DOI: 10.1002/slct.201900527
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Full Papers
z Catalysis
Acetone Iodination Kinetics in Flow with Online UV
Monitoring and Continuous Control
Xingjun Yao,*[a] Qiulin Deng,*[b] Shuhao Wang,*[a] Wei Wang,[a] YIxin Hou,[a] Zhibin Gao,[a]
Yingshuang Wu,[a] and Zengjing Guo[a]
Kinetics of acetone iodide synthesis was investigated in a
microchannel reaction system mainly composed of a micromixer and a tubular reactor. This system can be used as a plug
flow reactor, as proved by the low variance (0.006) of residence
time distribution detected by a step stimuli–response tracer. An
online ultraviolet monitoring system was built to fast and
reliably detect the transmittance of the flowing solution.
Reaction kinetics was tested at different reactant concentrations and temperatures (35-50 °C). Second-order kinetics concerning acetone and HCl was identified with activation energy
of 67.86 kJ/mol.
Introduction
The reactions between ketone (or aldehydes) and halogen are
widely involved in organic preparation ( and polymerization.[1]
Research on the reaction kinetics is contributive to revealing
the underlying rules,[2] and the kinetic data guide more
processes involving the reagents of carbonyl (or aldehyde) and
halogen group. Acetone iodination is a complex consecutive
reaction consisting of two successive but distinct subreactions.
Eliana Tapuhi et al. investigated the kinetics of acetone
iodination and bromination in basic solutions buffered with
trifluoroethanol, and found the rate-controlling step was
enolate ion halogenation.[3] However, accurate determination
of the kinetic constant is difficult due to the instability and
complication of the halogenating species in basic solutions.
Moreover, it is a monohalogenated reaction for an acid catalyst.
The side reactions (e. g. biiodine and triiodine reactions) can be
weakened or avoided when the catalyst of iodination was HCl,
which increased the iodine conversion. Reaction (1) is the
enolization of acetone, which is a very slow reversible reaction;
Reaction (2) is the iodization of enol, which is a fast and
complete reaction (Scheme 1).
Thus, acetone enolization is the rate-determining step for
the whole reaction of acetone iodination, and its reaction rate
depends on the concentrations of acetone and hydrogen ion.[4]
An aldehyde or ketone with a plurality of α-hydrogen,
[a] Prof. X. Yao, Prof. S. Wang, W. Wang, Y. Hou, Z. Gao, Y. Wu, Z. Guo
School of Chemistry and Chemical Engineering, Liaocheng University,
No1 Huhan Road, Liaocheng 252059, P. R. China
E-mail: y_xingjun@163.com
shuhao_wang@sina.com
[b] Prof. Q. Deng
School of Materials Science and Engineering, State Key Laboratory for
Environment-friendly Energy Materials, Southwest University of Science
and Technology, 59 Qinglong Road, Mianyang 621010, P. R. China
E-mail: qiulindeng0001@163.com
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/slct.201900527
ChemistrySelect 2019, 4, 5116 – 5121
Scheme 1. reaction mechanism of acetone iodination.
