Preparation method of p-methylsulfonyl benzaldehyde

Abstract

The invention belongs to the technical field of electrochemistry and organic chemical synthesis, and particularly relates to a preparation method of p-methylsulfonyl benzaldehyde, which comprises the following two main steps: (1) converting p-chlorotoluene serving as a raw material into p-chlorobenzaldehyde through electrochemical and hydrolysis reaction; and (2) carrying out substitution and oxidation reaction on the obtained p-chlorobenzaldehyde to finally prepare the p-methylsulfonyl benzaldehyde. According to the method, an electrolytic tank reactor is adopted, the reaction time is controllable, the conversion rate is high, few byproducts are produced, operation is easy and convenient, the production efficiency is greatly improved, and the problems that in a traditional synthesis method, aftertreatment is difficult, and safety is low are effectively solved. The invention provides a green process for synthesizing p-methylsulfonyl benzaldehyde under efficient and safe conditions, and the method has a good industrial application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical fields of organic chemistry and electrochemical synthesis, and particularly relates to a method for preparing 4-methylsulfonylbenzaldehyde. Background Art

[0002] 4-Methylsulfonylbenzaldehyde is an important intermediate widely used in the fields of pharmaceutical synthesis, pesticides, dyes, and other fine chemicals. Traditional methods usually involve multi-step reactions, including harsh reaction conditions and complex post-treatment processes, which lead to high production costs and many by-products. In traditional chemical reactions, strong oxidants or reductants are often used, causing environmental pollution and safety hazards. The existing synthesis methods mainly include the following:

[0003] (1) Using 4-methylsulfonyltoluene as the starting material, under the action of a catalyst, it undergoes a substitution reaction with chlorine or liquid bromine, and then hydrolysis and alkali washing to obtain 4-methylsulfonylbenzaldehyde. However, this process requires the use of chlorine or liquid bromine, which has high requirements for transportation and production safety, and at the same time, the steps are relatively cumbersome.

[0004] (2) Using 4-methylsulfonyltoluene as the starting material, directly undergoing an oxidation reaction under the action of a catalyst to obtain 4-methylsulfonylbenzaldehyde. This process uses the oxidation method, but the reaction is not complete. After the raw materials need to be separated from the product, they are recycled, and the oxidant used also needs to be oxidized and regenerated by an electrochemical method. Generally speaking, the equipment investment is large and the operation steps are many.

[0005] (3) Using 4-fluorobenzaldehyde as the starting material, reacting with sodium methanesulfonate to obtain 4-methylsulfonylbenzaldehyde. The raw material 4-fluorobenzaldehyde used in this process seriously corrodes the equipment, and at the same time, the by-product hydrogen cyanide gas generated by the reaction is highly toxic, posing a great safety hazard.

[0006] (4) Using 4-chlorobenzaldehyde as the starting material, undergoing a substitution reaction with sodium methyl mercaptide under the action of a phase transfer catalyst to generate 4-methylthiobenzaldehyde; 4-methylthiobenzaldehyde undergoes an oxidation reaction with hydrogen peroxide under the action of sulfuric acid and metal salt catalysts to obtain 4-methylsulfonylbenzaldehyde. The disadvantages of this process are as follows: the obtained 4-methylsulfonylbenzaldehyde has a low purity, generally about 96%, and can only reach more than 98% after refining to meet customer requirements. At the same time, sulfuric acid and heavy metal salts are required as catalysts, which are not friendly to the environment, and special attention needs to be paid to sulfuric acid during transportation and use.

[0007] Therefore, developing a method for synthesizing 4-methylsulfonylbenzaldehyde that is efficient, safe, and environmentally friendly is of great significance for improving the industrial production efficiency and safety of chemical products. Summary of the Invention

[0008] The object of the present invention is to provide a method for preparing p-methylsulfonylbenzaldehyde. This method uses p-chlorotoluene as a raw material, first converts it into p-chlorobenzaldehyde through electrochemical and hydrolysis reactions, and then further converts the obtained p-chlorobenzaldehyde into p-methylsulfonylbenzaldehyde through substitution and oxidation reactions. The reaction conditions in the whole synthesis process are mild, the product purity is high, and the by-products are few, which has high industrial application value.

[0009] In order to achieve the above object of the invention, the following technical solutions are adopted:

[0010] A method for preparing p-methylsulfonylbenzaldehyde is divided into two main steps:

[0011]

[0012] The first step is to convert p-chlorotoluene into p-chlorobenzaldehyde through electrochemical and hydrolysis reactions

[0013] Using p-chlorotoluene as a raw material, through the electrochemical reaction and hydrolysis reaction in the electrolytic cell, p-chlorotoluene is converted into p-chlorobenzaldehyde;

[0014]

[0015] The second step is to prepare p-methylsulfonylbenzaldehyde through substitution and oxidation reactions

[0016] First, the chlorine group in p-chlorobenzaldehyde is substituted with a methylthio group through a substitution reaction, and then an oxidant such as hydrogen peroxide reacts with p-methylthiobenzaldehyde through a substitution reaction to generate p-methylsulfonylbenzaldehyde.

