Subscriber access provided by UNIV TWENTE Article Dihydrolevoglucosenone (Cyrene™), a Bio-based Solvent for Liquid-Liquid Extraction Applications Thomas Brouwer, and Boelo Schuur ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.0c04159 • Publication Date (Web): 31 Aug 2020 Downloaded from pubs.acs.org on September 16, 2020

Just Accepted

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1 2 3 4 5 6 7 Dihydrolevoglucosenone (Cyrene™), a Bio-based 8 9 10 11 Solvent for Liquid-Liquid Extraction Applications 12 13 14 15 16 a a,* 17 Thomas Brouwer and Boelo Schuur 18 19 20 21 aSustainable Process Technology group, Process and Catalysis Engineering cluster, 22 23 24 25 Faculty of Science and Technology, University of Twente, Dienerlolaan 5, Meander 26 27 28 building, 7522 NB, Enschede, The Netherlands 29 30 31 32 *corresponding author: Meander building 221, 7522NB, Enschede, The Netherlands, 33 34 35 36 e: [email protected] , p: +31 53 489 2891 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 Abstract 5 6 7 Dihydrolevoglycosenone, commercially known as Cyrene™, is a versatile bio-based 8 9 10 11 solvent reported for various applications including being a medium of chemical 12 13 14 reactions and membrane manufacture. In this work, application of Cyrene™ in liquid- 15 16 17 18 liquid extractions has been investigated. Four ternary systems have been assessed at 19 20 21 298.15K, 323.15K and 348.15K, keeping CyreneTM and methylcyclohexane constant 22 23 24 25 and changing the third compound to toluene, cyclohexanol, cyclohexanone and 26 27 28 cyclopentyl methyl ether. Studying these selected ternary systems, yielded an 29 30 31 indication of applicability of Cyrene™ in related industrial separation processes such 32 33 34 35 as aromatic/aliphatic separations, and in separations of oxygenates in the cyclohexane 36 37 38 oxidation process. Key factors are biphasic system formation, distribution coefficients 39 40 41 42 and selectivity. All ternary systems showed type I liquid-liquid phase behavior with a 43 44 45 selective extraction of ternary components from methylcyclohexane by Cyrene™. The 46 47 48 49 highest selectivity at 298.15K was found for cyclohexanol with 61.4±4.33, followed by 50 51 52 cyclohexanone with 44.1±8.63, while toluene and cyclopentyl methyl ether had a 53 54 55 56 selectivity of respectively 12.0±0.89 and 6.4±0.08. Although CyreneTM is applicable in 57 58 59 all four ternary systems, the miscibility gap is narrow for the oxygenated species, 60

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1 2 3 4 indicating a limited operation window for liquid-liquid extraction which will be more 5 6 7 severe at higher temperatures. Overall, the studies showed that there are certainly 8 9 10 11 application windows for Cyrene™. In the case of oxygenate extraction, a process with 12 13 14 Cyrene™ appears energy-saving because the energy duty appears to be lower than 15 16 17 18 when using water, the best alternative solvent, which is a low boiling solvent for this 19 20 21 purpose. 22 23 24 25 TM 26 KEYWORDS: Dihydrolevoglucosenone, Cyrene , Bio-based Solvent, Liquid-Liquid 27 28 29 30 Equilibrium, Liquid-Liquid Extraction 31 32 33 34 Introduction 35 36 37 Insights in the liquid-liquid extraction (LLX) applicability of dihydrolevoglycosenone, 38 39 40 41 or Cyrene™, was obtained by performing LLX in four different ternary systems. 42 43 44 CyreneTM, a bio-based polar solvent, attracted recent attention as being versatile for 45 46 47 1-7 48 various applications, e.g. as a medium to perform chemical reactions and to prepare 49 50 51 membranes by phase inversion8, though no mention for LLX applications has been 52 53 54 55 found as of yet. 56 57 58 59 60

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1 2 3 TM 1, 8 4 Cyrene can be an alternative aprotic dipolar solvent , solvents of this class are 5 6 7 typically used in a range of molecular separations, from aromatic/aliphatic separation9- 8 9 10 11 12 11 to carboxylic acid separation from water. Industrially important members of the 12 13 14 solvent class of aprotic dipolar solvents include N-methylpyrrolidone (NMP) and N,N- 15 16 17 18 dimethylformamide (DMF), which both are considered toxic solvents and subject to 19 20 21 restrictive legislation. 13-15 CyreneTM is reported to have a much lower toxicity16-17, and 22 23 24 25 additionally since it is a biobased product, it offers chances for the chemical industry 26 27 28 to reduce the consumption of fossil oil by replacing their toxic fossil oil-based solvents 29 30 31 for a much more benign biobased alternative.18 In a recent communication, the Circa 32 33 34 35 Group announced a production capacity of CyreneTM of 1 kton per annum, which 36 37 38 signifies the mass production of this new biobased solvent.19 Although, bulk prices may 39 40 41 42 not be publically available, Krishna et al. state that the bulk price of CyreneTM may be 43 44 45 approximately to be 2 €/kg 20 which is comparable with traditional solvents. 46 47 48 49 Two key classes of molecular separation processes using solvents include extractive 50 51 52 distillation (ED) and LLX. In another article21, we showed the potential of Cyrene™ as 53 54 55 56 entrainer in ED of aromatic/aliphatic mixtures and paraffin/olefin mixtures. Similarly, 57 58 59 next to the already proven entrainer function in extractive distillations, Cyrene™ may 60

