Decoding Reactions in Process Chemistry: A Quarter-Century Analysis of Trends and Transformations in <i>OPR&amp;D</i>

This study presents the first comprehensive analysis of synthetic chemistry practices in process development through a systematic examination of Organic Process Research & Development (OPR&D) publications from 2000–2025 each indexed and collected by the CAS Content Collection. We analyzed over 4,800 original research articles encompassing more than 34,000 reactions to characterize the synthetic methods, reagent choices, solvent preferences, and experimental conditions employed in scalable chemical processes. Industrial organizations account for 65% of publications, reflecting the strong applied focus of process chemistry research. Although cross-coupling reactions, particularly Suzuki cross-coupling, dominate today’s literature with the highest publication frequency, acylation and alkylation transformations are the most frequently performed reactions in practice. The field is characterized by rapid (15 min–1 h reaction time) and high-yielding transformations (predominantly >90% yield) conducted at ambient pressure with moderate heating (50–100 °C), with tetrahydrofuran (THF) and dichloromethane (DCM) remaining the most prevalent solvents despite increased regulation of DCM use. Palladium-based catalysts still predominate in metal-catalyzed processes. EDC [1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide] is the most common coupling reagent in process chemistry for amide bond formation. Flow chemistry has emerged as an enabling technology over the past two decades, appearing in an increasing proportion of highly cited research articles. Our data-driven analysis provides process chemists with evidence-based guidance while documenting the field’s evolution with respect to synthetic methods, reagent choices, solvent preferences, and experimental conditions.