Síntese e estudo supramolecular de bis-ureias trissubstituídas: mecanismos de cristalização

Abstract

This work presents the synthesis and molecular and supramolecular study of an unprecedented series of trisubstituted bis-ureas. In all, six molecules were synthesized, in which the substituents were varied and the methylene spacer between the urea groups. The formation of appropriate crystalline and single crystal phases for the six molecules allowed molecular geometries to be obtained through single crystal X-Ray diffraction and crystal engineering studies to be performed. The supramolecular cluster was used to determine the molecular coordination number, the contact area and the stabilization energy, which allowed to propose crystallization mechanisms and crystallization parameters for each stage. For the stabilization energy values, quantum mechanics calculations were used at the theory level ωB97x-D/cc-pVDZ. It was observed that diisobutylamine-substituted compounds had water in the crystal lattice – that is, crystalline hydrates. Furthermore, three of the compounds had more than one bis-urea molecule in the asymmetric unit, the conformational isomorphs. One of the conformational isomorphs was analyzed by powder X-rays and 13C solid state nuclear magnetic resonance and it was possible to observe the chemically equivalent atoms with distinct environments leading to signal complexity in the solid state compared to the liquid state. Intermolecular interactions were analyzed by QTAIM and also by 1H NMR experiments of varying concentration – being possible to correlate theoretical data with experimental data. For the six compounds, four proposals for distinct crystallization mechanisms were reported. Given the complexity of phase 6a, an unprecedented treatment of the supramolecular cluster was used to make a coherent proposal for the crystallization mechanism, and experimental NMR data were essential for understanding the initial nucleus. QTAIM revealed that compounds 6a, 7a-b and 8a presented hydrogen bonds as the one that most contributed to the formation of the more energetic nucleus (NH···O=C and/or CH···O=C), while that for compound 8b the interactions that contribute most are the CH···HC, and for 7b the interactions CH···π. In compounds 7a-b, despite the CH···π interactions not being the most energetic, they were significantly complementary to the formation of the 1D nucleus still in solution. Thus, it was possible to demonstrate in this work that interactions considered to be weak and/or dispersive by the scientific literature can have a great contribution and even directionality in the formation of the more energetic nucleus in solution of bis-urea molecules – contributing to the crystalline design.