Br?nsted acidic ionic liquid-catalyzed dehydrative formation of isosorbide from sorbitol: Introduction of a continuous process

Article abstract of DOI:10.1039/c7cy00512a

A highly efficient synthesis of isosorbide from sorbitol was developed using Br?nsted acidic ionic liquids (BILs) as the catalyst for the first time. The structure-performance relationship was discussed extensively and a proper value of the Gutmann acceptor number (AN) rather than the inherent of acidity was found to be essential for an optimized yield of isosorbide. In addition, the excellent behavior of preferred BIL-4 in the consecutive recycling tests renders the construction of a continuous process probable. Systematic optimization demonstrated that a yield of 82% of isosorbide with a purity of 99.3% could be reached at balance.

Full text of DOI:10.1039/c7cy00512a

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Brønsted acidic ionic liquid-catalyzed dehydrative
formation of isosorbide from sorbitol:
Cite this: DOI: 10.1039/c7cy00512a
introduction of a continuous process†
b
b
b
a
Jie Deng,‡a Bao-Hua Xu,
Yao-Feng Wang, Xian-En Mo,§ Rui Zhang,
*
You Li§b and Suo-Jiang Zhang
b
*
A highly efficient synthesis of isosorbide from sorbitol was developed using Brønsted acidic ionic liquids
(BILs) as the catalyst for the first time. The structure–performance relationship was discussed extensively
and a proper value of the Gutmann acceptor number (AN) rather than the inherent of acidity was found to
be essential for an optimized yield of isosorbide. In addition, the excellent behavior of preferred BIL-4 in
the consecutive recycling tests renders the construction of a continuous process probable. Systematic op-
timization demonstrated that a yield of 82% of isosorbide with a purity of 99.3% could be reached at
balance.
Received 16th March 2017,
Accepted 5th April 2017
DOI: 10.1039/c7cy00512a
rsc.li/catalysis
dustry, a sulphuric acid catalyzed batch reaction is popular.
However, it has serious drawbacks of environmental pollution
Introduction
Isosorbide is one of the most high-value chemicals arising
from biomass transformation and has wide applications in
the synthesis of several pharmaceutical molecules,1 fine
chemicals2 and various polymers.3 Recent reports by Mitsu-
bishi demonstrated the promise of isosorbide to replace
bisphenol A in the synthesis of polycarbonate with excellent
optical properties.4 However, the challenge in promoting such
technologies using isosorbide as the synthon is the high cost
of isosorbide (more than 10 times that of bisphenol A)
resulting from low efficiency and high-energy consumption of
production.5 The most notable reaction is the dehydration of
sorbitol, which is the final step of industrial process for
isosorbide from starch. It is an acid-catalyzed pathway,
involving the preferential protonation of the primary
hydroxyl group (at C1 position), followed by cyclization with
the carbon atom at the C4 position. A second protonation of
the last primary hydroxyl group at the C6 position and
cyclization with the carbon atom at the C3 position leads to
the formation of the second ring of isosorbide.6 In the in-
arising from base–acid neutralization post-treatment, signifi-
cant handling risk, corrosive nature of the catalyst and stabil-
ity issues of the products.7 To address these issues, consider-
able efforts have been made for the development of practical
and efficient strategies.8 The most attractive solution is to de-
sign a proper solid acid as the catalyst and thereby construct
a continuous manufacturing process attributed to convenient
catalyst separation from reaction system.9 However, the results
of such systems still lack practical value because of the require-
ment of a high reaction temperature,10–12 long reaction time,13
abundant catalyst loading11 and limited yield of isosorbide as
well.14,15 In other words, the dehydration efficiency is reduced
remarkably in the case of a heterogeneous catalytic pathway.
