Solvatomorphism in (Z)-4-fluoro-N′-(3-fluorophenyl)benzimidamide: the role of intermolecular O–H⋯F interaction

Abstract

The synthesized compound (Z)-4-fluoro-N′-(3-fluorophenyl)benzimidamide exhibits solvatomorphism in the solid state. The anhydrous and the hydrate forms were obtained at room temperature from slow evaporation of cyclohexane and hexane solvents, respectively. Both forms crystallize in the triclinic P1 with two symmetry-independent molecules in the asymmetric unit. The crystal packing of the anhydrous form is stabilized via a strong N-H⋯N chain, whereas the hydrate form is stabilized via a strong (N-H⋯N)-(N-H⋯O)-(O-H⋯N) chain. The water molecule plays an important role in the crystal packing by the formation of "extremely short" N-H⋯O and O-H⋯N hydrogen bonds, which are further supported by weak O-H⋯F-C and C-H⋯O interactions. The basic structural building motifs were structurally and energetically equivalent in both forms. PIXEL and QTAIM approaches provide quantitative insights into the nature and energetics of strong as well as weak intermolecular interactions. The NCI descriptor shows the "attractive" nature of the rarely observed O-H⋯F interaction. The thermal stabilities of the solvatomorphs were characterized via differential scanning calorimetry, hot stage microscopy, and thermogravimetric analysis. Hirshfeld surface analysis and 2D fingerprint plots of the individual molecules present in both forms differentiate the trends in crystal packing as well as the contribution from the different intermolecular interactions.

Engineering of Solvatomorphs of the Luminescent Complex of ortho-Phenylenediboronic Acid and 8-Hydroxyquinoline

“…Interestingly, among numerous solvatomorphs (or solvates) reported in the literature (for some notable examples see works by Guru Row and co-workers − ), such series of isostructural structures are clearly less common (see Supporting Information for the related Web of Science database search). These include well-known examples of betulin, dasatinib, phenylbutazone, or dirithromycin .…”

Synthesis of a series of Pd(ii) complexes of the type [Pd(1,10-phen)(SRF)2]: an interesting case of solvatomorphism

“…[1][2][3][4][5][6] On the other hand, solvatomorphism occurs when a substance exhibits various crystalline forms, and its elemental composition varies due to the entrapment of solvent molecules. [1][2][3][4][5][6] Solvatomorphism is often called pseudopolymorphism, 7,8 an intriguing phenomenon that produces diverse molecular species of the same substance with different solvents (solvatomorphs). 6,9 Solvatomorphism has great impacts on pharmaceutical and pigment industries, and materials sciences.…”

Investigating the Role of Weak Interactions to Explore the Polymorphic Diversity in Difluorinated Isomeric N-Phenylcinnamamides

“…Fluorine chemistry − has experienced an exponential growth, from representing a small subfield of organic chemistry into a major area of multidisciplinary research of drug design that involves health and food industries. − The previous few decades have witnessed the evolution of fluorine substitution as one of the structural trends in the world of medicinal chemistry, where nearly 50% of all the blockbuster drug molecules contain fluorine atoms. − Peptide/protein engineering relies on structure tailoring of fluorinated amino acids and their subsequent tactical amalgamation into the peptide chain in order to achieve a three-dimensional view of peptide–receptor interactions. − The possibility of obtaining polymorphism and pseudopolymorphism is quite high among active pharmaceutical ingredients, and this phenomenon can be considered either a blessing or a nuisance in different stages of drug design, as it might have direct medical implications. − The term “polymorphs” include those crystal systems in which a substance can crystallize in multiple crystal structures having different unit cell parameters, where each form displays the same empirical formula. − Solvatomorphs or pseudopolymorphs, on the other hand, include crystal systems with different unit cell parameters, where the unit cells differ in their elemental composition only through the inclusion of one or more solvent molecules. − Concomitant polymorphs are defined as the simultaneous crystallization of two or more forms due to their concurrent nucleation, and their formation is controlled by both the kinetics of crystallization and thermodynamics of crystal packing. − Packing polymorphs include crystal systems having similar molecular conformations, differing only in the arrangement of molecules in their crystal packing environment. − The polymorphic forms of a drug may exhibit distinct solid-state physicochemical properties such as intrinsic dissolution rate, , solubility, tabletability, , thermal stability, flowability, hygroscopicity, , etc. and also various drug outcomes such as drug efficacy, bioavailability, and toxicity. ...…”