Green metrics in chalcone synthesis via Claisen-Schmidt condensation: a critical mini review.

Chalcones are important scaffolds in medicinal chemistry and functional materials, commonly synthesized via the Claisen-Schmidt condensation. In recent years, numerous methodologies have been proposed to improve the sustainability of this transformation, including solvent-free conditions, heterogeneous catalysis, alternative solvents, and process-intensification strategies. However, the lack of standardized and quantitative assessment often limits meaningful comparison between reported approaches. This mini review critically examines recent advances in sustainable Claisen-Schmidt condensations through the lens of green chemistry metrics, with particular emphasis on reaction mass efficiency, process mass intensity, E-factor, and specific energy consumption as complementary descriptors of process performance. By analyzing representative methodologies under comparable criteria, the review highlights inconsistencies in reporting practices and identifies key parameters that influence the overall environmental footprint of the process. Beyond summarizing current strategies, the article discusses methodological limitations, common sources of bias in metric evaluation, and ongoing debates regarding the actual sustainability of widely adopted approaches. Finally, perspectives are provided on the need for standardized reporting protocols, broader integration of energy-related metrics, and the adoption of data-driven and life cycle-oriented frameworks to enable more reliable benchmarking and the rational design of greener synthetic routes to bioactive chalcones.