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Dihydrolevoglucosenone (Cyrene™), a Bio-based Solvent for Liquid-Liquid Extraction Applications


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Dihydrolevoglycosenone, commercially known as Cyrene™, is a versatile bio-based solvent reported for various applications including being a medium of chemical reactions and membrane manufacture. In this work, application of Cyrene™ in liquid-liquid extractions has been investigated. Four ternary systems have been assessed at 298.15K, 323.15K and 348.15K, keeping CyreneTM and methylcyclohexane constant and changing the third compound to toluene, cyclohexanol, cyclohexanone and cyclopentyl methyl ether. Studying these selected ternary systems, yielded an indication of applicability of Cyrene™ in related industrial separation processes such as aromatic/aliphatic separations, and in separations of oxygenates in the cyclohexane oxidation process. Key factors are biphasic system formation, distribution coefficients and selectivity. All ternary systems showed type I liquid-liquid phase behavior with a selective extraction of ternary components from methylcyclohexane by Cyrene™. The highest selectivity at 298.15K was found for cyclohexanol with 61.4±4.33, followed by cyclohexanone with 44.1±8.63, while toluene and cyclopentyl methyl ether had a selectivity of respectively 12.0±0.89 and 6.4±0.08. Although CyreneTM is applicable in all four ternary systems, the miscibility gap is narrow for the oxygenated species, indicating a limited operation window for liquid-liquid extraction which will be more severe at higher temperatures. Overall, the studies showed that there are certainly application windows for Cyrene™. In the case of oxygenate extraction, a process with Cyrene™ appears energy-saving because the energy duty appears to be lower than when using water, the best alternative solvent, which is a low boiling solvent for this purpose.
Dihydrolevoglucosenone (Cyrene), a Biobased Solvent for Liquid
Liquid Extraction Applications
Thomas Brouwer and Boelo Schuur*
Cite This: ACS Sustainable Chem. Eng. 2020, 8, 1480714817
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sıSupporting Information
ABSTRACT: Dihydrolevoglycosenone, commercially known as Cyrene, is a versatile
biobased solvent reported for various applications including being a medium of chemical
reactions and membrane manufacture. In this work, application of Cyrene in liquid
liquid extractions has been investigated. Four ternary systems have been assessed at
298.15 K, 323.15 K, and 348.15 K, keeping Cyrene and methylcyclohexane constant and
changing the third compound to toluene, cyclohexanol, cyclohexanone, and cyclopentyl
methyl ether. Studying these selected ternary systems yielded an indication of applicability
of Cyrene in related industrial separation processes such as aromatic/aliphatic separations
and in separations of oxygenates in the cyclohexane oxidation process. Key factors are
biphasic system formation, distribution coecients, and selectivity. All ternary systems
showed type I liquidliquid phase behavior with a selective extraction of ternary
components from methylcyclohexane by Cyrene. The highest selectivity at 298.15 K was
found for cyclohexanol with 61.4 ±4.33, followed by cyclohexanone with 44.1 ±8.63,
while toluene and cyclopentyl methyl ether had a selectivity of, respectively, 12.0 ±0.89 and 6.4 ±0.08. Although Cyrene is
applicable in all four ternary systems, the miscibility gap is narrow for the oxygenated species, indicating a limited operation window
for liquidliquid extraction which will be more severe at higher temperatures. Overall, the studies showed that there are certainly
application windows for Cyrene. In the case of oxygenate extraction, a process with Cyrene appears energy-saving because the energy
duty appears to be lower than when using water, the best alternative solvent, which is a low boiling solvent for this purpose.
KEYWORDS: Dihydrolevoglucosenone, Cyrene, Biobased solvent, Liquidliquid equilibrium, Liquidliquid extraction
Insights in the liquidliquid extraction (LLX) applicability of
dihydrolevoglycosenone, or Cyrene, were obtained by perform-
ing LLX in four dierent ternary systems. Cyrene, a biobased
polar solvent, attracted recent attention as being versatile for
various applications, e.g., as a medium to perform chemical
and to prepare membranes by phase inversion,
though no mention for LLX applications has been found as of
Cyrene can be an alternative aprotic dipolar solvent;
solvents of this class are typically used in a range of molecular
separations, from aromatic/aliphatic separation
to carbox-
ylic acid separation from water.
Industrially important
members of the solvent class of aprotic dipolar solvents include
N-methylpyrrolidone (NMP) and N,N-dimethylformamide
(DMF), which both are considered toxic solvents and subject
to restrictive legislation.
Cyrene is reported to have a much
lower toxicity,
and additionally since it is a biobased
product, it oers chances for the chemical industry to reduce the
consumption of fossil oil by replacing their toxic fossil oil-based
solvents for a much more benign biobased alternative.
In a
recent communication, the Circa Group announced a
production capacity of Cyrene of 1 kton per annum, which
signies the mass production of this new biobased solvent.
Although bulk prices may not be publically available, Krishna et
al. state that the bulk price of Cyrene may be approximately 2
which is comparable with traditional solvents.
Two key classes of molecular separation processes using
solvents include extractive distillation (ED) and LLX. In another
we showed the potential of Cyrene as an entrainer in
the ED of aromatic/aliphatic mixtures and paran/olen
mixtures. Similarly, next to the already proven entrainer function
in extractive distillations, Cyrene may be useful for LLX as well.
In order to investigate the applicability of Cyrene in LLX
processes, we assessed the liquidliquid equilibrium (LLE)
behavior of several ternary systems formed with Cyrene. The
investigated systems include (1) methylcyclohexane (MCH)
and toluene (TOL), (2) MCH and cyclohexanol (CHOH), (3)
MCH and cyclohexanone (CHO), and (4) MCH and
cyclopentyl methyl ether (CPME). The molecular structures
of all species used in this study are displayed in Figure 1.
Received: June 8, 2020
Revised: August 19, 2020
Published: August 31, 2020
Research Article
© 2020 American Chemical Society 14807
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These ternary mixtures have specically been chosen to rst
represent aromatics/aliphatics separations. These separations
using LLX have been the subject of study for a variety of model
compounds, including benzene, toluene, xylenes, (methyl)-
cyclohexane, and n-alkanes.
The model systems vary as the
related industrial mixture is complex.
The results in this study
on liquidliquid equilibria with Cyrene, MCH, and TOL will be
compared to the elaborate work done in the past concerning
molecular solvents,
ionic liquids (ILs),
and deep
eutectic solvents (DESs).
