- PROCESS FOR PRODUCING TOLUENE DERIVATIVES
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A toluene derivative of the general formula (2) wherein R denotes a fluorine atom, a chlorine atom, an alkoxy group, or an alkylthio group, and X denotes a halogen atom, is prepared by reacting metallic magnesium with a 2-chloro-6-substituted toluene derivative of the general formula (1) wherein R is as defined above, in an ethereal solvent in the presence of a lower alkyl bromide.
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- Directed lithiation of unprotected benzoic acids
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Benzoic acid gives the ortho-lithiated species 1 under standard conditions (s-BuLi-TMEDA-THF, -90 deg C).Reaction of 1 at -78 deg C with either methyl iodide, dimethyl disulfide, hexachloroethane, or 1,2-dibromotetrachloroethane gives the ortho-substituted product.Intramolecular competition between the carboxylic acid and methoxy, chloro, fluoro, or diethylamido functions in ortho- and -para-substituted benzoic acids establishes the carboxylic acid group to be of intermediate capacity in directing metallation.Complimentarity of directing effects is observed with the chloro and fluoro groups in the meta-substituted benzoic acid but not with the methoxy and trifluoromethyl groups.Electrophile introduction into meta- and para-lithiated benzoates occurs with equal efficacy and comparable scope.The 2,4-dihalogenobenzoic acids undergo hydrogen/metal exchange at the position flanked by both halogen substituents. 2,2-Difluoro-1,3-benzodioxole-4-carboxylic acid undergoes lithiation adjacent to the oxygen atom.By use of such methods, routes to benzoic acids contiguously tri- and tetra-substituted with a variety of functionalities have been developed.
- Bennetau, Bernard,Mortier, Jacques,Moyroud, Joel,Guesnet, Jean-Luc
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p. 1265 - 1272
(2007/10/02)
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