Proposal for crystallization of 3-amino-4-halo-5-methylisoxazoles: an energetic and topological approach

Abstract

a The supramolecular structure of 3-amino-4-halo-5-methylisoxazoles (with halo = Cl, Br, I) was investigated in order to suggest a route for crystallization of small molecules. The hierarchy of intermolecular interactions during the growth of the crystal was established by x-ray diffraction, 1 H NMR titration, QTAIM analysis and quantum mechanical calculations. The relationship between QTAIM and energetic data was the fundamental innovation in this work. It allowed the partitioning of the dimer interaction energy between interacting atoms. Partitioning shows the cooperation of intermolecular interactions in the stabilization of dimers and led to observation of the energetic consequences that small changes in the molecular structure of each compound may have on the crystal packing. The proposed route for crystallization of the supramolecular cluster was based on the energetic hierarchy, in which the hydrogen bond is the strongest interaction and the first to form, and the π-interactions are weaker than the hydrogen bond and cannot compete with it. However, the πinteractions are responsible for the growth of the crystal connecting the rising layers of the hydrogen bond dimers. The other interaction formed, the halogen bond, is too weak to compete with the other two interactions, but it is fundamental for linking the layer that leads to the final three-dimensional arrangement. Finally, a new way of understanding the crystallization process and the design of new materials is presented. 11-13Our objective herein is to further our study of the analysis of the crystal packing of heterocycles, taking into account consequences arising from small changes in molecular

Crystallization Mechanisms Applied to Understand the Crystal Formation of Rotaxanes

“…It was also observed that, regardless of the investigated rotaxane, a preferential formation of a one‐dimensional block for the first nuclei and in fewer cases the formation of dimers is observed in the first stage. This is different from the behavior of smaller molecules previously described by our research group , , , . The formation of one‐dimensional blocks corroborates with crystallization mechanisms proposed for polymorphs of [2]rotaxanes recently reported …”

“…A large contact area involved in the molecule interactions in the first steps of crystallization was observed, making it difficult for unique interactions to direct crystal formation, which is different from what is easily observed in other classes of small molecules, such as triazenes N ‐oxides . With the study of different classes of structures using this approach, some patterns may be observed and generic crystallization routes summarized for the investigated organic crystal structures (Figure ).…”

“…It was proposed crystallization mechanisms using a retrocrystallization process, which uses formed crystal data to presume how the stages of crystallization process occurred. Some investigations reported by our research group proposed crystallization mechanisms for a series of isoxazoles, triazenes N ‐oxides, substituted pyrazoles, N ‐phenilamides, and polymorph of [2]rotaxane …”

Conformer Distribution in Rotaxanes Containing Nonsymmetric Threads: A Systematic Approach

“…Correlations between the sum of the electron density (Σ ρ int ) at the BCP and the sum of the stabilization energy can be performed. This allows the partitioning of the atom ··· atom interaction energy, providing insights into the energetic contribution of each interaction (Figure ) . The types of atom ··· atom intramolecular interactions and QTAIM data are listed in the Supporting Information (Table S4).…”

[2]Rotaxanes Bearing a Tetralactam Macrocycle: The Role of a Trifurcated Hydrogen Bond in the Crystalline State

“…The interaction stabilization energies of each “furcated” system were obtained using the G AI analysis, following a procedure already reported in studies using different kind of molecules , , , , . The G AI analysis furnished the energy of each atom ··· atom interaction correlating Quantum Theory of Atoms in Molecules (QTAIM) data and intercomponent stabilization energy.…”