An ionic liquid catalyzed probase method for one-pot synthesis of α,β-unsaturated esters from esters and aldehydes under mild conditions

Article abstract of DOI:10.1039/c7gc02265d

A one-pot synthesis of α,β-unsaturated esters from unactivated esters and aldehydes using strong bases, such as sodium alkoxide and potassium tert-butoxide, was reported. However, the ionic liquid (IL) catalyzed probase method for producing α,β-unsaturated esters was not reported until now. In this work, a series of ILs with fluoride anions were firstly prepared and used as catalysts in combination with the probase N,O-bis(trimethylsilyl) acetamide (BSA) for the α,β-unsaturated esters synthesis. This process could also be promoted through the introduction of another IL with Lewis acid sites. The yield and selectivity of the product could reach up to 84.2% and 95.0%, respectively, when [Bmim]F was used in combination with [Bmim]Cl/AlCl₃ (the molar fraction of AlCl₃ is 0.67). The mechanism investigation through GC-MS indicates that BSA would convert into onium amide, which acted as a strong base for α-H abstraction, with the catalysis of [Bmim]F. Meanwhile, [Bmim]Cl/AlCl₃ played an important role in the condensation step between enolates and aldehydes. On the basis of mechanism insights, kinetic and thermodynamic studies were also carried out for a better understanding of this new route.

Full text of DOI:10.1039/c7gc02265d

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Page 1 of 26
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DOI: 10.1039/C7GC02265D
Ionic Liquid Catalyzed Probase Method for One-pot Synthesis of α,
β-Unsaturated Esters from Esters and Aldehydes at Mild Condition
Gang Wang, a, bYiming Xu, cSuojiang Zhang,bZengxi Li, *a, bChunshan Li*a, b
a College of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences,
Beijing, 100049, People’s Republic of China
b Beijing Key Laboratory of Green Process and Engineering, Key Laboratory of Ionic Liquids
Clean Process and State Key Laboratory of Multiphase Complex Systems, The National Key
Laboratory of Clean and Efficient Coking Technology, Institute of Process Engineering, Chinese
Academy of Sciences, Beijing, 100190, People’s Republic of China
cSchool of Chemical Engineering, East China University of Science and Technology, Shanghai,
200237, People’s Republic of China
Corresponding E-mail: csli@ipe.ac.cn (C. S. Li)
zxli@ipe.ac.cn (Z. X. Li)
One-pot synthesis ofα, β-unsaturated estersfrom unactivated esters and aldehydes using strong
bases, such as sodium alkoxide and potassium tert-butoxide, were reported. However, the ionic
liquids (ILs) catalyzed probase method for producingα, β-unsaturated esters was not reporteduntil
now. In this work, series of ILs with fluoride anion were firstly prepared and used as the catalysts
in combination with the probase of N,O-Bis(trimethylsilyl) acetamide (BSA) for α, β-unsaturated
esters synthesis. Thisprocesscould also be promoted through the introduction of another IL with
Lewis acid sites. The yield and selectivity of product could reach up to 84.2 % and 95.0 % when
[Bmim]F was used in cooperation with [Bmim]Cl/AlCl3 (the molar fraction of AlCl3 is 0.67).
Mechanism investigation through GC-MS indicate that the BSA would convert into onium amide,
which acted asa strong base for α-H abstraction, with the catalysis of [Bmim]F. Meanwhile,
[Bmim]Cl/AlCl3 played an important role in the condensation step between enolates and
aldehydes. On the basis of mechanism insights, the kinetic and thermodynamic studies were
carried out in supplementary for better understanding of this new route.
Keywords: α, β-Unsaturated esters; Ionic liquids; Silyl enol ether; Kinetic; Thermodynamic
Introduction
1

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α, β-Unsaturated esters as important chemical intermediates and products are
[1]
widely used in the field of polymer materials production,
paints and coatings
[2]
preparation,
adhesives and textiles synthesis,[3]pharmaceutical and essences
fabrication.
