Ketoprofen

Salve KS, et al. Journal of the Indian Chemical Society, 2024, 101(12), 101471.

This study presents the synthesis and pharmacological evaluation of a novel mutual prodrug combining Ketoprofen (KF), a nonsteroidal anti-inflammatory drug (NSAID), with Chlorzoxazone (CZX), a skeletal muscle relaxant.
Synthesis of KF Acid Chloride
The acid chloride of KF was synthesized by reacting KF with an excess of thionyl chloride. The reaction mixture was heated for 2 hours in a round-bottom flask equipped with a water condenser. Upon completion of the reaction, the mixture was cooled to room temperature, and the excess thionyl chloride was removed. The resulting product was then washed with water to yield the acid halide of ketoprofen.
Synthesis of the Mutual Prodrug from Acid Chloride
In the next step, 0.77 mol of dry CZX, 0.84 mol of pure N,N-dimethylaniline, and anhydrous ether were placed into a flask and stirred. The mixture was gently refluxed on a water bath. Following this, 0.79 mol of redistilled KF acid chloride was added. The reaction was allowed to reflux vigorously, then rapidly cooled to room temperature. Approximately 10 mL of distilled water was added, and stirring was continued until the precipitate dissolved completely. The ether layer was separated and extracted with 10% sulfuric acid until the aqueous extract remained clear after alkalization with NaOH. The solution was then washed with 15 mL of saturated sodium bicarbonate solution, and the ether was dried over 1 g of anhydrous sodium sulfate overnight. The ether was removed by distillation using a fractionating column, and the final product was collected.

Aguilar J, et al. Journal of Photochemistry and Photobiology A: Chemistry, 2025, 458, 115974.

This study investigates the photocatalytic degradation of Ketoprofen (KET) in aqueous media using titanium dioxide (TiO2) as a photocatalyst. The degradation mechanism was monitored using a combination of analytical techniques, including TOC, HPLC, UV-Vis, IR, 1H NMR, and HPLC-MS. Initial TOC measurements revealed that KET undergoes rapid transformation into intermediate compounds, achieving 70% mineralization after five hours of irradiation.
HPLC and UV-Vis analyses indicated that KET is quickly converted into aromatic intermediates such as 3-hydroxy-benzophenone, phenol, 1,4-hydroquinone, 1,2,4-benzenetriol, and catechol. These compounds undergo further degradation into lower molecular weight acids, as confirmed by IR and 1H NMR studies. The photocatalytic pathway involves two main routes: one where decarboxylation followed by oxidation occurs, and another where hydroxyl radicals insert into the aromatic rings of KET, producing hydroxylated derivatives.
The study identifies a complete photocatalytic degradation mechanism: initially, KET is transformed into benzophenone-like structures, which then degrade into polyhydroxylated aromatic compounds. These intermediates are strongly adsorbed onto the TiO2 surface and further oxidized, ultimately mineralizing into carbon dioxide and water.