Journal of Molecular Liquids 340 (2021) 116837

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Journal of Molecular Liquids

journal homepage: www.elsevier.com/locate/molliq

Molecular interaction mechanism and performance evaluation in the

liquid-liquid extraction process of ionic liquid-heptane-tertiary butanol
based on molecular dynamics
Zhengrun Chen a, Yuanyuan Shen a, Hongru Zhang a, Yasen Dai a, Yajuan Qu a, Zhaoyou Zhu a, Peizhe Cui a,
Yixin Ma b, Yinglong Wang a,⇑
a
College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, People’s Republic of China
b
College of Chemical and Environmental Engineering, Shandong University of Science and Technology, 579 Qianwangang Road, Qingdao 266590, People’s Republic of China

a r t i c l e i n f o a b s t r a c t

Article history: Nowadays, organic solvents are more and more widely used in chemical industry, If the waste liquid is
Received 11 April 2021 not recovered in time, this will also cause serious damage to the environment. In this work, [HMIM]
Accepted 25 June 2021 [OTF] and [BMIM][OTF], [OMIM][OTF] were used to separate n-heptane-t-butanol azeotropic system.
Available online 29 June 2021
From the molecular level, through the analysis of non-bonding interaction energy, spatial distribution
function, radial distribution function and self-diffusion coefficient, explore [HMIM][OTF] and [BMIM]
Keywords: [OTF], [OMIM][OTF] to separate n-heptane-tertiary butanol mixture Extraction mechanism. According
Liquid-liquid extractive
to the MD simulation results, the non-bond interaction energy, radial distribution function, spatial distri-
Molecular dynamics simulation
Ionic liquid
bution function and self-diffusion coefficient of different ionic liquid and different components were cal-
Toxicity analysis culated and compared. The accuracy of force field parameters is verified by the density of each
Process simulation component. The results show that electrostatic energy plays a key role in the extraction process. The
radial distribution function shows that [OTF]- plays a leading role in the extraction process. With the con-
tinuous growth of carbon chain, the extraction ability of ionic liquid is enhanced, but the solubility of raf-
finate is also enhanced. At the same time, ECOSAR toxicity analysis software also showed that [OMIM]+
had strong biological toxicity and was not suitable to be used as extractant. After comprehensive consid-
eration, [HMIM][OTF] is selected as the best extractant. Finally, using [HMIM][OTF] as extractant, the pro-
cess is designed and optimized. The final mole fraction of NHP is 99.73%, and the recovery of ionic liquid
is 99.97%. This study provides certain guidance for the screening of ionic liquids as extractants.
Ó 2021 Elsevier B.V. All rights reserved.

1. Introduction be separated by ordinary distillation. ordinary distillation cannot

Clofarabine [1] is an effective drug in the treatment of child-
hood acute lymphoblastic leukemia, which is commonly used in
clinic. However, organic solvents such as tert-butyl alcohol (TBA)
and n-heptane (HEP) are needed in the production of this drug. If
these organic solvents are not treated, a large amount of waste liq-
uid will be produced. The existence of these waste liquids will not
only cause huge costs, but also cause great damage to the environ-
ment [2]. Therefore, it is very important to recycle these organic
solvents.
Among them, tertiary butanol and n-heptane are azeotropic,
The molar ratio is xTBA:xHEP = 0.5930:0.4070 at 1 bar, so it can not
⇑ Corresponding author at: College of Chemical Engineering, Qingdao University
of Science and Technology 266042, Qingdao, People’s Republic of China.
E-mail address: wangyinglong@qust.edu.cn (Y. Wang).
separate them. Therefore, the commonly used methods include
extractive distillation [3–5], reactive distillation [6–7], membrane
separation [8–9], azeotropic distillation [10–11], liquid–liquid
extraction [12–13], etc. Liquid-liquid extraction is often used in
industrial separation because of its large capacity, good separation
effect, high recovery rate, continuous operation and easy automatic
control.
As the most basic and simplest separation method, liquid–liq-
uid extraction (LLE) is to add solvent to the mixture, so that the
content of the original component in the two phases is different,
so as to realize the separation of the mixture [14]. LLE has the
advantages of simple operation, low cost and low requirement
for experimental equipment, and it shows good extraction perfor-
mance in separating azeotrope. As a new kind of excellent solvent,
ionic liquids (ILs) has made great progress in LLE extraction. Ionic
liquids are considered to be the most promising solvents because

https://doi.org/10.1016/j.molliq.2021.116837
0167-7322/Ó 2021 Elsevier B.V. All rights reserved.
Z. Chen, Y. Shen, H. Zhang et al.
Nomenclature
IL Ionic liquid
TBA tertiary butanol
HEP n-heptane
MD Molecular dynamics
[HMIM][OTF] 1-hexyl-3-methylimidazolium trifluo-
romethansulfonate
[BMIM][OTF] 1-n-butyl-3-methylimidazolium trifluoromethane-
sulfonate
[OMIM][OTF] 1-methyl-3-octylimidazolium trifluoromet
of their advantages of free matching ion combination, nonvolatile,
strong solubility, nonflammability, good thermal and chemical sta-
bility, and are widely used in environmental, pharmaceutical and
other fields.
