Packing Modes in Some Mono‐ and Disubstituted Phenylpropiolic Acids: Repeated Occurrence of the Rare syn,anti Catemer

Abstract

The catemer is an infinite one-dimensional pattern formed by the carboxylic acid group in crystals, and is constituted with O-H...O hydrogen bonds. The catemer is uncommon and may be contrasted with the ubiquitous carboxylic acid dimer, the favored mode of association of this functional group. Both catemers and dimers, however, have two O-H...O hydrogen bonds for each carboxy group, so the reasons for the rarity of the catemer must lie elsewhere. In this paper, we describe a group of around 25 phenylpropiolic acids in which the catemer is the default packing mode. Exceptionally, the particular catemer that is found in this family is of the very rare syn,anti variety. We show that a necessary ingredient in catemer formation is a supportive C-H...O hydrogen bond from a proximal C-H group, which is located on the phenyl ring, ortho to the ethynyl group, and suitably activated by electron withdrawing substituents. When steric factors become noteworthy, alternative patterns are adopted, such as the syn,syn catemer and, in one case, a rare cisoid dimer. When electron-donating groups, either through inductive effect such as methyl or through resonance such as halogens, are present on the phenyl ring, the dimer is formed in all but one case. Polymorphism seems not to be an issue in these carboxylic acids in that no compound would generally crystallize as both a dimer and a catemer. It may be concluded that a supporting interaction, in this case a C-H...O hydrogen bond, is the essential condition for the formation of any carboxylic acid catemer. Catemers are so rare because it is difficult to set up this type of supporting interaction in most carboxylic acids.

Not Your Usual Bioisostere: Solid State Study of 3D Interactions in Cubanes

“…Previous studies by Desiraju and co-workers on crystal engineering of cubane scaffolds focused on the series of 4-(R)-substituted-1-cubanecarboxylic acids. [5,6] Within this series,t hey demonstratedt he presence of rare syn-anti catemers in the formation of the hydrogen bonds ( Figure 1). This was theorized to be ad irect result of as econdary binding motif between the cubane hydrogen and carbonyl groups leading to am ore fa-vored syn-anti catemer formation.…”

“…Considering the average occurrence for this motif in the literature is quite low, this high average within a specific family is quite unique . Das and Desiraju have previously stated that the propensity for this motif is stabilized by a supportive C−H⋅⋅⋅O interaction . It appears that the natural 3D conformation of cubane containing six available C−H interactive groups in a spatially defined pattern increases the potential of these contacts.…”

“…Previous studies by Desiraju and co‐workers on crystal engineering of cubane scaffolds focused on the series of 4‐( R )‐substituted‐1‐cubanecarboxylic acids . Within this series, they demonstrated the presence of rare syn‐anti catemers in the formation of the hydrogen bonds (Figure ).…”

Crystal Engineering: A Holistic View

“…A recent study from our group shows that the formation of the catemer is only possible if there is a supporting hydrogen bond (say, CÀH···O) from another location on the molecule. [40] This condition prevails in the family of substituted phenylpropiolic acids. When, why, and how this supporting interaction manifests itself is not easy to establish.…”

Kristall‐Engineering: eine holistische Darstellung

“…In diesen Fällen sind entropische Betrachtungen von größter Bedeutung, und das Supramolekül liegt in Lösung vor, bevor es einen Kristall bildet -letzterer mag für eine strukturelle Charakterisierung vielleicht erforderlich sein, die Kristallisation ist dabei aber nicht Teil der eigentlichen Synthese. [40] Diese Bedingung ist innerhalb der Familie der substituierten Phenylpropiolsäuren weitgehend erfüllt. Es ist nicht leicht zu ermitteln, wann, warum und wie diese unterstützende Wechselwirkung auftritt.…”