14C-labeling of bromobutide, 2-bromo-3,3-dimethyl-N-(α,α-dimethylbenzyl)butyramide

Bromobutide, a novel herbicide, was labeled with carbon-14 independently at the carbonyl group and the phenyl ring for use in metabolic studies. 14C-Carbonation of neopentylmagnesium chloride gave 3,3-dimethyl[1-14C]butyric acid quantitatively. Chlorination of 3,3-dimethyl[1-14C]butyric acid with thionyl chloride followed by α-bromination with bromine yielded 2-bromo-3,3-dimethyl[1-14C]butyryl halide, which was subsequently condensed with α,α-dimethybenzylamine to afford [carbonyl-14C]bromobutide. The overall yield of [carbonyl-14C]bromobutide was 76% from barium [14C]carbonate. Similarly, condensation of α,α-dimenthyl[phenyl-14C]benzylamine, which was prepared from α-methyl[phenyl-U-14C]styrene in three steps, with 2-bromo-3,3-dimethylbutyryl halide gave [phenyl-14C]bromobutide in 67% yield after purification. The specific activities of [carbonyl-14C]bromobutide and [phenyl-14C]bromobutide were 1.38 and 0.781 GBq/mmol (37.2 and 21.1 mCi/mmol), respectively. (author)