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1 2 3 4 be useful for LLX as well. In order to investigate the applicability of Cyrene™ in LLX 5 6 7 processes, we assessed the liquid-liquid equilibrium (LLE) behavior of several ternary 8 9 10 11 systems formed with Cyrene™. The investigated systems include (1) 12 13 14 methylcyclohexane (MCH) and toluene (TOL), (2) MCH and cyclohexanol (CHOH), (3) 15 16 17 18 MCH and cyclohexanone (CHO) and (4) MCH and cyclopentyl methyl ether (CPME). 19 20 21 The molecular structures of all species used in this study are displayed in figure 1. 22 23 24 OH O O 25 O 26 27 28 29 30 O 31 O 32 33 34 35 methylcylohexan toluene Cyclohexanol cyclohexanone Cyclopenthyl Dihydrolevoglucose- 36 e methyl ether none 37 (MCH) (TOL) (CHOH) (CHO) (CPME) (CyreneTM) 38 39 40 Figure 1. Structures of the molecules used in this study. 41 42 43 44 These ternary mixtures have specifically been chosen to firstly represent 45 46 47 aromatics/aliphatics separations. These separations using LLX has been subject of 48 49 50 51 study for a variety of model compounds, including benzene, toluene, xylenes, 52 53 54 (methyl)cyclohexane and n-alkanes.22-27 The model systems vary as the related 55 56 57 58 industrial mixture is complex.28 The results in this study on liquid-liquid equilibria with 59 60

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1 2 3 TM 4 Cyrene , MCH and TOL will be compared to the elaborate work done in the past 5 6 7 concerning molecular solvents22-24, ionic liquids (ILs)25, 29-30 and deep eutectic solvents 8 9 10 31-33 11 (DESs). 12 13 14 The separation of alcohols and ketones from aliphatics was chosen because the 15 16 17 18 compounds possess either an alcohol or a ketone functionality, and they are relevant 19 20 21 industrial chemicals, for example in the industrial oxidation process of cyclohexane to 22 23 24 34-35 25 CHO and CHOH . Kim et al. and Pei et al. investigated similar systems with CHO 26 27 28 and CHOH, though used cyclohexane as hydrocarbon and studied dimethyl sulfoxide 29 30 31 (DMSO) and water as a solvent.36-37 32 33 34 35 The last ternary mixture with MCH and CPME was chosen for the CPME ether 36 37 38 functionality. CPME also has the potential of being a biobased solvent.38-40 The 39 40 41 42 extraction of CPME from an aliphatic stream has not been studied yet. 43 44 45 Next to evaluation of the extraction performance of Cyrene™ for each of the systems, 46 47 48 49 the LLE were also correlated using the UNIQUAC model. Lastly, by maintaining MCH 50 51 52 as the constant, it became possible to compare all the systems with each other and 53 54 55 56 investigate trends between different functional groups, and thus study the applicability 57 58 59 of CyreneTM for separating molecules with these different functional groups. 60

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1 2 3 4 Experimental Section 5 6 7 Materials 8 9 10 11 Chemicals, if not otherwise specified, where used as received without any additional 12 13 14 purification. Cyclopentyl methyl ether (≥ 99.9%), cyclohexanone (≥ 99.9%) and 15 16 17 18 cyclohexanol (99%) were obtained from Sigma Aldrich, while methylcylohexane 19 20 21 (Reagent Grade. 99%) was purchased from Honeywell. Toluene (ACS, reag.Ph.Eu) 22 23 24 25 was procured from VWR Chemicals, while analytical acetone (LiChrosolv®) was 26 27 28 acquired from Merck. A 1L bottle of dihydrolevoglucosenone, or CyreneTM, (99.3%) 29 30 31 was supplied by the Circa Group. 32 33 34 35 Liquid-Liquid Extraction Procedure 36 37 38 For the liquid-liquid extraction experiments closed 10mL glass vials were used. All 39 40 41 42 compounds were weighed with an accuracy of 0.5 mg on an analytical balance. 43 44 45 Consecutively a vortex mixer and a temperature-controlled shaking bath were used in 46 47 48 49 the equilibration. The mixture was shaken at 200 rpm for at least 12h at a constant 50 51 52 temperature and subsequently settled for at least 1h prior to sample-taking. The 53 54 55 56 experiments were conducted at 298.15K, 323.15K or 348.15K with a temperature 57 58 59 variation of 0.02K. A solvent to feed ratio on mass basis of 1 was maintained and the 60

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1 2 3 4 total mass of each phase was kept approximately at 3 grams. A sample of 0.5-1.0 mL 5 6 7 was taken with a 2mL syringe with an injection needle from both phases. Both phases 8 9 10 11 were analyzed following the analysis produce. 12 13 14 Analysis Procedure 15 16 17 18 A Thermo Scientific Trace 1300 gas chromatograph with two parallel ovens and 19 20 21 an autosampler TriPlus for 100 liquid samples was used for the analyses. Each system 22 23 24 25 was analyzed using an Agilent DB-1MS column (60m × 0.25mm × 0.25μm) with an 26 27 28 injection volume of 1 μl diluted in analytical acetone. The same instrumental method 29 30 31 was used for every system with a ramped temperature profile following the program of 32 33 34 35 initial temperature at 50oC, followed by a direct ramp of 10 oC/min to 200oC. The 36 37 38 second ramp, which was directly initiated after reaching 200oC, of 50 oC/min to 320 oC 39 40 41 42 finished the program, which lasts 20 min. The FID temperature was 330oC. A column 43 44 45 flow of 2 ml/min with a split ratio of 5, an airflow of 350 ml/min, a helium make-up flow 46 47 48 49 of 40 ml/min and a hydrogen flow of 35 ml/min were used. 50 51 52 Fitting Procedure 53 54 55 56 57 58 59 60

