Microfluidic electrosynthesis of thiuram disulfides

Article abstract of DOI:10.1039/d0gc03336g

An electrolytic approach to sodium dithiocarbamates based on a microfluidic reactor is proposed for the green synthesis of thiuram disulfides, which are versatile free radical initiators. The electro-oxidation reactions avoid the over-oxidation of sodium dithiocarbamates and the generation of waste salts, which have perplexed the industry for a long time. This microfluidic electrolysis method prevents solid deposition by introducing liquid-liquid Taylor flow into the microchannel, and promotes the synthesis efficiency of thiuram disulfides with the enlargement of the electrode-specific surface area. The highest yield of thiuram disulfide was 88% in the experiment without any oxidation by-products. The Faraday efficiencies of most reactions are higher than 96%, showing the excellent electronic utilization. In addition to improving the environmental friendliness of sodium dithiocarbamate oxidation, the electrosynthesis method helps to create a cyclic technology of thiuram disulfide synthesis via the combination of sodium dithiocarbamate generation in a packed bed reactor. The cyclic technology finally achieved >99% atom utilization in thiuram disulfide synthesis from secondary amines and carbon disulfide. This journal is

Full text of DOI:10.1039/d0gc03336g

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Microfluidic electrosynthesis of thiuram disulfides†
Siyuan Zheng, Kai Wang * and Guangsheng Luo
Cite this: Green Chem., 2021, 23,
582
An electrolytic approach to sodium dithiocarbamates based on a microfluidic reactor is proposed for the
green synthesis of thiuram disulfides, which are versatile free radical initiators. The electro-oxidation reac-
tions avoid the over-oxidation of sodium dithiocarbamates and the generation of waste salts, which have
perplexed the industry for a long time. This microfluidic electrolysis method prevents solid deposition by
introducing liquid–liquid Taylor flow into the microchannel, and promotes the synthesis efficiency of
thiuram disulfides with the enlargement of the electrode-specific surface area. The highest yield of
thiuram disulfide was 88% in the experiment without any oxidation by-products. The Faraday efficiencies
of most reactions are higher than 96%, showing the excellent electronic utilization. In addition to improv-
ing the environmental friendliness of sodium dithiocarbamate oxidation, the electrosynthesis method
helps to create a cyclic technology of thiuram disulfide synthesis via the combination of sodium dithiocar-
bamate generation in a packed bed reactor. The cyclic technology finally achieved >99% atom utilization
in thiuram disulfide synthesis from secondary amines and carbon disulfide.
Received 3rd October 2020,
Accepted 10th December 2020
DOI: 10.1039/d0gc03336g
rsc.li/greenchem
peroxide or chlorine in solution. During the oxidation, thiocar-
boxylic acid is easily over-oxidized to sulfonates and their
Introduction
Thiuram disulfides, also called thioperoxydicarbonic diamides derivatives,10 which lead to high chemical oxygen demand
(1 in Scheme 1), are versatile polysulfide compounds. Since they (COD) of the wastewater. Therefore, batch reactors fed an acid
are able to rapidly decompose into free radicals when heated,1 and oxidant mixture with slow dripping are commonly used in
thiuram disulfides are highly efficient free radical initiators in the synthesis of thiuram disulfides. Moreover, waste salts,
C–S coupling reactions,2,3 oxidative-addition reactions,4 and free such as Na2SO4 and NaCl, have been listed as hazardous
radical polymerization reactions.5 Thiuram disulfides were once wastes by governments, because they containe a lot of organic
developed as medicines to cure chronic alcohol dependence.6 componds as impurities. To improve its environmental friend-
Now they are normally applied as vulcanization accelerators in liness, the use of oxygen was once proposed, instead of strong
the rubber industry. Thiuram disulfides are also fungicides and oxidants, in thiuram disulfide synthesis reaction.11 Although
animal repellents in agriculture.7,8
over-oxidization can be prevented by the decrease of reactant
Traditionally, thiuram disulfides are synthesized in two activity, the low reaction rate and high safety risk of using
steps: (1) a condensation reaction of secondary amine (2 in oxygen in the reaction system containing carbon disulfide still
Scheme 2) and carbon disulfide (CS2) to form dithiocarbamate restricts its industrial application.
and (2) an oxidation reaction of the dithiocarbamate
In addition to the traditional chemical oxidation
(Scheme 2) to form a disulfide bond.9 Since dithiocarbamate approaches, an electrolysis method (Scheme 3) was proposed
is not stable, it has to be converted to ions, for example the in the 1970s with new advantages.9 Employing electrodes to
sodium salt (3) in Scheme 2, which have good water solubility displace chemical reagents, this method has excellent atom
and better stability for storage. However, when transiting economy and more adjustable oxidation ability. More impor-
sodium dithiocarbamate into thiuram disulfide, dithiocarba- tantly, the electrolysis reaction does not produce waste salts,
mate has to be regenerated from the salt solution by adding which is crucial for increasing the environmental friendliness
H2SO4 or HCl, and simultaneously oxidized using hydrogen of thiuram disulfide syntheses. However, the conversion of
The State Key Lab of Chemical Engineering, Department of Chemical Engineering,
Tsinghua University, Beijing 100084, China. E-mail: kaiwang@tsinghua.edu.cn;
Fax: +8610 6278 8568; Tel: +86 10 6278 8568
†Electronic supplementary information (ESI) available: Details of reaction plat-
forms, electrochemical characterization, and HPLC spectra. See DOI: 10.1039/
d0gc03336g
Scheme 1 Structure of thiuram disulfides (R is an alkyl group).
