Catalytic synthesis of methacrolein: Via the condensation of formaldehyde and propionaldehyde with l-proline

Article abstract of DOI:10.1039/d0gc00726a

Methacrolein (MAL) is an important chemical for the manufacture of methyl methacrylate and a key monomer in many polymerization reactions. In this study, l-proline was investigated as the catalyst for the aldol condensation of formaldehyde and propionaldehyde to produce MAL. The catalytic activity of the reaction system was closely related to the competition between the main reaction synthesizing MAL and the side reaction producing 2-methyl-2-pentenal, which could be modified by adjusting the operating parameters. The influences of several operating conditions, including temperature, reaction time and water content, on the catalytic performance of the system were systematically studied via a series of single-factor experiments, and the optimized reaction conditions were obtained. The mechanistic investigation via ESI-MS indicated that the reaction pathway followed the Mannich route. Experimental and theoretical kinetic analyses of the l-proline-catalyzed aldol condensation reaction were performed, and the reaction orders of the reactants were obtained by regression. The results showed that l-proline was an efficient catalyst for the production of MAL via aldol condensation under mild conditions.

Full text of DOI:10.1039/d0gc00726a

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Page 1 of 22
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1
Catalytic Synthesis of Methacrolein via the Condensation of
2
3
Formaldehyde and Propionaldehyde with L-proline
Jiayuan Yua,b, Anker Degn Jensenc, Lei Wang*,a, Chunshan Lia, Suojiang Zhang*,a
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a. CAS Key Laboratory of Green Process and Engineering, State Key Laboratory of
Multiphase Complex Systems, Beijing Key Laboratory of Ionic Liquids Clean
Process, Innovation Academy for Green Manufacture, Chinese Academy of
Sciences,
Beijing
100190,
China.
E-mail:
lwang@home.ipe.ac.cn.
sjzhang@ipe.ac.cn.
9
10
b. Sino-Danish College, University of the Chinese Academy of Sciences, Beijing
100049, China
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c. Department of Chemical and Biochemical Engineering, Technical University of
Denmark, 2800 Kgs Lyngby, Denmark.
13
Abstract
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Methacrolein (MAL) is an important chemical for the manufacture of methyl
methacrylate and a key monomer in many polymerization reactions. In this study, L-
proline was investigated as catalyst for the aldol condensation of formaldehyde and
propionaldehyde to produce MAL. The catalytic activity of the reaction system was
closely related to the competition between the main reaction synthesizing MAL and the
side reaction producing 2-methyl-2-pentenal, which could be modified by adjusting the
operating parameters. The influences of several operating conditions, including
temperature, reaction time and water content, on the catalytic performance of the system
were systematically studied via a series of single-factor experiments, and the optimized
reaction conditions were obtained. The mechanism discussion via ESI indicated that
the reaction pathway followed the Mannich route. Experimental and theoretical kinetic
analyses of the L-proline-catalyzed aldol condensation reaction were performed, and
the reaction orders of the reactants were obtained by regression. The results showed
that L-proline was an efficient catalyst for the production of MAL via aldol
condensation under mild condition.
29
Keywords: methacrolein, aldol condensation, L-proline, kinetics
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30 1. Introduction
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Methacrolein (MAL) is a key chemical widely used in the production of polymers
and resins.1,2 It is also applied as a raw material for the synthesis of unsaturated esters3,4
and diacetates5,6, which act as monomers for thermoplastics7 and intermediates for
various chemical reactions. MAL production is mainly realized via two routes: the
direct oxidation of isobutene and the aldol condensation of formaldehyde (FA) and
propionaldehyde (PA).8 The isobutene direct-oxidation route, generally catalyzed with
Mo-Bi composite, is limited by its low yield of MAL.9 While the aldol condensation
process, which can occur at mild conditions with relatively high yield, is a clean
technological route with good industrial prospects, the development of an efficient
catalyst and technology is required.
