By ERNST D . BERGMANN, S. COHEN, and I. SHAHAK. Ethyl bromo(or ch1oro)acetate condenses with ethyl fluoroacetate, and ethyl chlorofluoroacetate with ethyl acetate, in Reformatzky-type reactions to give ethyl yand a-fluoroacetoacetate, respectively. The enol from ethyl fluoroacetate condensed with acetyl chloride, benzoyl chloride, ethyl trifluoroacetate, and ethyl pentafluoropropionate to give the P-keto-esters. Fluoroacetone and acetic anhydride under catalysis by boron trifluoride give a P-diketone, probably 3-fl~oropentane-2~4-dione.By condensation of the available P-diketo-compounds with S-ethylisothiouronium bromide or urea, acetamidine, and guanidine several fluorinecontaining pyrimidines have been prepared. Their ultraviolet and infrared spectra are discussed.THE purpose of the present study was to prepare fluoropyrimidines, which we expected to be antagonists of the corresponding hydrogen compounds. This expectation, which was based on the powerful antimetabolite properties of, e.g., fluorophenylalanines and 5-fluorotryptophan, has meanwhile been borne out to some extent for 5-fluorouracil, 5-fluoro-orotic acid, and 5-fluoroadenine. are known, but their preparation is not always easy. Ethyl y-fluoroacetoacetate, for example, has been prepared by Szinai2 from fluoroacetyl chloride and ethyl dihydropyranyl malonate, and from ethyl t-butyl malonate (Fraser et d 2 ) , but both methods are cumbersome, and the product requires lengthy p~rification.~ It has now been found that ethyl y-fluoroacetoacetate is easily accessible by reaction between ethyl bromoacetate (or better chloroacetate), ethyl fluoroacetate, and activated magnesium, though in +40% yield. The reaction has been extended to the preparation of ethyl a-methyl-and (not quite pure) a-ethyl-y-fluoroacetoacetate from ethyl a-bromo-propionate and -butyrate, respectively. The analogous reaction between ethyl bromofluoroacetate (which has already been used for Reformatzky reactions with aldehydes and ketones 4), zinc, and ethyl acetate to give ethyl a-fluoroacetoacetate was made impracticable by the difficulty of preparing the brominated ester and its in~tability.~ However, the analogous ethyl chlorofluoroacetate, which is accessible both by chlorination of ethyl fluoroacetate and by hydrolysis of the ethanol adduct of chlorotrifluoroethylene,~ gives the same Refomatzky-type reaction as the bromo-analogue.* Thus, ethyl a-fluoroacetoacetate was obtained from ethyl chlorofluoroacetate, an excess of ethyl acetate, and activated magnesium in 20% yield. As a by-product, ethyl y-chloro-ay-difluoroacetoacetate was formed. The latter was the principal product , when ethereal ethyl chlorofluoroacetate was refluxed with activated magnesium. Acceptable yields of ethyl a-fluoroacetoacetate can also be obtained by the reaction between the enol of ethyl fluoroacetate (prepared with sodium