Silicone Oil Induced Spontaneous Single-Crystal-to-Single-Crystal Phase Transitions in Ethynyl Substituted <i>ortho</i>- and <i>meta</i>-Fluorinated Benzamides

We present an unusual observation of facile single-crystal-to-single-crystal phase transition induced in hydrophobic silicone oil at ambient conditions which is fast in <i>ortho</i>-fluoro substituted ethynyl phenyl benzamide and relatively slow for the <i>meta</i>-isomer. These phase transitions are also observed in crystals, on heating, at high temperature, and in the absence of silicone oil. The extensive thermal and structural analyses reveal that the phase transition between the two polymorphs of the <i>ortho</i>-isomer is monotropic in nature and involves large supramolecular rearrangements, wherein for the <i>meta</i>-isomer the same is enantiotropic and is driven by altered molecular conformations. The structural features demonstrate the absence of prevalent and strong NH···OC hydrogen bonds in the crystal structures of both polymorphs of the <i>ortho</i>-fluoro substituted benzamide. A plausible molecular mechanism based on energetically favored “structural motifs” has been proposed which depicts that rotational and translational motion between the molecules present in the crystal relates molecular motifs and provides a rationale for the origin of the nucleation and growth process during the phase transition

Experimental and Theoretical Characterization of Short H‑Bonds with Organic Fluorine in Molecular Crystals

The existence of short H-bonds with organic fluorine is still under debate. We report herein the occurrence and nature of such short contacts to fluorine connected to an aromatic ring in the block form of <i>N</i>-(4-fluorophenyl)-3-(trifluoromethyl) benzamide and 4-fluoro-<i>N</i>-[3-(trifluoromethyl)­phenyl]­benzamide. The magnitude of the stabilizing interaction energy is −2.15 and −2.89 kcal/mol, respectively. It is important to note that such contacts have been observed in the presence of strong NH···OC H-bonds whose energies are in the range of 6.0–8.0 kcal/mol. Thus, the observed strength of an H-bond with fluorine is ∼30–40% of the strength of a strong traditional H-bond in amides. The acidic hydrogens were observed to be involved in the formation of a short CH···F contact, the interaction energy having a substantial Coulombic contribution in comparison to the other weak interactions which are primarily of a dispersive character as obtained by PIXEL method. A full topological analysis does establish the fact that CH···F interactions at short distances are indeed a “true H-bond”. These are not a consequence of crystal packing and have implications in the generation of polymorphs in the solid state. This is expected to have implications in the binding of a ligand (organic molecule containing fluorine) with the protein active site

Exploring the Role of Substitution on the Formation of Se···O/N Noncovalent Bonds

In this article, we have examined the effect of substitution on the formation of neutral XHSe···O/N (X = −H, −F, −CH₃, −CF₃, −Cl, −OH, −OCH₃, −NH₂, −NHCH₃, −CN) noncovalent bonds with the oxygen atom from H₂O molecule and the nitrogen atom from NH₃ being the electron donor atoms, respectively. In addition to this, analysis has also been performed on XMeSe···O/N complexes to study the effect of the role of hydrogen bonding with the hydrogen atoms of the methyl group on Se···O/N interactions. Binding energy calculations were performed to determine the strength of these contacts. The obtained results establish the fact that the presence of a methyl group influences the strength of the observed Se···O/N interactions. Also in some cases, the O–H···Se interaction was observed to be more preferable over the Se···O interaction. The major contribution for stabilization of such Se···O/N interactions is from an interplay among the electrostatics and the exchange energy. To obtain deeper insights and understanding of such Se···O/N contacts, a topological analysis, using the QTAIM approach were also performed. This analysis showed that although the presence of a Me group modifies the Se···O/N interaction, it does not necessitate the formation of hydrogen bonds. To obtain insights into the orbital contributions, a natural bond orbital (NBO) analysis were performed which depicts that the strength of such interactions were derived via charge transfer from the oxygen/nitrogen lone pair to the σ* orbital of the Se–X bond

Observation of Rapid Desolvation of Hexafluorobenzene Involving Single-Crystal-to-Single-Crystal Phase Transition in a Nonporous Organic Host

We report an unusual occurrence of an extremely fast single-crystal-to-single-crystal phase transition induced by rapid desolvation of hexafluorobenzene at room temperature mediated by a subtle interplay of π···π stacking interactions in <i>N</i>-(3-ethynylphenyl)-4-fluorobenzamide. The nature of the host–guest stacking interaction has been explored in terms of interaction energy, electrostatic complementarity, and topological analysis with the inputs from reduced density gradient-noncovalent interactions fingerprint descriptor. Furthermore, the compound also exists in two other nonsolvated polymorphic forms

Assessing the Significance of Hexafluorobenzene as a Unique Guest Agent through Stacking Interactions in Substituted Ethynylphenyl Benzamides

A series of differently substituted host molecules have been employed to systematically investigate the nature and strength of the stacking interactions with hexafluorobenzene in the solid state. The hexafluorobenzene guest binds to the crystal lattice of the parent compound, the <i>N</i>-ethynylphenyl benzamide host and its nine other halogenated (-F/-CF3/-Cl/-Br at ortho/meta/para positions individually) analogues via stacking of aromatic rings. The geometrical and energetic features of intermolecular interactions in host–guest molecules have been investigated, and the results elucidate the dominancy of dispersion in the stabilization of the aryl-hexafluorobenzene stacking, while the electrostatic component also plays an important role. The plots of the molecular electrostatic potential provide a fundamental basis of the electrostatic complementarity that exists in between the host and the guest. The topological characterization reveals unambiguous evidence for the direct participation of the substituents in closed-shell bonding interactions with the aromatic rings at the local geometry, which remarkably controls the nature and energetics of such motifs. Additionally, the observed upfield 19F NMR chemical shifts for perfluorinated guest upon complexation with the host compounds provide evidence for the existence of the host–guest stacking interaction also in the solution state