[0017] In the synthesis method, the electrochemical method in the first step has high controllability, can effectively improve the conversion rate of the raw material, and because the reaction conditions are relatively mild, there are few by-products, and the purity of the generated p-chlorobenzaldehyde is relatively high. Synthesizing p-chlorobenzaldehyde by the electrochemical method simplifies the multi-step operations common in traditional chemical methods and greatly shortens the reaction time.

[0018] Preferably, the method for preparing p-methylsulfonylbenzaldehyde is specifically as follows:

[0019] 1.1) Electrochemical reaction: Add bromide salt, water and concentrated sulfuric acid into the electrolytic cell, and turn on the electrochemical workstation; under stirring, add p-chlorotoluene and a phase transfer catalyst, and continue the reaction until p-chlorotoluene completely reacts to obtain a brominated intermediate;

[0020] 1.2) Hydrolysis reaction: Water is added to the brominated intermediate obtained in step 1.1), and the pH value is adjusted to 9 - 10 (preferably using sodium hydroxide to adjust the pH); the reaction system is heated to reflux with stirring until the brominated intermediate completely reacts, and then cooled to room temperature; then the pH value is adjusted to weakly alkaline (preferably using sodium hydroxide to adjust the pH); after extraction with an organic solvent (preferably dichloromethane), the solvent is removed to obtain white solid p-chlorobenzaldehyde;

[0021] 2.1) Substitution reaction: p-Chlorobenzaldehyde obtained in step 1.2), a phase transfer catalyst, and an aqueous solution of sodium methyl mercaptide (preferably with a mass concentration of 10 - 30%) are added to a reaction vessel, and the temperature is raised to 50 - 70 °C with stirring for reaction until p-chlorobenzaldehyde completely reacts; water is added for extraction to obtain p-methylthio benzaldehyde;

[0022] 2.2) Oxidation reaction: p-Methylthio benzaldehyde obtained in step 2.1), an Na 2 WO 4 solution, an H 2 SO 4 aqueous solution, and water are mixed evenly; an oxidizing agent (preferably hydrogen peroxide is slowly added dropwise) is added with stirring, and the temperature is raised to 70 - 80 °C for reaction until p-methylthio benzaldehyde completely reacts; the temperature is lowered, filtered, and washed to obtain p-methylsulfonyl benzaldehyde.

[0023] Preferably, in the preparation method, 1.1) and 1.2) are replaced with the following steps:

[0024] 1.3) Under light, a bromide salt, water, and concentrated sulfuric acid are added to an electrolytic cell, and an electrochemical workstation is turned on; with stirring, p-chlorotoluene and a phase transfer catalyst are added, and the reaction continues until p-chlorotoluene completely reacts to obtain a brominated intermediate; the electrochemical workstation is turned off, and the light is continued until the brominated intermediate completely reacts, and then cooled to room temperature; then the pH value is adjusted to weakly alkaline (preferably using sodium hydroxide to adjust the pH), and after extraction with an organic solvent (preferably dichloromethane), the solvent is removed to obtain white solid p-chlorobenzaldehyde.

[0025] Preferably, the bromide salt is one or more of NaBr, KBr, NH 4 Br, MgBr 2 , CsBr.

[0026] Preferably, in 1.1) and 1.3), the molar ratio of p-chlorotoluene:bromide salt:concentrated sulfuric acid:phase transfer catalyst is 1:2 - 10:1 - 3:0.01 - 0.15, preferably 1:6.15:1.25:0.12.

[0027] Preferably, the molar ratio of 4-chlorobenzaldehyde: sodium methyl mercaptide: oxidant: concentrated sulfuric acid: sodium tungstate, phase transfer catalyst in 2.1) and 2.2) is 1: 1-2: 2-4: 0.01-0.4: 0.005-0.05: 0.01-0.1, preferably 1: 1.3: 2.5: 0.035: 0.016: 0.07.

[0028] Preferably, the molar ratio of 4-chlorobenzaldehyde to sodium methyl mercaptide is 1: 1-1.5.

[0029] Preferably, the phase transfer catalyst is tetrabutylammonium bromide.

[0030] Preferably, when using an electrochemical workstation, a three-electrode system is selected, and the current is output and the reaction is controlled through i-t; and / or

[0031] The output voltage of the electrochemical workstation is 0.2-0.5 V (preferably 0.35 V), the interval time is 0.1 s, the running time is 1-24 h, and the sensitivity is 0.1-0.0001.

[0032] Preferably, the light used in 1.3) is an incandescent lamp (45 W) or an LED lamp (5 W).

[0033] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows:

[0034] The present invention is particularly suitable for the industrial production of fine chemical intermediates, and has the characteristics of simple operation and environmental friendliness as follows:

[0035] Environmentally friendly: Electrochemical synthesis uses current as the energy source, avoiding the use of harmful chemical reagents and reducing environmental pollution and waste treatment problems.

