A Novel Technology for the Separation of Binary Eutectic-forming

Subscriber access provided by UNIV OF LOUISIANA

Separations

A Novel Technology for the Separation of Binary Eutectic-forming Mixture by Co-Crystallization into Different Sizes Combined with Particle Size Fraction Shihao Zhang, Yaohui Huang, Ling Zhou, Yongfan Yang, Chuang Xie, Zhao Wang, Baohong Hou, Hongxun Hao, Ying Bao, and Qiuxiang Yin Ind. Eng. Chem. Res., Just Accepted Manuscript • DOI: 10.1021/acs.iecr.9b01293 • Publication Date (Web): 02 May 2019 Downloaded from http://pubs.acs.org on May 3, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Industrial & Engineering Chemistry Research

A Novel Technology for the Separation of Binary Eutectic-forming Mixture by Co-Crystallization into Different Sizes Combined with Particle Size Fraction

Shihao Zhanga,c, Yaohui Huanga, Ling Zhoua,*, Yongfan Yanga,c, Chuang Xiea,c, Zhao Wanga,c, Baohong Houa,c, Hongxun Haoa,c, Ying Baoa,c, Qiuxiang Yina,c,*

a School

of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, People’s Republic of China.

c The

Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin 300072, People’s Republic of China.

1

ACS Paragon Plus Environment

Industrial & Engineering Chemistry Research 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 34

Abstract

Separation of eutectic-forming mixture is a challenge in the manufacturing process of fine chemical products. In this paper, a novel separation technology for binary eutectic mixture by solution crystallization combined with particle size fraction was proposed. Eutectic-forming mixture of fluorene and fluorenone were used as the model compounds. Base on the determined fluorenefluorenone-cyclohexane ternary solid-liquid equilibrium phase diagrams, isothermal and polythermal crystallization experiments of fluorene-fluorenone eutectic mixture with different concentration were performed in cyclohexane. Results showed that two product-rich part (fluorene-rich part and fluorenone-rich part) and a mixture part were obtained at the same time under isothermal and polythermal mode by sieve fraction. Furthermore, changing the initial composition slightly from the eutectic point could improve the polythermal crystallization process significantly and achieve a higher yield. In addition, an enhanced online removal separation process was employed after crystallization, and it attained two products of fluorene and fluorenone with a purity of 90.17 wt% and 95.30 wt%, respectively. Up to now, this was the first experiment that attempted to separate eutectic system from the view of particles size and purity.

1. Introduction Crystallization is a traditional unit operation for separating mixtures of compounds, and it is vital for chemical industry due to low cost and relative simple operation.1-3 Crystallization design requires a relevant phase diagram, which depicts the equilibria between solid and liquid phases over a wide range of temperatures and compositions. Thereinto, the relevant phase diagrams for crystallization separation and purification of binary mixture can be classified to solvent-free binary melt phase 2


Page 3 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


diagram which describes the melting behavior of the mixture and ternary solubility phase diagram which depicts the solubility behavior of each compound in a specific solvent. Examples of systematic studies of binary and ternary phase diagrams are given in literatures from the research groups of Grant and Klussmann.4, 5 According to the characteristics of phase diagrams, binary mixtures can be divided into three categories, including eutectic-forming system6, 7, solid solution system7,

8

and new

compound/phase-forming (e.g. solvate9, 10, oiling-out11, and other situation12-14) system.

Figure 1. Ternary phase diagram of the eutectic-forming system Among the binary mixtures, eutectic-forming system is the most typical and common one. Figure 1 shows a typical eutectic-forming ternary phase diagram under a given temperature, in which point A and point B refer to the solubility of each substance S1 and S2 in pure solvent S, respectively. Two solid-liquid equilibrium curves AE and BE intersect at the eutectic point E. The whole ternary phase diagram can be divided into one unsaturated region where only clear solution exists and three saturated regions where one or two solid phases coexist with the saturated solution. In industry, most crystallization processes for separation and purification of eutectic-forming mixture are carried out with an initial feed far from the eutectic composition and stopped before another component crystallize11, 15. In other words, this crystallization process is normally operated within the 3



Page 4 of 34

two-phase region. As shown in Figure 2(a), by cooling a saturated solution with composition represented by point O from T1 to a relative lower temperature T2, solid S2 will crystallize gradually, and the mother liquor composition trajectory will move from point O to point A. Thus, compound S2 could be separated from the mixture. However, if the crystallization process is operated within the three-phase region, the purpose of separation could not be achieved. As illustrated in Figure 2(b), when a saturated solution with eutectic composition represented by point E1 is cooled, both S1 and S2 will crystallize simultaneously, and the mother liquor composition trajectory will move towards eutectic point E2 from eutectic point E1. As a result, the final product will be a heterogeneous mixture of crystals S1 and S2. Obviously, separation of eutectic-forming mixture is a challenging and key issue in the manufacturing process of fine chemical products.

Figure 2. Illustration of co-crystallization of eutectic-forming mixture for (a) starting far from eutectic composition, (b) starting from eutectic composition Thus, it is of great importance to find an alternative way to separate the eutectic mixture and to obtain the two components simultaneously. In this respect, some remarkable work based on the different principles have been attempted. Eutectic freeze crystallization (EFC) is a kind of technology used to separate aqueous inorganic eutectic solutions.16-19 By operating below the eutectic temperature, 4


Page 5 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


ice and salt can crystallize simultaneously as two separate solid phases. After stop stirring, due to their density difference, ice floats on the surface of solution, while salt settles to the bottom. This asymmetrical distribution of the floating ice and settled salt in the solution makes the separation of both components at same time feasible by collecting top floating ice and bottom settled salt separately. Therefore, EFC has been employed to recover the ice and salt simultaneously from waste water20, 21. Based on the EFC separation process, a new type of crystallizer -- the cooling disk column crystallizer (CDCC) is designed. CDCC crystallizer consists of several compartments separated by two perforated and cooling disks. Cooling is provided by means of disks. The feed streams enter the crystallizer at the center of the column. Then the crystals (ice and salt) are formed simultaneously and transported axially through orifices in the cooling disks. The ice and salt are discharged continuously at the top and bottom of CDCC respectively16,

22, 23.

