Influence of structural isomerism and fluorine atom substitution on the self-association of naphthoic acid.

Abstract

The self-association of small aromatic systems driven by π-π stacking and hydrophobic interactions is well-known. Understanding the nature of these interactions is important if they are to be used to control association. Here, we present results of an NMR study into the self-association of two isomers of naphthoic acid along with an investigation into the role of a fluorine substituent on that self-association. We interpret the results in terms of a simple isodesmic model of self-association and show that the addition of the fluorine atom appears to increase the stability of the aggregates by an order of magnitude (e.g., 1-naphthoic acid vs 4-fluoro-1-naphthoic acid, Keq = 0.05 increases to 0.35 M(-1)), a result which is supported by computational studies in the literature on the role of substituent effects on interaction energy. The use of fluorinated isomers to probe the assembly is also presented, with differing trends in fluorine-19 chemical shifts observed depending on the isomer substitution pattern.