Proton mobility in 2-substituted 1,3-dichlorobenzenes: "ortho" or "meta" metalation?
2006
Abstract
Nine 1,3-dichlorobenzene congeners were selected as model compds. to assess the relative rates of proton abstraction from 4- and 5-positions ("ortho" vs. "meta" metalation). Using lithium 2,2,6,6-tetramethylpiperidide as the basic reagent, the chlorine-adjacent 4-position underwent metalation exclusively. In contrast, attack at the chlorine-remote 5-position became significant even in the case of moderately sized 2-substituents (such as dimethylamino or ethyl) when sec-butyllithium was employed. The "ortho/para" (4-/5-) ratios ranged from 80:20 to 65:35. The more pronounced "meta-orienting" effect of silicon as opposed to carbon substituents can be attributed to dissimilarities in the pi polarization of the arom. ring. [on SciFinder (R)]
Details
Title
Proton mobility in 2-substituted 1,3-dichlorobenzenes: "ortho" or "meta" metalation?
Author(s)
Schlosser, Manfred ; Heiss, Christophe ; Marzi, Elena ; Scopelliti, Rosario
Published in
European Journal of Organic Chemistry
Issue
19
Pages
4398-4404
Date
2006
ISSN
1434-193X
Keywords
Note
CAN 146:27345
22-4
Physical Organic Chemistry
Institute of Chemical Sciences and Engineering,Ecole Polytechnique Federale, BCh,Lausanne,Switz.
Journal
written in English.
3032-81-3 (1,3-Dichloro-5-iodobenzene) Role: RCT (Reactant), RACT (Reactant or reagent) (alkylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 915144-98-8P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (bromination; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 697-88-1 (4-Bromo-2,6-dichloroaniline) Role: RCT (Reactant), RACT (Reactant or reagent) (carbamoylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 811720-20-4P (1,2-Dibromo-3,4,5-trichlorobenzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (debromination; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 915145-00-5P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (decarboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 541-73-1 (1,3-Dichlorobenzene) Role: RCT (Reactant), RACT (Reactant or reagent) (ethylation, iodination, carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 811720-26-0P (1,5-Dibromo-2,3,4-trichlorobenzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (halogen migration; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 598-30-1 (sec-Butyllithium); 38227-87-1 (Lithium 2,2,6,6-tetramethylpiperidide) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RGT (Reagent), PROC (Process), RACT (Reactant or reagent) (lithiation agent; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 4111-54-0 (Lithium diisopropylamide) Role: RGT (Reagent), RACT (Reactant or reagent) (lithiation agent; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 56961-05-8 (2,6-Dichloro-N,N-dimethylaniline) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RCT (Reactant), PROC (Process), RACT (Reactant or reagent) (lithiation/carboxylation and bromination; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 87-61-6 (1,2,3-Trichlorobenzene) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RCT (Reactant), PROC (Process), RACT (Reactant or reagent) (lithiation/carboxylation and silylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 118-69-4 (2,6-Dichlorotoluene); 1984-65-2 (2,6-Dichloroanisole); 2268-05-5 (1,3-Dichloro-2-fluorobenzene); 56700-68-6 (tert-Butyl (2,6-dichlorophenyl)carbamate) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RCT (Reactant), PROC (Process), RACT (Reactant or reagent) (lithiation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 33407-02-2P ((2,6-Dichlorophenyl)ethane); 104359-35-5P (1,3-Dichloro-2-(trifluoromethyl)benzene); 915144-96-6P ((2,6-Dichlorophenoxy)triethylsilane) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), PROC (Process), RACT (Reactant or reagent) (lithiation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 95-50-1 (1,2-Dichlorobenzene); 19240-91-6 (4-Bromo-2,6-dichloroanisole) Role: RCT (Reactant), RACT (Re ctant or reagent) (lithiation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 