Sun et al. [15] used [HMIM][FEP] to extract 1-butanol from
dilute solutions, which has high selectivity and partition coeffi-
cient. Zhu et al. [16] compared the potential of the three ionic liq-
uids in separating methanol and n-hexane, and finally obtained
[BMIM][NTF2] with good results in extracting methanol. Jiao
et al. [17] studied the use of deep co-solvent (DES) as the extrac-
tant, and the final extraction effect can exceed 90%, showing good
extraction performance and super high extraction effect. Zhang
et al. [18] studied the recovery of n-hexane from methanol by ionic
liquid extraction. The recoveries of methanol and ionic liquids
were 94.11% and 99.32%, respectively. The total annual cost of liq-
uid–liquid extraction can be reduced by 17.31% Gao et al. [19]
studied the extraction effect of [EMIM][SCN] for p-cresol, and the
key experimental factors such as the mass ratio of extractant to
model oil, extraction temperature and extraction time were stud-
ied and optimized. Under the optimum conditions, the extraction
rate was 98.25%. It can be seen that the use of liquid–liquid extrac-
tion can achieve a better separation effect.
González et al. [20] used selective ionic liquids and ionic liquid/
salt mixtures as entrainers to separate n-heptane from toluene.
The results showed that adding ionic liquids can increase the rela-
tive volatility of n-heptane in toluene. Corderí et al. [21] used ionic
liquid as a solvent to separate the n-hexane/ethanol azeotropic
mixture, and the selectivity of ionic liquid was that the selectivity
value decreased in turn [HMIM][N(CN)2] > [HMIM][TFO] > [HMIM]
[NTF2], and regarding the alkyl chain length of the ion with [NTF2]
anion, S decreases as the cationic chain length increases. Blahut
et al. [22] studied [EMIM][TCB] as an entrainer to separate
methanol-dimethyl carbonate (DMC) azeotropic mixture through
extractive distillation, and finally obtained it, which is compatible
with other IL and non-IL entrainers studied in the literature. In
comparison, [EMIM][TCB] is one of the best performance products.
Zhang et al. [23] studied three ionic liquids as entrainers to sepa-
rate methyl acetate and methanol. The results showed that all
three ionic liquids can produce a salting-out effect on methyl acet-
ate, thereby increasing the relative volatility. Therefore, it can be
seen that as a green solvent, ionic liquids are widely used in sepa-
ration technology and can achieve better separation.
In recent years, with the development of molecular dynamics
simulation, more and more people have applied molecular dynam-
ics to explore the process of liquid–liquid extraction and separa-
tion, explore the interaction between molecules, and select
efficient and green extractants. As a new method for screening
new solvents, combining it with experiments can play a positive
role. For example, Dehury et al. [24] used liquid–liquid equilibrium
experiments (LLE) and MD to explore the effectiveness of 1-meth
yl-3-octylimidazoliumbis(trifluoromethylsulfonyl)imide ([OMIM]
2
Journal of Molecular Liquids 340 (2021) 116837
GAFF Generalized amber force field
RESP Restrained electrostatic potential
PBC Periodic boundary conditions
VMD Visual molecular dynamics
RDF Radial distribution function
SDF Spatial distribution functions
D self-diffusion coefficient
AIMD ab initio molecular dynamics
[NTF2]) in extracting butanol from water-butanol systems.
Stephenson et al. [25] used to explore the microscopic mechanism
of removing ethanol from water. The results show that the position
of the hydroxyl group has an important influence on the overall
hydrogen bond structure. Taha et al. [26] are studying the MD
mechanism of using biological buffers to extract organic solvents
from water solvents. They explored the interaction between water
and organic solvents at the molecular level, and calculated hydro-
gen bonds, hydrogen bond lifetimes, and radial directions between
different pairs. Distribution function, coordination number, etc. It
can be seen that MD plays an increasingly important role in sepa-
ration technology, which can provide guidance for the selection of
extractants.
In this work, [HMIM][OTF], [BMIM][OTF], [OMIM][OTF] were
used to separate TBA-HEP. The non-bond interaction energy, spa-
tial distribution function, radial distribution function and self-
diffusion coefficient were calculated by GROMACS. Through the
study of its mechanism, the effect of ionic liquid on the separation
of TBA-HEP system was observed, and the best ionic liquid for the
separation of TBA-HEP system was found. At the same time, the
accuracy of GROMACS force field parameters is verified, which
proves that molecular dynamics simulation is reliable in the selec-
tion process of extractant. The prediction of molecular simulation
calculation can provide guidance for the experiment. At the same
time, ECOSAR toxicity analysis software was used to analyze the
biological toxicity of different cations and cations. Finally, the opti-
mum extractant was designed and optimized. This provided guid-
ance for the green and sustainable application of extractant.
2. Molecular dynamics details
Gaussview software to draw the initial molecular structure of
[HMIM][OTF], [BMIM][OTF], [OMIM][OTF], tertiary butanol, n-
heptane. The B3LYP/6-311G* basis set to optimize the structure
of each atom using Gaussian 16 [27–28]. As shown in Fig. 1, the
atomic structure of all substances after optimization is displayed.
Amber and Gaussian to calculate restrained electrostatic potential
(RESP) charge [29], and finally get the partial charge of all mole-
cules. The ANTECHAMBER module in the Generalized Amber Force
Field (GAFF) function to get the force field parameters [30].
The ILs, tert-butyl alcohol and n-heptane molecules were set to
440, 350 and 550 respectively according to a certain proportion to
construct the simulation system. The packmol program to put ILs,
tertiary butanol, and n-heptane in the same simulation box, fill the
two ends of the cube box, let the tertiary butanol and n-heptane be
randomly distributed in the middle of the IL liquid, and finally
Obtain a 14
14
14 nm3 simulation box, all atoms are randomly
distributed in the simulation box [31].
All molecules were simulated by MD in the GROMACS software
[32–33]. At constant temperature (298.15 K) and constant pressure
Z. Chen, Y. Shen, H. Zhang et al.
Fig. 1. Optimized molecular structure. (Dark blue represents N atoms, Light blue represents C atoms, Pink represents H atoms, Yellow represents S atoms, Red represents O
atoms, Green represents F atoms.)
