Two tautomers in the same crystal: 3-(4-fluoro-phen-yl)-1H-pyrazole and 5-(4-fluoro-phen-yl)-1H-pyrazole

Area of Science:

• Crystallography
• Supramolecular Chemistry
• Organic Chemistry

Background:

• Pyrazole derivatives are important scaffolds in medicinal chemistry and materials science.
• Understanding crystal packing and intermolecular interactions is crucial for designing novel functional materials.
• Co-crystals offer a versatile approach to modify the physical and chemical properties of active pharmaceutical ingredients.

Purpose of the Study:

• To characterize the crystal structure of the 3,5-bis(4-fluorophenyl)-1H-pyrazole co-crystal.
• To investigate the tautomerism and intermolecular interactions present in the crystal lattice.
• To elucidate the role of hydrogen bonding and other weak interactions in stabilizing the crystal structure.

Main Methods:

• Single-crystal X-ray diffraction was employed to determine the crystal structure.
• Analysis of crystallographic data included bond lengths, bond angles, and dihedral angles.
• Intermolecular interactions such as hydrogen bonds and C-H···F interactions were identified and analyzed.

Main Results:

• The co-crystal crystallizes with four independent molecules (A, B, C, D) in the asymmetric unit.
• Two tautomeric forms were observed due to N-H proton exchange within the pyrazole ring.
• Dihedral angles between pyrazole and benzene rings varied across the independent molecules.
• N-H⋯N hydrogen bonds formed an R4(4)(12) ring motif, linking molecules in the asymmetric unit.
• Weak C-H⋯F interactions contributed to the formation of a three-dimensional crystal network.

Conclusions:

• The crystal structure of the 3,5-bis(4-fluorophenyl)-1H-pyrazole co-crystal is characterized by the presence of tautomerism and diverse intermolecular interactions.
• Hydrogen bonding plays a significant role in the self-assembly of these molecules into a specific supramolecular architecture.
• The observed weak C-H⋯F interactions further stabilize the three-dimensional network, highlighting their importance in crystal engineering.