Brønsted acidic ionic liquids (BILs), on introducing
Brønsted substituents into the cation/anion of the ionic liq-
uids (ILs), show flexible acidity, which can be regulated ac-
cordingly by functionalizing the organic backbone.16 BILs
have attracted special attention for use as efficient catalysts
for the synthesis of valuable chemicals in reactions, such as
alkylation, esterification, condensation and rearrangement
reactions.17 For example, the acid-catalyzed dehydration of
fructose to 5-hydroxymethylfurfural was explored extensively
using BILs as a catalyst, which allowed the reaction to pro-
ceed more rapidly with high yields under mild conditions
(around 100 °C, ordinary pressure).18 Importantly, BILs were
used to replace conventional mineral acids as the liquid cata-
lyst due to their advantages of non-volatility and non-
corrosivity, which enabled catalyst recyclation.19 We, there-
fore, envisioned that a continuous process leading to iso-
sorbide from sorbitol can be constructed using –SO3H-based
a State Key Laboratory of Chemical Engineering, East China University of Science
and Technology, Shanghai 200237, China
b Beijing Key Laboratory of Ionic Liquids Clean Process, Key Laboratory of Green
Process and Engineering, State Key Laboratory of Multiphase Complex Systems,
Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR
China. E-mail: sjzhang@ipe.ac.cn, r.zhang@ecust.edu.cn
† Electronic supplementary information (ESI) available. CCDC 1523385. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c7cy00512a
‡ On leave to Institute of Process Engineering.
§ Dynamics simulation and system integration.
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BILs as the catalyst. However, the challenge remains in
searching a proper structure of BIL to retain a relatively fast
rate in the formation of adducts with 1,4-sorbitan, as illus-
trated by Fukuoka and co-workers.20 Further understanding
of the structure–performance relationship, particularly in
terms of the second dehydration, deserves further investigation.
°C for 30 min, followed by reaction for 4 h, under 3 kPa. The
pressure was then recharged to 1 atm, the total mass of the
flask was recorded as Wn and liquid sample of a few milli-
grams (wn) was withdrawn and analyzed by HPLC. The reac-
tion solution was then divided into two components upon
treatment at 170 °C under 9–15 Pa, with only a part of
isosorbide (Wison) being distilled. The mass of residue was
recorded as Wn′; a liquid sample of a few milligrams (wn′)
was withdrawn and analyzed by HPLC. Thereafter, fresh
sorbitol (Wsor(n+1)) was added to the flask for the next run.
Procedures for HPLC analysis: The sample obtained from
Experimental
All reagents were used as received from Acros or Alfa Aesar.
Solvents (AR grade) were commercially available unless other-
wise stated.
the reaction, such as wn and wn′, was dissolved in water (4
n
mL). The peak areas of sorbitol (Ssorn) and isosorbide (Siso
)
Synthesis
were determined by HPLC analysis. Thereafter, the molar
concentration of each (Ciso and Csor (mM)) was obtained
according to eqn (1) and (2) arising from a linearity fitting
standard curve.
Preparation of BILs. The preparation of BIL-1–8 was
achieved by two general steps: formation of the correspond-
ing zwitterionic precursor and subsequent protonation by
various mineral acids, whereas BIL-9 was provided by double
replacement between its chloride counterpart and CF3SO3H.21
To obtain BILs of extreme purity, it is essential to wash the
raw products repeatedly with dry diethylether, followed by de-
hydration under high vacuum (10 Pa) at 80 °C for 24 h. All
BILs, except BIL-1, 2 and 9, were treated with active carbon to
remove the colored impurities. In addition, care was taken
for the preparation of BIL-2 and BIL-9, which are potentially
sensitive to moisture and temperature. The quality of BILs
under study was characterized by a combination of NMR
spectroscopy, Karl Fisher titration, acid–base titration, ESI de-
tection, and TGA analysis. Caution: The moisture concentration
Cison/n′ = 5.58 × 10−4Sison/n′ + 1.8 (R‐Square: 0.99945) (1)
n/n′
n/n′
Csor
= 3.98 × 10−4Ssor
+ 0.92 (R‐Square: 0.99962) (2)
For run 1:
Csor1 = 1 − [4(W1 − W0)Csor1/w1]/0.5 = 1 − 8(W1 − W0)Csor1/w1
Yiso = [4(W1 − W0)Ciso1/w1]/0.5 = 8(W1 − W0)Ciso1/w1
1
(χH O: nwater/nIl) of these neat BILs is controlled to be less than 2
For run n:
2
× 10−3 determined by Karl Fischer titration. For the detail syn-
thetic method and characterization data, see the ESI.† All of
the BILs were stored in glass vials in an argon-filled glovebox
(<0.1 ppm H2O) at 25 °C.
Catalytic reaction. The reactions were carried out in a
three-necked flask (50 mL) equipped with a vacuum distilla-
tion apparatus and a magnetic stirrer. Sorbitol (36.4 g, 0.2
mol) was stirred and heated to 130 °C until it completely
melted and became transparent within 30 min. The respec-
tive neat BIL (1.2 mmol, 0.6 mol%) was added to the flask
with continuous stirring and the pressure was kept at 3 kPa.
