Preparation method of sulfoxide compound

Abstract

The invention discloses a preparation method of a sulfoxide compound, which comprises the following steps: in a room-temperature water phase, taking multiple helicene as a photocatalyst, and under the irradiation of visible light, carrying out photocatalytic reaction on thioether and oxygen in air to generate the sulfoxide compound. According to the method, thioether is used as a raw material, multiple helicene is used as a metal-free photocatalyst, oxygen in air is used as an oxidizing agent, and the thioether is efficiently and selectively converted into the sulfoxide compound through photocatalysis under the irradiation of visible light under the condition of a room temperature water phase. By using the method, the sulfoxide compound can be generated in an environment-friendly and high-selectivity manner with ultra-low catalyst dosage.

Description

Technical Field

[0001] The present invention relates to the technical field of organic compound synthesis, and in particular to a method for preparing a sulfoxide compound. Background Art

[0002] Sulfoxide compounds are important organic synthesis intermediates with widespread applications in pharmaceutical synthesis and functional materials. Traditional synthesis methods often rely on metal catalysts (such as vanadium and titanium) or strong oxidants (such as hydrogen peroxide and ozone). These methods present several challenges: metal contamination, catalyst residues that create an environmental burden, and purification difficulties; byproduct formation, which can lead to excessive oxidation reactions and reduced selectivity; and harsh conditions requiring high temperatures, high pressures, or inert gas protection, resulting in complex operations and high energy consumption.

[0003] Oxygen in air is a safe, inexpensive, and environmentally friendly oxidant. Photooxidation of sulfides using oxygen as an oxidant is an ideal method for the chemoselective synthesis of sulfoxides. Therefore, there is a need to find effective photocatalysts to selectively catalyze the conversion of sulfides into sulfoxides. Related art, such as Chinese invention patent application CN 110256307A, uses perylene imide compounds as metal-free photocatalysts to catalyze the oxidation of sulfides to sulfoxides under visible light. Although this method avoids metal contamination and achieves high selectivity, it still has the following limitations: solvent restrictions, requiring the use of organic solvents such as methanol, which increases the environmental burden and hinders product separation. The catalyst dosage is high, with the PDI dosage being 0.5 mol% (i.e., 5 mol%) of the sulfide, making it uneconomical. Substrate applicability is limited, and the catalytic efficiency is low for sulfides containing strong electron-withdrawing groups (such as nitro groups).

[0004] Furthermore, aqueous reaction systems, which do not require organic solvents, are more in line with the trend of green chemistry. Using water as a reaction medium is not only environmentally friendly, but also allows for separation and purification of the organic products after the reaction, as the organic products separate from the aqueous phase without the use of organic solvents. Catalytic sulfide oxidation is one of the most direct and effective pathways to obtain chiral sulfoxides. However, limited by the water solubility of the substrates and catalysts, the catalytic oxidation of sulfides in aqueous phase to synthesize chiral sulfoxides has been rarely reported. Therefore, developing an aqueous, ultra-low catalyst dosage, and broadly applicable method for preparing sulfoxides has become a pressing challenge in this field. Summary of the Invention

[0005] In order to solve the above problems, the present invention provides a method for preparing sulfoxide compounds, which can be used to generate sulfoxide compounds in an environmentally friendly manner, with ultra-low catalyst usage and high selectivity.

[0006] In order to achieve the above object, an embodiment of the present invention provides a method for preparing a sulfoxide compound, which comprises:

[0007] In room temperature water phase, using multiple helicene as a photocatalyst, under visible light irradiation, photocatalytic sulfide reacts with oxygen in the air to form sulfoxide compounds;

[0008] The structural formula of the multihelicene is as follows:

[0009]

[0010] According to an embodiment of the present invention, a method for preparing sulfoxide compounds is provided. This method achieves efficient and selective conversion of sulfides into sulfoxide compounds through photocatalysis. The photocatalyst can absorb natural light at all wavelengths, has strong light absorption capacity, and requires a small amount of catalyst, which is only one ten-thousandth of the substrate amount. The catalyst is a metal-free photocatalyst, non-toxic and does not pollute the environment. It can efficiently and selectively convert sulfides into sulfoxide compounds without producing sulfone by-products. The reaction conditions are mild, and pure water is used as a solvent. This method has the advantages of being green, energy-saving, environmentally friendly, low cost, good compatibility with functional groups, and high yield.

