Detection of Isotopic Atropisomerism Based on -H/D Discrimination.

Racemic and optically active 3-(2-deuteriophenyl)-2-(1-phenylpropan-2-yl)quinazoline-4-thiones were prepared. The nuclear magnetic resonance spectra clearly show that they exist as a 1:1 mixture of diastereomers due to the isotopic atropisomerism based on -H/D discrimination (N-C axial chirality) and a chiral carbon.

N-C Axially Chiral Compounds with an ortho-Fluoro Substituent and Steric Discrimination between Hydrogen and Fluorine Atoms Based on a Diastereoselective Model Reaction.

The fluorine atom is the second smallest atom; nevertheless, the ortho-fluoro group may lead to stable N-aryl atropisomers when the steric demand of the flanking substituents is large enough. 2-Alkyl-3-(2-fluorophenyl)quinazolin-4-ones and 3-(2-fluorophenyl)-4-methylthiazoline-2-thione were found to be the first N-aryl axially chiral compounds bearing an ortho-fluoro group whose enantiomers were isolated at ambient temperature. The reaction of alkyl halides with the anionic species prepared from 2-ethyl-3-(2-fluorophenyl)quinazolin-4-one presenting an N-C axial chirality provided a model reaction for quantitative evaluation of the steric discrimination (slight difference of steric factor) between hydrogen and fluorine atoms.