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1 2 3 4 Each ternary system was correlated for all temperatures simultaneously with the 5 6 7 UNIQUAC model. This model predicts the activity coefficient as the summation of the 8 9 10 푐 푅 41 11 combinatorial (훾푖 ) and residual (훾푖 ) term of the activity coefficient, see equation 1. 12 13 푐 푅 14 ln 훾푖 = ln 훾푖 + ln 훾푖 (1) 15 16 17 The combinatorial term, using the Guggenheim-Stavermann approximation42, 18 19 20 21 accounts for the influence of shape differences between the molecules and the 22 23 24 corresponding entropy effects. This contribution of the activity coefficient is elaborated 25 26 27 28 in equations 2, 3 and 4. 29 30 훷푖 훷푖 훷푖 훷푖 31 푐 (2) 32 ln 훾푖 = ln + 1 ― ― 5푞푖 ln + 1 ― (푥푖 ) 푥푖 ( (휃푖) 휃푖) 33 34 푥푖푟푖 (3) 35 훷 = 푖 ∑ 36 푗푥푗푟푗 37 푥 푞 38 푖 푖 (4) 휃푖 = 39 ∑ 푗푥푗푞푗 40 41 Where, 훷 is the volume fraction, 휃 is the surface area fraction, 푥 is the molar fraction 42 푖 푖 푖 43 44 45 and the Van der Waals volume, 푟푖 , and surface area, 푞푖 , of each component. 46 47 48 49 50 The residual term, see equations 5 and 6, is determined using the same parameters, 51 52 53 and the additional empirical binary interaction parameters 휏 . This value is fitted using 54 푖푗 55 56 57 58 59 60

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1 2 3 4 the temperature independent parameter (퐴푖푗 ) and temperature-dependent parameter ( 5 6 7 퐵푖푗). 8 9 10 ∑ 푗푞푗푥푗휏푗푖 푞푗푥푗휏푗푖 (5) 11 푅 ln 훾푖 = 푞푖 1 ― ln ― ∑ 12 ( ∑ 푞푗푥푗 ) ∑ 푞푘푥푘휏푘푗 ( 푗 푗 푘 ) 13 14 퐵푖푗 (6) 15 휏푖푗 = 퐴푖푗 + 16 푇(퐾) 17 18 19 For the correlation, known Van der Waals volumes and surface areas were used, 20 21 22 TM 23 see table 1. For Cyrene , the parameters were not available in the literature, and were 24 25 26 estimated with Density Functional Theory with a B3LYP 6-311+G** parameterization 27 28 29 43 30 in combination with the methodology of Banerjee et al. 31 32 33 Table 1.Van der Waals volumes and surface areas of all components 34 35 36 Component r q 37 i i 38 39 Methylcyclohexane22 5.174 4.396 40 41 Toluene44 3.920 2.970 42 43 Cyclohexanol37 4.274 3.284 44 45 46 Cyclohexanone37 4.114 3.340 47 48 CPME45 4.214 3.248 49 50 CyreneTM 4.843 3.322 51 52 53 54 55 56 Results and Discussion 57 58 59 60

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1 2 3 4 The four ternary LLE systems that were investigated in this study are presented in a 5 6 7 subsection for each of the systems. All of the systems showed type I phase behavior46 8 9 10 11 for all temperatures investigated. For each of the ternary systems the selectivity (푆푖푗 ) 12 13 14 of the solute (i), being toluene, cyclohexanol, cyclohexanone or CPME, over MCH (j) 15 16 17 18 was examined (equation 8). This selectivity is defined as the ratio of the distribution 19 20 21 coefficients (퐾퐷,푖 ) of each of the solutes, which in turn is defined as the ratio of the 22 23 24 [푋 ] 25 concentration of the solute, on a weight basis, in the solvent (푖 푆 ) and the organic 26 27 28 phase ([푋푖]푂 ) as in equation 7. 29 30 31 [푋푖]푆 (7) 32 퐾 = 퐷,푖 [푋 ] 33 푖 푂 34 퐾퐷,푖 (8) 35 푆푖푗 = 36 퐾퐷,푗 37 38 39 All experimental results have been correlated using the UNIQUAC model, which was 40 41 42 43 checked on its thermodynamic consistency using the Hessian Matrix test. This 44 45 46 information is provided in the Supporting Information (SI),47-48 as well as tables with all 47 48 49 50 the measured data and calculated distribution coefficients and selectivities. This allows 51 52 53 an approximate description of the binodal curve and the tielines. After describing the 54 55 56 57 results for each of the ternary systems individually, in the last subsection, all ternary 58 59 60 systems are compared to enable a general description of the affinities of CyreneTM

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1 2 3 4 towards different moieties. Additionally, rough short-cut calculations were performed 5 6 7 of the combined CHOH/MCH and CHO/MCH cases to assess the potential of CyreneTM 8 9 10 11 in a LLX process. In the SI, all the weight fractions, distribution coefficients and 12 13 14 selectivities of the ternary diagrams are displayed and/or tableted. 15 16 17 TM 18 Methylcyclohexane – Toluene - Cyrene 19 20 21 The results for the MCH – toluene – Cyrene™ ternary system are displayed in figure 22 23 24 25 2. As can be seen from the binodal curves, a significant miscibility region can be seen. 26 27 28 For 298.15K, only below ~35 wt. % toluene a biphasic system is observed, which 29 30 31 further reduces with increasing temperatures. This is in line with our work on extractive 32 33 34 35 distillation at a temperature above 373K, where no phase splitting was observed for 36 37 38 this system.21 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 TM 42 Figure 2. The ternary diagrams of the LLE of toluene, MCH and Cyrene with the lie- 43 44 45 lines, feed compositions and binodal curves at (a) 298.15K, (b) 323.15K and (c) 46 47 48 TM 49 348.15K, and (d) the STOL,MCH of Cyrene at the same temperatures. The UNIQUAC 50 51 52 fit is added throughout. 53 54 55 56 A selectivity of 11.99±0.89 was induced with a toluene concentration of ~0.74 wt. % 57 58 59 60 in the CyreneTM phase at 298.15K. This selectivity decreases to 6.76±0.65 and