The separation of alcohols and ketones from aliphatics was
chosen because the compounds possess either an alcohol or a
ketone functionality, and they are relevant industrial chemicals,
for example, in the industrial oxidation process of cyclohexane to
Kim et al. and Pei et al. investigated
similar systems with CHO and CHOH, though they used
cyclohexane as a hydrocarbon and studied dimethyl sulfoxide
(DMSO) and water as a solvent.
The last ternary mixture with MCH and CPME was chosen
for the CPME ether functionality. CPME also has the potential
of being a biobased solvent.
The extraction of CPME from
an aliphatic stream has not been studied yet.
Next to evaluation of the extraction performance of Cyrene
for each of the systems, the LLE was also correlated using the
UNIQUAC model. Last, by maintaining MCH as the constant,
it became possible to compare all the systems with each other
and investigate trends between dierent functional groups and
thus study the applicability of Cyrene for separating molecules
with these dierent functional groups.
Materials. Chemicals, if not otherwise specied, were used as
received without any additional purication. Cyclopentyl
methyl ether (99.9%), cyclohexanone (99.9%), and cyclo-
hexanol (99%) were obtained from Sigma-Aldrich, while
methylcylohexane (reagent grade, 99%) was purchased from
Honeywell. Toluene (ACS, reag.Ph.Eu) was procured from
VWR Chemicals, while analytical acetone (LiChrosolv) was
acquired from Merck. A 1 L bottle of dihydrolevoglucosenone,
or Cyrene (99.3%), was supplied by the Circa Group.
LiquidLiquid Extraction Procedure. For the liquid
liquid extraction experiments, closed 10 mL glass vials were
used. All compounds were weighed with an accuracy of 0.5 mg
on an analytical balance. Consecutively, a vortex mixer and a
temperature-controlled shaking bath were used in the
equilibration. The mixture was shaken at 200 rpm for at least
12 h at a constant temperature and subsequently settled for at
least 1 h prior to sample taking. The experiments were
conducted at 298.15 K, 323.15 K, or 348.15 K with a
temperature variation of 0.02K. A solvent to feed ratio on a
mass basis of 1 was maintained, and the total mass of each phase
was kept approximately at 3 g. A sample of 0.51.0 mL was taken
with a 2 mL syringe with an injection needle from both phases.
Both phases were analyzed following the analysis produced.
Analysis Procedure. A Thermo Scientic Trace 1300 gas
chromatograph with two parallel ovens and an autosampler
TriPlus for 100 liquid samples was used for the analyses. Each
system was analyzed using an Agilent DB-1MS column (60m ×
0.25 mm ×0.25 μm) with an injection volume of 1 μL diluted in
analytical acetone. The same instrumental method was used for
every system with a ramped temperature prole following the
program of initial temperature at 50 °C, followed by a direct
ramp of 10 °C/min to 200 °C. The second ramp, which was
directly initiated after reaching 200 °C, of 50 °C/min to 320 °C
nished the program, which lasted 20 min. The FID temperature
was 330 °C. A column ow of 2 mL/min with a split ratio of 5, an
airow of 350 mL/min, a helium makeup ow of 40 mL/min,
and a hydrogen ow of 35 mL/min were used.
Fitting Procedure. Each ternary system was correlated for
all temperatures simultaneously with the UNIQUAC model.
This model predicts the activity coecient as the summation of
the combinatorial (γi
c) and residual (γi
R) terms of the activity
coecient, see eq 1.
γγ γ=+
nln ln
ii i
cR (1)
The combinatorial term, using the GuggenheimStavermann
accounts for the inuence of shape dierences
between the molecules and the corresponding entropy eects.
This contribution of the activity coecient is elaborated in eqs 2,
3, and 4.
nln1 5ln1
jjj (3)
where Φiis the volume fraction, θiis the surface area fraction, xi
is the molar fraction, riis the van der Waals volume, and qiis the
surface area of each component.
Figure 1. Structures of the molecules used in this study.
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The residual term, see eqs 5 and 6, is determined using the
same parameters and the additional empirical binary interaction
parameters τij. This value is tted using the temperature
independent parameter (Aij) and temperature-dependent
parameter (Bij).
kkkkj (5)
ij ij
For the correlation, known van der Waals volumes and surface
areas were used, see Table 1. For Cyrene, the parameters were
not available in the literature and were estimated with Density
Functional Theory with a B3LYP 6-311+G** parametrization in
combination with the methodology of Banerjee et al.
The four ternary LLE systems that were investigated in this
study are presented in a subsection for each of the systems. All of
the systems showed type I phase behavior
for all temperatures
investigated. For each of the ternary systems, the selectivity (Sij)
of the solute (i), being toluene, cyclohexanol, cyclohexanone, or
CPME, over MCH (j) was examined (eq 8). This selectivity is
dened as the ratio of the distribution coecients (KD,i) of each
of the solutes, which in turn is dened as the ratio of the
concentration of the solute, on a weight basis, in the solvent
([Xi]S) and the organic phase ([Xi]O)asineq 7.
D, (8)
All experimental results have been correlated using the
UNIQUAC model, which was checked on its thermodynamic
consistency using the Hessian matrix test. This information is
provided in the Supporting Information (SI),
as well as
tables with all the measured data and calculated distribution
coecients and selectivities. This allows an approximate
description of the binodal curve and the tielines. After describing
the results for each of the ternary systems individually, in the last
subsection, all ternary systems are compared to enable a general
description of the anities of Cyrene toward dierent moieties.
Additionally, rough short-cut calculations were performed of the
combined CHOH/MCH and CHO/MCH cases to assess the
potential of Cyrene in an LLX process.
MethylcyclohexaneTolueneCyrene. The results for
the MCHtolueneCyrene ternary system are displayed in
Figure 2. As can be seen from the binodal curves, a signicant
miscibility region can be seen. For 298.15 K, only below 35 wt
% toluene is a biphasic system observed, which further reduces
with increasing temperatures. This is in line with our work on
extractive distillation at a temperature above 373 K, where no
phase splitting was observed for this system.
A selectivity of 11.99 ±0.89 was induced with a toluene
concentration of 0.74 wt % in the Cyrene phase at 298.15K.
