5-Ethoxy-3-(trichloromethyl)-1,2,4-oxadiazole

5-Ethoxy-3-(trichloromethyl)-1, 2, 4-oxadiazole (V) was synthesized to elucidate the chemistry involved in the preparation of the hitherto unreported alkoxy-1, 2, 4-oxadiazoles and to determine the effect of the isosteric replacement of sulfur by oxygen on antifungal activity. Heating the “amino-oxime” tautomer II of trichloroacetamidoxime with ethyl chloroformate furnished exclusively the O-acylated product III. The trans configuration of III accounts for its resistance to cyclize under a variety of conditions, in contrast to the general behaviour of acylated amidoximes. Pyrolysis of III at 160° yielded IV which exists in the keto form. Refluxing IV with ethyl iodide in the presence of silver oxide gave an isomeric mixture which was separated by v.p.c. to give V and VI. Compound V retained 60% of the overall activity of the corresponding sulfur analog.