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1 2 3 4 4.91±0.58 at respectively 353.15K and 348.15K for similar toluene concentrations. 5 6 7 This is due to a lower activity coefficient of MCH in CyreneTM, a consequence of a 8 9 10 11 polarity decrease of the solvent phase, which is a consequence of the higher 12 13 14 hydrocarbon (MCH and TOL) solubility at elevated temperatures which in turn is 15 16 17 18 caused by the larger entropic contribution at higher temperatures. The correlated 19 20 21 UNIQUAC parameters are given in table 2. 22 23 24 TM 25 Table 2. Correlated UNIQUAC parameter for the MCH-toluene-Cyrene system 26 27 28 Component Component j Aij Aji Bij Bji 29 i 30 31 32 0 0 - 171, Toluene 33 191,0 5 34 MCH 35 4,58 - -1749 773, 36 37 7 2,627 7 38 CyreneTM 39 2,70 - - 1463 40 Toluene 41 8 4,999 772,6 42 43 44 45 46 TM 47 The LLX performance of Cyrene has been put in perspective by the comparison 48 49 50 with other solvents, such as SulfolaneTM, n-formylmorpholine26, methanol27 and various 51 52 53 49 50 50 51 54 ILs, EMIM][ESO4] , [HMIM][B(CN)4] , [BMIM][B(CN)4] and [BMIM][MSO4] . 55 56 57 58 59 60

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1 2 3 TM TM 4 As can be seen in figure 3, Sulfolane is outperforming Cyrene regarding 5 6 7 selectivity and n-formylmorpholine26 has a higher selectivity at high toluene fractions 8 9 10 11 in the solvent phase. Also, both solvents have a more significant phase split than 12 13 14 CyreneTM. Comparable performance was seen towards methanol,27 though CyreneTM 15 16 17 18 has a more significant phase split. 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 Figure 3. (left) A comparison of (left) the LLE and (right) STOL,MCH at 298.15K of several 43 44 45 TM TM 26 27 49 solvents; Cyrene , Sulfolane , n-formylmorpholine , methanol , [EMIM][ESO4] , 46 47 48 *50 *50 51 * 49 [HMIM][B(CN)4] , [BMIM][B(CN)4] and [BMIM][MSO4] . These systems were 50 51 52 measured at 293.15K. 53 54 55 56 The ILs induce an almost complete immiscibility, due to lower distribution coefficients 57 58 59 60 compared to traditional solvents. This immiscibility is due to their ionic nature, which

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1 2 3 4 does not allow to stabilize in the highly apolar hydrocarbon mixture. Additionally, for 5 6 7 low toluene fractions in the solvent phase, a similar selectivity towards toluene is 8 9 10 TM 11 observed for the ILs compared to Sulfolane . Although, at higher toluene fraction the 12 13 14 tetracyanoborate ILs50 are able to retain a higher selectivity compared to SulfolaneTM. 15 16 17 18 A consequence of lower distribution coefficients in ILs is however that a larger solvent 19 20 21 quantity is required for the LLX, and the equipment diameter will increase. On the other 22 23 24 25 hand, due to the larger selectivity, less stages are required, reducing the equipment 26 27 28 height. Higher selectivity means that less aliphatics need to be boiled from the solvent 29 30 31 in the solvent regeneration, which is beneficial for the energy requirement, which 32 33 34 35 seems to be in favor for ILs. Overall, it is not straight forward to decide which solvent 36 37 38 is better and a more thorough process simulation including total annual cost estimation 39 40 41 42 is suggested but outside the scope of this paper. 43 44 45 46 47 48 49 Methylcyclohexane – Cyclopentyl methyl ether - CyreneTM 50 51 52 As can be seen in figure 4, CyreneTM induces a selectivity of 6.42±0.08, 4.55±0.41 53 54 55 56 and 3.91±0.31 at respectively 298.15K, 323.15K and 348.15K for ~0.65 wt. % of CPME 57 58 59 in the solvent phase. 60

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Figure 4. The ternary diagrams of the LLE of CPME, MCH and CyreneTM with the lie- 44 45 46 lines, feed compositions and binodal curves at (a) 298.15K, (b) 323.15K and (c) 47 48 49 TM 50 348.15K, and (d) the SCPME,MCH of Cyrene at the same temperatures. The UNIQUAC 51 52 53 fit is added throughout. 54 55 56 57 58 59 60

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1 2 3 TM 4 The results indicate that Cyrene is selective towards the polar ether moiety over 5 6 7 the aliphatic MCH. A substantial miscibility region at CPME contents over ~35 wt. % 8 9 10 11 CPME is observed, which resembles LLX-application window of the MCH-toluene 12 13 14 case. In table 3, the UNIQUAC parameters of the correlation are displayed. This 15 16 17 18 indicates that the dipolar characteristics of the ether moiety induces similar 19 20 21 intermolecular interactions as the delocalized π-system of toluene. 22 23 24 25 26 27 28 Table 3. Correlated UNIQUAC parameter for the MCH-CPME-CyreneTM system 29 30 31 Component Component j Aij Aji Bij Bji 32 33 i 34 35 0 0 - 19,2 36 CPME 37 61,53 1 38 MCH 39 3,33 - -1356 588, 40 2 2,020 3 41 TM 42 Cyrene 43 2,31 - - 899, CPME 44 9 3,522 661,0 1 45 46 47 48 49 50 Methylcyclohexane – Cyclohexanol - CyreneTM 51 52 53 TM 54 The results for the system MCH – CHOH – Cyrene™ are given in figure 5. Cyrene 55 56 57 induces a selectivity of 61.42±4.33, 32.8±5.83 and 16.6±2.26 at respectively 298.15K, 58 59 60

