“Greener” synthesis of bisphosphonic/dronic acid derivatives

• Main Authors: Kovács Rita, Grün Alajos, Garadnay Sándor, Greiner István, Keglevich György
• Format: Article
• Language: English
• Published: De Gruyter 2014-04-01
• Series: Green Processing and Synthesis
• Subjects: carboxylic acids; dronic acid derivatives; optimization; phosphorus trichloride; synthesis
• Online Access: https://doi.org/10.1515/gps-2013-0107

According to literature, the synthesis of dronic acid derivatives from the corresponding carboxylic acids using phosphorus trichloride and phosphorous acid as the P-reactants is controversial, due to the wide range of molar ratios and diverse conditions. In this minireview, we summarize our results on the clarification of these problems. For example, with zoledronic acid and risedronic acid, we found that, using methanesulfonic acid (MSA) as the solvent, 3.2 equivalents of phosphorus trichloride was enough. Generalizing this optimized method, etidronate, fenidronate, ibandronate and alendronate were obtained in yields of 38%–57%, which is reasonable for valuable dronates, and in most cases, with high purities. Mechanistic aspects are also discussed.