This time was assigned as t = 0 h. After a reaction for 4 h, the
pressure was recharged to 1 atm. The products-distribution
of the resulting solution was analyzed by HPLC.
Wsorn = (Wiso(n−1)/Miso) × Msor(Miso = 146; Msor = 182)
Csorn = 1 − [4(Wn − W0)Csorn/wn]/[Wiso(n−1)/Miso + 4(W(n−1)′
− W0)Csor(n−1)′/w(n−1)′
]
Yiso − 4[(Wn − W0)Cison/wn − (W(n−1)′ − W0)Ciso(n−1)′/w(n−1)′]/
[Wiso(n−1)/Miso + 4(W(n−1)′ − W0)Csor(n−1)′/w(n−1)′
n
]
Analysis
Dynamic experiments. Sorbitol (36.4 g, 0.2 mol) was
stirred and heated to a temperature at which it completely
melted. The respective neat BIL-4 (0.42 g, 1.2 mmol, 0.6
mol%) was added to the flask under continuous stirring and
kept at a pressure of 3 kPa. This time was assigned as t = 0 h.
Liquid samples of a few milligrams were withdrawn and ana-
lyzed by HPLC.
Recycling experiments. In the typical recycling experiment,
a mixture of sorbitol (91.0 g, 0.5 mol) and neat BIL-4 (1.06 g,
3.0 mmol, 0.6 mol%) was added in a three-necked flask (100
mL, W0) equipped with a vacuum distillation apparatus and
a magnetic stirrer. The mixture was stirred vigorously at 130
HPLC chromatography. HPLC analysis was performed
using a Phenomenex Rezex RCM-monosaccharide column
(8%; Ca2+, 300 × 7.80 mm) at 80 °C, with degassed demi wa-
ter as the eluent using a differential refractive index as the
detector.
NMR spectroscopy. For NMR of neat ionic liquids, each
dry ionic liquid was loaded into NMR tubes with d6-
1
dimethylphosphine as an external lock. The H NMR spectra
were recorded using
spectrometer.
a Bruker Avance III 600 MHz
Acceptor number determination. The method for
obtaining the AN value of each BIL is reported
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elsewhere.16c,22 For each BIL, three samples with different tri-
ethylphospine oxide (TEPO) concentrations (3–10 mol%) were
prepared in a glovebox. The solutions were loaded into NMR
tubes (after ensuring TEPO dissolution) containing sealed
capillaries with d6-dimethylsulfoxide as an external lock. The
31P{1H} NMR spectra were recorded at 80 °C, using a Bruker
AvanceIII 600 MHz spectrometer.
Three solutions of TEPO in extremely dry hexane were
measured at 27 °C. For each TEPO ionic liquid system, the
31P{1H} NMR chemical shift for the infinite dilution of TEPO,
δinf, was determined by extrapolation from the 31P{1H} NMR
chemical shifts measured at different TEPO concentrations.
The chemical shift of TEPO in hexane, extrapolated to infi-
Fig. 2 BILs prepared and screened as the catalyst.
nite dilution, δinf hex, was used as a reference (δinf
=
hex
0 ppm).
The AN values for all samples were calculated using the
following formula: AN = 2.348 × δinf
equivalent of NaOH consumption was also detected for BIL-2
and BIL-9. Cross experiments attributed it to the respective
hydrolysis of BF4 in BIL-2 (ref. 23) and weak N–S bond in
.
−
BIL-9 (ref. 21) under strongly basic conditions (Table S1†). In
the experiments, such instability of BIL-2 and BIL-9 against
moisture was also detected during their respective prepara-
tion or storage. Therefore, additional care was taken when ei-
ther BIL-2 or BIL-9 was introduced as a catalyst in the pres-
ence of H2O, particularly at high temperatures.
Thermogravimetric analysis (TGA) with scanning rate of 10
°C min−1 was also conducted for BIL-2–9, indicating that
these BILs are thermally stable (Td > 300 °C, Fig. S1†)
enough for the catalytic conversion of sorbitol to isosorbide.