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1 2 3 4 323.15K and 348.15K at ~0.80 wt. % of CHOH in the solvent phase. This is lower than 5 6 7 observed with DMSO36 and water37, which have a selectivity of resp. 155 and 1450, at 8 9 10 11 low CHOH concentrations. 12 13 14 The lower selectivity of CyreneTM can mainly be attributed to the larger hydrocarbon 15 16 17 TM 18 backbone of Cyrene , compared to the small DMSO and water molecules, which 19 20 21 mitigates the multipole interactions with the relatively unselective London dispersion 22 23 24 52 25 interactions. 26 27 28 Also in the ternary system MCH – CHOH – Cyrene™ a large miscibility region is 29 30 31 observed, for concentrations above ~25 wt. % cyclohexanol. Due to the large miscibility 32 33 34 35 in the system, only a small operation window is available for LLX, and the two phase 36 37 38 region decreases at increasing temperature. The larger miscibility region indicates also 39 40 41 TM 42 that the capacity of Cyrene (퐾퐷,퐶퐻푂퐻 = 4.64 at ~0.80 wt. % of CHOH in the solvent 43 44 45 phase) for CHOH is larger than water (퐾 = 1.60Ɨ,37). 46 퐷,퐶퐻푂퐻 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Figure 5. The ternary diagrams of the LLE of cyclohexanol, MCH and CyreneTM with 44 45 46 the lie-lines, feed compositions and binodal curves at (a) 298.15K, (b) 323.15K and (c) 47 48 49 TM 50 348.15K, and (d) the SCPME,MCH of Cyrene at the same temperatures. The UNIQUAC 51 52 53 fit is added throughout. 54 55 56 57 58 59 60

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1 2 3 TM 4 Cyrene would be preferred when high CHOH capacities are required, while water 5 6 7 is preferred when a larger immiscibility and selectivity is required. DMSO has been 8 9 10 53 11 shown to be quite toxic and is for that reason not the preferred choice. The UNIQUAC 12 13 14 parameters for this system are present in table 4. 15 16 17 TM 18 Table 4. Correlated UNIQUAC parameter for the MCH-cyclohexanol-Cyrene system 19 20 21 Component Component j Aij Aji Bij Bji 22 i 23 24 25 Cyclohexano - - - 239, 26 l 0,1112 0,1675 435,6 5 27 MCH 28 1,738 - - 153, 29 30 0,7045 817,2 3 31 CyreneTM 32 Cyclohexan 0 0 - 12,0 33 34 ol 128,7 5 35 36 37 38 39 TM 40 Methylcyclohexane – Cyclohexanone - Cyrene 41 42 43 The results for the ternary system MCH – CHO – Cyrene™ are given in figure 6. 44 45 46 TM 47 Cyrene induces a selectivity of 44.07±8.63, 32.14±2.78 and 19.25±2.00 at 48 49 50 respectively 298.15K, 323.15K and 348.15K for the lowest amount of CHO in the 51 52 53 54 solvent phase (~0.60 wt. %). Also in this case, the selectivity is lower than reported for 55 56 57 DMSO36 and water37, which have been reported to be 42.9 and 1202. Also in this case, 58 59 60

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1 2 3 4 a significant miscibility region is observed at CHO contents higher than ~23 wt. %. The 5 6 7 single phase region is larger than compared to the previous systems, indicating a 8 9 10 11 narrower LLX application window. This is due to the mutual presence of ketone 12 13 14 functionality in CHO and CyreneTM resulting in a significant mutual solubility. Hence 15 16 17 TM 18 Cyrene has a larger capacity for CHO (퐾퐷,퐶퐻푂 = 4.47 at ~0.60 wt. % of CHO in the 19 20 Ɨ,37 TM 21 solvent phase) than water (퐾퐷,퐶퐻푂 = 2.79 ). Also for this case, Cyrene and water 22 23 24 25 may be preferred solvent choices, if either CHO capacity or immiscibly window and 26 27 28 selectivity are the selection criteria. As previously mentioned, DMSO is toxic and is 29 30 31 preferentially avoided. In table 5, the UNIQUAC parameters of the correlation are 32 33 34 35 displayed. 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Figure 6. The ternary diagrams of the LLE of cyclohexanone, MCH and CyreneTM with 44 45 46 the lie-lines, feed compositions and binodal curves at (a) 298.15K, (b) 323.15K and (c) 47 48 49 TM 50 348.15K, and (d) the SCPME,MCH of Cyrene at the same temperatures. The UNIQUAC 51 52 53 fit is added throughout. 54 55 56 57 58 59 60

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1 2 3 TM 4 Table 5. Correlated UNIQUAC parameter for the MCH-cyclohexanone-Cyrene 5 6 7 system 8 9 10 Component i Component j A A B B 11 ij ji ij ji 12 13 Cyclohexanon - - 364,9 364, 14 e 1,090 1,090 9 15 MCH 16 17 4,587 - -1749 773, 18 2,627 7 19 CyreneTM 20 Cyclohexanon 2,507 - - 2133 21 22 e 7,521 531,6 23 24 25 26 27 28 Comparative Study 29 30 31 By considering the combined data from all ternary systems with toluene (TOL), 32 33 34 35 cyclohexanol (CHOH), cyclohexanone (CHO) and CPME, from MCH, the performance 36 37 38 of CyreneTM towards particular moieties can be evaluated. CyreneTM is a bi-cyclic 39 40 41 42 organic molecule in which a double ether moiety, one in each ring, and a ketone 43 44 45 functionality is present. All moieties are aprotic and therefore can only act as a 46 47 48 49 hydrogen bond acceptor and will induce next to the omnipresent London dispersion 50 51 52 interactions also Keesom and Debye interactions.52 Comparing the results, see table 53 54 55 56 6 and from the figures 2, 4, 5 and 6, it is concluded that selectivity order is found to be 57 58 59 mostly 퐶퐻푂퐻 > 퐶퐻푂 ≫ 푇푂퐿 > 퐶푃푀퐸. A larger temperature-dependency is seen for 60