[0036] Atom economy: Electrochemical synthesis usually has high selectivity, which means high atomic utilization rate and few by-products in the reaction process, meeting the principles of green chemistry.

[0037] Mild reaction conditions: Many electrochemical synthesis reactions can be carried out at room temperature and normal pressure, without extreme conditions such as high temperature and high pressure, reducing the risk and energy consumption of the reaction.

[0038] Simple operation: The electrochemical synthesis device is relatively simple, easy to operate and control, and suitable for laboratory and industrial production.

[0039] Adjustable and controllable: The adjustment of reaction conditions (such as potential, current, time) can precisely control the reaction process and achieve the precise synthesis of products.

[0040] Energy efficiency: Electrochemical assisted synthesis can directly use electrical energy, and has higher energy conversion efficiency compared with traditional heat-driven reactions.

[0041] Safety: Since there is no need to use flammable and explosive chemical reagents, electrochemical synthesis has advantages in terms of safety.

[0042] Scalability: Electrochemical synthesis technology can be scaled up from laboratory scale to industrial scale, with good amplification potential. Description of the Drawings

[0043] Figure 1 It is the gas chromatogram of 4-methylsulfonylbenzaldehyde in Example 4.

[0044] Figure 2 It is the mass spectrum of 4-methylsulfonylbenzaldehyde in Example 4.

[0045] Figure 3 It is the liquid chromatogram of 4-methylsulfonylbenzaldehyde in Examples 5 and 6. Detailed Embodiments

[0046] The technical solutions of the present invention will be further described below in conjunction with specific embodiments.

[0047] The preparation method of 4-methylsulfonylbenzaldehyde in the embodiments of the present invention includes the following steps:

[0048] In the first step, electrochemical and hydrolysis reactions convert p-chlorotoluene into p-chlorobenzaldehyde

[0049] Using p-chlorotoluene as the raw material, through the electrochemical reaction in the electrolytic cell for 5 - 14 hours, after adjusting the pH value, heating under reflux, extracting with dichloromethane, and concentrating the organic layer under reduced pressure to obtain p-chlorobenzaldehyde. In the reaction, a three-electrode system is selected (working electrode: platinum electrode; counter electrode: platinum electrode; reference electrode: saturated potassium bromide electrode), and the reaction is controlled by outputting current through i-t.

[0050] In the second step, substitution and oxidation reactions are carried out to prepare 4-methylsulfonylbenzaldehyde

[0051] First, the chlorine group in p-chlorobenzaldehyde is substituted with a methylthio group through a substitution reaction, and then an oxidation reaction occurs between the resulting p-methylthiobenzaldehyde and a sulfur oxidizing agent such as hydrogen peroxide to generate 4-methylsulfonylbenzaldehyde.

[0052] The preparation method of 4-methylsulfonylbenzaldehyde in Example 1 is as follows:

[0053] In step A), the molar ratio of p-chlorotoluene: sodium bromide: concentrated sulfuric acid: tetrabutylammonium bromide is 1:6.15:2.5:0.04.

[0054] The voltage output by the electrochemical workstation during operation is 0.25V, the interval time is 0.1s, the running time is 14h, the sensitivity is 0.001, and there is no light illumination.

[0055] In step B), the molar ratio of p-chlorobenzaldehyde : sodium methyl mercaptide : hydrogen peroxide : concentrated sulfuric acid : sodium tungstate : tetrabutylammonium bromide TBAB is 1:1.3:3.7:0.042:0.014:0.014.

[0056] Step A):

[0057] A.1) Electrochemical reaction: Add 30 g of sodium bromide to an electrolytic cell, add 120 mL of water to dissolve it, and add 12 g of concentrated sulfuric acid (98 wt%, the same below) dropwise to the solution. Under stirring, turn on the electrochemical workstation chi920d, and use the electrochemical workstation to output a voltage of (0.25 V). Add 6.0 g of p-chlorotoluene and 600 mg of tetrabutylammonium bromide to the reaction system. Monitor the reaction by TLC (the developing agent is V 石油醚 :V 二氯甲烷 = 2:1, the same below), and after reacting for 14 h, the raw material spot disappears, and the reaction ends to obtain a yellow oil-water mixture - brominated intermediate.

[0058] A.2) Hydrolysis reaction: Continue to add 100 ml of water to the above reaction system, adjust the pH = 9 - 10 with 10% sodium hydroxide solution (mass concentration, the same below), heat the reaction system to 100 °C for reflux, monitor the reaction by TLC, and after reacting for 8 h, the brominated intermediate completely disappears and the reaction reaches the end point. Then cool the reaction system to room temperature (25 °C, the same below), adjust it to weakly alkaline pH = 8 with 10% aqueous sodium hydroxide solution, and the oily liquid in the reaction system becomes solid. Extract with dichloromethane, take the organic phase, and remove the solvent under reduced pressure to obtain white solid p-chlorobenzaldehyde.

