Process for continuous flow oxidation of thioethers to sulfones

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for preparing sulphone through continuous flow oxidation of thioether. The method comprises the following steps: carrying out oxidation reaction on a mixed material and an oxidizing agent in a continuous flow reactor; the mixed material comprises thioether, a catalyst and a solvent, and the catalyst comprises ferric iron salt and tetrabutylammonium bromide; in the mixed material, the molar ratio of the ferric salt to the thioether is (0.05-0.1): 1, and the molar ratio of the tetrabutylammonium bromide to the thioether is (0.05-0.5): 1; the solvent comprises at least one of acetonitrile, dichloromethane, dichloroethane, toluene and ethyl acetate; the oxidizing agent comprises oxygen and ozone. According to the method, ozone / oxygen is used as an oxidizing agent, ferric iron salt and tetrabutylammonium bromide are used as catalysts, continuous flow oxidation of thioether into sulfone can be achieved, the production efficiency and the safety coefficient are remarkably improved, and the selectivity and the yield of thioether oxidation are high.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, in particular to a method for continuously oxidizing sulfide into sulfone. Background Art

[0002] Sulfone compounds are an important class of organosulfur compounds with extensive application value in medicine, pesticides, polymer materials, catalysts, and other fields. Therefore, the efficient, economical, and safe synthesis of sulfone compounds has become a key focus in related fields.

[0003] Traditional methods for synthesizing sulfone compounds typically involve the oxidation of sulfides. Commonly used oxidants include hydrogen peroxide, percarboxylic acids, hypohalites, permanganates, chromates, and some metal catalyst-oxidant systems. However, these traditional methods often have limitations, such as the need to use metered or excessive amounts of expensive, highly toxic, or corrosive oxidants; harsh reaction conditions (such as high temperatures and strong acid / base environments); the potential production of large amounts of environmentally unfriendly byproducts; difficult to control reaction selectivity, prone to side reactions or overoxidation, which affect the yield and purity of the target product; and complex post-processing. These factors limit the application of traditional methods in large-scale industrial production.

[0004] Ozone (O3) is a powerful oxidant with a high oxidation potential and unique reactivity. Most importantly, ozone decomposes into non-toxic oxygen (O2) after the reaction, making it a "green" oxidant. The use of ozone for organic synthesis oxidation reactions theoretically has the advantages of environmental friendliness and atom economy. However, ozone oxidation reactions, especially when carried out in traditional batch reactors, have significant safety hazards. This is because unstable intermediates with potential explosion risks, such as ozonides or peroxides, may be generated during the reaction. In addition, ozone itself is toxic, and the subsequent reaction quenching is usually an exothermic process that requires precise and efficient temperature control. It can be said that given the danger of explosive intermediates that may be produced during the reaction and the toxicity of ozone itself, traditional batch ozonation reactions are difficult to be fully incorporated into a safe and controllable experimental operation system in synthetic chemistry.

[0005] To overcome the safety and efficiency challenges of traditional batch reactions involving highly exothermic reactions, hazardous reagents, or intermediates, continuous flow processes and microreactor technology have attracted increasing attention as a promising alternative. However, the efficient and selective continuous flow oxidation of sulfides to high-valent sulfones remains a challenging task. In continuous flow reactions, to ensure synthesis efficiency, the residence time of the reactants is typically short, typically ranging from seconds to minutes. For multiphase reactions involving gases (such as ozone) and liquid reactants, rapid gas flow can further shorten the actual residence time or mass transfer time of the liquid phase, placing higher demands on reaction kinetics. Although ozone has strong oxidizing power, the reaction rate of the two-step oxidation (sulfide to sulfoxide, sulfoxide to sulfone) may be insufficient to achieve high conversion and selectivity of sulfide to sulfone within short residence times, especially under mild conditions. For example, in 2011, the Kappe team reported a method for preparing sulfoxides by continuous flow ozone oxidation of sulfides using a microreactor (Organic Letters, 13, 984-987.). This method mainly produces sulfoxides in a short residence time, accompanied by partial peroxidation to form sulfones. To obtain a pure sulfone product, the reaction mixture must be removed and then subjected to an additional traditional oxidation step (such as using hydrogen peroxide), which increases the number of steps and costs and does not achieve a single-step, efficient, and continuous conversion of sulfides to sulfones. Currently, there are no publicly reported methods that can directly, efficiently, and highly selectively convert sulfides to sulfones by ozone oxidation using a continuous flow reactor in a short residence time.

[0006] In view of this, the following invention is proposed. Summary of the Invention

[0007] The object of the present invention is to provide a method for achieving a single-step efficient conversion of sulfide to sulfone by using a mixed system of ozone and oxygen as an oxidant, using trivalent iron salts and tetrabutylammonium bromide, which are abundant in resources and low in cost, as catalysts, in combination with optional photocatalysis and continuous flow synthesis methods. The method of the present invention has high selectivity, high yield, high safety and low raw material cost.

[0008] In order to achieve the above object of the present invention, the present invention provides a method for continuous flow oxidation of sulfide to sulfone, comprising the following steps: mixing a material and an oxidant to carry out oxidation reaction in a continuous flow reactor;

[0009] The mixed material includes sulfide, a catalyst and a solvent, the catalyst includes a trivalent iron salt and tetrabutylammonium bromide; in the mixed material, the molar ratio of the trivalent iron salt to the sulfide is (0.05-0.1):1, and the molar ratio of the tetrabutylammonium bromide to the sulfide is (0.05-0.5):1; the solvent includes at least one of acetonitrile, dichloromethane, dichloroethane, toluene and ethyl acetate; and the oxidant includes oxygen and ozone.

[0010] In a specific embodiment of the present invention, in the catalyst, the molar ratio of the trivalent iron salt to the tetrabutylammonium bromide is 1:(1-5), further 1:2.

[0011] In a specific embodiment of the present invention, the ferric salt includes at least one of ferric nitrate, ferric p-toluenesulfonate, ferric bromide and ferric chloride. Further, the ferric salt is ferric nitrate.

