Heterocycles as Supramolecular Handles for Crystal Engineering: A Case Study with 7-(diethylamino)coumarin Derivatives

In this study, we present the synthesis and detailed solid-state structural characterization of a Schiff-base-bridged derivative of 7-(diethyl)aminocoumarin (DAC) to carry out a comparative crystallographic analysis, within the broader context of a curated dataset of 50 DAC-containing molecules, retrieved from the literature, and their corresponding crystal packing. We uncover that the DAC moiety leverages its pronounced local dipole moment and inherently planar configuration to facilitate different modes of π-stacking interaction. These are strongly directed by C-H···O interactions between the coumarin carbonyl group with the ethyl-residue or the 3-substituent of adjacent molecules. In solution, the presence of a 7-diethylamino group is shown to enhance solubility through its conformational flexibility, while in the crystalline matrix it primarily acts as a structural spacer that favors π-stacking interactions. Our findings present a comprehensive analysis of the preferential arrangements of the DAC fragment in various (supra)molecular scenarios, including cases where its influence is overridden. We thus present the entire 7-(diethylamino)coumarin block as (a) mobile but mostly planar, (b) prone to antiparallel aggregation, and (c) 90% likely to pack via π-stacking supported by hydrogen- bonding interactions, enriching the palette of supramolecular motifs for the programmed assembly of molecular solids.