Catalytic reactions. The catalytic performance of these
characterized BILs was subsequently evaluated (Table 1). The
Results and discussion
Synthesis and catalytic performance
BIL synthesis. To explore structure–performance relation-
ship, readily tunable imidazolium was selected as the back-
bone of BILs to be screened. As depicted in Fig. 1, consider-
ations in terms of the structural design included the anion
types, the substituents on the C2–H position, the length of
hydrophobic chain, and the functionalization/length of the
bridge chain.
A series of BILs were synthesized (Fig. 2). The preparation
of BIL-1–8 was achieved by two general steps: formation of
the corresponding zwitterionic precursor and subsequent
protonation by various mineral acids. In contrast, BIL-9 was
provided by double replacement between its chloride coun-
terpart and CF3SO3H.21 The preparation of BIL-1–8 was
achieved by two general steps: formation of the correspond-
ing zwitterionic precursor and subsequent protonation by
various mineral acids. However, BIL-9 was provided by dou-
ble replacement between its chloride counterpart and
CF3SO3H.21 Monitored by acid–base titration, full protonation
or replacement was obtained with all mineral acids except
the relatively weak HCl. Evidently, the corresponding BIL-1 of
fresh preparation only consumes 40 mol% of NaOH at room
temperature. On the other hand, the titration value of ap-
proximately 2 for BIL-3 is rationalized by the reactivity of its
moisture content (χH O = nwater/nIl) in each BIL under study was
2
less than 2 × 10−3, as determined by a Karl Fischer titration. All
reactions were conducted in the presence of BIL (0.6 mol%) un-
der vacuum (3 kPa) at 130 °C for 4 h, by generating a mixture
of 1,4-sorbitan and isosorbide as the major product, together
with traces of others upon dehydration, such as 1,5-sorbitan
and 3,6-sorbitan. In addition, the performance of two mineral
acids, H2SO4 and CF3SO3H, was also studied for comparison.
As listed in Table 1, the performance of these screened
BILs is nearly the same in the first dehydration; however, it
varies significantly in the second. The efficiency of dehydra-
tion was increased upon adjusting the anionic structure of
−
−
−
BILs, displaying an order of BF4 < HSO4 < CF3SO3 . The ac-
tivity of BIL-3 (entry 2) is comparable to that of the commer-
cial catalyst (H2SO4, entry 9) under identical conditions. In
contrast, the second dehydration proceeded efficiently in the
presence of BIL-3 (entry 3) compared with that of its anionic
counter-acid (CF3SO3H, entry 10). The reactivity was increased
when the strength of the H-donor at the C2-position was
weakened, as presented by BIL-4/6 versus BIL-5 (entries 3–5).
Unfortunately, the yield of isosorbide was not improved fur-
ther by rendering the amphipathic BIL either more hydro-
phobic (BIL-7, entry 6) or more strongly acidic (BIL-8, entry
7). Finally, BIL-9, in which the imidazole ring was substituted
directly with sulfonic acid group, behaved sluggishly, partially
arising from its instability.
−
two subunits, −SO3H and HSO4 , towards NaOH. An extra
Fig. 1 Schematic of the structural consideration for BIL.
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Table 1 BILs-catalyzed dehydrative formation of isosorbide from sorbitola c
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,
Conv.b (%)
YSorbitan (%)
YIsosorbideb (%)
b
Entry
Cat.
1
2
3
4
5
6
7
8
9
BIL-2
BIL-3
BIL-4
BIL-5
BIL-6
BIL-7
BIL-8
BIL-9
H2SO4
CF3SO3H
91.5 ( 1.0)
98.0 ( 1.0)
98.3 ( 0.8)
99.8 ( 0.8)
98.0 ( 0.5)
99.8 ( 0.8)
98.8 ( 0.8)
98.8 ( 0.4)
97.5 ( 0.5)
98.0 ( 0.5)
76.5 ( 2.5)
53.3 ( 2.3)
10.3 ( 2.3)
4.3 ( 1.5)
37.0 ( 0.5)
8.3 ( 0.8)
38.3 ( 1.9)
66.5 ( 1.0)
56.8 ( 0.8)
77.8 ( 0.9)
11.8 ( 2.0)
40.5 ( 2.0)
75.5 ( 1.0)
84.5 ( 1.0)
55.0 ( 1.0)
77.3 ( 1.3)
62.8 ( 1.9)
21.8 ( 1.8)
34.5 ( 1.0)
16.8 ( 0.8)
10
a
b
Reaction conditions: sorbitol 0.2 mol, catalyst 0.6 mol%, 130 °C, 3 kPa, 4 h. Determined by HPLC with a Phenomenex Rezex RCM-
monosaccharide column (8%; Ca2+, 300 × 7.80 mm) at 80 °C, degassed demi water as eluent. c The formation of punds could not be completely
ruled out.