[4]Approaches
to
such
compounds
include
direct
esterification,[5]Reformasky
reaction,[6]
Doebner
method,[7]
dehydrogenation,[8]Knoevenagel condensation,[9]oxidative esterification, [10]Witting
[11]
reaction,
Horner-Wadsworth-Emmons reaction [12]and aldol condensation.[4,
13-15]The direct esterification is the simplest among these routes, while α,
β-unsaturated acid should be prepared firstly. Itcould also be obtained from
α-haloesters using zinc as catalyst through Reformasky reaction and from
α-cyanoestersin the presence of base viaKnoevenagel reaction, respectively.But the
zinc halides could not be recycled and the preparation of α-cyanoesters often need
poisonous cyanide reagent. Although dehydrogenation and oxidative esterification
methods seem to environmental friendly and green sustainable,these technologies
usually require novel metal catalysts and the catalysts are hard to recycle. Witting and
Horner-Wadsworth-Emmons reactionsneedphosphine reagents, which are often toxic
and environmental-unfriendly. Aldol condensation is considered as a key and efficient
reaction for the construction of carbon-carbon bond to form α-hydroxyland α,
β-unsaturatedcarbonyl compounds.[16-27]
Unactivated esters with high pKa value of α-H, unlike aldehydes or ketones,
should be enolized during aldol condensation. Typically, alkoxide salts are able to
deprotonate the α-H of esters, generating active enolate intermediatesthat are required
for the following carbon-carbon coupling reactions.[28, 29]However, it is difficult to
avoid side reactions for the solubility of these salts in common solvents as well as
their nucleophilicity. Otherwise, alkali metal amides, such as lithium
hexamethyldisilazide (LiHMDS), lithium diisopropylamide (LDA) andlithium
tetramethylpiperidide (LiTMP), are also commonly used in organic chemistry as
strongnon-nucleophilic bases. But these reaction temperature should be decreased to
2

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below 0℃and the operation should be also careful due to the high activityand air (or
water) sensitivityof such strong bases. Followed by Kondo’s researches on
in-situmethod that to produce base through fluoride anion catalysis of aminosilanes,
[30,
31]Teng found the pentanidium- and bisguanidinium-salts catalyzed probase
method for alkylation of lactones using silylamide. [32]Compared with the strong bases,
the probase is relatively stable and it is more convenient for operation. In addition, ILs
as green and environmental-protection reagents are universally applied in the
replacement of traditional solvents and acidic (or basic) catalysts, result from the low
vapor pressure, easy recycle and high catalytic performance in most organic reactions.
[33-39]
Scheme 1 ILs catalyzed probase method for α, β-unsaturated esters production
Inspired from the work of Teng and Kondo, the ILscatalyzed probase
strategyshown in Scheme 1 was envisioned for producing α, β-unsaturated esters from
unactivated esters and aldehydes at mild condition, which has not been reported up to
now. In present work, N,O-bis(trimethylsilyl) acetamide (BSA) was selected as the
probase and the ILs with fluoride anion (ILs-F) were designed and selected as
catalysts to catalytic decompose BSA into strong base of onium amide.The α-H
deprotonation and ester enolization would occur in the presence of onium amide.
Another ILs with Lewis acid sites(ILs-L) were also used in cooperation to catalyze
the aldol condensation step between enolates and aldehydes. The effectof cation (for
ILs-F), Lewis acidity concentration (for ILs-L) and solvent on this catalytic process
were also studied. The reaction mechanism was also analyzed and investigated in
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detailsby using GC-MS. On the basis of mechanism insights, kinetic and
thermodynamic studies were also carried out for better understanding of this new
process.
Experimental
Materials
Dichloromethane (purity ≥ 99.5%) was supplied byXilong Chemical Co., Ltd.,
(China). Esters (purity ≥ 99.0%), aldehydes (purity ≥ 99.0%), AgF (purity of 99.0%)
and N,O-bis(trimethylsilyl) acetamide (purity ≥97.0%) were purchased from J&K
Scientific Ltd. (China). Octane (purity ≥ 99.5%) was provided by Aladdin Industrial
Co.,(China). ILs (purity ≥ 99.0%) were supported by Linzhou Keneng Materials
Technology Co., Ltd., (China).The solventsused for synthesis reaction should be
dehydrated with calcium hydride under reflux for about 24 h and the dry solvents
could be obtained after distillation. The reactants also should be dehydrated with 4 Å
molecular sieves.
Preparation of ILs-F
The ILs-F were prepared fromAgF and ILs that with bromine (or chloride) anion
(ILs-Br or ILs-Cl) as shown in Scheme 2. The solution of ILs-Br (or ILs-Cl, 1 eq.)
was firstly fabricated in ethanol, followed by being addeddropwise the AgF (1.03 eq.)
aqueous solution at room temperature under suitable stirring speed. Another 5 min
stirring was kept after AgF solution was added. The formed light yellow (or white)
precipitates were filtered off and the solvent was removed under high vacuum at 30℃.
The obtained crude ILs-Fwere dissolved in ethanol and filtered off to remove the
remaining AgF. Then the ethanol was removed under high vacuum at 30℃and the
relatively high pure ILs-F were obtained. The purityand NMR spectra of each
prepared IL-F wasprovided in Electronic Supporting Information.
Scheme 2 Preparation mechanism of ILs-F
Preparation of ILs-L
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In the glove box, the metal chlorides (ZnCl2, CuCl, FeCl3, AlCl3) were weighted
in suitable amount and charged into a flask. Then the flask was sealed and kept in
alcohol bath under -20℃. After that, the dried [Bmim]Cl (in high vacuum at 90℃ for
about 24h) in corresponding molar ratio was injected into the flask by dropping and
mixed with metal chloride power under the Ar (or N2) atmosphere. The mixture was
kept stirring under -20℃ for about 4 h. The ILs with Lewis acid sites (ILs-L)
[Bmim]Cl/MClx (M=Zn2+, Cu+, Fe3+, Al3+) could be obtained (the FT-IR spectra were
provided in Electronic Supporting Information). The prepared ILs-L should be stored
in the glove box or inert gas atmosphere in avoidance of hydrolysis.