(1 bar), GROMACS software was used Berendsen thermostat and
Berendsen barostat to calculate the equilibrium phase, and use
V-rescale thermostat and Parrinello-Rahman barostat to calculate
the generated phase. The Velocity Verlet algorithm to minimize
the energy of the system to make the energy < 100 to eliminate
the repulsive force in the system and avoid the collapse of the sim-
ulation due to excessive force on some atoms. Periodic boundary
conditions (PBC) are the key to simulating condensed phase sys-
tems. Three directions were set during the system simulation,
and the time step was set at 1 fs. The hydrogen bond was restricted
during the simulation. The cut-off method with a cut-off radius of
12 Å is used to deal with the long-distance electrostatic interaction
between molecules. The neighbor list uses the Verlet algorithm. In
the calculation of electrostatic interaction, in order to make the
simulation as accurate as possible, we calculate the MD trajectory
in PME technique and then modify it to cut off technique. Among
them, the dispersion effect attenuates with distance 1/r6, which
is a short-range effect, and the electrostatic interaction between
charged particles attenuates 1/r, which is a long-range effect. For
isolated systems, due to the limited size, the cutoff is often set to
a very large value to calculate the electrostatic interaction between
all particles. When considering periodicity, the total electrostatic
interaction energy of particles in the center box includes not only
the interaction between these particles and other particles in the
box, but also the interaction with other particles in the mirror box.
The system is gradually heated from 0 K to 298.15 K, and
the system is balanced in the NVT ensemble for 5 ns. After
the temperature equilibrium is reached, the NPT ensemble of
50 ns is carried out under isothermal and isobaric conditions.
After making the system reach a sufficient balance, perform
molecular dynamics simulation on the system, and save the tra-
jectory data every 1000 ps during the operation. Finally, the
visual molecular dynamics (VMD) program is used to analyze
the trajectory [34].
3
Journal of Molecular Liquids 340 (2021) 116837
2.1. Molecular dynamics analysis
2.1.1. Verification of force field parameters
Force field verification is a more complex phenomenon, involv-
ing properties such as enthalpy of evaporation, dielectric constant,
surface tension, viscosity and heat capacity. In recent years, the
radial distribution function obtained from ab initio molecular
dynamics has also been used as an advanced method to verify
the force field. Priest et al [35] Used ab initio molecular dynamics
(AIMD) simulation of organophosphorus (OP) and organochlorine
(OC) compounds to evaluate the results of full atomic force field
molecular dynamics (FFMD) simulation and generalized AMBER
force field (GAFF), and verified the applicability of the force field
by using radial distribution functions (RDF). This method is extre-
mely interesting and meaningful. In addition, Zhang et al [36] ver-
ified the force field parameters by calculating the pure material
density when using molecular dynamics to evaluate the removal
of acid gas in SNG by ionic liquids.
In this work, we use the most basic properties of single mole-
cule to verify the accuracy of molecular dynamics simulation.
The density, viscosity and heat capacity of each molecule were cal-
culated using GROMACS software to further verify the force field
parameters (Table S1-S3). Finally, compared with the literature,
the deviation of all pure materials is less than 5%, which shows that
the force field is applicable.
2.1.2. Non-bonded interaction
Non-bonded interaction is a concept in the molecular mechan-
ics model of physical organic chemistry. The size of the non-
bonding interaction can be expressed by its potential energy func-
tion. The potential energy function of the non-bonding interaction
is usually the most important part of any molecular force field. The
equation used to describe the degree of molecular distortion and
energy. In this study, MD was set at the trajectory of
Z. Chen, Y. Shen, H. Zhang et al.
Fig. 2. The interaction energies (kJ / mol) of different il-tba-hep systems were calculated by MD.
T = 298.15 K, P = 1 atm, and the interaction energy between ILS and
TBA-HEP and the total non-bonding interaction energy (including
static pressure energy and van der Waals force) were calculated.
The total non-bonded interaction energy (Etotal) was divided into
electrostatic energy (Eelec) and van der Waals (Evdw) energy. The
calculated interaction energy is shown in Table S4. The total non-
bonded interaction energy (Etotal) was expressed by Equation (1):


1
DEtotal kJmol ¼ 2625:5½Eelec ða:u:Þ þ Ev dw ða:u:Þ
Fig. 2 shows the interaction energies of different ILs with TBA
and HEP, respectively. It can be seen from the figure that in the sys-
tem, the interaction energy between [HMIM][OTF], [BMIM][OTF],
[OMIM][OTF] and TBA is greater than that between IL and HEP.
Therefore, all the three ionic liquids have extraction effect on
TBA. It can be seen from the figure that anions have more influence
on TBA than cations, but with the growth of cationic carbon chain,
the influence of cations on TBA is increasing. However, with the
growth of carbon chain, the effect of ILs on HEP also increases.
Therefore, the effect of ionic liquids on extraction ability should
be considered comprehensively. Therefore, the order of interaction
between ionic liquids and TBA is as follows: [OMIM][OTF] > [HMI
M][OTF] > [BMIM][OTF]. However, [OMIM][OTF] has higher extrac-
Fig. 3. RDF diagram between different ions and HEP: (a) Cation-HEP; (b) anion-TBA.
Journal of Molecular Liquids 340 (2021) 116837
tion ability for HEP. This will lead to the use of [OMIM][OTF] as
extractant will also extract more HEP, which is extremely unfavor-
able for the separation process. Through comprehensive compar-
ison [HMIM][OTF] is the best Extractant to separate TBA-HEP.
