Towards greener-by-design fine chemicals. Part 1: synthetic frontiers
Theodore A. Gazis, Jonas Wuyts, Areti Moutsiou, Giulio Volpin, Mark J. Ford, Rodolfo I. Teixeira, Katherine M. P. Wheelhouse, Philipp Natho, Polona Žnidaršič‐Plazl, Sonja Jost, Renzo Luisi, Brahim Benyahia, Bert U. W. Maes, Gianvito Vilé
Abstract
In the face of intensifying market needs and mounting environmental pressures, the pharmaceutical and agrochemical sectors must revisit core aspects of process design. This review proposes a forward-looking framework for "greener-by-design" manufacturing, emphasizing the integration of sustainability from the earliest stages of synthetic planning through to industrial implementation. We focus on four interdependent levers that collectively enable this transformation: (i) solvent choice, with an emphasis on minimization, substitution, or complete elimination; (ii) substrate sourcing, favoring renewable and biomass-derived feedstocks to reduce fossil dependency; (iii) catalyst development, exploring the use of base metals, novel heterogeneous systems, and biocatalysts; and (iv) continuous-flow processing, which enhances safety, scalability, and process control. These strategies are not meant to be applied in isolation but rather in a synergistic, end-to-end manner that accounts for the full lifecycle of chemical products. By aligning synthetic efficiency with environmental responsibility, this review outlines a practical and actionable roadmap for the sustainable production of high-value fine chemicals. The convergence of synthetic chemistry with process engineering, data science, and life cycle thinking will be critical to realizing this vision, ultimately enabling more robust, circular, and future-proof manufacturing paradigms.