Facile Preparation of N -Alkyl-2-pyrrolidones in a Continuous-Flow Microreactor

Article abstract of DOI:10.1021/acs.oprd.7b00392

N-Alkyl-2-pyrrolidones have been widely used in the petrochemical industry, the agricultural chemical industry, electronic materials, etc. The distinct advantages of using N-alkyl-2-pyrrolidones as solvents or reaction media make them particularly important. A continuous-flow microreactor was exploited for the preparation of N-methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP) in a highly controlled and safe manner; thus, its use improved the efficiency of the process. Various conditions (temperature, residence time, molar ratio of amine to γ-butyrolactone (GBL), GBL concentration, water content, and presence of H₃BO₃ catalyst) were investigated to improve the synthesis of NMP/NEP. A microreactor was employed for the conversion of GBL to NMP and NEP, and the yields reached 94.7% for NMP and 93.9% for NEP under the optimized conditions. Furthermore, a kinetic model based on the reaction mechanism was proposed to guide the design and optimization of the synthesis of NMP/NEP.

Full text of DOI:10.1021/acs.oprd.7b00392

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Facile preparation of N-alkyl-2-pyrrolidones in a continuous-flow microreactor
Feng Zhou, Boyu Zhang, Hongchen Liu, Zhenghui Wen, Kejun Wang, and Guangwen Chen
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.7b00392 • Publication Date (Web): 08 Mar 2018
Downloaded from http://pubs.acs.org on March 8, 2018
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Facile preparation of Nꢀalkylꢀ2ꢀpyrrolidones
in a continuousꢀflow microreactor
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Feng Zhou1,2, Boyu Zhang1, Hongchen Liu1,2, Zhenghui Wen1,2, Kejun Wang1,2,
Guangwen Chen1*
1 Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese
Academy of Sciences, Dalian 116023, China.
2 University of Chinese Academy of Sciences, Beijing 100049, China.
* G.W. Chen. Eꢀmails: gwchen@dicp.ac.cn.
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TABLE OF CONTENTS
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ABSTRACT
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Nꢀalkylꢀ2ꢀpyrrolidones have been widely used in the petrochemical industry, agricultural
chemical industry, for electronic materials, etc. The distinct advantages of using
Nꢀalkylꢀ2ꢀpyrrolidones as solvents or reaction media make them particularly important. A
continuousꢀflow microreactor was exploited for the preparation of Nꢀmethylꢀ2ꢀpyrrolidone
(NMP)/Nꢀethylꢀ2ꢀpyrrolidone (NEP) in a highly controlled and safe manner; thus, its use
improved the efficiency of the process. Various conditions (temperature, residence time, molar
ratio of amine to γꢀbutyrolactone (GBL), GBL concentration, water content and presence of
H3BO3 catalyst) were investigated to improve the synthesis of NMP/NEP. A microreactor was
employed for the conversion of GBL to NMP and NEP, and the yields were up to 94.7 % for NMP
and 93.9 % for NEP under the optimized conditions. Furthermore, a kinetic model, based on the
reaction mechanism, was proposed to guide the design and optimization of the synthesis of
NMP/NEP.
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Keywords: microreactor, kinetic, γꢀbutyrolactone, Nꢀalkylꢀ2ꢀpyrrolidone, NMP, NEP
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INTRODUCTION
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Thanks to the fundamental work by W. Reppe1 on acetylene chemistry, pyrrolidones became
industrially available and have been widely applied in the petrochemical industry, the agricultural
chemical industry, electronic materials, etc.1ꢀ3 In the above applications, Nꢀalkylꢀ2ꢀpyrrolidones
are important solvents, extractants and reaction media. Among Nꢀalkylꢀ2ꢀpyrrolidones, NMP and
NEP are the most versatile industrial solvents due to their unique properties, such as superior
solubility, chemical stability, and low volatility.1,3 Therefore, investigations into the syntheses of
NMP and NEP are of great significance from an industrial perspective.
