Synthesis and chiral separation of atropisomers of 4,5‐Di methyl ∆⁴ N‐phenyl N‐aryl imidazoline‐2‐thione derivatives

Abstract

Synthesis of three chiral 4,5-Di methyl Δ 4 N-phenyl N-aryl imidazole-2-thione derivatives was obtained by the condensation reaction of thiourea derivatives with α-hydroxy ketone. The structure of these compounds has been characterized by using spectroscopic methods (UV, IR, 1 H NMR, and 13 C NMR). The 4,5-Di methyl Δ 4 N-phenyl N-aryl imidazole-2-thiones display a chiral axis around the N-C bond linking between the nitrogen of the heterocyclic framework and the carbon of the aryl group. Screening on chiral analysis of the atropisomers of these derivatives was performed by high-performance liquid chromatography method on seven chiral selectors based on polysaccharides consisting of amylose and cellulose, namely, Chiralpak®AD, Chiralcel® OD, Chiralcel® OD-H, Chiralcel® OJ, Chiralcel® OD-3R, Chiralcel® OZ-3, and Chiralpak® AS-3R. The impact of ortho-substituent in the resolution of 4,5-Di methyl Δ 4 N-phenyl N-aryl imidazole-2-thione derivatives was also studied in this work.

A nonneglectable stereochemical factor in drug development: Atropisomerism

“…41 With the increasing attention on atropisomerism, research on various aspects of the asymmetric synthesis, resolution, and biological evaluation of atropisomers is substantially increasing. 4,30,[42][43][44][45][46][47][48][49][50] Herein, we focus on the biological activities and pharmacokinetic and toxicity properties of various atropisomers and highlight the role of atropisomerism in drug design.…”

Enantioseparation and antioxidant activity of novel diarylpyrazoline derivatives

“…The chiral recognition mechanism of polysaccharide‐based stationary phases undergoes to various interactions: π‐π interactions, hydrogen bondings, dipole‐dipole interactions, van der Waals forces, and steric effects are also highly relevant 22,31–33 . Apart from these interactions, the π–π interaction may play a significant role in chiral discrimination on polysaccharide chiral stationary phases between complementary aromatic moieties of these phases and solute 34–37 …”

“…22,[31][32][33] Apart from these interactions, the π-π interaction may play a significant role in chiral discrimination on polysaccharide chiral stationary phases between complementary aromatic moieties of these phases and solute. [34][35][36][37]…”

Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity

“…Since our Ibuprofen-based compounds are racemic and have one stereogenic center, all methylene hydrogens in these structures are chemically non-equivalent and they are diastereotopic [58,59]. In case of free rotation inhibition around one single bond, the molecule becomes atropisomeric [60][61][62]. According to Frączek et al, atropisomeric molecule's methylene hydrogens become chemically non-equivalent and interact with each other geminally [60].…”