Characterization and structure–performance relationship
value around 4 ppm. This was attributed to proton exchange
between –SO3H and H2O, which approaches equilibrium with
a certain amount of H2O. In addition, we were able to detect
a linear dependence of the integration of labile proton on
To address the above issue of remarkably different perfor-
mance of BILs in the second dehydration, structures of neat
BILs and their ability to protonate nucleophiles were exam-
ined via a combination of 1H NMR and Gutmann acceptor
number (AN).
χH O. It is likely that a multi-nuclear complex of [SO3–
2
HIJH2O)⋯anion] for BIL was generated in the presence of
H2O. Even so, the effect of H2O on the BIL property could be
Interaction between BIL and nucleophilic H2O. The diffi-
culty in removing traces of H2O from BILs is because of their
extensive interactions arising from H-bonding.24 Conse-
quently, significant care should be taken when preparing
these BILs and applying in dehydrated reactions as well. The
χH O –acidity plot and acceptable χH O for a neat BIL should
considered negligible when χH O is controlled to be less than
2
2 × 10−3, which was used in the catalytic reaction and subse-
quent structural analysis, unless otherwise stated.
1H NMR spectroscopy of neat BILs. The labile proton in
BILs is potentially involved in a H-bond with two H-acceptors:
2
2
−
1
the anion (X) and alkyl sulfonate anion (−RSO3 ), each instan-
be defined before respective structural analysis. Therefore, H
NMR detection of a mixture of BIL-4 and H2O in a variant ra-
tio was conducted using DMSO-d6 as an external lock. As in-
dicated in Fig. 3, the value of both chemical shift and labile
taneously H-bonds with imidazolium cation via C2–H. NMR
studies were carried out for neat BIL-2–9 but BIL-7, which
was solid at the experimental temperature (80 °C). The mea-
surement was carried out using DMSO-d6 as an external lock
to evaluate the inherent H-bond strength raised by the labile
protons. The most downfield signal (δ: ppm) of BIL-2 (10.43),
BIL-4 (11.81), and BIL-8 (14.51) corresponds to the proton of
the –SO3H group, respectively (Fig. 4). This is indicated either
proton integration depends on the value of χH O. There is an
2
up field shift of the labile proton of –SO3H accompanied by
increasing χH O, and a significant reduction of δ(ppm) is ob-
2
served within a range of 0 < χH O < 15, followed by a steady δ
2
−
−
replacing BF4 by CF3SO3 or functionalizing the bridge chain
with an electron-withdrawing fluorine group renders the la-
bile proton more deshielded. The decreased chemical shift
demonstrates that its assigned proton is partaking in H-bond
with a stronger H-acceptor. The chemical shift of BIL-5, bear-
ing C2–CH3 versus C2–H, is further downfield shifted (δ:
11.93 ppm) compared to that of BIL-4. It is likely that the
weak interaction between the anion and imidazolium-ring
resulted in stronger H-bonding between the anion and the
active proton in –SO3H.
The most downfield-shifted signal (δ: ppm) for BIL-3
(12.20) and BIL-6 (7.23), each integrated to two protons, was
located on their respective multi-nuclear cluster (Fig. 5). In
BIL-3, protons represented in [(HSO4)IJHSO3IJCH2)n−)] are
deshielded relative to –SO3H proton either in BIL-2 or BIL-4.
Fig. 3 Variation of the 1H NMR signal of labile proton in BIL-4 with
χH O (detected by 1H NMR (600 MHz, external DMSO-d6 lock, 80 °C)).
2
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Fig. 6 Schematic diagram of the structural speculation for BIL-3 (A)
and BIL-6 (B).
weakly basic probe molecule, TEPO. Changes in the 31P{1H}
NMR chemical shift were induced through the formation of
acid–base adducts with partial protonation by Brønsted acids.
The recorded 31P{1H} NMR signals of the protonated probe
were found to be slightly concentration-dependent. The ANs,
along with the errors derived from the linear extrapolation,
are listed and compared in Table 2.