[0011] Optionally, the structural formula of the thioether is The structural formula of the sulfoxide compound is

[0012] Wherein, R1 and R2 are electron-donating groups or electron-withdrawing groups.

[0013] Furthermore, the electron-donating group is methyl, ethyl, phenyl, p-methoxyphenyl, p-ethoxyphenyl, m-methoxyphenyl, m-ethoxyphenyl, o-methoxyphenyl or o-ethoxyphenyl; the electron-withdrawing group is p-bromophenyl, p-chlorophenyl, m-bromophenyl, m-chlorophenyl, o-bromophenyl or o-chlorophenyl.

[0014] Optionally, the visible light is an energy-saving lamp with a power of 50W.

[0015] Optionally, the reaction time is 20h-46h.

[0016] Optionally, the aqueous phase is pure water.

[0017] Optionally, the added amount of the multi-helicene is 0.01% of the thioether.

[0018] Optionally, the method further comprises: after the reaction is completed, adding water to the reaction solution, extracting with ether, and concentrating the organic solvent to obtain the sulfoxide compound.

[0019] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1is the hydrogen nuclear magnetic resonance spectrum of phenylethyl sulfoxide according to Example 1 of the present invention;

[0021] Figure 2 is the carbon NMR spectrum of phenylethyl sulfoxide according to Example 1 of the present invention;

[0022] Figure 3 is the hydrogen nuclear magnetic resonance spectrum of phenylmethyl sulfoxide according to Example 2 of the present invention;

[0023] Figure 4 is the carbon NMR spectrum of phenylmethyl sulfoxide according to Example 2 of the present invention;

[0024] Figure 5 is the hydrogen nuclear magnetic resonance spectrum of p-methoxyphenyl methyl sulfoxide according to Example 3 of the present invention;

[0025] Figure 6 is the carbon-13 NMR spectrum of p-methoxyphenyl methyl sulfoxide according to Example 3 of the present invention;

[0026] Figure 7 is the hydrogen nuclear magnetic resonance spectrum of p-bromophenyl methyl sulfoxide according to Example 4 of the present invention;

[0027] Figure 8 is the carbon NMR spectrum of p-bromophenyl methyl sulfoxide according to Example 4 of the present invention;

[0028] Figure 9 is the hydrogen nuclear magnetic resonance spectrum of m-bromophenyl methyl sulfoxide according to Example 5 of the present invention;

[0029] Figure 10 is the carbon NMR spectrum of m-bromophenyl methyl sulfoxide according to Example 5 of the present invention;

[0030] Figure 11 is the hydrogen nuclear magnetic resonance spectrum of o-bromophenyl methyl sulfoxide according to Example 6 of the present invention;

[0031] Figure 12 is the carbon NMR spectrum of o-bromophenyl methyl sulfoxide according to Example 6 of the present invention;

[0032] Figure 13 is the hydrogen nuclear magnetic resonance spectrum of p-chlorophenyl methyl sulfoxide according to Example 7 of the present invention;

[0033] Figure 14 It is the carbon nuclear magnetic resonance spectrum of 4-chlorophenyl methyl sulfoxide according to Example 7 of the present invention. DETAILED DESCRIPTION

[0034] The technical solution of the present invention is described below through specific examples. It should be understood that the one or more method steps mentioned in the present invention do not exclude the presence of other method steps before and after the combination step or the insertion of other method steps between these explicitly mentioned steps; it should also be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention. Moreover, unless otherwise specified, the numbering of each method step is only a convenient tool for identifying each method step, and is not intended to limit the order of arrangement of each method step or to define the scope of the present invention. Changes or adjustments in their relative relationships, without substantially changing the technical content, should also be regarded as the scope of the present invention.