582 | Green Chem., 2021, 23, 582–591
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achieve the synthesis of thiuram disulfides from the basic sec-
ondary amines and carbon disulfide with the assistance of
microfluidic electrosynthesis, which realizes the green syn-
thesis of thiuram disulfides.
Results and discussion
Scheme 2 Conventional reactions for synthesizing thiuram disulfides.
Electrolysis of sodium dithiocarbamate in an electrolyser
Before developing the microfluidic electrosynthesis techno-
logy, we implemented the electrolysis of sodium dithiocarba-
mate via a batch electrolyser at first to understand the charac-
teristics of the oxidation reaction. The synthesis of tetraethyl-
thiuram disulfide (TETD) was selected as a representative,
since it is more widely used in applications. The experiment
started from a 0.15 mol L−1 sodium diethyldithiocarbamate
(NaEt2DTC) aqueous solution, whose cyclic voltammetry on a
Pt work electrode was detected by a workstation (PARSTAT
Scheme 3 Electrolysis of sodium dithiocarbamate to generate thiuram
disulfide.
3000A-DX, AMETEK Inc.) with
a 3-electrode electrolyser
sodium dithiocarbamate was only in the range of 10% to 25%
in the literature,12 and still needs improvement. In addition,
different from the study focusing on the electrosynthesis of
disulfides in liquid states,13 the sediment of thiuram disulfide
on the electrode finally limited the application of this
advanced synthesis method.
(Fig. S1 in the ESI†). Fig. 1(a) shows the result. The growth of
oxidative current above 0.5 V in the positive scan shows that
the electrolysis of NaEt2DTC is accessible at low potentials in
contrast to standard calomel electrode. No other oxidative
peaks were observed at less than 3 V. An irreversible process is
shown by the negative scan. The potential scan was performed
for 2 cycles, and the second cycle showed much lower oxidative
current for the deposition of TETD on the anode during the
electrolysis process. Based on the idea of in situ dissolution of
thiuram disulfide during electrolysis, toluene, with acceptable
solubility of TETD (about 73 g in 100 g toluene at 25 °C), was
employed, and the result is given in Fig. 1(b). 100 mL toluene
and 100 mL NaEt2DTC aqueous solution formed an emulsified
electrolyte in the electrolysis experiment. Although the oxi-
dative current of the second scan in Fig. 1(b) was still a little
lower than in the first scan, the improvement of the electroly-
sis environment due to this solvent dissolution method exhi-
bits its advantage. A photo in the ESI (Fig. S6a†) shows the
electrodes during the multiphasic electrolysis experiment.
After studying the cyclic voltammograms of NaEt2DTC elec-
trolysis, a potentiostatic electrolysis experiment was carried
With the development of electrochemical technologies and
equipment, the microfluidic electro-oxidation method opens a
new door to implement the electrosynthesis of thiuram disul-
fides. Microfluidic electrosynthesis, also called flow electro-
synthesis and microreaction electrosynthesis,14,15 has the
advantages of microfluidics, flow chemistry, and electro-
chemistry technology,16–19 which overcomes the difficulties of
conventionally organic synthesis by creating a new reaction
method. The investigation of microfluidic electrosynthesis also
helps us to understand more about flow and transport of the
electrochemical process.20 The distances between electrodes in
microfluidic reactors are greatly reduced promoting ionic con-
duction
by
reducing
the
ohmic
resistance.16,18,21
Microchannels are employed as the reaction chambers, which
improve the mass and heat transfer rates of reactions in con-
trast to the thick chamber in traditional electrolysers.22,23
Moreover, the regular flow patterns in micro-fluidic reactors,
such as liquid–liquid parallel flow that employs stable laminar
fluids, are able to improve the controllability of electro-
chemical reactions.24,25 In addition, the microfluidic electro-
synthesis reactor is also an important element of the flow
chemistry system,26 which is able to achieve end-to-end
organic chemical production.27
In this paper, a microfluidic electrosynthesis method for
the preparation of thiuram disulfides is proposed, which
employed sodium dithiocarbamate electrolysis in microchan-
nel reactors with parallel electrodes. A multiphasic electrolysis
process was proposed to dissolve thiuram disulfides on elec-
trodes in situ to avoid solid sediment. The electrolytic method
exhibits excellent yields, production purities, and Faraday
Fig. 1 Cyclic voltammograms of NaEt2DTC solutions on Pt electrodes
at 25 °C. (a) Scans of a 150 mL 0.15 mol L−1 NaEt2DTC aqueous solution.
