Fluorocarboxylic acids and derivatives containing an oxygen atom as a chain member

In view of the strong evidence for the yff-oxidation of u-fluoro-carboxylic acids (p. 151) in vivo and for the inhibition of/ -oxida-tion when such compounds were blocked in the a- and in the / -position (p. 157), it was decided to investigate the effect of introducing an oxygen atom as a chain member at some appropriate point. For this purpose eleven compounds were synthesized and examined pharmacologically.  

The formation of the bromoethoxycarbinol was unexpected, as there seems to be no previous record in the literature of the substitution of one hsdogen for another by a Grignard reagent. Even with a deficiency of the reagent, the only product whi h could again be isolated was the bromoethoxycarbinol. Hie replacement of an unreactive fiuorine atom by the more reactive bromine is worthy of further investigation. 

The reduction of 2-2 -fluoroethoxyethyl cyanide, using Raney nickel and hydrogen, was examined under a variety of conditions. Defluorination readily took place, but finally conditions were found which permitted the conversion of CN to CHj-NHg without the removal of the fluorine atom, giving 3-2 -fluoro-ethoxypropylamine as a stable distillable liquid. 

Ethyl 2-fluoroethoxyacetate, F-[CHJj O CHj COjEt, could not be prepared by the action of ethyl diazoacetate on pure redistilled 2-fluoroethyl alcohol, and the addition of a small qumi-iity of concentrated hydrochloric acid had no effect, which is rather surprising in view of the known catalytic action of acids on the decomposition of the diazoacetic ester. However, fluoroethyl alcohol which had not been specially dried reacted immediately with ethyl diazoacetate with a vigorous evolution of nitrogen and the simultaneous disappearance of the yellow colour of the diazo ester. 

The reaction between 2-fluoroethyl alcohol and ethyl chloro-formate at 100° for 10 hr. gave pure ethyl 2-fluoroethyl carbonate, F [CHjlg O COjEt. 

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Fluorocarboxylic Acids and Derivatives containing an Oxygen Atom as a Chain Member... 

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