Retrosynthetic Network Assessment (ReNA): Automative Retrosynthesis Opens Pathways To Integrate Life Cycle Thinking into Green Chemistry Metrics

A novel methodology, Retrosynthetic Network Assessment (ReNA), has been developed to evaluate the environmental sustainability of fine chemical synthetic routes at early development stages. ReNA harnesses automative retrosynthesis tools to quantify a set of metrics that integrate green chemistry with life cycle thinking. A stepwise procedure is presented to construct retrosynthetic networks, tracing synthetic pathways back to a selection of 174 commodity chemicals. The retrosynthetic networks enable the calculation of new sustainability metrics that quantify the network complexity and the carbon footprint of commodity chemicals in the network. The use of averaged carbon footprint values for the commodity chemicals, derived through clustering techniques, is also explored. The method is demonstrated in a case study on the synthesis of rosefuran, an industrially important aroma chemical, for which seven published routes are compared. ReNA indicators are shown to be complementary to traditional green chemistry metrics, providing a more informed comparison of synthetic pathways and revealing optimization opportunities early in the innovation pipeline, at a stage where the detailed process data required for LCA are not yet available. ReNA is therefore intended as an early-stage screening tool that complements, rather than replaces, LCA.