Fig.1. Theapparatus for preparing ILs-L
1-flask, 2-stir, 3-rubber plug, 4-injector, 5-glass valve
General synthesis
All synthesis reactions were carried out in a round-bottomed flask under 1 atm and the
air in flask was replaced with N2or Ar before the dehydrated solvent and reagents
were added into it. The reaction mixture was kept at 283 K-298
Kwithatemperature-controlled water bath equipped with magnetic stirring. And
typical reaction solution consisted of aldehyde (0.1Min solvent), ester,BSA, ILsand
octane which was used as internal standard. To keep molar concentrations consistent,
solutions for reactions with other reagents were prepared to have the same
concentration of aldehyde (0.1M). The aldehydein suitable molar ratio to ester,
octaneand ILs(for cation effect investigation, only ILs-F were used, and for other
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synthesis reaction, both ILs-F and ILs-L were used) in appreciate percentage were
firstly mixed insolvent before being introduced into the flask. Then BSA was injected
dropwise into former solution with syringeunder suitable stirring speed. Product
samples were periodically collected and analyzed with GC-MS.
Analysis methods
1H-NMR, 13C-NMR and 19F-NMR analysis were carried out onBrukerAVANCE
instrument (600 MHz), and the spectra were collected at ambient temperature.
Chemical shifts were reported in ppm relative to the residual solvent signal (D2O:
4.79 ppm).
Product samples were analyzed and quantified in the meantime with GC-MS
apparatus (QP2020,Shimadzu) equipped with a Rtx-5MS column (30 m, 0.32 mm,
0.25 ꢀm). Products were identified by comparison to standards and MS
information,carrier gas, He; temperature, 40℃ (2 min) to 300℃ at 15℃/min and
hold for 5min; detector temperature, 250 ℃; injector temperature, 300 ℃.The
concentration of each reactant and product wereobtained by using octane as internal
standard. The mass correction factor of each substance relative to octane was
determined from mixtures of standard sample that diluted withCH2Cl2. For others that
without standard sample, it was estimated by using effective carbon number method,
[40, 41]respectively.
All the FT-IR samplesof ILs-L were spread into liquid films on KBr window.
The spectra were recorded on a Nicolet Fourier transform infrared spectrophotometer
at room temperature. The pyridine probing IR for Lewis acidicconcentration
measurement was similar to former operation, the samples were prepared by mixing
pyridine, which was dried with solid KOH and distilled over 4Å molecular
sieves,with ILs-L in the volume ratio of 1:5in glove box.
Results and discussion
Cation effect of ILs-F
To
investigate
this
ILs
catalyzed
probase
method,the
6

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condensationofbenzaldehydewith methyl acetate to methyl cinnamate was selected as
the model reaction. According to the research results of Kondo and Teng, [32, 42, 43] the
cation of in-situ formed strong base onium amide would affect the reaction results.
Thusthe cation effect of ILs-F was firstly explored. The ILs-F with different cations
wereprepared as described in experimental section and the structure was confirmed
1
through H-NMR, 13C-NMR and 19F-NMR, which were illustrated in Electronic
Supporting Information. And the synthetic results using ILs-F with different cation
were shown in Fig.2.
90
Yield
Selectivity
80
70
60
50
40
30
20
10
0
Fig. 2.Catalytic performance of ILs-F with different cations
Reaction condition: benzaldehyde (0.2 mmol, 0.1 M in CH2Cl2), the molar ratio of methyl acetate
to BSA and benzaldehyde was 2:2:1, [Bmim]F: 20 mol.%, reaction temperature: 20℃, reaction
time: 4 h.
As mentioned above, the cation has good influence on the yield and selectivity of
methyl cinnamate. The resultsshowed the [Bmim]F has the best performance. In
addition, it could be discovered that the chain length in the cation could directly affect
the results. The data of pyridine- and imidazole-type ILs-F obviously indicate that
with the increase of chain length, the catalyticperformance attains to the peak and then
reduces down. It was considered that the Si-O bond in BSA could be broken with the
catalysis of fluoride anion in ILs-F, followed by generating acetamide anion,then
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onium amide base would form through the interaction between acetamide anionand
cation that fromILs-F according to the reported results. [32, 42, 43]Although the catalytic
function focuses on the fluoride anion, the molecular voidage of ILs-F would increase
with the extension of chain length, which would be beneficial for the capacity of BSA
molecules in ILs-F clusters. Therefore, the catalytic decomposition of BSA into
strong base acetamide anion could be promoted in some degree, leading to be
conducive to the enolization of methyl acetate. [44, 45]The onium amide base, in
thisreaction, plays a role of strong base to abstract the α-H of esters, producing the
enolate for the next aldol condensation step.So the increasing chain length would also
enhance the steric hindrance of the α-H abstraction step. Moreover, for imidazole-type
ILs-F, the 2-C of imidazole ring would transform to carbene due to the active 2-H.