[0059] Step B):

[0060] B.1) Substitution reaction: Add 3 g of p-chlorobenzaldehyde synthesized in step A), 90 mg of TBAB, and 10 g of 20% NaSCH 3 aqueous solution (mass concentration, the same below) to a three-necked flask, mechanically stir and heat to 50 °C, and stir for 2 h. Then heat to 62 °C and continue stirring the reaction, and monitor the reaction by TLC. After 9 h, the raw materials completely disappear and the reaction reaches the end point. Add 100 mL of water for liquid separation, take the lower organic phase, and the organic phase is the p-methylthio-benzaldehyde intermediate, about 3.1 g.

[0061] B.2) Oxidation reaction: Add 3 g of the p-methylthio-benzaldehyde intermediate obtained from the substitution reaction, Na 2 WO 4 solution (90 mg of Na 2 WO 4 ·2H 2 O dissolved in 1 g of H 2 O), H 2 SO 4 solution (containing 90 mg of concentrated sulfuric acid, 1 g of H2 O), 5 g of H 2 O. Stir at room temperature for 10 min. Then slowly add dropwise 4.5 g of hydrogen peroxide (30 wt% hydrogen peroxide, the same below) to it (the reaction is very rapid during this process, releasing a large amount of heat, and the dropping process should be extremely slow, so the dropping rate is adjusted by the amount of reactants and the temperature in the system. The optimal dropping rate of hydrogen peroxide for the oxidation reaction is 1 - 3 drops / second. In this example, the dropping rate of hydrogen peroxide is maintained at 2 drops / second, the same below). Keep the temperature of the reaction system at 40 ± 5 °C. After the dropping is complete, continue to add dropwise 4.5 g of hydrogen peroxide, and control the temperature at 50 ± 10 °C during this process. After the dropping is complete, white solid will be produced, and the whole reactant presents a light yellow solid-liquid mixture state. Then raise the temperature to 80 °C and react for 1 h. Monitor the reaction by TLC. When the raw materials completely disappear, the reaction reaches the end point. Finally, cool down to 5 °C, carry out suction filtration, wash the filter cake with water, neutralize it to neutral (pH = 7, the same below) with 10% NaOH aqueous solution, carry out suction filtration again, wash the filter cake with a small amount of water, and dry it in an oven at 60 °C to obtain 2.7 g of p-methylsulfonylbenzaldehyde.

[0062] Example 2 Preparation method of p-methylsulfonylbenzaldehyde, the specific steps are as follows:

[0063] In step A, the molar ratio of p-chlorotoluene: sodium bromide: concentrated sulfuric acid: tetrabutylammonium bromide for feeding is 1:6.15:1.25:0.04.

[0064] The output voltage of the electrochemical workstation is 0.35 V, the interval time is 0.1 s, the running time is 8 h, the sensitivity is 0.001, and there is no light irradiation.

[0065] In step B, the molar ratio of p-chlorobenzaldehyde: sodium methyl mercaptide: hydrogen peroxide: concentrated sulfuric acid: sodium tungstate: tetrabutylammonium bromide is 1:1.3:2.5:0.028:0.014:0.02.

[0066] Step A:

[0067] A.1) Electrochemical reaction: Add 30 g of sodium bromide to the electrolytic cell, add 120 mL of water to dissolve it, and add 6 g of concentrated sulfuric acid dropwise to the solution. Under stirring, turn on the electrochemical workstation chi920d, and use the output voltage of the electrochemical workstation (0.35 V) to add 6.0 g of p-chlorotoluene and 600 mg of tetrabutylammonium bromide to the reaction system. Monitor the reaction by TLC. When the raw material spots disappear after reacting for 8 h, the reaction ends to obtain a yellow oil-water mixture - brominated intermediate.

[0068] A.2) Hydrolysis reaction: Continuously add 100 ml of water to the above reaction system, and adjust the pH to 9 - 10 with 10% sodium hydroxide solution. Heat the reaction system to reflux at 100 °C, monitor the reaction by TLC. After 8 h of reaction, the bromination intermediate completely disappears and the reaction reaches the end point. Cool to room temperature, adjust to weakly alkaline pH = 8 with 10% sodium hydroxide solution, and the oily liquid becomes solid. Extract with dichloromethane, take the organic phase, and remove the solvent under reduced pressure to obtain white solid p-chlorobenzaldehyde.

[0069] Step B:

[0070] B.1) Substitution reaction: Add 3 g of p-chlorobenzaldehyde synthesized in step A, 150 mg of TBAB, and 10 g of 20% NaSCH 3 aqueous solution to a three-necked flask, stir mechanically and heat to 50 °C, and stir for 2 h. Then heat to 62 °C and continue stirring the reaction, monitoring the reaction by TLC. After 7 h, the raw materials completely disappear and the reaction reaches the end point. Add 100 mL of water for liquid separation, take the lower organic phase, and the organic phase is the p-methylthiobenzaldehyde intermediate, about 3.1 g.