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Acidic or alkaline substances can enhance the reaction of the aldehydes via the
direct aldol condensation pathway, but they can also act as catalysts for the self-
condensation of PA and the polymerization of the unsaturated aldehydes, the selectivity
for the target product MAL is unsatisfactory.10 More efficient catalytic process was
expected to accomplish the MAL synthesis. The amine-assisted aldol condensation
process to prepare MAL with FA and PA first came into use in the 1950s, when molten
salts of monoamine were introduced as catalysts by Bortnick et al.11 Since then, several
attempts to realize the commercial production of MAL via the amine-assisted Mannich
reaction have been carried out, and many catalytic systems have been proposed.
Mironov et al.12 argued that the pH of the reaction system was directly related to its
catalytic activity, and obtained a yield of 97 % at 313–323 K in the pH range of 6–7.
Dashko et al.13 reported that increased basicity of the amino catalysts and the solvents
favored the cross-condensation reaction in the system. Erkkila et al.14 reported the
catalytic abilities of different secondary amine/carboxylic acid combinations on the
condensation of diverse aldehydes and FA under mild conditions and obtained a MAL
yield of 90% in the pyrrolidine/propionic acid co-catalyst system. Besides, the acidities
of co-catalysts were found to be closely related with the catalytic performance.15 Lei et
2

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al.16 investigated the possibility of preparing MAL with high selectivity via the
condensation of aldehydes at temperatures in the range of 373-483 K and short
residence times of a few seconds; the results of this group indicated that appropriately
shortened residence time increased the selectivity of MAL with 99.9% conversion of
PA. Li et al.17 found diethylamine/acetic acid was the optimal catalyst for the Mannich
synthesis of MAL from FA and PA, among the various combinations of secondary
amines and acetic acid, with a conversion of 97% and yield of 94%. The experimental
kinetic results indicated that the reaction activation energy of the diethylamine
catalyzed process was 62.45 kJ/mol.18 Compared with the direct aldol condensation
pathway, the Mannich route shows obvious superiority on the high catalytic efficiency
and relatively lower harm on environment. Unfortunately, the stability of secondary
amine/carboxylic acid catalysts during recycling was challenged because the carboxylic
acids drained away during distillation. To overcome this issue, amines were
immobilized on cation exchange resins and applied to the MAL synthesis process, yet
low conversions of aldehydes were obtained.19 Pyo et al.20 found more aldehyde were
transformed into a β-hydroxy aldehyde, the selectivity of the dehydration product MAL
was quite low.
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Scheme 1. MAL synthesis routes (a) isobutene selective oxidation, (b) direct aldol condensation and
(c) Mannich pathway
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Considering the above researches, homogeneous single-molecular catalysts
containing both a secondary amine group and a carboxyl group may be an effective
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means to complete the aldol condensation reaction. L-proline and its derivatives can be
introduced to the synthesis of MAL on account of their ability to form iminiums.21
These organocatalysts are green and environmentally benign compounds, which act as
enzymes, may potentially catalyze the synthesis reaction of MAL under mild conditions
with high efficiency and low toxicity to humans and the environment. This reaction
process presents competitiveness in aspects of efficiency, safety, and sustainability,
satisfies the green chemistry criteria highlighted in the recent catalytic
methodologies.22-25
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In this work, L-proline was proposed as a single-molecular catalyst for the
synthesis of MAL from the aldol condensation of FA and PA. The optimal reaction
parameters for the system were investigated using a series of single-factor experiments.
Furthermore, a kinetic model of the reaction was established based on experimental and
theoretical analyses, the reaction mechanism was verified and the rate-controlling step
was determined. L-proline catalyzed condensation reaction was discovered as an
efficient process for MAL synthesis.
95 2. Experimental section
96
2.1 Materials
FA (about 37%), methanol ( 99.5%), ethanol ( 99.9%), sodium sulfite
97
98
≥
≥
anhydrous ( 97%), diethylamine ( 99%) were purchased from Xilong Scientific
≥
≥
99
Co., Ltd. (China), while acetic acid ( 99.5%), sulfuric acid ( 97%) were provided
≥ ≥
100
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103
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by Beijing Chemical Factory (China), PA ( 97%) was obtained from Aladdin
≥
Industrial Inc. L-proline ( 99%), sarcosine ( 99%), L-pipecolic ( 99%),
≥
≥
≥
hydroxyproline ( 99%) were also supplied by Aladdin Industrial Inc. and used as
≥
catalysts. All these chemicals were used without further purification. The concentration
of FA was determined with the sodium sulfite titration method before each experiment.
