(41b) Kinetic Resolution of 1-Phenylethanol in the Spinning Mesh Disc Reactor: A Techno-Economic Analysis

An increasingly important reaction in the pharmaceutical and fine chemicals industry is the kinetic resolution of racemates; a result of the demand for chiral intermediates growing from both pharmaceutical and agricultural industries [1]. An example of this is the kinetic resolution of 1-phenylethanol. 1-phenylethanol can undergo an acylation reaction when in the presence of an enzyme that produces the ester, R-1-phenylethyl acetate at a rate much greater than the optically opposite ester. This allows for the separation of the two enantiomers to be used in their respective applications.

Process intensification is generally a development that leads to a more environmentally and economically efficient process [2]. For the kinetic resolution reaction, this has come in a multitude of forms. One solution is the spinning mesh disc reactor (SMDR). Developed from the concept of a spinning disc reactor (SDR), with the addition of a mesh housing purposed for the immobilisation of enzymes, the SMDR has shown to achieve process intensification [3]. The advantages of the SMDR in comparison to a traditional batch reactor lie in its enhanced mass transfer (due to the thinly sheared film of reactant fluid spread across the rotating discs surface), residence time distribution and ability to protect the enzymes from shear forces [4]. It also has faster mixing and can reduce the need for large quantities of enzyme by increasing reusability in comparison to a batch reactor using free enzyme. So far, the SMDR has shown success on the laboratory scale but no research has been conducted on the economic feasibility of the reactor. Techno-economic analysis (TEA) is a tool that can determine economic viability beyond the lab scale and sensitivity analysis can be used to determine the uncertainty in the model. Within this study, we have carried out a comparative TEA of the kinetic resolution of 1-phenylethanol in a batch reactor and the SMDR.

Two production scales of 100 and 20 tonnes per year were considered – the former being the most competitive economically. Energy consumption in the SMDR was higher than that of the batch process, requiring 120,000 kWh per year compared to 19,000 kWh at the 100 t/y scale. The difference was almost five times greater at the smaller scale. Uncertainty in the process design and prices used for modelling cost was high. Therefore, probabilistic estimates of the cost of manufacture (COM) were generated using Monte Carlo simulations. At both scales, variation in COM was higher in the batch reactor. For 100 t/y, a 50% confidence interval surrounding the mean confirmed the COM for the SMDR would be lower than that of the batch reactor. The batch process had a 50% probability of costing between £18,433 and £21,229 per tonne of product. For the SMDR the range fell between £16,413 and £18,171. At 20 t/y, the batch and SMDR processes had significant overlap of estimated costs and a much lower probability that the SMDR would be cheaper than the batch reactor. Minimum estimated selling price (MESP) was determined to be most sensitive to the conversion of the reaction and the cost of raw materials. Specifically, the batch process was most sensitive to lipase cost (as 11 times the amount was required compared to the SMDR) and the SMDR to 1-phenylethanol cost.

To the best of the authors’ knowledge, this is the first study on the economic feasibility of using the novel SMDR for kinetic resolution of 1-phenylethanol. The SMDR has clear economic advantages derived from its enhanced mass transfer and enzyme immobilisation, in comparison to traditional batch reactor at large scales. The implementation of the SMDR in industry for reactions of this nature is likely to be beneficial in both long and short-term applications.

References:

[1] M. Habulin and Z. Knez, "Optimization of (R,S)-1-phenylethanol kinetic resolution over Candida antarctica lipase B in ionic liquids," Journal of Molecular Catalysis B: Enzymatic, vol. 58, pp. 24-28, 2009.

[2] G. Keller and P. Bryan, "Process engineering: moving in new directions," Chemical Engineering Progress, pp. 41-50, 2000.

[3] P. Shivaprasad, M. D. Jones, D. A. Patterson and E. A. C. Emanuelsson, "Kinetic resolution of 1-phenylethanol in the spinning mesh disc reactor: Investigating the reactor performance using immobilised lipase catalyst," Chemical Engineering and Processing - Process Intensification, vol. 132, pp. 56-64, 2018.

[4] P. Oxley, C. Brechtelsbauer, F. Ricard, N. Lewis and C. Ramshaw, "Evaluation of Spinning Disk Reactor Technology for the Manufacture of Pharmaceuticals," Industrial & Engineering Chemistry Research, vol. 39, no. 7, pp. 2175-2182, 2000.