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The many practical applications of NMP/NEP in industry have inspired increasing research
interest in their syntheses, and various attempts have been made to make the preparation of
NMP/NEP less expensive, greener and more efficient.1ꢀ10 In general, there are two main methods
for synthesizing NMP/NEP on an industrial scale. One is the catalytic hydrogenation of maleic
anhydride, maleic acid or succinic acid with the corresponding primary amine in the presence of a
catalyst. Many attempts focusing on developing more effective hydrogenation catalysts have been
conducted to optimize this method.4,5 The second, which involves the condensation of
γꢀbutyrolactone (GBL) with the corresponding primary amine with or without a catalyst, is
preferred in industry over the first method. Therefore, much more attention has been focused on
improving this synthetic method.3,6,9,10 For example, Reppe proposed an industrial process, in
which both methylamine and GBL served as starting materials in the presence of a dehydrating
catalyst, and this method produced NMP in 85~90% yield.10 Microwave irradiation, a promising
strategy for improving these methods, was introduced into the synthesis of NMP/NEP. The work
of Jumbam and coꢀworkers showed that a satisfactory yield of NMP could be obtained using
highly active copper powder as the catalyst in conjunction with microwave irradiation.8 Khatri et
al. developed a process of reacting a dicarboxylic acid or corresponding anhydride with
methylamine by heating via microwave irradiation to obtain an Nꢀmethyl imide and then
converted the imide to NMP in a second step. Compared to the conventional heating, the reaction
time was drastically reduced, and an 85~93 % yield of NMP was achieved.2
Although the aforementioned developed processes for the preparation of NMP/NEP have
achieved some successes, a few obvious disadvantages including excessively high reaction
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temperatures and pressures, long reaction times and safety risks still exist in the processes. These
drawbacks would greatly limit the application of these modified synthetic processes from both
economic and reaction performance perspectives. The rapid developments in flow chemistry in
recent years11ꢀ13 have inspired us to consider utilizing microreactors as effective tools to avoid the
existing problems since microreactors possess significant advantages in terms of heat and mass
transfer,14ꢀ18 ease of manipulating reaction conditions,19, 20 productivity,21 efficiency22, 23 and
safety.24, 25 Although the industrial syntheses of NMP/NEP have been developed over several
decades, the behavior of this reaction system has not been sufficiently explored. Since the
behaviors are apt to deviate substantially from the expected reaction conditions once converted to
a batch process, exploring the details of the reaction behavior and overcoming the drawbacks in
batchꢀmode when using microreactors are necessary to improve upon the conventional NMP/NEP
preparation processes. Moreover, due to the ease of pressurizing microreactors, the boiling point
limit can be readily eliminated. Hence, the reaction system can be kept in a superheated status
using a safe and simple procedure and operated in an extended temperature range.
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In this work, a continuousꢀflow microreactor was exploited to obtain an improved and more
efficient process for preparing NMP/NEP. Various conditions (temperature, residence time, molar
ratio of amine to GBL (Mꢀratio), GBL concentration, water content and presence of H3BO3
catalyst) were explored under continuousꢀflow conditions to elucidate the benefits of using a
microreactor. A kinetic model was developed to guide the design and optimization of the synthesis
of NMP/NEP.
RESULTS AND DISCUSSION
Viscosities of GBL/NMP/NEP in glycol
Conventionally, the preparation of NMP/NEP at high temperature must avoid the boiling
point limitations of the raw materials by elevating the pressure, which allows the system to operate
in the liquid phase. The introduction of glycol, a highꢀboiling solvent with good intersolubility
with the raw materials, into the reaction system could greatly decrease the pressure required to
overcome the boiling point limitations, thus making the operation safer. However, glycol is more
viscous than many other solvents and the high viscosity could increase energy consumption by the
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pump and even increase the risk of blockage. The viscosities of GBL, NMP and NEP in glycol
were measured under various conditions (Figure 1).
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Figure 1. Viscosities of GBL/NMP/NEP in glycol at different temperatures
Both increasing the temperature (from 5 to 55 °C) and increasing the mass fraction of
GBL/NMP/NEP in glycol decreased the viscosity and lowered the energy consumed in the
delivery of the reagents in the synthesis of NMP/NEP. Moreover, decreasing the viscosity in the
reaction system could also increase the rate of heat and mass transfer,12 allowing the process to
operate in a more controlled manner.