Isothermal preferential crystallization24 is another widely used

technology in the separation process of enantiomers conglomerates which belongs to the eutecticforming system25. By introducing homochiral seeds to the isothermal supersaturated solution, the single enantiomer will crystallize at first, and then pure enantiomer could be harvested when the crystallization process is stopped at a proper time. This method has been applied in the industrial production of broad-spectrum antibiotics such as chloramphenicol, thiamphenicol, and betalactames.26 Based on the above traditional isothermal single vessel preferential crystallization, an enhanced polythermal preferential crystallization technology in two coupled vessels was put forward by Martin Peter Elsner.27 More specifically, enantiomers crystallize in two independent vessels at the same time by adding homochiral seeds to corresponding vessel and exchanging their liquid phase, and this mode could improve preferential crystallization yield.

5



Page 6 of 34

However, EFC is feasible only when obvious density difference exists. Therefore, EFC is widely used in the separation of aqueous inorganic eutectic solutions. The separation of organic eutectic mixture by EFC has not been reported yet. The preferential crystallization is a complex and difficult separation process, because it must be interrupted at a proper time to avoid nucleation of the counterenantiomer, while estimating the time is difficult since the induction time is uncertain under different crystallization conditions27. Although a lot of work has been attempted to improve the yield, limited progress has been made due to the narrow operable temperature range. In fact, different compounds may precipitate as crystalline particles with different morphologies and particle sizes due to their different inherent properties. For eutectic-forming mixture, if components can crystallize simultaneously into crystals with different size and when the size based fractionation is carried out, the separation of the mixture could be achieved. However, researches based on the relationship between crystal size and purity have not been reported. It is well known that not only the inherent property of substance but also the surrounding environment will influence the nucleation and growth behavior of crystals, and then affect the characteristics of the final crystals.

28-31

Since it is

difficult to change the inherent properties of substance, altering the physical(e.g. magnet32, ultrasonic33, 34

and microwave35) and chemical (e.g. solvent30,

36,

additives21,

37

and supersaturation38,

39)

environments are regarded as the frequently used methods to control the properties of final crystal products. In particular, the supersaturation is one of the most important factors to control the particle size distribution of final crystal products.40, 41 The purpose of this paper is to verify experimentally the feasibility of separating binary eutecticforming mixture by co-crystallization combined with particle size fraction. A differentiated supersaturation consumption strategy is used to enhance the particle size difference via seeding 6


Page 7 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


selectively. The mixture of fluorene and fluorenone is a typical eutectic-forming system42 and is chosen as the model compounds. Their eutectic mixture is firstly co-crystallized into heterogeneous particles with different sizes, and then the crystals are classified into different products according to the particle size, which contains different amount of fluorene and fluorenone.

2. Experimental Method. 2.1 Materials Fluorene (CAS registration No. 86-73-7, Figure 3(a)) and fluorenone (CAS registration No. 486-259, Figure 3(b)) were supplied by Henan Baoshun technology Co. Ltd. with the purity of more than 99.5 wt%. Cyclohexane (>99.5 wt%) and acetonitrile (chromatographically pure) were purchased from Tianjin Kewei Chemical Reagent Co.Ltd. of China and used as solvents without further purification.

Figure 3. Chemical structure of (a) fluorene and (b) fluorenone

2.2 Experiments 2.2.1 Determination of Ternary Phase Diagram The ternary phase diagram of fluorene-fluorenone-cyclohexane was determined by an analytical method. The measurement was carried out in a sealed 37 mL jacketed glass vessel. The solution was stirred by a magnetic stirrer and kept at a series of gradient temperature (from 10 ℃ to 40℃ at intervals of 10 ℃) by a thermostat (XOYS-2006N, Nanjing Xianou Instruments Manufacture Co.,Ltd., China) with uncertainty of ± 0.01 ℃. The apparatus is depicted in Figure 4. Different composition of fluorene 7



Page 8 of 34

and fluorenone mixture (ranging from 0 to 100 wt% at intervals of 10 wt%) was grinded at first. Then the well-mixed mixture was gradually added into 10 g cyclohexane to measure the solubility. At the same time, the mixture was analyzed by the powder X-ray diffraction (D/Max 2500, Rigaku, Japan) to determine the solid forms. When no more particles could be dissolved, the solution was subsequently kept at corresponding temperature for 30 mins to reach the equilibrium. The suspension was kept still for 1 h to make fine crystals settled completely. 2 mL upper saturated clear solution was withdrawn to a pre-weighted glass dish by a pre-heated/cooled syringe equipped with a 0.22 μm filter, then the liquid sample was evaporated in a vacuum oven (DZ-2BCIV, Taisite, China) at 40 ℃ for 6 h. Solvent mass fraction was obtained by calculating the weight loss of liquid sample before and after drying liquid sample. Solute mass fraction was obtained by analyzing the dried residue with the aid of gas chromatograph (SCION 456-GC, Bruker, USA). The dried residue was dissolved in acetonitrile, and then diluted to 10 mg/mL. After that, 10 uL diluted liquid sample was injected into a low polarity capillary column (TG-5MS, Thermo Fisher Scientific, USA) by autosampler and analyzed with FID detector. The temperature programming used started from 150 ℃ and maintained for 2 mins, then raised to 250 ℃ at a heating rate of 20 ℃/min. Both the temperature of injection and detector were 300 ℃ and the spilt ratio was 60. The experiment was repeated three times at the same temperature. And the average value was chosen as the solubility. The precise composition of the eutectic point was measured by adding excess fluorene and fluorenone to the same apparatus and analyzed by the same method.

8


Page 9 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 4. Apparatus for ternary phase diagram measurement.

