Integrating flow & batch
Dr Ulrich Mayerhöffer of Arxada shares some case studies of reactions using a combination of techniques
Flow chemistry and batch or semi-batch processes represent two fundamentally different approaches to chemical synthesis. Each method comes with its own set of strengths and limitations, and the choice between them depends on various factors, including reaction type, production scale, safety profile and regulatory considerations.
Flow pros & cons
Flow chemistry enhances safety by limiting the amount of hazardous material in the system at any given time, thanks to small reactor volumes and improved heat and mass transfer. This is particularly valuable for highly exothermic or potent reactions. Moreover, flow processes are inherently scalable, by extending run time or employing multiple reactors in parallel. This offers a flexible path from development to commercial scale.
Flow chemistry enables precise regulation of temperature, pressure and residence time, allowing for tighter control over reaction outcomes. This precision often translates to increased efficiency, with shorter reaction times and higher yields thanks to better energy input and mixing. Sustainability is also improved, as flow reactions tend to consume less solvent and energy. Additionally, the steady-state nature of continuous manufacturing delivers consistent product quality and reduces batch-to-batch variability. Despite these strengths, flow chemistry also presents challenges. Setting up a continuous process requires specialised equipment and considerable development effort.
Figure 2- HCN network
1
2 3
Not all reactions are easily adapted to flow conditions, particularly those involving highly viscous materials, suspensions or solid-forming intermediates. There is also the risk of reactor clogging due to precipitate formation or side reactions. Furthermore, optimal operation often depends on real-time monitoring and control systems, which increase the complexity and cost of the set-up.
Batch & semi-batch
In contrast, batch and semi-batch chemistry offer high flexibility, making them well suited to diverse chemistries, especially those involving solids, multi-phase
3
4
1
2
4
5
6
5
Figure 1- Ketene / diketene network
Note: E-MMA = methyl( E)-3-methoxyacrylate; TFAAEt = ethyl 4,4,4-trifluoroacetoacetate
systems or slower reaction kinetics. The equipment and workflows are widely understood and relatively simple to operate, and they allow for easier troubleshooting and manual intervention, an important advantage during early-stage development or custom manufacturing.
However, scaling up batch processes can introduce safety and quality issues due to poor heat or mass transfer in large reactors. These methods can also be less efficient, with longer reaction times, greater solvent usage and increased waste generation. Additionally, operational downtime between
54 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981