Thermal and X-ray powder diffraction structural characterization of two benfluorex hydrochloride polymorphs

Two polymorphic forms of benfluorex hydrochloride, phases land II, were isolated as monophasic polycrystalline samples, and structurally characterized using ab initio X-ray powder diffraction methods and a global optimization strategy (simulated annealing). Form I crystallizes in monoclinic system, space group P2(1)/n, with Z=4, a=21.0719(10)angstrom, b=7.0563(4)angstrom, c=14.8684(7)angstrom, beta=116.998(3)degrees, V=1969.8(2)angstrom(3), while Form II crystallizes in the orthorhombic space group Pbca, with Z=8, a=33.8031(2)angstrom, b=15.1451(8)angstrom, c=7.6138(6)angstrom, V=3897.9(4)angstrom(3). Crystals of Form land Form II of benfluorex hydrochloride are based upon an ionic packing of protonated benfluorex molecules at the most basic site, the N1 atoms, and chloride anions. Form I shows the presence of mu-Cl ions, generating centrosymmetric dimers with a N(2)Cl(2) moiety, while Form II contains antiparallel chains of C-H center dot center dot center dot O hydrogen-bonded molecules running along c axis. DSC and thermodiffractometric measurements showed that heating progressively Form II from ambient temperature to 160 degrees C causes a phase transition to the thermodynamically stable Form I, immediately followed by the sample melting, near 165 degrees C. Recrystallization directly to Form I is observed when the melt is cooled back to ambient temperature, with a significant hysteresis (this event being centered near 130 degrees C).