The raw material benzaldehyde could react with the carbene, leading to reduce of the
product selectivity. But the prolonged chain length could also impede this process.
Therefore, the suitable chain length would promote the formation of onium amide
base and enolization of esters.
Effect of ILs-L
On the basis of the cation effect analysis, [Bmim] was confirmed as the optimum
one.According to Scheme 1, the benzaldehyde would condense with
1-methoxy-1-trimethylsilyloxyethene (enolate of methyl acetate) to produce methyl
cinnamate, which is also called Mukaiyama reaction. And as it known to all, Lewis
acid catalysts could promote Mukaiyama reaction. When [Bmim]Clwas mixed with
Lewis acidic metal chloride in suitable molar ratio, the ILs-L([Bmim]Cl/MClx) would
exhibit Lewis acidity. Based on the research results of Kou, [46]when the molar
fraction of metal chloride (CuCl, FeCl3, ZnCl2 and AlCl3) in [Bmim]Cl/MClx attaches
to 0.67, the ILs-L would present strong Lewis acidity. So a series of ILs-L
([Bmim]Cl/MClx), with metal chloride molar fraction of 0.67, were prepared and
applied in combinationwith [Bmim]F for catalytic condensation of methyl acetate
with benzaldehyde. And the experimental results were shown as Fig. 3.It
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indicatesthatwith the addition of ILs-L, the yield and selectivity of methyl
cinnamatecould be enhanced obviously. And the increasing tendency could be ranked
as [Bmim]Cl/CuCl＜[Bmim]Cl/FeCl3＜[Bmim]Cl/ZnCl2＜[Bmim]Cl/AlCl3. Then the
pyridine probing IR was conducted for acidic concentration measurement, which were
described in Fig. 4. It shows that these four types of ILs-L all have Lewis acid sites,
[Bmim]Cl/CuCl and [Bmim]Cl/AlCl3 also haveBrΦnsted acid sites. By comparing the
IR spectra, the Lewis acidconcentration could also be ranked as [Bmim]Cl/CuCl
＜
[Bmim]Cl/FeCl3 [Bmim]Cl/ZnCl2 [Bmim]Cl/AlCl3, which is in accordance with
＜
＜
the activity order. So it can be considered that the catalytic performance of ILs-L is
related to the amount of Lewis acid sites.
100
Yield /%
Selectivity /%
80
60
40
20
0
Fig. 3. Catalytic performance of different ILs-L
Reaction condition: benzaldehyde (0.2 mmol, 0.1 M in CH2Cl2), the molar ratio of methyl acetate
to BSA and benzaldehyde was 2:2:1, [Bmim]F: 20 mol.%, ILs-L: 20 mol.% (molar fraction of
MClx in ILs-L was 0.67), reaction temperature: 20℃, reaction time: 4 h.
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[Bmim]Cl/FeCl (molar fraction of CuCl is 0.67)
3
[Bmim]Cl/CuCl
(molar fraction of FeCl is 0.67)
3
[Bmim]Cl/ZnCl
(
molar fraction of ZnCl is 0.67)
2
2
[Bmim]Cl/AlCl
(
molar fraction of AlCl is 0.67
)
3
3
L B
1000 1100 1200 1300 1400 1500 1600 1700 1800
Wavenumber / cm-1
Fig. 4.Pyridine probing IR for acidity measurement
100
80
60
40
20
0
Yield
Selectivity
0.50
0.55
0.60
0.65
0.70
molar fraction of AlCl3
Fig. 5. Catalytic performance of [Bmim]Cl/AlCl3 with different molar fraction of AlCl3
Reaction condition: benzaldehyde (0.2 mmol, 0.1 M in CH2Cl2), the molar ratio of methyl acetate
to BSA and benzaldehyde was 2:2:1, [Bmim]F: 20 mol. %, [Bmim]Cl/AlCl3 (molar fraction of
AlCl3 changes from 0.50 to 0.67): 20 mol. %, reaction temperature: 20℃, reaction time: 4 h.
The effect of molar fraction ofAlCl3 was also investigated and the results were
presented in Fig. 5. As it can been seen, with the increasing molar fraction of AlCl3,
the yield and selectivity ofmethyl cinnamate alsorise apparently. According to
pyridine probing measurement results published by Kou and listed in Table 1, [46] with
the molar fraction of AlCl3 changing from 0.5 to 0.67, the predominant anionic
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species in [Bmim]Cl/AlCl3 varies from [AlCl4]- to [Al2Cl7]-. The experimental results
indicate that the [Al2Cl7]-species play the important role on catalytic condensation
between 1-methoxy-1-trimethylsilyloxyethene and benzaldehyde, while [AlCl4]-
shows no activity. In fact, when the molar fraction is 0.5, the [Bmim]Cl/AlCl3 is
neutral, but when it reaches to 0.67, [Bmim]Cl/AlCl3 possesses strong Lewis acidity,
which would be beneficial for the condensation step.Therefore, the [Bmim]Cl/AlCl3,
in which the molar fraction of AlCl3 is 0.67, could be used in cooperation well with
[Bmim]F for one-pot synthesis of methyl cinnamate from methyl acetate and
benzaldehyde at mild condition.
