Enzymatic Synthesis of Trimethyl-ϵ-caprolactone: Process Intensification and Demonstration on a 100 L Scale

14Citations
Citations of this article
25Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Optimization and scaling up of the Baeyer-Villiger oxidation of 3,3,5-trimethyl-cyclohexanone to trimethyl-ϵ-caprolactones (CHLs) were studied to demonstrate this technology on a 100 L pilot plant scale. The reaction was catalyzed by a cyclohexanone monooxygenase from Thermocrispum municipale that utilizes the costly redox cofactor nicotinamide adenine dinucleotide phosphate (reduced form), which was regenerated by a glucose dehydrogenase (GDH). As a first stage, different cyclohexanone monooxygenase formulations were tested: Cell-free extract, whole cells, fermentation broth, and sonicated fermentation broth. Using broth resulted in the highest yield (63%) and required the least biocatalyst preparation effort. Two commercial glucose dehydrogenases (GDH-105 and GDH-01) were evaluated, resulting in similar performances. Substrate dosing rates and biocatalyst loadings were optimized. On a 30 mL scale, the best conditions were found when 30 mM h-1 dosing rate, 10% (v/v) cyclohexanone monooxygenase broth, and 0.05% (v/v) of glucose dehydrogenase (GDH-01) liquid enzyme formulation were applied. These same conditions (with oxygen instead of air) were applied on a 1 L scale with 92% conversion, achieving a specific activity of 13.3 U gcell wet weight (cww)-1, a space time yield of 3.4 gCHL L-1 h-1, and a biocatalyst yield of 0.83 gCHL gcww-1. A final 100 L demonstration was performed in a pilot plant facility. After 9 h, the reaction reached 85% conversion, 12.8 U gcww-1, a space time yield of 2.7 g L-1 h-1, and a biocatalyst yield of 0.60 gCHL gcww-1. The extraction of product resulted in 2.58 kg of isolated final product. The overall isolated CHL yield was 76% (distal lactone 47% and proximal lactone 53%).

Cite

CITATION STYLE

APA

Solé, J., Brummund, J., Caminal, G., Álvaro, G., Schürmann, M., & Guillén, M. (2019). Enzymatic Synthesis of Trimethyl-ϵ-caprolactone: Process Intensification and Demonstration on a 100 L Scale. Organic Process Research and Development, 23(11), 2336–2344. https://doi.org/10.1021/acs.oprd.9b00185

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free