A method for synthesizing S-(p-tolyl) 4-methylbenzenesulfinate

Abstract

The present invention provides a method for synthesizing S-(p-tolyl) 4-methylbenzenesulfite, comprising the following steps: a) mixing p-methylthiophenol, benzaldehyde, an electrolyte and a solvent to obtain a mixed solution; b) performing an electrolytic reaction using the mixed solution as an electrolyte to obtain a reaction mixed solution; c) subjecting the reaction mixed solution to extraction, concentration and separation and purification to obtain S-(p-tolyl) 4-methylbenzenesulfite. The synthesis method provided by the present invention can avoid using transition metals and excessive oxidants that are toxic to the human body, is green and environmentally friendly, and can ensure the yield at the same time.

Description

Technical Field

[0001] The present invention relates to the field of chemical synthesis, and particularly to a method for synthesizing S-(p-tolyl) 4-methylbenzenesulfinate. Background Art

[0002] S-(p-tolyl) 4-methylbenzenesulfinate is a very valuable precursor in organic synthesis and can act as an electrophilic or nucleophilic reagent depending on the reaction conditions. Given the emergence of sulfinates as potential coupling partners and their biological importance, from the perspective of synthetic organic chemistry, practical metal-free sulfinylation involving TosMIC will be of great interest. Generally, sulfinates can be produced from sulfinyl chlorides, sodium sulfinates, and sulfinic acids. Common sulfinyl halides are liquids with limited stability, and the preparation of pure samples is cumbersome. In addition, sulfinic acids and their salts are not strong nucleophiles, and the simple alkylation reaction of sulfinate anions is not easy and usually requires adjustment of reaction conditions.

[0003] According to the scheme disclosed in the prior art such as the literature [Molecules 2015, 20, 10748-10762], disulfides are oxidized to thiol sulfinates using hydrogen peroxide and cyclic selenate esters as catalysts. This method uses catalysts that are expensive, difficult to obtain, and environmentally polluting, and the reaction does not conform to green chemistry. The reaction is complex and has high requirements for operation, and the yield is poor.

[0004] In view of the above-mentioned unfavorable factors in industrial production, it is necessary to improve the existing process and develop a synthesis method with the advantages of mild reaction conditions, high efficiency, and low production cost, providing a new technology for the synthesis of S-(p-tolyl) 4-methylbenzenesulfinate. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a method for synthesizing S-(p-tolyl) 4-methylbenzenesulfinate. The synthesis method provided by the present invention can avoid using transition metals and excessive oxidants that are toxic to the human body, is green and environmentally friendly, and can ensure the yield at the same time.

[0006] The present invention provides a method for synthesizing S-(p-tolyl) 4-methylbenzenesulfinate, comprising the following steps:

[0007] a) Mix p-methylthiophenol, benzaldehyde, an electrolyte, and a solvent to obtain a mixed solution;

[0008] b) Perform an electrolytic reaction using the mixed solution as an electrolyte to obtain a reaction mixed solution;

[0009] c) Extract, concentrate, and separate and purify the reaction mixed solution to obtain S-(p-tolyl) 4-methylbenzenesulfinate.

[0010] Preferably, in the step a), the electrolyte is selected from at least one of KI, NaI, TBAI, and KBr.

[0011] Preferably, in the step a), the solvent is a mixed solvent of an organic solvent and water;

[0012] wherein the organic solvent is selected from at least one of acetonitrile, tetrahydrofuran, ethanol, ethylene glycol, N,N-dimethylformamide, chloroform, dichloromethane, 1,2-dichloroethane, and ether;

[0013] The volume ratio of the organic solvent to water is 1∶(0.5 - 9).

[0014] Preferably, in the step b), the conditions for the electrolytic reaction are: current 5 - 30 mA, temperature 25 - 80 °C, and time 4 - 6 h.

[0015] Preferably, in the step b), in the electrolytic reaction, both the anode and the cathode are platinum sheets.