[0012] In a specific embodiment of the present invention, the thioether includes at least one of methylphenyl sulfide, diphenyl sulfide, ethylphenyl sulfide, 4-methoxythioanisole, cyclopropylphenyl sulfide, 4-methylthioanisole, 4-bromothioanisole, 4-chlorothioanisole, benzyl methyl sulfide, 2-methylthiopyridine, 4-nitrothioanisole, 2-chloroethylphenyl sulfide, dibenzothiophene, 3-methoxythioanisole, 4-(methylthio)benzonitrile, 4-(methylthio)phenol, thiochroman-4-one, 2-methoxythioanisole, 2-bromothioanisole, phenylbenzyl sulfide, methoxymethylphenyl sulfide, 2-(methylthio)naphthalene, 4-(methylthio)acetophenone, methyl 2-chloro-4-(methylthio)benzoate, 1-(2-ethyl-thioethyl)-2-methyl-5-nitroimidazole and mesitylene-(4-methoxyphenyl)sulfane.

[0013] In a specific embodiment of the present invention, the molar concentration of the sulfide in the mixture is 0.01 to 0.02 mmol / mL.

[0014] In a specific embodiment of the present invention, in the continuous flow reactor, the flow rate of the mixed material is 0.4 to 1.2 mL / min.

[0015] In a specific embodiment of the present invention, the continuous flow reaction wherein the flow rate of the oxidant is 18 to 20 mL / min. Furthermore, the concentration of the ozone in the oxidant is 140 to 160 mg / L.

[0016] In a specific embodiment of the present invention, the temperature of the oxidation reaction is ≤40°C, preferably ≤20°C, and more preferably 0-5°C.

[0017] In a specific embodiment of the present invention, the oxidation reaction is carried out under light, or the oxidation reaction is carried out in the absence of light. Further, when the oxidation reaction is carried out under light, the wavelength of the light is 365 to 610 nm.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] (1) The present invention utilizes ozone / oxygen as an oxidant and trivalent iron salt and tetrabutylammonium bromide as catalysts to achieve continuous flow oxidation of sulfides to sulfones, significantly improving production efficiency and safety factors;

[0020] (2) The present invention adopts certain oxidants and catalysts, and further improves the selectivity and yield of sulfide oxidation by adjusting the material composition and feed conditions; moreover, the method of the present invention is applicable to the oxidation of various sulfide compounds and has certain universality. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0022] Figure 1 Schematic diagram of a reaction device for continuous flow oxidation of sulfide to sulfone provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0023] The technical scheme of the present invention will be clearly and completely described below in conjunction with the accompanying drawings and specific embodiments, but it will be understood by those skilled in the art that the following described embodiments are part of embodiments of the present invention, rather than all embodiments, and are only used to illustrate the present invention, and should not be considered as limiting the scope of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work are within the scope of protection of the present invention. Those who do not specify specific conditions in the embodiments are carried out according to normal conditions or the conditions recommended by the manufacturer. Those whose reagents or instruments are not specified by the manufacturer are conventional products that can be purchased commercially.

[0024] The "continuous flow reactor" in the present invention is a unique reactor, which is essentially different from the traditional kettle reactor. The continuous flow reactor adopts a microchannel mode design. Through the new process intensification technology, the fluid is repeatedly impacted and cross-mixed through the microchannel to achieve efficient mass transfer and efficient heat exchange performance, and can also greatly improve the mixing efficiency of heterogeneous reactions. The continuous flow reactor has the characteristics of high-speed mixing, high-speed heat transfer, narrow distribution of reactant residence time, good repeatability, rapid system response and easy operation. The continuous flow reactor has multiple feed ports, and multiple different reactants can be input simultaneously or sequentially through a feed pump.

[0025] The "microchannel continuous flow reactor" of this invention is a representative device capable of continuous operation, enabling continuous flow reactions. Compared to traditional chemical reaction systems, microchannel reactors offer advantages such as microscale, large surface area, compact size, high-throughput screening, rapid scale-up, continuous process, flexible production, process safety, and decentralized production. They also demonstrate exceptional heat and mass transfer capabilities. Microchannel reactors are suitable for a variety of low-temperature, high-temperature, high-risk, and heterogeneous chemical reactions.

[0026] As used herein, "residence time" refers to the time the reactants spend flowing through a continuous flow reactor. The materials react under the repeated impact and mixing of the solvent and, under the pressure of the reactor's feed pump, flow continuously through the reactor's microchannels before exiting the reactor. The residence time is the time between the reaction material entering the reactor and the reaction material exiting the reactor.

[0027] A method for continuous flow oxidation of sulfide to sulfone comprises the following steps: mixing a material and an oxidant to carry out oxidation reaction in a continuous flow reactor;

[0028] The mixture includes sulfide, a catalyst and a solvent, the catalyst includes a trivalent iron salt and tetrabutylammonium bromide; in the mixture, the molar ratio of the trivalent iron salt to the sulfide is (0.05-0.1):1, and the molar ratio of the tetrabutylammonium bromide to the sulfide is (0.05-0.5):1; the solvent includes at least one of acetonitrile, dichloromethane, dichloroethane, toluene and ethyl acetate; and the oxidant includes oxygen and ozone.

[0029] The present invention utilizes ozone / oxygen as oxidants and trivalent iron salts and tetrabutylammonium bromide as catalysts to achieve continuous flow oxidation of sulfides to sulfones, significantly improving production efficiency and safety. The high mass transfer efficiency of the continuous flow reactor, combined with the type of catalyst employed, allows the oxidant gas to rapidly and fully combine with the sulfide, thereby enhancing reaction efficiency.

[0030] The catalyst used in the present invention can, on the one hand, catalyze the reaction smoothly in a continuous flow system, while other iron salts cannot achieve the same effect. On the other hand, ferric iron salts and tetrabutylammonium bromide are widely available and low in cost, which can reduce the cost of reaction raw materials. The ferric iron salt can be in any form, including any one or more of ferric iron salts and their hydrates (such as ferric nitrate nonahydrate).

[0031] The oxidant used in the present invention includes both oxygen and ozone, which greatly improves the oxidation ability and the reaction rate, and can significantly reduce the reaction temperature, thereby avoiding the safety hazards caused by high temperature.