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2.2 General synthesis experiments
The synthesis experiments were conducted in a 250 ml three necked round bottom
4

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107
flask at atmospheric pressure. The reaction temperature was controlled to 308–323 K
by a water bath with a magnetic stirrer. The diffusion resistance had been eliminated.
L-proline crystals (0.15 mol) were dissolved in water (30 g) and then injected into the
flask. An aqueous mixture of PA and FA (37 wt%) was dripped into the L-proline
solution while stirring at a speed of 1.2 ml/min, avoiding any abrupt temperature
increase in the system (The optimization of the drop rate was shown in Supporting
Information). The molar ratio of FA/PA/L-proline was 1:1:1, and the resulting system
was stirred for 10 min. After completion of the reaction, methanol (0.5 mol) was added
to the system with mixing to form a homogeneous solution. The product was collected
and analyzed with gas chromatography (GC).
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The catalytic performance of the catalyst was evaluated based on the conversion
of PA, the selectivity of MAL and the yield of MAL. The corresponding expressions of
these parameters were as followed:
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Conversion of PA:
푛푃퐴,푖푛 ― 푛푃퐴,표푢푡
Eq. 1
Eq. 2
Eq. 3
푋푃퐴
=
× 100%
× 100%
푛푃퐴,푖푛
Selectivity to MAL:
Yield of MAL:
푛푀퐴퐿,표푢푡
푆푀퐴퐿
=
푛푃퐴,푖푛 ― 푛푃퐴,표푢푡
푛푀퐴퐿,표푢푡
푌푀퐴퐿
=
× 100%
푛푃퐴,푖푛
123
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In these equations,
and
is the moles of PA existing in the system
푛푃퐴,푖푛
푛푃퐴,표푢푡
before and after the reaction respectively,
in this reaction.
is the moles of MAL synthesized
푛푀퐴퐿,표푢푡
126
127
2.3 Kinetic study
The kinetic study was carried out in a 500 ml three-necked glass-jacketed reactor.
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The experiments were conducted in the temperature range of 273–293 K controlled by
the ethanol bath pumped into the jacket. Mechanical stirring was utilized to ensure the
uniform mixing of the reaction solution. Exactly 0.75 mol of L-proline, aqueous FA
solution containing 0.75 mol of the aldehyde, and the corresponding amount of PA were
quickly mixed with distilled water to obtain a mixture with a total volume of 240 ml.
Samples (0.5 g) were regularly collected from this reaction system and analyzed by GC.
The weights of the products and sampling times were recorded accurately.
135
136
The reaction rate for the aldol condensation reaction of FA 1 with PA 2 to produce
MAL 3 and water 4 can be expressed with a power-law equation as:
CH2O (ퟏ) + C3H6O(ퟐ) L ― proline C4H6O (ퟑ) + H2O(ퟒ)
137
d[ퟐ]
= 푘푇[ퟏ]푎[ퟐ]푏 푘 ―푇[ퟑ]푐[ퟒ]푑
Eq. 4
푟 = ―
-
d푡
mol ∙ L ―1 ∙ min ―1 푘푇
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where, r represents the reaction rate with a unit of
,
and
is
푘 ―푇
the forward and reverse rate constants of the aldol condensation reaction,
reaction order of FA, PA, MAL and water respectively.
is the
푎,푏,푐,푑
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Besides, the MAL synthetic process could be considered as an irreversible reaction
in the current system as no PA was detected when MAL and L-proline solution were
mixed at 293 K. The equation could be simplified as:
푟 = 푘푇[ퟏ]푎[ퟐ]푏
Eq. 5
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The reaction orders of PA and FA were determined in sequence based on the
concentration changes of PA. Three runs of experiments with FA in excess were
designed to measure the order of PA. The molar ratios of FA and PA were set to 1:0.1,
1:0.15, and 1:0.2. Under this circumstance, the concentration change of FA was quite
small, and hence considered constant. The reaction rate equation was converted to:
d[ퟐ]
= (푘푇[ퟏ]푎)[ퟐ]푏 = 푘′[ퟐ]푏
Eq. 6
푟 = ―
d푡
ln푟 = ln푘′ + 푏ln[ퟐ]
Eq. 7
푘′
was the rate constant.
