Intrinsic nucleofugality scale within the framework of density functional reactivity theory

Area of Science:

• Physical Organic Chemistry
• Computational Chemistry
• Quantum Chemistry

Background:

• Leaving group ability is crucial for understanding substitution and elimination reaction mechanisms.
• Traditional assessments of leaving group quality often rely on empirical trends and experimental data.
• Conceptual Density Functional Theory (DFT) offers a theoretical framework to quantify chemical reactivity and properties.

Purpose of the Study:

• To calculate nucleofugality for common organic leaving groups using conceptual DFT.
• To establish an intrinsic nucleofugality scale and compare it with established chemical principles.
• To investigate the influence of solvent effects and acidity on nucleofugality.

Main Methods:

• Conceptual DFT calculations were employed to determine nucleofugality.
• Calculations were performed for various organic leaving groups in the gas phase and in dichloromethane and methanol solvents.
• Correlations with experimental data, including pK(a) values and solvolysis rate constants, were analyzed.

Main Results:

• An intrinsic nucleofugality scale was successfully constructed, showing good agreement with classical leaving group trends.
• The study explored relationships between nucleofugality, acidity, and experimental reaction kinetics.
• A novel DFT-based formula was derived to predict the impact of solvation energy on nucleofugality, showing excellent correlation with explicit calculations.

Conclusions:

• Conceptual DFT provides a robust theoretical method for assessing nucleofugality.
• The derived nucleofugality scale offers valuable insights into leaving group behavior in organic reactions.
• The developed formula accurately describes the significant role of solvation in modulating leaving group effectiveness.