2.2.2 Pure material crystallization. The crystallization of pure fluorene or fluorenone was carried out in a 250 mL jacketed glass vessel equipped with an overhead mechanical stirring (JHS-2/90, Hangzhou Meters & Instruments Co., Ltd. China) and a thermostat (XOYS-2006N, Nanjing Xianou Instruments Manufacture Co.,Ltd., China) with uncertainty of ± 0.01 ℃ (depicted in Figure 5(a)). 9.3400 g fluorene was added to 100 g cyclohexane according to the solubility at 30 ℃ (for fluorenone, 4.2920 g fluorenone was added to 100 g cyclohexane). In order to dissolve the solute completely, the solution was heated up to 40 ℃ and maintained for 30 mins. Then, the solution was cooled down to 10 ℃ at 0.25 ℃/min, and the 1 wt% (based on the initial mass of corresponding solute) seeds were introduced at 29.5 ℃. After crystallization, the crystals were filtered and dried. The crystal morphology was observed using a stereo-microscope (Stemi 508, Zeiss, Germany). The bulk density of fluorene and fluorenone was determined by measuring the weight in a certain volume. 2.2.3 Isothermal and polythermal crystallization at eutectic composition The control experiment (without seeding operation) was performed in the same apparatus as shown in Figure 5(a). Eutectic composition at 30℃ was chosen as saturated concentration, which consists of 57.1 wt% fluorene, 42.9 wt% fluorenone. 15.6700 g fluorene and 11.7900 g fluorenone were added to 100 g cyclohexane according to the saturated composition, and dissolved at 40 ℃ for 30 mins, then it was cooled down to the saturated temperature 30 ℃. For the control experiment, the solution was cooled to 10 ℃ at a constant rate of 0.25 ℃/min.

9



Page 10 of 34

For isothermal crystallization process, the solution was subcooled to 26 ℃ at constant cooling rate of 1 ℃/min, and then 1 wt% fluorenone seeds (based on the initial mass of fluorenone) were introduced to the vessel. After 60 mins, crystallization process was stopped. For polythermal crystallization process, the solution was cooled to 10 ℃ at 0.25 ℃/min, and 1 wt% fluorenone seeds were introduced to solution at 29.5 ℃. Crystallization process was stopped at 10 ℃. After ending the crystallization process, the crystals were filtrated and dried. The dried solids were sieved by standard sieve (Shangyu Mold, China) ranging from 0.05 mm to 0.45mm at intervals of 0.05 mm. The purity of crystals obtained in different sieves was analyzed by the gas chromatograph using the same measurement procedure described in the section 2.2.1. The crystal morphology was observed using a stereo-microscope (Stemi 508, Zeiss, Germany).

2.2.4 Polythermal crystallization at near-eutectic composition The near-eutectic composition crystallization process was performed in the same apparatus showed in Figure 5(a). The near-eutectic composition with 50.0 wt% fluorene and 50.0 wt% fluorenone was chosen as initial concentration, which is saturated at 30 ℃ as well. Equivalent amounts (6.8750 g) of components fluorene and fluorenone were added to 100 g cyclohexane. Then the crystallization process was conducted under the same conditions of the previous polythermal crystallization process. 2.2.5 Polythermal crystallization with removal separation at near-eutectic composition Based on the previous apparatus showed in Figure 5(a), the apparatus was retrofitted for removing fluorene particles online, as shown in Figure 5(b), with an additional jacketed sintered glass filter equipped at the top of the vessel and a pump (Model BT100-1F, Baoding Longer, China) used to withdraw the upper liquid. The solution composition is the same as that of previous near-eutectic 10


Page 11 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


composition. After crystallization, the stirring rate was slowed down to a suitable level. A silicone tube was introduced underneath the mother liquor surface. Subsequently, the upper suspension was pumped into the sintered glass filter, and the filtrated clear solution was returned to the vessel. The separated solids in the filter and residual solids in vessel were dried, sieved and analyzed using the same procedures.

Figure 5. Experiment apparatus for (a) crystallization of pure material and mixture (b) crystallization of mixture with online removal separation.

3 Results and Discussion 3.1 Ternary Phase diagram and pure material crystallization The co-crystal may be formed in cooling crystallization process owing to the similar molecular structure of fluorene and fluorenone. Hence, the grinded mixture of fluorene and fluorenone and the solids crystallized from saturation solution were primarily checked by powder X-ray diffraction (PXRD). The results of PXRD pattern, presented in Figure 6, show that the peaks of grinded mixture are the combination of fluorene and fluorenone, and there is no new peak. It indicates that the product is heterogeneous mixture, and the co-crystal is not formed before and after crystallization. 11



12000

10000

(a)fluorenone 8000

Intensity

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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 34

(b)fluorene 6000

4000

(c)crystallization

2000

(d)grinded 0 5

10

15

20

25

30

35

40

2Theta(degree)

Figure 6. Powder X-ray diffraction pattern. (a) pure fluorenone, (b) pure fluorene, (c) cooling crystallization products and (d) grinded mixture.

The solubility diagram provides the fundamental thermodynamic data for the design of the crystallization process. Therefore, the ternary phase diagram of the fluorene-fluorenone-cyclohexane from 10 ℃ to 40 ℃ was determined and showed in Figure 7. It can be seen that the solubility strongly depends on temperature and binary mixture composition. As temperature increases from 10 ℃ to 40 ℃, the solubility of fluorene and fluorenone in cyclohexane rises, especially for the eutectic point composition, showing a rapid raise form 7 wt% to 56 wt%. Furthermore, the composition of solutes also has a great influence on the solubility, the solubility isotherms shift almost vertically to the opposite triangle sides at a relative higher temperature. In other words, the solubility of fluorene or fluorenone is strongly affected by the presence of the other component, which indicates this system is far away from the ideal solution behavior.

12


Page 13 of 34

0.0 1.0

10℃ 20℃ 30℃ 40℃

0.1 0.9 0.2

Flu ore no ne

0.8

0.3

e an hex clo Cy

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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


0.7

0.4 0.6 0.5 0.5 0.6 0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.4

Fluorene

Figure 7. Ternary phase diagram of fluorenone-fluorene-cyclohexane from 10 ℃ to 40 ℃

The pure fluorene and fluorenone morphology in cyclohexane is investigated as well. Even though they have the similar molecular structures, they show completely different crystal morphologies. As shown in Figure 8, the fluorene shows a white plate-like shape with bulk density of 1.20 g/mL, while the fluorenone shows a yellow rhombic bipyramidal shape with a relative greater bulk density of 1.43 g/mL. Furthermore, in the same cooling temperature from 30 to 10 ℃, fluorene shows a similar relative supersaturation S of 1.2 to fluorenone of 1.4. The relative supersaturation S is calculated as S = (C2C1)/C1, where C1 and C

2

represent the saturated concentration at 10 ℃ and 30 ℃, respectively.