Table 1The effect of molar fraction ofAlCl3 on anionic species
Molar fraction of AlCl3 in [Bmim]Cl/AlCl3 Predominant anionic species
0.5
0.55
0.6
[AlCl4]-
[AlCl4]- and [Al2Cl7]-
[AlCl4]- and [Al2Cl7]-
[Al2Cl7]-
0.67
Effect of solvent
In addition, the effect of solvent on the methyl cinnamate synthesis was also
researched. It has been well known to all that the polar solvent would be benefit for
polarity of α-(C-H) bond and α-H abstraction of carbonyl compounds. Thus, series
polar solvents were selected for our reaction system. Interestingly, the influence of
most polar solvent of THF and acetonitrile as shown in Table 2 are not as well as
CH2Cl2 and CH2Cl-CH2Cl. Our experimental results show that the [Bmim]F and
[Bmim]Cl/AlCl3 has better solubility in CH2Cl2 and CH2Cl-CH2Cl than others. So it
could be considered that in solvent of CH2Cl2 or CH2Cl-CH2Cl, the reaction could be
treated as homogeneous catalysis systems, while it was liquid-liquid heterogeneous
catalysts in others. Otherwise the onium enolate complexes should transfer from IL
phase into the organic phase, which is also inefficient for the whole catalytic
procedure. In addition, the polarity of CH2Cl2 is also suitable for α-proton abstraction,
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which could be supported by the research work of Atsushi and Downey. [47, 48]So it
can be concluded that the solvent selected for the ILs catalyzed probase method
should be polar and could as far as possible dissolve the [Bmim]F and
[Bmim]Cl/AlCl3 as well.
Table 2Effect of solvent on synthetic results
Entry
Solvent
CH2Cl2
Yield /%
82.8
Selectivity /%
94.6
1
2
3
4
5
THF
70.4
92.1
CH2Cl-CH2Cl
toluene
75.5
93.2
52.7
75.4
acetonitrile
61.2
80.7
Reaction condition: benzaldehyde (0.2 mmol, 0.1 M in solvent), the molar ratio of methyl acetate
to BSA and benzaldehyde was 2:2:1, [Bmim]F: 20 mol.%, [Bmim]Cl/AlCl3 (the molar fraction of
AlCl3 was 0.67): 20 mol.%, reaction temperature: 20℃, reaction time: 4 h.
Mechanism analysis and kinetic studies
On the basis of impact analysis of cation, ILs-L, and solvent, the mechanism of
one-pot synthesis of methyl cinnamate from methyl acetate and benzaldehyde using
[Bmim]F in combination with [Bmim]Cl/AlCl3 was investigated. In the light of the
intermediates that detected with GC-MS (for MS information, ESI), the main reaction
mechanism was illustrated as Scheme 3. The BSA firstly converted into strong base
onium amide with the catalysis of [Bmim]F, then the α-H of methyl acetate was
abstracted by such onium amide, generating N-trimethylsilyl acetamideand onium
enolate. The onium amide could be in-situ recycled when onium enolate transformed
into 1-methoxy-1-trimethylsilyloxyethene, followed by condensing with
benzaldehyde to β-O-(trimethylsilyl) methyl phenylpropionatewith the catalysis of
[Bmim]Cl/AlCl3. The intermediate of β-O-(trimethylsilyl) methyl phenylpropionate
could be further converted into methyl cinnamateand hydroxytrimethylsilanewith the
catalysis of [Bmim]F. The GC-MS testing results also revealed that
hydroxytrimethylsilaneand methyl cinnamate would convert into hexamethyl
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disiloxaneand trimethylsilyl cinnamaterespectively with prolonging reaction time.
Scheme 3Mechanismanalysis for synthesis of methyl cinnamate catalyzed with [Bmim]F and
[Bmim]Cl/AlCl3 (the molar fraction of AlCl3 is 0.67) using BSA as probase
Scheme 4 Mechanism-based kinetic model forone-pot synthesis of methyl cinnamate from methyl
acetate and benzaldehyde catalyzed with [Bmim]F and [Bmim]Cl/AlCl3 (the molar fraction of
AlCl3 is 0.67), using BSA as probase
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According to above mechanism analysis, the reaction in 3h at 283 K-298 K was
selected for kinetic studies, resulting from the ignorable side reactions. And the
elementary reactions from (1-1) to (1-7) were listed in Scheme 4. The reaction steps
of (1-1), (1-2)and (1-3)were set as reversible and keep equilibrium due to the slow
rate of (1-5). And reaction (1-6) was also considered as equilibrium due to the high
activity of amide anion and [TMS-O]-.According to the reaction steady-equilibrium
principle, the equilibrium equations of (1-2),(1-3) and (1-8) could be obtained as
formulas (1), (2), (3) and (4).