(b) Scans of an emulsified solution with 100 mL 0.15 mol L−1 NaEt2DTC
efficiencies. A solution cyclic technology is finally created to aqueous solution and 100 mL toluene. Both scan rates were 0.1 V s−1
.
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Table 1 Results of batch electrolysis experiment using 0.15 mol L−1
NaEt2DTC aqueous solution with toluene as the solvent
out with a multiphasic system containing 100 mL of 0.15 mol
L−1 NaEt2DTC solution and 100 mL toluene in the batch elec-
trolyser. Within 100 min of electrolysis at 2.0 V, only the peaks
of NaEt2DTC, toluene, and TETD were obviously observed in
the HPLC spectra after electrolysis (Fig. S9†). According to our
previous result,28 the over-oxidation products also have UV
absorbance at 254 nm, which is the HPLC detection wave-
length in this study, but they were not detected. Another
advantage of employing toluene is its weak wetting ability on a
Pt electrode, which provides better contact of NaEt2DTC solu-
tion with the anode. Fig. S5(a) and S5(b)† show that the
Potential
(V)
NaEt2DTC solution/
Electrolysis time Yield of
toluene (mL mL−1
)
(min)
TETD (%)
2.0
2.0
2.0
2.0
2.0
100/100
100/100
100/100
100/100
100/100
20
40
60
80
100
2%
4%
7%
11%
15%
liquid–liquid contact angle of toluene on a platinum surface is distance between electrodes is also best to reduce to a small
about 100°. The electrolysis reaction was also found to have value to increase the electrode specific surface area in the flow
little effect on the wetting property of toluene. Above all, cell and maintain the stability of liquid–liquid segmented flow
Fig. 2(a) shows a schematic of the electrolysis process. At the via the capillary effect. Based on this idea, a microchannel
anode, Et2DTC− loses an electron to form a free radical,29 reactor containing platinum electrodes was created as shown
which quickly self-condensed to TETD. Then, TETD moves to in Fig. 3. In the centre of the reactor, a 61, 97, or 245 mm long
the organic phase, after it contacts with the toluene droplets. microchannel with 2 mm width was curved in 0.3 mm thick
H2 is generated at the cathode, which leaves NaOH in the fluorinated ethylene propylene (FEP) plates working as the
aqueous phase. Although effective mixing of the electrolyte reaction channel. Beside the channel plate, Pt electrodes were
solution and toluene had been achieved in the experiment, the parallelly placed. The channel thickness was selected based on
TETD yields of a series of experiments in the batch electrolyser the balance between reactant residence time and electrode dis-
were found only between 2% and 15%, even at 2.0 V electroly- tance, which had increased the specific area of the work elec-
sis potential as shown in Table 1. This phenomenon implies trode to 33 cm2 mL−1, more than 4000 times that in the batch
that the small specific area of the work electrode (2 cm2 per electrolyser. Pt wires were welded on both electrodes to
250 mL) in the batch reactor and random contact of toluene connect to the external circuit. The channel plate was sealed
droplets on electrodes influence the apparent rate of the reac- by 0.5 mm Teflon plates. The sealing plates were sandwiched
tion, which should be improved using a more advantageous by polyvinylidene fluoride (PVDF) modules for connection
reactor.
with tube fittings. The whole reactor was finally fixed by shells
with fastening screws. Both wires and tubes (perfluoroalkoxy
alkanes, PFA) in this reactor were sealed by commercial fittings
(PEEK, Idex Health & Science) as shown in Fig. 3(b). Some
photos of the reactor are given in Fig. S2(a) and (b) in the ESI.†
Employing the microfluidic reactor as the core equipment,
we built a continuous electrosynthesis reaction platform as
shown in Fig. 4(a). In this platform, sodium dithiocarbamate
solution and toluene, delivered by continuous syringe pumps
(MSP1-E1, Longer) individually, were premixed in a biphasic
mixer, which had a coaxial internal structure.30,31 Fig. S2(c)†
shows that the interior of the mixer was a stainless-steel capil-
lary with 0.6 mm outer diameter, and the tunnel of the mixer
was a PFA tube with 1.0 mm inner diameter (Idex Health &
Science). Both the tube and the capillary were assembled in a
Tee-connector (PEEK, Idex Health & Science). Sodium dithio-
carbamate solution from the capillary was dispersed as dro-
plets in toluene, forming a regular liquid–liquid Taylor
flow32,33 in the tube before flowing into the microfluidic
reactor, as shown by Fig. 4(b). The droplet length was consist-
ent in each test, but it varied from 1.4 to 2.5 mm in different
tests due to variation of flow rates. The regular flow pattern
ensured a periodic electrolysis and electrode washing, which
maintained the reaction stability. However, H2 from the
cathode mixed into the biphasic mixture, making the reaction
a gas–liquid–liquid triphasic system. Due to the appearances
of bubble and droplet coalescence, the droplet and bubbles
are not uniform at the outlet.