This selectivity decreases to 6.76 ±0.65 and 4.91 ±0.58 at,
respectively, 353.15 K and 348.15 K for similar toluene
concentrations. This is due to a lower activity coecient of
MCH in Cyrene, a consequence of a polarity decrease of the
solvent phase, which is a consequence of the higher hydrocarbon
(MCH and TOL) solubility at elevated temperatures, which in
turn is caused by the larger entropic contribution at higher
temperatures. The correlated UNIQUAC parameters are given
in Table 2.
The LLX performance of Cyrene has been put in perspective
by the comparison with other solvents, such as Sulfolane, n-
and various ILs, EMIM]-
As can be seen in Figure 3, Sulfolane is outperforming Cyrene
regarding selectivity, and n-formylmorpholine
has a higher
selectivity at high toluene fractions in the solvent phase. Also,
both solvents have a more signicant phase split than Cyrene.
Comparable performance was seen toward methanol,
Cyrene has a more signicant phase split.
The ILs induce an almost complete immiscibility, due to
lower distribution coecients compared to traditional solvents.
This immiscibility is due to their ionic nature, which does not
allow stabilization in the highly apolar hydrocarbon mixture.
Additionally, for low toluene fractions in the solvent phase, a
similar selectivity toward toluene is observed for the ILs
compared to Sulfolane. Although, at a higher toluene fraction,
the tetracyanoborate ILs
are able to retain a higher selectivity
compared to Sulfolane. A consequence of lower distribution
coecients in ILs is however that a larger solvent quantity is
required for the LLX, and the equipment diameter will increase.
On the other hand, due to the larger selectivity, fewer stages are
required, reducing the equipment height. Higher selectivity
means that fewer aliphatics need to be boiled from the solvent in
the solvent regeneration, which is benecial for the energy
requirement, which seems to be in favor for ILs. Overall, it is not
straightforward to decide which solvent is better, and a more
thorough process simulation including total annual cost
estimation is suggested but outside the scope of this paper.
MethylcyclohexaneCyclopentyl Methyl EtherCy-
rene. As can be seen in Figure 4, Cyrene induces a selectivity
of 6.42 ±0.08, 4.55 ±0.41, and 3.91 ±0.31 at, respectively,
298.15 K, 323.15 K, and 348.15 K for 0.65 wt % of CPME in
the solvent phase.
The results indicate that Cyrene is selective toward the polar
ether moiety over the aliphatic MCH. A substantial miscibility
region at CPME contents over 35 wt % CPME is observed,
which resembles the LLX-application window of the MCH
toluene case. In Table 3, the UNIQUAC parameters of the
correlation are displayed. This indicates that the dipolar
characteristics of the ether moiety induce similar intermolecular
interactions to those of the delocalized π-system of toluene.
MethylcyclohexaneCyclohexanolCyrene. The re-
sults for the system MCHCHOHCyrene are given in Figure
5. Cyrene induces a selectivity of 61.42 ±4.33, 32.8 ±5.83, and
Table 1. van der Waals Volumes and Surface Areas of All
component riqi
5.174 4.396
3.920 2.970
4.274 3.284
4.114 3.340
4.214 3.248
Cyrene 4.843 3.322
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16.6 ±2.26 at, respectively, 298.15 K, 323.15 K, and 348.15 K at
0.80 wt % of CHOH in the solvent phase. This is lower than
observed with DMSO
and water,
which have a selectivity of,
respectively, 155 and 1450, at low CHOH concentrations.
The lower selectivity of Cyrene can mainly be attributed to the
larger hydrocarbon backbone of Cyrene, compared to the small
DMSO and water molecules, which mitigates the multipole
interactions with the relatively unselective London dispersion
Also in the ternary system MCHCHOHCyrene, a large
miscibility region is observed, for concentrations above 25 wt
% cyclohexanol. Due to the large miscibility in the system, only a
small operation window is available for LLX, and the two phase
region decreases at increasing temperature. The larger
miscibility region indicates also that the capacity of Cyrene
(KD,CHOH = 4.64 at 0.80 wt % of CHOH in the solvent phase)
for CHOH is larger than that for water (KD,CHOH = 1.60I̵,
Cyrene would be preferred when high CHOH capacities are
required, while water is preferred when a larger immiscibility and
selectivity is required. DMSO has been shown to be quite toxic
and is for that reason not the preferred choice. The UNIQUAC
parameters for this system are present in Table 4.
MethylcyclohexaneCyclohexanoneCyrene. The re-
sults for the ternary system MCHCHOCyrene are given in
Figure 6. Cyrene induces selectivities of 44.07 ±8.63, 32.14 ±
2.78, and 19.25 ±2.00 at, respectively, 298.15 K, 323.15 K, and
348.15 K for the lowest amount of CHO in the solvent phase
(0.60 wt %). Also in this case, the selectivity is lower than
reported for DMSO
and water,
which have been reported to
be 42.9 and 1202. Also in this case, a signicant miscibility
region is observed at CHO contents higher than 23 wt %. The
single phase region is larger compared to the previous systems,
indicating a narrower LLX application window. This is due to
the mutual presence of ketone functionality in CHO and
Cyrene, resulting in a signicant mutual solubility. Hence,
Cyrene has a larger capacity for CHO (KD,CHO = 4.47 at 0.60
wt % of CHO in the solvent phase) than water (KD,CHO =
Figure 2. Ternary diagrams of the LLE of toluene, MCH, and Cyrene with the tielines, feed compositions, and binodal curves at (a) 298.15 K, (b)
323.15 K, and (c) 348.15 K, and (d) the STOL,MCH of Cyrene at the same temperatures. The UNIQUAC t is added throughout.
Table 2. Correlated UNIQUAC Parameter for the MCH
TolueneCyrene System
component icomponent jA
ij Aji Bij Bji
MCH toluene 0 0 191.0 171.5
Cyrene 4.587 2.627 1749 773.7
toluene 2.708 4.999 772.6 1463
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Figure 3. A comparison of (left) the LLE and (right) STOL,MCH at 298.15 K of several solvents: Cyrene, sulfolane, n-formylmorpholine,
and [BMIM][MSO4].
*These systems were measured at 293.15 K.
