Learning To Predict Reaction Conditions: Relationships between Solvent, Molecular Structure, and Catalyst

Reaction databases provide a great deal of useful information to assist planning of experiments, but do not provide any interpretation or chemical concepts to accompany this information. In this work reactions are labeled with experimental conditions and network analysis shows that consistencies within clusters of data points can be leveraged to organize this information. In particular, this analysis shows how particular experimental conditions (specifically solvent) are effective in enabling specific organic reactions (Friedel-Crafts, Aldol addition, Claisen condensation, Diels-Alder, and Wittig), including variations within each reaction class. An example of network analysis is shown in the graphical abstract, where data points for a Claisen condensation reaction break into clusters that depend on the catalyst and chemical structure. This type of clustering, which mimics how a chemist reasons, is derived directly from the network. Therefore the findings of this work could augment synthesis planning by providing predictions in a fashion that mimics human chemists. To numerically evaluate solvent prediction ability, three methods are compared: network analysis (through the k-nearest neighbor algorithm), a support vector machine, and a deep neural network. The most accurate method in 4 of the 5 test cases is the network analysis, with deep neural networks also showing good prediction scores. The network analysis tool was evaluated by an expert panel of chemists, who generally agreed that the algorithm produced accurate solvent choices while simultaneously being transparent in the underlying reasons for its predictions.