Investigation of the role of stereoelectronic effects in the conformation of piperidones by NMR spectroscopy and X-ray diffraction.

This paper reports the synthesis of a series of piperidones 1-8 by the Mannich reaction and analysis of their structures and conformations in solution by NMR and mass spectrometry. The six-membered rings in 2,4,6,8-tetraphenyl-3,7-diazabicyclo[3.3.1]nonan-9-ones, compounds 1 and 2, adopt a chair-boat conformation, while those in 2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-ones, compounds 3-8, adopt a chair-chair conformation because of stereoelectronic effects. These stereoelectronic effects were analyzed by the (1) J C-H coupling constants, which were measured in the (13)C satellites of the (1)H NMR spectra obtained with the hetero-dqf pulse sequence. In the solid state, these stereoelectronic effects were investigated by measurement of X-ray diffraction data, the molecular geometry (torsional bond angles and bond distances), and inter- and intramolecular interactions, and by natural bond orbital analysis, which was performed using density functional theory at the ωB97XD/6311++G(d,p) level. We found that one of the main factors influencing the conformational stability of 3-8 is the interaction between the lone-pair electrons of nitrogen and the antibonding sigma orbital of C(7)-Heq (nN→σ*C-H(7)eq), a type of hyperconjugative interaction.

Los cocristales farmacéuticos: conceptos generales / Pharmaceutical Cocrystals: General concepts

Los cocristales farmacéuticos surgen como una posibilidad para mejorar las propiedades biofarmacéuticas y farmacotécnicas de un IFA (Ingrediente Farmacéutico Activo). Los cocristales farmacéuticos son sólidos cristalinos constituidos por un IFA y un formador, los cuales se encuentran en la misma celda cristalina. La búsqueda de nuevos cocristales farmacéuticos es competencia de la química supramolecular, ya que el IFA y el formador se mantienen juntos mediante interacciones no covalentes. Existen métodos en solución y en sólidos para la formación de cocristales. Además, este campo ofrece una posibilidad de desarrollo intelectual debido a la posibilidad de patentar los productos, considerando los parámetros regulatorios. Este trabajo presenta los principales conceptos que se consideran para el estudio de estos sólidos farmacéuticos

Pharmaceutical co-crystals emerge as a possibility to improve the biopharmaceutical properties and pharmacotechnical of an Active Pharmaceutical Ingredient (API). Theco-crystalsare crystalline solids composed of an API and a former, which are located in the same crystal cell. The search for new pharmaceutical co-crystals is the responsibility of supramolecular chemistry, since the formerand the API are held together by non-covalent interactions. Solution and solid state methods are employed for the formation of cocrystals. In addition, this field offers a possibility of intellectual development due to the patentability of products, without neglecting the regulatory aspects. This work presents the main concepts considered for the study of these pharmaceutical solids

NMR structural study of the prototropic equilibrium in solution of Schiff bases as model compounds.

An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ΔKNHO on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by 1H-, 13C- and 15N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pKa, ΔKNHO and ΔΔG°) were obtained from 1H-NMR titration data and pH measurements. The Henderson-Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster-Lachmann δ-diagram analysis and Perrin model data linearization.

(E)-4-Hy-droxy-2-{[(2-phenyl-eth-yl)iminium-yl]meth-yl}phenolate.

The title Schiff base compound, C(15)H(15)NO(2), crystallized as the iminium-phenolate zwitterion. The H atom is localized on the imine N atom, forming a strong intra-molecular hydrogen bond with the phenolate O atom, and giving rise to an S(6) ring motif. The mol-ecule has an E conformation about the C=N bond. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming chains propagating along [010]. There are also C-H⋯O inter-actions present.

3-(Piperidin-1-ium-1-yl)-6-azoniaspiro-[5.5]undecane dibromide monohydrate.

The title compound, C(15)H(30)N(2) (2+)·2Br(-)·H(2)O, was synthesized by reaction of 4-piperidino-piperidine with dibromo-pentane. The dication is built up from three linked piperidine rings, two of which have one quaternary N atom in common (azoniaspiro), whereas the third is N-C bonded to the azoniaspiro system and protonated on the N atom (piperidinium). All three piperidine rings adopt chair conformations. The crystal structure features O-H⋯Br and N-H⋯Br hydrogen bonds.