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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.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|June 5, 2025
Summary
This study quantifies the electrophilic reactivity of para-quinone methides (pQMs) using kinetic data. Electrophilicity parameters (E) predict reaction outcomes with various nucleophiles, aiding in designing new pQM compounds.
Area of Science:
- Organic Chemistry
- Physical Chemistry
Background:
- Para-quinone methides (pQMs) are reactive intermediates crucial in organic synthesis.
- Understanding their electrophilic reactivity is key to controlling reaction pathways and outcomes.
Purpose of the Study:
- To determine the electrophilic reactivities of functionalized pQMs.
- To establish a predictive model for pQM reactions based on electrophilicity descriptors.
- To correlate these descriptors with quantum chemical calculations and steric factors.
Main Methods:
- Kinetic studies of pQM reactions with carbanions in DMSO at 20 °C.
- Photometric monitoring of reaction progress.
- Application of the Mayr-Patz equation to determine second-order rate constants (k2).
- Calculation of electrophilicity (E) parameters.
Main Results:
- Experimental second-order rate constants (k2) were evaluated using the Mayr-Patz equation.
- Electrophilicity parameters (E) were determined for various pQMs.
- The E parameters successfully predicted the reactivity scope with C-, H-, N-, O-, and S-centered nucleophiles.
- A linear correlation was found between E and a combination of methyl anion affinities (MAAs) and buried volumes (%Vbur).
Conclusions:
- Electrophilicity parameters (E) provide a reliable measure of pQM reactivity.
- MAAs and %Vbur are important factors influencing pQM reactivity, reflecting thermodynamic and steric effects, respectively.
- This knowledge facilitates the rational design of novel pQMs with tailored reactivity.
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