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Réactions de métallation régioflexibles des acides alkoxybenzoïques non protégés. Possibilités, limitations et mécanisme.

Abstract : Metalation reactions of mono methoxybenzoic acids at different positions by strong alkyllithium bases, bulky lithium amides and superbase (n-BuLi/t-BuOK) are described. Compared to others well-known ortho directing groups, the CO2H function has a moderate ortho-directing power. This feature is an advantage. Indeed, it is possible to modify the metalation site by changing the base and/or the experimental conditions. Moreover, the steps of protection and deprotection of the carboxylic acid group, wich are usually required, are thus avoided.
With alkyllithium bases, a prelithiation complex is formed (CIPE effect). Generally, the most stable complex is that formed between the carboxylate and the lithium base. Amide bases metalate the thermodynamically most acidic position (the inductive and resonance effects predominate) and the regioselectivity is generally different. The Lochmann-Schlosser superbases, which are less sensitive to steric hindrance, preferably deprotonate the ortho site of the methoxy function. An expeditive synthesis of lunularic acid is described.
The mechanism of the directed ortholithiation is discussed.
2-Fluoro- and 2-methoxybenzoic acids give aromatic nucleophilic substitution reactions (ipso-substitution) with organolithiums. Introducing a silicon atom in the C-6 position reduces the reactivity of the carboxylate toward the base. The first example of a brome-lithium exchange in the presence of heavy water is reported. An interpretation of this phenomenon is given.
Finally, the mechanism of the metalation of phenothiazine is re-examined. A careful analysis of results obtained by different authors allowed us to unravel the pathway of the metalation reaction of phenothiazine by n-BuLi. The reaction is shown not to yield a dilithio species as believed. Electrophiles such as benzamide and CO2 assist a second deprotonation.
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Submitted on : Thursday, October 19, 2006 - 5:39:49 PM
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Thi Huu Nguyen. Réactions de métallation régioflexibles des acides alkoxybenzoïques non protégés. Possibilités, limitations et mécanisme.. Matériaux. Université du Maine, 2006. Français. ⟨tel-00108157⟩

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