Simons electrochemical fluorination process

Perfluoro-l-fluoropiperidine (1) is synthesized by the Simons electrochemical fluorination process (8% from pyridine,20 13% from 2-fluoropyridine21). It is a seemingly innocuous liquid (bp 49.5 °C) which holds the distinction of being only the second compound to be identified as an electrophilic fluorinating agent. It decomposes rapidly at 50-70°C. 

Although NiF4 and NiFs in acidified aHF (see Chap. 8) rival cationic Ag in oxidizing power, they are also valuable in carrying out F for H ligand substitutions in organic molecules. These oxidations are done in aHF at room temperature (see Refs. Ill and 116). In such reactions the nickel fluorides appear to carry out the same chemistry as the Simons electrochemical fluorination process, which uses a... 

Electrochemical Fluorination. In the Simons electrochemical fluorination (ECF) process the organic reactant is dissolved in anhydrous hydrogen fluoride and fluorinated at the anode, usually nickel, of an electrochemical ceU. This process has been reviewed (6). Essentially all hydrogen atoms are substituted by fluorine atoms carbon—carbon multiple bonds are saturated. The product phase is heavier than the HF phase and insoluble in it and is recovered by phase separation. 

Electrochemical fluorination in anhydrous hydrogen fluoride (Simons process) involves electrolysis of organic compounds (ahphatic hydrocarbons, haloalkanes, acid halides, esters, ethers, amines) at nickel electrodes. It leads mostly to perfluori-nated compounds, but is accompanied to a high extent by cleavage and rearrangement reactions. The mechanism of the formation of carbocations according to Eq. (1) and Scheme 1 is assumed... 

The Simons Process or Electrochemical Fluorination (ECF) was devised during the 1940s, as part of the Manhattan Project, with a view to synthesising perfluo-rinated materials capable of tolerating the aggressive conditions encountered in the uranium hexafluoride diffusion process for the preparation and separation of uranium isotopes. 

In addition to the electrolytic preparation of fluorine, the electrochemical fluorination of carboxylic acid and sulfonic acid derivatives have also become important industrially. The Simons process (Ni anodes, HF as solvent) has been realized industrially by 3 M 69). The most important products are perfluorooctanecarboxylic and perfluorooctanesulfonic acids, which are used as surfactants and for surface treatments. 

The Simons process of electrochemical fluorination can be operated batchwise or continuously [126, 127]. By-products of the process are mixtures resulting from the CC bond cleavage and chain cyclisation. The yield usually does not exceed 65 % when = 3 and highly decreases as n rises. This process was brought into commercial practice by 3M, BASF, Bayer, Dainippon Ink Chemicals, GIPKh (Russia) and Tohoku Hiryo. 

As mentioned earlier, perfluorooctanesulfonyl fluoride and its homologues are prepared by electrochemical fluorination of organic compounds. " During the process, which was invented by Simons, the corresponding hydrocarbon sulfonyl fluoride or chloride is fluorinated in anhydrous HF by applying a direct electrical current with a voltage typically between 5 and 7 The elec-... 

Work on the production of trifluoroacetyl fluoride via electrochemical fluorination (Simons process) of ethylene glycol, ethylene chlorohydrin, or l,3-dichloro-2-hydroxypropane (the last two also give chlorodifluoroacetyl fluoride) has been reported." Similar electrochemical conversion of benzoyl chloride into perfluoro(fluorocarbonylcyclohexane) and its ring-contracted... 

The use of fluorine, a pyridine-fluorine complex, or trifluoromethyl hypofluorite for the preparation of 5-fluorouracil and related compounds has already been mentioned (see p. 262, particularly ref. 357). Electrochemical fluorination (Simons process) of uracil also gives 5-fluorouracil, > and trifluoromethyl hypofluorite has been applied to the preparation of l-(tetra-hydro-2-furanyl)-5-fluorouracil (Ftorafur) (Scheme 49), which is claimed to have a greater activity towards cancer of the breast and the gastrointestinal tract than 5-fluorouracil, while being considerably less toxic. 6-Fluoro-thyamine (245) has been prepared from 2,4,6-trifluoro-5-methylpyrimidine... 

The direction of F anion attack is consistent with the distribution of the density of positive charge [64,65]. The soft electrochemical fluorination very soon attracted attention in the West and is extensively used and developed [70]. Ionic liquids [71], alkali metal fluorides in poly(ethylene glycol) [72], etc., were proposed to be used instead of organic solvents. Just as the hard electrochemical fluorination was called the Simons process the soft fluorination should be referred rightfully to as the Rozhkov—Knunyants reaction ... 

Electrochemical fluorination of carboxylic acids in anhydrous hydrofluoric acid was invented by Simons [106,107]. A process developed by the 3M Co. [108,109] yields perfluorocarboxylic acid fluoride, which can be converted to esters, amides, or other intermediates for the production of repellents ... 

Almost all of the biomedical research done in the 25 years following the liquid-breathing work was conducted with commercially available fluorocarbons manufactured for various industnal uses by the electrochemical Simons process (fluonnation in a hydrofluoric acid solution) or the cobalt fluoride process (fluori-nation with this solid in a furnace at about 200 C) These processes tended to yield many by-products, partly because they were, to some extent, free radical reactions and partly because it was difficult to easily achieve complete fluonnation Aromatic hydrocarbons gave better products with the cobalt tnfluonde [73] method, whereas saturated hydrocarbons yielded better products with fluonnation using diluted or cooled gaseous fluorine (Lagow) Incompletely fluormated matenal was either... 

Simons process — Electrochemical polyfluorination reactions of organic compounds are the only efficient way to industrial production of perfluorinated compounds. The reaction proceeds in the solution of KF in liquid HF (b.p. 19.5 °C), where the starting substances as alcohols, amines, ethers, esters, aliphatic hydrocarbons and halo-hydrocarbons, aromatic and heterocyclic compounds, sulfo- or carboxylic acids are dissolved. During anodic oxidation, splitting of the C-H bonds and saturation of the C=C bonds occur and fluorine atoms are introduced. 

An important industrial process for the conversion of organic precursors to fully fluorinated derivatives (perfluo-rocarbon compounds) is the Simons Process. The Simons Process [1-9] uses an electrochemical cell to oxidize per-hydro-organic materials, at a nickel anode, to their perfluoro-relatives. The electrolyte for that process is liquid anhydrous hydrogen fluoride in which sodium fluoride, or other ionizing solutes, are dissolved (the latter, to provide for electrical conductance). 

---