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1 2 3 4 CHOH, likely due to intra- and intermolecular hydrogen bonding, resulting in lower 5 6 7 selectivity than CHO at higher temperatures. 8 9 10 11 12 13 14 Table 6. A comparison between the distribution coefficient and selectivity found for 15 16 17 18 CHOH, CHO, TOL and CPME at similar low weight percentage in the solvent phase at 19 20 21 298.15K, 323.15K and 348.15K 22 23 24 Component j in Distribution Coefficient 25 solvent phase component j (-) Selectivity (-) 26 Component Component 27 (wt.%) 28 i j 29 30 (298.15K / 323.15K / 348.15K ) 31 32 CHOH 0.80 / 0.65 / 0.51 4.64 / 2.94 / 1.64 61.4 / 32.8 / 16.6 33 34 CHO 0.87 / 0.60 / 0.56 4.47 / 3.15 / 2.20 44.1 / 32.1 / 19.3 35 MCH 36 37 TOL 0.74 / 0.82 / 0.72 0.98 / 0.54 / 0.51 12.0 / 5.80 / 5.32 38 39 CPME 0.83 / 0.63 / 0.57 0.30 / 0.40 / 0.40 5.15 / 4.27 / 3.54 40 41 42 43 44 45 CHOH and CHO are extracted with significantly higher selectivity than toluene and 46 47 48 CPME. This is due to respectively the hydrogen bond donating character of CHOH and 49 50 51 52 the significant dipole moment of 2.75D54 of CHO which induces substantial Keesom 53 54 55 and Debye interactions with CyreneTM. Toluene and CPME do not have hydrogen 56 57 58 59 bonding donating capabilities and have much lower dipole moments compared to 60

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1 2 3 55 56 4 CHO, respectively 0.37D and 1.27D , hence a lower selectivity is induced. Toluene 5 6 7 does however exhibit a significant quadrupole moment,57 which is responsible for more 8 9 10 11 extensive Keesom and Debye interactions and therefore a larger selectivity is induced 12 13 14 compared to CPME. 15 16 17 18 When the CHO and CHOH cases are combined and their extraction performances 19 20 21 are compared, a measure of selectivity towards both solutes may be estimated for the 22 23 24 25 lowest weight fractions of solute in the solvent phase. A selectivity ratio (SCHOH,MCH/ 26 27 37 TM 28 SCHO,MCH) of 1.42 and 1.21 is obtained for resp. Cyrene and water. We speculate 29 30 31 that CyreneTM is a slightly more selective solvent for the combined extraction of CHO 32 33 34 35 and CHOH than water, though this may be caused by the different alkane used in both 36 37 38 studies. A CyreneTM-based LLX process for this separation was further investigated by 39 40 41 42 short-cut energy calculations in the next section. 43 44 45 46 47 48 49 Process Considerations 50 51 52 Liquid-Liquid Equilibria are cornerstones in an accurate description of Liquid-Liquid 53 54 55 56 Extractions (LLX) that arguably form the heart of LLX processes. As solvents are rarely 57 58 59 completely immiscible and selective, several additional purification steps are required 60

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1 2 3 4 to recover the solvent and obtain a pure product. An example is given by an de Graff 5 6 7 et al.58 where two distillation columns are used to recover the solvent and pure products 8 9 10 11 from a LLX column. The raffinate can also be distilled to recovery the solvent, though 12 13 14 for polar solvents the use of a water wash column to recover the solvent can be applied 15 16 17 18 to save energy. Subsequently, the water is then evaporated from the solvent-rich water 19 20 21 phase and the vapor is used to strip extracted solutes from the extract stream.59-61 To 22 23 24 25 thoroughly compare Cyrene™ with all conventional solvents for all studied applications 26 27 28 will require rigorous process simulations for all these process steps, and even 29 30 31 consideration on which of the steps are required and preferred. This is beyond the 32 33 34 35 scope of this paper, in which the applicability of Cyrene™ is explored and a first 36 37 38 indication of the usefulness of the application is discussed on the basis of miscibility , 39 40 41 42 distribution coefficients and selectivity. On the basis of a short-cut calculation an 43 44 45 estimation of the required heat duty will be given for the combined case of MCH/CHO 46 47 48 49 and MCH/CHOH. This case was chosen as being most interesting for industrial 50 51 52 application in the industrial oxidation process of cyclohexane to CHO and CHOH34-35. 53 54 55 56 The MCH-TOL case which certainly is also of industrial interest was not simulated 57 58 59 because on the basis of the liquid-liquid equilibrium data it can be seen that both 60

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1 2 3 4 Sulfolane and ILs are clearly superior over Cyrene™ with regard to selectivity and 5 6 7 immiscibility. 8 9 10 TM 11 The most significant difference between water and Cyrene is related to the 12 13 14 recovery of the CHO and CHOH from the solvent, which boil at resp. 429K and 433K. 15 16 17 TM 8 18 Cyrene is a high-boiling solvent (bp: 500K ), whereas water is a low-boiling solvent 19 20 21 (bp: 373K). Recovery of water thus implies that the solvent has to be boiled off from 22 23 24 TM 25 the solutes, whereas the solutes can be boiled off from the Cyrene™. Cyrene has 26 27 28 therefore a significant advantage over water, due to the fact the energy-penalty 29 30 31 associated with the evaporation enthalpy of the solvent is avoided in using the high- 32 33 34 35 boiling CyreneTM. Also, the capacity of CHO and CHOH in water is lower compared to 36 37 38 CyreneTM. This entails a larger amount of water is required to extract a certain amount 39 40 41 42 of CHO and/or CHOH than CyreneTM. 43 44 45 In order to estimate the magnitude of the energy advantage, a set of rough 46 47 48 49 calculations on the heat duty in the recovery processes were performed. Using the LLE 50 51 52 description by UNIQUAC, the minimum solvent to feed (S:F) ratio (on mass basis) was 53 54 55 56 determined by simulation in ASPEN Plus of the LLX process with 1000 equilibrium 57 58 59 stages, a feed containing 90 wt. % MCH, and obtaining >99.9 wt. % MCH purity. 60

