PhD Defence Lisette Sprakel

molecular design and engineering for affinity separations of polar systems using isothermal titration calorimetry and molecular modeling

Lisette Sprakel is a PhD student in the Sustainable Process Technology group. Her supervisor is prof.dr.ir. B. Schuur from the Faculty of Science and Technology. 

There is a continuous incentive to improve industrial processes, not only from an economic and energy point of view, but also from the increasingly important perspective of green chemistry and bio-based production. The demand for the production of chemicals based on renewable feedstock and the design for energy efficiency is therefore increasing. For diluted aqueous streams ordinary distillation would require evaporation of large amounts of water and is therefore energy intensive. Also for mixtures of components with a low relative volatility ordinary distillation is energy intensive and in the case of azeotropes this separation process may even be impossible. Furthermore, some components that are applied in industry may even decompose at elevated temperatures. In these cases, affinity separations such as liquid-liquid extraction (LLX), extractive distillation (XD) and adsorption based processes are promising alternatives, as they improve or enable the separation by adding an affinity agent.

In affinity based separation processes there is a second column, next to the initial separation column, in which the regeneration of the affinity agent takes place. This is an important step for the overall feasibility of the process. In the case of LLX and XD the solvent is (or contains) the affinity agent and is regenerated in this second column, after which the solvent is recycled to the first column. Generally there is a trade-off between the LLX or XD step and the regeneration step in terms of the required energy input and other costs.

This thesis focuses on two main subjects. The first subject is liquid-liquid extraction of polar components such as acids from dilute aqueous streams and the second main subject is the separation of close-boiling mixtures of polar components by extractive distillation. LLX is already applied in industry for separation of carboxylic acids, which are polar components that are often present in highly diluted aqueous streams. Carboxylic acids are building blocks in the production of many bio-based plastics and other chemicals in the pharmaceutical, food and chemical industry. As a consequence there is a strong desire to produce these acids through fermentation, after which they are present in (dilute) aqueous streams and separation processes are required. Also in other diluted industrial (waste) streams a variety of valuable polar components or contaminants is present for which separation processes are required. Non-aqueous streams of polar components are studied for the second main subject of this thesis. Also for these components industrial application of affinity based separation can be of interest. For example in the case of very low relative volatility or azeotrope formation, XD is a promising technique instead of ordinary distillation.

Both LLX and XD are solvent based processes. There is a widespread interest in solvent selection criteria and methods. Initial selection can be based either on practical considerations, one of the several solvent scales that have been developed, empirical data and predictions or calculations based on activity coefficients. However, prediction of solvent effects on the relative volatility or acid distribution is a challenging task, especially for the (close-boiling) polar mixtures that are central to this thesis and in which specific and strong interactions, azeotropes and non-ideality are all common. Moreover, the feasibility of the regeneration should always be taken into account, for which more research and data may be required than only the solvent effects in the initial separation step.

Ideally, solvent selection should be simple, time-efficient and include considerations on the regeneration. The development of such a procedure requires fundamental understanding of the mechanisms and phenomena involved in LLX and XD. The use of isothermal titration calorimetry (ITC), and molecular modeling (MM) to characterize mechanisms, interactions and the effect of extractant and solvent composition on liquid-liquid equilibria (LLE) and vapor-liquid equilibria (VLE) were studied in this thesis. The thesis consists of two parts that each deal with affinity separations of close-boiling polar compounds. In the first part (Chapters 4-7) the focus is on LLX of acids and other polar compounds from aqueous solutions, while the second part (Chapters 8-9) focuses on extractive distillation processes of non-aqueous polar mixtures. The methods applied (ITC and MM) are introduced in the Chapters 2 and 3.

The study on the use of ITC to analyze acid-base interactions relevant for LLX is described in Chapter 2. The concentrations applied in LLX are up to a factor thousand higher than those applied in the biotechnology field where ITC is commonly applied. As complexation constants appeared to be extractant concentration dependent, a thorough analysis of the accuracy of ITC applied in the molar concentration domain applicable to LLX, is presented. Standard deviations were determined for the calculated thermodynamic parameters. Two different reaction models, based on either a single reaction or sequential reactions were compared for their applicability in acid-base interactions in LLX. The sequential reaction model is most suitable to fit ITC-results for acid-base titration in the system of acetic acid and trioctylamine (TOA) in toluene. Fitting of the sequential reaction model was found to be sensitive to the initial values as local minima do occur as a result of the number of parameters, indicating the importance of good initial guess values. Chapter 3 describes the method and calculation options of molecular modeling with Spartan’16 Parallel software. Furthermore, it includes a validation of the calculation levels applied and the assumptions related to molecular geometry and the incorporation of water molecules in the molecular modeling calculations.

Chapter 4 is the first chapter in the part of this thesis focusing on LLX and reviews solvent developments for LLX of carboxylic acids for three main categories of solvents, i.e. nitrogen-based extractants, phosphorous based extractants and ionic liquids. The mechanism of extraction is influenced by multiple variables, including extractant type, solvent composition and specific interactions with the diluent. Combining both active and inactive diluents was shown to be a promising approach.  No single parameter can describe all solvent effects on the LLE. Based on a comparison of different regeneration strategies for a typical LLX process, a diluent-swing based process appeared to be the most feasible. For a viable process, focusing on the change in acid distribution that can be achieved between the extraction and regeneration step is more important than the absolute distribution ratio itself. For temperature-swing regeneration processes this change can be related to the enthalpy of complex formation between acid and extractant. Therefore a study on the effect of extractant structure and composition on the enthalpy of complexation (Chapter 6) can strongly contribute to design of solvents.