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where
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The reaction rates were obtained through the differentiation of the [2]-t curves.
Linear fitting was conducted for the lnr-ln[2] plot, and the slope intrinsically indicates
the reaction order of PA in the tests with FA in excess.
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Tests were then conducted under various temperatures in the range of 273-293 K
with the molar ratio of FA and PA set as 1:1 to investigate the reaction order of FA.
Under this condition, the conversion of FA could be described via the PA concentration,
the reaction rate equation was rearranged as Eq 8.
푟 = 푘푇[ퟏ]푎[ퟐ]푏 = 푘푇[ퟐ]푎 + 푏
Eq. 8
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158
According to the Arrhenius equation (Eq. 9), the linear regression of lnk as a
function of 1/T provides the frequency factor and
of the L-proline catalyzed
퐸푎
159
process as shown in Eq. 10.
퐸푎
푘T = 퐴 × 푒 ―
Eq. 9
푅푇
Eq. 10
퐸푎
푅
1
ln푘T = ―
×
+ ln퐴
푇
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where A is the frequency factor, Ea is the activation energy (J/mol), T is the temperature
(K), and R is the gas constant, (8.314 J/(mol K)).
162
2.4 Analytical methods
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The sodium sulfite titration method was used to detect the amount of FA in the
aqueous solution. GC analysis was employed to analyzed the amount of PA, MAL and
MP in the system, with ethanol as the internal standard. A Q-HT chromatographic
column (27.5 m×0.32 mm×10 μm) was selected. He (30 mL/min) was used as the
carrier gas with a split ratio of 300:1, and the front inlet temperature was set as 523 K.
The oven had an initial temperature of 393 K, and was heated at a rate of 30 K/min to
513 K, and then held for 10 min. A FID detector with a temperature of 573 K was also
used. The accuracy of MAL analysis was confirmed with its isolated yield obtained by
extraction separation (see Supporting Information).
172
The ESI-MS spectra were obtained on a Bruker micrOTOF-QII mass spectrometer.
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173 3. Results and discussion
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3.1 Screening of the catalyst
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Previous work conducted by our group verified that diethylamine/acetic acid could
effectively catalyze the MAL synthesis process17, however, the acidic catalytic
component was lost during recycling. To overcome this problem, several bifunctional
molecules containing both a secondary amine group and a carboxyl group were selected
as catalysts and tested in the present system. The results of these experiments were
shown in Table 1.
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Table 1. MAL production with different catalysts
푋
푆
푃퐴/%
푀퐴퐿/%
84.3
Entry
1
Catalyst
92.0
52.2
2
87.0
3
4
96.5
94.1
96.8
91.9
푛
푛
푛catalyst
= 0.15
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Reaction condition: content of reaction system, FA= 0.15 mol, PA= 0.15 mol,
mol; water content = 40 wt%; reaction temperature, 316 K; reaction time, 30 min.
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As expected, the investigated single-molecular organocatalysts were effective for
the aldol condensation reaction with satisfactory yield of MAL.26 L-proline (entry 3)
exhibited the best result among the catalysts investigated. While moderate conversion
was observed for L-pipecolic acid (entry 2), a small amount of by-products, i.e., dimers
of the aldehydes, was also detected; this result indicated that the reaction rate of this
system was relatively slow and that the hexatomic ring structure suppressed the activity
of the secondary amine. Sarcosine (entry 1) has a straight-chain structure and features
the simplest molecular structure among the selected catalysts; however, the selectivity
of this catalyst was far from optimal. The data of these two entries indicated that the
five-membered pyrrolidine ring containing a secondary amine in L-proline was the
8

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most suitable structure to catalyze the aldol condensation reaction, likely because the
spatial proximity of the acid and base of this structure was beneficial to the catalytic
reaction.27 The L-proline derivative hydroxyproline (entry 4) showed no improvement
in compared with the result of L-proline, probably because the hydroxyl group had little
effect on the dissociation constant and steric hindrance of the catalyst.28
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3.2 Optimization of aldol condensation with L-proline
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The effects of reaction temperature, solvent content, reaction time and molar ratio
of reactants were studied to determine the optimal reaction conditions resulting in the
maximum yield of MAL.
