Continuous Flow Synthesis and Kinetic Study of Diphenyl Sulfoxide in a Microreactor
微反应器中二苯基亚砜的连续流合成与动力学研究

Hongrui Zhang, Feng Xu, Xiang Zhou, Zhiquan Chen, Juncheng Jiang, Gang Fu,* and Lei Ni*
张宏瑞、徐峰、周翔、陈志权、蒋俊成、付刚*和倪磊*

Cite This: https://doi.org/10.1021/acs.oprd.5c00018
引用： https://doi.org/10.1021/acs.oprd.5c00018

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Abstract 摘要

The oxidation of diphenyl sulfide (DPS) by hydrogen peroxide $(H_{2} O_{2})$ to synthesize diphenyl sulfoxide (DPSO) is extremely exothermic and has a high thermal risk. When thermal runaway happens, it may lead to equipment damage or even explosions. Therefore, in this work, a microreactor was adopted to reduce reaction thermal risk and process conditions were optimized. Phosphotungstic acid (PTA) was used as the catalyst, and the effects of process conditions, including reaction temperature, residence time, catalyst concentration, and molar ratio on the conversion and yield were systematically investigated. The results showed that the DPSO yield could reach up to $84.3 %$ under the condition of $0.75 %$ catalyst loading, 25 min residence time, $70^{\circ} C$ reaction temperature, and $H_{2} O_{2} -$ DPS molar ratio of 2 . Then, apparent reaction kinetics were studied, and a kinetic model was established and validated. By varying the initial concentrations of $H_{2} O_{2}$ and DPS, the reaction was determined to be of second-order, with an activation energy of $57.5 kJ \cdot {mol}^{- 1}$ and a pre-exponential factor of $2.96 \times 10^{7} {mol}^{- 1} \cdot L \cdot \min^{- 1}$ . Furthermore, the temperature distribution along the microreactor was estimated by combining the thermal equilibrium with the reaction kinetics. The results indicated that in a $1 / 16 in$ . microreactor, the reaction was nearly isothermal. Temperature distributions were also predicted for microreactors with different diameters and materials. It was demonstrated that the reaction could be safely scaled up to a $3 / 8 in$ . microreactor at a reaction temperature of $55^{\circ} C$ , with the maximum temperature rise remaining below $5^{\circ} C$ and no decline in DPSO yield. This study provided a convenient method to guide the safe sizing-up of the reaction in flow reactors.
过氧化氢氧化二苯基硫醚（DPS） $(H_{2} O_{2})$ 以合成二苯基亚砜（DPSO）的过程极易放热，具有很高的热风险。一旦发生热失控，可能会导致设备损坏甚至爆炸。因此，本研究采用了微反应器来降低反应热风险，并对工艺条件进行了优化。以磷钨酸（PTA）为催化剂，系统研究了反应温度、停留时间、催化剂浓度和摩尔比等工艺条件对转化率和产率的影响。结果表明，在催化剂装填量 $0.75 %$ 、停留时间 25 分钟、反应温度 $70^{\circ} C$ 、DPS 摩尔比 $H_{2} O_{2} -$ 为 2 的条件下，DPSO 收率可达 $84.3 %$ 。然后研究了表观反应动力学，建立并验证了动力学模型。通过改变 $H_{2} O_{2}$ 和 DPS 的初始浓度，确定反应为二阶反应，活化能为 $57.5 kJ \cdot {mol}^{- 1}$ ，前指数为 $2.96 \times 10^{7} {mol}^{- 1} \cdot L \cdot \min^{- 1}$ 。此外，还结合热平衡和反应动力学估算了沿微反应器的温度分布。结果表明，在 $1 / 16 in$ .微反应器中，反应几乎是等温的。还预测了不同直径和材料的微反应器的温度分布。结果表明，在反应温度为 $55^{\circ} C$ 时，反应可以安全地放大到 $3 / 8 in$ .微反应器，最大温升保持在 $5^{\circ} C$ 以下，且 DPSO 产率不会下降。这项研究为指导流动反应器中反应的安全放大提供了便捷的方法。

KEYWORDS: thermal risk, reaction kinetics, microreactor, oxidation, temperature distribution
关键词：热风险、反应动力学、微反应器、氧化、温度分布

1. INTRODUCTION 1.引言

Diphenyl sulfoxide (DPSO) is one of the sulfoxides, which can serve as a catalyst or solvent for the synthesis of various organic compounds.

^{1}

It is also extensively used in fine chemicals, pesticides, enzyme activation, heavy metal extraction, and other fields.

^{2, 3}

The most traditional preparation method for DPSO is through the oxidation of its corresponding thioether, namely, diphenyl sulfide (DPS).

^{4, 5}

With the extensive application of sulfoxides and the continuous increase of their value in the pharmaceutical industry, e.g., noncardiac chest pain and depression therapy, the safe and efficient synthesis of diphenyl sulfoxide has become a vital issue to be addressed.

^{6}

二苯基亚砜（DPSO）是硫醚的一种，可用作合成各种有机化合物的催化剂或溶剂。

^{1}

它还广泛应用于精细化工、农药、酶活化、重金属提取等领域。

^{2, 3}

DPSO 最传统的制备方法是通过氧化其相应的硫醚，即二苯基硫醚（DPS）。

^{4, 5}

随着硫醚的广泛应用及其在医药行业（如非心源性胸痛和抑郁症治疗）价值的不断提高，安全高效地合成二苯基亚砜已成为亟待解决的重要问题。

^{6}

In recent years, different metal salts have been used as catalysts and oxidants for the preparation of sulfoxides from their thioethers. Liu et al.

^{7}

proposed a practical synthesis method for diphenyl sulfoxide, using readily available ferric nitrate hydrate as a catalyst and oxygen as a green oxidant to selectively oxidize thioethers to sulfoxides. Pace et al.

^{8}

used aryl allylic sulfides as raw materials and oxidized them into aryl allylic sulfoxides by using calcium hypobromite. During the reaction process, no phenomenon of overoxidation was observed. This method has a high degree of chemical selectivity and provides a new and effective approach for the synthesis of aryl allylic sulfoxides. Firouzabadi et al.

^{9}

used manganese dioxide as an oxidant and sulfuric acid/silica gel as a catalyst to oxidize methyl phenyl sulfide to methyl phenyl sulfoxide under solvent-free conditions, providing a new pathway for the synthesis of sulfoxides. Hydrogen peroxide
近年来，人们使用不同的金属盐作为催化剂和氧化剂，从硫醚中制备氧化硫。Liu 等人

^{7}

提出了一种实用的二苯基亚砜合成方法，使用易得的硝酸铁水合物作为催化剂，氧气作为绿色氧化剂，选择性地将硫醚氧化成亚砜。Pace 等人

^{8}

以芳基烯丙基硫化物为原料，利用次溴酸钙将其氧化成芳基烯丙基硫醚。在反应过程中，没有观察到过氧化现象。该方法具有高度的化学选择性，为合成芳基烯丙基硫醚提供了一种新的有效方法。Firouzabadi 等人

^{9}

以二氧化锰为氧化剂，硫酸/硅胶为催化剂，在无溶剂条件下将甲基苯基硫醚氧化成甲基苯基亚砜，为合成亚砜类化合物提供了一条新途径。过氧化氢

(H_{2} O_{2})

is a well-known oxidant due to its unique advantages such as effective oxygen content, environmental friendliness, and low cost. Its use for the oxidation of sulfides to sulfoxides has been proven to be one of the most attractive options.

^{10}

For example, Bakavoli et al.

^{11}

reported a new and effective method to selectively oxidize methyl phenyl sulfide to methyl phenyl sulfoxide.

H_{2} O_{2}

was used as an oxidant and DBUH-

{Br}_{3}

as a catalyst. The reaction could be conducted under mild conditions, and this method provided a new pathway for the synthesis of sulfenoids with the features of high efficiency, green processes, and simplicity. Golchoubian et al.

^{12}

developed a “green” method for the highly selective oxidation of methyl phenyl sulfides, diaryl sulfides, benzyl-alkyl sulfides, etc., to the corresponding sulfoxides using

H_{2} O_{2}

and glacial acetic acid in the absence of transition metals under mild conditions. This method was clean, safe, and operationally simple, and the yields of the products were high (

90 - 99 %

(H_{2} O_{2})

是一种众所周知的氧化剂，具有有效含氧量高、环保和成本低等独特优势。事实证明，将其用于将硫化物氧化成硫醚是最具吸引力的选择之一。

^{10}

例如，Bakavoli 等人

^{11}

报道了一种将甲基苯基硫醚选择性氧化为甲基苯基亚砜的有效新方法。

H_{2} O_{2}

用作氧化剂，DBUH-

{Br}_{3}

用作催化剂。反应可在温和的条件下进行，该方法为亚硒酸类化合物的合成提供了一条新途径，具有高效、绿色、工艺简单等特点。Golchoubian 等人

^{12}

开发了一种 "绿色 "方法，利用

H_{2} O_{2}

和冰乙酸，在没有过渡金属的温和条件下，将甲基苯基硫化物、二芳基硫化物、苄基烷基硫化物等高选择性地氧化成相应的硫醚。这种方法清洁、安全、操作简单，而且产物的收率高（

90 - 99 %

）。

However, the oxidation of thioether is usually carried out in a batch or semibatch process, which is accompanied by significant heat release. Inadequate heat removal during these processes can lead to heat accumulation and even thermal
然而，硫醚的氧化通常是在间歇或半间歇工艺中进行的，伴随着大量的热量释放。在这些过程中，如果热量去除不充分，就会导致热量积累，甚至产生热效应。

Side reaction: 副作用

Figure 1. Reaction for the oxidation of DPS by

H_{2} O_{2}

.
图 1.

H_{2} O_{2}

氧化 DPS 的反应。

Figure 2. Experimental system of a microchannel continuous flow reactor.
图 2.微通道连续流反应器的实验系统。
runaway.

^{13, 14}

In our previous work,

^{15}

the oxidation of diphenyl sulfide was studied in a semibatch mode. The process conditions were optimized, and the reaction enthalpy was determined to be

240.13 kJ \cdot {mol}^{- 1}

. According to the reaction assessment by the risk matrix method and Stoessel criticality diagram, an unacceptable risk was obtained. And most of the numerous accidents are closely related to reactive hazards.

^{16}

Therefore, considering the high exothermicity and heat accumulation during the reaction, it is necessary to adopt measures to reduce its thermal risk.
失控。

^{13, 14}

在我们之前的工作中，

^{15}

以半间歇模式研究了二苯基硫醚的氧化。对工艺条件进行了优化，确定反应焓为

240.13 kJ \cdot {mol}^{- 1}

。根据风险矩阵法和斯托塞尔临界图对反应进行评估，得出了不可接受的风险。而众多事故大多与反应性危险密切相关。

^{16}

因此，考虑到反应过程中的高放热性和热积累，有必要采取措施降低其热风险。

With the development and application of microchemical technology, the microreactor has emerged as a powerful tool for the safer thermal management of highly exothermic chemical reactions.

^{17}

Microreactors possess various characteristics, such as high surface-to-volume ratio and low total inventory.

^{18}

Compared to conventional batch reactors, microchannel continuous-flow reactors offer high reaction efficiency, superior heat and mass transfer performance, and precise control over temperature.

^{19, 20}

These features enable them to handle demanding process requirements and improve reaction safety.

^{21 - 23}

Therefore, microreactors are widely used in highrisk chemical processes such as nitration,

^{24}

oxidation,

^{25}

peroxidation,

^{26}

sulfonation,

^{27}

and acylation.

^{28}

Chen et al.

^{29}

proposed a strategy for the continuous synthesis of dimethyl sulfone by oxidizing dimethyl sulfoxide with

H_{2} O_{2}

in a microchannel reactor. The reaction parameters were optimized, and the processes were successfully scaled up with high production efficiency. Wu et al.

^{30}

studied the synthesis of styrene oxide in a continuous-flow microreactor system. High styrene conversion (94.6%) and excellent product selectivity (

\geq 94 %

) were achieved. Sun et al.

