Structural and energetic aspects of a new bupropion hydrochloride polymorph.

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)Å, b=8.7184(3)Å, c=12.0422(3)Å, V=2864.7(1)ų, as centrosymmetric dimers, thanks to the presence of N-H…Cl interactions, and µ2-bridging chloride ions, each connected to two protonated amine moieties.

Structures from powders: bupropion hydrochloride.

The crystal structure of bupropion hydrochloride, 1, was fully characterized from powdered crystalline samples, using the ab-initio XRPD technique and a global optimization strategy (simulated annealing), adopting, as starting model, the already known molecular structure of its ethanol solvate, 2. Bupropion hydrochloride crystallizes as a racemate in monoclinic system, space group P2(1)/c with Z=4, a=14.3406(3)A, b=8.7564(2)A, c=11.8801(2)A, beta=78.025(2) degrees , V=1459.34(5)A(3). In the crystals of 1 the molecules interact via strong NH[...]Cl contacts, generating dimeric entities with mu-Cl ions. Further stabilizing contacts, of the CH[...]O are at work, but differently organized in the 1 and 2 phases. The thermal behaviour of the product was assessed by differential scanning calorimetry.