Thesis
Novel methods and processes for the chiral resolution of fine chemicals
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2020
- Thesis identifier
- T15800
- Person Identifier (Local)
- 201778036
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Chiral molecules occur in left- and right-handed configurations that can be considered asmirror images (enantiomers), and that, like hands, cannot be superimposed onto each other.Despite their similarity, the biological activity of enantiomers inside living organisms can becompletely different. While one enantiomer may have a desirable therapeutic effect, the othermay induce no response or even be harmful. Most pharmaceuticals and agrochemicals arechiral. The search of this specificity at the molecular level led to the development of manyasymmetric syntheses. However, the enantioselective synthetic approach is not alwayspossible and the mixture of equal amounts of both enantiomers (racemate) is obtained instead.Then, the separation of these enantiomers, known as chiral resolution, becomes the alternativepathway. Chiral resolution techniques have already been developed, but they still presentsome limitations. For that, the aim of this thesis is to develop novel methodologies andprocesses that integrate membrane filtration, crystallisation, and extraction technologiesfor the chiral resolution of fine chemical racemates.In chapter 3, the effects of pH and temperature on the solubility and phase diagrams ofthree racemic compound-forming systems are described. This preliminary study of effectspermits the development of a method to accurately estimate the eutectic points and phasediagrams of these systems. Additionally, the method also gives the possibility to determinethe class of crystal lattice (conglomerate, racemic compound, or solid solution) of any chiralcompound. The ultimate objective of this chapter is to provide a workflow process todetermine fast and accurately the phase diagrams of racemic compounds.The chiral resolution of conglomerates has been successful by means of crystallisationbased techniques such as preferential crystallisation. Nevertheless, this type of chiralcompounds alongside solid solutions are rare with racemic compounds being the mostabundant. The latter class requires an initial enantiomeric enrichment which must go beyondthe eutectic composition to after being able to selectively crystallise an enantiopure product.The main objective of chapter 4 is to assess if the combination of membrane filtration andcrystallisation technologies enables the continuous chiral resolution of racemic compounds.This has been carried out through computerised modelling and optimisation of the integratedVIIprocess and has shown potential to further explore and test the process with other chiralsystems.The separation of enantiomers can also be attempted by leveraging the potential distinctiveenantiospecific interactions between enantiomers and chiral solvents. In that way, chapter 5evaluates the chiral recognition capacity of the relatively new chiral solvent cyrene and findsits potential for chiral resolution process applications founded on both enantioselective liquidliquid extraction and crystallisation.The work in this thesis has achieved its aim in developing novel methodologies andprocesses for the chiral resolution of fine chemical racemates by providing a less laboriousworkflow process for the fast and accurate determination of ternary phase diagrams ofracemic compounds, which has served to propose a novel chiral resolution process for thisclass of chiral compounds that integrates both membrane filtration and crystallisationtechnologies. In addition, the enantiomeric discrimination power found in the chiralsolvent cyrene has made possible to propose this solvent for its use in the separation ofenantiomers by means of enantioselective liquid-liquid extraction and crystallisation. Thefindings described in this text will then facilitate the study, understanding, andcharacterisation of chiral resolution processes based on enantioselective interactions inseparation techniques, such as membrane filtration, crystallisation, and extraction. Thenew methodologies and processes developed in this thesis have the potential to addresscurrent and future challenges in the separation of enantiomers, which is of high interestfor the fine chemical industry.
- Advisor / supervisor
- Ter Horst, Joop H.
- Resource Type
- Note
- Previously held under moratorium from 1st March 2021 until 1st March 2023
- DOI
- Date Created
- 2020
- Former identifier
- 9912955389202996
- Funder
Relações
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PDF of thesis T15800 | 2021-07-02 | Público | Baixar |