However, as shown in Figure 8, the crystal size of fluorenone is estimated to be around 0.2 mm whereas the crystal size of fluorene is estimated to be less than 0.1 mm. These results indicate that the fluorenone is a kind of easy-growing crystal compared with fluorene. The different growth property

13



Page 14 of 34

makes it possible to separate eutectic-forming system of fluorene and fluorenone on the basis of particle size.

Figure 8. Pure crystals obtained from cyclohexane solution (a) fluorene and (b) fluorenone 3.2 Isothermal and polythermal crystallization at eutectic composition To evaluate the effect of seeding operation, an additional experiment at eutectic composition without seeding operation was carried out in polythermal. After a series of process, including crystallization, drying and sieve fraction, different amount of crystals were obtained in each standard sieves. The purity of crystals in each sieve was analyzed by the gas chromatograph, and the mass percentage of each component was calculated by the following equation: 𝜔𝑖,𝑗 =

𝑚𝑗 𝑚total

× 𝑝𝑖,𝑗

where 𝜔𝑖,𝑗 represents the mass percentage of component i (fluorene or fluorenone) in sieve j. mj and mtotal represent the masses in sieve j and all sieves, respectively. pi represents the purity of component i in sieve j. As showed in Figure 9, and it could be seen that the purity of fluorene or fluorenone changes slightly with particle size increasing, mainly around 50 wt%. Furthermore, both fluorene and fluorenone crystals distributes mainly in the segments from 0.05 to 0.20 mm, and takes almost 85 wt% of all crystals. Because the most of crystals are produced by the primary nucleation, the maximum crystal size in this experiment is below 0.35 mm. The crystals whose size ranges from 0.05-0.10 mm and 0.1514


Page 15 of 34

0.20 mm are showed in Figure 10 (a) and (b). Same amount of the white crystals and yellow crystals can be observed, and aggregation appears when the crystal size is above 0.15 mm. These results indicate that fluorene and fluorenone crystals have similar size distribution when seeding operation is not employed. Therefore, the separation of eutectic mixture of fluorene and fluorenone could not be realized. 100%

50% Purity of Fluorene Purity of Fluorenone Mass Percentage of Fluorene Mass Percentage of Fluorenone

40%

Mass percentage(%)

80%

Purity (%)

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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


60%

30%

40%

20%

20%

10%

0%

0 .1 -0 05 . 0

5 .1 -0 10 . 0

0 .2 -0 15 . 0

25 0. 20.

0 .3 -0 25 . 0

35 0. 30.

0%

Partice Size (um)

Figure 9. Purity trend and mass distribution of fluorene and fluorenone by polythermal crystallization at eutectic composition without seeding operation. The blue and yellow lines represent purity of fluorene and fluorenone, and the blue and yellow bars represent mass percentage of fluorene and fluorenone, respectively.

Figure 10. Images of crystals obtained from different part by polythermal crystallization at eutectic composition without seeding operation. (a) 0.05-0.10 mm, (b) 0.15-0.20 mm. 15



Page 16 of 34

On the basis of previous experiment, seeding operation is employed to selectively promote the growth process of fluorenone and to achieve an obvious particle size difference between two components. The reason selecting fluorenone to be introduced is that fluorenone is a kind of easygrowing compound compared with fluorene. Seeding operation was conducted in both isothermal and polythermal modes to make a comparison. During isothermal crystallization process, growth of fluorenone seeds started after introducing the fluorenone seeds, and after a while, the large fluorenone crystalline crystals was observed, (it is easy to distinguish fluorenone crystal for its bright yellow color). Besides, the increase of the fluorenone crystals numbers was also observed as secondary nucleation occurred. As expected, after a certain time (depends on experimental condition and on property of substance), spontaneous crystallization of fluorene occurred, since a large amount of white fine crystals were observed in the vessel. Figure 11(a) shows the purity trend and mass distribution of products at different particle size. The products with purity of fluorene above 70 wt% are classified into fluorene-rich part, and the same rule applies for fluorenone-rich part. The products with purity below 70 wt% are classified into mixture part. Therefore, the products can be divided into three different parts in the figure 11(a) including fluorenerich part, mixture-part and fluorenone-rich part separated by the gray dash line. The fluorene-rich part mainly covers the small particle size area, ranging from 0.05 to 0.15 mm, where the majority is fine fluorene crystals with a purity of 85.86 - 86.34 wt%. The narrow mixture part refers to the mixture of fluorene and fluorenone crystals, ranging from 0.15 to 0.20 mm, where the fluorene purity decreases as particle size increases, while, the other component shows an opposite trend. Compared with the former two parts, the fluorenone-rich part is much wider. It distributes in large size segments from 0.20 to 0.45 mm with the purity ranging from 74.00 to 90.17 wt%. In fact, the range of fluorenone16


Page 17 of 34

rich part could be much wider if the experimental cutoff particle size exceeds 0.45 mm. In this paper, the max sieve size of 0.45 mm was employed, because the purity trend feature had been already presented clearly in the selected range, increasing the maximum sieve size had little meaning for analyzing. Therefore, by collecting crystals with size below 0.15 mm and above 0.2 mm separately, fluorene and fluorenone products could be harvested independently at the same time. (a)

100%

50% Fluorene-rich Mixture

Fluorenone-rich

Mass percentage(%)

40%

Purity of Fluorene Purity of Fluorenone Mass Percentage of Fluorene Mass Percentage of Fluorenone

60%

30%

40%

20%

20%

10%

0%

10 0. 50 0.

15 0. 01 0.

20 0. 51 0.

25 0. 2. 0

30 0. 52 0.

35 0. 3. 0

40 0. 53 0.

5 .4 e0 v bo A

45 0. 04 0.

