Synthesis of Atropisomeric Quinazolin-4-one Derivatives Based on Remote H/D and 12C/13C Discrimination

Yuka Watanabe; Utae Take; Ryunosuke Senda; Azusa Sato; Osamu Kitagawa

doi:10.1021/acs.joc.4c02772

Synthesis of Atropisomeric Quinazolin-4-one Derivatives Based on Remote H/D and ¹²C/¹³C Discrimination

J Org Chem. 2025 Jan 10;90(1):784-793. doi: 10.1021/acs.joc.4c02772. Epub 2024 Dec 27.

Authors

Yuka Watanabe¹, Utae Take¹, Ryunosuke Senda¹, Azusa Sato², Osamu Kitagawa¹

Affiliations

¹ Chemistry and Materials Program, College of Engineering, Shibaura Institute of Technology, 3-7-5 Toyosu, Kohto-ku, Tokyo 135-8548, Japan.
² School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

PMID: 39727323
DOI: 10.1021/acs.joc.4c02772

Abstract

Both enantiomers of 2-ethylquinazolin-4-ones bearing ortho-CH₃O/CD₃O and CH₃O/¹³CH₃O phenyl groups at the N3 position were prepared. These are isotopic atropisomeric compounds based on a remote and conformationally flexible H/D and ¹²C/¹³C discrimination, and it was found that a CHCl₃ solution of ortho-CH₃O/CD₃O derivative shows a slight specific optical rotation. Furthermore, diastereomeric quinazolinone derivatives bearing a chiral carbon were prepared, and their stereochemical purities and rotational stability as well as the isotopic atropisomerism were verified by ¹H NMR and chiral high-performance liquid chromatography (HPLC) analyses.