^{31}

developed a novel continuous-flow method for the synthesis of various C-alkyl
随着微化学技术的发展和应用，微反应器已成为对高放热化学反应进行更安全热管理的有力工具。

^{17}

微反应器具有表面体积比高、总库存低等各种特点。

^{18}

与传统的间歇式反应器相比，微通道连续流反应器具有较高的反应效率、出色的传热和传质性能以及精确的温度控制。

^{19, 20}

这些特点使它们能够满足苛刻的工艺要求，并提高反应安全性。

^{21 - 23}

因此，微反应器被广泛应用于硝化、

^{24}

氧化、

^{25}

过氧化、

^{26}

磺化、

^{27}

和酰化等高风险化学过程。

^{28}

Chen 等人

^{29}

提出了在微通道反应器中用

H_{2} O_{2}

氧化二甲亚砜连续合成二甲基砜的策略。对反应参数进行了优化，并成功地扩大了工艺规模，提高了生产效率。Wu 等人

^{30}

研究了在连续流微反应器系统中合成氧化苯乙烯的过程。研究实现了较高的苯乙烯转化率（94.6%）和优异的产品选择性（

\geq 94 %

）。Sun 等人

^{31}

开发了一种新颖的连续流方法，用于合成各种 C-alkyl
and C-aryl aziridinyl oxides under mild conditions. The reaction could be completed efficiently within just a few seconds. Given the unique advantages of microchannel reactors in thermal management, switching from traditional batch processes to continuous-flow processes is expected to reduce the thermal risks associated with thioether oxidation reactions.
和 C-芳基氮丙啶氧化物的温和条件下进行。反应可在几秒钟内高效完成。鉴于微通道反应器在热管理方面的独特优势，将传统的间歇式工艺转换为连续流动工艺有望降低硫醚氧化反应的热风险。

Reaction kinetics can establish a quantitative relationship between reaction rates and operation parameters, allowing for the identification of optimal operating conditions and prediction of reaction progress. Additionally, studying reaction kinetics is crucial for effective scaling up. By establishing accurate reaction kinetics models, one can predict the behavior of reactions at different scales and guide the design of reactors. For example, the heat transfer properties in a channel change during size scaling and kinetic studies can predict the trend in heat transfer efficiency after size scaling to determine the temperature distribution in the channel. Due to the ease of precise control over residence time, microreactors offer significant advantages for studying chemical reaction kinetics.

^{32}

Kockmann et al.

^{33}

established a scaling-up model based on simple correlations by studying the kinetic characteristics within the reactor. It can predict the performance of microreactors at different scales, providing a reliable design basis for industrial production. Lu et al.

^{34}

investigated continuous synthesis of

N, N

-dicyanoethyl aniline in a microreactor system. Based on the constructed reaction network, a reaction kinetic model was developed and was used to predict the product distribution with acceptable accuracy. It provided a theoretical basis for the scaling up of the cyanoethylation process in microreactors. Zhu et al.

^{35}

studied the oxidation of tert-Butyl hydroperoxide with

H_{2} O_{2}

in a microreactor. The
反应动力学可以建立反应速率与操作参数之间的定量关系，从而确定最佳操作条件并预测反应进程。此外，研究反应动力学对于有效扩大规模至关重要。通过建立精确的反应动力学模型，可以预测不同规模反应的行为，并指导反应器的设计。例如，通道中的传热特性在尺寸缩放过程中会发生变化，而动力学研究可以预测尺寸缩放后传热效率的变化趋势，从而确定通道中的温度分布。由于易于精确控制停留时间，微反应器在研究化学反应动力学方面具有显著优势。

^{32}

Kockmann 等人

^{33}

通过研究反应器内的动力学特性，建立了一个基于简单相关性的放大模型。它可以预测不同规模微反应器的性能，为工业生产提供可靠的设计依据。Lu 等

^{34}

研究了在微反应器系统中连续合成

N, N

-二氰基乙基苯胺。根据构建的反应网络，建立了反应动力学模型，并用该模型预测了产品的分布，其准确性可以接受。这为在微反应器中放大氰乙基化过程提供了理论依据。Zhu 等人

^{35}

在微反应器中研究了叔丁基过氧化氢与

H_{2} O_{2}

的氧化反应。结果表明
reaction conditions were optimized, and a reaction kinetic model was established. The kinetic model was further proven by simulation, which provided theoretical guidance for the industrial production of tert-Butyl hydroperoxide. However, to the best of our knowledge, the reaction kinetics of DPSO synthesis have not been investigated either in batch or flow.
对反应条件进行了优化，并建立了反应动力学模型。通过模拟进一步证实了该动力学模型，为叔丁基过氧化氢的工业生产提供了理论指导。然而，据我们所知，无论是间歇反应还是流动反应，都没有对 DPSO 合成的反应动力学进行过研究。

Synthesis of diphenyl sulfoxide by oxidation of diphenyl sulfide with hydrogen peroxide was investigated in the work described herein (Figure 1). Given the highly exothermic nature of the oxidation of DPS with

H_{2} O_{2}

, optimal reaction conditions for the process were determined in a microreactor system. The effects of reaction conditions on conversion and yield were analyzed. The reaction kinetics were studied, and a kinetic model was established. Additionally, by coupling the energy conservation equation with the reaction kinetics equation, the temperature distribution of the oxidation reaction in the microreactor was predicted. It provided a foundation for safely sizing up the reaction to industrial application and aided in optimizing reactor design.
本文所述工作研究了通过过氧化氢氧化二苯基硫醚合成二苯基亚砜的过程（图 1）。鉴于二苯基硫醚与

H_{2} O_{2}

氧化反应的高放热性质，在微反应器系统中确定了该过程的最佳反应条件。分析了反应条件对转化率和产率的影响。研究了反应动力学，并建立了动力学模型。此外，通过能量守恒方程与反应动力学方程的耦合，预测了微反应器中氧化反应的温度分布。这为工业应用中安全地确定反应规模奠定了基础，并有助于优化反应器设计。

2. EXPERIMENTAL SECTION 2.实验部分

2.1. Reagents. Diphenyl sulfide (98%), diphenyl sulfoxide (99%), diphenyl sulfone (99%), and acetonitrile (HPLC,

> 99.9 %

) were purchased from Shanghai Aladdin Reagent Co., Ltd. Hydrogen peroxide (

30 wt %

) and acetonitrile (AR) were obtained from Sinopharm Chemical Reagent Co., Ltd. Phosphotungstic acid (AR) was supplied by Bide Pharmaceutical Technology Co., Ltd. Deionized water was purchased from Nanjing Wanqing Chemical Glassware Instrument Co., Ltd. All chemical reagents were used directly without further purification.
2.1.试剂。二苯基硫醚（98%）、二苯基亚砜（99%）、二苯基砜（99%）和乙腈（HPLC，

> 99.9 %

）购自上海阿拉丁试剂有限公司。过氧化氢（

30 wt %

）和乙腈（AR）购自国药集团化学试剂有限公司。磷钨酸（AR）由比德医药科技有限公司提供。去离子水购自南京万年青化工玻璃仪器有限公司。所有化学试剂未经进一步纯化直接使用。
2.2. Experimental Setup. The experimental setup is shown in Figure 2. Solution A consisted of diphenyl sulfide (dissolved in acetonitrile,

C_{DPS} = 2.5 mol \cdot L^{- 1}

), while Solution B contained hydrogen peroxide and the catalyst phosphotungstic acid (dissolved in acetonitrile,

C_{H_{2} O_{2}} = 2.63 mol \cdot L^{- 1}

). Solution A and Solution B were loaded in two syringes (Jiangsu Kele Medical Equipment Co., Ltd., Volume

= 20 mL

) separately. Two syringe pumps (LSP02-02A, Baoding Longer Precision Pump Co., Ltd.) were used to pump Solution A and Solution B into preheating channels with a length of 2 m , respectively. Then, the solutions were mixed through a Tjunction and flowed into a homemade

1 / 16 - in

. channel (length

= 6 m)

for the reaction process. The preheating channel and reaction channel were all made of PTFE and had an inner diameter of 0.8 mm . The channels were immersed in a water bath for temperature control. The residence time of the reaction was adjusted by changing the reactants’ flow rates, while the molar ratio was controlled by regulating the volumetric flow rates of the two solutions. After reaching the steady state (

> 3 \times

residence time), the product was collected at the end of the reaction channel and immediately quenched with acetonitrile (approximately 10 g ). The quenched product was diluted with additional acetonitrile (approximately 1 mL ) and then analyzed by high-performance liquid chromatography (HPLC).
2.2.实验装置。实验装置如图 2 所示。溶液 A 包括二苯基硫醚（溶于乙腈，

C_{DPS} = 2.5 mol \cdot L^{- 1}

），溶液 B 包括过氧化氢和催化剂磷钨酸（溶于乙腈，

C_{H_{2} O_{2}} = 2.63 mol \cdot L^{- 1}

）。溶液 A 和溶液 B 分别装入两支注射器（江苏科乐医疗器械有限公司，

= 20 mL

）。用两台注射泵（LSP02-02A，保定朗格精密泵有限公司）分别将溶液 A 和溶液 B 打入长度为 2 m 的预热通道。然后，溶液通过 Tjunction 混合并流入自制的

1 / 16 - in

通道（长度为

= 6 m)

）进行反应。预热通道和反应通道均由聚四氟乙烯制成，内径为 0.8 毫米。通道浸没在水浴中以控制温度。通过改变反应物的流速来调节反应的停留时间，同时通过调节两种溶液的体积流量来控制摩尔比。达到稳定状态（

> 3 \times

停留时间）后，在反应通道末端收集产物，并立即用乙腈（约 10 克）淬火。用额外的乙腈（约 1 mL）稀释淬火产物，然后用高效液相色谱法（HPLC）进行分析。
2.3. Sample Analysis. HPLC analysis was performed on a Shimadzu LC-20AD system. It was equipped with a Shim-pack GIST C18-AQ column (particle size

5 μ m

, dimensions 150

mm \times 4.6 mm

) and a DAD detector. The analysis was carried out at

40^{\circ} C

at a flow rate of

1 mL \cdot \min^{- 1}

using the isocratic elution method (

65 %

acetonitrile and

35 %

water). The data
2.3.样品分析。采用岛津 LC-20AD 系统进行高效液相色谱分析。该系统配备了 Shim-pack GIST C18-AQ 色谱柱（粒度

5 μ m

，尺寸 150

mm \times 4.6 mm

）和 DAD 检测器。采用等度洗脱法（

65 %

乙腈和

35 %

水），在

40^{\circ} C

流速

1 mL \cdot \min^{- 1}

下进行分析。数据
analysis was performed at the wavelength of 254 nm . The injection volume for each sample was

1 μ L

. The working curves and a typical chromatogram are shown in Figures S1 to S4.
波长为 254 nm。每个样品的进样量为

1 μ L

。工作曲线和典型色谱图见图 S1 至 S4。

The conversion of phenyl sulfide

(X)

is given by the following equation
苯硫醚

(X)

的转化率由以下公式给出

X = 1 - \frac{ω_{DPS} / M_{DPS}}{ω_{DPS} / M_{DPS} + ω_{DPSO} / M_{DPSO} + ω_{{DPSO}_{2}} / M_{{DPSO}_{2}}}

The selectivity of diphenyl sulfoxide

(S)

is given by the following equation
二苯基亚砜

(S)

的选择性由以下公式给出

S = \frac{ω_{DPSO} / M_{DPSO}}{ω_{DPSO} / M_{DPSO} + ω_{{DPSO}_{2}} / M_{{DPSO}_{2}}}

The yield

(Y)

is given by the following equation
产量

(Y)

由以下公式得出

Y = X * S

where

ω_{DPS}, ω_{DPSO}

, and

ω_{{DPSO}_{2}}

are the mass fractions of phenyl sulfide, diphenyl sulfoxide, and diphenyl sulfone, respectively.

