M.F.A. and related compounds

The work described in this section was carried out in Cambridge during the war, and was originally submitted by us to the Ministry of Supply in communications entitled Fluoroacetates and related compounds . These communications were made available to American workers from the inception of the work. The present section is concerned mainly with a description of methyl fluoroacetate, CHjF-COaMe, and of certain other derivatives of fluoroacetic acid. 

In Chapter rv we have described toxic fluorine compounds containing the POF grouping. Such compounds possessed quick knock-out action, and many of them were powerful myotics. Compounds of the fluoroacetate series are characterized by the CH2F- group. Many of them are highly toxic with delayed action, but are completely devoid of myotic activity. The action is, broadly speaking, that of a convulsant poison (but see p. 136). 

Methyl fluoroacetate was first prepared by Swarts in small yield by the action of silver or mercurous fluoride on methyl iodoacetate. The method is impracticable for large-scale work and therefore the preparation was reinvestigated in detail. Methyl chloroacetate was used in place of the expensive iodoacetate, and a variety of fluorinating agents was tried. It was found that fluorination could be effected by heating methyl chloroacetate in a rotating autoclave with potassium fluoride at 220° for 4 hr. Sodium fluoride, on the other hand, was almost without action. 

Other methods are available for the preparation of M.F.A. without the use of an autoclave, but it is doubtful whether they possess advantages over the autoclave method having regard to quality of product and yield. 

Methyl fluoroacetate (M.F.A.) is a liquid of b.p. 104° and f.p. ca. — 32° and is almost odourless. During a 10 min. exposure to a lethal concentration of the vapour, small animals did not ap-pear to be affected in any way. After exposure, no very obvious symptoms developed until some 30-60 min. later (depending upon the concentration). The symptoms then shown depended to some extent upon the species, but all animals suffered con-vulsions, from which a partial recovery was sometimes made. Finally, however, a recurrence of the convulsions would cause death. 

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