Natural products

The production of target compounds from plants as renewable resources gains more and more interest. On the one hand the application of fossil resources might be partially replaced and, on the other hand, some particular complex molecules are only accessible via isolation from the natural plant origin. The projects in this frame are concerned with investigating the potential of crystallization processes for isolation of a certain target compound from plant-based extracts. This is exemplified on 1) separation and purification of pharmaceutically relevant substances (e.g. Artemisinin) and 2) the recovery of particulate lignin from lignocellulose within the biorefinery concept.

Separation and purification of natural products

The product of plant extraction or organic synthesis commonly represents a multicomponent mixture of the targeted natural compound with a great variety of structurally very similar undesired by-products. In dependence of the quality requirements for the final application, further purification of the target compound is frequently required. In order to provide the target component in the pure and crystalline form the crystallization as a highly selective separation technique is often applied as the final purification step.

Based on the profound knowledge of the fundamental solution equilibria as well as of the recrystallization and solid phase behavior of the pure target compound and in the presence of impurities, a crystallization separation process can be designed. In particular, appropriate seeding of the supersaturated solution of the component to be purified enables the selective separation of the target compound of desired purity from the complex mixture.

Currently the purification of the antimalarial artemisinin from the crude plant extract with an initial purity of less than 20% is investigated and optimized using a process combination of adsorption as a pre-purification unit and crystallization as the final purification step (Figure 1).

Figure 1: Schematic presentation of the final cooling crystallization for purification of artemisinin from the crude plant extract[Wünsche, S., Triemer, S., Vu, G.T., Seidel-Morgenstern, A., Lorenz, H. (2021). Crystallization-based purification of multicomponent plant extracts: The case study of artemisinin. Poster presented at ISIC 21 - 21 th International Symposium on Industrial Crystallization, Virtually.] — **Figure 1:** Schematic presentation of the final cooling crystallization for purification of artemisinin from the crude plant extract [Wünsche, S., Triemer, S., Vu, G.T., Seidel-Morgenstern, A., Lorenz, H. (2021). Crystallization-based purification of multicomponent plant extracts: The case study of artemisinin. Poster presented at ISIC 21 - 21 th International Symposium on Industrial Crystallization, Virtually.]

**Figure 1:** Schematic presentation of the final cooling crystallization for purification of artemisinin from the crude plant extract
[Wünsche, S., Triemer, S., Vu, G.T., Seidel-Morgenstern, A., Lorenz, H. (2021). Crystallization-based purification of multicomponent plant extracts: The case study of artemisinin. Poster presented at ISIC 21 - 21 th International Symposium on Industrial Crystallization, Virtually.]

Another crystallization-based approach to separate structurally similar substances includes altering their physico-chemical properties via the formation of solvates, or molecular compounds by co-crystallization. The latter method is currently studied on the example of the ternary system of the curcuminoids as constituents of the plant extract (Figure 2).

Figure 2: Binary phase diagram of the co-crystal forming system bis(demethoxy)curcumin and hydroxyquinol (HYQ) revealing an incongruent melting behavior[Wünsche, S., Yuan, L., Seidel-Morgenstern, A., Lorenz, H. (2021) A Contribution to the Solid State Forms of Bis(demethoxy)curcumin: Co-Crystal Screening and Characterization, Molecules 26 (3), p. 720.] — **Figure 2:** Binary phase diagram of the co-crystal forming system bis(demethoxy)curcumin and hydroxyquinol (HYQ) revealing an incongruent melting behavior [Wünsche, S., Yuan, L., Seidel-Morgenstern, A., Lorenz, H. (2021) A Contribution to the Solid State Forms of Bis(demethoxy)curcumin: Co-Crystal Screening and Characterization, Molecules 26 (3), p. 720.]

**Figure 2:** Binary phase diagram of the co-crystal forming system bis(demethoxy)curcumin and hydroxyquinol (HYQ) revealing an incongruent melting behavior
[Wünsche, S., Yuan, L., Seidel-Morgenstern, A., Lorenz, H. (2021) A Contribution to the Solid State Forms of Bis(demethoxy)curcumin: Co-Crystal Screening and Characterization, Molecules 26 (3), p. 720.]

References

Wünsche, S., Yuan, L., Seidel-Morgenstern, A., Lorenz, H. (2021). A Contribution to the Solid State Forms of Bis(demethoxy)curcumin: Co-Crystal Screening and Characterization, Molecules 26 (3), 720.

Triemer, S., Schulze, M., Wriedt, B., Schenkendorf, R., Ziegenbalg, D., Krewer, U., & Seidel-Morgenstern, A. (2021). Kinetic analysis of the partial synthesis of artemisinin: Photooxygenation to the intermediate hydroperoxide. Journal of Flow Chemistry. Journal of Flow Chemistry. 11, 641-659.

Horosanskaia, E., Yuan, L., Seidel-Morgenstern, A., Lorenz, H. (2020). Purification of Curcumin from Ternary Extract-Similar Mixtures of Curcuminoids in a Single Crystallization Step, Crystals 10 (3), 206.

Lorenz, H., & Seidel-Morgenstern, A. (2020). Separation Processes to Provide Pure Enantiomers and Plant Ingredients, Annual Review of Chemical and Biomolecular Engineering, 11, 469–502.

