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.
ABSTRACT
A selection of imines derived from phenyl t-butyl ketones and substituted 2-phenylethylamines or phenylalanine exhibit slow rotation around the arylimino bond at ambient temperature, resulting in a large non-equivalence of the ortho hydrogens in the 1H NMR spectra. This facilitates assessment of aryl substituent effects on the face tilted-T CHπ interaction between a phenyl ring (A) on the imino carbon proximate to the terminal phenyl ring (B). Analysis of the marked temperature dependence of the chemical shift of the interacting ortho hydrogen affords estimates of the opposing enthalpic and entropic factors involved in the rapid equilibrium between the closed edge-to-face conformation and alternative open conformations devoid of a CHπ interaction while in solution. Above ca. 80 °C the entropy term (TΔS) cancels out the enthalpy (ΔH) favouring the closed conformation and open conformations are preferred. Accordingly, commonly reported binding free energies may not be a good measure of the energetic strength of intramolecular aromatic interactions. Investigation of an ortho fluoro substituted compound indicates that a CFπ interaction is at least 1.0 kcal mol−1 weaker in enthalpy than the CHπ interaction. Several X-ray crystal structures depicting an intramolecular edge-to-face interaction are presented.
Subject(s)
Imines/chemistry , Crystallography, X-Ray , Ketones/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Phenethylamines/chemistry , Phenylalanine/chemistry , ThermodynamicsABSTRACT
NMR spectra of imines and nitrones derived from benzophenone and phenylalanine or tyrosine show clear evidence of an aromatic edge-to-face interaction in solution. At low temperatures the two ortho protons of the edge interacting phenyl ring become topically resolved with the ortho proton NMR signal involved in the CH-pi interactions shifted well upfield (delta 5.4-5.8 at -88 degrees C) of the other ortho signal. Introduction of a para substituent into the phenylalanine ring has a modest effect on the upfield shift. The edge-to-face arrangement also manifests in the X-ray crystal structures of two of these compounds. Barriers to rotation around the syn phenyl-imino bond are also reported (10.5-11.1 kcal mol(-1)).
Subject(s)
Phenylalanine/chemistry , Benzophenones/chemistry , Crystallography, X-Ray , Imines/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Nitrogen Oxides/chemistry , ThermodynamicsABSTRACT
An evaluation of the Bruker SMART X2S for the collection of crystallographic diffraction data, structure solution and refinement is carried out with a variety of materials with different electron densities, presenting some of the successes and challenges of automation in chemical crystallography.
ABSTRACT
As part of a search for systems that exhibit intramolecular aromatic edge-to-face interactions, a series of four biaryl compounds containing a phenethyl side chain were prepared. These compounds exist as a slowly interconverting mixture of two atropisomers due to steric hindrance to rotation about the biaryl bond. The more thermodynamically stable isomer exhibits an abnormal shielding of an ortho-proton in solution indicative of an edge-to-face CH-pi interaction with the terminal phenyl ring on the side chain. This tilted-T type of geometry was observed in the X-ray crystal structure of one of the compounds. The edge-to-face conformation in solution is estimated by variable temperature NMR studies to be energetically favored by ca. 1.6 kcal mol(-1) but entropically disfavored by ca. 5.0 cal K(-1) mol(-1).