M_{DPS}, M_{DPSO}

, and

M_{{DPSO}_{2}}

are the molar masses of phenyl sulfide, diphenyl sulfoxide, and diphenyl sulfone, respectively.
其中

ω_{DPS}, ω_{DPSO}

和

ω_{{DPSO}_{2}}

分别为苯基硫醚、二苯基亚砜和二苯基砜的质量分数。

M_{DPS}, M_{DPSO}

和

M_{{DPSO}_{2}}

分别是苯基硫醚、二苯基亚砜和二苯基砜的摩尔质量。

The residence time

t

of the reactants in the microreactor was calculated by the following equation
反应物在微反应器中的停留时间

t

按下式计算

t = \frac{V}{Q_{D P S} + Q_{H_{2} O_{2}}}

where

V

is the volume of the reaction channel,

Q_{DPS}

is the volumetric flow rate of diphenyl sulfide, and

Q_{H_{2} O_{2}}

is the volumetric flow rate of hydrogen peroxide.
其中

V

是反应通道的体积，

Q_{DPS}

是二苯基硫醚的体积流量，

Q_{H_{2} O_{2}}

是过氧化氢的体积流量。

3. RESULTS AND DISCUSSION
3.结果与讨论

3.1. Study on the Influence of Reaction Conditions. This section systematically investigated the effects of process conditions, including reaction temperature, residence time, catalyst concentration, and molar ratio, on conversion and yield of the reaction. To ensure the accuracy of the experiments, each condition was repeated three times. Average values were used in the figures, and standard deviations were used as error bars. The conditions were selected based on the knowledge of the batch reaction in our previous work and preliminary experiments in flow.
3.1.反应条件的影响研究。本节系统研究了反应温度、停留时间、催化剂浓度和摩尔比等工艺条件对反应转化率和产率的影响。为确保实验的准确性，每个条件均重复三次。图中使用的是平均值，标准偏差作为误差条。这些条件是根据我们以前工作中对批量反应的了解和初步的流动实验选定的。
3.1.1. Influence of Reaction Temperature and Residence Time. To study the influence of reaction temperature and residence time, the molar ratio of

H_{2} O_{2}

to DPS was kept at 2:1, and the catalyst concentration was set to

0.5 %

n (H_{2} O_{2})

. The conversion of DPSO at different temperatures and residence times is shown in Figure 3. In the selection of residence time and temperature, a shorter residence time (3

min)

and a lower temperature (

30^{\circ} C

) were tested in preliminary experiments. However, the conversion was extremely low. Therefore, further experiments were initiated from 5 min and

40^{\circ} C

. As can be seen, with the increase of residence time from 5 to 25 min , the reaction conversion increased for 25 to

35 %

under different temperatures. This is because the reaction was not completed and a longer residence time allowed the reaction to proceed further. Meanwhile, while the batch reactor requires a reaction time of

60 \min,^{15}

the microreactor achieves relatively high conversion at a residence time of just 25 min due to its efficient high efficiency in mass
3.1.1.反应温度和停留时间的影响。为了研究反应温度和停留时间的影响，将

H_{2} O_{2}

与 DPS 的摩尔比保持为 2:1，催化剂浓度设定为

0.5 %

对

n (H_{2} O_{2})

。不同温度和停留时间下 DPSO 的转化率如图 3 所示。在选择停留时间和温度时，初步实验测试了较短的停留时间（3

min)

）和较低的温度（

30^{\circ} C

）。然而，转化率极低。因此，进一步的实验从 5 分钟和

40^{\circ} C

开始。可以看出，随着停留时间从 5 分钟增加到 25 分钟，在不同温度下，25 至

35 %

的反应转化率都有所提高。这是因为反应尚未完成，而较长的停留时间可使反应进一步进行。同时，间歇反应器需要

60 \min,^{15}

的反应时间，而微反应器由于其高效的质量效率，只需 25 分钟的停留时间就能获得相对较高的转化率。

Figure 3. Effects of temperature and residence time on DPS conversion,

n (H_{2} O_{2}) / n (

DPS

) = 2 : 1

, PTA concentration

= 0.5 %

.
图 3.温度和停留时间对 DPS 转化的影响，

n (H_{2} O_{2}) / n (

DPS

) = 2 : 1

，PTA 浓度

= 0.5 %

。
and heat transfer. Therefore, 25 min was established as the upper limit for this study. On the other hand, the conversion of DPSO was always higher under higher reaction temperature at the same residence time. According to the Arrhenius equation, the reaction rate constant has an exponential relationship with temperature. At the same residence time, higher temperatures would lead to faster reaction rates, thereby accelerating the reaction process. Besides, increasing the temperature can effectively enable the reactant molecules to acquire sufficient energy to overcome the activation energy of the reaction and promote the reaction progress. However, experimental observations revealed that temperatures exceeding

70^{\circ} C

induced

H_{2} O_{2}

decomposition accompanied by bubble formation. By increasing the temperature from 70 to

80^{\circ} C

, the conversion only increased a bit, especially when the residence time was longer than 15 min . So, it is reasonable to assume the reaction was nearing the critical point of thermodynamic equilibrium. Although a further increase of temperature may enhance the kinetic rate, it will also accelerate the decomposition of hydrogen peroxide. Consequently, the upper temperature limit for this study was established at

80^{\circ} C

.
和传热。因此，本研究将 25 分钟设定为上限。另一方面，在相同的停留时间内，反应温度越高，DPSO 的转化率越高。根据阿伦尼乌斯方程，反应速率常数与温度呈指数关系。在相同的停留时间内，温度越高，反应速率越快，从而加速了反应过程。此外，提高温度还能有效地使反应物分子获得足够的能量，克服反应的活化能，促进反应的进行。然而，实验观察发现，温度超过

70^{\circ} C

会诱发

H_{2} O_{2}

分解，并伴随气泡的形成。温度从 70 升至

80^{\circ} C

时，转化率仅略有提高，尤其是当停留时间超过 15 分钟时。因此，有理由认为反应已接近热力学平衡临界点。虽然温度的进一步升高可能会提高动力学速率，但也会加速过氧化氢的分解。因此，本研究的温度上限定为

80^{\circ} C

。
3.1.2. Effect of Catalyst Phosphotungstic Acid Concentration. To study the effect of PTA concentration, the molar ratio of

H_{2} O_{2}

to DPS was kept at

2 : 1

and the residence time was set to 25 min . The result is illustrated in Figure 4. As the concentration of PTA increased, the conversion of DPS improved significantly under all studied temperatures. From the catalytic mechanism,

H_{2} O_{2}

would attack the metal center W of PTA and form an active intermediate with an

O - O

structure.

^{36, 37}

This active intermediate then interacts with DPS and oxidizes it to DPSO.

^{38}

As the concentration of PTA in the reaction system increased, more active intermediates were formed and participated in the reactive system. As a result, the reaction rate was accelerated and the conversion was increased, reaching a maximum of

84.5 %

at the PTA concentration of

0.75 %

.
3.1.2.催化剂磷钨酸浓度的影响。为了研究 PTA 浓度的影响，将

H_{2} O_{2}

与 DPS 的摩尔比保持为

2 : 1

，并将停留时间设定为 25 分钟。结果如图 4 所示。在所有研究温度下，随着 PTA 浓度的增加，DPS 的转化率显著提高。从催化机理来看，

H_{2} O_{2}

会攻击 PTA 的金属中心 W，形成具有

O - O

结构的活性中间体。

^{36, 37}

然后，这种活性中间体与 DPS 发生作用，将其氧化成 DPSO。

^{38}

随着反应体系中 PTA 浓度的增加，形成了更多的活性中间体并参与到反应体系中。因此，反应速率加快，转化率提高，在 PTA 浓度为

0.75 %

时达到最大值

84.5 %

。
3.1.3. Effect of Molar Ratio. To study the effect of molar ratio, reaction temperature was kept at

55^{\circ} C

and residence time was set to 15 min , and the initial concentration of DPS was kept constant at

2.5 mol \cdot L^{- 1}

. The experimental results are shown in Figure 5. As can be seen, with the increase in molar
3.1.3.摩尔比的影响。为了研究摩尔比的影响，将反应温度保持在

55^{\circ} C

，停留时间设定为 15 分钟，DPS 的初始浓度保持不变，为

2.5 mol \cdot L^{- 1}

。实验结果如图 5 所示。可以看出，随着摩尔浓度的增加

Figure 4. Effect of PTA concentration on DPS conversion,

n (H_{2} O_{2}) /

n (DPS) = 2 : 1, t = 25 \min

.
图 4.PTA 浓度对 DPS 转化率的影响，

n (H_{2} O_{2}) /

n (DPS) = 2 : 1, t = 25 \min

。

Figure 5. Effect of molar ratio on DPS conversion

T = 55^{\circ} C, t = 15

min.
图 5.摩尔比对 DPS 转化

T = 55^{\circ} C, t = 15

分钟的影响。
ratio, the conversion of DPS gradually increased. An increase in feed molar ratio meant an increase in the content of

H_{2} O_{2}

in the reaction system within the same period of time, thereby ensuring sufficient oxidant for the reaction with DPS. Second, a higher feed molar ratio accelerated the generation of active oxygen species, namely,

^{\circ} OH

radicals. Thus, the reaction rate was boosted and DPS conversion increased. Remarkably, the selectivity of DPSO remains above

99 %

under all molar ratio conditions. This reaction is a consecutive reaction, and diphenyl sulfone should be the main side-product. However, throughout the reaction, the conditions required for the formation of diphenyl sulfone are more stringent compared to the formation of diphenyl sulfoxide. The formation reaction of DPSO dominated the entire reaction process.
比，DPS 的转化率逐渐提高。进料摩尔比的增加意味着在同一时间内反应体系中

H_{2} O_{2}

的含量增加，从而确保与 DPS 反应有足够的氧化剂。其次，较高的进料摩尔比加速了活性氧（即

^{\circ} OH

自由基）的生成。因此，反应速度加快，DPS 转化率提高。值得注意的是，在所有摩尔比条件下，DPSO 的选择性都保持在

99 %

以上。该反应是一个连续反应，二苯砜应该是主要副产物。然而，在整个反应过程中，二苯砜的生成条件比二苯基亚砜的生成条件更为苛刻。二苯基砜的生成反应在整个反应过程中占主导地位。
3.1.4. Comparison between Semibatch Mode and Continuous Flow Mode. The results obtained here in the continuous flow mode were compared to our previous study in the semibatch mode,

^{15}

shown in Table 1. It can be seen that the continuous flow process achieved

84.3 %

DPSO yield with

99.8 %

selectivity at

70^{\circ} C

, outperforming the best result in the
3.1.4.半批量模式与连续流模式的比较。表 1 比较了连续流模式和半间歇模式下的研究结果，

^{15}

如表 1 所示。可以看出，连续流工艺在

70^{\circ} C

时实现了

84.3 %

DPSO 产率和

99.8 %

选择性，超过了半间歇模式的最佳结果。

Table 1. Comparison of the Performance Between Two Types of Reactors
表 1.两种反应堆的性能比较

parameter 规范	continuous mode $^{a}$ 连续模式 $^{a}$	semibatch mode $^{b}$ 半批处理模式 $^{b}$
conversion (%) 转换率 (%)	84.5	95.8
selectivity (%) 选择性 (%)	99.8	82.8
yield (%) 产量（%）	84.3	79.3

a_{n} (H_{2} O_{2}) / n (DPS) = 2 : 1, T = 70^{\circ} C

, and PTA concentration

=

0.75 %, t = 25 \min .^{b} n (H_{2} O_{2}) / n (DPS) = 1.08 : 1, T = 30^{\circ} C

, and PTA concentration

= 0.19 %, t = 60 \min

a_{n} (H_{2} O_{2}) / n (DPS) = 2 : 1, T = 70^{\circ} C

，以及 PTA 浓度

=

0.75 %, t = 25 \min .^{b} n (H_{2} O_{2}) / n (DPS) = 1.08 : 1, T = 30^{\circ} C

，以及 PTA 浓度

= 0.19 %, t = 60 \min

。
semibatch mode (

79.3 %

yield,

82.8 %

selectivity), especially for the selectivity. The possible explanation for this phenomenon was that the high specific surface area of the microreactor minimized the concentration gradient and avoided the local hot spots. As a result, the side reaction was suppressed and DPSO selectivity increased.
半批次模式（

79.3 %

产量，

82.8 %

选择性），尤其是选择性。造成这种现象的可能原因是，微反应器的高比表面积使浓度梯度最小化，避免了局部热点。因此，副反应受到抑制，DPSO 的选择性提高。
3.2. Establishment of the Reaction Kinetic Model. This section focused on studying the kinetics of the

H_{2} O_{2}

oxidation of DPS in a microreactor. To ensure the accuracy of the experimental results, the decomposition temperature of hydrogen peroxide was tested by differential scanning calorimetry (see Table S1 for details). The experimental results are shown in Figure 6. It can be observed that an
3.2.建立反应动力学模型。本节主要研究微反应器中 DPS 的

H_{2} O_{2}

氧化动力学。为确保实验结果的准确性，采用差示扫描量热法测试了过氧化氢的分解温度（详见表 S1）。实验结果如图 6 所示。从图中可以看出

Figure 6.