monohalogenated under acidic conditions, can be isomerized
to a halogenated enol, since the orphan electrons on the
halogen atom form a PΠ conjugate with C=C. Moreover, the
monohalogenated enol is more stable than the unhalogenated
enol and is easily formed but unreactive, contributing to the
formation of intramolecular hydrogen bonds, and thus mainly
monohalogenation is conducted. Accurate kinetic information
is critical for the design and use of a reactor, but is hard to
obtain for acetone iodination. Savannah explored the kinetics
of acetone iodine synthesis in a glass petri dish reactor under
isothermal condition at 30–45 °C for > 1 d and found overall
second-order kinetics, such as first order kinetics involving both
reactants.[5] In the transition state of the rate-controlling step of
acid-catalyzed ketonization, proton was transferred to carbon
when the bond between the enol oxygen and its hydrogen
atom was intact.[6] The reaction rate equation, reaction orders,
rate constant and activation energy can be determined by
using 8 groups of temporal changes of transmittance rates in a
50.0 mL reaction mixer during each experiment. However,
much waste is generated to cause serious pollution. Additionally, in this autocatalytic reaction, when more acid is generated,
the reaction proceeds more quickly, which complicates the
measurement method. Recently, the new process strengthening method of microstructure reactors is applied to autocata5116
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lytic reactions, such as biological process,[7] halogenation[8] and
nitrification reaction.[9] Pompano et al. showed the mixing rate
affects autocatalytic systems in two ways: 1), if the initial
activator concentration is near the threshold, both the complex
biochemical reaction of blood clotting and the chemical analog
can be started or stopped by changing the mixing rate; 2), if it
is far above the threshold, these reactions can be decelerated
by rapid blending.[6] They also explained the underlying
mechanism by using the Damkohler number to denote the
balance between reaction and mixing rates, and validated
through 2-D numerical simulation of threshold kinetics in an
irregularly mixed plug.[5] Niedl et al. increased the yields of
nitrophenols from phenol nitration in a microreactor irrespective the use of CH3CO2H, and attributed the increase to the
improvement in heat exchange, mixing rate and radical
migration in a fixed volume. Besides the small reacting volumes
at any time, the exothermic reactions can be better controlled
by the nonstop phenol nitration in a microreactor. The
occurrence of nitration within the microreactor can be ensured
only by more concentrated conditions and absence of solvent
and H2SO4 or CH3CO2H. Thus, the improved yields and process
safety make the microreactor technology applicable to autocatalytic reactions such as industrial nitration.[7] New methods
based on such improvement without causing extra problems
are needed.[10a–h] Yao et al. raised the yield of acetic acid esters
to 70.1%, 74.0%, 92.2% and 97.2% in a microchannel reactor
with the presence of ethanol, methanol, n-butanol and npropanol, respectively, during the 14.7 min of residence.[11]
Aromatic nitration of acetyl guaiacol is highly exothermic and
fast, and can be better controlled at high efficiency in the
microreactor due to the acceleration of mixing and heat
transfer. The yield of the desired 5-nitroguaiacol was 90.7%
under the optimized conditions of 40% nitric acid, a nitric acidacetyl guaiacol molar ratio of 2.6, temperature at 120 °C, and
residence time of 2 min. The microreactor outperformed the
traditional batch reactor owing to the higher yield and
selectivity, much shorter reaction time, and less use of nitric
acid.[12] Here, this need was addressed by describing a kinetic
determination method using a continuous-flow microchannel
reactor.
The microchannel reactor was developed to promote the
acetone iodination under acid catalyzed conditions. Then the
kinetics of acetone iodination in the microchannel reactor as
well as the residence time distribution was studied. A
comprehensive mathematic kinetic model was built based on
the results.
stay on one element reaction of iodinated acetone; Otherwise,
the reaction does not. The test wavelength changes with the
iodine concentration, which thus should not range too largely.
The reading of the absorbance should be in a reasonable range
so as to reduce the error caused by the reader. When the
concentration of each substance is selected, the reaction time
of each reaction system should not be too long. Meanwhile,
high HCl concentration and rapid reaction rate make few
measurement points available and increase the random error;
however, the smaller solution concentration leads to the slower
reaction rate and thereby prolongs the experimental time.
Considering the relationship between iodine consumption rate
and iodine concentration as well as the range of absorbance
measurement, we set the test wavelength at 565 nm and the
concentrations of acetone(Figure 1a), acid and iodine at 0.1-0.4,
Results and Discussion
Selection of test wavelength and solution oncentration
The main contents of kinetic experiments are to obtain a series
of reliable data with experimental methods and to establish a
kinetic equation based on these data. Generally, the reaction
rate of acetone iodization is measured by spectrophotometry.
When the iodine concentration is far smaller than the acetone
and acid concentrations (Cacid, Cacetone @ CI2), the reaction will
ChemistrySelect 2019, 4, 5116 – 5121
Figure 1. Absorbance of different iodine solution concentrations. (a) Absorbance versus wavelength; (b) Calibration curve of TU1810 ultraviolet visible
spectrophotometer
0.1-0.3 and 0.0001-0.003 mol⋅L 1 respectively.[13] We also provide the calibration curve to ensure that the concentration of
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iodine solutions does not saturate the detector of the UV-Vis
spectrometer (Figure 1b). (Adj.R-square is 0.9978).