[0016] Preferably, in the step a), the molar ratio of p-methylthiophenol to benzaldehyde is 1∶(0.5 - 2.5).

[0017] Preferably, in the step a), the molar ratio of p-methylthiophenol to the electrolyte is 1∶(0.3 - 3).

[0018] Preferably, in the step a), the volume ratio of p-methylthiophenol to the solvent is 1∶(0.02 - 0.1).

[0019] Preferably, in the step c), the extractant used for extraction is ethyl acetate; the concentration is concentration under reduced pressure.

[0020] Preferably, in the step c), the separation and purification is separation and purification by column chromatography;

[0021] The developing agent used in the column chromatography is a mixed solvent of petroleum ether and ethyl acetate.

[0022] The above synthesis method provided by the present invention formulates a mixed solution of p-methylthiophenol, benzaldehyde, and a specific electrolyte in a certain solvent, and then conducts an electrified reaction. Under the action of electrocatalysis, p-methylthiophenol undergoes a selective oxidation reaction in a heterogeneous reaction system of liquid-liquid two phases to generate S-(p-tolyl) 4-methylbenzenesulfinate, obtaining a reaction mixture containing S-(p-tolyl) 4-methylbenzenesulfinate; then, the above reaction mixture is successively subjected to extraction, concentration, and separation and purification to obtain S-(p-tolyl) 4-methylbenzenesulfinate. Compared with the prior art, the present invention adopts an electrochemical synthesis method. Under electrocatalytic conditions, no catalyst is used, avoiding the use of transition metals such as copper and cobalt and their oxides that are toxic to the human body, being green and pollution-free, and reducing wastewater discharge during the production process; moreover, under electrocatalysis, the liquid-liquid two phases proceed in a heterogeneous reaction system, the reaction rate is fast, and the product yield reaches more than 85%. Therefore, the method of the present invention has the advantages of simple preparation method, convenient operation, mild reaction conditions, and environmental friendliness, realizing the green synthesis of S-(p-tolyl) 4-methylbenzenesulfinate and having good industrial application prospects.

[0023] The experimental results show that the synthesis method provided by the present invention can make the product yield reach more than 55% and the purity reach more than 90%. When under the optimal conditions, that is, using acetonitrile and water as the solvent and controlling the volume ratio of acetonitrile: water to be 1:1, and controlling the electrified reaction current to be 10 mA and the temperature to be 60 °C, the product yield can reach 85% and the purity can reach 95%. Description of the Drawings

[0024] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only the embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained according to the provided drawings.

[0025] Figure 1 It is a schematic structural diagram of a current device;

[0026] Figure 2 It is a nuclear magnetic resonance hydrogen spectrum diagram of the product obtained in Example 1. Detailed Embodiments

[0027] The present invention provides a synthesis method of S-(p-tolyl) 4-methylbenzenesulfinate, including the following steps:

[0028] a) Mix p-methylthiophenol, benzaldehyde, an electrolyte, and a solvent to obtain a mixed solution;

[0029] b) Using the mixed solution as the electrolyte for an electrified reaction to obtain a reaction mixed solution;

[0030] c) Extracting, concentrating, and separating and purifying the reaction mixed solution to obtain S-(p-tolyl) 4-methylbenzenesulfinate.

[0031] In the above synthesis method provided by the present invention, p-methylthiophenol, benzaldehyde, and a specific electrolyte are formulated into a mixed solution in a certain solvent, and then an electrified reaction is carried out. Under the action of electrocatalysis, p-methylthiophenol undergoes a selective oxidation reaction in a heterogeneous reaction system of liquid-liquid two phases to generate S-(p-tolyl) 4-methylbenzenesulfinate, obtaining a reaction mixed solution containing S-(p-tolyl) 4-methylbenzenesulfinate; then, the above reaction mixed solution is successively subjected to extraction, concentration, and separation and purification to obtain S-(p-tolyl) 4-methylbenzenesulfinate. Compared with the prior art, the present invention adopts an electrochemical synthesis method. Under electrocatalytic conditions, no catalyst is used, avoiding the use of transition metals such as copper and cobalt and their oxides that are toxic to the human body, being green and pollution-free, and reducing wastewater discharge during the production process; moreover, under electrocatalysis, the liquid-liquid two phases are carried out in a heterogeneous reaction system, the reaction rate is fast, and the product yield reaches more than 85%.