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1 2 3 4 Afterwards, for the heat duty in the solvent recovery stage, a short-cut calculation was 5 6 7 applied. Assuming that most of the sensible heat may be recoverable using heat 8 9 10 11 exchangers, the latent heat of vaporization (ΔHvap) of the most volatile compound was 12 13 14 used as estimate. For water as solvent, a minimum S:F ratio of 1.8 was obtained for 15 16 17 18 CHOH and 7.3 for CHO. Since water for these systems is a volatile solvent, 19 20 21 evaporation of all the water resulted in a heat duty of 41.3 MJ/kgCHOH and 166 22 23 24 25 MJ/kgCHO. 26 27 28 For CyreneTM, a lower minimum S:F ratio was required which is a direct consequence 29 30 31 from the larger capacity towards CHO and CHOH, being 1.2 for CHOH and CHO. 32 33 34 35 Furthermore, since Cyrene™ in these systems is a high boiling solvent, the solutes 36 37 38 CHOH and CHO should be boiled off. Due to solvent leaching, MCH should be boiled 39 40 41 42 off from the raffinate to recover the solvent, and the evaporation of MCH from the 43 44 45 raffinate is included in the calculations. This resulted for CHOH in a heat duty of 3.86 46 47 48 49 MJ/kgCHOH and for CHO in 3.87 MJ/kgCHO. These short-cut calculations show that 50 51 52 extraction processes using CyreneTM instead of water may be 11 times more efficient 53 54 55 56 for the separation of CHOH from MCH and 43 times more efficient for CHO from MCH. 57 58 59 This is a rough heat duty estimate, and in an accurate process simulation, the final 60

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1 2 3 4 heat duty may be less beneficial. However, with the current figures, it shows high 5 6 7 potential for a significant advantage of the high boiling CyreneTM over the low boiling 8 9 10 11 water. The fact that most energy savings compared to water were accomplished by 12 13 14 the higher boiling point of the solvent, suggests that for this application the use of ionic 15 16 17 18 liquids (ILs) might be interesting too, on the condition that beneficial behavior is 19 20 21 observed in LLE. However, no LLE data has been found for MCH/CHOH or CHO with 22 23 24 25 an IL. 26 27 28 The separation of CHO and CHOH may also be accomplished with CyreneTM due to 29 30 31 the fact a larger selectivity is observed toward CHOH than CHO. Although no phase 32 33 34 35 separation is expected and LLX is not possible, other separation techniques may be 36 37 38 used such as extractive distillation or perhaps with a extractive divided wall 39 40 41 42 configuration. 43 44 45 46 47 48 49 Conclusion 50 51 52 Four biphasic ternary systems have been assessed in which methylcyclohexane 53 54 55 56 (MCH) and CyreneTM were kept constant. As third compound toluene, cyclohexanol, 57 58 59 cyclohexanone and cyclopentyl methyl ether (CPME) were applied. For each ternary 60

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1 2 3 4 system a selective extraction was found at the three studied temperatures of 298.15K, 5 6 7 323.15K and 348.15K. Cyclohexanol (up to SCHOH,MCH = 61.42±4.33) and 8 9 10 11 cyclohexanone (up to SCHO,MCH = 44.07±8.63) were most selectively extracted, while 12 13 14 toluene (up to STOL,MCH = 11.99±0.89) and CPME (up to SCPME,MCH = 6.42±0.08) were 15 16 17 TM 18 extracted with considerably lower selectivity. While Cyrene was outperformed by 19 20 21 SulfolaneTM and several ionic liquids in the extraction of toluene, the potential of 22 23 24 TM 25 Cyrene in the cyclohexanol/cyclohexanone systems was observed. Although a lower 26 27 28 selectivity was seen than with water, due to the high boiling point of Cyrene™, recovery 29 30 31 can be much less costly. Overall, we conclude that CyreneTM can be applied as 32 33 34 35 biobased extraction solvent for a variety of separations, although for several systems 36 37 38 the phase envelop is relatively narrow and narrower at higher temperatures. 39 40 41 42 43 44 45 Author Information 46 47 48 49 Boelo Schuur* 50 51 52 Sustainable Process Technology group, Process and Catalysis Engineering cluster, 53 54 55 56 Faculty of Science and Technology, University of Twente. The Netherlands 57 58 59 Meander building 221, PO Box 217, 7500 AE, Enschede, The Netherlands, 60

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1 2 3 4 Email: [email protected] , 5 6 7 Phone: +31 53 489 2891 8 9 10 11 ORCID: 0000-0001-5169-4311 12 13 14 Thomas Brouwer 15 16 17 18 Sustainable Process Technology group, Process and Catalysis Engineering cluster, 19 20 21 Faculty of Science and Technology, University of Twente. The Netherlands 22 23 24 25 Meander building 221, PO Box 217, 7500 AE, Enschede, The Netherlands, 26 27 28 ORCID: 0000-0002-3975-4710 29 30 31 Acknowledgments 32 33 34 35 36 This has been an ISPT (Institute for Sustainable Process Technology) project 37 38 39 (TEEI314006/BL-20-07), co-funded by the Topsector Energy by the Dutch Ministry of 40 41 42 43 Economic Affairs and Climate Policy. We would like to acknowledge the Circa group 44 45 46 for sending us 1L of Cyrene™ to perform this research. 47 48 49 50 51 Supporting Information 52 53 54 55 Electronic Supporting Information is available online, and contains four tables with 56 57 58 all experimental data for figures 2, 4, 5 and 6, including weight percentages of all 59 60