Process optimization by a continuous-flow microreactor
In both the continuousꢀflow microreactor and the batch reactor, the reaction between GBL
with an amine consists primarily of the following two steps: GBL first reacts with the amine to
generate the intermediate Nꢀalkylꢀ4ꢀhydroxybutyramide, and then the intermediate is cyclized to
yield the anticipated product Nꢀalkylꢀ2ꢀpyrrolidone product with the concomitant elimination of a
water molecule (Scheme 1).8,9 Our efforts focused on a detailed exploration of various reaction
conditions to clarify the synthesis of NMP/NEP in the continuousꢀflow microreactor.
Scheme 1
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Considering that noncatalytic syntheses of NMP and NEP from GBL and the corresponding
amine are commonly conducted at high temperatures and pressures,3,9 the temperature in the
220~300 °C range were screened at 750 psi to elucidate the temperature dependence of the
synthesis of NMP/NEP in a continuousꢀflow microreactor (Figure 2). The microreactor guaranteed
the synthesis would be safer and more reliable than its batch counterparts, which are conducted
under harsh conditions. Elevation of the temperature had a minor influence on GBL conversion (X)
but caused a dramatic increase in the yield (Y) of NMP/NEP. As the temperature was increased
from 220 °C to 300 °C, the GBL conversion increased by approximately 18 %, while the
NMP/NEP yield increased by approximately 70 %. The sharp temperature dependence of the
NMP/NEP yield clearly indicated the presence of a wellꢀdefined energy barrier in the conversion
from the imide intermediate to NMP/NEP. Moreover, the GBL conversion for the preparation of
NMP was slightly higher than that of GBL to NEP, which shows methylamine is more reactive
than ethylamine.
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Figure 2. The temperature dependence of the preparation of NMP/NEP in a continuousꢀflow
microreactor. Reaction conditions: reaction temperature 220~300 °C, residence time 13.3 min,
GBL concentration 1.00 mol/L, and Mꢀratio 1.2.
Figure 3 shows the influence of the residence time on the GBL conversion and NMP/NEP
yield. With increasing residence time, the GBL conversion and NMP/NEP yield initially increased
and then plateaued. For example, 79 % GBL conversion (NEP) and 47 % NEP yield could be
obtained in the initial 2.7 min, but in the next 23.9 min the GBL conversion (NEP) and NEP yield
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increased by only 18 % and 44 % respectively. This result was mainly caused by the decrease in
the GBL concentration with the increase of residence time, which resulted in the sharp decrease in
reaction rate.
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Figure 3. Investigation of residence time dependence of the synthesis of NMP/NEP in a
continuousꢀflow microreactor. Reaction conditions: reaction temperature 275 °C, residence time
0~26.6 min, GBL concentration 1.00 mol/L, and Mꢀratio 1.2.
Methylamine and ethylamine in the experiments were used as aqueous solutions, thus it was
necessary to investigate the effect of the water content (WC) on the reaction. In our experiments,
elevating the WC had no significant impact on either the conversion of GBL or the yield of
NMP/NEP; the examined WC range was 5.65 ~ 8.43 mol/L for the synthesis of NMP and 1.39 ~
8.43 mol/L for the synthesis of NEP (Figure 4). The GBL conversion and NMP/NEP yield
remained constant with slight fluctuations, indicating that the reaction rate for the conversion from
imide to NMP/NEP was far greater than that of the reverse process.
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Figure 4. The effects of the WC on the syntheses of (a) NMP and (b) NEP under continuousꢀflow
conditions. Reaction conditions: reaction temperature 290 °C, residence time 0~13.3 min, GBL
concentration 1.00 mol/L, and Mꢀratio 1.2.
The screening of the Mꢀratio in the range 1.0~1.6 range at various residence times showed
that the condensation of the amine with GBL was not sensitive to an increase in the Mꢀratio; only
slight increases in the GBL conversion and the yield of NMP/NEP were observed then the Mꢀratio
was increased from 1.0 to 1.6 (Figure 5). A slight excess of amine (e.g., Mꢀratio 1.2) was adequate
for the preparation of NMP/NEP.