[0032] [Regarding step a]:

[0033] a) Mixing p-methylthiophenol, benzaldehyde, an electrolyte, and a solvent to obtain a mixed solution.

[0034] The present invention uses p-methylthiophenol and benzaldehyde as reaction raw materials to synthesize S-(p-tolyl) 4-methylbenzenesulfinate, and its reaction route is as follows:

[0035]

[0036] In the present invention, the sources of the reaction raw materials p-methylthiophenol and benzaldehyde are not particularly limited and can be commercially available products. In the present invention, the molar ratio of p-methylthiophenol to benzaldehyde is preferably 1:(0.5 - 2.5), specifically 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2.0, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, and more preferably 1:(1.0 - 2.0).

[0037] In the present invention, the electrolyte is preferably at least one of KI, NaI, TBAI (i.e., tetrabutylammonium iodide), and KBr, and more preferably KI. There are no special restrictions on the source of the electrolyte in the present invention, and it can be a commercially available product. In the present invention, the molar ratio of p-methylthiophenol to the electrolyte is preferably 1:(0.3 - 3), specifically 1:0.3, 1:0.5, 1:1.0, 1:1.5, 1:2.0, 1:2.5, 1:3.0. Moreover, the amount of the electrolyte used is ≥ 0.5% of the mass of p-methylthiophenol.

[0038] In the present invention, the solvent is a mixed solvent of an organic solvent and water. Among them, the organic solvent is preferably at least one of acetonitrile, tetrahydrofuran, ethanol, ethylene glycol, N,N-dimethylformamide, chloroform, dichloromethane, 1,2-dichloroethane, and ether, and more preferably acetonitrile. The present invention uses the above-mentioned specific organic solvent miscible with water in combination with water as the solvent to be conducive to obtaining good reaction effects. If water is used alone, the reaction cannot proceed, and if the above-mentioned organic solvent is used alone, only a small amount of reaction can occur. Among them, the reaction effect is the best when acetonitrile is combined with water. In the present invention, the volume ratio of the organic solvent to water is preferably 1:(0.5 - 9), specifically 1:0.5, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, more preferably 1:(0.5 - 1), and most preferably 1:1. When the ratio is 1:1, the reaction effect is the best.

[0039] In the present invention, the volume ratio of p-methylthiophenol to the solvent is 1:(0.02 - 0.1), and more preferably 1:(0.03 - 0.05). The present invention can ensure the effective and smooth progress of the reaction under the above-mentioned low solvent dosage. The low usage amount of the reaction solvent is conducive to reducing production costs and improving environmental protection.

[0040] In the present invention, there are no special restrictions on the method of mixing the four substances of p-methylthiophenol, benzaldehyde, electrolyte, and solvent. Any conventional mixing method in the art that can mix the materials evenly and dissolve each substance fully in the solvent can be used, such as stirring and mixing. In the present invention, there are no special restrictions on the temperature of the mixing, and it can be carried out at room temperature, specifically 16 - 25 °C. After mixing, a mixed solution is obtained.

[0041] [Regarding step b]:

[0042] b) Using the mixed solution as the electrolyte for an electrolytic reaction to obtain a reaction mixed solution.

[0043] In the present invention, using the mixed solution obtained in step a) as the electrolyte, applying an electric current to it for an electrochemical reaction to synthesize S-(p-tolyl) 4-methylbenzenesulfinate.