[0032] Figure 1 A schematic diagram of a reaction apparatus for the continuous flow oxidation of sulfide to sulfone provided in an embodiment of the present invention. In actual operation, a mixture of sulfide, catalyst, and solvent is fed as one stream into a continuous flow reactor through one feed port via a feed pump; an oxidant is fed as another stream into the continuous flow reactor through another feed port. After the reaction in the continuous flow reactor is completed, the reaction liquid can be collected by a gas-liquid separator.

[0033] In a specific embodiment of the present invention, the molar ratio of the trivalent iron salt to tetrabutylammonium bromide in the catalyst is 1:(1-5), for example, 1:1, 1:2, 1:3, 1:4, 1:5, or a range consisting of any two thereof, thereby further improving the reaction efficiency and significantly increasing the selectivity of sulfide oxidation to sulfone.

[0034] In a specific embodiment of the present invention, in the mixed material, the molar ratio of the trivalent iron salt to the sulfide is (0.05-0.1):1, for example, it can be 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.1:1 or a range consisting of any two thereof, and the molar ratio of tetrabutylammonium bromide to the sulfide is (0.05-0.5):1, for example, it can be 0.05:1, 0.1:1, 0.15:1, 0.2:1, 0.25:1, 0.3:1, 0.35:1, 0.4:1, 0.45:1, 0.5:1 or a range consisting of any two thereof, thereby further taking into account both the reaction rate and the selectivity of oxidation to sulfone.

[0035] In a specific embodiment of the present invention, the ferric salt includes at least one of ferric nitrate, ferric p-toluenesulfonate, ferric bromide and ferric chloride. Preferably, the ferric salt is ferric nitrate.

[0036] In a specific embodiment of the present invention, the thioether includes at least one of methylphenyl sulfide, diphenyl sulfide, ethylphenyl sulfide, 4-methoxythioanisole, cyclopropylphenyl sulfide, 4-methylthioanisole, 4-bromothioanisole, 4-chlorothioanisole, benzyl methyl sulfide, 2-methylthiopyridine, 4-nitrothioanisole, 2-chloroethylphenyl sulfide, dibenzothiophene, 3-methoxythioanisole, 4-(methylthio)benzonitrile, 4-(methylthio)phenol, thiochroman-4-one, 2-methoxythioanisole, 2-bromothioanisole, phenylbenzyl sulfide, methoxymethylphenyl sulfide, 2-(methylthio)naphthalene, 4-(methylthio)acetophenone, methyl 2-chloro-4-(methylthio)benzoate, 1-(2-ethyl-thioethyl)-2-methyl-5-nitroimidazole and mesitylene-(4-methoxyphenyl)sulfane. The above-mentioned sulfide compounds are suitable for the method of continuous oxidation to sulfones of the present invention.

[0037] In a specific embodiment of the present invention, the molar concentration of sulfide in the mixture is 0.01 to 0.02 mmol / mL, for example, 0.01 mmol / mL, 0.012 mmol / mL, 0.015 mmol / mL, 0.018 mmol / mL, 0.02 mmol / mL, or any two thereof, thereby further helping to improve the stability, safety, and product yield of the reaction process.

[0038] In a specific embodiment of the present invention, in a continuous flow reactor, the flow rate of the mixed material is 0.4 to 1.2 mL / min, for example, it can be 0.4 mL / min, 0.6 mL / min, 0.7 mL / min, 0.8 mL / min, 0.9 mL / min, 1 mL / min, 1.1 mL / min, 1.2 mL / min or a range consisting of any two thereof. If the flow rate of the mixed material is too slow, the production efficiency is affected; if the flow rate is too fast, on the one hand, the reaction is incomplete, and on the other hand, the selectivity is deteriorated. The present invention regulates the flow rate of the mixed material within the above range to take into account the raw material conversion rate, the oxidation to sulfone selectivity and the production efficiency for the oxidation to sulfone system of the present invention.

[0039] In a specific embodiment of the present invention, the continuous flow reaction wherein the flow rate of the oxidant is 18 to 20 mL / min, for example, 18 mL / min, 18.5 mL / min, 19 mL / min, 19.5 mL / min, 20 mL / min, or any two thereof. Furthermore, the concentration of ozone in the oxidant is 140 to 160 mg / L, for example, 140 mg / L, 145 mg / L, 150 mg / L, 155 mg / L, 160 mg / L, or any two thereof, thereby further helping to ensure the selectivity of the oxidation of sulfide to sulfone and the stability of the oxidation reaction.

[0040] Specifically, the oxidant is prepared by mixing oxygen provided by an oxygen cylinder with ozone. The present invention can convert oxygen into ozone through an ozone generator, and then combine it with oxygen to form an oxidant containing ozone and oxygen.

[0041] In a specific embodiment of the present invention, the pressure of the oxidant is 2.0 bar±0.5 bar, that is, the pressure of the mixed gas containing ozone and oxygen is 2.0 bar±0.5 bar.

[0042] The present invention uses ozone / oxygen as an oxidant and ferric nitrate and tetrabutylammonium bromide as catalysts, and further optimizes the catalyst ratio, mixed materials, and oxidant feed rate, so as to achieve extremely high selectivity and yield in the oxidation of sulfide.

[0043] In a specific embodiment of the present invention, the temperature of the oxidation reaction is ≤40°C, such as ≤20°C, and can further be 0-5°C, for example, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C or a range consisting of any two thereof.

[0044] In a specific embodiment of the present invention, the oxidation reaction is carried out under light. Further, during the light irradiation, the wavelength is 365 to 610 nm, for example, 365 nm, 385 nm, 405 nm, 475 nm, 610 nm, or any two thereof. Further, during the light irradiation, the intensity is 180 to 220 mW / cm 2 , for example, 180 mW / cm 2 、190mW / cm 2 , 200mW / cm 2 , 210mW / cm 2 , 220mW / cm 2 Or a range consisting of any two of them.

[0045] In a specific embodiment of the present invention, the oxidation reaction can be carried out in the absence of light.

[0046] In a specific embodiment of the present invention, the continuous flow reactor includes a microchannel continuous flow reactor. The continuous flow reactor used in the present invention includes but is not limited to a Corning LSR-photo continuous flow photocatalytic reactor. In actual operation, the light source of the photocatalytic reaction module can be adjusted to any wavelength within the range of 365 to 610 nm, such as 405 nm; the intensity can be adjusted to 180 to 220 mW / cm 2 Any intensity within the range, such as 200mW / cm 2 , in order to utilize the photocatalytic oxidation reaction.