Partice Size (um)

(b) 100%

0%

50% Fluorenone-rich

Mixture

Fluorene-rich


80%

40%

A

bo v

e0

-0 .4 5 0. 40

0. 35

0. 25

0. 15

0. 10

0. 05

.4 5

0% -0 .4 0

0% 0. 30. 35

10%

-0 .3 0

20%

0. 20. 25

20%

-0 .2 0

40%

-0 .1 5

30%

-0 .1 0

60%

Mass percentage (%)

Purity (%)

80%

Purity (%)

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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Partice Size (um)

17



Page 18 of 34

Figure 11. Purity trend and mass distribution of fluorene and fluorenone by crystallization at eutectic composition. (a) isothermal crystallization and (b) polythermal crystallization. The blue and yellow lines represent purity of fluorene and fluorenone, and the blue and yellow bars represent mass percentage of fluorene and fluorenone

Figure 12. Images of crystals obtained from different parts by crystallization at eutectic composition (a) isothermal, fluorene-rich part, 0.05-0.10 mm, (b) isothermal, mixture part, 0.15-0.20 mm, (c) isothermal, fluorenone-rich part, above 0.45 mm, (d) polythermal, fluorene-rich part, 0.05-0.10 mm, (e) polythermal, mixture part, particle size between 0.15-0.20 mm, (f) polythermal, fluorenone-rich part, above 0.45 mm

In the crystallization process, there are two different supersaturation consumption approaches of two components existing. This ideal crystallization process is illustrated in Figure 13. The point E1 represents the subcooled saturated solution with eutectic composition. After seeding fluorenone crystals to the subcooled solution, the crystallization of fluorenone is induced (whereas the fluorene

18


Page 19 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


solution remains in metastable zone), and fluorenone experiences a maximum growth rate for the maximum supersaturation. The mother liquor composition moves towards point P from point E1 (the orange liquid composition line runs under the blue equilibrium line due to the unideal solution behavior). During this process, the supersaturation of fluorenone is majorly consumed by crystal growth process, which produces large fluorenone crystals. The supersaturation consumption approach of fluorene is different. Because of lacking seeds, fluorene keeps in metastable zone until the spontaneous nucleation occurs at point P, where the fluorene has maximum nucleation rate. The trajectory will turn towards the equilibrium point E2 at temperature T2. During this process, the supersaturation of fluorene is majorly consumed by the primary nucleation, and the effect of the rest limited supersaturation on the growth of fluorene is negligible. Consequently, the fine fluorene crystal was obtained. Crystals with different size can be obtained in the solution. The results are summarized in Table 1. The above experiment shows that an apparent particle size difference is generated, which means that the separation of fluorene and fluorenone is feasible in isothermal crystallization process from the viewpoint of purity and particle size.

Figure 13. Illustration of crystallization process of isothermal crysallization process

19



Page 20 of 34

It should be noted that the morphology of crystals obtained from mixture differs from pure crystals. Fluorenone crystal obtained from mixture solution by isothermal crystallization shows an irregular crystal morphology with extremely rough surface (as shown in Figure 12(c)). The PXRD patterns in Figure 6 show that their structures are same, which indicates that no polymorphism or co-crystal is formed. The reason for the crystal morphology change is that the heavy collision of particles during crystallization process break the sharp margin of fluorenone crystals, thus, the irregular morphology of fluorenone crystals are observed.

Table 1. Comparison of experimentally determined mass of products, yields, and maximum purity for different crystallization mode at eutectic composition Polythermal

Isothermal

Polythermal

without seeding

with seeding

with seeding

Obtained products / g

19.20

3.7909

19.4409

Yield / %

70.0

14.82

70.49

Maximum purity of fluorene / wt%

59.38

86.34

81.19

Maximum purity of fluorenone / wt%

52.82

90.17

81.44

Mode

The maximum supersaturation of isothermal crystallization process has already been determined since the crystallization temperature is fixed, thus, the narrow operable temperature range results an unsatisfied yield of 14.82 %. In comparison with the isothermal process, polythermal crystallization process could provide a decreasing temperature for further increase of driving force to enhance crystallization process.

20


Page 21 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


The purity trend and mass distribution results of polythermal crystallization are presented in Figure 11(b). Three similar parts can be found in Figure 11(b), including a relative narrow fluorene-rich part with a purity from 77.36 to 81.19 wt% and a fluorenone-rich part with a purity from 80.87 to 81.44 wt% and a mixture part. While, some conspicuous changes can be seen in the mixture part, the width is extended to 0.15 – 0.35 mm significantly compared with isothermal crystallization process where the width is 0.15 - 0.20 mm. Since the fluorene crystals produced by primary nucleation grow under the supersaturation as a result, fine fluorene crystals grow and spread to a wider particle size range from 0.15 – 0.35mm. Therefore, the maximum purity showed in Table 1 has an obvious decrease compared with isothermal crystallization. The crystal morphology in different part are shown in Figure 12, which exhibits the similar crystal morphologies of the fluorene-rich part and mixture part of polythermal crystallization compared to the isothermal crystallization. However, a heavy aggregation is observed in the fluorenone rich part as shown in Figure 12 (f) after employing the polythermal mode. The polythermal crystallization will provide further supersaturation to crystallization which achieved a satisfying high yield of 70.49 %. But in the meanwhile, it results in a wider mixture part which is against the separation process. The existence of two component rich part with a relative high purity still makes it feasible to separate fluorene and fluorenone. It is worth noticing that the fluorene is supposed to remain fine particles and concentrate in low particle size part for primary nucleation always produces fine crystals. However, the fluorene can be found in the whole range whether isothermal crystallization or polythermal crystallization. Because it is impossible to keep fine fluorene particles from adsorbing on the large fluorenone crystal surface. This could be confirmed from the microscope images, in Figure 12, white crystal could be seen on the surface of the large fluorenone crystals. Moreover, the components of fluorene and fluorenone in 21



residual solution may crystalize on the crystal surface and form agglomerates during the dying process. This problem will be discussed in section 3.4.

3.3 Polythermal crystallization at near-eutectic composition Previous experiments were performed under at eutectic composition. However, the composition of industrial raw materials always differs from the exact eutectic composition. Therefore, experiment at near-eutectic was carried out in this part. As shown in Figure 14, after changing the initial composition to the near-eutectic, a higher purity (87.48 - 87.52 wt% and 90.0 - 93.1 wt%) of fluorene and fluorenone in each rich part has been achieved by using polythermal crystallization at near-eutectic composition. What’s more, the region of mixture part is narrowed to 0.15 - 0.20 mm significantly compared with polythermal crystallization where the mixture part is from 0.15 mm to 0.35 mm. Narrowing the width of mixture part is beneficial to the separation process. 100%

50%

Fluorenone-rich

Fluorene-rich Mixture

40%


60%

30%

40%

20%

20%

10%

0%

10 0. 50 0.

