A new, fast and highly sensitive lead-sensitive solid-state electrode containing PbO2, Ag powder and CuS salts was prepared. The electrode was measured to be sensitive to 1.0 × 10–6 – 0.1 mol/dm3 Pb(II) concentration with a slope of 32 ± 0.5 mV. With this value, it showed a behaviour in accordance with the Nernst equation. The response time of the electrode was determined to be 10 s and the working range between pH 1 and 9. The interference effect of the electrode was investigated. Validation values of the electrode were measured. The LOD value of the electrode was calculated as 1.5 × 10−8 mol/dm3. This feature made the electrode important for the analysis of low concentration Pb(II). Determination of lead in drinking water was performed with both the electrode and ICP-OES and the results were compared.
Epoxidation of alkenes is a fundamental transformation in organic synthesis, enabling the formation of epoxides that function as valuable intermediates in the preparation of pharmaceuticals, natural products, and specialty chemicals. This review provides an in-depth overview of alkene epoxidation mediated by osmium- and ruthenium-based catalysts, with a focus on their historical evolution, mechanistic pathways, and practical applications in synthesis. Special emphasis is placed on asymmetric epoxidation approaches, along with the impact of oxidants, ligand design, and reaction conditions on catalytic efficiency and selectivity. Although these catalytic systems are highly effective, their broader use is constrained by issues such as toxicity, limited availability, high cost, and sustainability concerns. Overall, this work highlights the significant contributions of osmium and ruthenium catalysts to contemporary epoxidation chemistry while offering perspectives for the advancement of more environmentally benign and sustainable alternatives.
During stability studies of scale-up batches of a rivaroxaban amino intermediate prepared using an improved manufacturing process, an unexpected increase in a known phthalimide-related impurity resulted in out-of-specification (OOS) results. Investigation revealed that a phthalamic acid derivative formed during synthesis acted as a precursor and converted to the phthalimide impurity under acidic conditions. The precursor impurity was synthesized and characterized by 1H NMR, 13C NMR, LC–MS, and IR spectroscopy. Based on these findings, a control strategy was established by introducing a specification limit for the precursor impurity and optimizing the isolation process to minimize residual acidity. Spike-and-purge studies demonstrated the effective removal of the impurity during downstream processing, resulting in negligible carryover to the final rivaroxaban API. Implementation of these controls enabled robust commercial manufacturing while maintaining API quality. This study highlights a practical approach for impurity investigation, control strategy development, and pharmaceutical manufacturing process optimization.
The synthesis of phthalazines and their phthalazinone derivatives has attracted considerable attention due to their biologically and pharmacologically significant heterocyclic scaffolds, which are present in numerous marketed drugs and are increasingly utilized in fluorescence probes and luminescent materials. This review aims to provide an up-to-date record of the synthesis of 2-(cyanoacetyl)-1,2,3,4-tetrahydrophthalazine-1,4-dione and their chemical transformation. The main synthetic routes to the title compound involve either ring opening of phthalic anhydride with ethyl cyanohydrazide followed by cyclization, or direct cyclization of diethyl phthalate or phthaloyl dichloride with ethyl cyanohydrazide. Moreover, the reactions of the target compound with various reagents reported to date have been thoroughly described, covering a wide range of reaction types, conditions, and mechanistic pathways. We hope this review will assist medicinal chemistry researchers in the design and synthesis of novel derivatives or analogues for therapeutic applications.
A sustainable one-pot process for the synthesis of an advanced intermediate of mirabegron is described. The developed methodology eliminates the isolation of genotoxic intermediates, minimizes solvent usage and reduces reliance on hazardous reagents used in previously reported routes. The process integrates esterification, reductive amination, and nitro reduction into a single reaction vessel, thereby simplifying manufacturing operations and improving process safety. The optimized process affords the advanced intermediate in 92
