Single crystal XRD, vibrational and quantum chemical calculation of pharmaceutical drug paracetamol: A new synthesis form

• PAR was crystallized by the slow evaporation method.
• The single crystal X-ray studies shows that the drug crystallized in the monoclinic system.
• The complete spectroscopic analysis of PAR has been carried out.
• Natural Bond Orbital (NBO), HOMO/LUMO and thermodynamical properties were analyzed.

The common house hold pharmaceutical drug, paracetamol (PAR), has been synthesized from 4-chloroaniline as a first ever report. After the synthesis, good quality single crystals were obtained for slow evaporation technique under the room temperature. The crystal and molecular structures were re-determined by the single crystal X-ray diffraction. The vibrational spectral measurements were carried out using FT-IR and FT-Raman spectroscopy in the range of 4000–400 cm−1. The single crystal X-ray studies shows that the drug crystallized in the monoclinic system polymorph (Form-I). The crystal packing is dominated by NH⋯O and OH⋯O classical hydrogen bonds. The ac diagonal of the unit cell features two chain C(7) and C(9) motifs running in the opposite directions. These two chain motifs are cross-linked to each other to form a ring R44(22) motif and a chain C22(6) motif which is running along the a-axis of the unit cell. Along with the classical hydrogen bonds, the methyl group forms a weak CH⋯O interactions in the crystal packing. It offers the support for molecular assembly especially in the hydrophilic regions. Further, the strength of the hydrogen bonds are studied the shifting of vibrational bands. Geometrical optimizations of the drug molecule were done by the Density Functional Theory (DFT) using the B3LYP function and Hartree–Fock (HF) level with 6-311++G(d,p) basis set. The optimized molecular geometry and computed vibrational spectra are compared with experimental results which show significant agreement. The factor group analysis of the molecule was carried out by the various molecular symmetry, site and factor group species using the standard correlation method. The Natural Bond Orbital (NBO) analysis was carried out to interpret hyperconjugative interaction and intramolecular charge transfer (ICT). The chemical softness, chemical hardness, electro-negativity, chemical potential and electrophilicity index of the molecule were found out first time by HOMO–LUMO plot. The frontier orbitals shows lower band gap values signify the possible biological/pharmaceutical activity of the molecule. The thermodynamical properties are also obtained from the calculated frequencies of the optimized structures.

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