Fluorocarboxylic acid

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). 

Extension by three carbon atoms is possible with methyl glutarate [183], by the isoprene unit with ethyl 3-methyl adipate [184], by four carbon atoms with methyl adipate [143], by five carbon atoms with methyl pimelate [185] and by six carbon atoms with methyl suberate [186]. A series of branched -fluorocarboxylic acids were prepared by cross-coupling with oo-fluorocarboxylic acids [187]. For further examples see Tables 6, 7. 

Low temperature fluorination of fluorocarboxylic acids to give explosive 1,1-bis(fluoroxy)perfluoroalkanes occasionally led to explosive reactions. Thus diflu-oroacetic acid led to explosion at —195°, and perfluorosuccinic acid at —1110 or —20°C. 

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. 

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

Bis(fluorooxy)tetrafluoroethane, 0641 2-Chloro-1,1 -bis(fluorooxy)trifluoroethane, 0595 1, l,4,4-Tetrakis(fluoroxy)hexafluorobutane, 1374 See Fluorine Fluorocarboxylic acids, etc., 4310 See related HYPOHALITES... 

D. Block, H.H. Coenen, G. Stocklin, N.C.A. F-Fluoroacylation via fluorocarboxylic acid esters, J. Label. Compds Radiopharm. 15 (1988) 185-200. 

Recently, Yoneda et al. [52] have reported an interesting electrochemical fluori-native a-cleavage reaction of cyclic ketones as a route to fluorocarboxylic acid esters. The reaction is carried out in the presence of Et3N 5HF as electrolyte, when the 2,2-disubstituted cyclic ketone is subject to selective cleavage of the C-C bond between the carbonyl carbon and the substituted a-carbon. 

HF-pyridine reagent, however, can also be used for the hy-drofluorination of alkenes,7 alkynes,7 cyclopropanes,7 and diazo compounds,8 the halofluonnation of alkenes,9 the preparation of fluoroformates from carbamates,10 the preparation of a-fluorocarboxylic acids from a-amino acids,11 and as a deprotecting reagent in peptide chemistry.12 Examples of the hydrofluonnation of alkenes with HF-pyridine are given in Table II. 

Takeuchi and co-workers5 have recently prepared a number of a-fluorocarboxylic acid derivatives 1 and 2 and it is very interesting that they emphasized that no explosion occurred in more than 200 fluorinations performed 17 however, they recommend the use of perchloryl fluoride diluted with nitrogen and synthesized in the laboratory. 

Direct conversion of aldehydes 14 to a-fluorocarboxylic acids 16 by generating dichloroepoxides 15 in situ in the presence of a fluoride ion has been skillfully effected.169... 

The reduction of amides of fluorocarboxylic acids with the tetrahydroaluminate appears generally hazardous at all stages. During reduction of /V-ethylheptafluor-obutyramide in ether, violent and prolonged gas evolution caused a fire. Towards the end of reduction of trifluoroacetamide in ether, solid separated and stopped the stirrer. Attempts to restart the stirrer by hand caused a violent explosion [1]. During decomposition by water of the reaction complex formed by interaction... 

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