2.1.3. Radial and spatial distribution functions
Radial distribution function (RDF) was used to analyze the
ð1Þ interaction between different extractants and azeotrope. Among
them, RDF selects an atom in the extractant as the central atom,
and determines the interaction between the two by observing
the probability of the appearance of other matter atoms around
the central atom. The peak position of RDF plays an important
role. The interaction between extractant and TBA was positively
correlated with the peak height. Secondly, the intermolecular
interaction is negatively correlated with the peak position. In
RDF, the peak height is positively correlated with the peak position,
and a maximum value appears at a certain position. Then the peak
height is negatively correlated with the peak position and tends to
be stable in the fluctuation.
As shown in the Fig. 3, it is shown that the S1 atom of the anion,
the N1 and N2 atoms of the cation, and the C1 atom of the TBA are
considered to generate RDF. It can be seen from Fig. 3 (a) is greater
4
Z. Chen, Y. Shen, H. Zhang et al.
Fig. 4. SDF between different ions and TER: (a) [BMIM]+-TBA; (b) [HMIM]+-TBA; (c) [OMIM]+-TBA; (d) [OTF]- -TBA. (isovalue = 1.2 nm3).
than N2-C1, indicating that N1 plays a leading role in the relation-
ship between cation and TBA. The interaction between the two
reaches the maximum at 5 Å. According to the RDF generated by
the interaction between all cations (N1) and TBA(C1), we can get:
[OMIM]+>[HMIM]+>[BMIM]+. Therefore, [HMIM]+ extraction TBA
effect is relatively better in the three ionic liquids. As shown in
Fig. 3(b), the maximum value between [OTF](S1) and TBA(C1) is
at 5 Å. By comparing the peak heights of [HMIM]+ and [OTF]-, we
can conclude that [OTF]- plays a dominant role in the extraction
process. Therefore, the ionic liquid with the best extraction effect
is [HMIM][OTF].
The spatial distribution function (SDF) reveals the distribution
characteristics of the environment around the particles through
the angle of the three-dimensional space. Use TRAVIS software to
draw SDF [37]. As shown in Fig. 4, (a), (b) and (c) respectively indi-
cate that the active center is [BMIM]+, [HMIM]+, [OMIM]+ and is
covered by TBA. Under the same isosurface, the larger the area of
the component surrounding the central atom, the greater the inter-
action between them. By comparing the component areas of the
three cations, the order is: [OMIM]+ > [HMIM]+ > [BMIM]+. How-
ever, [OMIM]+ has stronger interaction with HEP than other cations
by analyzing the RDF of different cations on HEP and non-bonded
interaction. It means that HEP is more easily soluble in
[OMIM] + than other other cations. Therefore, the extraction effect
of TBA by [HMIM] + is relatively good in three ILs.As shown in Fig. 4
(b), we can see that the area of the anion is much larger than that of
the cation, so the interaction between [OTF]- and TBA is much lar-
ger than that of other cations. So [OTF]- plays a dominant role in
the extraction process. This is consistent with the result of RDF.
2.1.4. Self-diffusion coefficient
In the process of IL liquid–liquid extraction and separation of
TBA-HEP, because molecules diffuse freely and randomly, studying
how molecules diffuse is also helpful to determine the best ionic
liquid. The self-diffusion coefficient (D) can be obtained from for-
mula (2) [38,39]. In the process of calculating the diffusion coeffi-
cient, it is necessary to determine which period of time to use for
fitting. Liu et al [40] and Maginn [41] used b factor to test the state
of diffusion. This method is very significant for determining the dif-
fusion process. In this work, the slope is obtained by linear fitting
of the 10%  90% interval of the trajectory, and then the diffusion
coefficient is obtained. By comparing the deviation with D, if it is
5
Journal of Molecular Liquids 340 (2021) 116837
significantly less than D, it indicates that the selected interval is
meaningful.
1 d X N
D¼ lim ½ jri ðtÞ  ri ð0Þj2  ð2Þ
6 t!1 dt i1
where jri ðtÞ-ri ð0Þj is the displacement of the ith numerator from time
P
0 to t. ½ Ni-1 jri ðtÞ-ri ð0Þj2  is the mean square displacement. The D
value of each molecule was calculated by MSD. As shown in table
S5, the self-diffusion coefficients of different ionic liquids and azeo-
tropes were calculated. The smaller the D value, the harder it is for
the molecule to diffuse.
Fig. 5 shows the solubility diagram and MSD diagram of TBA
and HEP in different ILs. The larger the slope of MSD curve, the
more difficult the extraction. It can be seen from the Fig. 5 (b) that
the slope of TBA is smaller than that of HEP, so the self-diffusion
coefficient of TBA in ILs is smaller than that of HEP, so TBA can
be extracted by ionic liquid. As shown in the figure, with the exten-
sion of time, the slope of TBA gradually decreases, that is, the D
value gradually decreases, indicating that TBA has entered the IL
rich stage. Therefore, the solubility order of TBA in ionic liquids
is: [OMIM][OTF] > [HMIM][OTF] > [OMIM][OTF]. However, we
can see that the slope of the MSD diagram of HEP in [OMIM]
[OTF] deviates greatly from that of other ionic liquids. Therefore,
the solubility of HEP in [OMIM][OTF] is also very high. In conclu-
sion, the ionic liquid of [HMIM][OTF] has better extraction effect.
3. Toxicity evaluation
Almost all manufacturing processes in modern society are
inseparable from chemicals, which makes chemical production
the most important and global industry in the world economy.
