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Updated: Sep 19, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Reactivity of δ-Functionalized Para-Quinone Methides in Nucleophilic Addition Reactions
Christoph Gross1, Andreas Eitzinger1,2, Peter Mayer1
1Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, München, Germany.
Abstract:
The electrophilic reactivities of para-quinone methides (pQMs) with functional groups (FG) at the exocyclic polarized carbon-carbon double bond were determined by photometrically monitoring the kinetics of their reactions with carbanions in dimethyl sulfoxide (DMSO) at 20 °C. The experimental second-order rate constants k2 were evaluated by the Mayr-Patz equation, that is, the linear free energy relationship lg k2 = sN(N + E), which was leveraged to determine the electrophilicity descriptors E of the pQMs. These electrophilicity parameters E were subsequently used to successfully predict the scope of the pQM reactions with C-, H-, N-, O-, and S-centered nucleophiles. Moreover, the electrophilicity parameters E correlate linearly with a linear combination of quantum-chemically calculated methyl anion affinities (MAAs) and buried volumes (%Vbur). While MAA values mainly reflect the thermodynamic driving force of the carbon-carbon bond formation, %Vbur values take account of the variable steric effects of substituents at the electrophilic δ-position of the pQMs. Knowledge of MAA and %Vbur thus enables chemists to tailor novel pQMs with predictable reactivity properties.
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