THE SYNTHESIS OF [U-C-14-PHENYL] LS-840606, AN AGRICULTURAL FUNGICIDE

2,2',4'-Trichloro-[ring U-C-14]acetophenone 3 was the key intermediate of this synthesis patterned after the industrial route. An unexpected poor yield was observed during the preparation of 3 by the Friedel-Cr afts reaction of chloroacetyl chloride with 1,3-dichloro-[U-C-14]benze ne 10, possibly the result of an isotope effect although this poor yie ld might be explained by other factors. Two routes were checked for th e preparation of 1,3-dichloro-[U-C-14]benzene 10. The action of CCl4 w ith 1,3-dinitro-[U-C-14]benzene at 280 degrees C was entailed with exp losions. A safer route started from [U-C-14]aniline via 2,4-dichloro-[ ring U-C-14]acetanilide. Friedel-Crafts reaction of 10 with acetyl chl oride gave rise in 52% yield to 2',4'-dichloro-[ring U-C-14]acetopheno ne 16 which was brominated to 2-bromo-2',4'-dichloro-[ring U-C-14]acet ophenone 17;17 was condensed with 2,2-(ethylenedioxy)ethylmagnesium br omide to compound 18;18 was condensed with 1,2,4-triazole to 5 then su ccessively treated with HCl:water:dioxane and 2,2,2-trifluoroethanol/H Cl. Separation of the two diastereomers by medium pressure liquid chro matography. 7% overall radioactive yield from [U-C-14]aniline. Radioch emical purity 99%.