Abstract
The title compound, C15H15NO, is an enanti-opure small mol-ecule, which has been synthesized many times, although its crystal structure was never determined. By recrystallization from a variety of solvent mixtures (pure aceto-nitrile, ethanol-water, toluene-ethanol, THF-methanol), we obtained three unsolvated polymorphs, in space groups P21 and P212121. Form I is obtained from aceto-nitrile, without admixture of other forms, whereas forms II and III are obtained simultaneously by concomitant crystallizations from alcohol-based solvent mixtures. All forms share the same supra-molecular structure, based on infinite C 1 1(4) chain motifs formed by N-H⋯O inter-molecular hydrogen bonds, as usual for non-sterically hindered amides. However, a conformational modification of the mol-ecular structure, related to the rotation of the phenyl rings, alters the packing of the chains in the crystal structures. The orientation of the chain axis is perpendicular and parallel to the crystallographic twofold screw axis of space group P21 in forms I and II, respectively. As for form III, the asymmetric unit contains two independent mol-ecules forming parallel chains in space group P212121, and the crystal structure combines features of monoclinic forms I and II.
Highlights
The study of polymorphism is paramount in the field of organic materials, especially in the design of new active pharmaceutical ingredients, either for tailoring their bioavailability, or for legal reasons related to patent rights and intellectual property
The rules allowing a molecular system to crystallize with several forms are not fully understood, assessing the risk of polymorphism is workable to some extent
It is not surprising that, for example, well-characterized hexamorphism is exceptional (Yu et al, 2000). Another empirical observation is that more polymorphs are reported for small molecules compared to large ones, because of the correlation between molecular complexity and the difficulty of synthesizing large molecules. These observations are in line with McCrone’s statement, and today there is a consensus that polymorphism is a pervasive phenomenon, which occurs on a random basis and remains poorly predictable (Cruz-Cabeza et al, 2015)
Summary
The study of polymorphism is paramount in the field of organic materials, especially in the design of new active pharmaceutical ingredients, either for tailoring their bioavailability, or for legal reasons related to patent rights and intellectual property. It is not surprising that, for example, well-characterized hexamorphism is exceptional (Yu et al, 2000) Another empirical observation is that more polymorphs are reported for small molecules (less than 30 C atoms per formula) compared to large ones, because of the correlation between molecular complexity and the difficulty of synthesizing large molecules. These observations are in line with McCrone’s statement, and today there is a consensus that polymorphism is a pervasive phenomenon, which occurs on a random basis and remains poorly predictable (Cruz-Cabeza et al, 2015) Within this context, we report a case of trimorphism, for a low-molecular-weight chiral molecule, for which the crystal structure was never established, even though many researchers have used it as a reagent since its first reported synthesis (Bezruchko et al, 1967). The conformation of the molecule is modified by rotation of the phenyl ring C3–C8 bonded to the chiral centre, while the
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