title: Propensity of salicylamide and ethenzamide cocrystallization with aromatic carboxylic acids.
abstract: The cocrystallization of salicylamide (2-hydroxybenzamide, SMD) and ethenzamide (2-ethoxybenzamide, EMD) with aromatic carboxylic acids was examined both experimentally and theoretically. The supramolecular synthesis taking advantage of the droplet evaporative crystallization (DEC) technique was combined with powder diffraction and vibrational spectroscopy as the analytical tools. This led to identification of eleven new cocrystals including pharmaceutically relevant coformers such as mono- and dihydroxybenzoic acids. The cocrystallization abilities of SMD and EMD with aromatic carboxylic acids were found to be unexpectedly divers despite high formal similarities of these two benzamides and ability of the R2,2(8) heterosynthon formation. The source of diversities of the cocrystallization landscapes is the difference in the stabilization of possible conformers by adopting alternative intramolecular hydrogen boding patterns. The stronger intramolecular hydrogen bonding the weaker affinity toward intermolecular complexation potential. The substituent effects on R2,2(8) heterosynthon properties are also discussed.
authors.affiliation: Department of Physical Chemistry, Pharmacy Faculty, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń, Kurpińskiego 5, 85-950 Bydgoszcz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Przybyłek
authors.affiliation: University of Technology and Life Sciences in Bydgoszcz, Faculty of Chemical Technology and Engineering, Seminaryjna 3, 85-326 Bydgoszcz, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Ziółkowska
authors.affiliation: Research Laboratory, Faculty of Chemical Technology and Engineering, Seminaryjna 3, 85-326 Bydgoszcz, Poland.
authors.forename: Karina
authors.initials: K
authors.lastname: Mroczyńska
authors.affiliation: Department of Physical Chemistry, Pharmacy Faculty, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń, Kurpińskiego 5, 85-950 Bydgoszcz, Poland. Electronic address: piotr.cysewski@cm.umk.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Cysewski
mesh_terms: D001549:Benzamides / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D003460:Crystallization; D006860:Hydrogen Bonding; D033362:Powder Diffraction / Q000379:methods; D012457:Salicylamides / Q000737:chemistry*
chemical_list: C524082:2-hydroxybenzamide; D001549:Benzamides; D002264:Carboxylic Acids; D012457:Salicylamides; C018935:ethenzamide
keywords: 2,4-Dihydroxybenzoic acid (PubChem CID: 1491); 2,6-Dihydroxybenzoic acid (PubChem CID: 9338); 3,4-Dihydroxybenzoic acid (PubChem CID: 72); 4-Acetamidobenzoic acid (PubChem CID: 19266); 4-Hydroxybenzoic acid (PubChem CID: 135); Acetylsalicylic acid (PubChem CID: 2244); Aromatic carboxylic acids; Benzoic acid (PubChem CID: 243); Ethenzamide; Ethenzamide (PubChem CID: 3282); Miscibility; Pharmaceutical cocrystals; Salicylamide; Salicylamide (PubChem CID: 5147); Salicylic acid (PubChem CID: 338)