H_{2} O_{2}

heat flow vs temperature curve from the DSC test.
图 6.DSC 测试得出的

H_{2} O_{2}

热流量与温度关系曲线。
exothermic phenomenon occurred at

71.98^{\circ} C

, indicating the onset of

H_{2} O_{2}

decomposition. The decomposition of

H_{2} O_{2}

was completed when the temperature reached approximately

108^{\circ} C

. Subsequently, an endothermic phenomenon occurred due to the vaporization of water. Therefore, the selected temperature for the kinetic study should be lower than the decomposition temperature of

H_{2} O_{2} (71.98^{\circ} C)

71.98^{\circ} C

时出现放热现象，表明

H_{2} O_{2}

开始分解。当温度达到约

108^{\circ} C

时，

H_{2} O_{2}

分解完成。随后，由于水的汽化，出现了内热现象。因此，动力学研究选择的温度应低于

H_{2} O_{2} (71.98^{\circ} C)

的分解温度。

In this reaction,

H_{2} O_{2}

reacts with DPS in a

1 : 1

molar ratio to produce DPSO theoretically. Under certain conditions, DPS will continue to react with

H_{2} O_{2}

to produce the side product

{DPSO}_{2}

. Therefore, the reaction rate equations for each substance can be derived as follows
在该反应中，

H_{2} O_{2}

与 DPS 以

1 : 1

摩尔比发生反应，理论上生成 DPSO。在一定条件下，DPS 会继续与

H_{2} O_{2}

反应，生成副产物

{DPSO}_{2}

。因此，每种物质的反应速率方程可推导如下

r (DPS) = \frac{- d c (DPS)}{d t} = k_{1} C_{DPS}^{α} C_{H_{2} O_{2}}^{β}

\begin{aligned} r (DPSO) & = \frac{d c (DPSO)}{d t} \\ = k_{1} C_{DPS}^{α} C_{H_{2} O_{2}}^{β} - k_{2} C_{DPSO}^{γ} C_{H_{2} O_{2}}^{δ} \\ r ({DPSO}_{2}) & = \frac{- d c ({DPSO}_{2})}{d t} = k_{2} C_{DPSO}^{γ} C_{H_{2} O_{2}}^{δ} \end{aligned}

where

r

(DPS) and

r

(DPSO) denote the consumption rate and generation rate of DPS and DPSO, respectively.

r ({DPSO}_{2})

denotes the generation rate of

{DPSO}_{2}

and

C_{DPS}, C_{H_{2} O_{2}}

, and

C_{DPSO}

denote the concentrations of DPS,

H_{2} O_{2}

, and DPSO, respectively.

α, β, γ

, and

δ

denoted the reaction orders of the corresponding components and

k_{1}

and

k_{2}

were the main and side reaction rate constants.
其中

r

（DPS）和

r

（DPSO）分别表示 DPS 和 DPSO 的消耗率和生成率。

r ({DPSO}_{2})

表示

{DPSO}_{2}

和

C_{DPS}, C_{H_{2} O_{2}}

的生成率，

C_{DPSO}

分别表示 DPS、

H_{2} O_{2}

和 DPSO 的浓度。

α, β, γ

和

δ

表示相应组分的反应顺序，

k_{1}

和

k_{2}

分别为主反应速率常数和副反应速率常数。
3.2.1. Determination of Reaction Orders. To determine the reaction orders of DPS and

H_{2} O_{2}

, the effect of initial concentrations of

H_{2} O_{2}

and DPS on the reaction rate was investigated. The reaction temperature was set at

30^{\circ} C

.
3.2.1.确定反应顺序。为了确定 DPS 和

H_{2} O_{2}

的反应顺序，研究了

H_{2} O_{2}

和 DPS 初始浓度对反应速率的影响。反应温度设定为

30^{\circ} C

。

Figure 7 shows the influence of the initial concentrations of

H_{2} O_{2}

and DPS on the reaction conversion. In Figure 7a, the concentration of DPS was kept constant at

2 mol \cdot L^{- 1}

. It can be seen that at the same residence time, with the increase of concentration of

H_{2} O_{2}

, the conversion of DPS increased. This indicated the existence of a correlation between the reaction rate and the concentration of

H_{2} O_{2}

. Similarly, it can be observed that the initial concentration of DPS also had an effect on the conversion, while the initial concentration of

H_{2} O_{2}

was kept constant at

5 mol \cdot L^{- 1}

(Figure 7b). With the increase of the initial concentration of DPS, the conversion of DPS increased accordingly. Therefore, it can be concluded that the concentrations of both

H_{2} O_{2}

and DPS directly affected the reaction rate, indicating that their reaction orders were not 0 .
图 7 显示了

H_{2} O_{2}

和 DPS 初始浓度对反应转化率的影响。在图 7a 中，DPS 的浓度保持不变，为

2 mol \cdot L^{- 1}

。可以看出，在相同的停留时间内，随着

H_{2} O_{2}

浓度的增加，DPS 的转化率也增加了。这表明反应速率与

H_{2} O_{2}

的浓度之间存在相关性。同样，可以观察到 DPS 的初始浓度对转化率也有影响，而

H_{2} O_{2}

的初始浓度保持在

5 mol \cdot L^{- 1}

不变（图 7b）。随着 DPS 初始浓度的增加，DPS 的转化率也相应增加。因此，可以得出结论：

H_{2} O_{2}

和 DPS 的浓度都直接影响反应速率，表明它们的反应顺序不是 0。
To determine the reaction order of DPS, the feed molar ratio of

H_{2} O_{2}

to DPS was set to 10:1, resulting in an excess of

H_{2} O_{2}

in the reaction system. Due to the excessive presence of

H_{2} O_{2}

, its concentration change can be neglected in the reaction system. From the aforementioned experiments, it was found that the selectivity of DPSO was over

99 %

throughout the reaction. Hence, the generation of

{DPSO}_{2}

can also be neglected. As a result, the consumption rate of DPS can be expressed as follows
为了确定 DPS 的反应顺序，将

H_{2} O_{2}

与 DPS 的进料摩尔比设定为 10:1，从而导致反应体系中

H_{2} O_{2}

过量。由于

H_{2} O_{2}

的过量存在，其在反应体系中的浓度变化可以忽略不计。通过上述实验发现，在整个反应过程中，DPSO 的选择性超过了

99 %

。因此，

{DPSO}_{2}

的生成也可以忽略。因此，DPS 的消耗率可表示为

r (DPS) = \frac{- d c (DPS)}{d t} = k_{1} C_{DPS}^{α} C_{H_{2} O_{2}}^{β} \approx K_{1} C_{DPS}^{α}

The graphing method

^{39}

was employed to determine the reaction order of DPS. If

α = 1

, then eq 8 can be transformed into eqs 9 and 10. It can be seen that there was a linear correlation between reaction time and conversion. The experimental results are plotted in Figure 8a. If

α = 2

, then eq 8 can be transformed into eq 11 . The experimental results are plotted in Figure 8b for this case. By comparing the two sets of experimental results, it can be seen that when

α = 1

, the linear fit was better with

R^{2} = 0.997

. Therefore, the reaction order

α

of DPS was 1 .
采用图解法

^{39}

确定 DPS 的反应顺序。如果

α = 1

，则公式 8 可转化为公式 9 和 10。可以看出，反应时间和转化率之间呈线性关系。实验结果见图 8a。如果

α = 2

，则公式 8 可转化为公式 11。这种情况下的实验结果见图 8b。通过比较两组实验结果可以看出，当

α = 1

时，

R^{2} = 0.997

的线性拟合效果更好。因此，DPS 的反应顺序

α

为 1 。

\begin{aligned} r (DPS) = C_{0, DPS} \frac{- d X}{d t} = K_{1} C_{0, DPS} (1 - X) \\ \ln (1 - X) = K_{1} t \\ \frac{1}{(1 - X)} = K_{1} t \end{aligned}

Figure 7. (a) Effect of

H_{2} O_{2}

concentration on the conversion,

C_{DPS} = 2 mol \cdot L^{- 1}, T = 30^{\circ} C

, and PTA concentration

= 0.25 %

; (b) Effect of DPS concentration on the conversion,

C_{H 2 O 2} = 5 mol \cdot L^{- 1}, T = 30^{\circ} C

, and PTA concentration

= 0.25 %

.
图 7 (a)

H_{2} O_{2}

浓度对转化率

C_{DPS} = 2 mol \cdot L^{- 1}, T = 30^{\circ} C

和 PTA 浓度

= 0.25 %

的影响；(b) DPS 浓度对转化率

C_{H 2 O 2} = 5 mol \cdot L^{- 1}, T = 30^{\circ} C

和 PTA 浓度

= 0.25 %

的影响。

Figure 8.

n (H_{2} O_{2}) / n (DPS) = 10 : 1, T = 30^{\circ} C

, and PTA concentration

= 0.5 %

(a) Fitting of

\ln (1 - X)

t

; (b) Fitting of

1 / (1 - X)

t

.
图 8.

n (H_{2} O_{2}) / n (DPS) = 10 : 1, T = 30^{\circ} C

和 PTA 浓度

= 0.5 %

(a)

\ln (1 - X)

与

t

的拟合；(b)

1 / (1 - X)

与

t

的拟合。

C_{0, DPS} = \frac{n}{Q_{DPS} + Q_{H_{2} O_{2}}}

where

K_{1}

represents the apparent reaction rate constant when

H_{2} O_{2}

is in excess,

C_{0, DPS}

represents the initial concentration of DPS, and it can be calculated from eq 12 (in this study,

C_{0, DPS}

= 1.111 mol \cdot L^{- 1}) . n

represents the molar flow rate of the DPS.
其中

K_{1}

表示

H_{2} O_{2}

过量时的表观反应速率常数，

C_{0, DPS}

表示 DPS 的初始浓度，可根据公式 12 计算得出（在本研究中，

C_{0, DPS}

= 1.111 mol \cdot L^{- 1}) . n

表示 DPS 的摩尔流速）。

Using the same method, the feed molar ratio of DPS to

H_{2} O_{2}

was set to

10 : 1

. Assuming

β = 1

, the consumption rate of DPS can be expressed by eqs 13 and 14 .
使用同样的方法，将 DPS 与

H_{2} O_{2}

的进料摩尔比设定为

10 : 1

。假设

β = 1

，DPS 的消耗率可用公式 13 和 14 表示。

\begin{aligned} r (DPS) = C_{0, DPS} \frac{- d X}{d t} = k_{1} C_{0}^{2}_{DPS} (1 - X) (M - X) \\ \frac{1}{C_{0, DPS} (M - 1)} \ln [\frac{M - X}{M (1 - X)}] = - k_{1} t \end{aligned}

Let

K_{2} = - (C_{0, DPS} (M - 1) k_{1})

, then eq 14 can be transformed into eq 15. The experimental results were plotted and fitted, as shown in Figure 9. It can be seen that when

β = 1, R^{2}

reached up to 0.994 , which meant a good linear fitting. This proved that the reaction order of

H_{2} O_{2}

was also 1 .
设

K_{2} = - (C_{0, DPS} (M - 1) k_{1})

，则公式 14 可转化为公式 15。实验结果经绘图拟合后如图 9 所示。可以看出，当

β = 1, R^{2}

达到 0.994 时，表示线性拟合良好。这证明

H_{2} O_{2}

的反应顺序也是 1。

G = \ln [\frac{M - X}{M (1 - X)}] = K_{2} t

3.2.2. Reaction Rate Constant and Activation Energy. To determine the reaction rate constant, the initial concentrations of

H_{2} O_{2}

and DPS were set to 2 and

5 mol \cdot L^{- 1}

, respectively. The conversion of DPS was measured in the temperature range of 35 to

55^{\circ} C

, and the reaction rate constants for the oxidation were obtained.
3.2.2.反应速率常数和活化能。为了确定反应速率常数，将

H_{2} O_{2}

和 DPS 的初始浓度分别设定为 2 和

5 mol \cdot L^{- 1}

。在 35 至

55^{\circ} C

的温度范围内测量 DPS 的转化率，得出氧化反应的反应速率常数。

Figure 10a shows the DPS conversion at temperatures ranging from 35 to

55^{\circ} C

. It can be observed that the influence of residence time and temperature on conversion was
图 10a 显示了温度为 35 至

55^{\circ} C

时的 DPS 转化率。可以看出，停留时间和温度对转化率的影响是

Figure 9. Fitting of

\ln [\frac{M - X}{M (1 - X)}]

t . n (DPS) : n (H_{2} O_{2}) = 10 : 1, T = 30

^{\circ} C

, PTA concentration

= 0.5 %

.
图 9.

