W-fluorocarboxylic acids

The writer was able to demonstrate a most striking alternation in the toxic properties of w-fluorocarboxylic acids 3 it was found that, in compounds of the type F(CH2)nCOOH, if n was odd the compound was very toxic, whereas if n was even the compound was non-toxic. 

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-... 

We then set out to determine whether this remarkable alternation in toxic properties could be observed among other w-fluorocarboxylic acids. 

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. 

Synthetic methods employed in this series of compounds As direct chlorination or bromination of a carboxylic acid usually gives the a-substituted acid, such methods are useless for the preparation of the w-substituted acids ad hoc methods therefore had to be found for the preparation of each individual w-fluorocarboxylic acid and its derivatives. 

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