[0071] B.2) Oxidation reaction: Add 3 g of the intermediate obtained from the substitution reaction to a three-necked flask, Na 2 WO 4 solution (90 mg of Na 2 WO 4 ·2H 2 O dissolved in 1 g of H 2 O), H 2 SO 4 solution (containing 60 mg of concentrated H 2 SO 4 、1 g of H 2 O), 5 g of H 2 O, stir at room temperature for 10 min. Then slowly add 3 g of hydrogen peroxide dropwise to it, keep the temperature of the reaction system at 40 ± 5 °C, and continue to add 3 g of hydrogen peroxide after dropping. Control the temperature at 50 ± 10 °C during this process. After dropping, there will be white solid, and the whole reactant presents a light yellow solid-liquid state. Then heat to 80 °C and react for 2 h, monitoring the reaction by TLC. The raw materials completely disappear and the reaction reaches the end point. Finally, cool to 5 °C, filter by suction, wash the filter cake with water, and neutralize it to neutral with 10% NaOH solution. Filter by suction again, wash the filter cake with a small amount of water and dry it in an oven at 60 °C to obtain 3.1 g of p-methylsulfonylbenzaldehyde.

[0072] The preparation method of p-methylsulfonylbenzaldehyde in Example 3 is as follows:

[0073] In step A), the molar ratio of p-chlorotoluene: sodium bromide: concentrated sulfuric acid: tetrabutylammonium bromide is 1:6.25:1.25:0.12.

[0074] The output voltage of the electrochemical workstation is 0.35 V, the interval time is 0.1 s, the running time is 5 h, the sensitivity is 0.001, and LED light illumination is used.

[0075] In step B), the molar ratio of p-chlorobenzaldehyde : sodium methyl mercaptide : hydrogen peroxide : concentrated sulfuric acid : sodium tungstate : tetrabutylammonium bromide is 1:1.3:2.5:0.072:0.032:0.073.

[0076] Step A:

[0077] Under the irradiation of an LED lamp (5 W), add 30 g of sodium bromide to the electrolytic cell, add 120 mL of water to dissolve it, and add 6 g of concentrated sulfuric acid dropwise to the solution. With stirring, turn on the electrochemical workstation chi920d, and use the electrochemical workstation to output a voltage (0.35 V). Add 6 g of p-chlorotoluene and 1.8 g of tetrabutylammonium bromide to the reaction system. Detect the reaction by TLC. A small amount of p-chlorobenzaldehyde is formed during the reaction. After 5 h, the raw material spot disappears, and a yellow oil-water mixture is obtained. Turn off the electrochemical workstation and continue to irradiate with the LED lamp. Monitor the reaction by TLC during the process. Continue irradiating for 24 h until the bromination intermediate completely disappears, and the reaction reaches the end point. Cool to room temperature, adjust to weak alkaline pH = 8 with 10% sodium hydroxide solution, extract with dichloromethane, take the organic phase, and remove the solvent under reduced pressure to obtain white solid p-chlorobenzaldehyde.

[0078] Step B:

[0079] B.1) Substitution reaction: Add 3 g of p-chlorobenzaldehyde synthesized in step A, 500 mg of TBAB, and 10 g of 20% NaSCH 3 aqueous solution to the three-necked flask, mechanically stir and heat to 50 °C, and stir for 2 h. Then heat to 62 °C and continue stirring the reaction, and monitor the reaction by TLC. After 5 h, the raw materials completely disappear, and the reaction reaches the end point. Add 100 mL of water for liquid separation, take the lower organic phase, and the organic phase is the p-methylthio benzaldehyde intermediate, about 3.1 g.

[0080] B.2) Oxidation reaction: Add 3 g of the p-methylthio benzaldehyde intermediate obtained from the substitution reaction to the three-necked flask, Na 2 WO 4 solution (200 mg of Na 2 WO 4 ·2H 2 O dissolved in 1 g of H 2 O), H 2 SO 4 solution (containing 150 mg of concentrated H 2 SO 4 、1 g of H 2 O), 5 g of H 2O. Stir at room temperature for 10 min, then slowly add 3 g of hydrogen peroxide dropwise thereto, and keep the temperature of the reaction system at 40 ± 5 °C. After the addition, continue to add 3 g of hydrogen peroxide dropwise, and control the temperature at 50 ± 10 °C during this process. After the addition, there will be a white solid, and the whole reactant presents a pale yellow solid-liquid state. Then raise the temperature to 80 °C and react for 2 h. Monitor the reaction by TLC. When the raw materials completely disappear, the reaction reaches the end point. Finally, cool down to 5 °C, filter by suction, wash the filter cake with water, neutralize it to neutral with 10% NaOH solution, filter by suction again, wash the filter cake with a small amount of water, and dry it in an oven at 60 °C to obtain 3 g of 4-methylsulfonylbenzaldehyde.

[0081] Preparation method of 4-methylsulfonylbenzaldehyde in Example 4, the specific steps are as follows:

[0082] In step A), the molar ratio of p-chlorotoluene: sodium bromide: concentrated sulfuric acid: tetrabutylammonium bromide is 1: 6.25: 1.25: 0.12.