Figure 4. Ternary diagrams of the LLE of CPME, MCH, and Cyrene with the tielines, feed compositions, and binodal curves at (a) 298.15 K, (b)
323.15 K, and (c) 348.15 K, and (d) the SCPME,MCH of Cyrene at the same temperatures. The UNIQUAC t is added throughout.
ACS Sustainable Chemistry & Engineering Research Article
ACS Sustainable Chem. Eng. 2020, 8, 1480714817
). Also for this case, Cyrene and water may be preferred
solvent choices, if either CHO capacity or immiscibly window
and selectivity are the selection criteria. As previously
mentioned, DMSO is toxic and is preferentially avoided. In
Table 5, the UNIQUAC parameters of the correlation are
Comparative Study. By considering the combined data
from all ternary systems with toluene (TOL), cyclohexanol
(CHOH), cyclohexanone (CHO), and CPME, from MCH, the
performance of Cyrene toward particular moieties can be
evaluated. Cyrene is a bicyclic organic molecule in which a
double ether moiety, one in each ring, and a ketone functionality
are present. All moieties are aprotic and therefore can only act as
a hydrogen bond acceptor and will induce next to the
omnipresent London dispersion interactions also Keesom and
Debye interactions.
To see a comparison of the results, see
Table 6, and from Figures 2,4,5, and 6, it is concluded that
selectivity order is found to be mostly CHOH > CHO TOL >
CPME. A larger temperature dependency is seen for CHOH,
likely due to intra- and intermolecular hydrogen bonding,
resulting in lower selectivity than CHO at higher temperatures.
CHOH and CHO are extracted with signicantly higher
selectivity than toluene and CPME. This is due to respectively
the hydrogen bond donating character of CHOH and the
signicant dipole moment of 2.75 D
of CHO, which induces
substantial Keesom and Debye interactions with Cyrene.
Toluene and CPME do not have hydrogen bonding donating
capabilities and have much lower dipole moments compared to
CHO, respectively, 0.37 D
and 1.27 D,
hence a lower
selectivity is induced. Toluene does however exhibit a signicant
quadrupole moment,
which is responsible for more extensive
Keesom and Debye interactions, and therefore a larger
selectivity is induced compared to CPME.
When the CHO and CHOH cases are combined and their
extraction performances are compared, a measure of selectivity
toward both solutes may be estimated for the lowest weight
Table 3. Correlated UNIQUAC Parameter for the MCH
CPMECyrene System
component icomponent jA
ij Aji Bij Bji
MCH CPME 0 0 61.53 19.21
Cyrene 3.332 2.020 1356 588.3
CPME 2.319 3.522 661.0 899.1
Figure 5. Ternary diagrams of the LLE of cyclohexanol, MCH, and Cyrene with the tielines, feed compositions and binodal curves at (a) 298.15K, (b)
323.15K and (c) 348.15K, and (d) the SCHOH,MCH of Cyrene at the same temperatures. The UNIQUAC t is added throughout.
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fractions of solute in the solvent phase. A selectivity ratio
(SCHOH,MCH/SCHO,MCH) of 1.42 and 1.21
is obtained for,
respectively, Cyrene and water. We speculate that Cyrene is a
slightly more selective solvent for the combined extraction of
CHO and CHOH than water, though this may be caused by the
dierent alkane used in both studies. A Cyrene-based LLX
process for this separation was further investigated by short-cut
energy calculations in the next section.
Process Considerations. Liquidliquid equilibria are
cornerstones in an accurate description of liquidliquid
Table 4. Correlated UNIQUAC parameter for the MCHCyclohexanolCyrene System
component icomponent jA
ij Aji Bij Bji
MCH cyclohexanol 0.1112 0.1675 435.6 239.5
Cyrene 1.738 0.7045 817.2 153.3
cyclohexanol 0 0 128.7 12.05
Figure 6. Ternary diagrams of the LLE of cyclohexanone, MCH, and Cyrene with the tielines, feed compositions, and binodal curves at (a) 298.15 K,
(b) 323.15 K, and (c) 348.15 K, and (d) the SCHO,MCH of Cyrene at the same temperatures. The UNIQUAC t is added throughout.
Table 5. Correlated UNIQUAC Parameter for the MCHCyclohexanoneCyrene System
component icomponent jA
ij Aji Bij Bji
MCH cyclohexanone 1.090 1.090 364.9 364.9
Cyrene 4.587 2.627 1749 773.7
cyclohexanone 2.507 7.521 531.6 2133
Table 6. A Comparison between the Distribution Coecient and Selectivity Found for CHOH, CHO, TOL, and CPME at Similar
Low Weight Percentage in the Solvent Phase at 298.15 K, 323.15 K, and 348.15 K
component icomponent jcomponent jin solvent phase (wt %) distribution coecient component j() selectivity ()
(298.15 K/323.15 K/348.15 K)
MCH CHOH 0.80/0.65/0.51 4.64/2.94/1.64 61.4/32.8/16.6
CHO 0.87/0.60/0.56 4.47/3.15/2.20 44.1/32.1/19.3
TOL 0.74/0.82/0.72 0.98/0.54/0.51 12.0/5.80/5.32
CPME 0.83/0.63/0.57 0.30/0.40/0.40 5.15/4.27/3.54
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extractions (LLX) that arguably form the heart of LLX
processes. As solvents are rarely completely immiscible and
selective, several additional purication steps are required to
recover the solvent and obtain a pure product. An example is
given by de Graet al.
where two distillation columns are used
to recover the solvent and pure products from an LLX column.
The ranate can also be distilled to recover the solvent, though
for polar solvents the use of a water wash column to recover the
solvent can be applied to save energy. Subsequently, the water is
then evaporated from the solvent-rich water phase, and the
vapor is used to strip extracted solutes from the extract
To thoroughly compare Cyrene with all conven-
tional solvents for all studied applications, it will require rigorous
process simulations for all of these process steps, and even
consideration on which of the steps are required and preferred.
This is beyond the scope of this paper, in which the applicability
of Cyrene is explored, and a rst indication of the usefulness of
the application is discussed on the basis of miscibility,
distribution coecients, and selectivity. On the basis of a
short-cut calculation, an estimation of the required heat duty will
be given for the combined case of MCH/CHO and MCH/
CHOH. This case was chosen as being most interesting for
industrial application in the industrial oxidation process of
cyclohexane to CHO and CHOH.
The MCH-TOL case,
which certainly is also of industrial interest, was not simulated
because, on the basis of the liquidliquid equilibrium data, it can
be seen that both Sulfolane and ILs are clearly superior over
Cyrene with regard to selectivity and immiscibility.
