Stereodynamics and edge-to-face CH–π aromatic interactions in imino compounds containing heterocyclic rings

Abstract

By comparison with close contact interactions between benzene rings there is a paucity of experimental data available for attractive interactions involving aromatic heterocyclic rings, especially for small molecules in solution. Herein we describe aromatic heterocyclic and carbocyclic edge-to face interactions and conformational stereodynamics of N-1,2-diphenylethyl imines bearing a phenyl group and either a 2-pyridyl, 3-pyridyl, 2-thiophene or 2-furanyl moiety on the imino carbon. X-ray crystal structures have been determined for two compounds. Slow rotation about the phenyl-imino bond in the E-isomers and around the heterocycle-imino bond in the Z-isomers of the pyridyl compounds was observed at low temperatures by NMR. Abnormally large shielding of one ortho hydrogen indicates that both the imino phenyl and heterocycle rings can engage in an edge-to-face interaction with the N-terminal phenyl moiety in the appropriate isomer. Some rotational barriers around the phenyl-imino and heterocycle-imino bonds were measured.

Monooxygenase- and Dioxygenase-Catalyzed Oxidative Dearomatization of Thiophenes by Sulfoxidation, cis-Dihydroxylation and Epoxidation

“…Attractive edge-to-face interactions are also found between phenyl rings of TDO (Phe-216) and of substrates 1g (Figure 2A) and 1k (Figure 3B). Edge-to-face interactions, between phenyl and thienyl groups, were earlier identified by NMR and X-ray crystallographic studies of imines [80]. Similar novel edge-to-face interactions are observed between phenyl (Phe-216) and thienyl rings in substrates 1a (Figure 1A,B), 1g (Figure 2A,B), 1k (Figure 3A-C).…”

Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides

“…Previous docking studies of arene substrates with TDO indicated that the preferred orientations were controlled by: (i) attractive edge-toface T shaped interactions with the orthogonal phenyl group of Phe-216 and imidazole ring of His 222 and (ii) Van der Waals interactions with the proximate hydrophobic amino acids Ile-276, Leu-272, Ile-324, Val-309, Leu-272, Phe-352 (Hoering et al, 2016;Vila et al, 2016aVila et al, ,b, 2017Boyd et al, 2017Boyd et al, , 2019. Theoretical, crystallographic and experimental support for phenyl-phenyl and phenyl-pyridyl edge-to-face bonding (Tbonding) interactions, between arene and heteroarene rings, has been reported (Jennings et al, 2001;Escudero et al, 2009;Gonzalez-Rosende et al, 2017;Aliev and Motherwell, 2019). Little evidence was available, from crystalline protein structures, for similar edge-to-face interactions between the imidazole ring of histidine with other aromatic residues, e.g., Phe, Tyr, Trp, His (Bhattacharyya et al, 2003).…”

Cis‐Dihydroxylation of Tricyclic Arenes and Heteroarenes Catalyzed by Toluene Dioxygenase: A Molecular Docking Study and Experimental Validation

“…Edge‐to face interactions between phenyl rings have been widely reported in reviews, but much less information is available on similar interactions between phenyl groups and five membered heterocyclic rings . Recently, evidence for the edge‐ to‐face interactions between benzene and furan or thiophene rings has been reported . To date little evidence for edge‐to‐face bonding between benzene and imidazole rings appears to have been been reported.…”