Four Polymorphs of Methyl Paraben: Structural Relationships and Relative Energy Differences

Abstract

Four polymorphic forms of methyl paraben (methyl 4-hydroxybenzoate, 1), denoted 1-I (melting point 126 °C), 1-III (109 °C), 1-107 (107 °C), and 1-112 (112 °C), have been investigated by thermomicroscopy, infrared spectroscopy, and X-ray crystallography. The crystal structures of the metastable forms 1-III, 1-107, and 1-112 have been determined. All polymorphs contain the same O–H···O=C connected catemer motif, but the geometry of the resulting H-bonded chain is different in each form. The Z′ = 3 structure of 1-I (stable form; space group Cc) contains local symmetry elements. The crystal packing of each of the four known crystal structures of 1 was compared with the crystal structures of 12 chemical analogues. Close two-dimensional relationships exist between 1-112 and a form of methyl 4-aminobenzoate and between 1-107 and dimethyl terephthalate. The lattice energies of the four methyl paraben structures have been calculated with a range of methods based on ab initio electronic calculations on either the crystal or single molecule. This shows that the differences in the induction energy of the different hydrogen-bonded chain geometries have a significant effect on relative lattice energies, but that conformational energy, repulsion, dispersion, and electrostatic also contribute.

Why don't we find more polymorphs?

“…If there is a large spread in densities, free-energy calculations are likely to rerank structures that are close in lattice energy, whereas if there are significant differences in conformation and types of hydrogen bonding then it is more effective to assess the sensitivity to different approaches of lattice energy calculation and quality of wavefunction. It can be desirable to contrast a range of different electronic structure based methods of calculating lattice energies (Gelbrich et al, 2013;. If the aim is to interpret the experimental evidence for additional polymorphs or forms of disorder, then comparisons of calculated spectra or diffractograms and the link between the structures and observed transformations may give a very strong indication of the type of structure responsible.…”

Review on Life Cycle of Parabens: Synthesis, Degradation, Characterization and Safety Analysis

“…Polymorph II was finally reported and confirmed in 2011 [81], followed by the discovery more MP polymorphs. Four polymorphs of MP were characterized and compared in 2013, showing distinct crystal structures and lattice energy [82]. Other parabens are less polymorphic, till now only one polymorph was reported for EP, PP and BP [49,73,83].…”

General Computational Algorithms for Ab Initio Crystal Structure Prediction for Organic Molecules

“…The codes have also been used separately, e.g. Gelbrich et al [44] report a recent application of CrystalOptimizer to the study of four polymorphs of methyl paraben.…”