Microfluidic electrosynthesis of thiuram disulfides
In order to develop an efficient electrolysis reactor to syn-
thesize thiuram disulfides, an ideal reaction cell should have a
structure shown in Fig. 2(b). The aqueous and the organic
phases flow alternately through parallel electrodes to continu-
ously carry out the oxidation and dissolution processes. The
Fig. 2 Schematics of electrolyses of NaEt2DTC solution in multiphasic
reactors. (a) In batch electrolyser with stirring flow. (b) In microchannel
reactor with segmented flow. The anode region shows the main reaction
to create TETD, and the cathode region shows the generation of H2
bubbles and the formation of NaOH in the aqueous phases.
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Fig. 3 Schematics of the microfluidic reactor for the electrosynthesis of thiuram disulfides. (a) Assembling sequence of the reactor. Different
materials are shown by different colours. (b) The assembled reactor and its connections.
Fig. 4 Continuous reaction platform for the electrosynthesis of thiuram
disulfides. (a) Schematics of the microfluidic platform. (b) Pictures of the
liquid–liquid Taylor flow at the inlet of the microfluidic reactor and the
gas–liquid–liquid triphasic flow at the outlet of the reactor. Fig. S2(d)†
shows a picture of the microfluidic reaction platform in the ESI.†
With the microfluidic electrosynthesis platform, continuous
electrolysis of NaEt2DTC solution was carried out. The effect of
cell potential was first investigated. Fig. 5(a) shows the linear
sweep voltammetry on the Pt anode of the microfluidic reactor
with the opposite Pt sheet acting as both the counter electrode
Fig. 5 Current curves of electrolysis experiment via the microfluidic
electrosynthesis reactor. (a) Positive scan of NaEt2DTC solution in
and reference electrode. Different from the cyclic voltammetry
experiments in the batch electrolyser, the segmented flow and
the generation of hydrogen bubbles in the reaction channel
led to oscillating currents, which had been observed in other
previous reports.34,35 After smoothing the current curves, a
peak current was found at about 2.0 V, and the curves of two
scans fit well with each other. Considering that low voltage
would lead to a low reaction rate, we further carried out a
potentiostatic electrolysis experiment in the range of 2–3 V.
Fig. 5(b) shows the results. Although higher voltage led to
larger current, a spontaneous emulsification phenomenon was
observed in the outlet solution at the voltage more than 2.0 V,
which brought difficulty in phase separation. Besides, NaOH is
one of the products of the cathodic process and a competitive
liquid–liquid Taylor flow. The experiment was carried out at 0.05 mol
L−1 NaEt2DTC, 0.5 mL min−1 total flow rate, 1 : 1 flow rate ratio of liquid
phases, 0.037 mL reactor volume, and 0.01 V s−1 potential scan rate. (b)
Potentiostatic electrolysis of NaEt2DTC solution via the microfluidic
electrolysis reactor. The experiment was carried out at 0.05 mol L−1
NaEt2DTC, 1.5 mL min−1 total flow rate, 2 : 1 flow rate ratio of the
aqueous phase to the organic phase, and 0.037 mL reactor volume.
Smoothing was carried out by MATLAB 2019.
reaction between OH− and Et2DTC− exists under electrolysis
potential more than 2.0 V, according to Fig. S7.† Thus, 2.0 V
seems to be an optimized potential from the engineering
point of view. Fig. S6(b) and S6(c)† show the electrode surfaces
after electrolysis. Since TETD had been well dissolved in
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Table 2 Effects of different operating parameters on the electrosynthesis of TETD at 2.0 V (25 °C)
Total flow rate of liquids
Reaction channel
volume (mL)
Flow rate ratio of NaEt2DTC solution
to toluene (v/v)
Concentration of NaEt2DTC
TETD yield
(%)
Entry
(mL min−1
)
(mol L−1
)
1
2
3
4
5
6
7
8
0.5
0.7
1.0
1.2
1.5
1.8
1.0
1.0
1.0
1.0
1.0
1.0
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.06
0.06
0.06
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 3
2 : 3
3 : 1
1 : 1
1 : 1
1 : 1
0.075
0.075
0.075
0.075
0.075
0.075
0.075
0.075
0.075
0.140
0.250
0.490
69%
63%
57%
53%
48%
43%
70%
64%
49%
38%
36%
34%
9
10
11
12
toluene, the electrode surface was protected by the multiphasic NaEt2DTC solution to toluene, and 0.15 mL reactor volume.
system. The results showed that 3.14 g TETD (about 10 mmol) was
After confirming the cell potential of the microfluidic obtained with 47% yield and 100% Faraday efficiency. Besides,
reactor, the effects of operating parameters including reactor larger scaled reactions can also be achieved using parallel
volume, flow rate, and NaEt2DTC concentration were studied. microfluidic electrolysis reactors. As shown in Fig. S3,† when
Entries 1–6 in Table 2 show that the TETD yield increases as using two reactors with total reaction channel of 0.3 mL,
the liquid flow rate decreases due to the extension of residence 3.07 g TETD was synthesized within 1.5 h with 46.5% yield
time in the reactor. For the effect of flow rates of the aqueous and 100% Faraday efficiency. In contrast, the batch electrolysis
and organic phases, entries 7–9 in Table 2 indicate that a in Table 1 only produced 0.336 g TETD in the same reaction
higher flow rate ratio of the organic phase to the aqueous time. Therefore, the working ability of the microfluidic reactor
phase leads to higher yield due to the better dissolution of is nearly 10 times higher than that of the batch reactor.