[0047] In a specific embodiment of the present invention, the mixing residence time of the mixed material in the reaction zone of the continuous flow reactor is 8 to 9 seconds.

[0048] In a specific embodiment of the present invention, the process further includes: allowing the material after the oxidation reaction to stand, extracting it 2-3 times with ethyl acetate and water, drying the organic layer to remove water, and then rotary evaporating it to obtain a crude product; and subjecting the crude product to column chromatography to obtain a pure product. The eluent for column chromatography separation may include, but is not limited to, petroleum ether and ethyl acetate in a volume ratio of 50:1.

[0049] Example 1

[0050] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0051]

[0052] The specific method includes the following steps:

[0053] (1) To a beaker, 1.25 mmol of the substrate methylphenyl sulfide, 50.5 mg of ferric nitrate nonahydrate, and 80.5 mg of tetrabutylammonium bromide were added, followed by 73 mL of acetonitrile. The mixture was ultrasonically treated for 5 to 10 minutes, filtered, and the filtrate was collected and transferred to a clean 150 mL conical flask to obtain a mixed material.

[0054] (2) The mixed material obtained in step (1) was introduced into a continuous flow reactor as a stream of material using a plunger pump, and the flow rate of the mixed material was controlled to be 0.8 mL / min. The ozone / oxygen mixed gas was introduced into the continuous flow reactor as another stream of material, and the flow rate of the mixed gas was controlled to be 20 mL / min. The light source of the continuous flow reactor was set to 200 mW / cm 2 , 405nm LED, set the reaction temperature to 0°C, and the total reaction time to 8s. After the reaction, the reaction solution was collected and allowed to stand. The ozone / oxygen mixture had a mixed gas pressure of 2 bar and an ozone concentration of 150mg / L.

[0055] Examples 2-3

[0056] Examples 2-3 provide a method for the continuous flow oxidation of sulfides to sulfones, with reference to Example 1, except that the flow rate of the mixture in step (2) is different.

[0057] The flow rate of the mixture in step (2) of Examples 1 to 3, as well as the conversion rate of the raw material sulfide and the total yield of sulfone after the reaction are specifically shown in Table 1. The reaction solution after the reaction was detected by high performance liquid chromatography, and the conversion rate of the raw material sulfide and the total yield of sulfone were calculated based on the peak position and area (the same method was used in the subsequent Examples and Comparative Examples).

[0058] Table 1 Mixed material flow rate and analysis results of Examples 1 to 3

[0059] serial number Mixed material flow rate Sulfide conversion rate Total yield of sulfone Example 1 0.8mL / min 100％ 91％ Example 2 1.0mL / min 100％ 94％ Example 3 1.2mL / min 100％ 96％

[0060] Example 4

[0061] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0062]

[0063] The specific method includes the following steps:

[0064] (1) Add 1.25 mmol of substrate diphenyl sulfide, 50.5 mg of ferric nitrate nonahydrate, and 80.5 mg of tetrabutylammonium bromide to a beaker, then add 73 mL of acetonitrile, ultrasonicate for 5-10 min, filter, collect the filtrate, and transfer it to a clean 150 mL conical flask to obtain a mixed material.

[0065] (2) The mixed material obtained in step (1) was introduced into a continuous flow reactor as a stream of material using a plunger pump, and the flow rate of the mixed material was controlled to be 1 mL / min. The ozone / oxygen mixed gas was introduced into the continuous flow reactor as another stream of material, and the flow rate of the mixed gas was controlled to be 20 mL / min. The light source of the continuous flow reactor was set to 200 mW / cm 2 , 405nm LED, set the reaction temperature to 0°C, and the total reaction time to 8s. After the reaction, the reaction solution was collected and allowed to stand. The ozone / oxygen mixture had a mixed gas pressure of 2 bar and an ozone concentration of 150mg / L.

[0066] Examples 5 to 8

[0067] Examples 5 to 8 provide methods for the continuous flow oxidation of sulfides to sulfones, with reference to Example 4, except that the flow rate of the mixed material and / or the flow rate of the mixed gas in step (2) is different.

[0068] The flow rate of the mixed material, the flow rate of the mixed gas in step (2) of Examples 4 to 8, the conversion rate of the raw material sulfide after the reaction, and the total yield of sulfone are specifically shown in Table 2.

[0069] Table 2 Mixed material flow rate, mixed gas flow rate and analysis results of Examples 4 to 8

[0070] serial number Mixed material flow rate Mixed gas flow rate Sulfide conversion rate Total yield of sulfone Example 4 1.0mL / min 20mL / min 100％ 83％ Example 5 0.8mL / min 20mL / min 100％ 85％ Example 6 0.8mL / min 18mL / min 100％ 86％ Example 7 0.6mL / min 20mL / min 100％ 92％ Example 8 0.6mL / min 18mL / min 100％ 93％

[0071] Example 9

[0072] Example 9 provides a method for the continuous flow oxidation of sulfide to sulfone, referring to Example 4, with the only difference being that in step (2), the light source is not turned on.

[0073] The materials after the reaction were analyzed. The conversion rate of sulfide using the method of this example was 100%, and the total yield of sulfone was 74%.

[0074] Example 10

[0075] Example 10 provides a method for oxidizing a sulfide to a sulfone, comprising the steps of:

[0076] (1) To a beaker, 1.25 mmol of the substrate methylphenyl sulfide, 50.5 mg of ferric nitrate nonahydrate, and 80.5 mg of tetrabutylammonium bromide were added, followed by 73 mL of acetonitrile. The mixture was ultrasonically treated for 5 to 10 minutes, filtered, and the filtrate was collected and transferred to a clean 150 mL conical flask to obtain a mixed material.

[0077] (2) 9 mL of the mixture from step (1) was added to a photoreaction tube. Illumination was performed using a 400 nm light source (15 W illumination power). An ozone / oxygen mixture was introduced into the mixture at a flow rate of 20 mL / min. The mixture was reacted at 0° C. for 9 min. The reaction solution was collected and allowed to stand. The ozone / oxygen mixture was the same as in Example 1.