Fig. 4 1H NMR spectra (600 MHz, 80 °C, neat) of BIL-2, 4, 5, and 8 (δ:
ppm).
All the BILs studied, except for BIL-7, show high acidity,
with ANs falling within the region referred to as super-acidity
(AN = 114–118).22 The ANs measurement of BIL-2 gave two
minor 31P{1H} signals at approximately δ 92 and 85 ppm
other than the primary one at δ 81 ppm, indicating that the
decomposition of BIL-2 had occurred. This outcome could be
−
rationalized by the sensitivity of its BF4 group to nucleo-
philes, as detected by hydrolysis in the presence of H2O.23
The most up-field peak was assigned to the interaction of
TEPO with labile protons in BIL-2, generating an AN value of
93.1.
As detected for BIL-2–4, ANs vary significantly by tuning
the anion structure, with the value increased with decreasing
−
−
basicity of the anion (AN = 93.1 (BF4 ), 115.9 (HSO4 ), 119.0
−
−
(CF3SO3 )). Neither C2–H nor proton in [HSO4 ] can compete
effectively with [SO3H] for TEPO. However, they may form a
strong H-bond towards [SO3H] via H⋯O–S, causing an in-
crease in the protonation ability of the labile proton. Conse-
quently, blocking C2–H with a methyl group resulted in a re-
duced AN for IL-5 (117.5). In contrast, AN of BIL-6 (119.2)
was increased slightly by grafting –CH2OH at the C2-position,
a stronger H-donor than C2–H. It is also a benefit to intro-
duce a strong electron-withdrawing group to the bridge
chain, as evidenced by BIL-8 (AN = 119.1).
Fig. 5 1H NMR spectra (600 MHz, 80 °C, neat) of BIL-3, 4, and 6 (δ:
ppm).
This is likely because they are partaking in a strong H-bond,
each shared between two oxygen atoms: S–O–H⋯O–S
(Fig. 6A). Interestingly, a system of three-centre two protons
bonding was probably presented in BIL-6 (Fig. 6B). In these
two cases, an intermolecular interaction of an identical
H-bond involving two cations cannot be excluded. The signif-
icant up-field shifted signal at 7.23 ppm indicates that the
protons are prone to interact with the nonbonding electron
pair on oxygen of –CH2O− group. The resistance to exchange
between the cluster leads to a broad signal.
Interaction between BILs and nucleophilic TEPO
(Gutmann acceptor number). Information on the acceptor
number (AN) of BIL could help predict the intermolecular in-
teractions of nucleophiles or electron-rich substrates with the
labile protons in BILs. In this study, ANs were determined by
31P{1H} NMR spectroscopy, using small quantities of the
Key parameters affect the reaction efficiency. The yield of
isosorbide produced using different BIL, and ANs and chemi-
1
cal shift of labile proton in H NMR observed for those BILs
are compared in Fig. 7. This demonstrated that the reactivity
Table 2 Water content and Gutmann acceptor number (AN) value of
BILs used in this study
BILs
χH O (× 10−3
)
AN
93.1(3)
115.9(8)
119.0(7)
117.5(5)
119.2(9)
119.1(1)
131.7(2)
2
BIL-2
BIL-3
BIL-4
BIL-5
BIL-6
BIL-8
BIL-9
2
1
1
1
2
2
1
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ation was increased with a higher AN. However, it was
unfavourable to the desired reaction, leading to isosorbide by
strengthening either of the two side interactions. In other
words, to attain an optimized yield of isosorbide, a proper
AN value of the acidic catalyst was required.
Kinetic study on BIL-4-catalyzed dehydration of sorbitol.
Kinetic study on BIL-4-catalyzed dehydration of sorbitol was
conducted at 130, 140, and 150 °C (Fig. S4†), respectively, to
further understand the structure–performance relationship.
The time-course plot at 130 °C was depicted as a typical ex-
ample in Fig. 9. This demonstrated that only a small amount
of isosorbide was formed in the first 1 h regardless of the ac-
cumulation of 1,4-sorbitan. Thereafter, the yield of isosorbide
increased at an accelerated pace to maximum. This suggests
that the reaction is controlled by pre-equilibrium, which is
the association equilibrium between the reactant and BIL-4
in this case.
