OPRD-Imp: a dataset of experimentally observed impurities and side products in multi-step pharmaceutical syntheses
Authors: Heejeong Kim, Seonbin Kim, Jihwan Kim, Tim Pinkhassik, Magdalena Lederbauer, Suong Tran, Connor W. Coley, Juyoung Yoon, Joonyoung F. Joung
Organizations: Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, South Korea · Department of Chemistry, Kookmin University, Seoul, 02707, South Korea · Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA · Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA · Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA
Predicting reaction impurities is a critical yet persistently data-limited challenge in pharmaceutical process chemistry. While machine learning models for reaction outcome prediction have advanced rapidly, benchmarking their ability to predict impurities remains impractical due to the absence of curated, publicly accessible datasets. We present OPRD-Imp, a dataset of 229 organic reactions drawn from 62 publications in Organic Process Research & Development, each annotated with experimentally observed impurities and their mechanistic origins. A total of 784 impurity entries is provided, classified into four origin categories. Reactions are represented as reaction SMILES and impurities as individual SMILES strings, with multi-step synthetic route connectivity preserved. All data were manually extracted from the source publications by trained chemists following a standardized extraction protocol, with expert chemical validation and manual structure drawing. OPRD-Imp is intended to serve as a benchmark resource for evaluating models that predict reaction impurities, providing experimentally reported impurity annotations and mechanistic origin labels that are not systematically represented in conventional reaction datasets.
Chemical reaction datasets such as USPTO suffer from substantial incompleteness, frequently missing byproducts, co-reactants, and stoichiometric coefficients. This limits their applicability and reliability in downstream applications. Here, we introduce CompleteRXN, a large-scale supervised benchmark for reaction completion under realistic missing-data conditions. We construct a dataset of aligned incomplete and atom-balanced reactions by mapping USPTO records to curated mechanistic reactions. We evaluate representative baselines, including a novel encoder-decoder reaction completion model with constrained decoding, the Constrained Reaction Balancer (CRB), and a recent algorithmic method, SynRBL. On our CompleteRXN benchmark, the CRB achieves high performance across splits of increasing difficulty, reaching 99.28% equivalence accuracy on the random split and 91.71% on the extreme out-of-distribution split. SynRBL produces many balanced and chemically plausible completions, but with lower accuracy on the benchmark test splits. Across all methods, performance degrades with increasing incompleteness. We observe a substantial drop when evaluating on reactions outside the benchmark (full uncurated USPTO), highlighting the gap between benchmark performance and practical robustness and motivating future work. Data, code and models can be found at: https://github.com/Intelligent-molecular-systems/CompleteRxn-Benchmarking.
Gabriel Vogel, Minouk Noordsij, Evgeny Pidko +1
Department of Intelligent Systems, Delft University of Technology, Delft, 2629 HZ, The Netherlands · Department of Chemical Engineering, Delft University of Technology, Delft, 2629 HZ, The Netherlands
High-quality structured organic reaction data are essential for developing artificial intelligence for chemistry (AI4Chem), yet much of this knowledge remains dispersed across patent text, images, and reaction schemes. We present DianShi-RxnDB, a large-scale, fine-grained organic reaction data platform built via a fully automated extraction and normalization pipeline integrating patent text, images, and reaction schemes. Its corpus covers organic synthesis patents from the USPTO and EPO published between 1976 and 2025, yielding approximately 24 million reaction instances, of which approximately 14.8 million (61.7%) pass automated qualification checks. Each instance represents a specific single-step experiment recording participants, roles, quantities, temperatures, reaction times, yields, experimental procedures, and provenance links to source patents. In a manual evaluation of 1,300 sampled qualified instances, the micro-averaged field-level accuracy was 92.95%. A matched comparison with Pistachio further indicated advantages in deduplicated record counts, representation granularity, and field-level exact agreement. The platform provides a Web research workbench for searching, filtering, comparing, and source-verifying records, and a Model Context Protocol (MCP) service offering AI agents composable structured retrieval tools. DianShi-RxnDB is available at https://dianshi.opendatalab.org.cn/ .
Screen Tables and Substrate Scopes are information-dense figures widely used in synthetic chemistry literature, yet automated extraction of structured reaction data from them remains challenging. We introduce RxnExBench, a multimodal benchmark for fine-grained reaction-level evaluation. Built from high-impact chemistry journals, it contains 3,565 expert-annotated reactions and 2,361 molecular structures. The dataset adopts a unified schema with 15 reaction roles and 26 core fields, supporting downstream AI-for-Chemistry tasks such as retrosynthetic planning, yield prediction, and reaction condition recommendation. RxnExBench further provides a reasoning-driven difficulty taxonomy, a modular annotation pipeline, and the Oracle-MolRec protocol, which disentangles molecular recognition from higher-level reasoning. Evaluation of 9 state-of-the-art VLMs shows that performance degrades substantially as schema complexity and reasoning demands increase. Under the Oracle-MolRec setting, results further reveal that accurate molecular recognition alone is insufficient, with multimodal integration and chemistry-aware reasoning remaining the primary bottlenecks. We release all data and code to facilitate future research in chemistry-aware multimodal understanding and AI-for-Chemistry dataset construction. The dataset and code will be released at https://github.com/opendatalab/RxnExBench.
Jiaxing Sun, Junyuan Gao, Ruikang Zhang +16
Shanghai Artificial Intelligence Laboratory · Peking University · South China Normal University +7