[0044] In the present invention, in the power-on reaction, a direct current power source is used as the power supply in the current device, and an electrocatalytic reaction is carried out under the action of a constant direct current. The current device preferably uses two platinum sheets as the anode and the cathode respectively. More specifically, a platinum wire is connected to the platinum sheet, and the platinum wire is wound with a copper wire and fixed to the container rubber stopper, and then fixed with a sealing film. See Figure 1 , Figure 1 which is a schematic structural diagram of the current device, where 1 is a platinum sheet, 2 is a platinum wire, and 3 is a copper wire.

[0045] In the present invention, the conditions of the power-on reaction are preferably: current 5 - 30 mA, temperature 25 - 80 °C, time 4 - 6 h. Among them, the current can specifically be 5 mA, 10 mA, 15 mA, 20 mA, 25 mA, 30 mA, and more preferably 10 mA. The temperature can specifically be 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C, 65 °C, 70 °C, 75 °C, 80 °C, and more preferably 60 °C. The time can specifically be 4 h, 4.5 h, 5 h, 5.5 h, 6 h. After the power-on reaction, S-(p-tolyl) 4-methylbenzenesulfinate is generated in the system, and a reaction mixture containing S-(p-tolyl) 4-methylbenzenesulfinate is obtained.

[0046] [Regarding step c]:

[0047] c) Extract, concentrate, and separate and purify the reaction mixture to obtain S-(p-tolyl) 4-methylbenzenesulfinate.

[0048] In the present invention, the extraction agent used for extraction is preferably ethyl acetate. After extraction in the present invention, the organic phase is retained for subsequent treatment.

[0049] In the present invention, after the above extraction, concentration is carried out. In the present invention, the concentration is preferably vacuum concentration. In the present invention, the conditions for vacuum concentration are preferably: 0.090 Mpa ≤ pressure < 0.100 Mpa, temperature 40 - 70 °C. In the present invention, vacuum concentration is used to remove the residual extraction agent in the extracted organic phase and the solvent introduced in step a), facilitating subsequent separation and purification.

[0050] In the present invention, after the above concentration, separation and purification are carried out. In the present invention, the separation and purification is preferably column chromatography separation and purification. Among them, the eluent used is preferably a mixed solvent of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate is preferably (10 - 25):1, and more preferably 20:1. After separation and purification, an S-(p-tolyl) 4-methylbenzenesulfinate product is obtained.

[0051] In the above synthesis method provided by the present invention, p-methylthiophenol, benzaldehyde and a specific electrolyte are formulated into a mixed solution in a certain solvent, and then an electrified reaction is carried out. Under the action of electrocatalysis, p-methylthiophenol undergoes a selective oxidation reaction in a heterogeneous reaction system of liquid-liquid two-phase to generate S-(p-tolyl) 4-methylbenzenesulfinate, and a reaction mixture containing S-(p-tolyl) 4-methylbenzenesulfinate is obtained; then, the above reaction mixture is successively subjected to extraction, concentration and separation and purification to obtain S-(p-tolyl) 4-methylbenzenesulfinate. Compared with the prior art, the present invention adopts an electrochemical synthesis method. Under electrocatalytic conditions, no catalyst is used, avoiding the use of transition metals such as copper and cobalt and their oxides that are toxic to the human body, being green and pollution-free, and reducing wastewater discharge during the production process; moreover, under electrocatalysis, the liquid-liquid two-phase is carried out in a heterogeneous reaction system, the reaction rate is fast, and the product yield reaches more than 85%. Therefore, the method of the present invention has the advantages of simple preparation method, convenient operation, mild reaction conditions, green environmental protection, etc., realizing the green synthesis of S-(p-tolyl) 4-methylbenzenesulfinate and having good industrial application prospects.

[0052] The experimental results show that the synthesis method provided by the present invention can make the product yield reach more than 55% and the purity reach more than 90%. When under the optimal conditions, that is, using acetonitrile and water in combination as the solvent and controlling the volume ratio of acetonitrile: water to be 1:1, and controlling the current of the electrified reaction to be 10 mA and the temperature to be 60 °C, the product yield can reach 85% and the purity can reach 95%.