\ln [\frac{M - X}{M (1 - X)}]

与

t . n (DPS) : n (H_{2} O_{2}) = 10 : 1, T = 30

^{\circ} C

的拟合，PTA 浓度

= 0.5 %

。
consistent as aforementioned in Section 3.1.1. By fitting the conversion at different temperatures using eq

15 \ln [\frac{M - X}{M (1 - X)}]

against

t

, the reaction rate constants

k_{1}

at different temperatures were obtained, as shown in Figure 10b. The reaction rate constants at different temperatures are listed in Table 2.
与第 3.1.1 节所述一致。利用公式

15 \ln [\frac{M - X}{M (1 - X)}]

与

t

对不同温度下的转化率进行拟合，得到了不同温度下的反应速率常数

k_{1}

，如图 10b 所示。表 2 列出了不同温度下的反应速率常数。

From Figure 10b, it can be seen that the increment of the reaction rate constant

k_{1}

became progressively larger as the reaction temperature increased. This indicated that, within a certain temperature range, increasing the temperature is favorable for the reaction.
从图 10b 可以看出，随着反应温度的升高，反应速率常数

k_{1}

的增量逐渐变大。这表明，在一定的温度范围内，温度升高有利于反应的进行。

Then Arrhenius eq (eq 16) was used to determine the activation energy and the pre-exponential factor for the reaction, shown in Figure 11. The activation energy of the reaction was

57.5 kJ \cdot {mol}^{- 1}

, and the pre-exponential factor was

2.96 \times 10^{7} {mol}^{- 1} \cdot L \cdot \min^{- 1}

.
然后利用 Arrhenius 公式（公式 16）确定了反应的活化能和预指数，如图 11 所示。反应的活化能为

57.5 kJ \cdot {mol}^{- 1}

，预指数为

2.96 \times 10^{7} {mol}^{- 1} \cdot L \cdot \min^{- 1}

。

Table 2. Reaction Rate Constants

k_{1}

35 - 55^{\circ} C

表 2.

35 - 55^{\circ} C

时

k_{1}

的反应速率常数

$T (^{\circ} C)$	$k_{1} ({mol}^{- 1} \cdot L \cdot \min^{- 1})$
35	$2.49 \times 10^{- 3}$
40	$3.08 \times 10^{- 3}$
45	$4.48 \times 10^{- 3}$
50	$6.15 \times 10^{- 3}$
55	$10.45 \times 10^{- 3}$

Figure 11. Fitting of

\ln k_{1}

1 / T

35 - 55^{\circ} C

.
图 11.

\ln k_{1}

与

1 / T

在

35 - 55^{\circ} C

处的拟合。

\ln k_{1} = \ln A - \frac{E_{a}}{R T}

where

E_{a}

is the activation energy,

A

is the pre-exponential factor,

R

is the gas constant, and

T

is the temperature in Kelvin.
其中，

E_{a}

是活化能，

A

是前指数因子，

R

是气体常数，

T

是开尔文温度。
3.2.3. Kinetic Model Validation. Validation of the kinetic model is essential to ensure its accuracy. The kinetic model described above allowed for the prediction of the conversion at different residence times. The predicted value was compared to the experimental results for validation. First, the initial DPS
3.2.3.动力学模型验证。动力学模型的验证对于确保其准确性至关重要。上述动力学模型可以预测不同停留时间下的转化率。将预测值与实验结果进行比较，以进行验证。首先，初始 DPS

Figure 10. (a) Conversion of DPS,

n (H_{2} O_{2}) / n (DPS) = 2 : 1

, PTA concentration

= 0.5 %

; (b) Fitting of

k_{1}

values at

35 - 55^{\circ} C

.
图 10.(a) DPS、

n (H_{2} O_{2}) / n (DPS) = 2 : 1

和 PTA 浓度

= 0.5 %

的转换；(b)

k_{1}

值在

35 - 55^{\circ} C

时的拟合。

Figure 12. (a) Comparison of experimental and predicted DPS conversion at 60 and

65^{\circ} C, C_{0, DPS} = 1.111 mol \cdot L^{- 1}, n (H_{2} O_{2}) / n (DPS) = 2 : 1

, and PTA concentration

= 0.5 %

; (b) Comparison of experimental and predicted DPS conversion at

35 - 55^{\circ} C, C_{0, DPS} = 1.2 mol \cdot L^{- 1}, n (H_{2} O_{2}) / n (DPS)

= 2 : 1

, and PTA concentration

= 0.5 %

.
图 12.(a) 在 60 和

65^{\circ} C, C_{0, DPS} = 1.111 mol \cdot L^{- 1}, n (H_{2} O_{2}) / n (DPS) = 2 : 1

以及 PTA 浓度

= 0.5 %

时，实验和预测的 DPS 转化率比较；(b) 在

35 - 55^{\circ} C, C_{0, DPS} = 1.2 mol \cdot L^{- 1}, n (H_{2} O_{2}) / n (DPS)

= 2 : 1

以及 PTA 浓度

= 0.5 %

时，实验和预测的 DPS 转化率比较。
concentration was kept at

1.111 mol \cdot L^{- 1}

constant and the reaction temperature was increased to 60 and

65^{\circ} C

. The experimental and predicted values of DPS conversion are shown in Figure 12a. Similarly, when the initial concentration of DPS was raised to

1.2 mol \cdot L^{- 1}

and the reaction temperature was increased from 35 to

55^{\circ} C

, the experimental and predicted values of DPS conversion are shown in Figure 12b. It can be seen that the experimental and predicted values under different residence times and temperatures were in good agreement. Therefore, it can be concluded that the developed reaction model was accurate.
浓度保持

1.111 mol \cdot L^{- 1}

不变，反应温度升至 60 和

65^{\circ} C

。DPS 转化率的实验值和预测值如图 12a 所示。同样，当 DPS 的初始浓度升高到

1.2 mol \cdot L^{- 1}

，反应温度从 35 升高到

55^{\circ} C

时，DPS 转化率的实验值和预测值如图 12b 所示。可以看出，在不同的停留时间和温度下，实验值和预测值非常吻合。因此，可以认为所建立的反应模型是准确的。
3.3. Assessment of Heat Transfer and Prediction of Temperature Distribution. Temperature is closely related to the safety of the reaction process.

^{40}

The reaction studied herein was highly exothermic, whose reaction enthalpy reached up to

240.13 kJ \cdot {mol}^{- 1}

. Hence, it is necessary to give full consideration to temperature distribution in the reactor, especially for the sizing-up of the microreactor and the reaction. With the increase of channel diameter, the surface-tovolume ratio would decrease dramatically, and so would the heat transfer efficiency. This may lead to the formation of hot spots or even thermal runaway, which was not likely to happen in microscale.

^{41}

3.3.传热评估和温度分布预测。温度与反应过程的安全性密切相关。

^{40}

本文研究的反应是高放热反应，其反应焓高达

240.13 kJ \cdot {mol}^{- 1}

。因此，有必要充分考虑反应器中的温度分布，特别是微反应器和反应的大小。随着通道直径的增大，表面体积比会急剧下降，传热效率也会随之降低。这可能导致形成热点甚至热失控，而这在微尺度中是不可能发生的。

^{41}

The heat balance equation for the oxidation of DPS by

H_{2} O_{2}

was combined with the reaction kinetic equation. Through the coupled equations, the temperature distribution inside the channel could be obtained and the change of yield inside the whole system caused by the change of temperature could be predicted.

^{42, 43}

The heat balance equation is as follows

^{44}

H_{2} O_{2}

氧化 DPS 的热平衡方程与反应动力学方程相结合。通过耦合方程，可以得到通道内的温度分布，并预测温度变化引起的整个系统内部产率的变化。

^{42, 43}

热平衡方程如下

^{44}

ρ c_{p} \frac{Q}{S_{r}} \frac{d T}{d Z} = \frac{Q}{S_{r}} C_{0, DPS} (- Δ H_{r}) \frac{d X}{d Z} - \frac{4 U}{d_{i}} (T - T_{C})

where

ρ

is the average mass density of the whole homogeneous system (

0.88 g \cdot {cm}^{- 3}

c_{p}

is the average specific heat capacity

(1.96 J \cdot g^{- 1} \cdot K^{- 1}), Q

is the total volume flow rate,

Δ H r

is the molar heat of reaction (

- 240.13 kJ \cdot {mol}^{- 1}

), and

Z

is the channel length.

S_{r}

is the cross-sectional area of the microreactor channel,

T

is the temperature of the reactants inside the
式中：

ρ

为整个均质系统的平均质量密度（

0.88 g \cdot {cm}^{- 3}

）；

c_{p}

为平均比热容；

(1.96 J \cdot g^{- 1} \cdot K^{- 1}), Q

为总体积流量；

Δ H r

为摩尔反应热（

- 240.13 kJ \cdot {mol}^{- 1}

）；

Z

为通道长度。

S_{r}

是微反应器通道的横截面积，

T

是反应器内反应物的温度。
reactor,

T_{c}

is the temperature of the coolant,

X

denotes the conversion of the DPS,

d_{i}

denotes the inner diameter of the channel, and

U

is the total heat transfer coefficient, defined by eq 18 .
反应器，

T_{c}

是冷却剂的温度，

X

表示 DPS 的转换率，

d_{i}

表示通道的内径，

U

是总传热系数，由公式 18 定义。

U = \frac{1}{\frac{1}{h} + \frac{b d_{i}}{λ_{w} d_{m}}}

where

h

is the convective heat transfer coefficient in the microreactor,

b

is the wall thickness, and

λ_{w}

is the thermal conductivity of the channel wall. The channel material is PTFE, and the thermal conductivity of each material and reaction fluid is shown in Table 3.

d_{m}

denotes the average value
其中，

h

是微反应器中的对流传热系数，

b

是壁厚，

λ_{w}

是通道壁的导热系数。通道材料为聚四氟乙烯，各种材料和反应流体的导热系数如表 3 所示。

d_{m}

表示平均值

Table 3. Thermal Conductivity of Materials and Reaction Fluids
表 3.材料和反应流体的导热系数

	thermal conductivity $(W \cdot m^{- 1} \cdot K^{- 1})$ 导热性 $(W \cdot m^{- 1} \cdot K^{- 1})$
reactant fluid 反应液	0.25
PTFE	0.26
quartz glass 石英玻璃	1.35
stainless steel (316L) 不锈钢（316L）	15.1

of the inner and outer diameters of the channel. To simplify the calculation, the outer wall temperature was assumed to be a constant. In this case,

N u

was equal to 3.66 and the convective heat transfer coefficient

h

can be calculated by eq 19 .
通道的内径和外径。为简化计算，假定外壁温度为常数。在这种情况下，

N u

等于 3.66，对流传热系数

h

可通过公式 19 计算得出。

h = \frac{N u λ_{f}}{d_{i}}

where

λ_{f}

is the thermal conductivity of the reactant fluid.
其中

λ_{f}

是反应流体的导热系数。
The above obtained reaction kinetic equation (eq 13) can be transformed into eq 20
上述反应动力学方程（式 13）可转化为式 20

\frac{d X}{d Z} = \frac{A e^{- E_{a} / R T} C_{0, DPS} (1 - X) (M - X)}{\frac{Q}{S_{r}}}

Then, the heat balance equation (eq 17) and reaction kinetic eq (eq 20) were solved. The reactants’ temperatures at different positions of the microreactor and their corresponding conversion were obtained. The temperature distribution in the microreactor is shown in Figure 13. As can be seen, there was
然后，求解了热平衡方程（公式 17）和反应动力学方程（公式 20）。得出了微反应器不同位置的反应物温度及其相应的转化率。微反应器中的温度分布如图 13 所示。从图中可以看出

Figure 13. Predicted temperature distribution inside the

1 / 16 in

. channel at

T = 55^{\circ} C

and

t = 15 \min, C_{0, DPS} = 1.111 mol \cdot L^{- 1}

n (H_{2} O_{2}) / n (DPS) = 2 : 1

, and PTA concentration

= 0.5 %

.
图 13.在

T = 55^{\circ} C

和

t = 15 \min, C_{0, DPS} = 1.111 mol \cdot L^{- 1}

、

n (H_{2} O_{2}) / n (DPS) = 2 : 1

以及 PTA 浓度

= 0.5 %

时，

1 / 16 in

通道内的预测温度分布。
no temperature change inside the

1 / 16 in

. microreactor, and the entire reaction process can be viewed as isothermal. This isothermal phenomenon showcased the accurate temperature control of the microreactor.