TETD. However, the heavy use of solvent reduced the TETD
The microfluidic electrosynthesis method was then
concentration in the organic phase. Table 2 (entries 10–12) extended to the preparations of tetramethylthiuram disulfide
also shows the experimental results for different NaEt2DTC (TMTD) and tetrabutylthiuram disulfide (TBuTD) to test the
concentrations. It can be seen from these data that the generality of the method. Fig. S8† shows that the peak currents
NaEt2DTC concentration from 0.14 to 0.49 mol L−1 had little in both linear sweep voltammetries of sodium dimethyl-
effect on the TETD yield. The highest TETD yield in the experi- dithiocarbamate
(NaMe2DTC)
and
sodium
dibutyl-
ment reached 70% within 9 s (evaluated by dividing the reac- dithiocarbamate (NaBu2DTC) are at approximately 2.0 V, which
tion channel volume by the total liquid flow rate) showing the is the same as that of NaEt2DTC. The response currents in the
high working efficiency of the microfluidic reactor in contrast potentiostatic electrolysis experiments are depicted in Fig. 6.
to the batch electrolyser. The Faraday efficiencies of all tests In contrast to the syntheses of TETD and TBuTD, the current
were higher than 96%, which exhibited the high electronic
utilization of the microfluidic electrolysis process. It is worth
noting that we did not detect additional by-product in the
HPLC analysis and NMR analysis (Fig. S13c†) of the reaction
products.
In addition to the potentiostatic electrolysis, the galvano-
static electrolysis method was also tested in the experiment.
However, the Faraday efficiency of a galvanostatic electrolysis
experiment was only from 88% to 96% with currents between
10 and 40 mA as shown by Table S1 in the ESI,† which was
probably because of the competitive electrolysis of water. Since
the aim is to improve the environmental friendliness of
thiuram disulfide synthesis and to prevent the over-oxidation
of sodium dithiocarbamate, the potentiostatic method was
more suitable to the goal of this study, although it was not as
robust as the galvanostatic electrolysis method. In order to test
Fig. 6 Current curves for the electrosyntheses of TETD, TMTD, and
TBuTD in the microfluidic reactor. Experiments were implemented with
0.15 mol L−−1 NaEt2DTC/NaMe2DTC/NaBu2DTC solutions, and operated
the reliability of the potentiostatic electrolysis method, a
3-hour electrolysis experiment was carried out using 0.5 mol
at 0.5 mL min−1 total flow rate, 1 : 1 flow rate ratio of liquid phases, and
0.15 mL reactor volume. The data smoothing method was the same as
L−1 NaEt2DTC, 1.0 mL min−1 total flow rate, 1 : 1 rate ratio of above.
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Table 3 Typical results for the electrosynthesis of TMTD and TBuTD via the microfluidic reactor platform at 2.0 V (25 °C)
Total flow rate of
Microchannel
volume (mL)
Flow rate ratio of aqueous
solution to toluene (v/v)
Concentration of reactant Product yield
Entry Products liquids (mL min−1
)
(mol L−1
)
(%)
1
2
3
4
5
6
7
8
9
TMTD
TMTD
TMTD
TMTD
TBuTD
TBuTD
TBuTD
TBuTD
TBuTD
0.5
1.0
0.5
1.0
0.5
0.7
1.0
1.5
1.8
0.06
0.06
0.15
0.15
0.15
0.15
0.15
0.15
0.15
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
0.113
0.113
0.162
0.162
0.147
0.147
0.147
0.147
0.147
42%
31%
27%
25%
88%
81%
75%
64%
45%
of TMTD electrolysis synthesis is much lower. Table 3 (entries the unreacted sodium dithiocarbamate if the aqueous solution
1–4) also shows the yields of TMTD are much lower than that can be reused. Therefore, we further developed a flow techno-
of TBuTD. The Faraday efficiency of NaMe2DTC electrolysis logy for the condensation reaction based on a packed bed
was from 77% to 92% in those tests, which were different from reactor, as shown in Fig. 7. The reactor was built from an
the results of TETD either. However, no side reaction current empty HPLC column (4.6 mm inner diameter and 100 mm
peak was present in the linear sweep voltammetry of length, BAIJIALIDA Co., Ltd), fully packed with 0.9 mm stain-
NaMe2DTC, and no obviously by-product was detected with less-steel beads. Due to the low solubility of carbon disulfide
HPLC and NMR analyses, as shown by Fig. S10 and S13.† We in the aqueous phase, the beads helped to mix the biphasic
therefore suspected that electrolysis of water might appear in reactants in the tortuous interior space in the reactor. Taking
the reaction. The rules of TBuTD electrosynthesis are almost the synthesis of NaEt2DTC as an example, the water-soluble di-
the same as for TETD. 2.0 V cell potential was enough to avoid ethylamine was firstly added into the recycled aqueous solu-
severe emulsification and maintain high Faraday efficiency, tion during the experiment; then, a Tee-connector (0.5 mm
which were close to 100%. Entries 5–9 in Table 3 shows that inner diameter, VICI) shown by Fig. 7(a) was employed to
the yield of TBuTD increases obviously with the decrease of premix the aqueous solution and carbon disulfide fed by
total liquid flow rate, for the extension of residence time in the syringe pumps (Fusion 6000 and 4000, Chemyx). All the experi-
reactor. The highest yield of TBuTD is 88%. A potentiostatic ments used a constant molar ratio of reactants at NaOH/
electrolysis of NaBu2DTC in the batch reactor was also carried amine/CS2 = 1 : 1 : 1.5, and the excess carbon disulfide was
out in the experiment. For 100 mL 0.14 mol L−1 NaBu2DTC finally separated with gravity after reaction. A photo of the
solution with equal volume of toluene, only 12% TBuTD yield packed bed reactor platform is shown in the ESI (Fig. S4†) with
was obtained within 100 min of electrolysis. In contrast, more details.