Determination of residence time distribution (RTD)
Any ideal plug flow reactor (PFR) can be verified by RTD, which
measured using a stimuli– response tracer here. The tracer was
erioglaucine disodium salt (EDS; CAS No. 3844–45-9), a reactive
brilliant blue dye, and its levels were detected by an ultraviolet
visible (UV–vis) spectrophotometer at 629 nm.
The F curve of RTD in the reaction system was identified
using a step input. The reaction system was first fed with pure
water and an EDS water solution separately through two
syringe pumps. When the EDS concentration in the effluent
became constant and zero, the EDS pump was stopped and
restarted, respectively. Moreover, the liquid was sampled at the
outlet every 1 min. The F curve shows the temporal ratio of
EDS concentration in the effluent to that in the feed (Figure 2).
1
FðqÞ ¼ ½1
2
�
erf
�
pffiffiffiffiffi ð1 qÞ
Bo pffiffiffiffiffi �ð4Þ
4q
The residence time function was deduced from the
response signal of an auto-induced step function of tracer
concentration (Figure 2). Bo was determined by least-square
fitting the response signal curve. Then the dispersed plug flow
model was numerically fitted with Bo as the only parameter,
and was optimized at Bo of 13200. Surprisingly, this result
indicates low axial dispersion and suggests the microchannel
reactor is PFR.
Effect of feed flow rate on the synthesis of acetone
iodination
The same flow rate of acetone solution and the HCl and I2
mixed solution was investigated with a 0.4 mol/L acetone,
0.2 mol/LHCl, 0.006 mol/LI2, a liquid hourly space velocity
(LHSV) of 313.52 h 1, and a reaction temperature of 45 °C. The
results are presented in table 1. It shows that with the increase
Table 1. Iodination reaction at a given LHSV of 313.52 h 1 in the microchannel delay loop reactor with various flow rates and lengths of the
microchannel reactor
Figure 2. F curve of RTD measured by a step stimuli–response tracer method
at total flow rate of 4.0 mL/min.
Based on the results, the residence time at the stainless steel
tube length of 5 m was averaged to be 57.41 s, with the
variance (σ2θ) of 0.006.
The residence time behavior in flow channels was illustrated using a reported dispersion model.[14] Herein, the backmixing degree was denoted by the dimensionless Bodenstein
number Bo:
Bo ¼
uL
Dax
(3)
where the dispersion coefficient Dax reflects the influence of
axial back mixing in one parameter. With Eq. 3, the F-curve
under open boundary conditions (i. e., dispersion continuity)[15]
can be illustrated as follows:
ChemistrySelect 2019, 4, 5116 – 5121
Each feed flow rate
(ml/min)
Length of microchannel delay
loop (m)
Each feed flow rate
(ml/min)
1.0
1.5
2.0
2.5
3.0
1.0
2.50
3.75
5.00
6.25
7.50
2.50
46.3
51.2
58.7
60.4
62.8
46.3
of the total flow rate from 1.0 to 1.5 to 2.0 mL/min (corresponding to the increase of microchannel length from 2.50 to 3.75 to
5.00 m), the transmittance increases sharply with an increment
of 7.5%. Further increase of the flow rate to 2.5 and to 3.0 mL/
min, results in the slightly increase of transmittance. This may
be ascribed to the fact that the shear stress inside the pipeline
can eliminate the concentration gradient and temperature
gradient with the increase of the flow rate. The feed flow rate
of 2.0 mL/min was selected by the subsequent kinetic experiment.
Determination of reaction order, reaction rate constant and
active energy
A reliable kinetic model based on the reaction mechanism
(Eqs. (1) and (2)) was built and used to uncover the kinetics of
acetone iodination. The reaction order of I2, which did not
severely affect the reaction performance, was ignored in the
kinetic modeling.[13b] Consequently, the newly-designed kinetic
model involved reactants acetone (A) and HCl, which reacted
to form intermediate B, which was further iodinatized into
acetone iodine (E). Based on the reactions under the above
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conditions, the rate-determining step was acetone enolization.