[0035] In order to better understand the above technical solutions, exemplary embodiments of the present invention are described in more detail below. Although exemplary embodiments of the present invention are shown, it should be understood that the present invention can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present invention and to fully convey the scope of the present invention to those skilled in the art.

[0036] The test materials used in the present invention are all common commercial products and can be purchased in the market.

[0037] The present invention is described below with reference to specific examples. It should be noted that these examples are merely illustrative and do not limit the present invention in any way.

[0038] Example 1 Preparation of phenylethyl sulfoxide

[0039] The reaction equation is as follows:

[0040]

[0041] Phenylethyl sulfide (0.1 mmol), polyhelicene (0.00001 mmol), and 1 mL of pure water were added to a 10 mL open quartz vial under air and stirred at room temperature under 50 W energy-saving lamp illumination. Complete reaction was confirmed by TLC. Stirring was continued at room temperature for 24 hours. After completion of the reaction, 5 mL of water was added and the mixture was extracted with ether three times (5 mL each time). The organic solvent was concentrated to obtain phenylethyl sulfoxide directly in a 96% yield.

[0042] like Figure 1 As shown, the nuclear magnetic resonance hydrogen spectrum of phenylethyl sulfoxide is characterized as follows: 1 H NMR (300MHz, CDCl3) δ7.65–7.58(m,2H),7.57–7.44(m,3H),3.01–2.67(m,2H),1.20(t,J=7.4Hz,3H).

[0043] like Figure 2 As shown, the nuclear magnetic resonance carbon spectrum of phenylethyl sulfoxide is characterized as follows: 13 C NMR (75MHz, CDCl3) δ143.27,130.93,129.14,124.18,50.29,5.97.

[0044] Example 2 Preparation of phenylmethyl sulfoxide

[0045] The reaction equation is as follows:

[0046]

[0047] Thioanisole (0.1 mmol), polyhelicene (0.00001 mmol), and 1 mL of pure water were added to a 10 mL open quartz flask under air and stirred at room temperature under 50 W energy-saving lamp illumination. Complete reaction was confirmed by TLC. The mixture was stirred at room temperature for 22 h. After completion of the reaction, 5 mL of water was added and the mixture was extracted with ether three times (5 mL each time). The organic solvent was concentrated to directly obtain phenylethyl sulfoxide in a 97% yield.

[0048] like Figure 3 As shown, the nuclear magnetic resonance hydrogen spectrum of phenylmethyl sulfoxide is characterized as follows: 1 H NMR (300MHz, CDCl3) δ7.75–7.59(m,2H),7.59–7.44(m,3H),2.72(s,3H).

[0049] like Figure 4 As shown, the nuclear magnetic resonance carbon spectrum of phenylmethyl sulfoxide is characterized as follows: 13 C NMR (75MHz, CDCl3) δ145.60,131.06,129.37,123.49,43.90.

[0050] Example 3 Preparation of p-methoxyphenyl methyl sulfoxide

[0051] The reaction equation is as follows:

[0052]

[0053] Under air, p-methoxyphenyl methyl sulfide (0.1 mmol), multiple helicenes (0.00001 mmol), and 1 mL of pure water were added to a 10 mL open quartz flask and stirred at room temperature under 50 W energy-saving lamps. TLC was used to determine whether the raw materials had reacted completely. The mixture was stirred at room temperature for 20 h. After the reaction was completed, 5 mL of water was added and the mixture was extracted with ether three times (5 mL each time). The organic solvent was concentrated to directly obtain p-methoxyphenyl methyl sulfoxide (p-methoxyphenyl methyl sulfoxide) in a yield of 98%.

[0054] like Figure 5 As shown, the nuclear magnetic resonance hydrogen spectrum of p-methoxyphenyl methyl sulfoxide is characterized as follows: 1 H NMR (300MHz, CDCl3) δ7.58 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H), 2.69 (s, 3H).

[0055] like Figure 6 As shown, the nuclear magnetic resonance carbon spectrum of p-methoxyphenyl methyl sulfoxide is characterized as follows: 13 C NMR (75MHz, CDCl3) δ 161.98, 136.48, 125.47, 114.86, 55.53, 43.93. ESI-MS [M] + m / z 170.05.

