The synthesis of [U-14C phenyl] LS 840606, an agricultural fungicide

Article abstract of DOI:10.1002/jlcr.2580361203

2,2',4'-Trichloro-[ring U-¹⁴C]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-Crafts reaction of chloroacelyl chloride with 1,3-dichloro-[U-¹⁴C]benzene 10, possibly the result of an isotope effect although this poor yield might be explained by other factors. Two routes ware checked for the preparation of 1,3-dichloro-[U-¹⁴C]benzene 10. The action of CCl₄ with 1,3-dinitro-[U-¹⁴C]benzene at 280°C was entailed with explosions. A safer route started from [U-¹⁴C]aniline via 2,4-dichloro-[ring U-¹⁴C]acetanilide, Friedel-Crafts reaction of 10 with acetyl chloride gave rise in 52% yield to 2',4'-dichloro-[ring U-¹⁴C]acetophenone 16 which was brominated to 2-bromo-2',4'-dichloro-[ring U-¹⁴C]acetophenone 17; 17 was condensed with 2,2-(ethylenedioxy)ethylmagnesium bromide to compound 18; 18 was condensed with 1,2,4-triazole to 5 then successively treated with HCl:water:dioxane and 2,2,2-trifluaroethanol/HCl. Separation of the two diastereomers by medium pressure liquid chromatography. 7% overall radioactive yield from [U-¹⁴C]aniline. Radiochemical purity 99%.