2,4-Difluoropyridine, 2,4-dichloropyridine, 2,4,6-trifluoropyridine, 2,4,6-trichloropyridine and 2,3,4,6-tetrafluoropyridine react with std. nucleophiles exclusively at the 4-position under halogen displacement. However, the regioselectivity can be completely reversed if a trialkylsilyl group is introduced in the 5-position of the 2,4-dihalopyridines or in the 3-position of the 2,4,6-trihalopyridines or 2,3,4,6-tetrahalopyridine. Then only the halogen most remote from the bulky silyl unit (at the 2-position in the case of the 2,4-halopyridines, at the 6-position with the other substrates) gets involved in the exchange process. After removal of the silyl protective group the nucleophile is invariably found to occupy the nitrogen-neighboring position. [on SciFinder (R)]
Title
Regiochemically flexible substitutions of di-, tri-, and tetrahalopyridines: the trialkylsilyl trick
Published in
Journal of Organic Chemistry
Volume
70
Issue
7
Pages
2494-2502
Date
2005
Note
CAN 142:392259 27-16 Heterocyclic Compounds (One Hetero Atom) Institute of Chemical Sciences and Engineering (ISIC-BCh),Ecole Polytechnique Federale,Lausanne,Switz. Journal 0022-3263 written in English. 2402-78-0; 3512-13-8 (2,3,4,6-Tetrafluoropyridine); 3512-17-2 (2,4,6-Trifluoropyridine); 53939-30-3 (5-Bromo-2-chloropyridine); 98027-84-0 (2,6-Dichloro-4-iodopyridine) Role: RCT (Reactant), RACT (Reactant or reagent) (regiochem. flexible substitutions of di-, tri-, and tetrahalopyridines); 16063-69-7P (2,4,6-Trichloropyridine); 26452-80-2P (2,4-Dichloropyridine); 34941-90-7P (2,4-Difluoropyridine); 41404-63-1P (2-Bromo-4,6-difluoropyridine); 259675-77-9P (2,3,4,6-Tetrafluoro-5-trimethylsilylpyridine); 837364-88-2P (2,4-Difluoro-3-iodopyridine); 837364-89-3P (2,4-Difluoro-5-iodopyridine); 837364-90-6P (2,4-Difluoro-5-trimethylsilylpyridine); 837364-91-7P; 837364-95-1P (2,4,6-Trifluoro-5-triethylsilylpyridine); 837364-96-2P (4,6-Difluoro-2-hydrazino-5-triethylsilylpyridine); 837364-97-3P (2,4-Difluoro-3-triethylsilylpyridine); 837364-98-4P (4,6-Difluoro-2-hydrazinopyridine); 837364-99-5P (2,4-Dichloro-5-triethylsilylpyridine); 837365-00-1P (2,4,6-Trichloro-3-trimethylsilylpyridine); 837365-03-4P (2,4-Dichloro-6-hydrazinopyridine); 849937-81-1P (2,4-Difluoro-5-triethylsilylpyridine); 849937-85-5P (2,4,6-Trifluoro-5-trimethylsilylpyridine); 849937-92-4P (2,3,6-Trifluoro-4-hydrazinopyridine); 849937-94-6P (2,3,4,6-Tetrafluoro-5-triethylsilylpyridine); 849937-96-8P (5-Bromo-2,4-dichloropyridine); 849937-97-9P (4-Chloro-2-dimethylamino-5-triethylsilylpyridine); 849937-98-0P (2,4,6-Trichloro-3-triethylsilylpyridine) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (regiochem. flexible substitutions of di-, tri-, and tetrahalopyridines); 3512-18-3P (2,3,6-Trifluoropyridine); 59047-70-0P (2-Chloro-4-dimethylaminopyridine); 123506-94-5P (4-Chloro-3-triethylsilylpyridine); 175461-34-4P (2,6-Dichloro-4-dimethylaminopyridine); 735255-56-8P (4-Chloro-2-dimethylaminopyridine); 837364-87-1P (2-Fluoro-4-hydrazinopyridine); 837364-92-8P (4-Fluoro-2-hydrazino-pyridine); 837364-93-9P (4-Ethoxy-2,6-difluoropyridine); 837364-94-0P (2,6-Difluoro-4-hydrazinopyridine); 837365-04-5P (2,4,5-Trifluoropyridine); 849937-80-0P; 849937-82-2P (2-Dimethylamino-4-fluoro-5-triethylsilylpyridine); 849937-84-4P (4-Dimethylamino-2,6-difluoropyridine); 849937-87-7P (2-Ethoxy-4,6-difluoro-5-trimethylsilylpyridine); 849937-88-8P (6-Bromo-2,4-difluoro-3-triethylsilylpyridine); 849937-89-9P (4,6-Difluoropyridine-2-carboxylic acid); 849937-90-2P (2,4-Difluoropyridine-3-carboxylic acid); 849937-91-3P (2,4-Difluoropyridine-5-carboxylic acid); 849937-93-5P (4-Bromo-2,3,6-trifluoropyridine); 849937-95-7P (2-Bromo-3,4,6-trifluoro-5-triethylsilylpyridine); 849937-99-1P (2,4-Dichloro-6-dimethylaminopyridine); 851342-05-7P; 851345-12-5P (2-Dimethylamino-4,6-difluoro-5-triethylsilylpyridine) Role: SPN (Synthetic preparation), PREP (Preparation) (regiochem. flexible substitutions of di-, tri-, and tetrahalopyridines)
Record creation date
2006-03-03
