Data-Driven Recommendation of Agents, Temperature, and Equivalence Ratios for Organic Synthesis

Abstract

The identification of suitable reaction conditions is a crucial step in organic synthesis. Computer-aided synthesis planning promises to improve the efficiency of chemistry and enable robot-assisted workflows, but there remains a gap in bridging computational tools with experimental execution due to the challenge of reaction condition prediction. The conditions used to carry out a reaction consist of qualitative details, such as the discrete identities of “above-the-arrow” agents (catalysts, additives, solvents, etc.) as well as quantitative details, such as temperature and concentrations of both reactants (product contributing) and agents. These procedural aspects of organic chemistry exert a direct influence over the outcome of a chemical transformation and must be provided in any hypothetical autonomous synthesis workflow. In this work, we push beyond qualitative reaction condition recommendation by developing a data-driven framework that incorporates quantitative details, specifically equivalence ratios. We frame the condition recommendation problem as four sub-tasks: predicting agent identities, reaction temperature, reactant amounts, and agent amounts, and evaluate our model accordingly. We demonstrate improved performance over popularity and nearest neighbor baselines and highlight the model’s practical utility for predicting conditions in diverse reaction classes via representative case studies.