Physical-Organic Studies on Polar–π Interactions

Noncovalent interactions involving aromatic rings, such as π−π, cation−π, anion−π and XH−πinteractions, have been identified and widely used in biology and chemistry. To better understandthese interactions, seven small molecule model systems have been designed and synthesized. Thisthesis describes the physical-organic chemistry studies of π−π interactions, XH−π interactions, andthe features of boronic acid−π interactions through simple synthetic models.


Chapter 3 describes the studies of the arene-arene interactions in cyclophanes, containing an electronrich phenol and aniline with a tetra-H- and tetra-F-substituted benzene. The studies suggest that thetetra-F-template increases the acidity by stabilizing the π–π stacking interactions. Quantum chemicalanalysesfurthermore reveal that the fluorination enhancesthe π–π stacking interactions by reinforcingelectrostatic and orbital interactions, thus increases the acidity of phenols and anilines.


Chapter 4 describes the physical-organic studies on the noncovalent interactions betweenimidazole/imidazolium rings and two flanking aromatic rings with substituents at para/meta positionsin 2-(2’,6’-diaryphenyl)-1H-imidazole models. The studies reveal that the pK_a values and protonaffinities of para-substituted analogues correlate will with the Hammett sigma values. Furtherquantum chemical computations revealed that the π−π stacking interactions are dominant betweenthe imidazolium cation and each flanking aromatic ring, while the NH–π interactions only play aminor role.


Chapter 5 presents the synthetic, spectroscopic, structural and quantum chemical analyses on 2-arylphenyl-1H-tetrazoles and their deprotonated form to investigate the noncovalent interactionsbetween tetrazole and tetrazolide rings with flanking aromatic ring with substituents at para/metapositions. The studies show that pK_a values and proton affinities correlate well with Hammett sigmavalues of para-substituents at the neighboring rings. Additional molecular orbital and energydecomposition analyses reveal that both through-space NH−π interactions and π−π interactionscontribute to the trend of pK_a values and proton affinities of 2-arylphenyl-1H-tetrazoles.


Chapter 6 presents the synthesis and investigation of 2,6-diarylthiophenols that possess the centralthiophenol ring and two flanking aromatic rings with substituents at distant para/meta positions. Theresults show that pK_a values and proton affinities correlate well with Hammett sigma values of parasubstituents. Energy decomposition analysis reveals that both through-space SH-π interactions andS−-π interactions contribute to intramolecular stabilization of 2,6-diarylthiophenols. 

Chapter 7 describes our synthetic, spectroscopic, structural and quantum chemical analyses on 2,6-diarylbenzenesulfonamides. The results show that fine-tuning the aromatic character by substituentsIXon the flanking rings leads to linear trends in acidity and proton affinity of sulfonamides. Physicalorganic chemistry studies demonstrate that aromatic rings have a capacity to stabilize sulfonamidesvia through-space NH−π interactions. 


Chapter 8 introduces the structural, NMR spectroscopic, and computational analyses of thecompetition between halogen−π and CH−π interactions by molecular balances based on thedibenzobicyclo[3,2,2]nonane template. The studies reveal that the π systems can favorably interactboth with halogens and C−H functionalities, depending on the size of the functional group. 


Chapter 9 describes experimental and theoretical investigations of the Lewis acidity of 2,6-diarylphenylboronic acids. The results show that the acidity of 2,6-diarylphenylboronic acids remainsunchanged upon the introduction of EWG/EDG at the distant para position of the flanking aromaticrings. X-ray structures and computational studies demonstrate that polar-π interactions and solvationeffects contribute to the stabilization of boronic acids and boronate forms by aromatic rings.Advanced quantum chemistry highlights that boronic acids and boronates can be stabilized byaromatic systems. 

In general, this thesis addresses the origin of genuinely important noncovalent interactions that havebeen widely used in pharmaceutical chemistry, biology, supramolecular chemistry, and materialchemistry. Simple model systems were used to investigate the underlying noncovalent interactionsbetween aromatic rings and polar functionalities, the knowledge that is important for furtherexploration of application across molecular sciences.