Structure – Basicity Relationships of 4-Aryl Pyridine Moieties

Abstract

To examine the transmission and relative magnitude of substituent effects in biphenyl compounds, we have used 4-aryl pyridine moieties as probes. Accordingly, 58 4-aryl pyridine type compounds have been synthesized, characterised and the acid dissociation constants of their conjugate acids have been determined at 298 kelvin.
The parameter dΔG has been introduced and used to quantify substituent effects. It has been shown that a dichotomy exists between the transmission of electron-withdrawing substituents and electron donating substituents. Electron withdrawing groups in the 3 and 4 position exhibit effects of a similar magnitude while those in the 2 position exert a stronger effect. In contrast, electron donating groups have been shown to exert a significant effect only in the 2 and 4 position. Additionally, it has been found that the cyano substituent in the 2 position exerts an unexpectedly powerful effect while the nitro group in the same position exerts an unexpectedly weak effect. Crystal structures suggest the latter observation is due to the nitro group in the 2 position being twisted out of plane. These results indicate that secondary electronic effects and rotational freedom of functional groups might affect biphenyl geometry. Substituent effects in 4-aryl-3-picoline and 4-aryl-3,5-lutidine compounds have been found to be significantly weaker than in the analogous 4-aryl pyridine compounds, which suggests that resonance interactions between the two aryl rings are at least partially responsible for transmission of substituent effects.