k1CACD = k−1CBCC
k2CBCD = k−2CECF
k3CACE = k−3CBCG
k6CBCK = k−6CF CL
(1)
(2)
(3)
(4)
So the concentration of substrates C,GandLcould beexpressed asformula(5) and
(6),respectively.
k2k 3 C ACD
k−2k −3 CF
k1k6 C ACK
CG =
(5)
(6 )
CC CL =
k
−1 k −6 CF
Then the kinetic equations could be listed as (7) to (14) based on the model.
dCA
dt
k2k3k4CACDCH k1k6k7
−
=−k4CGCH −k7CCCL =−
(7)
k−2k−3CF
k2k3k4CACDCH
k−1k−6CF
dCD
dt
=−k4CGCH =−
(8)
(9)
k−2k−3CF
dCF
dt
k2k3k4CACDCH k1k6k7CACK
−
=−k4CGCH −k7CCCL =−
k−2k−3CF
k−1k−6CF
dCH
dt
k2k3k4CACDCH
=−k4CGCH =−
(10)
k−2k−3CF
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DOI: 10.1039/C7GC02265D
dCI
dt
k2k3k4CACDCH
=k4CGCH −k5CI =
= k5CI
−k5CI
(11)
k−2k−3CF
dCJ
dt
(12)
(13)
(14)
dCK
dt
k1k6k7CACK
=k5CI −k7CCCL =k5CI −
k−1k−6CF
dCK
dt
k1k6k7CACK
=k7CCCL =
k−1k−6CF
Computational simulationfor the mechanism-based kinetic model was conducted by
[14,
using Rung-Kutta method on matlab software.
40]The temperature and
concentration distribution under our reaction conditions could not been considered
into account. And the obtained results were also compared with experimental
concentration for the effect of reaction temperature and time, which were shown in
Fig. 6. The experimental concentration of β-O-(trimethylsilyl) methyl
phenylpropionateand hydroxytrimethylsilanewas also compared with the calculated
data, which were presented in Fig. 7. The pre-exponential factor and activation energy
of each elementary reaction were presented in Table 3.
283 K
288 K
293 K
283 K
288 K
293 K
0.20
0.18
0.16
0.14
0.12
0.10
0.20
0.16
0.12
0.08
0.04
0.00
298 K
298 K
line: model
line: model
0
20 40 60 80 100 120 140 160 180 200
t /min
0
20 40 60 80 100 120 140 160 180 200
t /min
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0.07
283K
288K
293K
0.10
0.08
0.06
0.04
0.02
0.00
283K
288K
293K
298K
0.06
0.05
0.04
0.03
0.02
0.01
0.00
298K
line: model
line: model
0
20 40 60 80 100 120 140 160 180 200
t /min
0
20 40 60 80 100 120 140 160 180 200
t/min
0.20
0.18
0.16
0.14
0.12
0.10
0.08
0.06
0.04
0.02
0.00
0.08
0.07
0.06
0.05
0.04
0.03
0.02
0.01
0.00
283K
288K
293K
298K
283K
288K
293K
298K
line:model
line: model
0
20 40 60 80 100 120 140 160 180 200
t/min
0
20 40 60 80 100 120 140 160 180 200
t /min
Fig. 6.Computational simulation results of kinetic model
From Fig. 6, it could be seen that the concentration of probase BSA,
rawmaterials of methyl acetate and benzaldehyde drop fast in100 min, after that, the
tendency becomes slow. While the concentration of methyl cinnamateand hexamethyl
disiloxane increase with reaction temperature and time. And the concentration of
N-trimethylsilyl acetamide enhances fast in 100 min, then tend to stable. Fig. 7 shows
the error of the kinetic model, for β-O-(trimethylsilyl)methyl phenylpropionateand
hydroxytrimethylsilane, the deviation between the calculated data and experimental
concentration are all around acceptable 5 %. So the kinetic model should be
believable at the temperatures from 283 K to 298 K and reaction times in180 min.