203
3.2.1 Effect of reaction temperature
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Temperature exerted significant influences on the reaction rate and preference
between main and side reactions. Detailed results of the changes observed at low
temperatures were illustrated in Figure 1(a).
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Conversion of PA increased gradually to 99.0% at 323 K. By contrast, MAL
selectivity first increased with increasing temperature and then abruptly decreased at
reaction temperatures higher than 320 K, giving a maximum yield of 97.4%. The
selectivity for the by-product 2-methyl-2-pentenal (MP) followed a raising trend,
reached 8.13% at 323 K.
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The rising trend of PA conversion with temperature is expected because the
reaction rate for most systems is accelerated at high temperatures. Competition between
main and side reactions is responsible for the trend observed in MAL selectivity. At
relatively low temperatures, the main aldol condensation reaction dominates the system,
and no obvious peak of the side product MP could be detected. However, the selectivity
obtained is lower than expected because the intermediate Mannich base is not fully
decomposed into MAL at low temperatures. At high reaction temperatures, side
reactions are preferred even though the overall reaction rates are enhanced. These
findings are in accordance with the results of Lei et al.16, who investigated the
continuous synthesis of MAL and showed that the contents of impurities varied with
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temperature.
3.2.2 Effect of water content
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The presence of water is known to affect the species and contents of intermediates
formed with L-proline and aldehydes and promote the aldol condensation reaction.29,30
The effect of water content on the present MAL formation reaction is illustrated in
Figure 1(b).
(a)
(b)
(c)
Figure 1. Catalytic performance as a function of various reaction parameters. (a) Effect of reaction
푛L ― proline
(d)
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230
231
푛
푛
temperature ( FA= 0.15 mol, PA= 0.15 mol,
= 0.15 mol, water content = 40 wt%, 25
푛
푛
푛L ― proline
min). (b) Effect of initial water content ( FA= 0.15 mol, PA= 0.15 mol, = 0.15 mol, 320
푛
푛
푛L ― proline
K, 25 min) (c) Effect of reaction time ( FA= 0.15 mol, PA= 0.15 mol, = 0.15 mol, water
10

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푛L ― proline
= 0.15 mol, water
푛
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content = 37 wt%, 320 K) (d) Effect of reactant ratio ( FA= 0.15 mol,
233
content = 37 wt%, 320 K, 25 min)
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The performance of L-proline in this aldol condensation reaction was
approximately unaltered as the water content of the system increased from 36% to 43%;
in particular, the conversion of PA was close to 100%. This result indicates that the
water content and reactant concentration have little effect on the aldol condensation
reaction under the chosen operating conditions.
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The pH of the reaction solutions was measured with a pH indicator. The L-proline
solutions were under approximately neutral conditions, and pH values decreased from
7.06 to 6.65 with increasing amount of water in the current systems. The same operation
was conducted on the mixtures obtained after the reaction, and pH values between 5
and 6 were obtained. These findings verify the existence of intermediates formed with
L-proline and aldehyde. The secondary amine forms bonds with the reactants, and the
hydrogen proton of the carboxyl group dissociates, thereby slightly increasing the
acidity of the system.
247
3.2.3 Effect of reaction time
248
249
The reaction time shown in Figure 1(c) refers to the sum of the dripping times of
the reactants (about 20 min) and the time these reactants are maintained in the flask.
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258
A slight increase in conversion was observed in the time interval of 20–35 min,
and conversion plateaued after 35 min. The occurrence of reversible elementary
reactions inhibited the reactants from converting completely, and the equilibrium
conversion was 99.3%. The curve for MAL selectivity followed an inverted U shape, a
maximum selectivity of 99.4% was achieved at 25 min, while the selectivity for MP
changed little in this time interval. When the reaction time was too short, a large amount
of the Mannich base, an intermediate, was observed in the system. With increasing time,
the side reaction consuming MAL molecules by self-polymerization became more
vigorous and led to the decline of reaction selectivity to MAL.