We simulated the time course of sorbitol dehydration by
assuming the Michaelis–Menten type mechanism24 involving
a pre-equilibrium of association and a subsequent dehydra-
tion step based on the important interaction of labile protons
in BILs with the substrate (Scheme 1). Herein, k1 and k2 are
rate constants for the dehydration of sorbitol and 1,4-
sorbitan, respectively, whereas k3, k4, and k5 are the rate con-
stants for side reactions of sorbitol, 1,4-sorbitan, and iso-
sorbide. In addition, the equilibrium constants for the associ-
ation of BIL with sorbitol, 1,4-sorbitan, and isosorbide are
denoted as K1, K2, and K3, respectively.
The simulation curves fitted well with the experimental
data (Fig. 9 and S4†). The proposed kinetic model accurately
predicted the product yields with an average deviation of less
than 0.2%. The calculated k3, k4 and k5 were apparently lower
than k1 and k2 (Table 3), which is in agreement with
1,4-sorbitan and isosorbide being the main products in the
reaction. We also found the decomposition rate of isosorbide,
which was explained by the constant k5, is the lowest, indicat-
ing that isosorbide is stable compared to its precursors, such
as sorbitol and sorbitans, under the reaction condition. To
our surprise, the rate constant k1 was lower than k2 at 130 °C.
Fig. 7 Yield of isosorbide in reactions catalyzed compared with AN
values and chemical shift (ppm) of proton (600 MHz, 80 °C, neat).
of respective BIL is closely related to its AN value rather than
the inherent acidity. Specifically, the yield of isosorbide was
first increased, which was followed by a sharp decrease, with
increasing AN value. The optimized yield (84.5%) was
obtained for BIL-5 with a moderate AN value of 117.5. Re-
markably, the mineral acid CF3SO3H of a high AN value22b
only offered the product in a yield of 16.8%.
Herein, the comparable lower boiling point of CF3SO3H
(b.p. (1 atm) = 132 °C) and the strict reaction conditions (un-
der 3 kPa at 130 °C) should be considered. Further experi-
ments demonstrated a small amount of acid (ca. 18 ‰ on
the basis of the pH value of the removed water) was indeed
lost together with the water vapor after reaction for 4 h in the
CF3SO3H-catalyzed process (Fig. S3†). In comparison, a de-
creased loss of acid (ca. 12 ‰) was detected for BIL-4 under
identical conditions.
The experimental proof of formation of multi-nuclear
complex [SO3–HIJH2O)n⋯anion] for a mixture of H2O and BIL
1
has been provided by H NMR detection using BIL-4 as an ex-
ample. The strength of the O–H bond in [SO3H] was weak-
ened significantly, particularly under reaction conditions,
rendering proton release in a form of HIJH2O)n⋯SO3CF3 prob-
able. Evidently, in the presence of stronger nucleophiles,
such as DMSO (as the solvent), the labile proton in BIL-4 was
−
removed together with CF3SO3 anion at 50 °C, with the re-
spective zwitterionic precursor generated (Fig. 8).24
Protonation of the formed H2O and other secondary hy-
droxyl groups at 1,4-sorbitan occurred coincidently with that
of the desired primary hydroxyl group at the C6 position dur-
ing the second dehydration. The ability of the acid in proton-
Fig. 8 ORTEP of the zwitterionic precursor of BIL-4 from the X-ray
single crystal structure.
Fig. 9 Experimental (dots) and simulated (lines) profiles for the BIL-4-
catalyzed dehydration of sorbitol at 130 °C.
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Scheme
1 Reaction schemes of BIL-4-catalyzed dehydration of
sorbitol.
Table
3 Rate constants and ratios of the association equilibrium
constants
Fig. 10 Conversion of sorbitol and yield of isosorbide from the BIL-4-
catalyzed dehydration of sorbitol in consecutive recycling cycles (con-
ditions: BIL-4: 0.6 mol%, 130 °C, 1.5 h).
T/°C
130
140
150
k1/h−1
k2/h−1
k3/h−1
k4/h−1
k5/h−1
K1
107.8
136.6
9.8
14.2
3.9
1.9
0.11
0.1448
240.3
109.8
21.1
12.3
18.6
1.4
347.7
98.6
86.9
1.8
27.8
1.3
librium.25 In this study, the treating capacity of sorbitol dehy-
dration plant was assumed to be 5 tons per year.