1 / 16 in

.微反应器内没有温度变化，整个反应过程可以看作是等温的。这种等温现象展示了微反应器的精确温度控制。
To study the safety of the sizing-up of the microreactor, PTFE channels with different diameters, including

1 / 8, 1 / 4, 3

/ 8 , and

1 / 2

in., were selected. Table 4 gives specific values for
为了研究微反应器尺寸调整的安全性，选择了不同直径的聚四氟乙烯通道，包括

1 / 8, 1 / 4, 3

/ 8 和

1 / 2

英寸。表 4 给出了

Table 4. Specification of the Used Channels
表 4.所用通道的规格

channel size 通道尺寸	inner $\times$ outer diameter $(mm)$
$1 / 8 in$ .	$1.60 \times 3.20$
$1 / 4 in$ .	$4.35 \times 6.35$
$3 / 8 in$ .	$6.35 \times 9.50$
$1 / 2 in$ .	$9.50 \times 12.70$

the inner and outer diameters of the channels. The temperature distributions inside the channels, as well as the yield, were calculated. The results are shown in Figure 14. It can be seen that there was an obvious temperature rise downside the mixer and as the reactants flowed downstream, the temperature gradually decreased. At the same time, with the increase of the channel diameter, the reaction was not isothermal anymore, and the larger the diameter, the higher the temperature. Also, the position of the maximum temperature is shifted downstream. The predicted maximum temperature was

0.30, 1.78, 4.16

, and

{9.70}^{\circ} C

, respectively. This was caused by the decrease of heat transfer efficiency with the increase of channel diameter as aforementioned. It can also noted from Figure 14 that due to the higher temperature rise inside the large-size channel, the reaction rate was accelerated, which in turn improved the DPSO yield.

As the overtemperature phenomenon inside the

1 / 2 in

. PTFE channel was prominent, and stainless steel (316L) and quartz glass were used as the material for the wall to further

Figure 14. Temperature distribution and yield prediction inside the channels with different PTFE channel diameters at

T = 55^{\circ} C, C_{0, DPS}

= 1.111 mol \cdot L^{- 1}

, and

n (H_{2} O_{2}) / n (DPS) = 2 : 1

.
improve heat transfer performance. The temperature distribution and yield along the channel are shown in Figure 15. It can

Figure 15. Temperature distribution and yield prediction inside the channels with different materials at

T = 55^{\circ} C, C_{0, DPS} = 1.111 mol \cdot L^{- 1}

, and

n (H_{2} O_{2}) / n (DPS) = 2 : 1

, with channel diameters of

1 / 2 in

.
be seen that the temperature rise of the reaction system inside the 316 L stainless steel microreactor was

5.75^{\circ} C

, while the temperature rise inside the PTFE material microreactor and quartz glass material microreactor was 9.70 and

{6.39}^{\circ} C

, respectively. The reason was the difference in thermal conductivity between different materials. The thermal conductivity of 316 L stainless steel is higher than that of PTFE. The higher the thermal conductivity, the faster the heat transfer efficiency. On the other hand, the increase in temperature promoted the reaction, thus accelerating the conversion of DPS to DPSO. As such, the yield of DPSO was higher in the microchannels made of PTFE compared to those made of 316 L or quartz glass.
In summary, the prediction of the temperature distribution provided a convenient method for selecting suitable microchannels. For highly exothermic reactions, sizing-up was limited according to the temperature rise inside the channel
to ensure reaction safety. Moreover, materials with high thermal conductivities can be used to further increase the heat transfer coefficient. As such, the temperature of the reaction system can be aligned with the temperature of the external coolant as soon as possible, avoiding a large temperature rise.

4. CONCLUSIONS

In this study, the oxidation of DPS by

H_{2} O_{2}

with PTA as the catalyst in a microreactor was investigated. A comprehensive analysis of operation parameters on the reaction was conducted. An apparent kinetic model was established, and the temperature distributions along the microreactor were predicted. The main conclusions were as follows:
(1) The effects of residence time, reaction temperature, catalyst concentration, and feed molar ratio on the oxidation reaction were systematically investigated. The results indicated that at the condition of reaction temperature of

70^{\circ} C

, residence time of 25 min , catalyst concentration of

0.75 %

, and feed molar ratio of

2 : 1

, the highest diphenyl sulfoxide yield could reach up to

84.3 %

.
(2) The kinetics of this oxidation reaction in the microreactor were studied, and a reaction kinetic model was established. Kinetic parameters, including the reaction order, activation energy, and pre-exponential factor, were determined. The accuracy of the kinetic model was verified through experiment. The study showed that the reaction was of second-order, with an activation energy of

57.5 kJ \cdot {mol}^{- 1}

and a pre-exponential factor of

2.96 \times

10^{7} {mol}^{- 1} \cdot L \cdot \min^{- 1}

. The experimental values were in good agreement with model predictions.
(3) The temperature distribution and yield variation inside the channel were predicted. The results showed that the reaction in a

1 / 16 in

. microreactor with an inner diameter of 0.8 mm was isothermal. This reaction can be safely scaled up to a

3 / 8 in

. microreactor, with the maximum temperature rise maintained below

5^{\circ} C

and without any reduction in the yield of diphenyl sulfoxide. However, the addition of acetonitrile solvent in this work may reduce the occurrence of hot spots and lower the thermal risk of the process.
This study showcased an efficient way to reduce the thermal risk of diphenyl sulfoxide synthesis in a microreactor. It also provided a convenient analysis method for the safe scale-up of reactors. It can serve as a guidance for handling highly exothermic reactions, which holds a significance for practical applications. Future research efforts should prioritize the development and implementation of real-time temperature/ pressure monitoring systems during microreactor scale-up processes, with subsequent extension to other high-risk exothermic systems (e.g., polymerization reactions). This integrated approach would substantially enhance the practical adoption of sustainable flow chemistry technologies in industrial applications.

- ASSOCIATED CONTENT

(5) Supporting Information

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.oprd.5c00018.

Detailed experimental information in the microreactor, including raw materials, product chromatographic analysis, and DSC test parameters (PDF)

- AUTHOR INFORMATION

Corresponding Authors

Gang Fu - Jiangsu Key Laboratory of Hazardous Chemicals Safety and Control, College of Safety Science and Engineering, Nanjing Tech University, Nanjing 211816, China; © orcid.org/0000-0001-8060-4215; Email: gang.fu@ njtech.edu.cn
Lei Ni - Jiangsu Key Laboratory of Hazardous Chemicals Safety and Control, College of Safety Science and Engineering, Nanjing Tech University, Nanjing 211816, China; © orcid.org/0000-0001-5941-6156; Email: lei_ni@ njtech.edu.cn

Authors

Hongrui Zhang - Jiangsu Key Laboratory of Hazardous Chemicals Safety and Control, College of Safety Science and Engineering, Nanjing Tech University, Nanjing 211816, China
Feng Xu - Jiangsu Key Laboratory of Hazardous Chemicals Safety and Control, College of Safety Science and Engineering, Nanjing Tech University, Nanjing 211816, China
Xiang Zhou - Jiangsu Key Laboratory of Hazardous Chemicals Safety and Control, College of Safety Science and Engineering, Nanjing Tech University, Nanjing 211816, China
Zhiquan Chen - Jiangsu Key Laboratory of Hazardous Chemicals Safety and Control, College of Safety Science and Engineering, Nanjing Tech University, Nanjing 211816, China
Juncheng Jiang - Jiangsu Key Laboratory of Hazardous Chemicals Safety and Control, College of Safety Science and Engineering, Nanjing Tech University, Nanjing 211816, China; © orcid.org/0000-0001-7018-2709
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.oprd.5c00018

Notes

The authors declare no competing financial interest.

ACKNOWLEDGMENTS

The authors are grateful for the support of the National Natural Science Foundation of China (No. 52274209, 52334006), Jiangsu Association for Science and Technology Youth Talent Support Program, and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX24_1539).

NOMENCLATURE

A	pre-exponential factor, ${mol}^{- 1} \cdot L \cdot \min^{- 1}$
$b$	wall thickness, m
$C_{0, DPS}$	initial concentration of phenyl sulfide, mol $\cdot L^{- 1}$
$C_{H_{2} O_{2}}$	concentration of hydrogen peroxide, $mol \cdot L^{- 1}$
$C_{DPS}$	concentration of phenyl sulfide, mol $\cdot L^{- 1}$
$C_{DPSO}$	concentration of diphenyl sulfoxide, mol $\cdot L^{- 1}$
$C_{{DPSO}_{2}}$	concentration of diphenyl sulfone, mol $\cdot L^{- 1}$
$^{p}$	average specific heat capacity, ${Jg}^{- 1} \cdot K^{- 1}$
$d_{i}$	inner diameter of channel, m
$d_{m}$	average value of outer and inner diameters, m
$E_{a}$	reaction activation energy, $kJ \cdot {mol}^{- 1}$
$h$	convective heat transfer coefficient, W $\cdot m^{- 2} \cdot K^{- 1}$
$k_{1}$	main reaction rate constants, ${mol}^{- 1} L \min^{- 1}$

k_{2}

side reaction rate constants,

{mol}^{- 1} L \min^{- 1}

K_{1}

k_{1} C_{H_{2} O_{2}^{β}}

K_{2}

- C_{0, DPS} (M - 1) k_{1}

molar ratio of hydrogen peroxide to phenyl sulfide

M_{DPS}

molar mass of phenyl sulfide,

g \cdot {mol}^{- 1}

M_{DPSO}

molar mass of diphenyl sulfoxide,

g {mol}^{- 1}

M_{{DPSO}_{2}}

molar mass of diphenyl sulfone,

g {mol}^{- 1}

n

molar flow rate of reactants,

mol \min^{- 1}

反应物的摩尔流速，

mol \min^{- 1}

Nu 努

Nusselt number 努塞尔特数

total volume flow rate,

mL \min^{- 1}

总体积流量，

mL \min^{- 1}

Q_{DPS}

volumetric flow rate of DPS,

mL \min^{- 1}

DPS 的体积流量，

mL \min^{- 1}

Q_{H_{2} O_{2}}

H_{2} O_{2}, mL \min^{- 1}

气体的体积流量常数，

J \cdot {mol}^{- 1} \cdot K^{- 1}

volumetric flow rate of

H_{2} O_{2}, mL \min^{- 1}

gas constant,

J \cdot {mol}^{- 1} \cdot K^{- 1}

S

diphenyl sulfoxide selectivity, %
二苯基亚砜选择性，%

S_{r}

channel cross-sectional area,

m^{2}

航道横截面积，

m^{2}

reaction temperature,

^{\circ} C

反应温度，

^{\circ} C

T_{c}

coolant bath temperature,

^{\circ} C

冷却液槽温度，

^{\circ} C

t

residence time, min 停留时间，分钟

total heat transfer coefficient,

W m^{- 2} K^{- 1}

总传热系数，

W m^{- 2} K^{- 1}

w_{DPS}

mass fraction of phenyl sulfide, %
苯基硫醚的质量分数，%

w_{DPSO}

mass fraction of diphenyl sulfoxide, %
二苯基亚砜的质量分数，%

w_{{DPSO}_{2}}

mass fraction of diphenyl sulfone, %
二苯砜的质量分数，%

diphenyl sulfide conversion, %
二苯基硫醚转化率，%

diphenyl sulfoxide yield, %
二苯基亚砜产量，%

channel length, m 航道长度，米

Δ H r

reaction enthalpy,

kJ {mol}^{- 1}

反应焓，

kJ {mol}^{- 1}

GREEK SYMBOLS 希腊符号

λ_{w}

thermal conductivity of channel wall,

W m^{- 1} K^{- 1}

λ_{w}

通道壁的导热系数，

W m^{- 1} K^{- 1}

λ_{f}

thermal conductivity of fluid,

W m^{- 1} K^{- 1}

λ_{f}

流体的热导率，

W m^{- 1} K^{- 1}

α

reaction order of DPS in the main reaction

α

主反应中 DPS 的反应顺序

β

reaction order of

H_{2} O_{2}

in the main reaction

β

主反应中

H_{2} O_{2}

的反应顺序

γ

reaction order of DPSO in the side reaction

γ

副反应中 DPSO 的反应顺序

δ

reaction order of

H_{2} O_{2}

in the side reaction

δ

副反应中

H_{2} O_{2}

的反应顺序

- REFERENCES - 参考文献

(1) Zhang, Y.-L.; Guo, R.-T.; Luo, H.; Liang, X.-S.; Wang, X.-C. Convergent Synthesis of Dihydropyrans from Catalytic ThreeComponent Reactions of Vinylcyclopropanes, Diazoesters, and Diphenyl Sulfoxide. Org. Lett. 2020, 22 (14), 5627-5632.
(1) Zhang, Y.-L.; Guo, R.-T.; Luo, H.; Liang, X.-S.; Wang, X.-C.乙烯基环丙烷、重氮酯和二苯基亚砜三组分催化反应中二氢吡喃的聚合。Org.2020, 22 (14), 5627-5632.
(2) Brasil, H.; de Carvalho, A. L. G.; Costa, F. F.; do Nascimento, L. A. S.; Mhadmhan, S.; Pineda, A.; Luque, R.; Valença, G. P. Preparation of novel mesoporous