[0053] In order to further understand the present invention, the preferred embodiments of the present invention will be described below in conjunction with examples. However, it should be understood that these descriptions are only to further illustrate the features and advantages of the present invention, rather than a limitation on the claims of the present invention.

[0054] Example 1

[0055] a) 0.5 mmol of p-methylthiophenol, 1.0 mmol of benzaldehyde, 0.25 mmol of KI, and 3 mL of solvent (volume ratio of acetonitrile: water = 1:1) are stirred and mixed at room temperature to obtain a mixed solution.

[0056] b) The mixed solution is used as the electrolyte, with a DC power supply as the power source, and both the anode and the cathode are platinum plates, and a constant direct current is passed for the reaction. The reaction conditions are as follows: current 10 mA, temperature 60 °C, reaction for 6 h. After the reaction, a reaction mixture is obtained.

[0057] c) The resulting reaction mixture was extracted with 20 mL of ethyl acetate. Then, the organic phase was concentrated under reduced pressure under the conditions of a pressure of 0.095 Mpa, a temperature of 60 °C, and a treatment duration of 0.2 h. After that, the resulting concentrate was separated and purified by column chromatography, and the developing agent used was a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 20:1. After the above treatment, 0.2227 g of S-(p-tolyl) 4-methylbenzenesulfinate product was obtained. The yield was calculated to be 85%.

[0058] The reaction route of the above synthesis method is as follows:

[0059]

[0060] The nuclear magnetic resonance hydrogen spectrum data of the obtained product are as follows: 1 H NMR (501 MHz, Chloroform-d) δ 7.45 (d, J = 8.2 Hz, 2H), 7.22 (dd, J = 14.0, 8.1 Hz, 4H), 7.14 (d, J = 7.8 Hz, 2H), 2.42 (s, 3H), 2.37 (s, 3H). See specifically Figure 1 , Figure 1 for the nuclear magnetic resonance hydrogen spectrum of the product obtained in Example 1.

[0061] Example 2

[0062] Implemented according to Example 1, except that acetonitrile in the solvent in step a) was replaced with tetrahydrofuran.

[0063] Example 3

[0064] Implemented according to Example 1, except that acetonitrile in the solvent in step a) was replaced with ethanol.

[0065] The preparation effects of Examples 1 to 3 are shown in Table 1:

[0066] Table 1: Preparation effects of Examples 1 to 3

[0067] Organic solvents in the solvent Product yield, % Product purity, % Example 1 Acetonitrile 85 95 Example 2 Tetrahydrofuran 62 92 Example 3 Ethanol 57 90

[0068] It can be seen that S-(p-tolyl) 4-methylbenzenesulfinate products can be effectively synthesized in Examples 1 - 3. Among them, the product obtained in Example 1 has the highest yield and purity, proving that the combination of acetonitrile and water has the best effect compared with the combination of other organic solvents and water.

[0069] Example 4

[0070] Implemented according to Example 1, except that the amount of acetonitrile in the solvent in step a) was adjusted so that the volume ratio of acetonitrile:water = 1:9.

[0071] Example 5

[0072] Implemented according to Example 1, except that the amount of acetonitrile in the solvent in step a) is adjusted so that the volume ratio of acetonitrile to water is 1:0.5.

[0073] For the preparation effects of Examples 1, 4 - 5, see Table 2:

[0074] Table 2: Preparation effects of Examples 1, 4 - 5

[0075] Volume ratio of acetonitrile to water in the solvent Product yield, % Product purity, % Example 1 1∶1 85 95 Example 4 1∶9 75 93 Example 5 1∶0.5 78 93

[0076] It can be seen that in Examples 1, 4 - 5, the product S-(p-tolyl) 4-methylbenzenesulfinate can be effectively synthesized. Among them, the yield and purity of the product obtained in Example 1 are the highest, proving that when the volume ratio of acetonitrile to water is 1:1, the reaction effect is the best.