15 0. 01 0.

20 0. 51 0.

25 0. 2. 0

30 0. 52 0.

35 0. 3. 0

Partice Size (um)

40 0. 53 0.

45 0. 04 0.

5 .4 e0 v bo A

22


0%

Mass percentage (%)

80%

Purity (%)

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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 22 of 34

Page 23 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 14. Purity and mass distribution of fluorene and fluorenone by polythermal crystallization at near-eutectic composition. The blue and yellow lines represent purity of fluorene and fluorenone, and the blue and yellow bars represent mass percentage of fluorene and fluorenone. Figure 15 shows the morphology of crystals in different parts obtained by polythermal crystallization at near-eutectic composition. It can be observed that similar crystal morphology is obtained compared with previous isothermal crystallization results, and aggregation in the fluorenone-rich part is weakened significantly. Furthermore, as shown in figure 15(c), white fine crystals can be found on the surface of the yellow crystals, indicating the adsorption of fluorene crystals on the fluorenone crystals happened. In principle, the polythermal mode can provide driving force for both fluorene and fluorenone particle growth resulting in a wide mixture part. However, the results show that the mixture part is not changed greatly in this experimental condition. Because the slight change of initial composition can decrease the concentration of solute greatly according to the determined ternary phase diagram. The initial concentration of both components decreased almost a half in this experiment. As a result, a mild supersaturation driving force is provided to crystal growth at the same temperature range compared with previous experiments at eutectic composition. It is remarkable that the yield of this mode is 283 % higher than that of the isothermal crystallization. These results demonstrates operating at near-eutectic will facilitate polythermal crystallization process by narrowing the mixture parts. Details are showed in Table 2.

23



Page 24 of 34

Figure 15. Images of crystals obtained from different parts by polythermal crystallization at neareutectic composition. (a) fluorene-rich part, 0.05-0.10 mm, (b) mixture part, 0.15-0.2 mm, and(c) fluorenone-rich part, above 0.45 mm

Table 2. Comparison of experimentally determined mass of products, yields, and maximum purity for different crystallization mode at near-eutectic composition Mode

Polythermal without removal

Polythermal with removal

Obtained products / g

5.7924

5.9414

Yield / %

41.92

43.00

Maximum purity of fluorene / wt%

87.52

90.17

Maximum purity of fluorenone / wt%

93.10

95.30

3.4 Polythermal crystallization with removal separation at near-eutectic composition Previous experiments have showed a successful polythermal crystallization process with a satisfying productivity at near-eutectic composition. However, no matter isothermal or polythermal crystallization process, the attachment of fluorene particles in growth of fluorenone has a negative effect on the purity, furthermore, sieving the solid mixture is extremely inconvenient in industry. For these many drawbacks, an online removal separation of the fluorene and fluorenone was attempted. After cooling crystallization, the stirring rate was slowed to a suitable level, at which, fluorene crystals and fluorenone crystals had different distribution in vessel for the different density. Large size and high density fluorenone crystals mainly kept down in vessel, conversely, small size and low density

24


Page 25 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


fluorene kept suspended at top. Then the fluorene and fluorenone could be separated by pumping the upper suspension that was abounded of fine fluorene crystals to a sintered glass filter. The product obtained from filter is showed in Figure 16(a). A large amount of white fluorene and very little fluorenone are separated with fluorene purity of 90.17 wt%, demonstrating that most of the fluorene crystals are separated by the removal operation. In order to further verify the separation degree of fluorene and fluorenone, the crystal remained in vessel was investigated as well. As expected, only mixture part and fluorenone-rich part are obtained after employing the online removal separation method, and the fluorene rich part is separated successfully. Crystal morphologies in these parts are presented in Figure 16 (b) and (c). Furthermore, as shown in Figure 17, fluorenone with a higher purity ranging from 93.4% to 95.30 wt% was obtained in fluorenone-rich part compared with previous experiments. The online removal separation of fine fluorene particles leads to a decrease of its number in the solution that weakens the attachment of fine fluorene onto the fluorenone crystal. Therefore, the purity of fluorenone is improved. Because it is impossible to guarantee the entirely identical conditions in every experiment during the process, the crystallization and secondary nucleation rate might differ slightly. Therefore, small differences of gained product and yield could be seen in Table 2.

Figure 16. Images of crystals obtained by polythermal crystallization at near-eutectic composition with the online removal separation. (a) crystals obtained from the filter and (b) crystals obtained from the vessel with particle size ranging from 0.10 to 0.15 mm, and (c) crystals obtained from the vessel with particle size above 0.45 mm 25



100%

50%

Fluorenone-rich

Mixture

80%

40%

60%

Mass percentage (%)


30%

0. 45 A bo ve

Partice Size (um)

0. 40 -0 .4 5

0. 35 -0 .4 0

0% 0. 30. 35

0% 0. 25 -0 .3 0

10%

0. 20. 25

20%

0. 15 -0 .2 0

20%

0. 10 -0 .1 5

40%

0. 05 -0 .1 0

Purity (%)

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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 26 of 34

Figure 17. Purity and mass distribution of fluorene and fluorenone by polythermal crystallization at near-eutectic composition with removal separation. The blue and yellow lines represent purity of fluorene and fluorenone, and the blue and yellow bars represent mass percentage of fluorene and fluorenone. It should be mentioned that the existence of the mixture part, in principle, has negative effects on the separation. However, the total mass of mixture part in this experiment is almost negligible. In other words, the crystals left in the vessel can be mainly considered as fluorenone products after employing the online removal separation. Therefore, it is reasonable to consider that the fluorenone and fluorenone are separated by solution crystallization combined with online removal separation successfully and perfectly.

