Fluorocarboxylic acids oxidation

Oxidation of a mixture of perfluorononene isomers to a mixture of per-fluorocarboxylic acids is accomplished with two agents, potassium permanganate and ruthenium tetroxide. Oxidation with potassium permanganate is slower and gives lower yields than oxidation with ruthenium tetroxide [40] (equation 32). 

In Chapter vm (p. 149) we discuss our suggestion that fS oxidation of w-fluorocarboxylic acids takes place in the animal body. Nevertheless, there is some indication that y-fluoro-butyrate (but not y-fluorocrotonate), even if it does undergo oxidation, also acts per se. For example, progressive cardiac failure without ventricular fibrillation is noted in Rhesus monkeys poisoned with fluorobutyrate. Rabbits poisoned with fluorobutyrate do indeed show ventricular fibrillations and weak convulsions, but in addition appear to manifest a para-... 

It will readily be seen in our series of w-fluorocarboxylic acids, that when n is odd, / -oxidation would yield the toxic fluoro-acetic acid, whereas when n is even, the compound would presumably be oxidized only as far as the non-toxic yff-fluoro-propionic acid.1 The pharmacological results obtained are in complete accord with this hypothesis, and provide verification, of a kind not hitherto achieved, of the process of / -oxidation in the living animal body. However, Weinhouse, Medes and Floyd2 have inoculated rat-liver slices with one or two fatty acids containing isotopic carbon, and have obtained some evidence for a process of /7-oxidation. 

Certain aspects of our results, however, while not invalidating the /7-oxidation theory of the w-fluorocarboxylic acids, do indicate that / -oxidation is not the only factor concerned with the alternation of toxic properties. 

Further evidence for the ft-oxidation of fluorocarboxylic acids in vivo... 

Scheme 1.3 The alternating toxicity of ft)-fluorocarboxylic acids can be explained by the oxidative metabolism of fatty acids in Cj units. Only if the number of carbon atoms is even the final oxidation product is the highly toxic fluoroacetate [36]. Odd-membered -fluoro fatty acids are metabolized to the less toxic 3-fluoropropionate.

Electi ochemical fluorination of carboxylic acids produces perfluoroalkanoic acid fluorides in a low yield (about 10-20%) [31] and water as a by-product. Water forms explosive oxygen difluoride and causes oxidative degradation of the carboxylic acid. For acids with six or more carbon atoms, cyclic perfluoroethers are among the by-products formed. The anhydrides of carboxylic acids give per-fluorocarboxylic acid fluorides in a higher yield than the parent carboxylic acids. The electrochemical fluorination of carboxylic acids or their anhydrides is now obsolete. 

It is thus apparent that, in this series of w-fluorocarboxylic esters, if n is odd the compound is highly toxic, whereas if n is even it is non-toxic. This striking alternation in toxicity provides a useful verification of the theory of /7-oxidation of fatty acids in the animal body. 

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