The GBL concentration was varied at various temperatures to elucidate the influence of GBL
concentration on the reaction performance (Figure 6). Increasing the GBL concentration
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noticeably increased both the GBL conversion and NMP/NEP yield, which was consistent with
our expectations. A high GBL concentration could also lead to a high spaceꢀtime yield.
Nevertheless, an excessively high concentration of GBL could increase the risk of system
instability due to the low boiling points of the amine and water.
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Considering that a previous study found that a small amount of H3BO3 was beneficial for
forming amides from carboxylic acids and amines,26 the influence of the catalyst (H3BO3) on the
synthesis of NMP/NEP under continuousꢀflow conditions was explored (Figure 7). As shown in
the figure, the addition of H3BO3 did not cause a dramatic improvement in the reaction
performance, and only a slight increase in the GBL conversion was obtained. This result might be
because the acceleration of the reaction rate caused by the addition of H3BO3 was masked by the
effect of the increased reaction temperature. Therefore, the addition of H3BO3 under
continuousꢀflow conditions was deprecated to make the process be more environmentally friendly.
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Figure 5. Screening of the Mꢀratio for the syntheses of (a) NMP and (b) NEP under
continuousꢀflow conditions. Reaction conditions: reaction temperature 290 °C, residence time
0~13.3 min, GBL concentration 1.00 mol/L, and Mꢀratio 1.0~1.6.
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Figure 6. Influence of the GBL concentration on the syntheses of (a) NMP and (b) NEP under
continuousꢀflow conditions. Reaction conditions: reaction temperature 260~300 °C, residence
time 13.3 min, GBL concentration 0.25~1.00 mol/L, and Mꢀratio 1.2.
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Figure 7. The influence of the catalyst (H3BO3) on the syntheses of (a) NMP and (b) NEP under
continuousꢀflow conditions. Reaction conditions: reaction temperature 220~300 °C, residence
time 13.3 min, GBL concentration 1.00 mol/L, Mꢀratio 1.2, and H3BO3: 2.4 % ( mole fraction
based on GBL).
Experimental and kinetic modeling investigation
To investigate the kinetics of the synthesis of Nꢀalkylꢀ2ꢀpyrrolidone, a reasonable kinetic
model should be first established based on the reaction mechanism (Scheme 1). Since as
previously discussed, the WC had no significant impact on the reaction performance, the reverse
reaction from NMP/NEP to intermediate was not considered in the kinetic modeling. Accordingly,
a kinetic model was proposed that involved the reactants (GBL and alkylamine (A)) combining in
a reversible way to form an intermediate (I), and then I further dehydrated to generate the
Nꢀalkylꢀ2ꢀpyrrolidone (P). Based on the results of the investigations conducted under the above
reaction conditions, the dehydration step was the rateꢀdetermination step, and k1+kꢁ1>>k2.
Therefore, a preꢀequilibrium between GBL, A and I could be established and the reaction rate
from I to P was too slow to affect the maintenance of the preꢀequilibrium (Hypothesis 1).27,28 Thus,
the equilibrium constant, K, of GBL, A and I can be described by Equation (1).
cI
k1
K =
=
(1)
cGBLcA k−1
The rate of the formation of P was derived as follows:
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dcP
= k2cI = k2 KcGBLcA
dt
(2)
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where ki was the rate constant for reaction i. According to the Arrhenius equation and the
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van’t Hoff equation, ki and
K
can be described by Equations (3) and (4).
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Ei
ln ki (T) = −
ln K(T) = −
+ ln A
(3)
(4)
i
RT
ꢀH φ ꢀSφ
RT
+
R
In the above equations, Ai and Ei denote preꢀexponential factor and activation energy
(kJ·molꢀ1), respectively, is the universal gas constant (8.314 J·molꢀ1·Kꢀ1 ),
T is the absolute
R
temperature (K), ꢂHΦ represents the standard molar enthalpy change (kJ·molꢀ1) and ꢂSΦ the
standard molar entropy change (J·molꢀ1·Kꢀ1).