[0078] According to the results of high performance liquid chromatography analysis, the sulfide raw material was completely converted, and the total yield of sulfone was 92%.

[0079] Example 11

[0080] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0081]

[0082] The specific method is as described in Example 3, except that the substrate methylphenyl sulfide in step (1) is replaced by an equal molar amount of substrate ethylphenyl sulfide (1.25 mmol).

[0083] According to the results of high performance liquid chromatography analysis, the sulfide raw material in this example was completely converted, and the total yield of sulfone was 98%.

[0084] Example 12

[0085] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0086]

[0087] The specific method is as in Example 2, except that the substrate methylphenyl sulfide in step (1) is replaced by an equimolar amount of substrate 4-methoxyanisole (1.25 mmol).

[0088] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 94%.

[0089] Example 13

[0090] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0091]

[0092] The specific method is as follows: refer to Example 3, except that the substrate methylphenyl sulfide in step (1) is replaced by an equal molar amount of substrate cyclopropylphenyl sulfide (1.25 mmol).

[0093] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 98%.

[0094] Example 14

[0095] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0096]

[0097] The specific method is as in Example 2, except that the substrate methylphenyl sulfide in step (1) is replaced by an equal molar amount of substrate 4-methylanisole (1.25 mmol).

[0098] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 90%.

[0099] Example 15

[0100] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0101]

[0102] The specific method is as described in Example 3, except that the substrate methylphenyl sulfide in step (1) is replaced by an equimolar amount of substrate 4-bromoanisole (1.25 mmol).

[0103] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 85%.

[0104] Example 16

[0105] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0106]

[0107] The specific method is as described in Example 7, except that the substrate diphenyl sulfide in step (1) is replaced by an equimolar amount of substrate 4-chloroanisole (1.25 mmol).

[0108] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 95%.

[0109] Example 17

[0110] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0111]

[0112] The specific method is as described in Example 7, except that the substrate diphenyl sulfide in step (1) is replaced by an equal molar amount of substrate benzyl methyl sulfide (1.25 mmol).

[0113] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 79%.

[0114] Example 18

[0115] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0116]

[0117] The specific method is as described in Example 1, except that the substrate methylphenyl sulfide in step (1) is replaced by an equimolar amount of substrate 2-methylthiopyridine (1.25 mmol).

[0118] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 79%.

[0119] Example 19

[0120] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0121]

[0122] The specific method is as described in Example 1, except that the substrate methylphenyl sulfide in step (1) is replaced by an equimolar amount of substrate 4-nitroanisole (1.25 mmol).

[0123] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 95%.

[0124] Example 20

[0125] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0126]

[0127] The specific method is as described in Example 1, except that the substrate methylphenyl sulfide in step (1) is replaced by an equal molar amount of substrate 2-chloroethylphenyl sulfide (1.25 mmol).

[0128] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 88%.

[0129] Example 21

[0130] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0131]

[0132] The specific method is as in Example 8, except that the substrate diphenyl sulfide in step (1) is replaced by an equimolar amount of substrate dibenzothiophene (1.25 mmol).

[0133] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 86%.

[0134] Example 22

[0135] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0136]

[0137] The specific method is as described in Example 3, except that the substrate methylphenyl sulfide in step (1) is replaced by an equal molar amount of substrate 3-methoxyanisole (1.25 mmol).

[0138] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 75%.

[0139] Example 23

[0140] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0141]

[0142] The specific method includes the following steps:

[0143] (1) Add 1.25 mmol of the substrate 4-(methylthio)benzonitrile, 50.5 mg of ferric nitrate nonahydrate, and 80.5 mg of tetrabutylammonium bromide to a beaker, then add 73 mL of acetonitrile. Ultrasonicate for 5-10 min, filter, collect the filtrate, and transfer it to a clean 150 mL conical flask to obtain a mixture.

[0144] (2) The mixed material obtained in step (1) was introduced into a continuous flow reactor as a stream of material using a plunger pump, and the flow rate of the mixed material was controlled to be 1.0 mL / min. The ozone / oxygen mixed gas was introduced into the continuous flow reactor as another stream of material, and the flow rate of the mixed gas was controlled to be 18 mL / min. The light source of the continuous flow reactor was set to 200 mW / cm 2 , 405nm LED, set the reaction temperature to 0°C, and the total reaction time to 9s. After the reaction, the reaction solution was collected and allowed to stand. The ozone / oxygen mixture had a mixed gas pressure of 2 bar and an ozone concentration of 150mg / L.

[0145] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was >99%.

[0146] Example 24

[0147] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0148]

[0149] The specific method is as in Example 8, except that the substrate diphenyl sulfide in step (1) is replaced by an equimolar amount of substrate 4-(methylthio)phenol (1.25 mmol).

[0150] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 86%.

[0151] Example 25

[0152] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0153]

[0154] The specific method is as described in Example 7, except that the substrate diphenyl sulfide in step (1) is replaced by an equal molar amount of substrate thiochroman-4-one (1.25 mmol).

[0155] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 81%.

[0156] Example 26

[0157] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0158]

[0159] The specific method is as in Example 8, except that the substrate diphenyl sulfide in step (1) is replaced by an equal molar amount of substrate 2-methoxyanisole (1.25 mmol).

[0160] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 81%.

[0161] Example 27

[0162] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0163]

[0164] The specific method is as in Example 2, except that the substrate methylphenyl sulfide in step (1) is replaced by an equimolar amount of substrate 2-bromoanisole (1.25 mmol).

[0165] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 39%.

[0166] Example 28

[0167] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0168]

[0169] The specific method is as shown in Example 23, except that the substrate 4-(methylthio)benzonitrile in step (1) is replaced by an equal molar amount of substrate phenylbenzyl sulfide (1.25 mmol).

[0170] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 86%.

[0171] Example 29

[0172] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0173]

[0174] The specific method includes the following steps:

[0175] (1) Add 1.25 mmol of the substrate methoxymethylphenyl sulfide, 50.5 mg of ferric nitrate nonahydrate, and 80.5 mg of tetrabutylammonium bromide to a beaker, then add 73 mL of acetonitrile, ultrasonicate for 5-10 min, filter, collect the filtrate, and transfer it to a clean 150 mL conical flask to obtain a mixed material.