[0083] The output voltage of the electrochemical workstation is 0.35 V, the interval time is 0.1 S, the running time is 5 h, the sensitivity is 0.001, and it is irradiated with incandescent light.

[0084] In step B), the molar ratio of p-chlorobenzaldehyde: sodium methyl mercaptide: hydrogen peroxide: concentrated sulfuric acid: sodium tungstate: tetrabutylammonium bromide is 1: 1.3: 2.5: 0.035: 0.016: 0.07.

[0085] Step A:

[0086] Under the irradiation of an incandescent lamp (45 W), add 30 g of sodium bromide to the electrolytic cell, add 120 mL of water to dissolve it, and add 6 g of concentrated sulfuric acid dropwise to the solution. Under stirring, turn on the electrochemical workstation to open chi920d, output the voltage (0.35 V) with the electrochemical workstation, and add 6 g of p-chlorotoluene and 1.8 g of tetrabutylammonium bromide to the reaction system. Detect the reaction by TCL. During the reaction, p-chlorobenzaldehyde is generated. After reacting for 5 h, the raw material spot disappears, and a yellow oil-water mixture is obtained. Turn off the electrochemical workstation, and continue to irradiate with an incandescent lamp. Monitor the reaction by TLC during the process, and continue to irradiate for 5 h until the bromination intermediate completely disappears, and the reaction reaches the end point. Cool to room temperature, adjust to weak alkaline pH = 8 with 10% sodium hydroxide solution, extract with dichloromethane, take the organic phase, and remove the solvent under reduced pressure to obtain white solid p-chlorobenzaldehyde.

[0087] Step B:

[0088] B.1) Substitution reaction: Add 3 g of p-chlorobenzaldehyde synthesized in step A, 450 mg of TBAB, and 10 g of 20% NaSCH 3An aqueous solution was heated to 50 °C with mechanical stirring and stirred for 2 h. Then it was heated to 62 °C and stirred. The reaction was monitored by TLC. After 5 h, the raw materials completely disappeared, indicating the reaction reached the end point. 100 mL of water was added for liquid separation, and the lower organic phase was taken. The organic phase was the p-methylthiophenylaldehyde intermediate, about 3.1 g.

[0089] B.2) Oxidation reaction: Add 3 g of the intermediate obtained from the substitution reaction to a three-necked flask, Na 2 WO 4 solution (100 mg of Na 2 WO 4 ·2H 2 O dissolved in 1 g of H 2 O), H 2 SO 4 solution (containing 72 mg of concentrated H 2 SO 4 、1 g of H 2 O), 5 g of H 2 O, and stir at room temperature for 10 min. Then slowly add 3 g of hydrogen peroxide dropwise thereto, and keep the temperature of the reaction system at 40 ± 5 °C. After dropping, continue to add 3 g of hydrogen peroxide dropwise, and control the temperature at 50 ± 10 °C during this process. After dropping, there will be a white solid, and the whole reaction system presents a pale yellow solid-liquid state. Then heat it to 80 °C and react for 2 h. Monitor the reaction by TLC. When the raw materials completely disappear, the reaction reaches the end point. Cool it to 5 °C, filter by suction, wash the filter cake with water, neutralize it to neutral with 10% NaOH solution, filter by suction again, wash the filter cake with a small amount of water, and dry it in an oven at 60 °C to obtain 3.2 g of p-methylsulfonylbenzaldehyde.

[0090] As Figure 1 and Figure 2 shown, the p-methylsulfonylbenzaldehyde product obtained in this example was subjected to structural characterization and purity detection. From the gas chromatogram ( Figure 1 ) results, it was found that the product had only one chromatographic peak. By integrating this chromatographic peak, the peak area, peak height, and purity values were obtained. The gas chromatography results showed that the purity of the product was close to 100%. The product was characterized by mass spectrometry ( Figure 2 ) and the molecular weight of the product was found to be 184, which was consistent with the molecular weight of p-methylsulfonylbenzaldehyde, indicating that the product was successfully synthesized.

[0091] The preparation method of p-methylsulfonylbenzaldehyde in Example 5 is as follows:

[0092] In step A), the molar ratio of p-chlorotoluene: sodium bromide: concentrated sulfuric acid: tetrabutylammonium bromide was 1:6.25:1.25:0.12.

[0093] The voltage output by the electrochemical workstation was 0.35 V, the interval time was 0.1 s, the running time was 5 h, the sensitivity was 0.001, and it was irradiated with incandescent light.

[0094] In step B), the molar ratio of 4-chlorobenzaldehyde: sodium methyl mercaptide: hydrogen peroxide: concentrated sulfuric acid: sodium tungstate: tetrabutylammonium bromide is 1:1.3:2.5:0.035:0.016:0.07.