The most signicant dierence between water and Cyrene is
related to the recovery of the CHO and CHOH from the
solvent, which boil at respectively 429 and 433 K. Cyrene is a
high-boiling solvent (bp: 500 K
), whereas water is a low-boiling
solvent (bp: 373 K). Recovery of water thus implies that the
solvent has to be boiled ofrom the solutes, whereas the solutes
can be boiled ofrom the Cyrene. Cyrene has therefore a
signicant advantage over water, due to the fact that the energy
penalty associated with the evaporation enthalpy of the solvent is
avoided in using the high-boiling Cyrene. Also, the capacity of
CHO and CHOH in water is lower compared to Cyrene. This
entails a larger amount of water being required to extract a
certain amount of CHO and/or CHOH than for Cyrene.
In order to estimate the magnitude of the energy advantage, a
set of rough calculations on the heat duty in the recovery
processes were performed. Using the LLE description by
UNIQUAC, the minimum solvent to feed (S:F) ratio (on mass
basis) was determined by simulation in ASPEN Plus of the LLX
process with 1000 equilibrium stages, a feed containing 90 wt %
MCH, and obtaining >99.9 wt % MCH purity. Afterward, for the
heat duty in the solvent recovery stage, a short-cut calculation
was applied. Assuming that most of the sensible heat may be
recoverable using heat exchangers, the latent heat of vapor-
ization (ΔHvap) of the most volatile compound was used as an
estimate. For water as solvent, a minimum S:F ratio of 1.8 was
obtained for CHOH and 7.3 for CHO. Since water for these
systems is a volatile solvent, evaporation of all the water resulted
in a heat duty of 41.3 MJ/kgCHOH and 166 MJ/kgCHO.
For Cyrene, a lower minimum S:F ratio was required, which is
a direct consequence from the larger capacity toward CHO and
CHOH, being 1.2 for CHOH and CHO. Furthermore, since
Cyrene in these systems is a high boiling solvent, the solutes
CHOH and CHO should be boiled o. Due to solvent leaching,
MCH should be boiled ofrom the ranate to recover the
solvent, and the evaporation of MCH from the ranate is
included in the calculations. This resulted for CHOH in a heat
duty of 3.86 MJ/kgCHOH and for CHO in 3.87 MJ/kgCHO. These
short-cut calculations show that extraction processes using
Cyrene instead of water may be 11 times more ecient for the
separation of CHOH from MCH and 43 times more ecient for
CHO from MCH. This is a rough heat duty estimate, and in an
accurate process simulation, the nal heat duty may be less
benecial. However, with the current gures, it shows high
potential for a signicant advantage of the high boiling Cyrene
over the low boiling water. The fact that most energy savings
compared to water were accomplished by the higher boiling
point of the solvent suggests that for this application the use of
ionic liquids (ILs) might be interesting too, on the condition
that benecial behavior is observed in LLE. However, no LLE
data have been found for MCH/CHOH or CHO with an IL.
The separation of CHO and CHOH may also be
accomplished with Cyrene due to the fact a larger selectivity is
observed toward CHOH than CHO. Although no phase
separation is expected and LLX is not possible, other separation
techniques may be used such as extractive distillation or perhaps
with an extractive divided wall conguration.
Four biphasic ternary systems have been assessed in which
methylcyclohexane (MCH) and Cyrene were kept constant. As
a third compound, toluene, cyclohexanol, cyclohexanone, and
cyclopentyl methyl ether (CPME) were applied. For each
ternary system, a selective extraction was found at the three
studied temperatures of 298.15 K, 323.15 K, and 348.15 K.
Cyclohexanol (up to SCHOH,MCH =61.42±4.33) and
cyclohexanone (up to SCHO,MCH = 44.07 ±8.63) were most
selectively extracted, while toluene (up to STOL,MCH = 11.99 ±
0.89) and CPME (up to SCPME,MCH = 6.42 ±0.08) were
extracted with considerably lower selectivity. While Cyrene was
outperformed by Sulfolane and several ionic liquids in the
extraction of toluene, the potential of Cyrene in the cyclo-
hexanol/cyclohexanone systems was observed. Although a lower
selectivity was seen than with water, due to the high boiling point
of Cyrene, recovery can be much less costly. Overall, we
conclude that Cyrene can be applied as a biobased extraction
solvent for a variety of separations, although for several systems
the phase envelope is relatively narrow and narrower at higher
sıSupporting Information
The Supporting Information is available free of charge at
Four tables with all experimental data for Figures 2,4,5
and 6, including weight percentages of all compounds in
each phase, the distribution coecient of MCH and the
solute (being TOL, CHO, CHOH or CPME), and the
selectivity of that solute over MCH; the thermodynamic
consistency of all UNIQUAC correlations was checked
using the determinant of the Hessian matrix ap-
and the results displayed in four gures
Corresponding Author
Boelo Schuur Sustainable Process Technology Group, Process
and Catalysis Engineering Cluster, Faculty of Science and
ACS Sustainable Chemistry & Engineering Research Article
ACS Sustainable Chem. Eng. 2020, 8, 1480714817
Technology, University of Twente, 7522 NB Enschede, The
Phone: +31 53 489 2891; Email:
Thomas Brouwer Sustainable Process Technology Group,
Process and Catalysis Engineering Cluster, Faculty of Science and
Technology, University of Twente, 7522 NB Enschede, The
Complete contact information is available at:
The authors declare no competing nancial interest.