To determine the changes in the concentrations of the reagents over time, the kinetic
experiments were performed in the continuousꢀflow microreactor at 260, 275 and 290 °C with the
concentration of GBL and amine being 1.0 mol·Lꢀ1 and 1.2 mol·Lꢀ1, respectively. Figure 8 shows
the experimental data from the given conditions, and the remaining data are given in the
Supporting Information (Figure S1). High selectivity for NMP/NEP was achieved when the
residence time was increased to 26.6 min at 290 °C. Meanwhile, a 94.7 % yield of NMP (Figure
8(a)) and 93.9 % yield of NEP (Figure 8(b)) could be achieved within 26.6 min at 290 oC.
Therefore, intermediate I can be considered as the sole byproduct in the reaction (Hypothesis 2).
Then, the concentration of I can be calculated by mass balance.
According to Scheme 1, the consumption of A and GBL was equivalent, so the
concentrations of the reaction species can be described as follows:
cA = cGBL + cA 0 − cGBL0
(5)
where cA0 and cGBL0 are the initial concentrations of A and GBL, respectively.
Substituting Equation (5) into Equation (1), the I concentration can be written as the
following:
cI = KcG2BL + KcGBLcA 0 − KcGBLcGBL0
(6)
Based on the mass balance, the concentration of P can be expressed as Equation (7).
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cP = cGBL0 − cGBL − cI
(7)
(8)
Combining Equations (6) and (7), the concentration of P can be written as Equation (8).
cP = cGBL0 −(KcA0 − KcGBL0 +1)cGBL − KcG2BL
9
Substituting Equations (5) and (8) into Equation (2) gives the following:
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dcGBL
dt
k2 KcGBL (cGBL + cA 0 − cGBL0 )
2KcGBL + KcA0 − KcGBL0 +1
= −
(9)
To fit the equation, the initial equilibrium concentration of GBL should be obtained according
to Equation (1). The relationship between the initial equilibrium concentration of A, I and GBL
(
cA* 0
,
cI*0 and cG* BL0 ) can be expressed as the following:
cA* 0 = cG* BL0 + cA0 − cGBL0
(10)
(11)
cI*0 = cGBL0 − cG* BL0
Combining Equations (1), (10) and (11), the initial equilibrium concentration of GBL can be
calculated from Equation (12).
KcGBL0 − KcA0 −1+ (KcA 0 − KcGBL0 +1)2 + 4KcA 0
2K
cG* BL0
=
(12)
The equilibrium constant, K, was first determined by Equation (1) based on the experimental
data (Figure 9). As shown in the figure, Hypothesis 1 caused the red points within 3 min, which is
a significant deviation from the kinetic model, while Hypothesis 2 caused the red points beyond 8
min. For example, methylamine was more reactive than ethylamine in the preparation of
NMP/NEP, which should cause a smaller deviation from Hypothesis 1. For this reason, the red
points within 3 min that significantly deviated from the kinetic model also appeared in the kinetic
model of NEP. All the red points were excluded in the determination of
fitted values at different temperatures are listed in Table 1. According to these results, increasing
the reaction decreased the value of , indicating that the forward reactions from GBL to I were
K. The corresponding
K
K
exothermic. Afterwards, k2 for NMP/NEP was obtained according to Equation (9) by fitting
experimental data, and the applied initial concentrations were the initial equilibrium
concentrations of GBL. The fitted rate constant k2 values at different temperatures are listed in
Table 1.
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The fitted
K
and k2 values at different temperatures were employed to construct a van’t Hoff
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plot and an Arrhenius plot (Figure 10) according to Equations (3) and (4), respectively. The
Φ) and entropy (ꢂ Φ) for the van’t Hoff correlation and the activation energy
reaction enthalpy (ꢂ
H
S
8
9
(
E2) and preꢀexponential factor (A2) for the Arrhenius correlation could be obtained from the slope
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and intercept, respectively. The results are given in Table 2.
