Creating structural manifolds from a common precursor: basicity gradient-driven isomerization of halopyridines
5-Chloro-2,3-difluoropyridine, an intermediate in the manufg. process of an industrial pesticide, can be hydrolyzed to 5-chloro-3-fluoro-2H-pyridinone and the latter converted into 2,5-dichloro-3-fluoropyridine, 2-bromo-5-chloro-3-fluoropyridine, 5-chloro-3-fluoro-2-iodopyridine and 3-chloro-5-fluoropyridine. Consecutive treatment of these four substrates with lithium diisopropylamide and carbon dioxide or lithium diisopropylamide and iodine affords the corresponding 4-pyridinecarboxylic acids and 4-iodopyridines, resp. Amide-promoted deprotonation of such 4-iodopyridines triggers an isomerization in which lithium and iodine change places. The resulting species can be trapped with carbon dioxide to give the acids I (X = Cl, Br, I) or neutralized to give the halopyridines II. The iodopyridines II (X = Cl, Br) can be converted into the acids III, the latter product leading also to the congeners III (X = I, H). The diiodopyridine II (X = I) provides an entry to the halopyridine II (X = H), which at the same time may act as the precursor to 3-chloro-5-fluoro-2,6-diiodo-4-pyridinecarboxylic acid, 5-chloro-3-fluoro-6-iodo-2-pyridinecarboxyic acid or 3-chloro-5-fluoro-2,6-pyridinecarboxylic acid. Finally, 5-chloro-3-fluoro-2-pyridinecarboxylic acid is accessible from either 2-bromo-5-chloro-3-fluoropyridine or 5-chloro-3-fluoro-2-iodopyridineone. [on SciFinder (R)]
WOS:000180032700010
2002
24
4174
4180
CAN 138:321107 27-16 Heterocyclic Compounds (One Hetero Atom) Institut de Chimie moleculaire et biologique,Ecole Polytechnique Federale,Lausanne,Switz. Journal 1434-193X written in English. 514798-04-0P; 514798-05-1P; 514798-06-2P; 514798-08-4P; 514798-09-5P; 514798-10-8P; 514798-11-9P; 514798-17-5P; 514798-19-7P; 514798-20-0P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (isomerization of intermediate lithiated halopyridines and derivatization to polyhalopyridines and pyridinecarboxylic acids); 128073-01-8P; 207994-08-9P; 514798-00-6P; 514798-01-7P; 514798-02-8P; 514798-03-9P; 514798-07-3P; 514798-12-0P; 514798-13-1P; 514798-14-2P; 514798-15-3P; 514798-16-4P; 514798-18-6P; 514798-21-1P; 514798-22-2P Role: SPN (Synthetic preparation), PREP (Preparation) (isomerization of intermediate lithiated halopyridines and derivatization to polyhalopyridines and pyridinecarboxylic acids); 514797-98-9P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of chlorofluoroiodopyridine via halogen/metal interconversion and subsequent addn. of iodine); 514797-99-0P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of chlorofluoropyridine via reductive dehalogenation of bromochlorofluoropyridine); 89402-43-7 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of dichlorofluoropyridine and bromochlorofluoropyridine via hydrolysis of chlorodifluoropyridine to chlorofluoropyridinone and subsequent treatment with corresponding phosphorous trihalide); 103999-77-5P; 514797-96-7P; 514797-97-8P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of dichlorofluoropyridine and bromochlorofluoropyridine via hydrolysis of chlorodifluoropyridine to chlorofluoropyridinone and subsequent treatment with corresponding phosphorous trihalide)
REVIEWED
EPFL