Rerouting Nucleophilic Substitution from the 4-Position to the 2- or 6-Position of 2,4-Dihalopyridines and 2,4,6-Trihalopyridines: The Solution to a Long-Standing Problem

2,4-Difluoro-, 2,4,6-trifluoro-, and 2,3,4,6-tetra(fluoro)pyridine undergo nucleophilic substitution preferentially if not exclusively at the 4-position. However, after the introduction of a trialkylsilyl group at C-3 or C-5, the halogen at the 6-(2-)position is displaced selectively. Bulky trialkylsilyl groups were found to suppress the nucleofugal mobility of neighboring halogen atoms. This synthetically valuable regiocontrol can also be realized with other halopyridines such as 2,4-dichloro- and 2,4,6-tri(chloro)pyridine. [on SciFinder (R)]


Published in:
Organic Letters, 7, 1, 127-129
Year:
2005
Keywords:
Note:
CAN 142:197829
27-16
Heterocyclic Compounds (One Hetero Atom)
Institute of Chemical Sciences and Engineering,Ecole Polytechnique Federale,Lausanne,Switz.
Journal
1523-7060
written in English.
302-01-2 (Hydrazine) Role: RCT (Reactant), RACT (Reactant or reagent) (nucleophilic substitution of di(halo)pyridine and dihalo(silyl)pyridine derivs. with hydrazine); 34941-90-7P (2,4-Difluoropyridine) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (nucleophilic substitution of di(halo)pyridine and dihalo(silyl)pyridine derivs. with hydrazine); 41404-63-1P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of (bromo)di(fluoro)pyridine using di(fluoro)(hydrazino)pyridine as synthetic intermediate); 837364-99-5 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of (fluoro)(silyl)pyridine by using regioselective, nucleophilic substitution of di(chloro)(silyl)pyridine with hydrazine as key synthetic step); 837365-02-3P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of (fluoro)(silyl)pyridine by using regioselective, nucleophilic substitution of di(chloro)(silyl)pyridine with hydrazine as key synthetic step); 123506-94-5P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of (fluoro)(silyl)pyridine by using regioselective, nucleophilic substitution of di(chloro)(silyl)pyridine with hydrazine as key synthetic step); 837364-94-0P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of 2,6-difluoro-4-(hydrazino)pyridine by regioselective, nucleophilic substitution of tri(fluoro)pyridine with hydrazine); 837364-87-1P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of 2-fluoro-4-(hydrazino)pyridine by regioselective, nucleophilic substitution of di(fluoro)pyridine with hydrazine); 837364-92-8P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of 4-fluoro-2-(hydrazino)pyridine by regioselective, nucleophilic substitution of difluoro(silyl)pyridine with hydrazine); 837365-00-1 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of di(chloro)pyridine by using regioselective, nucleophilic substitution of tri(chloro)(silyl)pyridine with hydrazine as key synthetic step); 837365-03-4P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of di(chloro)pyridine by using regioselective, nucleophilic substitution of tri(chloro)(silyl)pyridine with hydrazine as key synthetic step); 26452-80-2P (2,4-Dichloropyridine) Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of di(chloro)pyridine by using regioselective, nucleophilic substitution of tri(chloro)(silyl)pyridine with hydrazine as key synthetic step); 837364-96-2P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of di(fluoro)(hydrazino)(silyl)pyridine by regioselective, nucleophilic substitution of tri(fluoro)(triethylsilyl)pyridine with hydrazine); 3512-17-2 (2,4,6-Trifluoropyridine) Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of di(fluoro)(hydrazino)pyridine by regioselective, nucleophilic substitution of di(fluoro)(silyl)pyridine with hydrazine); 837364-95-1P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of di(fluoro)(hydrazino)pyridine by regioselective, nucleophilic substitution of tri(fluoro)(triethylsilyl)pyridine with hydrazine); 837364-98-4P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of di(fluoro)(hydrazino)pyridine using di(fluoro)(hydrazino)(silyl)pyridine as synthetic intermediate); 7790-99-0 (Iodine chloride (ICl) Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of di(fluoro)(iodo)pyridine by regioselective, nucleophilic substitution of di(fluoro)(silyl)pyridine with iodine chloride); 837364-97-3P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of di(fluoro)(iodo)pyridine by regioselective, nucleophilic substitution of di(fluoro)(silyl)pyridine with iodine chloride); 837364-88-2P; 837364-89-3P Role: RCT ( eactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of di(fluoro)(silyl)pyridine deriv. using di(fluoro)(iodo)pyridine as synthetic intermediate); 837364-93-9P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of di(fluoro)pyridinamine by regioselective, nucleophilic substitution of tri(fluoro)pyridine with amine); 259675-77-9 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of tri(fluoro)pyridine by using regioselective, nucleophilic substitution of tetra(fluoro)(silyl)pyridine with hydrazine as key synthetic step); 837365-01-2P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of tri(fluoro)pyridine by using regioselective, nucleophilic substitution of tetra(fluoro)(silyl)pyridine with hydrazine as key synthetic step); 837365-04-5P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of tri(fluoro)pyridine by using regioselective, nucleophilic substitution of tetra(fluoro)(silyl)pyridine with hydrazine as key synthetic step); 837364-90-6P; 837364-91-7P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (regioselective, nucleophilic substitution of di(halo)pyridine and di(fluoro)(trimethylsilyl)pyridine derivs. with hydrazine)
Laboratories:




 Record created 2006-03-03, last modified 2018-01-27


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