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3.2.4 Effect of molar ratio of reactants
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The ratio of substrates added is a key element, especially for reversible reactions,
because this parameter would determine the conversion of the reaction under chemical
equilibrium. Ganapati et al.31 observed enhancements in the yield of jasminaldehyde in
the vapor-phase aldol condensation of heptanal and benzaldehyde by adjusting the
molar ratio of substrates; the team attributed this finding to the competitive adsorption
of reactants on catalytic sites and dilution of substrates, which led to the displacement
of chemical equilibrium. To examine the optimal molar ratio of FA to PA, a set of
experiments was performed with different amounts of PA injection (Figure 1(d)).
268
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272
273
Higher conversions were observed when less PA was injected into the system. The
curve for selectivity peaked at 99.4% under the 1:1 reactant ratio condition. While the
amounts of MAL detected were approximately the same, in the experiments in which
the amounts of PA added were in no shortage. This result means increases in PA input
would not lead to higher production of MAL, but an ascending yield of the by-product
MP, because the content of FA in the system limited the conversion to MAL.
274
3.3 Recyclability of the catalyst
275
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283
284
285
The stability and life cycle of a catalyst are key considerations determining its
commercial application prospects. Low-pressure distillation was applied to the mixture
obtained after aldol condensation to obtain an L-proline aqueous solution. The excess
aldehydes, methanol and water in the system were separated by distillation at 323 K
under 13 kPa until the weight of the solution remaining in the round flask was less than
that of the L-proline solution added at the beginning of synthesis. The concentration of
L-proline was detected by liquid chromatography, and the amounts of catalyst in the
mixture were found to remain the same in over six runs. Water was added to the system
to maintain the same concentration of L-proline. The 6 runs of stability tests followed
the same procedure of the reactions discussed above, and the results are shown in Figure
2.
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287
The catalytic performance of L-proline was essentially maintained after six
repeated runs. This finding reveals that L-proline has relatively good recyclability and
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can be reused via distillation at reduced pressure.
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푛
푛PA
=
290
291
Figure 2. Recycling performance of L-proline on the MAL synthetic reaction ( FA= 0.15 mol,
푛L ― proline
0.15 mol,
= 0.15 mol, water content = 37 wt%, 320 K, 25 min)
292
3.4 Reaction mechanism
293
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295
296
297
The mechanisms of various L-proline-catalyzed C-C bond formation reactions
have been investigated in several studies, and generally two main mechanisms are
accepted for these L-proline catalyzed processes: the enamine pathway and the iminium
pathway.21,32-34 Based on the previous researches, two possible mechanisms were
proposed for this MAL synthesis process, as shown in Scheme 2.
298
299
300
301
In the enamine pathway, PA attacked the L-proline, forming the iminium ion 7,
which further transformed to enamine 8. A transition state is synthesized with the
activated enamine and FA, giving the aldol product 10. The aldol product 10 can
dehydrate to MAL 3.
302
303
304
305
The iminium pathway, which could also be called as Mannich route in this system,
start with the nucleophilic addition of FA and L-proline, generating the iminium ion 12,
and a molecule of water 4 is released. PA then reacts with the iminium ion 12 to form
the Mannich base 13, which later dissociates into MAL 3.
306
307
ESI-MS spectra were employed to verify the mechanism of the condensation
reaction. If the reaction follows the enamine route, the enamine 8 and aldol product 10
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could be detected in the reaction system. While if the intermediates 11, the iminium ion
12 and the Mannich base 13 exist, the Mannich mechanism applies to the condensation
reaction. As presented in Figure S1, the intermediates 8, 11, 12 and 13 were all observed
in the reaction system, but the intensity of enamine 8 was quite low, about 1/40 of the
iminium ion 12. This supported the claim that the L-proline catalyzed process followed
the Mannich pathway. This was also implied by the high selectivity of the MAL
synthesis reaction, as more aldol product 10 would be detected if the reaction followed
the enamine pathway. The existence of enamine 8 in the system may also devoted to
the production of by-product MP. The relative higher intensity of peak corresponding
to iminium ion 12 than intermediates 11 indicated that intermediates 11 tended to
transformed to rather stable iminium ion 12 in the system.