Therefore, a pre-equilibrium among acetone, I2 solution and
HCl could be established and was rarely affected by the very
slow reaction rate from A to B. Thus, the reaction rate r and
rate constant of A and HCl reaction can be described as
follows:
dCA dCE
¼
¼ k � CA � CHþ
dt
dt
r¼
(5)
According to Eq. (2), we have dCE/dt =-dCI2/dt.The change
in iodine concentration could be measured by the UV
spectrophotometer according to the color loss due and then
the loss of iodine, since iodine was the limiting reactant when
the acetone and HCl levels were excessive. If the iodine
concentrations at all time points during the reaction were
measured, dCE/dt can be acquired.
Then integrating both sides of Eq. (5), we could derive the
change of E concentration as follows,
Z
CE2
CE1
Z
dCE ¼
Figure 3. Investigation reciprocal of temperature dependence of the -LnK of
the reaction in microchannel reactor. Reaction conditions: temperature 35–
50 °C, residence time 34.35-149.27 s, 0.4 mol/L A, 0.2 mol/L H + + 0.006 mol/L
I2
t2
t1
K � CA � CHþ � dt
(6)
CE2 CE1 ¼ K � CA � CHþ � ðt2 t1 Þ
According to Lambert-Beer’s law,
lgT ¼
e � l � CI2
I dC
ForT ¼ ; E ¼
I0 dt
(7)
dCI2
,C C ¼ CI2 1 CI2 2
dt E2 E1
(8)
Substituting Eqs. (7) and (8) into Eq. (6), K can be written as
follows,
lgT2 lgT1 ¼ K � ðe � lÞ � CA � CHþ � ðt2 t1 Þ
(9)
lgT2 lgT1
1
�
ðelÞ � ðt2 t1 Þ CA � CHþ
(10)
or
K¼
In Eq. (10), ε can be calculated by substituting the transmittance of a known iodine concentration into Eq. (7), as long
as the transmittance of the reactant solution at different time
points was measured (Figure 3), and the A and H + concentrations were known, K can be calculated:
Lnki ðTÞ ¼
Ei
þLnAi
RT
(11)
where T, Ei, R and Ai are the absolute temperature (K),
activation energy (kJ⋅mol 1), universal gas constant
(8.314 J⋅mol 1⋅K 1 ), and pre-exponential factor, respectively.
To detect the temporal variation of reagent concentrations,
kinetic assay conditions in a continuous-flow microchannel
reactor were set at 35, 40, 45 and 50 °C at the A, HCl and I2
concentrations of 0.4, 0.2 and 0.006 mol⋅L 1 respectively. Other
kinetic experiments in Figure 4 show the experimental data
from the given conditions:
ChemistrySelect 2019, 4, 5116 – 5121
Figure 4. Investigation of residence time dependence of the iodination of
acetone in microchannel reactor. Reaction conditions: temperature 45 °C,
residence time 34.35-149.27 s, concentrations (all mol/L): (a) 0.4 A, 0.2 H + +
0.006 I2; (b) 0.4 A, 0.4 H + + 0.006 I2; (c) 0.4 A, 0.2 H + + 0.003 I2; (d) 0.8 A, 0.2
H + + 0.006 I2;
ri ¼
dð LgT%Þ 1
� ðMol=L=SÞ
dt
ei l
(12)
(ri ¼ kCaA � CbHþ � CgI2 ); α, β, γ represent the reaction orders of
A, H +, I2 respectively (Eq. 13). The order of the reaction,
describing the dependence of reaction rate on concentration,
may be figured out by plotting transmittance from each
reaction and adopting the most linear function. Reaction rate ri,
rate constant ki, reaction order and correlation coefficient Ri
detected at 45 °C and feed flow rates 2.0 mL/min were showed
in Table 2. The k fitted at different temperatures is listed in
Table 3.