This has been an ISPT (Institute for Sustainable Process
Technology) project (TEEI314006/BL-20-07), cofunded by
the Topsector Energy by the Dutch Ministry of Economic
Aairs and Climate Policy. We would like to acknowledge the
Circa group for sending us 1 L of Cyrene to perform this
[BMIM][B(CN)4] = 1-butyl-3-methylimidazolium tetracya-
[BMIM][MSO4] = 1-butyl-3-methylimidazolium methylsul-
[EMIM][ESO4] = 1-ethyl-3-methylimidazolium ethylsulfate
[HMIM][B(CN)4] = 1-hexyl-3-methylimidazolium tetracya-
[Xi]O= Weight fraction of compound iin the organic phase
[Xi]S= Weight fraction of compound iin the solvent phase
Aij = Temperature independent UNIQUAC t parameter
Bij = Temperature dependent UNIQUAC t parameter
Bp = boiling point
CHO = Cyclohexanone
CHOH = Cyclohexanol
CPME = Cyclopentyl methyl ether
Cyrene = Dihydrolevoglycosenone
D = Debye
DMF = N,N-dimethylformamide
DMSO = Dimethyl sulfoxide
ED = Extractive distillation
KD,i= Distributation coecient of solute i
LLE = Liquidliquid equilibrium
LLX = Liquidliquid extraction
MCH = Methylcyclohexane
NMP = N-methylpyrrolidone
qi= van der Waals surface area of solute i
ri= van der Waals volume of solute i
Sij = Selectivity of solute iover solute j
Sulfolane = Tetrahydrothiophene-1,1-dioxide
SI = Supporting Information
S:F ratio = Solvent to feed ratio (mass basis)
T(K) = Absolute temperature
TOL = Toluene
UNIQUAC = Universal quasichemical
yi= Activity coecient of solute i
C= Combinatorial term of the activity coecient of solute i
R= Residual term of activity coecient of solute i
ΦI= Volume fraction
θI= Surface area fraction
τij = Binary interaction parameter between solutes iand j
I̵= Extrapolated from corresponding literature to similar
solute concentration in solvent phase.
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ACS Sustainable Chemistry & Engineering Research Article
ACS Sustainable Chem. Eng. 2020, 8, 1480714817
... Moreover, chemical synthesis is usually unselective, resulting in unwanted side reactions and formation of byproducts, and consequently requires several protection/deprotection steps of phenolic groups, leading to poor atom economy and generating extra waste to dispose of [20]. Therefore, we designed a two-step continuous flow protocol in Cyrene, a biobased dipolar aprotic solvent [21,22], to obtain the desired MITO compounds. Cyrene has been successfully used for many important chemical reactions, such as amidation reactions, synthesis of ureas, SN 2 and carbon-carbon couplings, and its use under flow conditions could significantly expand its applicability [23]. ...
Full-text available
A series of phenolic derivatives designed to selectively target mitochondria were synthesized under flow conditions starting from natural phenolic acids. The two-step continuous flow protocol, performed in Cyrene, a bioavailable dipolar aprotic solvent, allowed the isolation of the MITO compounds in moderate to good yields. The MITO compounds obtained, as a first step, were tested for their safety by cell viability analysis. The cytocompatible dose, in human neuronal cell line SH-SH5Y, depends on the type of compound and the non-toxic dose is between 3.5 and 125 µM. Among the seven MITO compounds synthesized, two of them have shown interesting performances, being able to protect mitochondria from oxidative insult.
This work explores the use of cyrene as a green solvent to improve the cleaning performance on Islatravir, Doravirine and Olanzapine, which are challenging drugs to clean. Cyrene addition showed an improvement in aqueous and methanolic solubility, and ternary cyrene blends showed high solubility at high cyrene concentration, which did not directly translate into a reduction in cleaning time. The presence of cyrene and its geminal diol form reduced the API surface concentration after cleaning, thus improving the dissolution of the bound API layer. Cyrene was efficiently removed by water and left low residues. Higher cyrene concentrations (>20% vol) must be assessed for API solubility and suitability for CIP applications.
Levoglucosenone (LGO) - which possesses two chiral centers, a ketal and one α,β-unsaturated ketone moieties - is a high value renewable chiral building block that can be used for the production of a wide range of bio-based fine chemicals and polymers, as well as green solvents. This mini-review illustrates the different main strategies that have been developed to produce LGO from different starting materials such as lignocellulosic biomass, pure cellulose, sugars and non-sugar compounds.
The separation of short‐chain hydrocarbon mixtures is of great significance for the efficient utilization of fossil energy. Liquid‐liquid extraction, as one of the commonly used treatment methods, has significant advantages in terms of operation conditions and energy consumption. As a new dipolar aprotic solvent developed in recent years, dihydrolevoglucone (Cyrene) has a wide range of sources and green composition. In this paper, the liquid‐liquid equilibrium and extraction mechanism of Cyrene and five hydrocarbon mixtures with short carbon chains, including toluene/n‐heptane, toluene/cyclohexane, n‐hexane/cyclohexane, n‐pentane/pentene and n‐hexane/hexene, have been studied by combining experiments and quantum chemical calculations, and the extraction effects under different conditions have been investigated. The results showed that the forces between Cyrene and different solutes are mainly VDW forces dominated by dispersion forces, with some weak hydrogen bonds present. Due to the difference of interaction energy, the order of extraction selectivity was toluene‐n‐heptane > toluene‐cyclohexane > n‐hexane‐hexene > n‐hexane‐cyclohexane > n‐pentane‐pentene, and the order of distribution coefficients of the extracted components (aromatic, olefins and cycloalkanes) was toluene > pentene > hexene > cyclohexane. The dissolution processes of all systems were heat‐absorbing and all reached the extraction equilibrium within 60 s. The reliability of the experimental data was verified using the Othmer‐Tobias equation and the Hand equation, and the binary interaction parameters of all systems were obtained by the NRTL model, providing basic data and references for the subsequent studies on the separation of Cyrene and short‐chain hydrocarbons.
Green synthesis of renewable alternatives to fossil fuel-based (macro)molecules/polymers is more than ever a necessity. We recently developed a sustainable pathway to produce 6-hydroxy-5,7-dimethoxy-2-naphthoic acid (DMNA), which resembles the fossil-derived 6-hydroxy-2-naphthoic acid, from sinapic acid. To investigate the potential of DMNA as a building block for polymer syntheses, three novel DMNA-derived α,ω-dienes (M1-M3) were synthesized and engaged in acyclic-diene metathesis (ADMET) polymerization in a three-step study to prepare renewable aliphatic-aromatic polyesters (P1-P3). The first step aimed to evaluate the activity of seven commercial metathesis catalysts for the solvent-free ADMET polymerization of M3. Although most of the studied catalysts exhibited good reactivity, 2nd generation Hoveyda-Grubbs catalyst (C4) proved the best. The second step was then started by varying the catalyst loading and testing M1 and M2 toward ADMET polymerization. Aliphatic-aromatic polyesters with number-average molecular weight (Mn) up to 19.4 kDa (Đ = 1.88) were obtained. Furthermore, the results showed that the properties can be finely tuned depending on the monomer and catalyst loading. Thermal analysis demonstrated that glass transition temperature (Tg) and temperature at which 5% of the mass is lost (Td5%) varied depending on the alkene chain length. A general thermal trend was established: Tg(P1) > Tg(P2) > Tg(P3) and Td5%(P1) < Td5%(P2) < Td5%(P3). The third step of the ADMET study was to evaluate the tolerance of M1-M3 and C4 toward Cyrene™, a green and high boiling point solvent derived from cellulose. The results revealed that Cyrene™ merits further investigation as a “general” non-toxic solvent for ADMET polymerization of other monomers, particularly those with high melting points.
