  The cocrystallization landscape of benzamide and urea interacting with
aliphatic and aromatic carboxylic acids was studied both experimentally and
theoretically. Ten new cocrystals of benzamide were synthesized using an
oriented samples approach via a fast dropped evaporation technique. Information
about types of known bi-component cocrystals augmented with knowledge of simple
binary eutectic mixtures was used for the analysis of virtual screening
efficiency among 514 potential pairs involving aromatic carboxylic acids
interacting with urea or benzamide. Quantification of intermolecular
interaction was achieved by estimating the excess thermodynamic functions of
binary liquid mixtures under supercooled conditions within a COSMO-RS
framework. The smoothed histograms suggest that slightly more potential pairs
of benzamide are characterized in the attractive region compared to urea.
Finally, it is emphasized that prediction of cocrystals of urea is fairly
direct, while it remains ambiguous for benzamide paired with carboxylic acids.
The two known simple eutectics of urea are found within the first two quartiles
defined by excess thermodynamic functions, and all known cocrystals are outside
of this range belonging to the third or fourth quartile. On the contrary, such
a simple separation of positive and negative cases of benzamide miscibility in
the solid state is not observed. The difference in properties between urea and
benzamide R2,2(8) heterosynthons is also documented by alterations of
substituent effects...