K2
K3
0.27
0.0009
0.40
0.0089
The process flow diagram for the dehydration process is
explained in Fig. 11 and the detail mass balance is shown in
Tables S5–S7.† Sorbitol (68 kmol h−1) would be heated to melt
as a colorless transparent liquid in the E101 at 120 °C to ob-
tain good flowability. The pretreated sorbitol was then trans-
ferred into the R101 where isosorbide and 1,4-sorbitan could
be produced in the presence of BIL-4 at the optimized tem-
perature of 160 °C and under a pressure of 4 kPa. As calcu-
lated, the optimal retention time of the reaction mixture in
R101 was 90 min. Thereafter, it was transferred to V101 for
proceeding distillation at 230 °C under 4 kPa for 10 min to
obtain the raw isosorbide as a lighter composition. Notably, a
type of reaction-distillation was considered during this simu-
lation. 80 wt% of the heavier composition in V101 including
both by-product and catalyst was backflow into R101 for fur-
ther reaction with the fresh input of substrate (68 kmol h−1)
and catalyst (8.16 mol h−1). This demonstrated that a yield of
82% of isosorbide with a purity of 99.3% could be reached at
balance by this continuous process; this result and process is
However, the association equilibrium constant of K1 was
greater than that of either K2 or K3, indicating that pre-
equilibrium is the key parameter affecting the reaction rate
at low temperature, and the association of BIL-4 with sorbitol
is stronger than that with 1,4-sorbitan and isosorbide. With
increasing reaction temperature, the equilibrium constant K1
was reduced, concomitantly with a steadily increased K2. This
outcome suggests that the rate of formation of adducts be-
tween sorbitol and 1,4-sorbitan with the acid catalyst is dif-
ferent, which is likely to be crucial to tune the selectivity of
dehydration.
Consideration of a continuous process
Recycling study. The recyclability of BIL-4 was examined
with each cycle following a sequence of reaction-partial sepa-
ration by the distillation-fresh input of sorbitol, which
mimics a process of the desired continuous reaction. To keep
a constant mole ratio of catalyst/sorbitol at 0.6 mol% for each
run, the molar quantity of sorbitol of the new feed should be
the same as that of isosorbide separated from the previous
run. The conversion and selectivity of each group were the av-
erage values of at least three samples collected from different
areas of the reactor to reduce the experimental error. The re-
sults showed that BIL-4 has good catalytic activity in the con-
version of sorbitol to isosorbide. In five consecutive runs,
both the conversion of sorbitol and yield of isosorbide was
relatively stable at about 99% and 73%, respectively (Fig. 10).
Systematic optimization. The pilot-scale process simula-
tions of the dehydration process were carried out using As-
pen Plus v7.1. The process contains two key units: continu-
ous stirred tank reactor (CSTR) and evaporator. The
conditions were found to be optimal on the basis of dynamic
experiments and the documented data of vapor–liquid equi-
Fig. 11 Process flow diagram of the dehydration process.
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Catalysis Science & Technology
much higher and more efficient than that obtained by the
traditional batch process.26
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Conclusions
In summary, the structure–performance of BIL-catalyzed
dehydrative formation of isosorbide from sorbitol was ex-
plored extensively, thereby offering an efficient, eco-friendly
and reusable catalyst. Kinetic studies demonstrated that such
sequential steps are different in the rate of formation of ad-
ducts between sorbitol and 1,4-sorbitan with the acid. The re-
markable difference in performance in the second dehydra-
tion of various BILs was attributed to their respective ability
to protonate polyhydroxyl substrates. Consequently, a proper
value of AN rather than the inherent of acidity was found to
be essential for an optimized yield of isosorbide. A continu-
ous process was finally constructed upon system optimiza-
tion using the preferred BIL-4 as the catalyst, which gener-
ated a yield of 82% in isosorbide with a purity of 99.3% at
balance.
Acknowledgements
Financial support by the National Basic Research Program of
China (973 Program) 2015CB251401, the National Natural Sci-
ence Foundation of China (No. 21476240, 21606238,
21374029), the Instrument Developing Project of the Chinese
Academy of Sciences (No. YZ201521), the Shanghai education
commission key projects of scientific research and innovation
(14ZZ061), the Key Research Program of Frontier Sciences,
CAS (QYZDY-SSW-JSC011), CAS (Chinese Academy of Sci-
ences) 100-Talent Program (2014), and Key Research Program
of Frontier Sciences, CAS (QYZDY-SSW-JSCo11) is gratefully
acknowledged.
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