Biorefineries integrate processes for the sustainable conversion of biomass into chemicals, materials, and bioenergy so that resources are optimized and effluents are minimized. Despite the vast potential of lignocellulosic biorefineries, their success depends heavily on effective, economically viable, and sustainable biomass fractionation. Although efficient, organosolv pretreatment still faces challenges that must be overcome for its widespread utilization, mainly related to solvent type and recycling, robustness regarding biomass type and integration of hemicellulose recovery and use. This review shows the recent advances and state-of-the-art of organosolv pretreatment, discussing the advances, such as the use of biobased solvents, whilst also shedding light on the perspectives of using the streams — cellulose, hemicellulose, and lignin — to produce biofuels and products of high added value. In addition, it presents an overview of the existing industrial implementations of organosolv processes and, lastly, shows the main scientific and industrial challenges and opportunities for this process.
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N,N-Dimethylformamide (DMF) and N-methylpyrrolidinone (NMP) are two of the common organic solvents which are facing increasing restrictions in chemical safety and environmental regulations. Thus, seeking greener alternatives to replace them...
Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) obtained from waste/wastewater using a mixed microbial culture (MMC) usually varies in its properties due to daily variation in the waste/wastewater composition applied as feedstock. In the current study, the average molecular weight (MW) of PHBV was purposedly reduced from about 1 MDa to about 200 kDa by drying the PHBV-rich biomass at elevated temperature of 120 ˚C for 18 h to ease extraction and handling. Furthermore, conversion into value-added chemicals such as trans-crotonic acid (trans-CA) and trans-2-pentenoic acid (trans-PA) by thermal decomposition (pyrolysis) benefits from the lower MW. For the extraction of low MW PHBV, the use of the bio-based solvents 2-methyltetrahydroxy furan (2-MTHF) and dihydrolevoglucosenone (cyrene) was studied. The maximum extraction yield of 62±3% with purity of >99% was achieved with 2-MTHF at 80 ˚C for an hour with high biomass to solvent ratio of 5% (g/mL). Cyrene-based extractions resulted in the highest yield of 57±2% with purity of >99% at 120 ˚C in 2h with 5% (g/mL) biomass to solvent ratio. The mass balance closure over the extraction process indicated that about 15% and 10% of polymer has remained in the residual biomass after extraction by 2-MTHF and cyrene, respectively. The performance of these new solvents to extract polymers with various average MW was compared to the benchmark extractions using chloroform and dimethyl carbonate (DMC). It was found that for the polymers with low average MW the extraction efficiency of the proposed solvents exceeds the benchmark solvents.
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The use of a wide range of bio-based solvents as entrainers in extractive distillation applications was investigated. The separation of hydrocarbon mixtures containing aromatic and aliphatic compounds is highly relevant, and use of bio-based solvents for this was studied using the model system of methylcyclohexane and toluene. Additionally, the use of bio-based solvents for the difficult olefin/paraffin separation was studied using the model system of n-heptane and 1-heptene. From all of the bio-based solvents studied, CyreneTM showed the highest relative volatility in the methylcyclohexane-toluene system. At compositions up to 40 wt. % methylcyclohexane in the hydrocarbon mixture, with a relative volatility of 3.17 ± 0.16 at 1000 mbar, the selectivity is comparable with the state-of-the art industrial solvent, SulfolaneTM. At higher methylcyclohexane fractions, CyreneTM outperforms SulfolaneTM, resulting in a 43% reduction of the minimum reflux ratio, an excellent measure of energy efficiency. For the relative volatility of n-heptane over 1-heptene, CyreneTM also induces an increase in the relative volatility, but not as much as the industrial benchmark n-methylpyrrolidone (NMP). A relative volatility of 1.20 was measured at a solvent to feed ratio of 3 (mass based), which can be further increased by the addition of extra CyreneTM. This prospects that CyreneTM may be used for extractive distillation of olefin/paraffin separations, replacing NMP which is subject to severe environmental restrictions by the REACH agreement due to toxicity.
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In this manuscript carboxylic acid extraction processes are reviewed and compared on energy efficiency, especially in situations with very low carboxylic acid concentrations. Production of carboxylic acids by fermentation rather than petrochemical routes aims at reducing dependency on petroleum resources. Wastewater streams are potential carbon sources for fermentation. However, their limited carbon content results in low carboxylic acid concentrations (∼1 wt%) that render separation of waste-derived carboxylic acids challenging. This necessitates implementation of cost-effective separation concepts. The incentive to review liquid–liquid extraction (LLX)-based processes for carboxylic acids was to evaluate their applicability to low carboxylic acid concentrations. Although a thorough study of recent solvent developments was beyond the scope of this work, a brief discussion on their families supported the LLX-based process developments that were assessed in terms of energy demand by simulating their thermal unit operations with Aspen Plus. They were simulated both under their reported conditions and with their initial concentration set to 1 wt%. A process proposed by Urbas (1983) that makes use of CO2, CO2-switchable solvents and low-boiling organic solvents outperformed the others for low carboxylic acid feed concentrations. With a heating duty of about 36 MJ/kgproduct, it could recover both volatile and non-volatile carboxylic acids from fermentation broths with 1 wt% initial carboxylic acid loading. Future developments in the field may be based on this process design, but with more environmentally friendly solvents such as the bio-based furan derivatives.
The authors work at the Green Chemistry Centre of Excellence (GCCE) at the University of York and are all currently involved in the H2020-BBI-funded project ReSolve for the development of safer bio-based solvents. Solvent applications for dihydrolevoglucosenone (Cyrene) and 2,2,5,5-tetramethyloxloane (TMO) are among their prominent discoveries. Dr. James Sherwood leads the Alternative Solvents Technology Platform at the GCCE. His research interests include solvent effects in organic synthesis and the substitution of hazardous solvents with novel bio-based solvents. Dr. Thomas Farmer is leader of the Clean Synthesis Technology Platform in the GCCE. Tom works on the development of greener synthetic methods and the uses of bio-derived platform molecules. Prof. James Clark is the director of the GCCE and winner of the 2018 RSC Green Chemistry Award. He has published over 500 articles and is a member of the UK Government’s Chemical Stakeholder Forum.