Chapter 5 and 6 each focus on the understanding of mechanisms involved in LLX and study implications thereof on the molecular structure of good extractants. For these studies ITC was applied - supported by MM - on various acid-base interactions directly related to LLX. Chapter 5 focuses on the role of the diluent in the extraction mechanism for complexation of acetic acid and phenol with extractants TOA, trioctylphosphine oxide (TOPO) and tributylphosphate (TBP) in various diluents. With the help of ITC it was shown that increasing the temperature decreases all complexation constants and - supported by MM - that the diluent affects the mechanism of complexation, e.g. in the case of protic diluents there is competition between the acid and diluent, whereas inactive diluents resulted in more overloading of the amine. The method of ITC was validated with LLE experiments and the equilibrium model based on ITC data can also be used to directly predict LLE. The differences between phenol and acetic acid that were observed in the LLE experiments, and expected on the basis of ITC and MM, could be described using the  affinity scale for acetic acid and the hydrogen bond basicity  scale for phenol.

The effect of molecular structure of the extractant on the enthalpy of complexation and thereby the temperature sensitivity of the complexation reaction is the focus point of Chapter 6.  ITC and MM were applied to two cases, i.e. interaction of 4-cyanopyridine with (substituted) phenols and interaction of acetic acid with tertiary amines. A form of Entropy-Enthalpy-Compensation (EEC) was shown for extractants with varying side groups, which means that (small) changes in molecular structure hardly affect the complexation constant, but affect both the enthalpy and entropy of complexation. As a consequence, through optimizing the enthalpy of complexation, the temperature dependency of the equilibrium can be increased. The enthalpy of complexation itself appeared to increase with temperature, an effect that was stronger for tertiary amines with longer carbon chains compared to aminopyridines. For a typical system in LLX there is an optimum in Gibbs energy of complexation for every value of the enthalpy of complexation. Chapter 5 and 6 show that combination of ITC with MM is a strong approach to study the thermodynamics of interactions in LLX processes, by improving the understanding of the interaction mechanism and the effect of extractant structure thereon. 

Swing processes for solvent regeneration in LLX processes of succinic acid based on temperature and diluent-swing were compared in the study described in Chapter 7. Diluent-swing can be performed by either adding an anti-solvent or evaporating a part of the (active) diluent. Solvents composed of trioctylamine (TOA) in methyl isobutyl ketone (MIBK) showed the largest swing in acid distribution. The application of a gaseous anti-solvent has a high potential as regeneration can be performed by reducing the pressure, although extra compressors and pumps are required. With the gaseous ethane a swing in acid distribution was obtained similar to the swing with the liquid pentane. An evaluation on required investments and energy input performed using Aspen Plus showed that the ethane-based process is the most profitable process as the energy required is only 21% (13 MW/kg pure acid product) of what would be required for evaporation of water with a four-stage evaporator. The return of the increased capital investments required for this process requires 110 days of production. Combining both diluent-swing and temperature-swing was also beneficial as it results in higher product concentrations.

In XD of close-boiling polar compounds, strong interactions or azeotropes are common and prediction of VLE data is thus not always straightforward. Chapter 8 describes the study with the aim to find heuristics for a first selection of solvents for XD, based on three different mixtures of close-boiling polar compounds, i.e. a mixture of diethylmethylamine and diisopropylether, a mixture of valeric acid and its isomer 2-methylbutyric acid, and a mixture of 2-butanol and 2-butanone. Solvent effects were measured for solvents selected based on e.g. acidity, structural similarity, steric hindrance, polarity and hydrogen bonding affinity. For mixtures of very similar components in terms of acidity, boiling point and structure, stronger interaction with the solvent is required, although this is limited by the chemical stability. Therefore, solvents can be initially selected based on ITC or MM. This was further implemented in Chapter 9 in which a procedure was developed for solvent screening, combining MM and ITC to predict solvent effects on the relative volatility. The interaction energies of the mixture components and solvents were calculated with MM and the heat of mixing was measured with ITC and related to the solvent effect on the relative volatility. Guidelines for desired values of these energies and heats were defined and experimentally validated based on three cases; a) a mixture of octanoic and levulinic acid, b) the amine-ether mixture of Chapter 8, and c) the alcohol-ketone mixture of Chapter 8. With this solvent selection procedure the number of solvents, for which extensive experimental screening on the basis of VLE measurements is required, is strongly reduced.

Chapter 10 concludes this thesis by evaluating and comparing the results obtained for both LLX and XD systems. Moderate interactions are favored for both processes to allow for successful solvent regeneration and to avoid chemical or thermal instability. For LLX processes, affinity agents that form stronger interacting complexes with the mixture components based on proton transfer were successfully applied, whereas this type of interaction appeared too strong for XD processes where only interactions up to the strength of hydrogen bonding could successfully be applied. In an outlook regarding the international climate goals for 2050 opportunities for affinity fluid separations are discussed and directions for further research and applications are given.