16

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0.06
0.05
0.04
0.03
0.02
0.01
0.00
0.06
(B)
(A)
0.05
0.04
0.03
+5%
-5%
+5%
-5%
0.02
283K
288K
293K
298K
283K
288K
293K
298K
0.01
0.00
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.00
0.01
0.02
0.03
0.04
0.05
0.06
Experimentalconcentration/(mol/L)
Experimental concentration/ (mol/L)
Fig. 7.Comparison of the experimental concentration with calculateddata: (A) β-O-(trimethylsilyl)
methyl phenylpropionate, (B) hydroxytrimethylsilane
The pre-exponential factor and activation energy of each elementary reaction
were listed in Table 3. For all equilibrium reactions, the activation energy of all
forward reactions are lower than that of reverse, therefore, it is advantageous for the
direction of methyl cinnamate formation. The activation energy of decomposition of
BSA into amide anion is relatively low (23
1.2 kJ/mol), which indicates the
[Bmim]F has good catalytic performance. While the decomposition of
β-O-(trimethylsilyl) methyl phenylpropionate into methyl cinnamate is more difficult
than BSA with the catalysis of [Bmim]F.It is a common sense that the acidity of
α-proton in unsubstituted ester is weaker than that in ketone, β-dicarbonyl compounds
or esters that substituted with electron-accepting groups. So it is difficult for
deprotonating α-proton of methyl acetate, and the activation energy is relatively
high(33
1.7kJ/mol) by comparison with others.But it still indicates the in-situ
generated strong base onium amide is efficient for theα-proton abstraction process.
The activation energy of 1-methoxy-1-trimethylsilyloxyethene formation, namely the
recycle of onium amide, is low (18 0.9 kJ/mol), which means this process is easy to
proceed and the α-proton abstraction procedure could be also promoted. As for the
condensation step between 1-methoxy-1-trimethylsilyloxyethene and benzaldehyde,
the activation energy is the highest of all (43 2.2 kJ/mol). Thus,it is treated as the
rate-controllingstep. However, the energy barrier of hexamethyl disiloxane formation
17

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is the lowest among all steps.
Table 3Pre-exponential factor and activation energy of each elementary reaction
Reaction step
Reaction Name
A
Ea / (kJ/mol)
BSA decomposition
2.8×103
1.2×104
6.2×104
1.4×105
8.1×102
5.3×103
1.4×106
2.0×104
1.4×103
1.3×105
2.1×102
23 1.2
28 1.4
33 1.7
36 1.8
18 0.9
25 1.3
43 2.2
30 1.5
20 1.0
35 1.8
-
deprotonation
-
trimethylsilylation
-
condensation
product formation
-
5
0.3
The sensitivity analysis of significant reaction steps including BSA decomposition,
ester deprotonation, enolate trimethylsilylation, condensation and product formation
were carried out and the results were depicted in Fig. 8. It could be obviously
discovered the condensation step was the most sensitive to reaction temperature,
while the enolate trimethylsilylation was the adverse. The sequence could be ranked
as condensation＞ester deprotonation＞product formation＞BSA decomposition＞
enolate trimethylsilylation. And it is in accordance with the energy barrier of these
reaction steps.
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3.0
2.5
2.0
1.5
1.0
0.5
0.0
Fig. 8.Temperature sensitivity analysis for significant reaction steps
On the grounds of above kinetic studies, the equilibrium constant of each
reversible reaction was calculated with reaction rate constant at different temperature,
which was presented in Table 4. It could be believed that the rate constants of the
forward reactionsare all higher than that of reverse, which are all benefit for the
production of methyl cinnamate. By comparing these constants at different
temperature, the order can be ranked as K6 ＞K3 ＞K1 ＞K2, which means the
protonation of onium acetamide proceeds more thoroughly than other steps.
Table 4Equilibrium constant of each reversible reaction under different temperature
ln K
lnK1
lnK2
lnK3
lnK6
T/K
283
288
293
298
0.693
0.656
0.620
0.586
0.471
0.449
0.427
0.407
1.089
1.038
0.988
0.939
1.851
1.740
1.633
1.530
The enthalpy change (△H) is one of the most important thermodynamic
19

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parameters of reversible reactions. Thus, the enthalpy change of each reversible
reaction, exhibited in Table 5, was also calculated from equilibrium constant under
different temperatures through Van’t Hoff formula that expressed as formula (15).
And the Van’t Hoff plot over reaction temperature was shown in Fig. 9.The results
were also creditableowing to the acceptable error listed in Table 5.
ꢀH
RT
ln K = −
+ C
(15)
As shown in Table 5, it could be obtained that all the reversible reactions are
exothermal. The enthalpy change of the firstthree equilibrium reactions are close to
each other and the reason could be concluded as follows. The thermal effects of these
reactions are small, so the absolute value of enthalpy change are all small, which is in
agreement with the fact of room-temperature reaction.By comparing the absolute
value of enthalpy change with each other, the order could be ranked as △H6＞△H3＞
△H1 ＞ △H2.
The interaction betweenTMS+and[TMS-O]- is the highest, which
indicatesthis reaction is the most sensitive to reaction temperature among the
reversible reactions. However, as noted above, the absolute value of enthalpy change
are all relatively low. It reveals that the reaction temperature has little influence on
these equilibrium constants and the previous assumption of steady-equilibrium is
reasonable. These equilibrium reactions are very important for the formation of
methyl cinnamate. Therefore, the thermodynamic studies on equilibrium reactions
involving equilibrium constant and enthalpy change could make for understanding
this new catalytic process.
