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The synthesis of [U‐ 14 C phenyl] LS 840606, an agricultural fungicide
Author(s) -
Madegard G.,
Mestre P.,
Raimond P.,
Noël JP.
Publication year - 1995
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580361203
Subject(s) - chemistry , acetophenone , aniline , yield (engineering) , acetanilide , medicinal chemistry , benzene , ring (chemistry) , acetyl chloride , chloroacetyl chloride , chloride , phenylmagnesium bromide , bromide , friedel–crafts reaction , organic chemistry , nuclear chemistry , catalysis , reagent , materials science , metallurgy
2,2′4′‐Trichloro‐[ring U‐ 14 C]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 chloroacetyl chloride with 1,3‐dichloro‐[U‐ 14 C]benzene 10 , possibly the result of an isotope effect although this poor yield might be explained by other factors. Two routes were checked for the preparation of 1,3‐dichloro‐[U‐ 14 C]benzene 10 . The action of CCL 4 with 1,3‐dinitro‐[U‐ 14 C]benzene at 280°C was entailed with explosions. A safer route started from [U‐ 14 C]aniline via 2,4‐dichloro‐[ring U‐ 14 C]acetanilide. Friedel‐Crafts reaction of 10 with acetyl chloride gave rise in 52% yield to 2′,4′‐dichloro‐[ring U‐ 14 C]acetophenone 16 which was brominated to 2‐bromo‐2′,4′‐dichloro‐[ring U‐ 14 C]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‐trifluoroethanol/HCl. Separation of the two diastereomers by medium pressure liquid chromatography. 7% overall radioactive yield from [U‐ 14 C]aniline. Radiochemical purity 99%.