Between a reactant rock and a solvent hard place--molecular corrals guide aromatic substitutions.

Area of Science:

• Organic Chemistry
• Computational Chemistry

Background:

• Aromatic nucleophilic substitution reactions are fundamental in organic synthesis.
• Understanding reaction mechanisms is crucial for optimizing chemical processes.

Purpose of the Study:

• To elucidate the novel reaction mechanism of ortho-magnesium carboxylate driven aromatic nucleophilic substitution in naphthoic acids.
• To support theoretical findings with high-level computational methods.

Main Methods:

• Density Functional Theory (DFT) calculations using the CAM-B3LYP method.
• All-electron DZVP basis set and implicit/explicit solvent models (PCM, IDSCRF).
• Analysis of reaction barriers and free-energy contributions.

Main Results:

• Identified rate-determining step as R-group transfer from Grignard reagent Mg-atom to naphthalene C1-atom.
• Characterized a 'molecular corral' of solvent and substrate stabilizing the transition state.
• Observed agreement between calculated barriers and experimental trends.

Conclusions:

• The study presents a novel mechanism for a key organic reaction.
• Computational chemistry provides valuable insights into reaction dynamics and substituent effects.
• Experimental-theoretical synergy is vital for mechanistic understanding.