5-fluoropentanecarboxylic acid

XIV) was shown to be non-toxic, and cannot of course be oxidized to fluoroacetic acid. We also employed another method2 which threw some light on the phenomenon of alternating toxicities and the possible connexion with /(-oxidation. The principle was to replace a CHa group at some appropriate point in the chain by an oxygen atom and then to compare the toxic action of the new compound with that of the parent w-fluoro-carboxylic acid. Thus whereas 5-fluoropentanecarboxylic acid... 

The very high toxicity of ethyl 5-fluoropentanecarboxylate and its derivatives and the fluoroacetate-like symptoms produced seemed to us to be of particular interest, since by a process of /9-oxidation in the animal body 5-fluoropentanecarboxylic acid would readily give rise to the toxic fluoroacetic acid. Similar remarks apply to y-fluorobutyric acid and its derivatives prepared independently by American workers. The non-toxicity of /9-fluoropropionic acid and its derivatives may, on the other hand, be due to the inability of this acid to give the toxic fluoroacetic acid by a process of /9-oxidation. 

One further compound should be mentioned in this connexion, namely, p-fluorophenylacetic acid (XXII), which has the carbon skeleton of the highly toxic 5-fluoropentanecarboxylic acid (XXIII). It seemed unlikely that (XXII) could be broken down in vivo to fluoroacetic acid, and as expected it was non-toxic. It should be mentioned, however, that aromatic compounds are capable of certain types of oxidative breakdown in the animal body. Jaffe,1 for example, isolated small quantities of muconic acid from the urine of dogs and rabbits which had received considerable quantities of benzene. 

From a study of the fluoroacetates so far mentioned, it appears that any compound which can give rise to fluoroacetic acid (or the fluoroacetate ion), either by hydrolysis or by oxidation (or both), is toxic. The toxic grouping is thus F-CH2-CO, and any substitution in this radical destroys the toxicity as far as relatively simple compounds are concerned. We had reached this conclusion by May 1943.1 We subsequently showed that esters of / -fluoropropionic acid were non-toxic, whereas esters of y-fluorobutyric acid were shown by American workers to be toxic. In 19442 we reported the synthesis of ethyl 5-fluoro-pentanecarboxylate, F,[CH2]g C02Et (I). This is a stable, colourless liquid and we showed that it possessed very potent toxic properties of the fluoroacetate type. By subcutaneous injection of the propylene glycol solution into mice the l.d. 50 was 4 mg./kg. Methyl fluoroacetate (II) may be taken as a convenient standard (p. 115) and has a l.d. 50 of about 6 mg./kg. for saline solutions, and 15 mg./kg. for propylene glycol solution.3 Therefore ethyl 5-fluoropentanecarboxylate was about 7 times as toxic as methyl fluoroacetate (molecule for molecule).4... 

The starting point for the 5-fluoropentanecarboxylic esters was cyclohexanone, which was oxidized to 5-hydroxypentane-carboxylic acid by a modification of Robinson and Smith s method.3 This was then converted into the bromo acid by means of hydrogen bromide and sulphuric acid.4... 

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See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ ]

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