High-throughput on demand access of single enantiomers by a continuous flow crystallization process

Cameli, Fabio; Xiouras, Christos; Stefanidis, Georgios D.

doi:10.1039/d0ce00366b

Cited by 16 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…22 Over the last two decades, the continuous mode has gained the interest of industry and academia due to its many advantages 23 over discontinuous mode including better reproducibility and yields, 49,[51][52][53] shorter development period and costs, 30 smaller equipment footprint 55 (up to 20% reduction in the CapEx) 23 and precise control of process parameters. 54 There are some challenges found in literature associated with the scale-up of continuous crystallization including fouling, clogging, and encrustation. Such events are predominantly caused by heterogeneous nucleation due to insufficient heat transfer or equipment material differences between scales.…”

Section: Preferential Crystallizationmentioning

confidence: 99%

“…7). 91 Recently, Cameli et al 54 reported the continuous preferential crystallization of isoindoline-1-ones derivatives using a plug flow crystallizer immersed in two thermostatic baths set at different temperatures. This configuration allowed them to obtain productivities of 20 g L −1 h −1 due to the excellent heat transfer and low residence periods (Table 4 and Fig.…”

Section: Preferential Crystallizationmentioning

confidence: 99%

See 1 more Smart Citation

Semi-continuous and continuous processes for enantiomeric separation

2022

View full text Add to dashboard Cite

show abstract

Section: Preferential Crystallizationmentioning

confidence: 99%

Section: Preferential Crystallizationmentioning

confidence: 99%

Semi-continuous and continuous processes for enantiomeric separation

2022

View full text Add to dashboard Cite

show abstract

“… 24 Another step toward industrial application is based on the batch temperature cycling experiments carried out in a microwave reactor, 25 i.e., exploiting very fast heating and cooling rates, and its continuous alternative was presented by employing spatial thermal oscillations in a tubular flow millireactor. 26 In a recent work, the feasibility of performing continuous temperature cycles in a continuous tubular crystallizer was demonstrated. 27 Nevertheless, to the best of our knowledge, application of periodic temperature cycles in mixed suspension mixed product removal crystallizers (MSMPRCs) for the purpose of solid-state deracemization has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Solid-State Deracemization via Temperature Cycles in Continuous Operation: Model-Based Process Design

Bodák

Mazzotti

2022

Crystal Growth & Design

View full text Add to dashboard Cite

Solid-state deracemization via temperature cycles converts a racemic crystal mixture into an enantiopure product by periodic cycling of the temperature in the presence of a racemization catalyst. A continuous counterpart of this conventional batch-operated process is proposed that can be performed in mixed suspension mixed product removal crystallizers (MSMPRCs). More specifically, three different configurations are described to perform periodic forcing via temperature cycles, which differ from each other in the type of the feed and in the withdrawal system. We have developed a model by extending our recent population balance equation model of batch solid-state deracemization via temperature cycles, and we exploit this tool to analyze the start-up and periodic steady-state behavior. Moreover, we compare the performance of the different configurations based on the selected key performance indicators, namely, average periodic steady-state enantiomeric excess and productivity. The process with solution feed yields pure enantiomers, while the solid and suspension-fed process alternatives result in highly enantiomerically enriched crystals. We further design an MSMPRC cascade to overcome this purity limitation. This work discusses guidelines on how to transform the batch process of temperature cycles into a continuous operation, which enables stable, unattended operation and chiral crystal production with consistent product quality.

show abstract

“…The quantification of crystal growth, dissolution, and agglomeration kinetics provided here can be readily combined with previously existing breakage/secondary nucleation models 14,20,21 for sodium chlorate to quantitatively simulate complex crystallization processes such as deracemization through Viedma ripening or temperature cycling. 18,22 2. THEORY 2.1.…”

Section: Introductionmentioning

confidence: 99%

“…Finally, the dissolution rates of sodium chlorate are estimated under operating conditions similar to the ones used for the growth experiments. The quantification of crystal growth, dissolution, and agglomeration kinetics provided here can be readily combined with previously existing breakage/secondary nucleation models ,, for sodium chlorate to quantitatively simulate complex crystallization processes such as deracemization through Viedma ripening or temperature cycling. , …”

Section: Introductionmentioning

confidence: 99%

Crystal Growth, Dissolution, and Agglomeration Kinetics of Sodium Chlorate

Fytopoulos

Kavousanakis

Gerven

et al. 2021

Ind. Eng. Chem. Res.

Self Cite

View full text Add to dashboard Cite

The analysis, development, and implementation of novel complex industrial crystallization processes requires kinetic knowledge of not only crystal growth and nucleation but also breakage, dissolution, and agglomeration processes. In this work, the crystal growth, dissolution, and agglomeration kinetics of sodium chlorate (NaClO3) in aqueous solutions are estimated via seeded batch experiments with in-line particle size distribution measurements. Contrary to previous works, the growth/dissolution kinetics are expressed in terms of the fundamental driving force of crystallization calculated from the activity of supersaturated solutions. The activity-based driving force is roughly 2-fold higher than the commonly used representation, which assumes ideal solutions. By fitting experimental desupersaturation data to mechanistic and empirical growth models, we show that the growth of sodium chlorate is surface integration controlled and is best described by a two-dimensional birth and spread surface nucleation mechanism. The dissolution of sodium chlorate crystals is diffusion controlled and is ∼4 times faster than the growth at an equal initial driving force. Particle agglomeration is substantial in the early stages of crystallization experiments, likely due to a strong increase in the particle number due to initial breeding secondary nucleation upon seeding. The agglomeration rate constant increases with supersaturation and decreases at higher energy dissipation rate (by increased agitation) due to a strong decrease in the efficiency of interparticle collisions. Seeding with material of different sizes does not influence the agglomeration rate constant, although substantial amount of small particles was present in all seeding materials.

show abstract

High-throughput on demand access of single enantiomers by a continuous flow crystallization process

Abstract: A novel continuous flow reactive crystallization process for the in situ on-demand access of single enantiomer crystals is reported and exemplified for a chiral pharmaceutical intermediate that crystallizes as a racemic conglomerate.

Cited by 16 publications

References 32 publications

Semi-continuous and continuous processes for enantiomeric separation

Semi-continuous and continuous processes for enantiomeric separation

Solid-State Deracemization via Temperature Cycles in Continuous Operation: Model-Based Process Design

Crystal Growth, Dissolution, and Agglomeration Kinetics of Sodium Chlorate

Contact Info

Product

Resources

About