Automation has become increasingly popular among synthetic chemists over the past decade.

Recent advances in robotics and computer science have led to the emergence of laboratory automation systems for parallel synthesis, reaction discovery, reaction optimization, time course studies, and crystallization development.

While such systems offer many potential benefits, their implementation is rarely fully automated due to the highly specialized nature of synthetic procedures. Each reaction class requires the careful execution of a specific sequence of steps, the details of which vary with different conditions and chemical systems. The key to developing effective automated workflows is to carefully evaluate these key procedural requirements and identify the tools appropriate for efficient experimental execution. Even so, it is often difficult to get all the components of an automated system integrated and operational. Vendors also do not typically share the pain points and processes for implementing automated systems. This viewpoint outlines the current state of automation in synthetic chemistry at the benchtop scale, with a particular emphasis on core considerations and challenges faced in deploying systems.

Synthesis

Synthesis is often as much an art as a science. Successful synthesis requires the careful execution of a complex series of reactions and steps that are highly variable, not to mention the interaction with a wide range of equipment. Deciding what the next step in a particular workflow should be is often based on experience and the chemist's intuition. However, the work of a synthetic chemist is not all glamorous. Many of the steps involved involve repetitive, time-consuming tasks performed on essentially the same objects.

Advantages of Automation

Automation offers a way to reduce human intervention in such processes. In the 1960s, Merrifield and Stewart proposed the first automated system for solid-phase peptide synthesis, which successfully reduced the time required for stepwise additions and purifications, and reduced material losses. Since then, automation has gradually entered synthetic chemistry laboratories, initially in the form of mechanized systems that performed essentially the same tasks. These systems laid the foundation for the development of specialized platforms capable of automating combinatorial chemistry and high-throughput experimentation. More recently, there has been a shift toward flexible, modular systems with an emphasis on autonomous decision-making rather than simple automation.

The appeal of automation is often to increase efficiency (by offloading repetitive tasks and increasing throughput), reproducibility (given the high precision of robotic tools), and safety (hazardous chemicals or reactions can be performed with reduced human exposure). Importantly, automation opens up capabilities that are difficult for humans to perform in a practical manner (e.g., automatically sampling 10 reactions in parallel).