[0056] Example 4 Preparation of p-Bromophenyl Methyl Sulfoxide

[0057] The reaction equation is as follows:

[0058]

[0059] Under air, p-bromophenyl methyl sulfide (0.1 mmol), multiple helicene (0.00001 mmol), and 1 mL of pure water were added to a 10 mL open quartz bottle and stirred at room temperature under 50 W energy-saving lamp illumination. Complete reaction was confirmed by TLC. The mixture was stirred at room temperature for 28 h. After completion of the reaction, 5 mL of water was added and the mixture was extracted with ether three times (5 mL each time). The organic solvent was concentrated to directly obtain p-bromophenyl methyl sulfoxide in a yield of 95%.

[0060] like Figure 7 As shown, the nuclear magnetic resonance hydrogen spectrum of 4-bromophenyl methyl sulfoxide is characterized as follows: 1 H NMR (300MHz, CDCl3) δ7.72–7.62(m,2H),7.56–7.47(m,2H),2.71(s,3H).

[0061] like Figure 8 As shown, the nuclear magnetic resonance carbon spectrum of 4-bromophenyl methyl sulfoxide is characterized as follows: 13 C NMR (75MHz, CDCl3) δ144.87,132.59,125.48,125.15,43.99.

[0062] Example 5 Preparation of m-bromophenyl methyl sulfoxide

[0063] The reaction equation is as follows:

[0064]

[0065] Under air, m-bromophenyl methyl sulfide (0.1 mmol), multiple helicene (0.00001 mmol), and 1 mL of pure water were added to a 10 mL open quartz bottle and stirred at room temperature under 50 W energy-saving lamp illumination. Complete reaction was confirmed by TLC. The mixture was stirred at room temperature for 32 h. After completion of the reaction, 5 mL of water was added and the mixture was extracted with ether three times (5 mL each time). The organic solvent was concentrated to directly obtain m-bromophenyl methyl sulfoxide in a yield of 92%.

[0066] like Figure 9 As shown, the nuclear magnetic resonance hydrogen spectrum of m-bromophenyl methyl sulfoxide is characterized as follows: 1 H NMR (300MHz, CDCl3) δ7.83(t,J=1.8Hz,1H),7.65(ddd,J=7.9,1.9,1.1Hz,1H),7.57(dt,J=8.0,1.2Hz,1H),7.42(t,J=7.8Hz,1H),2.76(s,3H).

[0067] like Figure 10 As shown, the nuclear magnetic resonance carbon spectrum of m-bromophenyl methyl sulfoxide is characterized as follows: 13 C NMR (75MHz, CDCl3) δ148.02,134.13,130.84,126.50,123.61,122.08,44.06.

[0068] Example 6 Preparation of o-bromophenyl methyl sulfoxide

[0069] The reaction equation is as follows:

[0070]

[0071] Under air, o-bromophenyl methyl sulfide (0.1 mmol), polyhelicene (0.00001 mmol), and 1 mL of pure water were added to a 10 mL open quartz flask and stirred at room temperature under 50 W energy-saving lamp illumination. Complete reaction was confirmed by TLC. The mixture was stirred at room temperature for 46 h. After completion of the reaction, 5 mL of water was added and the mixture was extracted with ether three times (5 mL each time). The organic solvent was concentrated to directly obtain o-bromophenyl methyl sulfoxide in an 89% yield.

[0072] like Figure 11 As shown, the nuclear magnetic resonance hydrogen spectrum of o-bromophenyl methyl sulfoxide is characterized as follows: 1 H NMR (300MHz, CDCl3) δ7.97 (dd, J=7.7, 1.7Hz, 1H), 7.60 (ddd, J=8.7, 7.2, 1.4Hz, 2H), 7.46–7.32 (m, 1H), 2.84 (s, 3H).

[0073] like Figure 12 As shown, the nuclear magnetic resonance carbon spectrum of o-bromophenyl methyl sulfoxide is characterized as follows: 13 C NMR (75MHz, CDCl3) δ145.39,132.93,132.27,128.75,125.71,118.43,41.91.

