Determination of the activation parameters and the mechanism for atropisomerization of (S)-3-(2-chlorophenyl)-2-[2-(6-diethylaminomethylpyridin-2-yl)vinyl]-6-fluoroquinazolin-4(3H)-one

Abstract

Values of ΔH^‡ = 111.6 ± 0.3 kJ mol⁻¹ (26.7 ± 0.1 kcal mol⁻¹) and ΔS^‡ = −25.7 ± 0.9 J K⁻¹ mol⁻¹ (−6.1 ± 0.2 cal K⁻¹ mol⁻¹) have been determined for the atropisomerization of (S)-3-(2-chlorophenyl)-2-[2-(6-diethylaminomethylpyridin-2-yl)vinyl]-6-fluoroquinazolin-4(3H)-one in decane. Based on molecular mechanics calculations in the literature and an observation that more polar solvent does not increase isomerization rate, it is proposed that the isomerization occurs via a planar non-ionic transition state in which the carbonyl oxygen and the 6-chloro substituent are coplanar with each other.