(a)
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(b)
319
Scheme 2. Proposed catalytic cycle for the aldol reaction (a) the enamine pathway and (b) the
Mannich pathway
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3.5 Kinetic study
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323
The kinetic study of this condensation reaction was conducted both experimentally
and theoretically to further understand this reaction and the mechanism.
324
3.5.1 Experimental kinetic model
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327
328
329
330
As illustrated before, three runs of experiments with FA in excess were conducted
to discuss the order of PA. Because the conversion of PA slowed with time, as shown
in Figure 3, a positive reaction order was suggested for PA. The approximately
overlapping straight lines in the lnr-ln[2] plots (Figure S2) indicated that the
simplification of the power-law model was reasonable and the mean value of the
reaction order of PA was calculated as 0.980.
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333
Figure 3. Kinetic profiles for the L-proline catalyzed aldol reaction with [1]0 in different levels of
푛L ― proline
푛
excess with respect to [2]0 ( FA= 0.75 mol,
= 0.75 mol, total volume = 240 ml, 273 K)
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337
The reaction profile in the range of 273-293 K with the same initial concentrations
of FA and PA were shown in Figure 4. The nearly parallel linear fittings presented in
the Figure S3 indicated that the total order of the reaction was 1.494 and that the reaction
order of FA was 0.514.
338
The power-law kinetic model for the L-proline catalyzed process was:
푟 = 푘푇[ퟏ]0.514[ퟐ]0.980
Eq. 11
339
푛
=
FA
340
341
Figure 4. Kinetic profiles for the L-proline catalyzed aldol reaction at different temperatures (
푛
푛L ― proline
= 0.75 mol, total volume = 240 ml)
0.75 mol, PA= 0.75 mol,
342
The relationship of the rate constant kT and reaction temperature was described in
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of the L-proline
퐸푎
343
Figure 5. The pre-exponential factor A and the apparent energy
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346
catalyzed aldol reaction could be deduced from the intercept and slope of the straight
line as 2.47 109 min-1mol-0.494L0.494 and 61.1 kJ/mol, respectively. More details of the
×
experimental kinetic calculation were included in Supporting information.
347
348
ln푘T
Figure 5. Arrhenius curve of
versus 1/T
349
3.5.2 Theoretical derivation of kinetic model
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357
Knowledge of the reaction order of the reactants may help in the construction of
the reaction mechanism and determination of the rate-controlling step. According to the
power-law kinetic rate expression obtained in the discussion above, the reaction order
of PA is close to 1, which means it may be directly involved in the rate-determining
step. The reversible reaction of FA may contribute to its rate order, which is less than
1. Based on the information and knowledge of the reaction mechanism shown in
Scheme 2 (b), a more detailed rate equation for the reaction process is deduced as in
Eq. 12 (More information please see Supporting information).
푘1푘2푘3푘4[ퟏ][ퟓ]푡표푡[ퟐ]
Eq. 12
푟 =
(
)
(
)
푘 ―1푘 ―2(푘 -3 + 푘4)[ퟒ] + 푘1[ퟏ][푘2 푘 -3 + 푘4 + 푘2푘3[ퟐ] + 푘 ―2 푘 -3 + 푘4 [ퟒ]]
358
359
In Eq. 12,
is the initial concentration of L-proline,
is the concentration
[ퟒ]
[ퟓ]푡표푡
of water, which could be regarded as a constant since water is the solvent of the system.