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DOI: 10.1039/C7GC02265D
0.75
0.70
0.65
0.60
0.55
0.50
601.40
360.84
lnK1 =
−1.43
lnK2 =
−0.80
T
T
0.48
0.46
0.44
0.42
0.40
0.00330 0.00335 0.00340 0.00345 0.00350 0.00355 0.00360
0.00330 0.00335 0.00340 0.00345 0.00350 0.00355 0.00360
-1
-1
1/T
(K
)
1/T(K )
1.9
1.8
1.7
1.6
1.5
1804.19
841.95
1.08
1.04
1.00
0.96
0.92
lnK6 =
−4.52
lnK3 =
−1.89
T
T
0.00330 0.00335 0.00340 0.00345 0.00350 0.00355 0.00360
0.00330 0.00335 0.00340 0.00345 0.00350 0.00355 0.00360
-1
-1
1/T(K )
1/T(K )
Fig. 9.Van’t Hoff plot for enthalpy change of each reversible reaction
Table 5Enthalpy change of each equilibrium reaction
Equilibrium reaction
△H/ (kJ/mol)
C
R2
-5.00
-1.43
0.99
-3.00
-7.00
-0.80
-1.89
-4.52
0.99
0.99
0.99
-15.00
Substrates extension
In addition to methyl cinnamate, other unsubstituted acetateand propionates
esters for this one-pot condensation reaction in our ILs catalyzed system were also
evaluated, and the experimental results were presented in Table 6. A
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comparisonbetween benzaldehyde and acetate derivatives shows a decrease in yield
with the increasing length of carbon chain that combined with the oxygen atom in
ester bond. This observed decreasing tendency could be related to the increasing
difficulty in enolization of esters. The substituted methyl group of the α-carbon atom
and the length of carbon chain that combined with the oxygen atom in ester bond
could contribute to the steric hindrance and difficulty in polarizing carbonyl groups,
sequentially affecting the acidification and abstraction of the α-proton. The addition of
electron-donating group in benzaldehydes could promote the yield, while the
electron-withdrawing group decreases the yield.This results prove the catalytic
performance of ILs-L. However, thetrend is not very sharp, which shows a
cooperative effect between the strong basicity of onium amide and Lewis acidity of
[Bmim]Cl/AlCl3 (the molar fraction of AlCl3 is 0.67). The enolate anion generated
from the deprotonation of esters with onium amide could also condense with
benzaldehydes directly, during which the substituted electron-withdrawing group is
more advantageous.
Table 6One-pot synthesis of methyl cinnamate from esters and benzaldehyde catalyzed with
a
[Bmim] F and [Bmim]Cl/AlCl3
Entry
1
product
Yield /%b
79.5
Selectivity /%b
94.3
2
3
4
5
6
7
8
80.7
80.2
78.6
79.4
75.2
74.3
73.9
93.6
92.9
94.1
93.7
93.2
92.6
93.0
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9
70.1
93.2
89.9
95.0
94.0
93.8
92.9
10
11
12
13
14
68.8
84.2
79.5
80.3
81.2
aReaction condition: benzaldehyde (0.2 mmol, 0.1 M in CH2Cl2), the molar ratio of methyl acetate
to BSA and benzaldehyde was 2:2:1, [Bmim]F: 20 mol. %, [Bmim]Cl/AlCl3 (the molar fraction of
AlCl3 was 0.67): 20 mol. %, reaction temperature: 20℃, reaction time: 4 h.bdetermined by
GC-MS, GC part for quantification and MS part for structure confirmation.
Conclusions
A series of ILs-F were firstly prepared and applied in combination with ILs-L for
one-pot catalytic synthesis of α, β-unsaturated esters from esters and aldehydes.In this
catalytic system, BSA as a probase could be converted into strong base onium amide
with the catalysis of ILs-F, meanwhile esters could be deprotonated by such strong
base and transformed into enolates. The onium amide could be also recycled through
the trimethylsilyl etherification of enolates with BSA. While ILs-L play important
role in condensation between enol silyl ether and aldehyde. The cations of
ILs-F,Lewis acidic concentration and strength of ILs-Las well assolventhave effect on
this reaction. The kinetic parameters and equilibrium constants of each reaction step
were calculated through mechanism-based kinetic analysis and simulation. The results
also revealed the condensation process was the rate-controlled step, all the
equilibrium reactions were exothermal and insensitive to reaction temperature. This
ILs catalyzed probase method was also universal for synthesis of other α,
β-unsaturated esters besidesmethyl cinnamate.The yield and selectivity could reach up
84.2 % and 95.0 % respectively.
Acknowledgements
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The authors wish to acknowledgethe National Key Projects for Fundamental
Research and Development of China (2016YFB0601303).This work was also
financed by the National Science Fund for Excellent Young Scholars (No.
21422607),National Natural Science Fundation of China (No. 21676270),National
Natural Science Foundation of China (No. 21576261) and the NSFC-Key Projects of
Shanxi Coal Based Low Carbon Joint Fundation (No. U1610222). This research was
also supported by the CAS/SAFEA International Partnership Program for Creative
Research Teams.
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