One molecule, three crystal structures: conformational trimorphism of N-[(1S)-1-phenylethyl]benzamide

Abstract

<jats:p>The title compound, C<jats:sub>15</jats:sub>H<jats:sub>15</jats:sub>NO, is an enantiopure small molecule, which has been synthesized many times, although its crystal structure was never determined. By recrystallization from a variety of solvent mixtures (pure acetonitrile, ethanol–water, toluene–ethanol, THF–methanol), we obtained three unsolvated polymorphs, in space groups <jats:italic>P</jats:italic>2<jats:sub>1</jats:sub> and <jats:italic>P</jats:italic>2<jats:sub>1</jats:sub>2<jats:sub>1</jats:sub>2<jats:sub>1</jats:sub>. Form <jats:bold>I</jats:bold> is obtained from acetonitrile, without admixture of other forms, whereas forms <jats:bold>II</jats:bold> and <jats:bold>III</jats:bold> are obtained simultaneously by concomitant crystallizations from alcohol-based solvent mixtures. All forms share the same supramolecular structure, based on infinite <jats:italic>C</jats:italic> <jats:sub>1</jats:sub> <jats:sup>1</jats:sup>(4) chain motifs formed by N—H...O intermolecular hydrogen bonds, as usual for non-sterically hindered amides. However, a conformational modification of the molecular 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 <jats:italic>P</jats:italic>2<jats:sub>1</jats:sub> in forms <jats:bold>I</jats:bold> and <jats:bold>II</jats:bold>, respectively. As for form <jats:bold>III</jats:bold>, the asymmetric unit contains two independent molecules forming parallel chains in space group <jats:italic>P</jats:italic>2<jats:sub>1</jats:sub>2<jats:sub>1</jats:sub>2<jats:sub>1</jats:sub>, and the crystal structure combines features of monoclinic forms <jats:bold>I</jats:bold> and <jats:bold>II</jats:bold>.</jats:p>

Efficient iron-catalyzed direct acylation of amines with carboxylic acids and esters under oxygenated conditions

“…In addition, as with the aminolysis of esters 1 , the acylation of amines 3 with acids 2 occurred with complete retention of configuration, and both amides 4bh and 4ce were isolated as single enantiomers. 31,32…”

Packing and Conformational Polymorphism in 1,2-Bis(aminocarbonyl(1-tert-butyl-1H-pyrazol-(3)5-yl))ethanes: Illuminating Examples of Highly Flexible Molecules

“…29,30 Furthermore, substituent effects and steric hindrance have also been shown to affect the packing of these compounds with amides, 24,31 and numerous studies have sought to enhance the aqueous solubility 32 and investigate polymorphism control, 33 dissolution, 34 solubility, 35 chirality-dependent supramolecular synthons, 36 occurrence of concomitant polymorphs and desmotropy, 37 and influence of the solvent in obtaining specific polymorphs. 38,39 Given the above, molecular models and approaches that clarify the critical points for obtaining specific polymorphic forms are necessary. Hence, our research group has made great efforts to study the packing of a series of compounds using the demarcation of the supramolecular cluster and propose crystallization mechanisms.…”

“…Notably, amide-containing compounds are of great biological and synthetic importance and have attracted attention in crystal engineering mainly due to the directionality of their strong N–H···OC interactions, which favor bonds adjusting and controlling the molecular assemblies. This anchoring site significantly influences an increasing number of polymorphs, , and the appeal in understanding interactions ranges from small organic molecules to macromolecules. , Furthermore, substituent effects and steric hindrance have also been shown to affect the packing of these compounds with amides, , and numerous studies have sought to enhance the aqueous solubility and investigate polymorphism control, dissolution, solubility, chirality-dependent supramolecular synthons, occurrence of concomitant polymorphs and desmotropy, and influence of the solvent in obtaining specific polymorphs. , …”