[0176] (2) The mixed material obtained in step (1) was introduced into a continuous flow reactor as a stream of material using a plunger pump, and the flow rate of the mixed material was controlled to be 1.2 mL / min. The ozone / oxygen mixed gas was introduced into the continuous flow reactor as another stream of material, and the flow rate of the mixed gas was controlled to be 18 mL / min. The light source of the continuous flow reactor was set to 200 mW / cm 2 , 405nm LED, set the reaction temperature to 0°C, and the total reaction time to 8s. After the reaction, the reaction solution was collected and allowed to stand. The ozone / oxygen mixture had a mixed gas pressure of 2 bar and an ozone concentration of 150mg / L.

[0177] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 93%.

[0178] Example 30

[0179] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0180]

[0181] The specific method is as shown in Example 23, except that the substrate 4-(methylthio)benzonitrile in step (1) is replaced by an equimolar amount of substrate 2-(methylthio)naphthalene (1.25 mmol).

[0182] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 62%.

[0183] Example 31

[0184] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0185]

[0186] The specific method is as described in Example 6, except that the substrate diphenyl sulfide in step (1) is replaced by an equimolar amount of substrate 4-(methylthio)acetophenone (1.25 mmol).

[0187] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 94%.

[0188] Example 32

[0189] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0190]

[0191] The specific method includes the following steps:

[0192] (1) To a beaker, 1.25 mmol of the substrate methyl 2-chloro-4-(methylthio)benzoate, 50.5 mg of ferric nitrate nonahydrate, and 80.5 mg of tetrabutylammonium bromide were added, followed by 73 mL of acetonitrile. The mixture was ultrasonically treated for 5 to 10 minutes, filtered, and the filtrate was collected and transferred to a clean 150 mL conical flask to obtain a mixture.

[0193] (2) The mixed material obtained in step (1) was introduced into a continuous flow reactor as a stream of material using a plunger pump, and the flow rate of the mixed material was controlled to be 0.4 mL / min. The ozone / oxygen mixed gas was introduced into the continuous flow reactor as another stream of material, and the flow rate of the mixed gas was controlled to be 18 mL / min. The light source of the continuous flow reactor was set to 200 mW / cm 2 , 405nm LED, set the reaction temperature to 0°C, and the total reaction time to 9 seconds; collect the reaction liquid and perform secondary oxidation on it under the same conditions; after the reaction is completed, collect the reaction liquid and let it stand. The ozone / oxygen mixture has a mixed gas pressure of 2 bar and an ozone concentration of 150mg / L.

[0194] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 76%.

[0195] Example 33

[0196] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0197]

[0198] The specific method is as shown in Example 29, except that the substrate methoxymethylphenyl sulfide in step (1) is replaced by an equimolar amount of substrate 1-(2-ethyl-thioethyl)-2-methyl-5-nitroimidazole (1.25 mmol).

[0199] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 61%.

[0200] Example 34

[0201] This embodiment provides a method for the continuous flow oxidation of sulfide to sulfone, and the reaction scheme is as follows:

[0202]

[0203] The specific method is as described in Example 6, except that the substrate diphenyl sulfide in step (1) is replaced by an equimolar amount of substrate trimethyl (4-methoxyphenyl) sulfane (1.25 mmol).

[0204] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 78%.

[0205] Example 35

[0206] Example 35 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the acetonitrile in step (1) is replaced by an equal volume of dichloroethane (73 mL).

[0207] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 91%.

[0208] Example 36

[0209] Example 36 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the acetonitrile in step (1) is replaced by an equal volume of dichloromethane (73 mL).

[0210] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 88%.

[0211] Example 37

[0212] Example 37 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the acetonitrile in step (1) is replaced by an equal volume of toluene (73 mL).

[0213] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 87%.

[0214] Example 38

[0215] Example 38 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the acetonitrile in step (1) is replaced by an equal volume of ethyl acetate (73 mL).

[0216] According to the results of high performance liquid chromatography analysis, the conversion rate of the sulfide raw material in this example was 97%, and the total yield of sulfone was 94%.

[0217] Example 39

[0218] Example 39 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the reaction temperature in step (2) is set to 20°C.

[0219] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 85%.

[0220] Example 40

[0221] Example 40 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the reaction temperature in step (2) is set to 30°C.

[0222] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 81%.

[0223] Example 41

[0224] Example 41 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the reaction temperature in step (2) is set to 40°C.

[0225] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 89%.

[0226] Example 42

[0227] Example 42 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the amounts of the catalysts ferric nitrate nonahydrate and tetrabutylammonium bromide used in step (1) are different.

[0228] In this embodiment, in step (1), the amount of ferric nitrate nonahydrate is 25.3 mg (5 mmol%), and the amount of tetrabutylammonium bromide is 20.1 mg (5 mmol%).

[0229] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 69%.

[0230] Example 43

[0231] Example 43 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the amounts of the catalysts ferric nitrate nonahydrate and tetrabutylammonium bromide used in step (1) are different.

[0232] In this embodiment, in step (1), the amount of ferric nitrate nonahydrate is 25.3 mg (5 mmol%), and the amount of tetrabutylammonium bromide is 40.3 mg (10 mmol%).

[0233] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 73%.

[0234] Example 44

[0235] Example 44 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the amounts of the catalysts ferric nitrate nonahydrate and tetrabutylammonium bromide used in step (1) are different.

[0236] In this embodiment, in step (1), the amount of ferric nitrate nonahydrate is 50.5 mg (10 mmol%), and the amount of tetrabutylammonium bromide is 40.3 mg (10 mmol%).

[0237] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 84%.

[0238] Example 45

[0239] Example 45 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the amounts of the catalysts ferric nitrate nonahydrate and tetrabutylammonium bromide used in step (1) are different.

[0240] In this embodiment, in step (1), the amount of ferric nitrate nonahydrate is 50.5 mg (10 mmol%), and the amount of tetrabutylammonium bromide is 120.8 mg (30 mmol%).

