Resorcinol Crystallization from the Melt: A New Ambient Phase and New “Riddles”

Abstract

Structures of the α and β phases of resorcinol, a major commodity chemical in the pharmaceutical, agrichemical, and polymer industries, were the first polymorphic pair of molecular crystals solved by X-ray analysis. It was recently stated that "no additional phases can be found under atmospheric conditions" (Druzbicki, K. et al. J. Phys. Chem. B 2015, 119, 1681). Herein is described the growth and structure of a new ambient pressure phase, ε, through a combination of optical and X-ray crystallography and by computational crystal structure prediction algorithms. α-Resorcinol has long been a model for mechanistic crystal growth studies from both solution and vapor because prisms extended along the polar axis grow much faster in one direction than in the opposite direction. Research has focused on identifying the absolute sense of the fast direction-the so-called "resorcinol riddle"-with the aim of identifying how solvent controls crystal growth. Here, the growth velocity dissymmetry in the melt is analyzed for the β phase. The ε phase only grows from the melt, concomitant with the β phase, as polycrystalline, radially growing spherulites. If the radii are polar, then the sense of the polar axis is an essential feature of the form. Here, this determination is made for spherulites of β resorcinol (ε, point symmetry 222, does not have a polar axis) with additives that stereoselectively modify growth velocities. Both β and ε have the additional feature that individual radial lamellae may adopt helicoidal morphologies. We correlate the appearance of twisting in β and ε with the symmetry of twist-inducing additives.

Is zeroth order crystal structure prediction (CSP_0) coming to maturity? What should we aim for in an ideal crystal structure prediction code?

“…CSP is undoubtedly leading to an increase in the number of polymorphs whose structures are now known. The use of CSP has helped to solve the structures of extremely brous polymorphs of coumarin grown from the melt, 80 new needle forms of resorcinol 37 (another example of a new form being found despite published predictions that there were no more forms), and another form of aspirin 38 from the melt. The system ROY, with its various colours, is one where it has long been known that there are further uncharacterised forms 39 that exist at ambient, but CSP produces too many candidates.…”

“…57 Are these cases where full thermodynamic treatment including the interfacial effects would predict these structures? Concomitant polymorphs raise further questions 37,58,59 as to whether we could ever devise a computational method that would allow the condent prediction of the conditions needed to crystallise phase pure samples. Extensive crystallisation work could not obtain phase pure samples of the metastable forms II and III of olanzapine.…”

DDT Polymorphism and the Lethality of Crystal Forms

“…In order to assess the relative stabilities of Forms Iand II, and potentially undiscovered forms as well, prospective crystal structures were explored using systematic crystal structure prediction (CSP) based on an evolutionary algorithm, as implemented in the USPEX code, [30][31][32][33] an approach that uses only molecular geometry as input. Then umber of molecules per asymmetric unit (Z')a nd choices of space groups,s pecified by the user,d efine the extent of the crystal structure search.…”

Capturing the Role of Temperature and Entropy in Crystal Polymorphs Through Molecular Simulations

“…The structures that interconvert are demonstrated to have indistinguishable energies, free energies, and box volumes as described above. The above procedure is planned to be utilized on a real CSP of resorcinol [198] to determine the number of candidate structures that interconvert at ambient conditions.…”

“…Even in cases where an accurate result was obtained with a classical potential, the cheap potential is often first fitted to previously collected experimental or high-accuracy QM data [118,142,198,235]. In a 'true' crystal structure prediction study of a totally new and unstudied material, this data will not exist and a series of QM calculations will need to be run anyway.…”