Intermolecular Hydrogen Bonding in Alpha-Hydroxy Carboxylic Acids Crystals: Connectivity, Synthons, Supramolecular Motifs

Abstract

Synthon theory underlies the analysis and empirical prediction of the crystal structure. Supramolecular synthons (SMSs) formed by intermolecular hydrogen bonds, such as carboxylic R22(8) and C11(4) and alcoholic C11(2) ones, are among the most popular. The subject of this publication is the identification of specific synthons in alpha-hydroxycarboxylic acids (AHAs) crystals, in which carboxyl and alcohol fragments are present simultaneously. A series of 11 single-enantiomeric and racemic crystals of substituted lactic acids, the simplest chiral AHA family, were prepared and studied by the single-crystal X-ray diffraction (SC-XRD) method. Advanced analysis of our own and published (Cambridge Structural Database) data on the 33 crystal structures of lactic and achiral AHAs of diverse structures revealed that their supramolecular organization differs significantly from that of simple carboxylic acids. We found that in AHA crystals, hydrogen bonds RC(O)O−H···O(H)−C(R′R′′)C(O)OH (in our notation HB 12) and O=C(OH)C(R′R′′)−O−H···O=C(OH)R′ (HB 23) predominate. The frequency of intermolecular hydrogen bonds is interconnected with the frequency of SMSs. Thus, the synthons mentioned above occur but do not dominate in AHA crystals. Linear synthons C22(6):12/23 and cyclic synthons R22(10):23/23 and R33(11):12/23/23 are most often implemented. An essential role in the choice of cyclic synthons is played by the chiral characteristics of the sample.