RESUMEN
The effect of pressure on the α and ß polymorphs of a derivative of Blatter's radical, 3-phenyl-1-(pyrid-2-yl)-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl, has been investigated using single-crystal X-ray diffraction to maximum pressures of 5.76 and 7.42 GPa, respectively. The most compressible crystallographic direction in both structures lies parallel to π-stacking interactions, which semiempirical Pixel calculations indicate are also the strongest interactions present. The mechanism of compression in perpendicular directions is determined by void distributions. Discontinuities in the vibrational frequencies observed in Raman spectra measured between ambient pressure and â¼5.5 GPa show that both polymorphs undergo phase transitions, the α phase at 0.8 GPa and the ß phase at 2.1 GPa. The structural signatures of the transitions, which signal the onset of compression of initially more rigid intermolecular contacts, were identified from the trends in the occupied and unoccupied volumes of the unit cell with pressure and in the case of the ß phase by deviations from an ideal model of compression defined by Birch-Murnaghan equations of state.
RESUMEN
The crystal structure of Blatter's radical (1,3-diphenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl) has been investigated between ambient pressure and 6.07â GPa. The sample remains in a compressed form of the ambient-pressure phase up to 5.34â GPa, the largest direction of strain being parallel to the direction of π-stacking interactions. The bulk modulus is 7.4â (6)â GPa, with a pressure derivative equal to 9.33â (11). As pressure increases, the phenyl groups attached to the N1 and C3 positions of the triazinyl moieties of neighbouring pairs of molecules approach each other, causing the former to begin to rotate between 3.42 to 5.34â GPa. The onset of this phenyl rotation may be interpreted as a second-order phase transition which introduces a new mode for accommodating pressure. It is premonitory to a first-order isosymmetric phase transition which occurs on increasing pressure from 5.34 to 5.54â GPa. Although the phase transition is driven by volume minimization, rather than relief of unfavourable contacts, it is accompanied by a sharp jump in the orientation of the rotation angle of the phenyl group. DFT calculations suggest that the adoption of a more planar conformation by the triazinyl moiety at the phase transition can be attributed to relief of intramolecular H...H contacts at the transition. Although no dimerization of the radicals occurs, the π-stacking interactions are compressed by 0.341â (3)â Å between ambient pressure and 6.07â GPa.
Asunto(s)
Transición de Fase , Cristalografía por Rayos X , Teoría Funcional de la Densidad , Dimerización , Conformación Molecular , Presión , Triazinas/químicaRESUMEN
Time-resolved carbamazepine crystallization from wet ethanol has been monitored using a combination of cryoTEM and 3D electron diffraction. Carbamazepine is shown to crystallize exclusively as a dihydrate after 180â s. When the timescale was reduced to 30â s, three further polymorphs could be identified. At 20â s, the development of early stage carbamazepine dihydrate was observed through phase separation. This work reveals two possible crystallization pathways present in this active pharmaceutical ingredient.
RESUMEN
3D electron diffraction (3DED) has been used to follow polymorph evolution in the crystallization of glycine from aqueous solution. The three polymorphs of glycine which exist under ambient conditions follow the stability order ß < α < γ. The least stable ß polymorph forms within the first 3â min, but this begins to yield the α-form after only 1â min more. Both structures could be determined from continuous rotation electron diffraction data collected in less than 20â s on crystals of thickness â¼100â nm. Even though the γ-form is thermodynamically the most stable polymorph, kinetics favour the α-form, which dominates after prolonged standing. In the same sample, some ß and one crystallite of the γ polymorph were also observed.