The Role of Solvent Polarity on the Synthesis of Ibuprofen Molecule: A Density Functional Approach

In the present work, we intend to perform a computational study to explore the effects of solvent polarity for the synthesis of a well‐known nonsteroidal anti‐inflammatory drug, ibuprofen. For each and every step of ibuprofen synthesis, structure, energetics and spectral analysis are carried out to unveil the most suitable solvent among seven different ones with a wide range of polarity, namely, benzene (), carbon tetrachloride (), tetrahydrofuran (), acetone (), dichloromethane (), dimethyl sulfoxide [( and ethanol (). Our study reveals that the dipole moment of ibuprofen is highest in tetrahydrofuran (THF) medium, mainly arising due to medium polarity of both ibuprofen (polar protic ‐COOH group and hydrophobic isobutyl chain) and THF. On the other hand, thermodynamic calculations for the synthesis process of ibuprofen provide most negative in THF solvent indicating highest yield in this particular solvent. The higher dipole moment of ibuprofen in THF system is also reflected in the bond lengths as well as bathochromic shifts of IR spectral peaks of stretching and bending motions associated with the polar bonds C = O, C‐O and O‐H. UV and IR spectra of ibuprofen are also recorded experimentally in various solvents and solid state, respectively, which exhibit very close agreement with the theoretical findings.