21928-51-8P (5-Bromo-1,2,3-trichlorobenzene); 915145-01-6P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (lithiation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 177167-52-1P (2,6-Dichloro-4-iodotoluene); 915145-03-8P (1,3-Dichloro-2-ethyl-5-iodobenzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (metalation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 994-30-9 (Chlorotriethylsilane) Role: RCT (Reactant), RACT (Reactant or reagent) (silylation of phenol; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 87-65-0 (2,6-Dichlorophenol) Role: RCT (Reactant), RACT (Reactant or reagent) (silylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 915144-97-7P (Trimethyl(2,3,4-trichlorophenyl)silane) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (silylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 3336-41-2P (3,5-Dichloro-4-hydroxybenzoic acid); 83277-23-0P (2,4-Dichloro-3-methylbenzoic acid) Role: BYP (Byproduct), PREP (Preparation) (substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 6575-24-2 ((2,6-Dichlorophenyl)acetic acid) Role: RCT (Reactant), RACT (Reactant or reagent) (substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 915144-99-9P (4-Bromo-2,6-dichloro-N,N-dimethylaniline) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 50-30-6P (2,6-Dichlorobenzoic acid); 50-45-3P (2,3-Dichlorobenzoic acid); 50-75-9P (2,3,4-Trichlorobenzoic acid); 51-39-8P (3,4,5-Trichlorobenzoic acid); 37908-97-7P (3,5-Dichloro-4-methoxybenzoic acid); 39652-34-1P (3,5-Dichloro-4-methylbenzoic acid); 72228-74-1P (3,5-Dichloro-4-(dimethylamino)benzoic acid); 91658-93-4P (2,4-Dichloro-3-hydroxybenzoic acid); 115382-33-7P (2,4-Dichloro-3-methoxybenzoic acid); 161957-55-7P (3-Chloro-2-fluorobenzoic acid); 246161-04-6P (2,4-Dichloro-3-(dimethylamino)benzoic acid); 857061-43-9P (3-Chloro-2-(trifluoromethyl)benzoic acid); 871254-84-1P (2,4-Dichloro-3-(trifluoromethyl)benzoic acid); 915145-02-7P; 915145-04-9P (3,5-Dichloro-4-ethylbenzoic acid); 915145-05-0P (2,4-Dichloro-3-fluorobenzoic acid); 915145-06-1P (3-(tert-Butoxycarbonylamino)-2,4-dichlorobenzoic acid); 915145-07-2P (2,4-Dichloro-3-ethylbenzoic acid) Role: SPN (Synthetic preparation), PREP (Preparation) (substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 19230-28-5P (1,3-Dichloro-2-iodobenzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (trifluoromethylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes)
22-4
Physical Organic Chemistry
Institute of Chemical Sciences and Engineering,Ecole Polytechnique Federale, BCh,Lausanne,Switz.
Journal
written in English.
3032-81-3 (1,3-Dichloro-5-iodobenzene) Role: RCT (Reactant), RACT (Reactant or reagent) (alkylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 915144-98-8P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (bromination; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 697-88-1 (4-Bromo-2,6-dichloroaniline) Role: RCT (Reactant), RACT (Reactant or reagent) (carbamoylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 811720-20-4P (1,2-Dibromo-3,4,5-trichlorobenzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (debromination; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 915145-00-5P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (decarboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 541-73-1 (1,3-Dichlorobenzene) Role: RCT (Reactant), RACT (Reactant or reagent) (ethylation, iodination, carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 811720-26-0P (1,5-Dibromo-2,3,4-trichlorobenzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (halogen migration; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 598-30-1 (sec-Butyllithium); 38227-87-1 (Lithium 2,2,6,6-tetramethylpiperidide) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RGT (Reagent), PROC (Process), RACT (Reactant or reagent) (lithiation agent; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 4111-54-0 (Lithium diisopropylamide) Role: RGT (Reagent), RACT (Reactant or reagent) (lithiation agent; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 