[0077] Example 6

[0078] Implemented according to Example 1, except that the current in step b) is adjusted to 5 mA and the temperature is adjusted to 80 °C.

[0079] Example 7

[0080] Implemented according to Example 1, except that the current in step b) is adjusted to 30 mA and the temperature is adjusted to 25 °C.

[0081] For the preparation effects of Examples 1, 6 - 7, see Table 3:

[0082] Table 3: Preparation effects of Examples 1, 6 - 7

[0083] Reaction current, mA Reaction temperature, °C Product yield, % Product purity, % Example 1 10 60 85 95 Example 6 5 80 66 92 Example 7 30 25 59 90

[0084] It can be seen that in Examples 1, 6 - 7, the product S-(p-tolyl) 4-methylbenzenesulfinate can be effectively synthesized. Among them, the yield and purity of the product obtained in Example 1 are the highest, proving that when the reaction current is 10 mA and the reaction temperature is 60 °C, the reaction effect is the best.

[0085] In this article, specific examples are used to illustrate the principles and implementation modes of the present invention. The description of the above embodiments is only used to help understand the method and its core idea of the present invention, including the best mode, and also enables any person skilled in the art to practice the present invention, including manufacturing and using any device or system, and implementing any combined method. It should be noted that for those of ordinary skill in the art in the technical field, without departing from the principles of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention. The protection scope of the present invention patent is defined by the claims and may include other embodiments that can be conceived by those skilled in the art. If these other embodiments have structural elements similar to the literal description of the claims, or if they include equivalent structural elements that have no substantial difference from the literal description of the claims, then these other embodiments should also be included within the scope of the claims.

Claims

1. A method for synthesizing S-(p-tolyl) 4-methylbenzenesulfinate, characterized in that, It includes the following steps: a) Mix p-methylthiophenol, benzaldehyde, an electrolyte and a solvent to obtain a mixed solution; The electrolyte is selected from at least one of KI, NaI, TBAI and KBr; The solvent is a mixed solvent of an organic solvent and water; Among them, the organic solvent is selected from at least one of acetonitrile, tetrahydrofuran, ethanol, ethylene glycol, N,N-dimethylformamide, chloroform, dichloromethane, 1,2-dichloroethane and ether; b) Perform an electrolytic reaction using the mixed solution as the electrolyte to obtain a reaction mixed solution; c) Extract, concentrate and separate and purify the reaction mixed solution to obtain S-(p-tolyl) 4-methylbenzenesulfinate.

2. The synthesis method according to claim 1, wherein In step a), the volume ratio of the organic solvent to water is 1:(0.5 - 9).

3. The synthesis method according to claim 1, characterized in that, In step b), the conditions of the electrolytic reaction are: current 5 - 30 mA, temperature 25 - 80 °C, time 4 - 6 h.

4. The synthesis method according to claim 1 or 3, characterized in that, In step b), in the electrolytic reaction, both the anode and the cathode are platinum sheets.

5. The synthesis method according to claim 1, wherein In step a), the molar ratio of p-methylthiophenol to benzaldehyde is 1:(0.5 - 2.5).

6. The synthesis method according to claim 1, wherein In step a), the molar ratio of p-methylthiophenol to the electrolyte is 1:(0.3 - 3).

7. The synthesis method according to claim 1, wherein In step a), the volume ratio of p-methylthiophenol to the solvent is 1:(0.02 - 0.1).

8. The synthesis method according to claim 1, characterized in that, In step c), the extractant used for extraction is ethyl acetate; The concentration is carried out under reduced pressure.

9. The synthesis method according to claim 1, wherein In step c), the separation and purification is carried out by column chromatography; The eluent used in the column chromatography is a mixed solvent of petroleum ether and ethyl acetate.

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