Engenharia de cristais: estudo conformacional, topológico e energético de t-butilpirazóis e bis-t-butilpirazóis

Abstract

This work presents a proposed crystallization mechanism and conformational study of regioisomers of 5(3)-aryl-3(5)-carboxyethyl-1-(1,1-dimethylethyl)-1H-pyrazole (aryl, 4-X-C6H4, where X = H, F, Cl and Br) and a series of (1'-(1',1'-dimethylethyl)-1H-pyrazol-3'(5')- yl) ethane (bis-pyrazoles), based on the supramolecular cluster approach. For the development of this work analyzes of monocrystal X-ray diffraction, powder X-ray diffraction, solution infrared, solid-state nuclear magnetic resonance and solution, quantum mechanics calculations were performed. The 1,3-pyrazoles (carboxyethyl group in 3-position) crystallized in three different forms: s-cis, s-trans and s-cis + s-trans. On the other hand, 1,5-pyrazole crystallized only in the s-trans conformation. The 1.5-pyrazoles showed intramolecular interactions of the CH∙∙∙O=C type, between the carbonyl group and t-butyl, which was obtained by QTAIM analysis. This interaction can influence crystallization in the solid state. In contrast, the 1,3-pyrazoles did not showed this type of intramolecular interaction, and the conformation adopted in the solid state should be a consequence of the crystalline packaging. The QTAIM analysis of the more stable dimers s-trans∙∙∙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. The regioisomers of t-butylpyrazoles have two types of crystallization mechanisms, with two and three stages. The regioisomers 1,2-Bis(aminocarbonyl-(1'-(1',1'-dimethylethyl)-1H-pyrazole-3 '(5')-yl)ethane presented two types of conformations in the solid state: linear and curved. The powder X-ray diffraction and SSRMN 13C CPMAS analysis revealed that the anhydrous compounds had the same conformation as observed by single-crystal X-ray diffraction. The 1.5-regioisomer, which has 3-substituted pyrazole 4-Br-Ph, presented conformational polymorphs (linear and curved conformation), and by PXRD and SSRMN 13C, linear form was present in the bulk (polycrystalline material obtained after the synthesis). The QTAIM analysis for dimers with higher stabilizing energy, showed that the 1,3-bis-pyrazoles do not realize hydrogen bonds NH∙∙∙O type. However, for 1,5-bis-pyrazoles this type of interaction was observed. The same result was obtained by 1H NMR in solution, by concentration variation, where only the 1,5-regioisomer showed hydrogen bonds. The proposed of crystallization mechanisms revealed that the 1,3-diamides exhibit two and three stages of crystallization. The 1,5-bis-pyrazoles showed three stages of crystallization, except for the linear polymorph, that present the 4-Ph-Br subtituinte in 3-position of pyrazole, which revealed four stages of crystallization. In summary, the positional change of carbonyl group has altered the crystallization mechanism, the conformations of COOEt and prevent the hydrogen bonds in 1,3-bis-pyrazole compounds.