Relationship between physiological action and chemical constitution in the fluoroacetate series

Relationship between Physiological Action and Chemical Constitution in the Fluoroacetate Series  

A wide variety of compounds containing the C—F hnk has been described in this Chapter, and it is now convenient to classify them according to their physiological activity. In general, two types of assessment of animal toxicity have been made (a) by inhalation (hquids) and given as l.c. 50 in mg./l. (6) by injection (hquids and sohds) and given as l.d. in mg./kg. of body weight. 

Methyl fluoroacetate (M.F.A.) has a L.c. 50 of 0-1 mg./l. for rabbits, guinea-pigs and rats. The figure for fluoroethanol (F.E.A.) is similar. For intravenous injection into rabbits, M.F.A., F.E.A. and free fluoroacetate acid (a solid) have l.d. 50 s of the order of 0-25 mg./kg., and for subcutaneous injection 

For purposes of comparison the magnitude of the toxicity of fluoroacetic acid is represented B A indicates higher toxicity (up to a factor of 2) and C indicates a lower toxicity (down to about 1 /4 of that of fluoroacetic acid) D represents very low or negligible toxicity of the fluoroacetate type. 

In class B are placed all simple esters, CHjF CO i , of fluoro-aoetic acid, where iZ = Me, Et, Pr , Pr , Ph, etc. When substitution takes place in the a-hydrogen atoms, e.g. in methyl a-fluoropropionate or a-fluoroisobutyrate, then the compound is devoid of toxicity. This indicates the importance of the unsubstituted fluoromethyl group. On pp. 125 et seq. it was shown that fluoroacetamide and a variety of substituted amides such as CHjF CO NH CHg CHjCl were, molecule for molecule, equally toxic with fluoroacetic acid and produced the same symptoms. The 2 chloroethyl group therefore contributed nothing appreciable to the toxicity of the molecule. The majority of the esters of fluoroethanol showed the toxicity of the parent alcohol, e.g. 2-fluoroethyl chlorosulphonate, CHgF CHg O SOjCl, di-(2-fluoroethyl) sulphate and 2-fluoroethylglycine hydrochloride. 

All the toxic compounds mentioned above are either hydro-lysable or oxidizable to fluoroacetic acid. In this connexion it should be noted that l-chloro-2-fluoroethane was relatively nontoxic. The chlorine atom in this compound was shown to be rather unreactive chemically, hence hydrolysis to the toxic fluoroethanol in the animal body would be unlikely. 

Compounds in which the fluorine atom is very loosely bound are relatively non-toxic. Thus the COF group is not toxophoric 

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Relationship between physiological action and chemical constitution in the fluoroacetate series 133... 

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