However, chemicals are also a double-edged sword, and their
inherent dangerous characteristics will have adverse effects on
the environment and human health, which will bring many poten-
tial or direct consequences. Therefore, the selection of extractant
should also consider whether it has an impact on the environment,
so as to evaluate whether the chemical production can meet the
sustainable production. The ECOSAR procedure is a reliable method
and is often used to predict theoretical toxicity. ECOSAR is a model
in the EPI SUITE and can be run independently. It uses many QSAR
models based on LogKow chemical classification to predict the
acute and chronic toxicity of chemicals to aquatic organisms (fish,
Z. Chen, Y. Shen, H. Zhang et al.
Fig. 5. (a) Self-diffusion coefficients in ILs at 298.15 and 1 bar; (b) MSD diagram of three imidazole-based ILs-TBA-HEP ternary systems.
Daphnia, algae). According to the regulations of ‘‘globally harmo-
nized system of classification and labeling of chemicals” (GHS),
the toxicity values are divided into four categories: strong toxicity
(LC50 / EC50 / CHV  1mg/L), toxicity (10mgL  LC50 / EC50 /
CHV > 1mg/L), harmfulness (100mgl  LC50 / EC50 /
CHV > 10mg/L), and harmlessness (LC50 / EC50 / CHV > 100mg/L)
[42,43].
In this study, the acute and chronic toxicity of four cations and
five anions were calculated using ecosar program (table S1). Fig. 6
shows the biotoxicity map based on acute toxicity. We can easily
see from the figure that the toxicity is as follows: [OMIM]+ >
[HMIM]+ > [BMIM]+ > [EMIM]+. The biological toxicity of anionic
structure is as follows: [NTF2]- > [SCN]- > [BF4]- > [HSO4]-. There-
fore, in [OMIM]+ is very toxic, not suitable for sustainable concept,
so it is not suitable as an extractant. The minimum value of [OTF]-
in anions is 95268 mg / L, which is not toxic to aquatic organisms.
Therefore, comprehensive analysis of [HMIM][OTF] as extractant is
more appropriate.
4. Process simulation
Aspen Plus V11 was used to simulate the liquid–liquid extrac-
tion separation of HEP-TBA. First, define the ionic liquid in aspen
based on the UNIFAC-Lei model [44,45]. The parameters defining
the ionic liquid [HMIM][OTF] are shown in Table S6. Table S7 is
Fig. 6. The biotoxicity diagram based on acute toxicity.
6
Journal of Molecular Liquids 340 (2021) 116837
the parameter of goup parameters of volume (Rk) and surface area
(Qk). The binary interaction parameters are given in Tables S8 of
supporting information, which are used to describe the phase
behavior relationship of the system. The feed flow rate of raw
material is 100kmol / h, which is composed of 32% kmol/h TBA
and 68% kmol/h HEP, respectively. The pure component extractant
enters from the top of the extraction column, and then flows out
from the bottom of the extraction tower to the flash for further
separation. The mixed azeotrope enters into the bottom of the
extraction column, and more than 99.5% HEP is obtained at the
top of the extraction tower.
4.1. Sensitivity analysis
Firstly, the feed of extractant and the number of theoretical
plates were optimized by sensitivity analysis to determine the
optimal operation conditions. The relationship of NHP mole frac-
tion with extractant and theoretical plate is shown in Fig. 7. The
higher the feed of extractant, the higher the purity of NHP. How-
ever, when the feed of extractant reaches a certain level, the purity
of NHP will not increase. Therefore, it can be seen from the figure
that the best extraction effect is obtained when the feed rate of
extractant is 70 kmol / h. For the theoretical plate of the extraction
column, when the theoretical plate is larger than 4, the change of
the number of theoretical plates has little effect on the mole frac-
Z. Chen, Y. Shen, H. Zhang et al.
Fig. 7. Effect of theoretical plate and extractant feed on NHP mole fraction.
tion of NHP. Therefore, the feed rate of extractant is 70 kmol/ h and
the number of theoretical plates is 4, the mole fraction of NHP is
99.7%.
The recovery of extractant is also very important in the separa-
tion process. The purity of extractant recovery is also related to the
purity of NHP in the process. Through the sensitivity analysis of
flash pressure and temperature, the best industrial conditions are
determined to obtain high purity IL. Fig. 8 shows the effect of flash
temperature and flash pressure on the purity of IL. It can be seen
from the figure that temperature has a positive correlation with
IL, while pressure has a negative correlation with purity. Consider-
ing comprehensively, the temperature to be selected is 200 ℃, and
the pressure to be selected is 0.05 bar.
Fig. 9 shows the optimized process flow of liquid–liquid extrac-
tion of NHP-TBA azeotrope with [HMIM][OTF] as extractant. The
100 kmol / h azeotrope composed of 0.32 NHP and 0.68 TBA enters
from the bottom of the extraction column, 70 kmol / h fresh IL
enters the extraction column from the top. The temperature and
pressure of the two streams are 25 ℃ and 1 bar, respectively. After
Fig. 9. [HMIM][OTF] liquid–liquid extraction separation NHP-TBA process.
7
Journal of Molecular Liquids 340 (2021) 116837
Fig. 8. Effect of flash temperature and pressure on IL mole fraction.
passing through the extraction column with four theoretical plates,
59.769kmol/h raffinate phase with mole fraction of 0.9973 is dis-
charged from the top of the column, and the extracted phase is
pumped into the flash for further separation. In the flash, the tem-
perature and pressure are 200 ℃ and 1 bar, respectively. TBA rich
stream is obtained at the top of flash. A stream with mole fraction
of 0.999 [HMIM][OTF] is obtained at the bottom. The stream at the
bottom of the column is cooled and combined with fresh IL to enter
the extraction column.