Based on the obtained kinetic parameters, the corresponding equilibrium constants,
K, and
rate constants, k2, of the kinetic model at 260, 275 and 290 °C were calculated. Then, the kinetic
model was applied to calculate the reagent concentrations versus residence time for NMP/NEP
(Figures 8 and S1, solid lines). As shown in the figures, the calculated values were in good
agreement with the experimental values. The deviation between the measured and calculated
results was mainly due to the hypotheses employed in the kinetic model.
The kinetic model was applied to predict the conversion of GBL and yield of NMP/NEP at
different initial GBL concentrations and reaction temperatures to investigate the validity of the
model. The values predicted by the above kinetic model were compared with the observed
experimental data as shown in Figure 11. The model represents the data reasonably well, with
±10 % errors, which confirmed that it can effectively guide the preparation of NMP/NEP. In
addition to NMP and NEP, the other Nꢀalkylꢀ2ꢀpyrrolidones including Nꢀoctylꢀ2ꢀpyrrolidone,
Nꢀdodecylꢀ2ꢀpyrrolidone and Nꢀ(2ꢀhydroxyethyl)ꢀ2ꢀpyrrolidone are of practical application
value.1 The kinetic model proposed in this paper could be well applied to their syntheses processes
if the reactions are well consistent with the hypotheses adopted in this kinetic model.
1
(a) NMP
0.8
GBL, cal
I, cal
0.6
NMP, cal
GBL, exp
0.4
NMP, exp
I, cal
0.2
0
0
6
12
18
24
30
t / min
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(b) NEP
0.8
7
GBL, cal
8
9
I, cal
0.6
0.4
0.2
0
NEP, cal
GBL, exp
NEP, exp
I, cal
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0
6
12
18
24
30
t / min
Figure 8. Comparison of measured and calculated concentrations versus residence time at
different temperatures for (a) NMP and (b) NEP. Reaction conditions: reaction temperature 290 °C,
residence time 0~26.6 min, GBL concentration 1.00 mol/L, and Mꢀratio 1.2.
Table 1. Equilibrium constants,
K
, and kinetic rate constants, k2, for the syntheses of NMP
and NEP
Temperature
K
(NMP)
K
(NEP)
k2 (NMP)
k2 (NEP)
oC
L·molꢀ1
7.12
L·molꢀ1
4.86
minꢀ1
0.152
minꢀ1
0.132
260
275
290
5.92
5.05
3.87
3.10
0.261
0.425
0.226
0.456
Table 2. van’t Hoff and Arrhenius parameters determined from the current work
van’t Hoff Arrhenius
Category
ꢂ
HΦ
ꢂ
SΦ
E2
A2
kJ·molꢀ1
ꢀ28.60
J·molꢀ1·Kꢀ1
ꢀ37.34
kJ·molꢀ1
85.58
NMP
NEP
3.70×107
1.49×109
ꢀ37.41
ꢀ57.01
102.74
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9
(a) NMP
260
290
290
275
275
T / oC
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12
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4
0
0
6
12
18
24
30
t / min
16
12
8
(b) NEP
260
260
275
275
290
290
T / oC
4
0
0
6
12
18
24
30
t / min
Figure 9. Estimated equilibrium constants, K, from the kinetic model for (a) NMP and (b)
NEP at different temperatures
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2.5
KꢀNMP
KꢀNEP
(a)
lnK = 3439.5/T ꢀ 4.4909
R² = 0.9993
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1.5
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lnK = 4499.4/T ꢀ 6.8573
R² = 0.9999
0.5
0.00176
0.0018
0.00184
0.00188
0.00192
1/T / (1/K)
ꢀ0.5
ꢀ1
k2ꢀNMP
k2ꢀNEP
(b)
lnk 2 = ꢀ10293/T + 17.426
R² = 0.9998
ꢀ1.5
ꢀ2
lnk 2 = ꢀ12357/T + 21.123
R² = 0.9918
ꢀ2.5
0.00176
0.0018
0.00184
1/T / (1/K)
0.00188
0.00192
Figure 10. (a) van’t Hoff correlation between the temperature and equilibrium constant, K; (b)
Arrhenius correlation between the temperature and rate constant, k2
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8
80
60
40
20
0
X(NMP)
Y(NMP)
X(NEP)
Y(NEP)
+10%
ꢀ10%
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0
20
40
60
80
100
Predicted
X / Y (%)
Figure 11. Comparison of experimental and predicted GBL conversion (
X) and NMP/NEP
yield (
Y)
CONCLUSION
A novel continuousꢀflow strategy was developed for the synthesis of NMP/NEP in a highly
controlled and safe manner to improve the process efficiency. Various conditions (temperature,
residence time, Mꢀratio, GBL concentration, WC and presence of H3BO3 catalyst) were explored
under continuousꢀflow conditions to elucidate the synthesis of NMP/NEP. Up to 94.7 % yield of
NMP and 93.9 % yield of NEP could be achieved in the continuousꢀflow microreactor with a GBL
concentration of 1.00 mol·Lꢀ1 and an amine concentration of 1.20 mol·Lꢀ1 at 26.6 min and 290 °C.