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As Mannich base 13 is a poorly stable species,
is much greater than
3, and
푘 -
푘4
the equation simplifies to Eq. 13:
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푘1푘2푘3[ퟏ][ퟓ]푡표푡[ퟐ]
푘2푘3[ퟐ]
푟 =
Eq. 13
푘 ―1푘 ―2[ퟒ] + 푘1[ퟏ][푘2 +
+ 푘 ―2[ퟒ]]
푘4
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365
This equation agrees with the rate expressions of Blackmond and Orlandi.35,36 As
the concentrations of FA 1 and PA 2 are observed in the denominator of the expression,
the observed reaction orders may be less than 1. The reaction order of FA 1 is more
severely deviated from 1 when compared with that of PA 2. When
is characterized
푘4
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376
with larger orders of magnitude, the coefficient for PA in the denominator is reduced
to zero, and a nearly first-order reaction of PA is realized. The nonnegligible term of
the FA concentration in the denominator leads to its non-integer reaction order in the
current experimental kinetic analysis. The apparent dependence of the reaction on water
in the proposed system would show a negative order because of the existence of
[ퟒ]
in the denominator of Eq. 12. The addition of extra water shifts the chemical
equilibriums shown in Scheme 2 (b) and drives the intermediates decomposed back to
L-proline. Thus supposition is in accordance with a report by Zotova29. The
correspondence of the experimental kinetic data with the mechanism deduced
theoretical kinetic model supported the proposed Mannich mechanism for the L-proline
catalyzed reaction.
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381
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383
Comparing the experimental and theoretical equations obtained, the rate
determining step of the aldol condensation was determined. If the first step, i.e.,
nucleophilic addition of L-proline, is the rate-determining step, a first order of FA
concentration would be expected as shown in Eq. 14. If the iminium ion 12 formation
step acts as the rate-limiting step, the reaction rate could be given by Eq. 15 and the
reaction order of FA would be 1. These two assumptions do not match with the non-
integer reaction order of FA 1 obtained in the experimental rate equation.
푟 = 푘1[ퟏ][ퟓ]
Eq. 14
Eq. 15
푘1푘2[ퟏ][ퟓ]
푟 = 푘2[ퟏퟏ] =
푘 ―1
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384
When the addition of PA to iminium ion 12 or the Mannich base 13 dissociation
385
step is the controlling step, the rate could be described by Eq. 16 and 17 separately:
푟 = 푘3[ퟏퟐ][ퟐ]
푟 = 푘4[ퟏퟑ]
Eq. 16
Eq. 17
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392
Both the two equations satisfy the observed nearly first order of PA and the
fractional order of FA in the rate expressions obtained. The final controlling step in the
practical reaction process is related with the operating conditions, which affect the
corresponding rate constant of the two steps. Hence, the Mannich base 13 formation
and dissociation step were deduced to be the rate-determining steps of aldol
condensation of FA and PA, and the actual rate-limiting step was the slower step of the
two under the corresponding reaction condition.
393 4. Conclusion
394
395
396
397
398
399
400
401
402
403
In summary, the application of several single-molecular bifunctional catalysts to
form MAL from the aldol condensation of FA and PA was investigated, and the results
showed that L-proline was an effective catalyst for the aldol condensation to produce
MAL via Mannich pathway. Parameters with the most significant effects on MAL yield
were determined, and a high-yielding reaction was established. The catalytic yield of
MAL retained at 98% after six runs. A nearly first-order dependence on PA was
observed in the kinetic study, and the reaction order of FA was fractional with a value
of approximately 0.5. The apparent Ea of the proposed L-proline catalyzed aldol
reaction was calculated to be 61.1 kJ/mol. Hence, L-proline is an efficient and
recyclable catalyst for the aldol condensation reaction to synthesize MAL.
404 Conflicts of interest
405
There are no conflicts of interest to declare.
406 Acknowledgements
407
The authors gratefully acknowledge the financial supports of the National Natural
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409
410
Science Funds (21878293), Science Funds for Creative Research Groups of the
National Natural Science Foundation of China (21921005), and Key Research Program
of Frontier Sciences (CAS QYZDB-SSW-SLH022).
411 List of abbreviations and symbols
FA
PA
MAL
MP
k
Formaldehyde
Propionaldehyde
Methacrolein
2-methyl-2-pentenal
Rate constant
A
Pre-exponential factor
Temperature (K)
T
Ea
Activation energy (J/mol)
Gas constant, (8.314 J/(mol K))
Molar amount of chemical (mol)
Conversion of propionaldehyde
Selectivity to methacrolein
R
n
푋푃퐴
푆푀퐴퐿
Yield of methacrolein
푌푀퐴퐿
412 Reference
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414
415
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