100 min of electrolysis in the microfluidic reactor can treat
75 mL of 0.15 mol L−1 NaBu2DTC solution and resulted in
64% TBuTD yield as shown in Table 3 (entry 8).
Generation of sodium dithiocarbamates via a packed bed
reactor
In the above electrolysis experiment, high selectivity of
thiuram disulfides was successfully obtained in the microflui-
dic reactor. Although the reaction yields have been much
higher than those in the previous literature12 and the batch
electrolysis process in this study, they are still away from 100%
due to the low sodium dithiocarbamate conversions. In fact,
highly concentrated NaOH will be yielded when the sodium
dithiocarbamate conversion is high, which increases the possi-
bility of water electrolysis. Thus, it is better to reuse the
sodium dithiocarbamate in solution after electrolysis. At the
beginning of this paper, we have mentioned that the synthesis
of thiuram disulfides has two steps, and the first step is a con-
densation reaction between NaOH, secondary amine, and
Fig. 7 Packed bed reaction platforms for the condensation reactions of
secondary amine, CS2 and NaOH in the electrolysis product solutions.
(a) Schematics of the reaction set-up for NaEt2DTC and NaMe2DTC; (b)
carbon disulfide to prepare sodium dithiocarbamate. Owing to
the high selectivity of the electrolysis reaction, the NaOH in
the aqueous solution after electrolysis is an ideal source of the
set-up for NaBu2DTC synthesis. The void ratio of the packed bed reactor
condensation reaction, and it is also beneficial for recycling is 44.6%.
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Table 4 Results for the packed bed reaction for the synthesis of NaEt2DTC aqueous solution (25 °C)
Diethylamine
concentration
Recycled liquid
flow rate
NaEt2DTC concentration
NaOH concentration
CS2 flow rate
NaOH
conversion (%)
Product
pH
Entry
(mol L−1
)
(mol L−1
)
(mol L−1
)
(mL min−1
)
(μL min−1
)
1
2
3
4
5
0.040
0.045
0.054
0.061
0.067
0.110
0.105
0.096
0.089
0.083
0.110
0.105
0.096
0.089
0.083
0.25
0.25
0.25
0.25
0.25
2.47
2.37
2.16
2.00
1.86
99.95%
99.83%
99.95%
99.54%
99.60%
9.34
9.83
9.22
10.15
10.08
Typical results of the packed bed reaction are listed in thiosulfinates and thiosulfonates are generated from the over-
Table 4. The packed bed reactors provided proper environ- oxidation of sodium dithiocarbamates, which lead to high
ments, where the NaOH conversions were close to 100% in COD of the wastewater. A large amount of sodium sulfate is
2.9 min of residence time. The existing sodium dithiocarba- yielded (480 kg Na2SO4 per 1000 kg TETD), and it needs to be
mates in the reactant solutions have little effect on the reac- treated with burning. Usually, the condensation and oxidation
tion. The syntheses of NaMe2DTC and NaBu2DTC had almost reactions are carried out in 10 m3 batch reactors for about
the same results as the synthesis of NaEt2DTC, which are 10 hours, and carbon disulfide and hydrogen peroxide have to
shown by Tables S2 and S3 in the ESI.† The only difference be slowly added into the reactors. However, both sodium
between NaEt2DTC synthesis and the syntheses of NaMe2DTC hydroxide and water can be recycled in the present study, and
and NaBu2DTC was that dibutylamine was insoluble in no waste salts are produced. Another approach to develop a
recycled aqueous solution. Therefore,
a cross-connector new synthesis technology for thiuram disulfides by our group
(0.5 mm inner diameter, VICI) was employed to mix the can be found in ref. 28. Carbon dioxide was employed instead
recycled solution, amine, and carbon disulfide instead of the of the sulfuric acid, and the generated sodium carbonate was
Tee-connector, as shown in Fig. 7(b). The recycled sodium applied to replace the sodium hydroxide in the condensation
dithiocarbamate and the newly generated sodium dithiocarba- reaction. However, the weak alkaline nature of sodium carbon-
mate together formed the new source of the electrolysis reac- ate caused less than 90% yield of TETD and over-oxidation
tion, which had almost the same composition as the original cannot be avoided due to the application of hydrogen per-
solution as shown in Fig. S12 in the ESI.† Thus, the microflui- oxide. Other researchers also tried to use the advanced flow
dic electrolysis reaction and the packed bed reaction together chemistry method to avoid the use of sodium hydroxide in the
created a cyclic craft for the syntheses of thiuram disulfides whole reaction. However, the results from Yao et al.36 exhibited
from secondary amines and carbon disulfide, which had more <90% yields, which do not fit the industrial demand. In
than 99% atom utility.