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1 2 3 4 compounds in each phase, the distribution coefficient of MCH and the solute (being 5 6 7 TOL, CHO, CHOH or CPME), and the selectivity of that solute over MCH. The 8 9 10 11 thermodynamic consistency of all UNIQUAC correlations was checked using the 12 13 14 determinant of the Hessian matrix approach,47-48 and the results displayed in four 15 16 17 18 figures. 19 20 21 22 Abbreviations 23 24 [BMIM][B(CN) ] - 1-butyl-3-methylimidazolium tetracyanoborate 25 4 26 27 [BMIM][MSO4] - 1-butyl-3-methylimidazolium methylsulfate 28 29 30 [EMIM][ESO4] - 1-ethyl-3-methylimidazolium ethylsulfate 31 32 [HMIM][B(CN)4] - 1-hexyl-3-methylimidazolium tetracyanoborate 33 34 35 [Xi]O - Weight Fraction of compound i in the organic phase 36 37 [Xi]S - Weight Fraction of compound i in the solvent phase 38 39 40 Aij - Temperature independent UNIQUAC fit parameter 41 42 B - Temperature dependent UNIQUAC fit parameter 43 ij 44 45 Bp - boiling point 46 47 48 CHO - Cyclohexanone 49 50 CHOH - Cyclohexanol 51 52 53 CPME - Cyclopentyl methyl ether 54 55 CyreneTM - Dihydrolevoglycosenone 56 57 58 D - Debye 59 60

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1 2 3 4 DMF - N,N-dimethylformamide 5 6 DMSO - Dimethylsulfoxide 7 8 9 ED - Extractive Distillation 10 11 KD,i - Distributation coefficient of solute i 12 13 14 LLE - Liquid-liquid equilibrium 15 16 LLX - Liquid-liquid extraction 17 18 19 MCH - Methylcyclohexane 20 21 22 NMP - N-methylpyrrolidone 23 24 qi - Van der Waals surface area of solute i 25 26 27 ri - Van der Waals volume of solute i 28 29 S - Selectivity of solute i over solute j 30 ij 31 32 SulfolaneTM - Tetrahydrothiophene-1,1-dioxide 33 34 35 SI - Supporting Information 36 37 S:F ratio - Solvent to Feed ratio (mass basis) 38 39 40 T(K) - Absolute temperature 41 42 TOL - Toluene 43 44 45 UNIQUAC - Universal Quasichemical 46 47 푦 - Activity Coefficient of solute i 48 푖 49 푐 50 푦푖 - Combinatorial term of the activity Coefficient of solute i 51 52 푅 53 푦푖 - Residual term of activity Coefficient of solute i 54 55 훷푖 - volume fraction 56 57 58 휃푖 - surface area fraction 59 60

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1 2 3 4 휏푖푗 - binary interaction parameter between solutes i and j 5 6 Ɨ - Extrapolated from corresponding literature to similar solute 7 8 concentration in solvent phase. 9 10 11 References 12 13 14 1. Sherwood, J.; Constantinou, A.; Moity, L.; McElroy, C. R.; Farmer, T. J.; 15 16 Duncan, T.; Raverty, W.; Hunt, A. J.; Clark, J. H., Dihydrolevoglucosenone (Cyrene) 17 as a bio-based alternative for dipolar aprotic solvents. Chem. Commun. 2014, 50 18 19 (68), 9650-9652. https://doi.org/10.1039/C4CC04133J 20 21 2. Camp, J. E., Bio‐available Solvent Cyrene: Synthesis, Derivatization, and 22 23 Applications. ChemSusChem 2018, 11 (18), 3048-3055. 24 https://doi.org/10.1002/cssc.201801420 25 26 3. Wilson, K. L.; Kennedy, A. R.; Murray, J.; Greatrex, B.; Jamieson, C.; Watson, 27 28 A. J., Scope and limitations of a DMF bio-alternative within Sonogashira cross- 29 30 coupling and Cacchi-type annulation. Beilstein J. Org. Chem. 2016, 12 (1), 2005- 31 2011. https://doi.org/10.3762/bjoc.12.187 32 33 4. Wilson, K. L.; Murray, J.; Jamieson, C.; Watson, A. J., Cyrene as a Bio-Based 34 35 Solvent for the Suzuki–Miyaura Cross-Coupling. Synlett 2018, 29 (05), 650-654. DOI: 36 37 10.1055/s-0036-1589143 38 5. Wilson, K. L.; Murray, J.; Jamieson, C.; Watson, A. J., Cyrene as a bio-based 39 40 solvent for HATU mediated amide coupling. Org. Biomol. Chem. 2018, 16 (16), 2851- 41 42 2854. https://doi.org/10.1039/C8OB00653A 43 44 6. Mistry, L.; Mapesa, K.; Bousfield, T. W.; Camp, J. E., Synthesis of ureas in the 45 bio-alternative solvent Cyrene. Green Chem. 2017, 19 (9), 2123-2128. 46 47 https://doi.org/10.1039/C7GC00908A 48 49 7. Zhang, J.; White, G. B.; Ryan, M. D.; Hunt, A. J.; Katz, M. J., 50 51 Dihydrolevoglucosenone (Cyrene) as a green alternative to N, N-dimethylformamide 52 (DMF) in MOF synthesis. ACS Sustain. Chem. Eng. 2016, 4 (12), 7186-7192. 53 54 https://doi.org/10.1021/acssuschemeng.6b02115 55 56 8. Marino, T.; Galiano, F.; Molino, A.; Figoli, A., New frontiers in sustainable 57 58 membrane preparation: Cyrene™ as green bioderived solvent. J. Membr. Sci. 2019, 59 580, 224-234. https://doi.org/10.1016/j.memsci.2019.03.034 60

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1 2 3 4 For Table of Content Use Only 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Cyrene™ extracts solutes more polar than methylcyclohexane selectively from the 21 22 23 24 hydrocarbon phase 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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