26


Page 27 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


4. Conclusions In this paper, a novel separation technology for binary eutectic mixture, fluorene and fluorenone, by solution co-crystallization via differentiated supersaturation consumption strategy combined with particle size fraction has been presented. The determined fluorene-fluorenone-cyclohexane ternary phase diagram shows that solubility is strongly dependent on temperature and solute composition. In the isothermal crystallization process, two products of fluorene and fluorenone with maximum purity of 86.34 wt% and 90.17 wt% respectively were obtained at same time with a 14.82 % total yield. By comparison, polythermal crystallization provided a further supersaturation which reached a 70.49 % yield at the expense of decreasing the purity of fluorene and fluorenone products to 81.19 wt% and 81.44 wt% respectively. As a result, the width of mixture part is broadened, and that is negative to the separation process. However, changing the initial composition slightly from the eutectic point would narrow the mixture part significantly which facilitated the separation process. Therefore fluorene and fluorenone products with maximum purity of 87.52 wt% and 93.10 wt% respectively were obtained with a yield of 41.92 %. Furthermore, on the basis of density differences of two products, an online removal separation apparatus could separate fluorene and fluorenone independently, which reached higher purity of 90.17 wt% and 95.3 wt%, respectively, at a total yield of 43.00 %. These results demonstrate the feasibility and the potential productivity of separating eutectic-forming mixture by co-crystallization combined with particle size fraction.

Corresponding Author Zhou Ling*: [email protected] ；Yin Qiuxiang*: [email protected]

27



Page 28 of 34

ACKNOWLEDGMENT The authors are grateful for the financial support of the National Natural Science Foundation of China (No. 21506162), Tianjin Municipal Natural Science Foundation (No. 16JCZDJC32700), and the Major National Scientific Instrument Development Project (No. 21527812).

REFERENCES (1) Ulrich, J.; Frohberg, P., Problems, potentials and future of industrial crystallization. Front Chem Sci Eng 2013, 7, 1-8. (2) Malwade, C. R.; Buchholz, H.; Rong, B. G.; Qu, H. Y.; Christensen, L. P.; Lorenz, H.; SeidelMorgenstern, A., Crystallization of Artemisinin from Chromatography Fractions of Artemisia annua Extract. Org Process Res Dev 2016, 20, 646-652. (3) Wu, K. L.; Wang, H. Y.; Ward, J. D., Economic Comparison of Crystallization Technologies for Different Chemical Products. Ind Eng Chem Res 2018, 57, 12444-12457. (4) Klussmann, M.; White, A. J. P.; Armstrong, A.; Blackmond, D. G., Rationalization and Prediction of Solution Enantiomeric Excess in Ternary Phase Systems. Angewandte Chemie International Edition 2006, 45, 7985-7989. (5) Li, Z. J.; Zell, M. T.; Munson, E. J.; Grant, D. J. W., Characterization of Racemic Species of Chiral Drugs Using Thermal Analysis, Thermodynamic Calculation, and Structural Studies. J Pharm Sci-Us 1999, 88, 337-346.

28


Page 29 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(6) Wei, Y.; Dang, L.; Zhang, X.; Cui, W.; Wei, H., Solid-Liquid Phase Equilibrium and Solubility of Dibenzo b,d furan and 9H-Fluoren-9-one in Organic Solvents. J Chem Eng Data 2012, 57, 12791287. (7) Wei, Y.; Zhang, X.; Zhang, J.; Dang, L.; Wei, H., Solid-liquid equilibrium of some polycyclic aromatic hydrocarbons in wash oil. Fluid Phase Equilibr 2012, 319, 23-29. (8) Ding, S. P.; Yin, Q. X.; Du, W.; Sun, X. W.; Hou, B. H.; Zhang, M. J.; Wang, Z., Formation of Solid Solution and Ternary Phase Diagrams of Anthracene and Phenanthrene in Different Organic Solvents. J Chem Eng Data 2015, 60, 1401-1407. (9) Linnow, K.; Steiger, M.; Lemster, C.; De Clercq, H.; Jovanovic, M., In situ Raman observation of the crystallization in NaNO3-Na2SO4-H2O solution droplets. Environ. Earth Sci. 2013, 69, 16091620. (10) Wang, M.; Lei, L.; Guo, Y.; Meng, L.; Wang, S.; Deng, T., Phase Equilibria of the Reciprocal Quaternary System (Na+, Ca2+//Cl–, Borate–H2O) at 288.15 K and 0.1 MPa. Journal of Chemical & Engineering Data 2018, 63, 4005-4011. (11) Li, X.; Yin, Q. X.; Zhang, M. J.; Hou, B. H.; Bao, Y.; Gong, J. B.; Hao, H. X.; Wang, Y. L.; Wang, J. K.; Wang, Z., Process Design for Antisolvent Crystallization of Erythromycin Ethylsuccinate in Oiling-out System. Ind Eng Chem Res 2016, 55, 7484-7492. (12) Codan, L.; Casillo, S.; Bäbler, M. U.; Mazzotti, M., Phase Diagram of a Chiral Substance Exhibiting Oiling Out. 2. Racemic Compound Forming Ibuprofen in Water. Cryst Growth Des 2012, 12, 5298-5310. 29



Page 30 of 34

(13) Lorenz, H.; Sapoundjiev, D.; Seidel-Morgenstern, A., Enantiomeric mandelic acid systemmelting point phase diagram and solubility in water. J Chem Eng Data 2002, 47, 1280-1284. (14) Lorenz, H.; Sapoundjiev, D.; Seidel-Morgenstern, A., Solubility Equilibria in Chiral Systems and Their Importance for Enantioseparation. Engineering in Life Sciences 2003, 3, 132-136. (15) Li, X.; Yin, Q.; Zhang, M.; Hou, B.; Bao, Y.; Gong, J.; Hao, H.; Wang, Y.; Wang, J.; Wang, Z., Antisolvent Crystallization of Erythromycin Ethylsuccinate in the Presence of Liquid-Liquid Phase Separation. Ind Eng Chem Res 2016, 55, 766-776. (16) van der Ham, F.; Witkamp, G. J.; de Graauw, J.; van Rosmalen, G. M., Eutectic freeze crystallization simultaneous formation and separation of two solid phases. Journal of Crystal Growth 1999, 198, 744-748. (17) Chivavava, J.; Rodriguez-Pascual, M.; Lewis, A. E., Effect of Operating Conditions on Ice Characteristics in Continuous Eutectic Freeze Crystallization. Chem Eng Technol 2014, 37, 13141320. (18) Becheleni, E. M. A.; Rodriguez-Pascual, M.; Lewis, A. E.; Rocha, S. D. F., Influence of Phenol on the Crystallization Kinetics and Quality of Ice and Sodium Sulfate Decahydrate during Eutectic Freeze Crystallization. Ind Eng Chem Res 2017, 56, 11926-11935. (19) Hasan, M.; Louhi‐Kultanen, M., Determination of Pitzer Parameters for 1‐1 Nitrate and 1 ‐2 Sulfate Solutions from Freezing Point Data. Chem Eng Technol 2014, 37, 1340-1346.