[0241] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 88%.

[0242] Example 46

[0243] Example 46 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the amounts of the catalysts ferric nitrate nonahydrate and tetrabutylammonium bromide used in step (1) are different.

[0244] In this embodiment, in step (1), the amount of ferric nitrate nonahydrate is 50.5 mg (10 mmol%), and the amount of tetrabutylammonium bromide is 201.3 mg (50 mmol%).

[0245] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 79%.

[0246] Example 47

[0247] Example 47 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the light is not turned on in step (2).

[0248] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 81%.

[0249] Example 48

[0250] Example 48 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that: in step (2), 200mW / cm 2 , 405nm LED replaced with 200mW / cm 2 , 475nm LED.

[0251] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 90%.

[0252] Example 49

[0253] Example 49 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that: in step (2), 200 mW / cm 2 , 405nm LED replaced with 200mW / cm 2 , 365nm LED.

[0254] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 86%.

[0255] Example 50

[0256] Example 50 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that: in step (2), 200mW / cm 2 , 405nm LED replaced with 200mW / cm 2 , 385nm LED.

[0257] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 84%.

[0258] Example 51

[0259] Example 51 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that: in step (2), 200mW / cm 2 , 405nm LED replaced with 200mW / cm 2 , 610nm LED.

[0260] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 89%.

[0261] Example 52

[0262] Example 52 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the ferric nitrate nonahydrate in step (1) is replaced by an equimolar amount of ferric p-toluenesulfonate (28.5 mg, 10 mmol%).

[0263] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 70%.

[0264] Example 53

[0265] Example 53 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the ferric nitrate nonahydrate in step (1) is replaced by an equal mole of ferric bromide (36.9 mg, 10 mmol%).

[0266] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 78%.

[0267] Example 54

[0268] Example 54 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the ferric nitrate nonahydrate in step (1) is replaced by an equal mole of ferric chloride (20.3 mg, 10 mmol%).

[0269] According to the results of high performance liquid chromatography analysis, the sulfide raw material of this example was completely converted, and the total yield of sulfone was 65%.

[0270] Comparative Example 1

[0271] Comparative Example 1 provides a method for oxidizing sulfide to sulfone, comprising the following steps:

[0272] (1) Add 1.25 mmol of substrate methylphenyl sulfide and 73 mL of acetonitrile to a beaker, ultrasonicate for 5-10 min, filter, collect the filtrate and transfer it to a clean 150 mL conical flask to obtain a mixed material.

[0273] (2) 9 mL of the mixture from step (1) was added to a photoreaction tube. Illumination was performed using a 400 nm light source (15 W illumination power). An ozone / oxygen mixture was introduced into the mixture at a flow rate of 20 mL / min. The mixture was reacted at 0° C. for 9 min. The reaction solution was collected and allowed to stand. The ozone / oxygen mixture was the same as in Example 1.

[0274] According to the results of high performance liquid chromatography analysis, the sulfide raw material was completely converted, and the total yield of sulfone was 69%.

[0275] Comparative Example 2

[0276] Comparative Example 2 provides a method for oxidizing sulfide to sulfone, comprising the following steps:

[0277] (1) Add 1.25 mmol of substrate diphenyl sulfide and 73 mL of acetonitrile to a beaker, ultrasonicate for 5-10 min, filter, collect the filtrate and transfer it to a clean 150 mL conical flask to obtain a mixed material.

[0278] (2) The mixed material obtained in step (1) was introduced into a continuous flow reactor as a stream using a plunger pump, with the flow rate of the mixed material controlled at 1 mL / min. The ozone / oxygen mixed gas was introduced into the continuous flow reactor as another stream, with the flow rate of the mixed gas controlled at 20 mL / min. The light source was not turned on, the reaction temperature of the continuous flow reactor was set to 0°C, and the total reaction residence time was 8 s. After the reaction was completed, the reaction liquid was collected and allowed to stand. The ozone / oxygen mixed gas was the same as in Example 4.

[0279] According to the results of high performance liquid chromatography analysis, the total yield of sulfone is 14%.

[0280] Comparative Example 3

[0281] Comparative Example 3 provides a method for oxidizing sulfide to sulfone, comprising the following steps:

[0282] (1) Add 1.25 mmol of substrate diphenyl sulfide and 73 mL of acetonitrile to a beaker, ultrasonicate for 5-10 min, filter, collect the filtrate and transfer it to a clean 150 mL conical flask to obtain a mixed material.

[0283] (2) The mixed material obtained in step (1) was introduced into a continuous flow reactor as a stream of material using a plunger pump, and the flow rate of the mixed material was controlled to be 1 mL / min. The ozone / oxygen mixed gas was introduced into the continuous flow reactor as another stream of material, and the flow rate of the mixed gas was controlled to be 20 mL / min. The light source of the continuous flow reactor was set to 200 mW / cm 2, 405nm LED, set the reaction temperature to 0°C, and the total reaction time to 8s; after the reaction is completed, collect the reaction solution and let it stand. The ozone / oxygen mixed gas is the same as in Example 4.

[0284] According to the results of high performance liquid chromatography analysis, the total yield of sulfone is 17%.

[0285] Comparative Example 4

[0286] Comparative Example 4 provides a method for oxidizing sulfide to sulfone, comprising the following steps:

[0287] (1) Add 1.25 mmol of substrate diphenyl sulfide, 50.5 mg of ferric nitrate nonahydrate, and 80.5 mg of tetrabutylammonium bromide to a beaker, then add 73 mL of acetonitrile, ultrasonicate for 5-10 min, filter, collect the filtrate, and transfer it to a clean 150 mL conical flask to obtain a mixed material.

[0288] (2) 9 mL of the mixture from step (1) was added to a photoreaction tube. Illumination was performed using a 400 nm light source (15 W illumination power). An ozone / oxygen mixture was introduced into the mixture at a flow rate of 20 mL / min. The mixture was reacted at 0° C. for 9 min. The reaction solution was collected and allowed to stand. The ozone / oxygen mixture was the same as in Example 4.

[0289] According to the results of high performance liquid chromatography analysis, the sulfide raw material was completely converted, and the total yield of sulfone was 73%.

