Reaction solutions: Scale-up

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Scaling up reactions from lab to commercial pilot scale is a challenge that requires experience and an adaptable range of laboratory components. Setting up a pilot plant is never simple, and although costs are significantly lower than they could be with mistakes made in a commercial plant, it is still desirable to avoid them.

Pilot plants may be required to study a process prior to scale-up, to produce small-scale samples for testing, or to yield specialty chemicals for smaller markets. The pilot plant is an essential step [1] and the reasons include:

  • The prospective waste streams need to be considered i.e., disposal/recycling of solvent
  • Macro-processes need to be examined to understand the reaction on a larger scale
  • Process interactions i.e., mixing of large quantities of reactants
  • Process variations, how small changes can cause significant variation and side reactions
  • Process controls, how can the reaction be controlled on a larger scale by heating, cooling, stirring rate
  • Development of standard operating procedures (SOPs), at pilot scale the process can be better studied and SOPs can be safely developed and permitted

The Scale-up

Pilot plants vary from 10L to 1000L and this relies upon the objective of the scale-up and the processing of the reaction. Typically the pilot plant should be on the largest scale that is economically feasible and within acceptable safety parameters. The reaction vessel is central to the process and its design should begin with attention to the height to width aspect ratio of the lab scale vessel as this is one less variable to consider. Scalability should be discussed in the first instance with a reputable technology provider such as Julabo Reaction Solutions as they can produce reaction vessels of the requisite design, size and material. The pilot plant should mimic the intended commercial plant, as this initiates the development process and contributes to accurate data for scale-up. The geometry of the reaction vessel and additional transfer vessels or receivers should be akin to the lab scale plant and retained if feasible. The geometry affects agitation patterns and hence the mixing, heat transfer and mass transfer. These parameters are important as they can lead to different kinetics, heating/cooling times, longer reaction times and in some cases lowers the yield, quality and purity of the final product.

Fig 1. Bench Top Reactor

Reaction Kinetics

When the scale increases, the process changes and the reasons for this are varied. On lab scale raw materials and catalysts are of minimal quantities and a very high purity grade can be used. However, on larger scale high purity material might be expensive and commercial grade material will be used. This change might play a part in the reaction kinetics. Other important considerations [2, 3] include:

  • Efficient agitation or mixing to achieve the desired mixing profile. The speed required and the viscosity of the reaction mixture determines the size and type of the mixer required
  • How materials are added to the reaction vessel. This is rarely considered but on larger scale liquids and powders may need to be ‘metered in’ at a given rate and mixed quickly often under inert atmosphere
  • Temperature Control. Many reactions require critical temperature control to reduce side reactions that can affect yield
  • Condenser type, sizing, and temperature control. In reflux or distillation, condensers need to be of the correct size for the application. They should also be used with a dedicated temperature control chiller for precise reaction control
  • Reaction vessel port configuration and seal compatibility. Consideration needs to be given to the complexity of the process and how this changes upon scale-up. The compatibility of materials used in the plant such as seals and traps must also be considered.  

Fig 2 Large Scale Reactor

The Next Step

The pilot plant should be constructed of the same material as the one intended for scale-up to allow a study of the effect of the raw material or catalyst on the material such as corrosion. Some process conditions may not be the same e.g., heat transfer in a glass lined reactor is considerably lower than a stainless steel reactor [3,4]. There should be an option for modification of the pilot plant, either to change the process or because the plant could be multi-purpose. Pilot plants are hazardous and safety review and training are essential for the operators/staff. Logistics are also important as larger quantities of material and waste need to be handled.

Julabo Reaction Solutions and Cooling

Julabo provide a comprehensive range for pilot plant construction including reaction vessels, heating and cooling elements, mixers/stirrers and vacuum pumps. Their experience makes them an important resource for technical advice and design in any scale-up. Many scaled up reactions require precise temperature control and Julabo’s ‘highly dynamic temperature control systems’ provide the ability to handle challenging temperature change profiles.


  1. Frankie Wood-Black, Considerations for Scale-Up – Moving from the Bench to the Pilot Plant to Full Production, Academia and Industrial Pilot Plant Operations and Safety, ACS Symposium Series, Vol. 1163, Chapter 3, pp 37–45, DOI: 10.1021/bk-2014-1163.ch003
  2. B. Alhamad, R.Willis, J. A. Romagnoli, V. G. Gomes, Optimal Control Of Emulsion Copolymerization: Application to a Pilot-Scale Reactor Under a DCS Environment
  3. Magdalena M. Lozinska, Enzo Mangano et al., Cation Control of Molecular Sieving by Flexible Li-Containing Zeolite Rho, J. Phys. Chem. C, August 08, 2016, DOI: 10.1021/acs.jpcc.6b04837
  4. Soumitra R. Deshmukh, Anna Lee Y. Tonkovich, et al., Scale-Up of Microchannel Reactors For Fischer−Tropsch Synthesis, Ind. Eng. Chem. Res., 2010, 49 (21), pp 10883–10888, DOI: 10.1021/ie100518u


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