Fluoroacetamide and related compounds

Fluoroacetamide has also been prepared by heating a mixture of potassium fiuoride and chloroacetamide at 135° under reduced pressure when fiuoroacetamide and unchanged chloroacetamide distil over. The reaction can also be carried out in xylene solution at ordinary pressure, but the yield is only 55 per cent. However, the method has been improved lately, although the product still contains unchanged chloroacetamide.  

By distilling the amide with phosphoric oxide at ordinary pressure, fiuoromethyl cyanide was obtained as a colourless, mobile hquid. This compound had been obtained by Swarts, who claimed that it was necessary to distil the amide with 

The preparation of free fluoroacetic acid from methyl fluoroacetate via the barium salt is described on p. 121. An alternative and convenient method for preparing the free acid consists in treating fluoroacetamide with nitrous fumes, the pure acid being produced in 90 per cent yield. The two methods may be summarized thus  

It is noteworthy that the l.d. 50 by intravenous injection for fluoroacetic acid, methyl fluoroacetate and the amide are almost identical (0-25 mg./kg. for rabbits). 

The group C1-CH2-CH2-N occurs in the nitrogen mustards which are powerful vesicants, e.g. CH 3 N(CH2 CH2C1)2- It was decided therefore to introduce this group into the fluoroacetamide molecule in the hope of combining vesicant properties with the delayed convulsant action of the fluoroacetates. For this purpose N 2 hydroxyethylJluoroacetaniide (IV) was prepared by the action of monoethanolamine on methyl fluoroacetate and was readily converted into l 2 chloroethylfl uoroacetamide (V) by the action of thionyl chloride  

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