addition, the application of hydrogen peroxide undoubtedly
To show the advantages of this cyclic craft, a comparison of introduces excess water into the system, which has to be
the current status of industrial production, literature reports, turned into wastewater after the reaction. With the combi-
and the present result is listed in Table 5. In current industry, nation of electro-oxidation and flow condensation in this
sodium hydroxide, sulfuric acid, and hydrogen peroxide are study, we created a perfect water balance in theory, which does
consumed. Due to the strong oxidizing of hydrogen peroxide, not require any other chemicals except secondary amine and
Table 5 Comparison of chemical consumption, by-product and waste chemical generation from different reaction technologies11,28,36
Chemical
consumption except
of amine and CS2
Synthesis
environment
Waste
chemicals
Methods
Synthesis method
By-products
Yields
Industrial
method
Ref. 28
NaOH, H2SO4, H2O2, Aqueous solution at
and H2O 25–40 °C
CO2, H2O2, and H2O Aqueous solution at
30 °C
Batch reaction for
about 10 h
Batch reaction for
more than 40 min
Thiosulfinates and Na2SO4 and
>98%
89.7%
89.3%
thiosulfonates
Thiosulfonates
wastewater
Wastewater
Ref. 36
H2O2 and H2O
Eosin Y and air
None
EtOH–H2O solution at Continuous
Not mentioned
Not mentioned
None detected
Wastewater
25 °C (1st step) and
35 °C (2nd step)
EtOH solution at
room temperature
reaction
Ref. 11
Batch
Not
mentioned
45%
Quantitative yielda
photocatalytic
reaction for 4 h
Continuous
reaction
This work
Toluene/H2O mixture
at 25 °C
None
a For the cyclic reaction technology.
588 | Green Chem., 2021, 23, 582–591
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carbon disulfide after the first cycle. Beside the electrosynth- LANYI Chemical Reagent Co., Ltd), tetraethylthiuram disulfide
esis method, photochemical technology combining air as the (98%, DINGXIAN Biotechnology Co., Ltd), sodium N,N-diethyl-
oxidant also has the potential for the green synthesis of carbamodithioate trihydrate (≥99%, DIBAI Biotechnology Co.,
thiuram disulfide. However, this method still needs improve- Ltd), sodium N,N-dimethyldithiocarbaminate dehydrate (98%,
ment in accelerating the reaction rate as the example of Eosin LANYI Chemical Reagent Co., Ltd), sodium N,N-dibutyl-
Y-catalyzed photochemical reaction11 shows in Table 5. dithiocarbamate aqueous solution (40 wt%, HEOWNS
Although the present electrolysis method is still not good at Biochemical Technology Co., Ltd), sodium hydroxide (≥96%,
obtaining high sodium dithiocarbamate conversion, the yields TITAN Scientific Co., Ltd), carbon disulfide (≥99.9%, Macklin
of thiuram disulfide are able to reach 100% with the help of Biochemical Technology Co., Ltd), dimethylamine (40 wt%
the cyclic reactions. A possible shortcoming of the electro- aqueous solution, TITAN Scientific Co., Ltd), diethylamine
synthesis of thiuram disulfides is the high energy cost of such (>99%, Macklin Biochemical Technology Co., Ltd), dibutyl-
bulk chemicals. However, it is worth noting that sodium amine (99%, Macklin Biochemical Technology Co., Ltd),
hydroxide produced in the cathodic process is also produced toluene (AR, LANYI Chemical Reagent Co., Ltd), Chloroform-d
by the electrolysis method in the industry. Therefore, the cyclic (99.8%, Energy Chemical Co., Ltd) and acetonitrile (≥99.9%,
method of thiuram disulfide synthesis does not induce exces- Macklin Biochemical Technology Co., Ltd) were used as
sive energy consumption from the perspective of life cycle received without further purification.
analysis.
