Related Experiment Video
Updated: Jan 11, 2026
05:57
Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function
Published on: April 26, 2024
816
Predicting the Stability of Base-mediated C─H Carboxylation Adducts Using Data Science Tools
Maike Eckhoff1,2, Shubham Deolka2, Aleria Garcia-Roca2
1TU Braunschweig, Institute of Physical and Theoretical Chemistry, Gauss Str 17, 38106, Braunschweig, Germany.
Angewandte Chemie (International Ed. in English)
|November 19, 2025
Summary
This study introduces a computational method to predict the stability of carbon dioxide (CO2) adducts in organic synthesis. The workflow successfully identified stable CO2 adducts, validated by experimental results for carbanions.
Area of Science:
- Organic Chemistry
- Computational Chemistry
- Chemical Thermodynamics
Background:
- Base-mediated C-H carboxylation offers a route to utilize carbon dioxide (CO2) as a C1 building block.
- The thermodynamic stability of CO2 adducts limits this reaction to highly reactive nucleophiles.
Purpose of the Study:
- To develop a predictive computational workflow for assessing the stability of CO2 adducts.
- To identify novel carbon-centered nucleophiles capable of forming stable CO2 adducts.
Main Methods:
- Integration of quantum chemistry calculations with statistical modeling to predict CO2 affinity.
- Calculation of negative Gibbs free reaction energy to quantify adduct stability.
- Experimental validation using carbanions in DMSO.
Main Results:
- A predictive workflow was established to assess CO2 adduct stability.
- Sixty novel carbon-centered nucleophiles were computationally screened.
- Experimental validation confirmed predictions for five carbanions, distinguishing between stable and unstable adducts.
- Two additional carbanions predicted to form stable adducts were experimentally examined.
Conclusions:
- The computational workflow accurately predicts the stability of CO2 adducts.
- This approach expands the scope of CO2 utilization in organic synthesis by identifying suitable nucleophiles.
- The findings facilitate the design of new carboxylation reactions.
Related Concept Videos
02:30Stability of Substituted Cyclohexanes
14.7K
This lesson discusses the stability of substituted cyclohexanes with a focus on energies of various conformers and the effect of 1,3-diaxial interactions.
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
14.7K
02:10Carbocations
13.3K
Carbocations are one of the reaction intermediates formed during several nucleophilic substitutions or elimination reactions. A carbocation is an electron-deficient species with the central carbon atom having six electrons and three bonded atoms. The central carbon in a carbocation is sp2 hybridized with trigonal planar geometry. It has an empty p orbital perpendicular to the plane of the structure that can accept electrons. Thus, carbocations act as strong electrophiles and may react with any...
13.3K
01:09Complexation Equilibria: Factors Influencing Stability of Complexes
774
In complexation reactions, metal cations are the electron pair acceptors, and the ligands are the electron pair donors. The stability of the metal complexes depends primarily on the complexing ability of the central metal ion and the nature of the ligands. Generally, the complexing ability of the metal ion depends on the size and charge of the ion. As the metal ion size increases, the stability of the metal complexes decreases, provided that the valency of the metal ion and the ligands remain...
774
01:10Factors Affecting α-Alkylation of Ketones: Choice of Base
3.5K
α-Alkylation of ketones is achieved in the presence of alkyl halides and a base. The reaction proceeds via the formation of an enolate ion followed by nucleophilic substitution. The choice of base employed is essential as it is the key factor in determining the reaction outcome.
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence,...
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence,...
3.5K
01:13Relative Reactivity of Carboxylic Acid Derivatives
3.6K
Carboxylic acid derivatives such as acid halides, anhydrides, esters, and amides undergo nucleophilic acyl substitution reactions with varying degrees of reactivity.
A key factor in assessing the reactivity of the acid derivatives is the basicity of the substituent or the leaving group. The lower the basicity of the leaving group, the higher the reactivity of the derivative. The basicity of the leaving group follows this order:
Halide ions < Acyloxy ions < Alkoxy ions < Amine ions
A key factor in assessing the reactivity of the acid derivatives is the basicity of the substituent or the leaving group. The lower the basicity of the leaving group, the higher the reactivity of the derivative. The basicity of the leaving group follows this order:
Halide ions < Acyloxy ions < Alkoxy ions < Amine ions
3.6K
01:41Reactions of Carboxylic Acids: Introduction
3.8K
Carboxylic acids possess an acidic –COOH functional group. The acidity can be attributed to the resonance stabilization of their conjugate base, wherein the negative charge is delocalized over both oxygen atoms.
3.8K