Characterization and thermodynamic study of a new polymorphic form of Bupropion hydrochloride

Crystalline bupropion hydrochloride [(±)1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride], recently characterized as form 1, was found to undergo, upon storage at RT within months, a solid–solid conversion to a new polymorphic form, hereafter named form 2, containing a markedly different molecular conformer in the solid state. This new form, available only as a polycrystalline material, has been fully characterized using structural X-ray powder diffraction methods, coupled to thermoanalytical analyses. The relative stability of the two crystalline phases (forms 1 and 2) was compared by quantum mechanics calculations including density functional methods specific for solid state molecular systems. Bupropion hydrochloride form 2 crystallizes in the orthorhombic space group Pbca with Z = 8, a = 27.2853(5)A˚ , b = 8.7184(3)A˚ , c = 12.0422(3)A˚ , V = 2864.7(1)˚A3, as centrosymmetric dimers, thanks to the presence of N–H. . .Cl interactions, and 2-bridging chloride ions, each connected to two protonated amine moieties.