5. Conclusion
In this work, the micro mechanism of extraction of TBA by three
kinds of ionic liquids with [BMIM][OTF] and [HMIM][OTF], [OMIM]
[OTF] was studied by molecular dynamics simulation. Through the
analysis of non-bond interaction, spatial distribution function, self-
diffusion coefficient and self-diffusion coefficient, the electrostatic
energy plays a leading role in the extraction process. Among the
Z. Chen, Y. Shen, H. Zhang et al.
three ILs, [OMIM][OTF] has the highest interaction energy with
TBA. However, the effect of [OMIM][OTF] on HEP is obviously
stronger than that of other ILs. It is unfavorable to the extraction
process. According to the biological toxicity analysis, although
[HMIM]+ has certain toxicity, it meets the requirements of sustain-
able production. Therefore, [HMIM][OTF] is the best extractant
through comprehensive analysis of separation effect and sustain-
able requirements. Using [HMIM][OTF] as extractant, the process
is designed and optimized. The final mole fraction of NHP is
99.73%, and the recovery rate of IL was 99.97%. The feasibility of
ionic liquid as extractant is further verified, and the application
of ionic liquid in industry is expanded. In the case of insufficient
experimental data, it can provide some guidance for the calculation
and analysis of liquid–liquid equilibrium.
CRediT authorship contribution statement
Zhengrun Chen: Conceptualization, Methodology, Investiga-
tion, Writing - original draft. Yuanyuan Shen: Conceptualization,
Methodology, Investigation, Writing - original draft. Hongru
Zhang: Validation, Data curation, Visualization, Software, Writing
- review & editing. Yasen Dai: Visualization, Formal analysis.
Yajuan Qu: Validation, Formal analysis. Zhaoyou Zhu: Visualiza-
tion, Writing - review & editing. Peizhe Cui: Writing - review &
editing. Yixin Ma: Resources, Supervision, Writing - review & edit-
ing. Yinglong Wang: Resources, Supervision, Writing - review &
editing.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgement
This work is supported by National Natural Science Foundation
of China (No. 21776145) and National Natural Science Foundation
of China (No. 21808117).
Appendix A. Supplementary material
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.molliq.2021.116837.
References
[1] S. Jeha, V. Gandhi, K.W. Chan, L. McDonald, I. Ramirez, R. Madden, M. Rytting,
M. Brandt, M. Keating, W. Plunkett, H. Kantarjian, Clofarabine, a novel
nucleoside analog, is active in pediatric patients with advanced leukemia,
Blood 103 (3) (2004) 784–789, https://doi.org/10.1182/blood-2003-06-2122.
[2] Z. Hao, J. Cao, Y. Dang, Y. Wu, X. Zhao, X. Wei, Three-dimensional hierarchical
porous carbon with high oxygen content derived from organic waste liquid
with superior electric double layer performance, ACS. Sustain. Chem. Eng. 7 (4)
(2019) 4037–4046, https://doi.org/10.1021/acssuschemeng.8b05423.
[3] Y. Zhao, K. Ma, W. Bai, D. Du, Z. Zhu, Y. Wang, J. Gao, Energy-saving thermally
coupled ternary extractive distillation process by combining with mixed
entrainer for separating ternary mixture containing bioethanol, Energy. 148
(2018) 296–308, https://doi.org/10.1016/j.energy.2018.01.161.
[4] A. Yang, H. Zou, I.L. Chien, D. Wang, S. Wei, J. Ren, W. Shen, Optimal design and
effective control of triple-column extractive distillation for separating ethyl
acetate/ethanol/water with multiazeotrope, Ind. Eng. Chem. Res. 58 (17)
(2019) 7265–7283, https://doi.org/10.1021/acs.iecr.9b00466.
[5] Y. Zhang, A. Li, J. Gao, D. Xu, L. Zhang, Z. Zhang, Y. Wang, Thermal coupled
extractive distillation sequences with three entrainers for the separation of
azeotrope isopropyl alcohol + diisopropyl ether, J. Chem. Technol. Biot. 95 (5)
(2020) 1590–1603, https://doi.org/10.1002/jctb.6354.
[6] C. Wang, Z. Zhang, X. Zhang, J. Gao, B. Stewart, Energy-saving hybrid processes
combining pressure-swing reactive distillation and pervaporation membrane
for n-propyl acetate production, Sep. Purif. Techno. 221 (2019) 1–11, https://
doi.org/10.1016/j.seppur.2019.03.074.
8
Journal of Molecular Liquids 340 (2021) 116837
[7] G. Contreras-Zarazúa, J.A. Vázquez-Castillo, C. Ramírez-Márquez, G.A. Pontis, J.
G. Segovia-Hernández, J.R. Alcántara-Ávila, Comparison of intensified reactive
distillation configurations for the synthesis of diphenyl carbonate, Energy. 135
(2017) 637–649, https://doi.org/10.1016/j.seppur.2019.03.074.
[8] J.H. Jhaveri, Z.V.P. Murthy, A comprehensive review on anti-fouling
nanocomposite membranes for pressure driven membrane separation
processes, Desalination 379 (2016) 137–154, https://doi.org/10.1016/j.
desal.2015.11.009.
[9] A. Khalid, M. Aslam, M.A. Qyyum, A. Faisal, A.L. Khan, F. Ahmed, A.A. Bazmi,
Membrane separation processes for dehydration of bioethanol from
fermentation broths: Recent developments, challenges, and prospects,
Renew. Sust. Energ. Rev. 105 (2019) 427–443, https://doi.org/10.1016/j.
rser.2019.02.002.