Dimethyl sulfoxide (DMSO) is currently employed across the biomedical field, from cryopreservation to in vitro assays, despite the fact that it has been shown to have an assortment of biologically relevant effects. The amphiphilic nature of DMSO along with its relatively low toxicity at dilute concentrations make it a challenging solvent to replace. A possible alternative is Cyrene™ (dihydrolevoglucosenone), an aprotic dipolar solvent that is derived from waste biomass. In addition to being a green solvent, Cyrene™ has comparable solvation properties and is reported to have low toxicity. Herein the abilities of the two solvents to solubilize drug compounds and to act as non-participatory vehicles in drug discovery for antibacterials are compared. It was demonstrate that the results of standardised antimicrobial susceptibility testing do not differ between drugs prepared from either Cyrene™ or DMSO stock. Moreover, in contrast to DMSO, Cyrene™ does not offer protection from ROS mediated killing of bacteria and may therefore be an improvement over DMSO as a vehicle in antimicrobial drug discovery.
In this work, Cyrene™ was employed for the first time as solvent for polyethersulfone (PES) and poly(vinylidene fluoride) (PVDF) membrane preparation via phase inversion. The two selected polymers are among the most required materials in the industrial membrane field. PES and PVDF membranes were prepared by coupling Vapour Induced- and Non-solvent Induced Phase Separation (VIPS and NIPS, respectively) with the aim to study the influence of the adopted operational conditions on the final membrane structure and properties. By changing the exposure time to fixed atmospheric relative humidity (55%) and temperature (25 °C) in the range between 0 and 5 min, membranes with different features, pore size and pure water permeability (PWP) could be tailored. The experimental data were discussed with respect to the casting solution viscosity, ternary phase diagram, membrane morphology, thickness, porosity, contact angle, pore size and PWP. In the case of PVDF, additional differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) analysis were performed for evaluating the polymorphism and crystallinity change of the material, which influences the membrane properties too. By working in complete absence of additives and at room temperature, the combinations PES/Cyrene™ and PVDF/Cyrene™ allowed to develop a new sustainable approach of producing membranes for potential application in water treatment.
ABSTRACT The development of green solvents is one of the key tenets of Green Chemistry as solvents account for the majority of waste stemming from the production of the chemicals on which we have all come to rely. An important class of solvents is the dipolar aprotics, which include N,N‐dimethylformamide (DMF) and N‐methyl‐2‐pyrrolidone (NMP). In addition to being derived from non‐renewable resources, these solvents are also under increased regulatory pressures that will limit their industrial applications. This Concept will look at the bio‐available solvent Cyrene (dihydrolevoglucosenone) as a potential replacement for toxic dipolar aprotic solvents. An emphasis has been placed on examining the strengths and weaknesses of Cyrene as a solvent. This will be accomplished by looking at the synthesis, derivatization and application in synthetic protocols of Cyrene. With respect to the Twelve Principles of Green Chemistry, this Concept describes a bio‐available solvent that should have a disruptive effect on the use of traditional industrial dipolar aprotic solvents.
The separation of benzene and cyclohexane is considered as one of the most challenging processes in the petrochemical industry. In this paper, low transition temperature mixtures (LTTMs) were used as solvents for the separation of benzene and cyclohexane. The selected LTTMs were sulfolane - tetrabutylammonium bromide 5:1 and ethylene glycol - trimethylamine hydrochloride 5:1, and liquid-liquid equilibrium (LLE) data of benzene-cyclohexane-LTTMs were experimentally determined at 40oC under normal atmosphere. Moreover, the effects of the mole ratio of hydrogen bond donor (HBD) sulfolane and hydrogen bond acceptor (HBA) tetrabutylammonium bromide on extraction performance were also observed based on the LLE data. It is found that when the mole ratio of sulfolane to tetrabutylammonium bromide is 5:1, LTTM has the best extraction performance. In addition, the LLE data of benzene-cyclohexane-LTTMs ternary system were used to fit parameters of the NRTL activity coefficient model. Based on the NRTL model the continuous extraction process was simulated and the operating parameters were obtained, and high product purity (cyclohexane 0.997) and high recovery efficient (cyclohexane 93.28% and benzene 98.25%) can be achieved. In conclusion, the LTTM sulfolane - tetrabutylammonium bromide 5:1 is a promising solvent for the extractive separation of benzene-cyclohexane mixtures.
Extractive distillation (ED) processes are widely used for the separation of aromatic and non-aromatic hydrocarbons. Approximate boiling points of components and azeotropes in the mixture need solvents to aid the separation processes. A considerable mass flowrate and recovery of solvents in separation processes leads to significant energy requirement. This study provides a new extractive distillation process for the efficient separation of aromatic and non-aromatic hydrocarbons aided by sulfolane solution. A flash tank and a semi-lean solution stream are introduced to modify existing extractive distillation processes to reduce the reboiler heat duty of the entrainer recovery column and improve the separation performance of the extractive distillation column. The NRTL-RK property method and rigorous unit models in Aspen Plus are used to simulate new and existing processes. No-databank model parameters are regressed to improve the accuracy of simulations. A coordinative strategy is proposed to optimize the significant operating parameters for new and existing processes by combining Aspen Plus with MATLAB. Compared with the optimal existing extractive distillation process, the new extractive distillation process reduces the operating costs by 8.9% when heat integration is not considered, and 13.04% of the total annual cost can be reduced when a heat exchanger network is considered.
Amide bonds are one of the underpinning linkages in all living systems and are fundamental within drug discovery. Current methods towards their synthesis frequently rely on the use of dipolar aprotic solvents; however, due to increasingly stringent regulations and growing societal pressures, safe and more sustainable alternatives are highly sought after. Herein, we evaluate the application of the bio-based solvent Cyrene™ in the HATU mediated synthesis of amides and peptides. We found that Cyrene functioned as a competent replacement for DMF in the synthesis of a series of lead-like compounds and dipeptides (25 examples, 63-100%).