Predicting Cocrystallization Based on Heterodimer Energies: Part II

Many crystal engineering studies employ urea functionalities for their predictable association into one-dimensional hydrogen bonded chains. Previously, we showed (<i>Cryst. Growth Des.</i>, <b>2015</b>, <i>15</i> (10), 5068–5074) that the urea chain motif usually seen in structures of diphenylureas (PUs) with meta-substituents could be disrupted in several cases by cocrystallization with the strong hydrogen bond acceptor triphenylphosphine oxide (TPPO). Computed differences in the urea···urea and urea···TPPO dimer energies of ∼5.3–6 kcal/mol were a reasonably accurate indicator for cocrystallization success. The current study attempts to reassess the limits of this computational approach using a larger set of 16 <i>ortho</i>- and <i>para</i>-substituted PUs. Seven of the 10 PU systems predicted to cocrystallize on the basis of dimer energy calculations were experimentally realized, along with an eighth whose difference in homo/heterodimer energies fell below the threshold. The absence of cocrystallization in two of the predicted systems is likely due to preferred urea···substituent hydrogen bonding over both urea···urea and urea···TPPO interactions, a factor that was not considered in the homo/heterodimer energy comparisons. When taken in combination with the previous study, energy predictions were 87% accurate over the 30 systems investigated

Ortho-Substituent Effects on Diphenylurea Packing Motifs

Hydrogen bonding between urea groups is a widely used motif in crystal engineering and supramolecular chemistry studies. In an effort to discern how the steric and electronic properties of substituents affect the molecular conformation and crystal packing of ortho-substituted <i>N</i>,<i>N</i>′-diphenylureas (<i>o</i>PUs), herein we report the synthesis, characterization, and polymorph screening of eight members of this family. Of the 16 total <i>o</i>PU structures known (including nine structures from this study and seven previously reported), only two are isostructural. These 16 structures are sorted into three general architecture types based on their hydrogen bond topologies. In Type I, urea molecules related by translation form linear one-dimensional (1D) hydrogen bonded chains. In Type II, urea molecules rotate about a 1D hydrogen bond axis forming twisted chains. Urea groups do not hydrogen bond to one another in Type III. Energy calculations performed at the B3LYP/6-31G­(d,p) level show a higher rotational barrier about the amide bond in <i>o</i>PUs compared to meta-substituted diphenylureas (<i>m</i>PUs), which may explain the smaller range of torsion angles observed in <i>o</i>PUs compared to <i>m</i>PUs. Although ortho-substitution does not seem to limit the hydrogen bonding between urea groups in most cases, a notably higher percentage of <i>o</i>PU phases are polar compared to PUs with other substitution patterns. This suggests restricted conformations might offer some advantage in achieving acentric materials