[10] Y. Dai, F. Zheng, B. Xia, P. Cui, Y. Wang, J. Gao, Application of mixed solvent to
achieve an energy-saving hybrid process including liquid–liquid extraction
and heterogeneous azeotropic distillation, Ind. Eng. Chem. Res. 58 (6) (2019)
2379–2388, https://doi.org/10.1021/acs.iecr.8b04983.
[11] Y. Fan, Q. Ye, J. Chen, X. Chen, T. Liu, H. Cen, A systematic method for optimum
heterogeneous azeotropic distillation systems with vapor recompression,
Chem. Eng. Process. 143 (2019), 107597, https://doi.org/10.1016/j.cep.2019.
107597.
[12] S. Marsousi, J. Karimi-Sabet, M.A. Moosavian, Y. Amini, Liquid-liquid extraction
of calcium using ionic liquids in spiral microfluidics, Chem. Eng. J. 356 (2019)
492–505, https://doi.org/10.1016/j.cej.2018.09.030.
[13] R. Heydari, Z. Lotfi, M. Ramezani, Simultaneous determination of zidovudine
and lamivudine in plasma samples using miniaturized homogenous liquid-
liquid extraction and high-performance liquid chromatography, J. Anal. Chem.
73 (11) (2018) 1105–1110.
[14] W. Fan, H. Yan, H. Huang, Y. Ma, J. Gao, D. Xu, Y. Wang, Measurement and
thermodynamic modeling of ternary liquid-liquid equilibrium for extraction of
2, 6-xylenol from aromatic hydrocarbon mixtures with different solvents, J.
Chem. Eng. Data. 66 (1) (2021) 330–337, https://doi.org/10.1021/acs.
jced.0c00718.
[15] D. Sun, H. Feng, F. Xin, W. Li, Z. Zhang, Screening of ionic liquids as extractant
for 1-butanol extraction from dilute solution, J. Taiwan. Inst. Chem. E. 91
(2018) 119–129, https://doi.org/10.1016/j.jtice.2018.06.005.
[16] Z. Zhu, W. Bai, Y. Xu, H. Gong, Y. Wang, D. Xu, J. Gao, Liquid-liquid extraction of
methanol from its mixtures with hexane using three imidazolium-based ionic
liquids, J. chem. Thermodin. 138 (2019) 189–195, https://doi.org/10.1016/j.
jct.2019.06.024.
[17] T. Jiao, X. Zhuang, H. He, C. Li, H. Chen, S. Zhang, Separation of phenolic
compounds from coal tar via liquid–liquid extraction using amide compounds,
Ind. Eng. Chem. Res. 54 (9) (2015) 2573–2579, https://doi.org/10.1021/
ie504892g.
[18] W. Zhang, Z. Chen, Y. Shen, G. Li, Y. Dai, J. Qi, Wang, Y, Molecular mechanism
and extraction performance evaluation for separation of methanol and n-
hexane via ionic liquids as extractant, ACS. Sustain. Chem. Eng. 8 (23) (2020)
8700–8712, https://doi.org/10.1021/acssuschemeng.0c02234.
[19] A. Li, X. Xu, L. Zhang, J. Gao, D. Xu, Y. Wang, Separation of cresol from coal tar
by imidazolium-based ionic liquid [EMIM][SCN]: Interaction exploration and
extraction experiment, Fuel 264 (2020), 116908, https://doi.org/10.1016/
j.fuel.2019.116908.
[20] E.J. González, P. Navarro, M. Larriba, J. García, F. Rodríguez, Use of selective
ionic liquids and ionic liquid/salt mixtures as entrainer in a (vapor+ liquid)
system to separate n-heptane from toluene, J. chem. Thermodin. 91 (2015)
156–164, https://doi.org/10.1016/j.jct.2015.07.041.
[21] S. Corderí, B. González, Ethanol extraction from its azeotropic mixture with
hexane employing different ionic liquids as solvents, J. Chem. Thermodin. 55
(2012) 138–143, https://doi.org/10.1016/j.jct.2012.06.028.
[22] A. Blahut, V. Dohnal, Ionic liquid 1-ethyl-3-methylimidazolium tetracyanoborate:
an efficient entrainer to separate methanol+ dimethyl carbonate azeotropic
mixture, Fluid Phase Equilib. 423 (2016) 120–127, https://doi.org/10.1016/j.
fluid.2016.04.021.
[23] Z. Zhang, A. Hu, T. Zhang, Q. Zhang, M. Sun, D. Sun, W. Li, Separation of methyl
acetate+ methanol azeotropic mixture using ionic liquids as entrainers, Fluid
Phase Equilib. 401 (2015) 1–8, https://doi.org/10.1016/j.fluid.2015.04.018.
[24] P. Dehury, U. Mahanta, T. Banerjee, Partitioning of butanol between a
hydrophobic ionic liquid and aqueous phase: insights from Liquid-liquid
Equilibria measurements and Molecular Dynamics simulations, Fluid Phase
Equilib. 425 (2016) 421–431, https://doi.org/10.1016/j.fluid.2016.06.007.
[25] S.K. Stephenson, R.D. Offeman, G.H. Robertson, W.J. Orts, Ethanol and water
capacities of alcohols: a molecular dynamics study, Chem. Eng. Sci. 61 (17)
(2006) 5834–5840, https://doi.org/10.1016/j.ces.2006.05.004.
[26] M. Taha, M.J. Lee, TES buffer-induced phase separation of aqueous solutions of
several water-miscible organic solvents at 298.15 K: Phase diagrams and
molecular dynamic simulations, J. Chem. Phys. 138 (24) (2013), https://doi.
org/10.1063/1.4809995 244501.
