The combined role of catalysis and solvent effects on the biginelli reaction: improving efficiency and sustainability

James H Clark; Duncan J Macquarrie; James Sherwood

doi:10.1002/chem.201204396

The combined role of catalysis and solvent effects on the biginelli reaction: improving efficiency and sustainability

James H Clark, Duncan J Macquarrie, James Sherwood

Chemistry

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Abstract

The traditional Biginelli reaction is a three-component condensation between urea, benzaldehyde and an acetoacetate ester to give a dihydropyrimidinone. An investigation into catalytic and solvent effects has returned the conclusion that the diketo-enol tautomerisation equilibrium of the dicarbonyl reactant dictates the yield of the reaction. Whereas the solvent is responsible for the tautomerisation equilibrium position, the catalyst only serves to eliminate kinetic control from the reaction. Generally, to preserve reaction efficiency and improve sustainability, bio-derivable p-cymene was found to be a useful solvent. The metal-enolate intermediate that results from the application of a Lewis acidic catalyst often cited as promoting the reaction appears to hinder the reaction. In this instance, a Brønsted acidic solvent can be used to return greater reactivity to the dicarbonyl reagent.

Original language	English
Pages (from-to)	5174-5182
Journal	Chemistry - A European Journal
Volume	19
Issue number	16
DOIs	https://doi.org/10.1002/chem.201204396
Publication status	Published - 15 Apr 2013

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abstract = "The traditional Biginelli reaction is a three-component condensation between urea, benzaldehyde and an acetoacetate ester to give a dihydropyrimidinone. An investigation into catalytic and solvent effects has returned the conclusion that the diketo-enol tautomerisation equilibrium of the dicarbonyl reactant dictates the yield of the reaction. Whereas the solvent is responsible for the tautomerisation equilibrium position, the catalyst only serves to eliminate kinetic control from the reaction. Generally, to preserve reaction efficiency and improve sustainability, bio-derivable p-cymene was found to be a useful solvent. The metal-enolate intermediate that results from the application of a Lewis acidic catalyst often cited as promoting the reaction appears to hinder the reaction. In this instance, a Br{\o}nsted acidic solvent can be used to return greater reactivity to the dicarbonyl reagent.",

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The combined role of catalysis and solvent effects on the biginelli reaction: improving efficiency and sustainability

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