of monofluoroaliphatic compounds. Halogen addition to alkenes and alkynes Fluoroalkylamine reagent for replacement of a hydoxy group. Nitrosyl fluoride addition to an activated double bond Hypofluorites for electrophilic fluorination. Inorganic and heteroatom fluorides for replacement of halogen, hydroxyl, or ester groups Hydrogen fluoride for addition Perchloryl fluoride for hydrogen replacement Condensation of a monolfluorinated organic compound.

Fluorine Compounds, Organic

“…Sulfur tetrafluoride and the following compounds can be used for the controlled introduction of fluorine into organic compounds: Dialkylaminosulfur(IV) fluorides (R 2 NSF 3 ) [44][45][46], arylsulfurtrifluorides [47], fluoroalkylamines (e.g., 2-chloro-1,1,2-trifluoroethyldiethylamine or 1,1,2,3,3,3-hexafluoropropyldiethylamine), tetra-n-butylammonium fluoride, amine hydrofluorides, nitrosyl fluoride, perchloryl fluoride, fluoroxyfluoroalkanes (e.g., CF 3 OF) [48], xenon difluoride [49], CH 3 COOF [50], N-fluoropyridinium salts [51], N-fluorosulfonimides [52], and Selectfluor [53]. They are of commercial value for the fluorination of complex organic compounds, such as pharmaceuticals.…”

Introduction of Fluorine

“…The first electrophilic fluorination reagent with industrial relevance was perchloryl fluoride (FClO 3 )[188] (Scheme 2.87), a gas (m.p. −46.7 • C) which is thermally stable up to 500 • C[189]. −46.7 • C) which is thermally stable up to 500 • C[189].…”

“…−147.8 • C, b.p. It was used commercially from the beginning of the 1960s for the production of fluoropharmaceuticals, in particular fluorosteroids.KClO 4 + 2HF + SbF 5 40-50°C FClO 3 + KSbF 6 + H 2 O Scheme 2.87 Synthesis of perchloryl fluoride[189]. It was used commercially from the beginning of the 1960s for the production of fluoropharmaceuticals, in particular fluorosteroids.KClO 4 + 2HF + SbF 5 40-50°C FClO 3 + KSbF 6 + H 2 O Scheme 2.87 Synthesis of perchloryl fluoride[189].…”

Fluoroolefin-Amine Adduct Deoxofluorination

“…Fluoroolefin-amine adducts (FAAs) are one of the oldest group of organic fluorinating agents, which became very popular due to their availability, simple synthesis, and ability to convert alcohols and acids into alkyl and acyl fluorides. The application of the first representative of this groupadduct of chlorotrifluoroethylene and diethylamine (Yarovenko reagent)as a reagent for conversion of alcohols into alkyl fluorides was reported in 1959 [1].…”

“…The chemistry of FAAs and FAR was previously overviewed. Detailed reports can be found in the following articles: synthesis and chemistry of Yarovenko reagent [1], Yarovenko and Ishikawa reagents [2], TFEDMA reagent [3], adducts of amines and 2-H-pentafluoropropene [4], and FAR reagents [5].…”