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Table 2. Kinetic rate constants, reaction rate, reaction orders and correlation coefficient of acetone Iodination (feed flows of acetone solution and the HCl
and I2 mixed solution were both 2.0 mL/min)
Temperature (°C)
Molar concentration (mol/L)
Acetone solution
Mixer of HCl and I2 solution
Ri
ki (mol/L) 1⋅s
45
0.4
0.4
0.4
0.8
-0.99901
-0.99935
-0.99900
-0.99568
9.12E-04
8.33E-04
7.38E-04
10.11E-04
0.2, 0.006
0.4, 0.006
0.2, 0.003
0.2, 0.006
Table 3. Volume flows of acetone solution and the HCl + I2 mixed solution
at 2.0 mL/min
Temperature
(°C)
Molar concentration (mol/L)
Acetone
Mixer of HCl and I2
solution
solution
Ea (KJ/
mol)
Ai (mol/
L) 1⋅s 1
35-50
0.4
0.4
0.4
0.8
67.8637
5.527E7
0.2, 0.006
0.4, 0.006
0.2, 0.003
0.2, 0.006
Reaction rate equation and the possible course of the reaction are as
follows: ri = k⋅CA⋅CH +
r
a¼
Lgð r14 Þ
C
Lgð CA1
Þ
A4
r
r
;b ¼
Lgð r12 Þ
C
þ
Lgð CHH 12 Þ
;r ¼
þ
Lgð r13 Þ
C2
Lgð CII 12 Þ
(13)
2
r¼
1
ri (mol/L)⋅s
1.52E-05
3.33E-05
1.47E-05
4.05E-05
1
α,β,γ
α = 0.9890, β = 1.0363, γ = 0.0957
dCE K1 K2 KCA CHþ CI2
¼
� k1 kCA CHþ ¼ Ktotal CA CHþ
dt
K 1 CHþ þK2 CI2
(20)
If the reaction rate of enol D with I2 is much larger than that
with H +, k2⋅CI2 � k-1⋅CH +, then Eq. (20) can be approximated as
r = dCE/dt � k1kCACH + = Ktotal⋅CA⋅CH +, which is consistent with the
experimental results. When deducing rate equation from
reaction mechanism, steady-state approximation has more
general applicability than the equilibrium state hypothesis, and
more reflects the nature of the reaction mechanism.[16]
Results show the acetone iodination rate is consistent
between experiment and calculation. Further, it is foreseeable
that as the number of carbon atoms in the alkyl chain of the
ketone increases, the volume steric hindrance increases, the
water solubility of the ketone deteriorates (for example, methyl
ethyl ketone, 2-pentanone), and the inorganic acid catalytic
system of the ketone in the aqueous medium convers to
organic acids catalytic system in organic media, the reaction
mechanism will be more complicated.[17]
ð14Þ
Conclusions
ð15Þ
ð16Þ
Reaction (14) reaches equilibrium quickly, and its equilibrium constant is K:
CB ¼ KCA CHþ
(17)
dCD
¼ k1 CB ½k 1 CHþ þk2 CI2 �CD
dt
(18)
dCE
¼ k2 CI2 CD
dt
(19)
A novel continuous-flow microchannel reaction system (containing a micromixer and a microchannel reactor) was designed
for the well-controlled and efficient acetone iodination, and
was confirmed as a plug flow reactor through RTD measurement. The kinetics of the fast and endothermic acetone
iodination was explored in a case study. The iodination
conversion was rapidly and accurately measured online by a
UV spectrometer. This microchannel reaction system is feasible
for studying the kinetics of fast reaction with color change. The
iodination rate can be calculated from r = 5.527E7 exp ( 8.16/
T) CACH +. The reaction rate is independent of the iodine and
thus can be studied under presence of excessive acetone and
HCl. The reaction order and reaction activation energy were
determined to set up the reaction kinetic equation. In all, this
study provides ideas for automatic control of other halogenation reactions of aldehydes and ketones, which will be studied
by our team in the future.