Evaluation of the Role of Isostructurality in Fluorinated Phenyl Benzoates

In this report, the occurrence of three-, two-, and one-dimensional (3D, 2D, and 1D) isostructurality in phenyl benzoate (D00) and their fluorinated analogues was investigated in terms of their molecular assembly in solid state structures. A one-dimensional C–H···OC chain is observed as a robust motif (∼ −21 kJ/mol) in the formation of the supramolecular architectures in these isostructural compounds. The isomorphous crystal structures exhibit 3D isostructurality or vice versa. The crystal packing shows that weak intermolecular C–H···F, C–H···O, C–H···π interactions, and π···π stacking are the main contributors providing stability toward the crystal lattice. The nature and energetics of all the geometrically or energetically equivalent building blocks associated with similar or different intermolecular interactions delineate the role of different molecular pairs in the crystal structures. The fingerprint plots of the isostructural set of crystal structures help to understand the similarities and the differences in the various interatomic contacts. A comparison of these crystal structures with fluorinated <i>N</i>-phenyl benzamides shows the change in supramolecular assembly in terms of intermolecular interactions as well as the lattice energy due to the participation of a strong donor (N–H)

Crystallographic and Theoretical Investigation on the Nature and Characteristics of Type I CS···SC Interactions

In this study, we have performed an extensive crystallographic and theoretical analysis to explore the nature and characteristics of CS···SC interactions. A Cambridge Structural Database study revealed the abundance of CS···SC interactions wherein more than 70% of the crystal structures can be categorized as Type I chalcogen–chalcogen interactions. The binding energies for these contacts range in magnitudes from +2.02 kcal/mol (highly destabilized) to −1.67 kcal/mol (stabilized). Ab initio studies on (X₂CS)₂ models systems where X = −H, −NH₂, −OH, −F, −Cl reveals that CS···SC are governed by the presence of negative σ-holes for X = −NH₂, −OH, while the presence of a positive electrostatic region on sulfur is observed for the halogen substituted complexes. These interactions are of dispersive nature with electrostatics contributing to the destabilization in some cases

Quantitative Investigation of Polymorphism in 3‑(Trifluoromethyl)‑<i>N</i>‑[2-(trifluoromethyl)phenyl]benzamide

The occurrence of concomitant dimorphism has been observed in the case of trifluoromethyl substituted benzanilide, namely, 3-(trifluoromethyl)-<i>N</i>-[2-(trifluoromethyl)­phenyl]­benzamide, wherein both forms show the presence of a multiple number of molecules in the asymmetric unit (<i>Z</i>′ > 1). Thermal studies confirm the “extremely rare occurrence” of simultaneous melting and solid-to-solid phase transition at the same temperature from centrosymmetric, <i>Z</i>′ = 2 structure (triclinic, <i>P</i>1̅, form I) to noncentrosymmetric, <i>Z</i>′ = 4 structure (monoclinic, <i>Cc</i>). Both forms exhibit similar density and lattice energy. Conformationally different molecules in the asymmetric unit in both the high-<i>Z</i>′ structures are observed to be connected with strong N–H···OC and weak C–H···OC hydrogen bonds. The dissimilarities in the crystal packing were analyzed by Xpac method, and the molecule–molecule interaction energies were evaluated by the PIXEL method. The results revealed the presence of 2D isostructurality between the two forms which mainly consists of the most stabilized intermolecular interactions (namely, strong N- H···OC, C–H···OC, and C–H···π hydrogen bonds) in their crystal packing while differences in their crystal packing are mainly on account of the presence of weak C–H···F–C­(sp³) hydrogen bond and C­(sp³)–F···F–C­(sp³) interactions

Correction to Exploring Solid State Diversity and Solution Characteristics in a Fluorine-Containing Drug Riluzole

Correction to Exploring Solid State Diversity and Solution Characteristics in a Fluorine-Containing Drug Riluzol

Structural Investigation of Weak Intermolecular Interactions in Fluorine Substituted Isomeric <i>N</i>‑Benzylideneanilines

The study of the influence of aromatic C–F group in directing crystal packing is an important area of current research. The role of the aromatic C–F group in the formation of weak intermolecular interactions in the absence of strong hydrogen bond donors and acceptors has been analyzed in a series of 15 newly synthesized fluorine substituted (mono- and di-) isomeric <i>N-</i>benzylideneanilines. It was observed that five compounds (out of a total number of 15) were liquids at room temperature, while others have low melting points (<60 °C). <i>In situ</i> crystallization, using an optical heating and crystallization device (OHCD), has been used to crystallize and determine the crystal structures of three out of five compounds which were found to be liquids at 25 °C. A detailed investigation of the molecular conformation and the crystal packing in these compounds reveals that the presence of organic fluorine acts as a significant contributor in the construction of various supramolecular synthons, essentially using a variety of C–H···F intermolecular interactions. These have been found to generate different three-dimensional arrangements of molecules in the crystalline framework. In order to realize the stabilizing influence exerted by such weak interactions, intermolecular C–H···F interaction energies have been calculated using Firefly to quantify the strength of such interactions. Lattice energy calculations have been performed and the individual energies, namely, the Coulombic, polarization, dispersion, and repulsive contributions to the lattice energy have been determined using the CLP program. In addition to these, theoretical calculations have been performed at the density functional theory level, and the experimental geometry has been compared with the optimized geometry to highlight the importance of molecular conformation in the solid and gas phase. It is of interest to note that stabilization resulting from the presence of C–H···F interactions, albeit less, is not negligible and does contribute toward crystal packing