[0095] Step A:

[0096] Under the irradiation of an incandescent lamp (45 W), add 50 g of sodium bromide to the electrolytic cell, add 200 mL of water to dissolve it, and add 10 g of concentrated sulfuric acid dropwise to the solution. With stirring, turn on the electrochemical workstation to open chi920d, output a voltage of 0.35 V with the electrochemical workstation, and add 10 g of 4-chlorotoluene and 3 g of tetrabutylammonium bromide to the reaction system. Detect the reaction by TLC. During the reaction, 4-chlorobenzaldehyde is formed. After 5 h, the raw material spot disappears, and a yellow oil-water mixture is obtained. Turn off the electrochemical workstation and continue to irradiate with the incandescent lamp. Monitor the reaction by TLC during the process. Continue irradiation for 5 h until the bromination intermediate completely disappears, and the reaction reaches the end point. Cool to room temperature, adjust to a weak alkaline pH = 8 with 10% sodium hydroxide solution, extract with dichloromethane, take the organic phase, and remove the solvent under reduced pressure to obtain white solid 4-chlorobenzaldehyde.

[0097] Step B:

[0098] B.1) Substitution reaction: Add 10 g of 4-chlorobenzaldehyde synthesized in step A, 1.5 g of TBAB, and 33 g of 20% NaSCH 3 aqueous solution to the three-necked flask, stir mechanically and heat to 50 °C, and stir for 2 h. Then heat to 62 °C and stir. Monitor the reaction by TLC. After 5 h, the raw materials completely disappear, and the reaction reaches the end point. Add 100 mL of water for liquid separation, and take the lower organic phase. The organic phase is the intermediate p-methylthiobenzaldehyde, about 10.2 g.

[0099] B.2) Oxidation reaction: Add 10 g of the intermediate obtained from the substitution reaction to the three-necked flask, Na 2 WO 4 solution (330 mg of Na 2 WO 4 ·2H 2 O dissolved in 3 g of H 2 O), H 2 SO 4 solution (containing 240 mg of concentrated H 2 SO 4 、3 g of H 2 O), 15 g of H 2O. Stir at room temperature for 10 min. Then slowly add 10 g of hydrogen peroxide dropwise thereto, and keep the temperature of the reaction system at 40 ± 5 °C. After dropping, continue to add 10 g of hydrogen peroxide dropwise, and control the temperature at 50 ± 10 °C during this process. After dropping, there will be white solid, and the whole reaction system presents a light yellow solid-liquid state. Then raise the temperature to 80 °C and react for 2 h. Monitor the reaction by TLC. When the raw materials completely disappear, the reaction reaches the end point. Cool down to 5 °C, filter by suction, wash the filter cake with water, neutralize it to neutral with 10% NaOH solution, filter by suction again, wash the filter cake with a small amount of water, and dry it in an oven at 60 °C to obtain 10.3 g of p-methylsulfonylbenzaldehyde.

[0100] The preparation method of p-methylsulfonylbenzaldehyde in Example 6 is as follows:

[0101] In step A), the molar ratio of p-chlorotoluene: sodium bromide: concentrated sulfuric acid: tetrabutylammonium bromide is 1: 6.25: 1.25: 0.12.

[0102] The output voltage of the electrochemical workstation is 0.35 V, the interval time is 0.1 s, the running time is 5 h, the sensitivity is 0.001, and it is irradiated with incandescent light.

[0103] In step B), the molar ratio of p-chlorobenzaldehyde: sodium methyl mercaptide: hydrogen peroxide: concentrated sulfuric acid: sodium tungstate: tetrabutylammonium bromide is 1: 1.3: 2.5: 0.035: 0.016: 0.07.

[0104] Step A:

[0105] Under the irradiation of an incandescent lamp (45 W), add 500 g of sodium bromide to the electrolytic cell, add 2000 mL of water to dissolve it, and add 100 g of concentrated sulfuric acid dropwise to the solution. Under stirring, turn on the electrochemical workstation to open chi920d, output the voltage (0.35 V) with the electrochemical workstation, and add 100 g of p-chlorotoluene and 30 g of tetrabutylammonium bromide to the reaction system. Detect the reaction by TCL. During the reaction, p-chlorobenzaldehyde is generated. After reacting for 5 h, the raw material spot disappears, and a yellow oil-water mixture is obtained. Turn off the electrochemical workstation, and continue to irradiate with an incandescent lamp. Monitor the reaction by TLC during the process, and continue to irradiate for 5 h until the bromination intermediate completely disappears. The reaction reaches the end point. Cool to room temperature, adjust to weak alkaline pH = 8 with 10% sodium hydroxide solution, extract with dichloromethane, take the organic phase, and remove the solvent under reduced pressure to obtain white solid p-chlorobenzaldehyde.

[0106] Step B:

[0107] B.1) Substitution reaction: Add 100 g of p-chlorobenzaldehyde synthesized in step A, 15 g of TBAB, and 330 g of 20% NaSCH in a three-necked flask 3An aqueous solution was heated to 50 °C with mechanical stirring and stirred for 2 h. Then it was heated to 62 °C and stirred. The reaction was monitored by TLC. After 5 h, the raw materials completely disappeared and the reaction reached the end point. 100 mL of water was added for liquid separation, and the lower organic phase was taken. The organic phase was the p-methylthiophenylaldehyde intermediate, about 100 g.

