A series of seven N-phenylamides [R–C(O)NHPh, in which R: CH₃, C(CH₃)₃, Ph, CF₃, CCl₃, CBr₃, and H] were used as models in this study. Molecular packing and intermolecular interactions were evaluated by theoretical calculations, solution NMR, and quantum theory of atoms in molecules analyses. Crystallization mechanisms were proposed based on the energetic and topological parameters using the supramolecular cluster as demarcation. Concentration-dependent ¹H NMR experiments corroborated the proposed interactions between molecules. For all compounds (except for R: H, which initially formed tetramers), layers (two-dimensional) or chains (one-dimensional) were formed in the first stage of the proposed crystallization mechanisms. The presence of strong intermolecular NH···O═C interactions promoted the first stages. The study in solution provided different values of association constant (K_ass) governed by the hydrogen bond NH···O═C, showing that the stronger interactions are directly influenced by the substituent steric hindrance. A correlation between K_{ass(NH···O═C)} from the solution and the NH···O═C interaction energy in the crystal showed a good trend.

A series of N-arylbenzamides containing amide groups and phenyl–perfluorinated rings were used as the smallest molecules to investigate the direct influence of hydrogen bonds and aromatic donor–acceptor complementarity in the solid state. N-Phenylbenzamide and pentafluoro-N-(perfluorophenyl)benzamide were investigated in self-assembly as well as in cocrystal form. Moreover, the respective mixed phenyl–perfluorinated compounds were used in this study. Supramolecular cluster demarcation was used, and crystallization mechanisms were proposed based on the hierarchy of stabilization energies in one-, two-, or three-dimensional growth processes (1D, 2D, or 3D, respectively). At the molecular level, effects such as torsion, planes, and intramolecular interactions showed significant changes compared to the optimized structures, evidencing the supramolecular influence. When considering the supramolecular environment, crystallization mechanisms of the self-assembly of phenyl–phenyl amide offer a 2D → 3D process, whereas the other compounds were classified in a 1D (chains) → 2D (layers) → 3D stepwise process. The interchain links were driven by C–H⋯π interactions in the self-assembly and π⋯π interactions in the mixed compounds and cocrystal packing. QTAIM analysis evidences the importance and contribution of the strong NH⋯OC hydrogen bond of all crystals. MEP plots highlight the complementarity between amide sites and aromatic rings, helping to understand the cocrystal formation. Lastly, a comparison of the NH⋯OC bond strength of the cocrystal obtained (−11 kcal mol⁻¹) with those of similar cocrystals linked by amide bonds deposited in the CSD showed the highest value of the presented cocrystal. These findings will be helpful in the modulation and design of new molecular solids.

A series of 5(3)-aryl-3(5)-carboxyethyl-1-tert-butylpyrazoles (aryl, 4-X-C₆H₄, where X = H, F, Cl and Br) were studied in the solid state. The 1,3-regioisomers (carboxyethyl group in 3-position) of t-butylpyrazoles crystalized in three different forms: s-cis, s-trans or s-cis + s-trans. On the other hand, the 1,5-regioisomers (carboxyethyl group in 5-position) of t-butylpyrazoles showed only s-trans conformation. The ¹³C CPMAS and SCXRD data confirmed that each 1,3- and 1,5-regioisomers of t-butylpyrazoles crystallized only one of the three mentioned forms. The potential energy surface (PES) yielded insights regarding the formation of each conformer. In general, quantum mechanical calculations showed that the conformer s-trans is more stable than s-cis, and the calculated stability difference was 0.7 kcal mol⁻¹ for the 1,3-regioisomers and 3.5 kcal mol⁻¹ for the 1,5-regioisomers. Moreover, 1,5-regioisomers of t-butylpyrazoles showed intramolecular interactions of type CH⋯OC between the carbonyl and t-butyl group, which was obtained by QTAIM analysis. This interaction can influence the stabilization for s-trans conformation in the solid state. In contrast, the 1,3-regioisomers did not show intramolecular interaction with the COOEt group, and the conformation adopted in the solid state should be the consequence of the crystalline packing. The QTAIM analysis of the more stable dimers of s-trans-conformation for X = Cl, Br showed that the halogen atoms interact with the COOEt group, helping stabilize this conformation. On the other hand, in the s-cis⋯s-cis conformation dimer (X = Cl, Br), the COOEt group was stabilized by the phenyl group, which is the same stabilization for X = H.