Ca / P

MCM-41-based materials for mechanochemical diphenyl sulfide oxidation. Microporous Mesoporous Mater. 2020, 297, No. 110017.
(2) Brasil, H.; de Carvalho, A. L. G.; Costa, F. F.; do Nascimento, L. A. S.; Mhadmhan, S.; Pineda, A.; Luque, R.; Valença, G. P. Preparation of novel mesoporous

Ca / P

MCM-41-based materials for mechanochemical diphenyl sulfide oxidation.Microporous Mesoporous Mater.2020，297，第 110017 号。
(3) Kundu, B. K.; Das, M.; Ganguly, R.; Bhobe, P. A.; Mukhopadhyay, S. Role of zeolite encapsulated Cu (II) complexes in electron transfer as well as peroxy radical intermediates formation during oxidation of thioanisole. J. Catal. 2020, 389, 305-316.
(3) Kundu, B. K.; Das, M.; Ganguly, R.; Bhobe, P. A.; Mukhopadhyay, S. Role of zeolite encapsulated Cu (II) complexes in electron transfer as well as peroxy radical intermediates formation during oxidation of thioanisole.J. Catal.2020, 389, 305-316.
(4) Baig, N.; Madduluri, V. K.; Sah, A. K. Selective oxidation of organic sulfides to sulfoxides using sugar derived cis-dioxo molybdenum (vi) complexes: kinetic and mechanistic studies. RSC Adv. 2016, 6 (33), 28015-28022.
(4) Baig, N.; Madduluri, V. K.; Sah, A. K. 使用糖衍生的顺式二氧代钼 (vi) 复合物将有机硫化物选择性氧化为硫氧化物：动力学和机理研究。RSC Adv. 2016, 6 (33), 28015-28022.
(5) Rodríguez-Padrón, D.; Puente-Santiago, A. R.; Luna-Lama, F.; Caballero, A.; Munoz-Batista, M. J.; Luque, R. Versatile proteintemplated

{TiO}_{2}

nanocomposite for energy storage and catalytic applications. ACS Sustainable Chem. Eng. 2019, 7 (5), 5329-5337.
(5) Rodríguez-Padrón, D.; Puente-Santiago, A. R.; Luna-Lama, F.; Caballero, A.; Munoz-Batista, M. J.; Luque, R. Versatile proteintemplated

{TiO}_{2}

nanocomposite for energy storage and catalytic applications.ACS Sustainable Chem.2019, 7 (5), 5329-5337.
(6) Merkas, S.; Litvic, M.; Cepanec, I.; Vinkovic, V. Synthesis of novel, potentially biologically active dibenzosuberone derivatives. Molecules 2005, 10 (12), 1429-1437.
(6) Merkas, S.; Litvic, M.; Cepanec, I.; Vinkovic, V. Synthesis of novel, potentially biologically active dibenzosuberone derivatives.Molecules 2005, 10 (12), 1429-1437.
(7) Liu, K.; Meng, J.; Jiang, X. Gram-scale synthesis of sulfoxides via oxygen enabled by

Fe {({NO}_{3})}_{3} \cdot 9 H_{2} O

. Org. Process Res. Dev. 2023, 27 (7), 1198-1202.
(7) Liu, K.; Meng, J.; Jiang, X. Gram-scale synthesis of sulfoxides via oxygen enabled by

Fe {({NO}_{3})}_{3} \cdot 9 H_{2} O

.Org.Org.Dev.2023, 27 (7), 1198-1202.
(8) Pace, V.; Castoldi, L.; Holzer, W. Highly chemoselective synthesis of aryl allylic sulfoxides through calcium hypobromite
(8) Pace, V.; Castoldi, L.; Holzer, W. 通过次溴酸钙高化学选择性合成芳基烯丙基硫醚
oxidation of aryl allylic sulfides. Tetrahedron Lett. 2012, 53 (8), 967972.
氧化芳基烯丙基硫化物。Tetrahedron Lett.
(9) Firouzabadi, H.; Abbasi, M. Oxidation By Manganese Dioxide

({MnO}_{2})

Catalysed With

H_{2} {SO}_{4} /

silica gel. Efficient solvent-Free Oxdation Of Thioethers To Their Corresponding Sulfoxides. Synth. Coтmun. 1999, 29 (9), 1485-1491.
(9) Firouzabadi, H.; Abbasi, M. Oxidation By Manganese Dioxide

({MnO}_{2})

Catalysed With

H_{2} {SO}_{4} /

silica gel.硫醚与相应硫醚的高效无溶剂氧化。Synth.Coтmun.1999, 29 (9), 1485-1491.
(10) Kaczorowska, K.; Kolarska, Z.; Mitka, K.; Kowalski, P. Oxidation of sulfides to sulfoxides. Part 2: Oxidation by hydrogen peroxide. Tetrahedron 2005, 61 (35), 8315-8327.
(10) Kaczorowska, K.; Kolarska, Z.; Mitka, K.; Kowalski, P. 硫化物氧化成硫醚。第二部分：过氧化氢的氧化作用。Tetrahedron 2005, 61 (35), 8315-8327.
(11) Bakavoli, M.; Kakhky, A. M.; Shiri, A.; Ghabdian, M.; Davoodnia, A.; Eshghi, H.; Khatami, M. Selective and mild oxidation of sulfides to sulfoxides by

H_{2} O_{2}

using DBUH-Br3 as catalyst. Chin. Chem. Lett. 2010, 21 (6), 651-655.
(11) Bakavoli, M.; Kakhky, A. M.; Shiri, A.; Ghabdian, M.; Davoodnia, A.; Eshghi, H.; Khatami, M. 使用 DBUH-Br3 作为催化剂，通过

H_{2} O_{2}

将硫化物选择性温和氧化为硫氧化物。Chin.Chem.2010, 21 (6), 651-655.
(12) Golchoubian, H.; Hosseinpoor, F. Effective oxidation of sulfides to sulfoxides with hydrogen peroxide under transition-metal-free conditions. Molecules 2007, 12 (3), 304-311.
(12) Golchoubian, H.; Hosseinpoor, F. 在无过渡金属条件下用过氧化氢将硫化物有效氧化为硫氧化物。分子》，2007 年，12 (3)，304-311。
(13) Kummer, A.; Varga, T. Completion of thermal runaway criteria: Two new criteria to define runaway limits. Chem. Eng. Sci. 2019, 196, 277-290.
(13) Kummer, A.; Varga, T. 《完成热失控标准》：定义失控极限的两个新标准。Chem.Chem.Sci. 2019, 196, 277-290.
(14) Ni, L.; Jiang, J.; Mannan, M. S.; Mebarki, A.; Zhang, M.; Pan, X.; Pan, Y. Thermal runaway risk of semibatch processes: esterification reaction with autocatalytic behavior. Ind. Eng. Chem. Res. 2017, 56 (6), 1534-1542.
(14) Ni, L.; Jiang, J.; Mannan, M. S.; Mebarki, A.; Zhang, M.; Pan, X.; Pan, Y. 半批处理过程的热失控风险：具有自催化行为的酯化反应。Ind.Ind.Chem.2017, 56 (6), 1534-1542.
(15) Song, Q.; Ni, L.; Jiang, J.; Chen, Z.; Fu, G.; Yao, H.; Cheng, Z. Process optimization and thermal hazard analysis of the preparation of diphenyl sulfoxide using hydrogen peroxide as oxidant. Process Saf. Environ. Prot. 2022, 168, 698-711.
(15) Song, Q.; Ni, L.; Jiang, J.; Chen, Z.; Fu, G.; Yao, H.; Cheng, Z. 以过氧化氢为氧化剂制备二苯基亚砜的工艺优化和热危害分析。Process Saf.Environment.工艺安全、环境、保护。2022, 168, 698-711.
(16) Sun, Y.; Ni, L.; Papadaki, M.; Zhu, W.; Jiang, J.; Mashuga, C.; Wilhite, B.; Mannan, M. S. Process hazard evaluation for catalytic oxidation of 2 -octanol with hydrogen peroxide using calorimetry techniques. Chem. Eng. J. 2019, 378, No. 122018.
(16) Sun, Y.; Ni, L.; Papadaki, M.; Zhu, W.; Jiang, J.; Mashuga, C.; Wilhite, B.; Mannan, M. S. Process hazard evaluation for catalytic oxidation of 2 -octanol with hydrogen peroxide using calorimetry techniques.Chem.J. 2019, 378, No.J. 2019, 378, No.
(17) Gioiello, A.; Piccinno, A.; Lozza, A. M.; Cerra, B. The medicinal chemistry in the era of machines and automation: recent advances in continuous flow technology. J. Med. Chem. 2020, 63 (13), 66246647.
(17) Gioiello, A.; Piccinno, A.; Lozza, A. M.; Cerra, B. 机器和自动化时代的药物化学：连续流技术的最新进展。J. Med.Chem.2020, 63 (13), 66246647.
(18) He, W.; Li, Y.; Ni, L.; Zhu, W. Effect of stabilizer EDTA on the thermal hazard of green synthesis process of adipic acid and development of microchannel continuous flow process. Emerg. Manage. Sci. Technol. 2023, 3 (1), No. 22.
(18) He, W.; Li, Y.; Ni, L.; Zhu, W. 稳定剂 EDTA 对己二酸绿色合成工艺热危害的影响及微通道连续流工艺的开发。Emerg.Manage.Sci.2023, 3 (1), No.
(19) Tanimu, A.; Jaenicke, S.; Alhooshani, K. Heterogeneous catalysis in continuous flow microreactors: A review of methods and applications. Chem. Eng. J. 2017, 327, 792-821.
(19) Tanimu, A.; Jaenicke, S.; Alhooshani, K. Heterogeneous catalysis in continuous flow microreactors：方法与应用综述。Chem.Chem.J. 2017, 327, 792-821.
(20) Engelbrecht, N.; Everson, R. C.; Bessarabov, D.; Kolb, G. Microchannel reactor heat-exchangers: A review of design strategies for the effective thermal coupling of gas phase reactions. Chem. Eng. Process. 2020, 157, No. 108164.
(20) Engelbrecht, N.; Everson, R. C.; Bessarabov, D.; Kolb, G. Microchannel reactor heat-exchangers：气相反应有效热耦合设计策略综述。Chem.Chem.Process.2020，157，108164 号。
(21) Sathiyamoorthi, E.; Lee, J.; Devanesan, S.; Priya, S.; Shanmuganathan, R. Catalytic biodiesel production from Jatropha curcas oil: A comparative analysis of microchannel, fixed bed, and microwave reactor systems with recycled ZSM-5 catalyst. Environ. Res. 2024, 258, No. 119474.
(21) Sathiyamoorthi, E.; Lee, J.; Devanesan, S.; Priya, S.; Shanmuganathan, R. Catalytic biodiesel production from Jatropha curcas oil：使用再生 ZSM-5 催化剂的微通道、固定床和微波反应器系统的比较分析。Environ.2024, 258, No.
(22) Yue, J. Green process intensification using microreactor technology for the synthesis of biobased chemicals and fuels. Chem. Eng. Process. 2022, 177, No. 109002.
(22) Yue, J. 利用微反应器技术合成生物基化学品和燃料的绿色工艺强化。Chem.Chem.Process.2022, 177, No.
(23) Yin, L.; Ge, T.; Zuo, C.; Li, Y.; Wang, M.; Cui, G.; Guo, L.; Huang, H. Simulation and experimental study of homogeneous DielsAlder reaction in a microchannel reactor. Chem. Eng. Process. 2023, 192, No. 109520.
(23) Yin, L.; Ge, T.; Zuo, C.; Li, Y.; Wang, M.; Cui, G.; Guo, L.; Huang, H. Simulation and experimental study of homogeneous DielsAlder reaction in a microchannel reactor.Chem.Chem.Process.2023, 192, No.
(24) Guo, S.; Zhu, G.; Zhan, L.; Li, B. Continuous kilogram-scale process for the synthesis strategy of

