Energy barriers to rotation in axially chiral quinazoline-4-ones

Axially chiral 2-thioxo-3-(o-aryl)-quinazolin-4-ones and 2-(benzylthio)-3-(o-aryl)-quinazolin-4-ones were synthesized and their energy barriers to rotation about the N-3-C-aryl bond were determined by thermal racemization of the separated enantiomers. The rotational barriers were found to range from 112.7 to 140.8 kJ/mol, depending on size of the ortho substituent and to increase linearly with the size of the van der Waals radii of the ortho-halogen substituents. Although the isolation of the enantiomers of the N-C axially chiral compounds bearing an ortho-fluoro substituent are rare because of small size of fluorine atom, we found that the rotational barriers of quinazolin-4-ones bearing an ortho-fluoro group are high enough allowing the isolation of enantiomers. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

Axially chiral 2-thioxo-3-(o-aryl)-quinazolin-4-ones and 2-(benzylthio)-3-(o-aryl)-quinazolin-4-ones were synthesized, and the rotational barriers about the N-3-C-aryl bond were determined. The rotational barriers were found to increase linearly with the size of ortho substituents, and compounds bearing an ortho-fluoro group had high enough rotational barriers for enantiomer isolation.