[0074] Example 7 Preparation of p-chlorophenyl methyl sulfoxide

[0075] The reaction equation is as follows:

[0076]

[0077] Under air, p-chlorophenyl methyl sulfide (0.1 mmol), multiple helicene (0.00001 mmol), and 1 mL of pure water were added to a 10 mL open quartz bottle and stirred at room temperature for a period of time under irradiation with an energy-saving lamp (power 50 W). TLC was used to determine whether the raw materials had reacted completely. Stirring at room temperature for 26 hours, 5 mL of water was added after the reaction was completed, and the mixture was extracted with ether three times (5 mL each time). The organic solvent was concentrated to directly obtain p-chlorophenyl methyl sulfoxide in a productive rate of 93%.

[0078] like Figure 13 As shown, the nuclear magnetic resonance hydrogen spectrum of 4-chlorophenyl methyl sulfoxide is characterized as follows: 1 H NMR (300MHz, CDCl3) δ7.62–7.54 (m, 2H), 7.50 (d, J = 8.5Hz, 2H), 2.71 (s, 3H).

[0079] like Figure 14 As shown, the nuclear magnetic resonance carbon spectrum of 4-chlorophenyl methyl sulfoxide is characterized as follows: 13 C NMR (75MHz, CDCl3) δ144.22,137.26,129.67,124.98,44.05.

[0080] Example 8 Optimization of reaction conditions

[0081] 1. Optimization of catalyst dosage

[0082] In air, phenylethyl sulfide (0.1 mmol), multiple helicenes (different catalyst dosages), and 1 mL of pure water were added to a 10 mL open quartz bottle and stirred at room temperature under irradiation with an energy-saving lamp (power 50 W) for a period of time. The reaction was allowed to react for 24 hours. After the reaction was completed, 5 mL of water was added, and the mixture was extracted with ether three times (5 mL each time). The organic solvent was concentrated to directly obtain phenylethyl sulfoxide. The yields of the product phenylethyl sulfoxide at different catalyst dosages relative to the substrate were as follows:

[0083] Table 1 Product yields at different catalyst dosages

[0084] Serial number Catalyst dosage (%) Yield (%) 1 20 96 2 10 96 3 1 96 4 0.1 96 5 0.01 96 6 0.001 48 7 0 0

[0085] The above results show that for phenyl ethyl sulfide, since the yield is the same when the catalyst dosage is more than one ten-thousandth of the substrate (the first 6 results), one ten-thousandth of the substrate equivalent is the optimal catalyst dosage.

[0086] 2. Optimization of solvent dosage

[0087] Under air conditions, phenylethyl sulfide (0.1mmol), multiple helicene (0.00001mmol), and pure water (different amounts) were added to a 10mL open quartz bottle and stirred at room temperature for a period of time under irradiation with an energy-saving lamp (power 50W) for 24 hours. After the reaction, 5mL of water was added, and the mixture was extracted with diethyl ether three times (5mL each time). The organic solvent was concentrated to directly obtain phenylethyl sulfoxide. The yields of the product phenylethyl sulfoxide under different solvent amounts are as follows:

[0088] Table 2 Product yields at different solvent dosages

[0089]

[0090]

[0091] The above results show that for phenylethyl sulfide, the optimal solvent amount is 1 mL of solvent per 0.1 mmol of phenylethyl sulfide.

[0092] 3. Solvent optimization

[0093] In air, phenylethyl sulfide (0.1 mmol), multiple helicene (0.00001 mmol), and different solvents (1 mL) were added to a 10 mL open quartz bottle and stirred at room temperature under irradiation with an energy-saving lamp (power 50 W) for a period of time. The reaction was allowed to proceed for 24 hours. After the reaction, 5 mL of water was added and the mixture was extracted with ether three times (5 mL each time). The organic solvent was concentrated to directly obtain phenylethyl sulfoxide. The yields of the product phenylethyl sulfoxide under different solvents are as follows:

[0094] Table 3 Product yields under different solvents

[0095] Serial number Solvent (1 mL) Yield (%) 1 pure water 96 2 ethanol 94 3 Methanol 94 4 dimethyl sulfoxide 90 5 Ethyl acetate 81 6 dichloromethane 86 7 Dioxane 73 8 Tetrahydrofuran 85

[0096] The above results show that for phenyl ethyl sulfide, pure water is the optimal solvent among different solvents.