Supporting information summary
Readers can read the experimental section include the
chemicals, materials and experimental processes
Combining Eqs. (17) (18) (19), and using the steady-state
hypothesis dCD/dt = 0, we have:
ChemistrySelect 2019, 4, 5116 – 5121
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Acknowledgements
The authors are very grateful to acknowledge National Natural
Science Foundation of China (Grant No.21706109) and Foundation of Liaocheng University (Grant No. 318011508, 26312160520)
for financial support.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: Acetone Iodination · Kinetics · Microchannel
reactor · Synthesis
[1] a) J. Szudkowska-Fratczak, G. Hreczycho, P. Pawluc, Org. Chem. Front.
2015, 2, 730–738; b) M. Ehrlich, T. Carell, Eur. J. Org. Chem. 2013, 77–83.
[2] M. Amatore, T. D. Beeson, S. P. Brown, D. W. C. MacMillan, Angew. Chem.Int. Edit. 2009, 48, 5121–5124.
[3] E. Tapuhi, W. P. Jencks, J. Am. Chem. Soc. 1982, 104, 5758–5765.
[4] L. Uson, M. Arruebo, V. Sebastian, J. Santamaria, Chem. Eng. J. 2018, 340,
66–72.
[5] S. Carroll, A. Hughes, chemistry and physics lab, Department of
Chemistry University of Tennessee, Knoxville, TN, 2014.
[6] G. E. Lienhard, T.-C. Wang, J. Am. Chem. Soc. 1968, 91, 1146–1153.
[7] R. R. Pompano, H. W. Li, R. F. Ismagilov, Biophys. J. 2008, 95, 1531–1543.
[8] R. Niedl, I. Berenstein, C. Beta, Phys. Chem. Chem. Phys. 2016, 18, 6451–
6457.
ChemistrySelect 2019, 4, 5116 – 5121
[9] a) L. Ducry, D. M. Roberge, Angew. Chem.-Int. Edit. 2005, 44, 7972–7975;
b) N. Kockmann, D. M. Roberge, Chem. Eng. Technol. 2009, 32, 1682–
1694.
[10] a) F. Zhou, B. Y. Zhang, H. C. Liu, Z. H. Wen, K. J. Wang, G. W. Chen, Org.
Process Res. Dev. 2018, 22, 504–511; b) C. C. Du, J. S. Zhang, G. S. Luo,
Aiche J. 2018, 64, 571–577; c) J. Yue, Catal. Today 2018, 308, 3–19; d) L.
Tamborini, P. Fernandes, F. Paradisi, F. Molinari, Trends Biotechnol. 2018,
36, 73–88; e) A. Tanimu, S. Jaenicke, K. Alhooshani, Chem. Eng. J. 2017,
327, 792–821; f) A. Kecskemeti, A. Gaspar, Talanta 2018, 180, 211–228;
g) X. J. Yao, Y. Zhang, L. Y. Du, J. H. Liu, J. F. Yao, Renew. Sust. Energ. Rev.
2015, 47, 519–539; h) A. J. Bissette, S. P. Fletcher, Angew. Chem.-Int. Edit.
2013, 52, 12800–12826.
[11] X. J. Yao, J. F. Yao, L. X. Zhang, N. P. Xu, Catal. Lett. 2009, 132, 147–152.
[12] C. Y. Zhang, J. S. Zhang, G. S. Luo, J. Flow. Chem. 2016, 6, 309–314.
[13] a) D. Bascone, P. Angeli, E. S. Fraga, Nucl. Eng. Des. 2018, 332, 162–172;
b) G. Yueshu, Basic Physical Chemistry Experiment (III). Third edition,
Chemical Industry Press, Beijing, 2004.
[14] N. Zaborenko, M. W. Bedore, T. F. Jamison, K. F. Jensen, Org. Process Res.
Dev. 2011, 15, 131–139.
[15] P. Danckwerts, Chem. Eng. Sci. 1953, 2, 1–13.
[16] D. G. Han, Z. D. Gao, P. L. Gao, Physical Chemistry. Second edition,
Higher education press, Beijing, 2009.
[17] a) J. F. W. Keana, R. R. Schumaker, Tetrahedron Lett. 1970, 26, 5191–5194;
b) R. Becker, S. van den Broek, P. J. Nieuwland, K. Koch, F. Rutjes, J. Flow.
Chem. 2012, 2, 87–91.
Submitted: February 8, 2019
Accepted: April 11, 2019
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