30


Page 31 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(20) Lewis, A. E.; Nathoo, J.; Thomsen, K.; Kramer, H. J.; Witkamp, G. J.; Reddy, S. T.; Randall, D. G., Design of a Eutectic Freeze Crystallization process for multicomponent waste water stream. Chem Eng Res Des 2010, 88, 1290-1296. (21) Poornachary, S. K.; Chia, V. D.; Yani, Y.; Han, G. J.; Chow, P. S.; Tan, R. B. H., Anisotropic Crystal Growth Inhibition by Polymeric Additives: Impact on Modulation of Naproxen Crystal Shape and Size. Cryst Growth Des 2017, 17, 4844-4854. (22) Ham, F. V. D.; Seckler, M. M.; Witkamp, G. J., Eutectic freeze crystallization in a new apparatus: the cooled disk column crystallizer. Chemical Engineering & Processing Process Intensification 2004, 43, 161-167. (23) Vaessen, R.; Seckler, M.; Witkamp, G. J., Eutectic Freeze Crystallization with an Aqueous KNO 3 −HNO 3 Solution in a 100-L Cooled-Disk Column Crystallizer. Ind Eng Chem Res 2011, 42, 4874-4880. (24) Coquerel, G., Preferential Crystallization. Topics in Current Chemistry 2007, 269, 1. (25) Perez-Garcia, L.; Amabilino, D. B., Spontaneous resolution, whence and whither: from enantiomorphic solids to chiral liquid crystals, monolayers and macro- and supra-molecular polymers and assemblies. Chemical Society Reviews 2007, 36, 941-967. (26) Lorenz, H.; Seidel-Morgenstern, A., Processes To Separate Enantiomers. Angewandte Chemie International Edition 2014, 53, 1218-1250. (27) Elsner, M. P.; Ziomek, G.; Seidel-Morgenstern, A., Efficient separation of enantiomers by preferential crystallization in two coupled vessels. AIChE Journal 2009, 55, 640-649. 31



Page 32 of 34

(28) Desiraju, G. R., Crystal Engineering: From Molecule to Crystal. Journal of the American Chemical Society 2013, 135, 9952-9967. (29) Liu, G.; Liu, J.; Liu, Y.; Tao, X., Oriented Single-Crystal-to-Single-Crystal Phase Transition with Dramatic Changes in the Dimensions of Crystals. Journal of the American Chemical Society 2014, 136, 590-593. (30) Kulkarni, S. A.; McGarrity, E. S.; Meekes, H.; ter Horst, J. H., Isonicotinamide self-association: the link between solvent and polymorph nucleation.

···Chemical Communications 2012, 48, 4983-

4985. (31) Navarro, A.; Wu, H.-S.; Wang, S. S., Engineering problems in protein crystallization. Sep Purif Technol 2009, 68, 129-137. (32) Surade, S.; Ochi, T.; Nietlispach, D.; Chirgadze, D.; Moreno, A., Investigations into Protein Crystallization in the Presence of a Strong Magnetic Field. Cryst Growth Des 2010, 10, 691-699. (33) Guo, Z.; Jones, A. G.; Li, N., The effect of ultrasound on the homogeneous nucleation of BaSO4 during reactive crystallization. Chem. Eng. Sci. 2006, 61, 1617-1626. (34) Kordylla, A.; Krawczyk, T.; Tumakaka, F.; Schembecker, G., Modeling ultrasound-induced nucleation during cooling crystallization. Chem. Eng. Sci. 2009, 64, 1635-1642. (35) Galema, S. A., Microwave chemistry. Chemical Society Reviews 1997, 26, 233-238. (36) Moitra, S.; Kar, T., Studies on the crystal growth and characterization of urea L-malic acid single crystals grown from different solvents. Mater Lett 2008, 62, 1609-1612.

32


Page 33 of 34 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 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(37) Salvalaglio, M.; Vetter, T.; Giberti, F.; Mazzotti, M.; Parrinello, M., Uncovering Molecular Details of Urea Crystal Growth in the Presence of Additives. Journal of the American Chemical Society 2012, 134, 17221-17233. (38) Han, G. J.; Chow, P. S.; Tan, R. B. H., Precise Habit Modification of Polar DL-Alanine Crystal by Control of Supersaturation. Cryst Growth Des 2011, 11, 3941-3946. (39) Wang, C.; Zhang, X.; Du, W.; Huang, Y. H.; Guo, M. X.; Li, Y.; Zhang, Z. X.; Hou, B. H.; Yin, Q. X., Effects of solvent and supersaturation on crystal morphology of cefaclor dihydrate: a combined experimental and computer simulation study. Crystengcomm 2016, 18, 9085-9094. (40) Simone, E.; Klapwijk, A. R.; Wilson, C. C.; Nagy, Z. K., Investigation of the Evolution of Crystal Size and Shape during Temperature Cycling and in the Presence of a Polymeric Additive Using Combined Process Analytical Technologies. Cryst Growth Des 2017, 17, 1695-1706. (41) Wu, Z. H.; Yang, S. L.; Wu, W., Application of temperature cycling for crystal quality control during crystallization. Crystengcomm 2016, 18, 2222-2238. (42) Wei, Y.; Dang, L.; Zhang, X.; Cui, W.; Wei, H., Solid-liquid phase equilibrium of 9-fluorenone and several polynuclear aromatic hydrocarbons. Fluid Phase Equilibr 2012, 318, 13-18.

33



TOC：

34


Page 34 of 34

A Novel Technology for the Separation of Binary Eutectic-forming

Recommend Documents