Horosanskaia, E., Triemer, S., Seidel-Morgenstern, A., Lorenz, H. (2019). Purification of Artemisinin from the Product Solution of a Semisynthetic Reaction within a Single Crystallization Step, Organic Process Research & Development, 23 (9), 2074–2079.

Yuan, L., Horosanskaia, E., Engelhardt, F., Edelmann, F.T., Couvrat, N., Sanselme, M., Cartigny, Y. (2019). Solvate Formation of Bis(demethoxy)curcumin: Crystal Structure Analyses and Stability Investigations, Crystal Growth & Design 19 (2), 854–867.

Yuan, L., Lorenz, H. (2018). Solvate Formation of Bis(demethoxy)curcumin: Screening and Characterization, Crystals 8(11), 407.

Separation of lignin from organic solvent pulping liquors

A sustainable chemical industry also relies on renewable resources in the future. Lignin is the second most available vegetable compound in the world. Lignin, cellulose and hemicellulose are the main constituents of lignocellulosic biomass (e.g. wood and straw). A lignocellulose biorefinery that applies an organic solvent pulping process separates lignocellulosic biomass into mainly lignin, C5-sugars and cellulose (pulp) by percolating the biomass in an acidified solvent/water mixture. The resulting pulping liquor contains mainly the solvent, water, lignin and hemicellulose and is separated from the fibrous pulp (cellulose fraction). Afterwards lignin is precipitated from the pulping liquor and the solvent is recycled to the pulping process. The aqueous filtrate/hydrolysate contains mainly the C5 sugar fractions and degradation products (e.g. acetic acid and furfural). The separation of lignin from the pulping liquor is a critical process step. Lignin precipitation can be facilitated by decreasing the solvent concentration of the pulping liquor (e.g. by dilution or evaporation), as lignin has a very low solubility in water. Depending on the process applied, lignin particles can be sticky or very small and thus hard to handle in industrial processes.

LigniSep Process

The LigniSep technology solves the problems of sticky and small lignin particles, as well as solvent recycling and hydrolysate (pre-) concentration in a continuous process. Additionally, higher lignin yields and better filterability are achieved. The LigniSep process was developed on the basis of lignin phase behavior (lignin solubility and softening properties) in the respective solvent system (e.g. ethanol or acetone and water). Figure 3 shows the schematic process flowsheet of a LigniSep plant. Pulping liquor is continuously fed into system and is instantaneously diluted by lignin dispersion with low solvent content (typically < 10wt. %). Lignin precipitates due to its low solubility in the dispersion. The solvent is evaporated by means of a falling film evaporator at vacuum pressure and can be concentrated by rectification. The temperature of the dispersion controls the lignin softening and particle agglomeration, leading to bigger particles that are easily filterable.

In a cooperation with the Fraunhofer Center for Chemical-Biotechnological Processes CBP the LigniSep technology was successfully scaled up in a dedicated pilot plant.

LigniFrac Project

The major goal in this project is to design a process for the continuous lignin fractionation. In this regard, understanding of solution as well as solid properties of lignin is of crucial importance. This includes its solubility and phase behavior as well as its thermal properties. However, lignin is a disperse solid and thus a pseudo-component, which means that lignin is a collection of very many similar molecules, calling them ‘lignins’. In particular, its molecular weight distribution (MWD) affects lignin functionality and it is not fully understood how different MWDs influence lignin behavior. Thus, fundamental studies on precipitation and simultaneously fractionation of lignins into various molecular weight “classes” are of high interest from an industrial point of view. Therefore, in the LigniFrac project we investigate the solubility behavior of a range of organosolv lignins obtained from different feedstocks and use those as a design basis for a continuous lignin fractionation process.

References

Ponnudurai, A., Schulze, P., Seidel-Morgenstern, A., & Lorenz, H. (2021). Separation strategies for valorization of lignin by targeted molecular weight fractionation. Poster presented at ISIC 21 - 21st International Symposium on Industrial Crystallization., Virtually.

Schulze, P., Leschinsky, M., Seidel-Morgenstern, A., & Lorenz, H. (2019). Continuous Separation of Lignin from Organosolv Pulping Liquors: Combined Lignin Particle Formation and Solvent Recovery. Industrial and Engineering Chemistry Research, 58, 3797-3810. doi:10.1021/acs.iecr.8b04736.

P. Schulze (2018). Lignin Separation from Ethanol Water Pulping Liquors. PhD thesis, Otto von Guericke University, Magdeburg, doi: 10.13140/RG.2.2.24072.26887.

Schulze, P., Seidel-Morgenstern, A., Lorenz, H.: Solid-liquid and liquid-liquid phase equilibria in the pseudo-ternary lignin-ethanol-water system. Proceedings 15th European Workshop on Lignocellulosics and Pulp (EWLP 2018). Aveiro (Portugal), 415–418.

Leschinsky, M., Unkelbach, G., Schulze, P., Lorenz, H., Seidel-Morgenstern, A. (filed 2017). Method for precipitating lignin from organosolv pulping liquors, US2017/0247835 A1 (August 31, 2017), EP3209829 A1.

P. Schulze, H. Lorenz, A. Seidel-Morgenstern, M. Leschinsky, G. Unkelbach (2016). Advanced process for precipitation of lignin from ethanol organosolv spent liquors. Bioresource Technology, 199, 128-134.