1, 3, 5

-trimethyl-2-nitrobenzene in microreactor. Chem. Eng. Res. Des. 2022, 178, 179-188.
(24) Guo, S.; Zhu, G.; Zhan, L.; Li, B. 在微反应器中连续公斤级合成

1, 3, 5

-三甲基-2-硝基苯的工艺。Chem.Chem.Res.Des.2022, 178, 179-188.
(25) Zhao, H.; Liu, S.; Shang, M.; Su, Y. Direct oxidation of benzene to phenol in a microreactor: Process parameters and reaction kinetics study. Chem. Eng. Sci. 2021, 246, No. 116907.
(25) Zhao, H.; Liu, S.; Shang, M.; Su, Y. 在微反应器中将苯直接氧化为苯酚：工艺参数和反应动力学研究。Chem.Chem.2021, 246, No. 116907.
(26) Xia, S.; Yang, T.; Xu, J.; Chen, Z. Efficient continuous-flow synthesis of diacyl peroxide in a microreactor and the post-processing of its effluent. Chem. Eng. Sci. 2023, 281, No. 119140.
(26) Xia, S.; Yang, T.; Xu, J.; Chen, Z. 微反应器中过氧化二酰的高效连续流合成及其流出物的后处理。Chem.Chem.2023, 281, No.
(27) Ma, H.; Li, P.; Huang, A.; Zhao, W.; Zhang, X. The kinetics study on sulfonation reaction of continuous microfluidic synthesis of 1-tetradecene. Chem. Eng. Sci. 2024, 290, No. 119883.
(27) Ma, H.; Li, P.; Huang, A.; Zhao, W.; Zhang, X. 1-十四烯连续微流控合成磺化反应动力学研究。Chem.Chem. Eng.2024, 290, No. 119883.
(28) Xu, Q.; Fan, H.; Yao, H.; Wang, D.; Yu, H.; Chen, B.; Yu, Z.;

Su, W

. Understanding monoacylation of symmetrical diamines: A kinetic study of acylation reaction of

m

-phenylenediamine and benzoic anhydride in microreactor. Chem. Eng. J. 2020, 398, No. 125584.
(28) Xu, Q.; Fan, H.; Yao, H.; Wang, D.; Yu, H.; Chen, B.; Yu, Z.;

Su, W

.了解对称二胺的单酰化：

m

-苯二胺和苯甲酸酐在微反应器中酰化反应的动力学研究。Chem.Chem.J. 2020, 398, No.
(29) Chen, Z.; Liu, J.; Ni, L.; Jiang, J.; Yu, Y.; Pan, Y. ContinuousFlow Synthesis of Methyl Sulfone with Microchannel Reactors: A Safer and Efficient Production Strategy. Org. Process Res. Dev. 2023, 27 (8), 1445-1454.
(29) Chen, Z.; Liu, J.; Ni, L.; Jiang, J.; Yu, Y.; Pan, Y. 利用微通道反应器连续流合成甲基砜：更安全高效的生产策略。Org.Process Res.Dev.2023, 27 (8), 1445-1454.
(30) Wu, Y.; Chen, Z.; Wang, F.; Xu, J.; Wang, Y. Efficient organocatalytic synthesis of styrene oxide from styrene and its kinetic study in a continuous-flow microreaction system. Chem. Eng. Sci. 2022, 247, No. 117045.
(30) Wu, Y.; Chen, Z.; Wang, F.; Xu, J.; Wang, Y. Efficient organocatalytic synthesis of styrene oxide from styrene and its kinetic study in a continuous-flow microreaction system.Chem.Chem.2022, 247, No.
(31) Sun, H.-T.; Pan, B.; Zhang, S.-S.; Su, X.-B.; Xu, M.-R.; Hu, Z.Q.; Xu, G.-Z. Continuous flow synthesis of C-acyloxy-substituted aziridines in microchannel reactor: Addition of carboxylic acids to 2methylenaziridines. Tetrahedron Lett. 2024, 138, No. 154982.
(31) Sun, H.-T.; Pan, B.; Zhang, S.-S.; Su, X.-B.; Xu, M.-R.; Hu, Z.Q.; Xu, G.-Z.在微通道反应器中连续流合成 C-acyloxy 取代的氮丙啶：2methylenaziridines 的羧酸加成。Tetrahedron Lett.
(32) Ebrahimi, F.; Virkki-Hatakka, T.; Turunen, I. Safety analysis of intensified processes. Chem. Eng. Process. 2012, 52, 28-33.
(32) Ebrahimi, F.; Virkki-Hatakka, T.; Turunen, I. 强化过程的安全分析。Chem.Eng.Process.2012, 52, 28-33.
(33) Kockmann, N.; Gottsponer, M.; Roberge, D. M. Scale-up concept of single-channel microreactors from process development to industrial production. Chem. Eng. J. 2011, 167 (2-3), 718-726.
(33) Kockmann, N.; Gottsponer, M.; Roberge, D. M. 单通道微反应器从工艺开发到工业生产的放大概念。Chem.J. 2011, 167 (2).J. 2011, 167 (2-3), 718-726.
(34) Lu, P.; Li, Y.; Zhang, J.; Zhao, Y.; Wang, Q.; Chen, Y.; Jin, N.;

Yu, X

. Continuous synthesis of

N, N

-dicyanoethylaniline in microreactors: reaction kinetics and process intensification. Chin. J. Chem. Eng. 2024, 72, 95-105.
(34) Lu, P.; Li, Y.; Zhang, J.; Zhao, Y.; Wang, Q.; Chen, Y.; Jin, N.;

Yu, X

.在微反应器中连续合成

N, N

-dicyanoethylaniline: 反应动力学和过程强化.Chin.J. Chem.2024, 72, 95-105.
(35) Zhu, H.; Yan, J.; Zhang, Z.; Ren, J.; Zhu, Y.; Zhao, H.; Xu, W.; Sun, B.; Yang, C. Kinetics Study of the Peroxidation of tert-Butyl Alcohol to tert-Butyl Hydrogen Peroxide in a Microreactor. Org. Process Res. Dev. 2024, 28 (5), 1486-1493.
(35) Zhu, H.; Yan, J.; Zhang, Z.; Ren, J.; Zhu, Y.; Zhao, H.; Xu, W.; Sun, B.; Yang, C. Kinetics Study of Peroxidation of tert-Butyl Alcohol to tert-Butyl Hydrogen Peroxide in a Microreactor.Org.过程研究。Dev.2024, 28 (5), 1486-1493.
(36) Wang, H.; Shan, S.; Li, P.; Sun, J.; Lin, C.; Zhou, R.; Zeng, X. Deep oxidative desulfurization of model fuel catalyzed by phosphotungstic acid/mesoporous zeolite. React. Kinet., Mech. Catal. 2022, 135 (4), 1999-2012.
(36) Wang, H.; Shan, S.; Li, P.; Sun, J.; Lin, C.; Zhou, R.; Zeng, X. 磷钨酸/介孔沸石催化的模型燃料深度氧化脱硫。React.Kinet.Catal.2022, 135 (4), 1999-2012.
(37) He, H.; Zheng, M.; Liu, Q.; Liu, J.; Zhao, J.; Zhuang, Y.; Liu, X.; Xu, Q.; Kirk, S. R.; Yin, D. Hydroxyl-assisted selective epoxidation of perillyl alcohol with hydrogen peroxide by vanadium-substituted phosphotungstic acid hinged on imidazolyl activated carbon. New J. Chem. 2022, 46 (14), 6636-6645.
(37) He, H.; Zheng, M.; Liu, Q.; Liu, J.; Zhao, J.; Zhuang, Y.; Liu, X.; Xu, Q.; Kirk, S. R.; Yin, D. Huxyyl-assisted selective epoxidation of perillyl alcohol with hydrogen peroxide by vanadium-substituted phosphotungstic acid hinged on imidazolyl activated carbon.New J. Chem.2022, 46 (14), 6636-6645.
(38) Wang, J.; Mannan, M. S.; Wilhite, B. A. Integrated thermodynamic and kinetic model of homogeneous catalytic N oxidation processes. AIChE J. 2020, 66 (4), No. e16875.
(38) Wang, J.; Mannan, M. S.; Wilhite, B. A. 均相催化 N 氧化过程的综合热力学和动力学模型。AIChE J. 2020, 66 (4), No.
(39) Chen, Z.; Zhu, H.; Ni, L.; Jiang, J.; Yu, Y.; Pan, Y. Research on the crystallization clogging during reaction process in the microchannel continuous flow process. J. Ind. Eng. Chem. 2024, 136, 514523.
(39) Chen, Z.; Zhu, H.; Ni, L.; Jiang, J.; Yu, Y.; Pan, Y. 《微通道连续流工艺反应过程中结晶堵塞的研究》。J. Ind.Eng.Chem.2024, 136, 514523.
(40) Chen, Q.; Wang, J.; Gao, M.; Liu, L.; Tao, J. Review on loss prevention of chemical reaction thermal runaway: Principles and application. Emerg. Manage. Sci. Technol. 2022, 2 (1), 1-8.
(40) Chen, Q.; Wang, J.; Gao, M.; Liu, L.; Tao, J. Review on loss prevention of chemical reaction thermal runaway：Principles and Application.Emerg.Manage.科学与技术》（Emerg.2022, 2 (1), 1-8.
(41) Gemoets, H. P. L.; Su, Y.; Shang, M.; Hessel, V.; Luque, R.; Noël, T. Liquid phase oxidation chemistry in continuous-flow microreactors. Chem. Soc. Rev. 2016, 45 (1), 83-117.
(41) Gemoets, H. P. L.; Su, Y.; Shang, M.; Hessel, V.; Luque, R.; Noël, T. 连续流微反应器中的液相氧化化学。Chem. Soc.Soc. Rev. 2016, 45 (1), 83-117.
(42) Westermann, T.; Mleczko, L. Heat Management in Microreactors for Fast Exothermic Organic SynthesesFirst Design Principles. Org. Process Res. Dev. 2016, 20 (2), 487-494.
(42) Westermann, T.; Mleczko, L. 快速放热有机合成微反应器中的热量管理--初步设计原则。Org.工艺研究。Dev.2016, 20 (2), 487-494.
(43) Fath, V.; Szmais, S.; Lau, P.; Kockmann, N.; Röder, T. Modelbased scale-up predictions: from micro-to millireactors using inline fourier transform infrared spectroscopy. Org. Process Res. Dev. 2019, 23 (9), 2020-2030.
(43) Fath, V.; Szmais, S.; Lau, P.; Kockmann, N.; Röder, T. Modelbased scale-up predictions: From micro-to millireactors using inline fourier transform infrared spectroscopy.Org.Process Res.Dev.2019, 23 (9), 2020-2030.
(44) Xu, F.; Chen, Z. Q.; Ni, L.; Fu, G.; Liu, J.; Jiang, J. C. Study on Continuous Flow Nitration of Naphthalene. Org. Process Res. Dev. 2023, 27 (11), 2134-2145.
(44) Xu, F.; Chen, Z. Q.; Ni, L.; Fu, G.; Liu, J.; Jiang, J. C. Study on Continuous Flow Nitration of Naphthalene.Org.工艺研究。Dev.2023, 27 (11), 2134-2145.

Received: January 15, 2025
收到：2025 年 1 月 15 日
Revised: March 26, 2025
修订：2025 年 3 月 26 日
Accepted: April 3, 2025
接受：2025 年 4 月 3 日

Continuous Flow Synthesis and Kinetic Study of Diphenyl Sulfoxide in a Microreactor 微反应器中二苯基亚砜的连续流合成与动力学研究

Abstract 摘要

1. INTRODUCTION 1.引言

2. EXPERIMENTAL SECTION 2.实验部分

3. RESULTS AND DISCUSSION3.结果与讨论

4. CONCLUSIONS

- ASSOCIATED CONTENT

(5) Supporting Information

- AUTHOR INFORMATION

Corresponding Authors

Authors

Notes

ACKNOWLEDGMENTS

NOMENCLATURE

GREEK SYMBOLS 希腊符号

- REFERENCES - 参考文献

Continuous Flow Synthesis and Kinetic Study of Diphenyl Sulfoxide in a Microreactor
微反应器中二苯基亚砜的连续流合成与动力学研究

3. RESULTS AND DISCUSSION
3.结果与讨论