[0290] Comparative Example 5

[0291] Comparative Example 5 provides a method for oxidizing sulfide to sulfone, comprising the following steps:

[0292] (1) Add 1.25 mmol of substrate diphenyl sulfide and 73 mL of acetonitrile to a beaker, ultrasonicate for 5-10 min, filter, collect the filtrate and transfer it to a clean 150 mL conical flask to obtain a mixed material.

[0293] (2) 9 mL of the mixture from step (1) was added to a photoreaction tube. Illumination was performed using a 400 nm light source (15 W illumination power). An ozone / oxygen mixture was introduced into the mixture at a flow rate of 20 mL / min. The mixture was reacted at 0° C. for 9 min. The reaction solution was collected and allowed to stand. The ozone / oxygen mixture was the same as in Example 4.

[0294] According to the results of high performance liquid chromatography analysis, the sulfide raw material was completely converted, and the total yield of sulfone was 17%.

[0295] Comparative Example 6

[0296] Comparative Example 6 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that: no catalyst is added in step (1) (no ferric nitrate nonahydrate and tetrabutylammonium bromide are added).

[0297] According to the results of high performance liquid chromatography analysis, the sulfide raw material in Comparative Example 6 was completely converted, and the total yield of sulfone was 60%.

[0298] Comparative Example 7

[0299] Comparative Example 7 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the acetonitrile in step (1) is replaced by an equal volume of methanol (73 mL).

[0300] According to the results of high performance liquid chromatography analysis, the sulfide raw material in this comparative example was completely converted, and the total yield of sulfone was 11%.

[0301] Comparative Example 8

[0302] Comparative Example 8 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the acetonitrile in step (1) is replaced by an equal volume of tetrahydrofuran (73 mL).

[0303] According to the results of high performance liquid chromatography analysis, the conversion rate of the sulfide raw material in this comparative example was only 9%, and the total yield of sulfone was 0.

[0304] Comparative Example 9

[0305] Comparative Example 9 provides a method for oxidizing sulfide to sulfone, referring to Example 2, except that the acetonitrile in step (1) is replaced by an equal volume of N,N-dimethylformamide (73 mL).

[0306] According to the results of high performance liquid chromatography analysis, the sulfide raw material in this comparative example was completely converted, and the total yield of sulfone was 3%.

[0307] The test results above demonstrate that the present invention utilizes ozone / oxygen as oxidants and ferric nitrate and tetrabutylammonium bromide as catalysts to achieve continuous-flow oxidation of sulfides to sulfones, significantly improving production efficiency and safety. Furthermore, the present invention can further enhance the selectivity and yield of sulfide oxidation by employing specific oxidants and catalysts and adjusting the material composition and feed conditions.

[0308] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for the continuous flow oxidation of sulfides to sulfones, characterized in that The steps include: The mixed material and the oxidant are subjected to oxidation reaction in a continuous flow reactor; The mixed material includes thioether, a catalyst and a solvent, wherein the catalyst includes a trivalent iron salt and tetrabutylammonium bromide; in the mixed material, the molar ratio of the trivalent iron salt to the thioether is (0.05-0.1):1, and the molar ratio of the tetrabutylammonium bromide to the thioether is (0.05-0.5):1; the solvent includes at least one of acetonitrile, dichloromethane, dichloroethane, toluene and ethyl acetate; The oxidants include oxygen and ozone.

2. The method for continuous flow oxidation of sulfides to sulfones according to claim 1, characterized in that: In the catalyst, the molar ratio of the trivalent iron salt to the tetrabutylammonium bromide is 1:(1-5); Preferably, the molar ratio of the ferric salt to the tetrabutylammonium bromide is 1:

2.

3. The method for continuous flow oxidation of sulfide to sulfone according to claim 1, characterized in that: The trivalent iron salt includes at least one of ferric nitrate, ferric p-toluenesulfonate, ferric bromide and ferric chloride; Preferably, the trivalent iron salt is ferric nitrate.

4. The method for continuous flow oxidation of sulfide to sulfone according to claim 1, characterized in that: The thioether includes at least one of methylphenyl sulfide, diphenyl sulfide, ethylphenyl sulfide, 4-methoxythioanisole, cyclopropylphenyl sulfide, 4-methylthioanisole, 4-bromothioanisole, 4-chlorothioanisole, benzyl methyl sulfide, 2-methylthiopyridine, 4-nitrothioanisole, 2-chloroethylphenyl sulfide, dibenzothiophene, 3-methoxythioanisole, 4-(methylthio)benzonitrile, 4-(methylthio)phenol, thiochroman-4-one, 2-methoxythioanisole, 2-bromothioanisole, phenylbenzyl sulfide, methoxymethylphenyl sulfide, 2-(methylthio)naphthalene, 4-(methylthio)acetophenone, methyl 2-chloro-4-(methylthio)benzoate, 1-(2-ethyl-thioethyl)-2-methyl-5-nitroimidazole and mesitylene-(4-methoxyphenyl)sulfane.

5. The method for continuous flow oxidation of sulfide to sulfone according to claim 1, characterized in that: In the mixed material, the molar concentration of the sulfide is 0.01 to 0.02 mmol / mL.

6. The method for continuous flow oxidation of sulfide to sulfone according to claim 1, characterized in that: In the continuous flow reactor, the flow rate of the mixed material is 0.4 to 1.2 mL / min.

7. The method for continuous flow oxidation of sulfide to sulfone according to claim 1, characterized in that: The continuous flow reaction wherein the flow rate of the oxidant is 18 to 20 mL / min; Preferably, the concentration of ozone in the oxidant is 140-160 mg / L.

8. The method for continuous flow oxidation of sulfide to sulfone according to claim 1, characterized in that: The temperature of the oxidation reaction is ≤40°C; Preferably, the temperature of the oxidation reaction is ≤20°C; More preferably, the temperature of the oxidation reaction is 0-5°C.

9. The method for continuous flow oxidation of sulfide to sulfone according to claim 1, characterized in that: The oxidation reaction is carried out under light, or the oxidation reaction is carried out in the absence of light.

10. The method for continuous flow oxidation of sulfides to sulfones according to claim 9, characterized in that: In the illumination, the wavelength is 365 to 610 nm.

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