Exploring concomitant/conformational dimorphism in a difluoro-substituted phosphoramidate derivative

Abstract

The concomitant occurrence of dimorphs of diphenyl (3,4-difluorophenyl)phosphoramidate, C 18 H 14 F 2 NO 3 P, was observed via a solution-mediated crystallization process with variation in the symmetry-free molecules (Z 0 ). The existence of two forms, i.e. Form I (block, Z 0 = 1) and Form II (needle, Z 0 = 2), was characterized by single-crystal X-ray diffraction, differential scanning calorimetry and powder X-ray diffraction. Furthermore, a quantitative analysis of the energetics of the different intermolecular interactions was carried out via the energy decomposition method (PIXEL), which corroborates with inputs from the energy framework and looks at the topology of the various intermolecular interactions present in both forms. The unequivocally distinguished contribution of strong N-HÁ Á ÁO hydrogen bonds along with other interactions, such as C-HÁ Á ÁO, C-HÁ Á ÁF,and C-HÁ Á Á, mapped on the Hirshfeld surface is depicted by two-dimensional fingerprint plots. Apart from the major electrostatic contribution from N-HÁ Á ÁO hydrogen bonds, the crystal structures are stabilized by contributions from the dispersion energy. The closely related melting points and opposite trends in the calculated lattice energies are interesting to investigate with respect to the thermodynamic stability of the observed dimorphs. The significant variation in the torsion angles in both forms helps in classifying them in the category of conformational polymorphs.Displacement ellipsoid plots (50% probability) of (a) dimorph Form I (Z 0 = 1) and (b) dimorph Form II (Z 0 = 2). For Form II, molecule A is depicted in olive and molecule B in purple.

Tracing shape memory effect and elastic bending in a conformationally flexible organic salt

“…1) crystallizes in two different forms, Form I and Form III which are related through conformational changes. 31 Form I undergoes a reversible phase transition on lowering the temperature (between 258-273 K) and transforms to a new form, Form II, shown by the blue box in Fig. 2.…”

Investigation of crystal structures, energetics and isostructurality in halogen-substituted phosphoramidates

“…Group 4: 3F and 34FN. Analysis of the crystalline assembly of the dimorphs of 34F is given elsewhere (Hasija & Chopra, 2019). Forms I and II of compound 34F crystallize concomitantly.…”

“…Phosphoramidates-containing prodrugs are known to Computer programs: APEX2, SAINT (Bruker, 2015), SIR2014 (Burla et al, 2015), SADABS (Krause et al, 2015), SHELXS97 (Sheldrick, 2008), OLEX2.solve 1.3 (Bourhis et al, 2015), SHELXT2014/5 (Sheldrick, 2015a), SHELXL2016/6, SHELXL2018/3 (Sheldrick, 2015b), PLATON (Spek, 2009) and Mercury (Macrae et al, 2020), OLEX2 1.3 (Dolomanov et al, 2009), WinGX (Farrugia, 2012). † The crystal and refinement data for 34FB and 34FN are tabulated in Hasija & Chopra (2019) as form I and form II, respectively.…”

“…[CSD refcodes LEQRIK/LEQRIK01 (Gholivand et al, 2013) and HOBSID/HOBSID01 (Hasija & Chopra, 2019)]. On exploring more, derivatives of phosphoric acid have been unraveled, where the study encompasses the detailed investigation of the crystalline arrangement via the presence of different intermolecular interactions (DuPlessis et al, 1982;Tarahhomi et al, 2012Tarahhomi et al, , 2013Hamzehee et al, 2016;Farkhani et al, 2018;Taherzadeh et al, 2021).…”

Crystal structure of a new polymorph of 3-acetyl-8-methoxy-2H-chromen-2-one

“…The minor differences in which weak intermolecular interactions contribute to the formation of the crystal (Fig. 6), give rise to distinct polymorphs as suggested by Hasija & Chopra (2019). As can be seen in Fig.…”