A panoramic view of any scientific field, especially across decades, can be challenging and rewarding. In the case of process chemistry, individual case studies and lessons learned from specific scale‑up examples are available. However, a new collaboration between CAS and Lilly brought together scientists from both organizations to conduct the first large‑scale, data‑driven analysis of 25 years of process chemistry practice in the journal Organic Process Research & Development (OPR&D). What makes this collaboration particularly powerful is Lilly's deep industrial expertise in process chemistry, accumulated through decades of drug development and manufacturing, combined with the renowned data infrastructure and analytical capabilities of CAS. Together, these complementary strengths enabled a unique, joint analysis made possible by a combined team of expert colleagues with access to well-indexed data on thousands of chemical reactions from the CAS Content Collection™.
The team examined more than two decades of published process‑scale reactions to explore how the field has evolved, which methodologies dominate at scale, and how strategies have shifted as industry needs have changed. The dataset and its analysis offer a rare look at long-term, real‑world trends based on the structured analysis of thousands of experiments.
What decades of data can tell today’s process chemists
The CAS–Lilly team analyzed more than 34,000 reactions drawn from 4,805 original research articles published between 2000 and 2025. While someone working in the field may find their work reflected in any one trend, seeing the full scope quantified at this scale is exciting and rewarding.
For example:
- Rapid and high-yielding reactions conducted at ambient pressure with moderate heating tend to dominate.
- Tetrahydrofuran (THF) and dichloromethane (DCM) remain the solvent of choice, though a sizeable fraction of reactions report using water as the solvent.
- There is a strong and continued reliance on metal-based catalysts (especially palladium-based).
- A growing application/relevance of flow chemistry has emerged.
These findings rely on deep data curation, chemical-context tagging, and reaction-level indexing drawn from the CAS Content Collection. This foundation begins with technology but is not purely algorithmic: at its core is a team of specialized scientists and analysts who make connections and identify trends that require expert human judgment combined with advanced data technology. The depth and quality of this work make it possible to derive insights across a many parameters, including solvent usage, reaction conditions reported in the primary literature, and the types of reactions being conducted at commercial and industrial scales.
A picture of how the field has changed, and is still changing
The analysis highlights the resilience of established methodologies and the industry’s growing interest in new technologies. These results aren’t just observations; they form a dataset that can support more informed route design, benchmarking, and technology evaluation. Whether you're assessing a synthetic strategy for a new clinical candidate or evaluating alternative solvents and catalysts for an established process, this work provides a unique, empirical look at what the community has been doing.
The full peer-reviewed journal article provides detailed figures about reaction‑type trends, solvent and catalyst distributions, and a deep look at how process chemistry has evolved over the past quarter-century.
On a related note, we’d like to wish both Lilly and ACS (parent organization of CAS) a happy 150th anniversary! As ACS celebrates 150 years since the founding of the American Chemical Society and Lilly honors the founding of Eli Lilly, both in 1876, we can all applaud the positive impact each organization has had on many scientific fields and discoveries.
Read the full study, Decoding Reactions in Process Chemistry: A Quarter-Century Analysis of Trends and Transformations in OPR&D, to explore all the exclusive insights from this CAS–Lilly collaboration.