[27] A.D. Becke, Density-functional thermochemistry. III. The role of exact
exchange, J. Chem. Phys. 98 (7) (1993) 5648–5652.
[28] Stephens, P. J.; McCann, D. M.; Devlin, F. J.; Flood, T. C.; Butkus, E.; Stoncius, S.;
Cheeseman, J. R. Determination of molecular structure using vibrational
circular dichroism spectroscopy: the ketolactone product of Baeyer-Villiger
oxidation of (+)-(1R,5S) - bicyclo[3.3.1]nonane-2,7-dione. J. Org. Chem. 2005,
70(10): 3903-3913. https://doi.org/10.1021/jo047906y.
[29] C.I. Bayly, P. Cieplak, W. Cornell, P.A. Kollman, A wellbehaved electrostatic
potential based method using charge restraints for deriving atomic charges:
Z. Chen, Y. Shen, H. Zhang et al.
the RESP model, J. Phys. Chem. 97 (40) (1993) 10269–10280, https://doi.org/
10.1021/j100142a004.
[30] J. Wang, R.M. Wolf, J.W. Caldwell, P.A. Kollman, D.A. Case, Development and
testing of a general amber force field, J. Comput. Chem. 25 (9) (2004) 1157–
1174, https://doi.org/10.1002/jcc.20035.
[31] L. Martínez, R. Andrade, E.G. Birgin, J.M. Martínez, PACKMOL: a package for
building initial configurations for molecular dynamics simulations, J. Comput.
Chem. 30 (2009) 2157–2164, https://doi.org/10.1002/jcc.21224.
[32] M.J. Abraham, T. Murtola, R. Schulz, S. Páll, J.C. Smith, B. Hess, E. Lindahl,
GROMACS: High performance molecular simulations through multi-level
parallelism from laptops to supercomputers, SoftwareX. (2015) 19–25,
https://doi.org/10.1016/j.softx.2015.06.001.
[33] B. Hess, C. Kutzner, D. Van Der Spoel, E. Lindahl, GROMACS 4: algorithms for
highly efficient, load-balanced, and scalable molecular simulation, J. Chem. 4
(2008) 435–447, https://doi.org/10.1021/ct700301q.
[34] W. Humphrey, A. Dalke, K.V.M.D. Schulten, Visual molecular dynamics, J. Mol.
Graphics 14 (1996) 33–38, https://doi.org/10.1016/0263-7855(96)00018-5.
[35] C.W. Priest, J.A. Greathouse, M.K. Kinnan, P.D. Burton, S.B. Rempe, Ab initio and
force field molecular dynamics study of bulk organophosphorus and
organochlorine liquid structures, J. Chem. Phys. 154 (8) (2021) 084503.
[36] W. Zhang, X. Liu, H. Zhang, S. Li, J. Yang, P. Cui, Z. Zhu, Y. Ma, Y. Wang,
Molecular dynamics evaluation of removal of acid gases from SNG by ionic
liquid, ACS Sustain. Chem. Eng. 7 (21) (2019) 18093–18104.
[37] L. Zhang, X. Bing, Z. Cui, J.A. Labarta, D. Xu, J. Gao, S. Zhou, Y. Wang, Multiscale
exploration and experimental insights into separating neutral heterocyclic
nitrogen compounds using [emim][NO3] as an extractant, ACS. Sustain. Chem.
Journal of Molecular Liquids 340 (2021) 116837
Eng. 8 (14) (2020) 5662–5673, https://doi.org/10.1021/
acssuschemeng.0c00304.
[38] H. Liu, S. Dai, D. Jiang, Molecular dynamics simulation of anion effect
onsolubility, diffusivity, and permeability of carbon dioxide in ionic liquids,
Ind. Eng. Chem. Res 53 (25) (2014) 10485–10490.
[39] R. Biswas, V. Pasumarthi, T. Banerjee, P. Ghosh, S.M. Ali, Interfacial insightson
the dibenzo-based crown ether assisted cesium extraction in [BMIM][Tf2N]-
waterbinary system, J. Radioanal. Nucl. Ch. 311 (1) (2017) 427–438.
[40] Z. Liu, T. Chen, A. Bell, B. Smit, Improved united-atom force field for
1-alkyl-3-methylimidazolium chloride, J. Phys. Chem. B. 114 (13) (2010)
4572–4582.
[41] E.J. Maginn, Atomistic simulation of the thermodynamic and transport
properties of ionic liquids, Accounts. Chem. Res. 40 (11) (2007) 1200–1207.
[42] J.B. Wang, D. Zhi, H. Zhou, W. He, X. Zhang, Evaluating tetracycline degradation
pathway and intermediate toxicity during the electrochemical oxidation over
a Ti/Ti4O7 anode, Water Res. 137 (2018) 324–334, https://doi.org/10.1016/j.
watres.2018.03.030.
[43] F. Meng, W. Ma, Y. Wang, Z. Zhu, Z. Chen, G. Lu, A tribo-positive Fe@MoS2
piezocatalyst for the durable degradation of tetracycline: degradation
mechanism and toxicity assessment, Environ. Sci. Nano 7 (6) (2020) 1704–
1718, https://doi.org/10.1039/D0EN00284D.
[44] M. Taheri, C. Dai, Z. Lei, CO2 capture by methanol, ionic liquid, and their binary
mixtures: Experiments, modeling, and process simulation, AIChE. J. 64 (6)
(2018) 2168–2180, https://doi.org/10.1002/aic.16070.
[45] C. Dai, Z. Lei, B. Chen, Gas solubility in long-chain imidazolium-based ionic
liquids, AIChE. J. 63 (6) (2017) 1792–1798, https://doi.org/10.1002/aic.15711.