Hirshfeld Surface Investigation of Structure-Directing Interactions within Dipicolinic Acid Derivatives

Six compounds based on dipicolinic
acid esters have been synthesized
and Hirshfeld surfaces used to investigate the structure-directing
effects of functional groups in controlling their solid-state behavior.
Compounds 1–4 are 4-bromo dipicolinic
acid esters substituted with methyl, ethyl, propyl, and benzyl groups,
respectively. The main structure-directing motif within 1–3 is a pairwise O···H interaction
involving two carbonyl oxygen atoms and two aromatic H atoms. The
introduction of bulky benzyl groups in 4 forces a significant
change in the position of this interaction. Compounds 2 and 4 were used in Suzuki coupling reactions to prepare
extended analogues 5 and 6, respectively,
and their solid-state behavior was also studied using Hirshfeld surfaces.
Extension of these dipicolinic acid esters results in the complete
loss of the pairwise O···H interaction in 5, where the dominant structure-directing motifs are π-based
interactions. However, the pairwise O···H interaction
reappears for the more flexible 6, demonstrating control
of the solid-state structure of these dipicolinic acid derivatives
through the choice of functional groups.