Balancing Yields and Sustainability: An Eco-Friendly Approach to Losartan Synthesis Using Green Palladium Nanoparticles

This study presents a sustainable, environmentally friendly synthetic route for the production of key intermediates in losartan using palladium nanoparticles (PdNPs) derived from a brown seaweed, <i>Sargassum incisifolium</i>, as a recyclable nanocatalyst. A key intermediate, biaryl, was synthesized with an excellent yield (98%) via Suzuki-Miyaura coupling between 2-bromobenzonitrile and 4-methylphenylboronic acid, catalyzed using bio-derived PdNPs under mild conditions. Subsequent bromination using <i>N</i>-bromosuccinimide (NBS) under LED light, followed by imidazole coupling and tetrazole ring formation, allowed for the production of losartan with an overall yield of 27%. The PdNP catalyst exhibited high stability and recyclability, as well as strong catalytic activity, even at lower loadings, and nitrosamine formation was not detected. While the overall yield was lower than that of traditional industrial methods, this was due to the deliberate avoidance of the use of toxic reagents, hazardous solvents, and protection/deprotection steps commonly used in conventional routes. This trade-off marks a shift in pharmaceutical process development, where environmental and safety considerations are increasingly prioritized in line with green chemistry and regulatory frameworks. This study provides a foundation for green scaling up strategies, incorporating sustainability principles into drug synthesis.