56961-05-8 (2,6-Dichloro-N,N-dimethylaniline) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RCT (Reactant), PROC (Process), RACT (Reactant or reagent) (lithiation/carboxylation and bromination; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 87-61-6 (1,2,3-Trichlorobenzene) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RCT (Reactant), PROC (Process), RACT (Reactant or reagent) (lithiation/carboxylation and silylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 118-69-4 (2,6-Dichlorotoluene); 1984-65-2 (2,6-Dichloroanisole); 2268-05-5 (1,3-Dichloro-2-fluorobenzene); 56700-68-6 (tert-Butyl (2,6-dichlorophenyl)carbamate) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RCT (Reactant), PROC (Process), RACT (Reactant or reagent) (lithiation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 33407-02-2P ((2,6-Dichlorophenyl)ethane); 104359-35-5P (1,3-Dichloro-2-(trifluoromethyl)benzene); 915144-96-6P ((2,6-Dichlorophenoxy)triethylsilane) Role: CPS (Chemical process), PEP (Physical, engineering or chemical process), RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), PROC (Process), RACT (Reactant or reagent) (lithiation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 95-50-1 (1,2-Dichlorobenzene); 19240-91-6 (4-Bromo-2,6-dichloroanisole) Role: RCT (Reactant), RACT (Re ctant or reagent) (lithiation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 21928-51-8P (5-Bromo-1,2,3-trichlorobenzene); 915145-01-6P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (lithiation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 177167-52-1P (2,6-Dichloro-4-iodotoluene); 915145-03-8P (1,3-Dichloro-2-ethyl-5-iodobenzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (metalation/carboxylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 994-30-9 (Chlorotriethylsilane) Role: RCT (Reactant), RACT (Reactant or reagent) (silylation of phenol; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 87-65-0 (2,6-Dichlorophenol) Role: RCT (Reactant), RACT (Reactant or reagent) (silylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 915144-97-7P (Trimethyl(2,3,4-trichlorophenyl)silane) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (silylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 3336-41-2P (3,5-Dichloro-4-hydroxybenzoic acid); 83277-23-0P (2,4-Dichloro-3-methylbenzoic acid) Role: BYP (Byproduct), PREP (Preparation) (substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 6575-24-2 ((2,6-Dichlorophenyl)acetic acid) Role: RCT (Reactant), RACT (Reactant or reagent) (substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 915144-99-9P (4-Bromo-2,6-dichloro-N,N-dimethylaniline) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 50-30-6P (2,6-Dichlorobenzoic acid); 50-45-3P (2,3-Dichlorobenzoic acid); 50-75-9P (2,3,4-Trichlorobenzoic acid); 51-39-8P (3,4,5-Trichlorobenzoic acid); 37908-97-7P (3,5-Dichloro-4-methoxybenzoic acid); 39652-34-1P (3,5-Dichloro-4-methylbenzoic acid); 72228-74-1P (3,5-Dichloro-4-(dimethylamino)benzoic acid); 91658-93-4P (2,4-Dichloro-3-hydroxybenzoic acid); 115382-33-7P (2,4-Dichloro-3-methoxybenzoic acid); 161957-55-7P (3-Chloro-2-fluorobenzoic acid); 246161-04-6P (2,4-Dichloro-3-(dimethylamino)benzoic acid); 857061-43-9P (3-Chloro-2-(trifluoromethyl)benzoic acid); 871254-84-1P (2,4-Dichloro-3-(trifluoromethyl)benzoic acid); 915145-02-7P; 915145-04-9P (3,5-Dichloro-4-ethylbenzoic acid); 915145-05-0P (2,4-Dichloro-3-fluorobenzoic acid); 915145-06-1P (3-(tert-Butoxycarbonylamino)-2,4-dichlorobenzoic acid); 915145-07-2P (2,4-Dichloro-3-ethylbenzoic acid) Role: SPN (Synthetic preparation), PREP (Preparation) (substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes); 19230-28-5P (1,3-Dichloro-2-iodobenzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (trifluoromethylation; substituent effect on regiochem. of lithiation/carboxylation sequence of variably 2-substituted 1,3-dichlorobenzenes)
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DAR: 9408
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Record creation date
2007-03-07