[0097] 4. Optimization of protective atmosphere

[0098] Under different protective atmospheres, phenylethyl sulfide (0.1mmol), multiple helicene (0.00001mmol), and pure water (1mL) were added to a 10mL open quartz bottle and stirred at room temperature for a period of time under irradiation with an energy-saving lamp (power 50W) for 24 hours. After the reaction, 5mL of water was added, and the mixture was extracted with ether three times (5mL each time). The organic solvent was concentrated to directly obtain phenylethyl sulfoxide. The yields of the product phenylethyl sulfoxide under different protective atmospheres are as follows:

[0099] Table 4 Product yields under different protective atmospheres

[0100] Serial number Protective atmosphere Yield (%) 1 Air 96 2 Nitrogen 0 3 oxygen 96

[0101] The above results show that for phenyl ethyl sulfide, the yields under air and oxygen conditions are the same under different protection conditions. Air condition is the optimal protective atmosphere because of its simple operation.

[0102] In summary, according to the embodiments of the present invention, under room temperature aqueous phase conditions, using sulfide as a raw material, multiple helicenes as a metal-free photocatalyst, and oxygen in the air as an oxidant, under the irradiation of an energy-saving lamp, photocatalytic sulfide is efficiently and selectively converted into sulfoxide compounds; the efficient and selective conversion of sulfide into sulfoxide compounds is achieved through photocatalysis, the photocatalyst has the ability to absorb all wavelengths of natural light, has strong light absorption capacity, and the catalyst dosage is small, only one ten-thousandth of the substrate dosage; the catalyst is a metal-free photocatalyst, non-toxic and does not pollute the environment; sulfide is efficiently and selectively converted into sulfoxide compounds without sulfone by-products; the reaction conditions are mild, pure water is used as a solvent, it is green, energy-saving and environmentally friendly, the cost is low, the compatibility with functional groups is good, and the yield is high.

[0103] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example" or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic expressions of the above terms should not be understood as necessarily referring to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification.

[0104] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention.

Claims

1. A method for preparing a sulfoxide compound, characterized in that: include: In room temperature water phase, using multiple helicene as a photocatalyst, under visible light irradiation, photocatalytic sulfide reacts with oxygen in the air to form sulfoxide compounds; The structural formula of the multihelicene is as follows:

2. The method for preparing a sulfoxide compound according to claim 1, wherein The structural formula of the thioether is The structural formula of the sulfoxide compound is Wherein, R1 and R2 are electron-donating groups or electron-withdrawing groups.

3. The method for preparing a sulfoxide compound according to claim 2, wherein: The electron-donating group is methyl, ethyl, phenyl, p-methoxyphenyl, p-ethoxyphenyl, m-methoxyphenyl, m-ethoxyphenyl, o-methoxyphenyl or o-ethoxyphenyl; the electron-withdrawing group is p-bromophenyl, p-chlorophenyl, m-bromophenyl, m-chlorophenyl, o-bromophenyl or o-chlorophenyl.

4. The method for preparing a sulfoxide compound according to claim 1, wherein The visible light is an energy-saving lamp with a power of 50W.

5. The method for preparing a sulfoxide compound according to claim 1, wherein The reaction time is 20h-46h.

6. The method for preparing a sulfoxide compound according to claim 1, wherein The aqueous phase is pure water.

7. The method for preparing a sulfoxide compound according to claim 1, wherein The added amount of the multi-helicene is 0.01% of the thioether.

8. The method for preparing a sulfoxide compound according to claim 1, wherein: Also includes: After the reaction is completed, water is added to the reaction solution, and the mixture is extracted with ether. The organic solvent is concentrated to obtain the sulfoxide compound.

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