REACTOR TECHNOLOGY
amount of time to reach 90 % completion being very similar. Clearly, faster heating has the largest effect when the heating lag of the system has the biggest influence. During short reactions( i. e. < 4 hours) the time to reach 90 % conversion can be nearly 60 % less than that required by a conventional process reactor.
Controlling exothermic processes at scale
The monobenzylation of amines at large-scale is known to be a challenge due to the propensity for overalkylation. Chemists will often use alternative routes to achieve the same outcome, for example imine formation then reduction, but this approach is arguably less efficient in terms of time and resource.
The monobenzylation of aniline using LiHMDS and benzyl bromide was investigated on 1 L scale by Orito et al.( Figure 3). 3 They found that slow addition of the strong base was necessary to prevent the large exotherm, which was expected to be even more challenging to control as scale increased further.
Knowing that the monobenzylation of aniline is severely exothermic, and knowing the superior cooling capabilities of the PI QFlux, we therefore simulated this reaction at 1,000 L scale, with a cooling step to take the reactor from 15 ° C to 0 ° C undertaken prior to base addition. 2 Overall, 600 mol of LiHMDS were added to aniline( 600 mol) as a 1.5 mol / L solution in THF( 400 L) at a nominal dose rate of 1 L / s( Figure 3).
Figure 3- Conversion of aniline to N-benzylaniline by alkylation with benzylbromide in the presence of LiHMDS.
Due to the enhanced thermal control of the reactor vessel, the PI QFlux achieved this necessary pre-cooling in only 9 minutes, compared to the 38 minutes required for the conventional large-scale batch reactor.
Controlling the reaction exotherm was also more efficient. When the dosing rate was actively limited to maintain a reaction temperature of less than 10 ° C, the requisite precooling and addition of LiHMDS took 31 minutes in total, compared with 107 for the conventional batch reactor( Table 1). The yield of monobenzylated product was also slightly enhanced, at 90.6 % compared to 90.4 % for the traditional batch set-up.
Finally, in reactions where rapid heating and cooling is necessary to improve selectivity, the PI QFlux also proved superior. In a simulated reaction process, where the desired product is susceptible to degradation at the reaction temperature, rapid cooling and work-up was found to reduce degradation product contamination from 7.2 % to 4.7 %. 2
Outlook
Fast-batch reactor systems, such as the PI QFlux, could rapidly become a valuable, complementary tool to traditional process reactors and flow chemistry systems, providing superior heating and cooling performance under both experimental and simulated conditions. Their plug-and-play installation, similar footprint to existing reactors, and ability to provide favourable production outputs at much lower reactor volume sizes, means their implementation is possible without substantial amendments to existing infrastructure.
In addition, their similarity in operation to traditional jacketed reactors means that additional staff training is not necessary – and flexibility in duty and capability is retained – therefore the scale-up of key reactions can be undertaken much more quickly. ●
*- PI QFlux is a registered trademark of PTSC
Vessel |
T limit /° C |
Pre-cool time / min |
Dose time / min |
Yield % |
batch |
1 |
38 |
263 |
80.0 |
batch |
5 |
38 |
165 |
85.5 |
batch |
10 |
38 |
107 |
90.4 |
PI QFlux |
1 |
9 |
73 |
81.4 |
PI QFlux |
5 |
9 |
46 |
86.5 |
References: 1: M. C. Bannerman & P. Kechagiopoulos, Progress Report on Collaboration between the University of Aberdeen and PTSC Ltd., University of Aberdeen, Chemical & Materials Engineering Research Group, 2019. 2: B. J. Deadman, PI QFlux White Paper Series, BJ Deadman Consultancy Ltd, London, 2025. https:// www. ptscltd. co. uk / white-papers 3: Y. Orito, Org. Process Res. Dev., 2025, 29, 1757 – 1765.
PI QFlux 10 9 31 90.6
Table 1- Process time and yield in a simulated monobenzylation process at 1,000 L scale. Note: Vessel pre-cooled from 15 ° C to 0 ° C prior to dosing; exothermic dosing actively controlled to keep the temperature under the T limit
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60 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981