Using the pyridine and quinuclidine scaffolds for superbases: a DFT study

Area of Science:

• Organic Chemistry
• Computational Chemistry

Background:

• 2,6-Disubstituted pyridines and 2,6,7-trisubstituted quinuclidines are classes of organic compounds with potential as strong bases.
• Understanding the factors that influence basicity is crucial for designing new chemical reagents and catalysts.

Purpose of the Study:

• To screen pyridine and quinuclidine derivatives as potential strong bases.
• To investigate the effect of substituents on the basicity of these compounds.
• To identify the most potent organic bases within the screened sets.

Main Methods:

• Computational screening of 2,6-disubstituted pyridines and 2,6,7-trisubstituted quinuclidines.
• Calculation of relative proton affinities using the PBE1PBE/6-311G(d,p) method.
• Inclusion of gas and solution phase (THF) calculations with the IEFPCM solvation model.

Main Results:

• Basicity is significantly enhanced by substituents containing lone-pair possessing atoms.
• Hydrogen bonding interactions between substituents and the conjugate acid stabilize the protonated species.
• 2,6-bis(3-methoxy-2-furyl)-4-dimethylaminopyridine and 2,6-di(2-dimethylaminoethyl)pyridine were identified as the strongest bases.

Conclusions:

• Substituent effects, particularly those enabling hydrogen bonding, play a critical role in enhancing the basicity of pyridines and quinuclidines.
• Computational methods provide a reliable approach for predicting and identifying potent organic bases.
• The identified strong bases have potential applications in catalysis and organic synthesis.