The preparation of NMP/NEP using microreactors could be easily applied to a larger scale
reaction by simply numberingꢀup. In addition, the kinetic model, proposed based on the reaction
mechanism were proved to be valid for guiding the design and optimization of the preparation of
NMP/NEP.
EXPERIMENTAL SECTION
All chemicals were purchased from commercial sources and were used without further
purification. The contents of methylamine and ethylamine in their aqueous solutions were
determined by titration. The viscosities were measured by a viscometer from Brookfield. Gas
chromatography analyses were carried out on an Agilent 7890A gas chromatography. The
conditions for gas chromatography were as follows: PEGꢀ20 M column 30 m × 0.32 mm × 0.5 ꢃm,
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carrier gas: nitrogen, injection temperature: 260 °C, detector temperature: 270 °C, and oven
temperature: 150 °C (1 min hold ) to 260 °C ( 20 °C / min, 1 min hold ).
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Figure 12 Schematic overview of the continuousꢀflow microreactor system for the
preparation of NMP/NEP
A schematic overview of the continuousꢀflow microreactor system for the preparation of
NMP/NEP is shown in Figure 12. In the experiments, both aqueous methylamine/ethylamine and
GBL were dissolved in glycol and delivered into the system by metering pumps (Series II pump,
Chrom. Tech. Inc., USA). The check valves were installed in the reaction system to prevent the
reverse flow of the reactants. The mixing was performed in a stainless steel Tꢀshaped mixer with a
1.2 mm diameter throughꢀhole. The mixing time was in the order of hundreds of milliseconds,29, 30
which was far less than the reaction time and thus could be neglected in the analysis. A stainless
steel delay loop (internal diameter 0.6 mm) was directly connected to the micromixer to serve as
the reactor channel for the synthesis of NMP/NEP. The whole delay loop was divided into two
sections. One section was the reaction loop, which was 9.4 m long and was immersed in the air
bath to control the reaction temperature. The other section was the termination loop, which was
0.5 m long and immersed in an ice water bath to quench the reaction. The reaction system was
pressurized to 750 psi by a backꢀpressure valve to avoid the boiling point limitations. The
residence time inside the reaction loop was accurately controlled by altering the flow velocity.
Among all employed flow conditions, the Reynolds number for the reaction mixture in the delay
loop was between 0.5 and 30, indicating laminar flow inside the microreactor. During the
experiments, the quenched samples were collected for analysis after the system reached the steady
state. All samples were analyzed by GC 7890A with an FID detector.
AUTHOR INFORMATION
Corresponding Author
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*Eꢀmail address: gwchen@dicp.ac.cn
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NOTES
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
Authors would like to thank Hengqiang Li and Jiansheng Chu (engineers in our research
group) for their help in the fabrication of microreactor and the building of experimental setup. We
gratefully acknowledge the financial supports for this project from National Natural Science
Foundation of China (Nos. U1608221, 21506205 and U1662124), DICP (ZZBS201706), the
Youth Innovation Promotion Association CAS (No. 2017229) and the STS program of CAS.
SUPPORTING INFORMATION
Supporting Information Available: Comparison of measured and calculated concentrations
versus residence time at 260 and 275 °C for NMP/NEP.
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