Operation of microfluidic reaction platform
Sodium dithiocarbamate solution was prepared by dissolving a
certain amount of sodium dithiocarbamate in the oxygen-free
Conclusions
deionized water before any electrolysis experiment. Both the
A green synthesis method based on microfluidic electrolysis aqueous and organic solutions were fed into the microfluidic
was proposed for thiuram disulfides, which successfully pre- reactor simultaneously, and the flow rates were controlled by
vented the over-oxidation of reactants and did not produce syringe pumps. As the flow pattern in the inlet tube was stable,
waste salts.
cell potential was imposed. The chronoamperometry reactions
The microfluidic reactor with 33 cm2 mL−1 specific surface were running at least for 20 min. Samples of reaction products
area of the work electrode helped to increase the yields of were collected at the outlet. The samples after electrolysis were
thiuram disulfides up to 88% in a reaction time less than 18 s, separated and the NaOH concentration in the aqueous solu-
which was much shorter than the conventional batch electroly- tion was calculated from the reaction yields of thiuram disul-
sis process. Liquid–liquid Taylor flow was employed to feed fides. Corresponding amounts of amines and carbon disulfide
the microfluidic reactor for online dissolution of thiuram di- in the condensation reaction were set according to this calcu-
sulfide into toluene, helping the realization of a continuous lation. All reactants of the condensation reaction were fed to
electrolysis process in micro-channel space. As a typical the packed bed reactor together and the reaction was at least
example, the microfluidic electrolysis method could produce stable 30 min before sampling. All samples were collected in
3.14 g TETD within 3 h in the 0.15 mL reaction channel and glass bottles, and the excessive carbon disulfide was left in the
this productivity can be further improved by parallel scaling- bottom.
up of the microfluidic reactor. In addition to the microfluidic
electrolysis reactor, a packed bed reactor was proposed to gene-
Analysis methods
rate sodium dithiocarbamate solutions from the secondary The measurement of cyclic voltammetry was carried out in a
amine, carbon disulfide, and sodium hydroxide solution, 3-electrode batch electrolyser (250 mL) with a Pt anode (1 cm ×
which realized the circulation of the aqueous solution from 1 cm), a Pt cathode (1.5 cm × 1.5 cm), and a saturated calomel
electrolysis. The microfluidic electrolysis reaction and the reference electrode. The potentiostatic electrolysis experiments
packed bed reaction therefore created a cyclic technology for were also carried out by this electrolyser for batch reactions.
the synthesis of thiuram disulfides from secondary amines Substance concentrations were obtained from a high-perform-
and carbon disulfide with >99% atom utilization. In contrast ance liquid chromatograph (HPLC, Agilent 1260) with a C-18
to the industrial production method and corresponding column (PN 990967-902). In analysing TETD and TMTD, the
researches in the literatures, our laboratory research showed mobile phase was kept at 1 mL min−1 with a 70/30 volume
strong potential for developing an environmentally friendly ratio of acetonitrile/water, and the UV wavelength for detection
synthesis technology for thiuram disulfides.
was 254 nm. In analysing TBuTD, the mobile phase was 100%
acetonitrile at 1 mL min−1, and the UV wavelength was
220 nm. In all HPLC analyses, the aqueous samples were
diluted twice and the organic samples were diluted 51 times
by the mobile phase before injection. A 5 μL sample was used
for each analysis. Since the peaks of all sodium dithiocarba-
Chemical mates did not have linear relationships with their concen-
Experimental section
Chemicals
Tetraethylthiuram
disulfide
(97%,
Meryer
Technology Co., Ltd), tetramethylthiuram disulfide (97%, trations, those peaks were only used for qualitative descrip-
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tions in this study. The yields of thiuram disulfides were
obtained from the concentrations in the original and product
solutions and the sodium dithiocarbamate concentrations in
preparation, as shown by eqn (1).
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ꢀ
ꢁ
QOcp þ QA cpa ꢀ cp0
Yield ¼
ꢁ 100%
ð1Þ
QAc0
in which QO is the flow rate of organic phase, QA is the flow rate
of aqueous phase, cp is the thiuram disulfide concentration in
the organic product, cpa is the thiuram disulfide concentration
in the aqueous phase product of electrolysis, cp0 is the thiuram
disulfide concentration in the original aqueous phase, and c0 is
the sodium dithiocarbamate concentration in the raw solution.
In the calculation of Faraday efficiencies, the response currents
from the potentiostat electrolysis experiment were integrated in
MATLAB 2019 for a certain reaction time as the theoretical
outputs. The actual outputs were obtained from the reaction
yields and flow rates of solutions as shown by eqn (2).
F ꢂ QAc0 ꢂ yield ꢂ tR
Faraday efficiency ¼
ꢁ 100%
ð2Þ
Ð
tR
Idt
0
where F is the Faraday constant, tR is the experimental operat-
ing time for integration, and I is the reaction current. NaOH
conversions in the condensation reaction were evaluated by
the variation in pH during the experiment. Only the contri-
bution of NaOH to OH− was considered in the calculation,
which was deviated from the real situation. However, because
the ratio of secondary amine and NaOH was fixed to 1 in all
experiments, this deviation had little effect on the evaluated
values of NaOH conversion in such low concentrated alkaline
solutions.
Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
The authors acknowledge the support from the State Key Lab
of Chemical Engineering (No. SKL-ChE-20Z01) for this work.
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