Usage of Quantum Chemical Methods to Understand the Formation of Concomitant Polymorphs of Acetyl 2-(N-(2-Fluorophenyl)imino)coumarin-3-carboxamide

Abstract

Crystallization of concomitant polymorphs is a very intriguing process that is difficult to be studied experimentally. A comprehensive study of two polymorphic modifications of acetyl 2-(N-(2-fluorophenyl)imino)coumarin-3-carboxamide using quantum chemical methods has revealed molecular and crystal structure dependence on crystallization conditions. Fast crystallization associated with a kinetically controlled process results in the formation of a columnar structure with a nonequilibrium molecular conformation and more isotropic topology of interaction energies between molecules. Slow crystallization may be considered as a thermodynamically controlled process and leads to the formation of a layered crystal structure with the conformation of the molecule corresponding to local minima and anisotropic topology of interaction energies. Fast crystallization results in the formation of a lot of weak intermolecular interactions, while slow crystallization leads to the formation of small amounts of stronger interactions.

Scheme 1. Acetyl 2-(N-(2-Fluorophenyl)imino)coumarin-3-carboxamide

Figure 1

2-(N-(2-Fluorophenyl)imino)coumarin-3-carboxamide molecular structures in polymorphic modifications I (on the left) and II (on the right) according to the X-ray diffraction data.

Figure 2

Molecular structure of two equilibrium states (along the edges) and transition state (in the middle) according to the quantum chemical calculations.

Figure 3

Energy profile of the rotation around the N1–C10 bond in unsubstituted and ortho-fluorosubstituted molecules in vacuum (on the left) and taking into account the polarizing environment within the PCM model (solvent = isopropanol) according to the quantum chemical calculations by the m06-2x/cc-pVTZ method.

Figure 4

Intermolecular hydrogen bonds in polymorphic structure I.

Figure 5

Stacking interactions in crystals I (on the left) and II (on the right).

Figure 6

Crystal structures of polymorphic modification I (on the left) and II (on the right).

Figure 7

Hirshfeld surfaces with the mapped d_norm property for molecules in structures I (on the left) and II (on the right) projected and transparent to show the conformation of the molecules.

Figure 8

2D Hirshfeld fingerprint plots for structures I (on the left) and II (in the middle). Relative contribution of different types of intermolecular interactions to the total Hirshfeld surface area (in %) is shown as the histogram (on the right).

Figure 9

Column along the a crystallographic direction as the primary BSM shown as packing of molecules (a) and energy-vector diagrams (b) (projection along the b crystallographic direction) and packing of the columns, in terms of energy-vector diagrams (c) (projection along the a crystallographic direction) in structure I. The double column is highlighted blue.

Figure 10

Layer parallel to the bc crystallographic plane, projection along the a crystallographic direction (on the left) and packing of the layer, projection along the c crystallographic direction (on the right) in structure II. The layer is highlighted in red.

Figure 11

Stacked dimers with the strongest interaction energy in structure II.

Figure 12

Needle-like crystals of polymorph I (on the left) and prismatic crystals of polymorph II (on the right).