[0108] B.2) Oxidation reaction: 100 g of the intermediate obtained from the substitution reaction was added to a three-necked flask, Na 2 WO 4 solution (3.3 g of Na 2 WO 4 ·2H 2 O dissolved in 30 g of H 2 O), H 2 SO 4 solution (containing 2.4 g of concentrated H 2 SO 4 、30 g of H 2 O), 150 g of H 2 O, and stirred at room temperature for 10 min. Then 100 g of hydrogen peroxide was slowly added dropwise thereto, and the temperature of the reaction system was maintained at 40 ± 5 °C. After dropping, another 100 g of hydrogen peroxide was added dropwise, and the temperature was controlled at 50 ± 10 °C during this process. After dropping, there was a white solid, and the whole reaction system presented a pale yellow solid-liquid state. Then it was heated to 80 °C and reacted for 2 h. The reaction was monitored by TLC. The raw materials completely disappeared and the reaction reached the end point. It was cooled to 5 °C, filtered by suction, the filter cake was washed with water, neutralized to neutral with 10% NaOH solution, filtered by suction again, the filter cake was rinsed with a small amount of water and dried in an oven at 60 °C to obtain 102 g of p-methylsulfonylbenzaldehyde.

[0109] The products obtained in Example 5 and Example 6 were detected by liquid chromatography ( Figure 3 ) It was found that when the amount was scaled up, when the amount of p-chlorotoluene was scaled up to 10 g and 100 g, the purities of the obtained products were 10 g (100%) and 100 g (99%) respectively.

[0110] The optimal output voltage of the electrochemical workstation is 0.35 V. Because in this process, bromide ions are converted into liquid bromine by electrooxidation. If the produced liquid bromine is too fast, the reaction will be incomplete. Moreover, if the voltage is too high, the sensitivity of the electrochemical workstation is insufficient, resulting in a large change in the voltage on the surface of the platinum electrode, leading to an uncontrollable reaction system and poor reproducibility. When the output voltage of the electrochemical workstation is less than 0.35 V, the reaction time becomes longer.

[0111] When irradiated by an incandescent lamp (45W), since liquid bromine will generate bromine free radicals under light irradiation, which will undergo a free radical substitution reaction with p-chlorotoluene (the amount of bromine free radicals generated increases with the increase of the light irradiation power), and under the irradiation of a 45W incandescent lamp, the temperature will also increase, further promoting the hydrolysis of the bromination intermediate to generate p-chlorobenzaldehyde, so the yield is increased.

Claims

1. A method for preparing p-methylsulfonylbenzaldehyde, comprising the following steps: In the first step, electrochemical and hydrolytic reactions convert p-chlorotoluene into p-chlorobenzaldehyde Using para-chlorotoluene as raw material, para-chlorotoluene is converted into para-chlorobenzaldehyde through electrochemical reaction and hydrolysis reaction in an electrolytic cell; The second step is to prepare p-methylsulfonylbenzaldehyde by substitution and oxidation reaction. Firstly, the chlorine group in p-chlorobenzaldehyde is replaced by methylthio group through substitution reaction, and then an oxidant is used to react with p-methylthiobenzaldehyde to generate p-methylsulfonylbenzaldehyde.

2. The preparation method according to claim 1, characterized in that: The preparation method is specifically as follows: 1.1) Electrochemical reaction: Add bromide salt, water and concentrated sulfuric acid to the electrolytic cell and turn on the electrochemical workstation; add para-chlorotoluene and phase transfer catalyst under stirring, and continue the reaction until the para-chlorotoluene is completely reacted to obtain a brominated intermediate; 1.2) Hydrolysis reaction: add water to the brominated intermediate obtained in step 1.1) and adjust the pH value to 9-10; heat the reaction system under reflux with stirring until the brominated intermediate is completely reacted, cool to room temperature; then adjust the pH value to a weak alkaline value; extract with an organic solvent and remove the solvent to obtain white solid p-chlorobenzaldehyde; 2.1) Substitution reaction: add the p-chlorobenzaldehyde obtained in step 1.2), a phase transfer catalyst and an aqueous solution of sodium methylthiolate to a reaction vessel, raise the temperature to 50-70°C under stirring, and react until the p-chlorobenzaldehyde reacts completely; add water for extraction to obtain p-methylthiobenzaldehyde; 2.2) Oxidation reaction: add the p-methylthiobenzaldehyde obtained in step 2.1), Na2WO4 solution, H2SO4 aqueous solution and water into a reaction vessel and mix them evenly; add an oxidant under stirring, raise the temperature to 70-80°C and react until the p-methylthiobenzaldehyde reacts completely; cool, filter and wash to obtain p-methylsulfonylbenzaldehyde.

3. The preparation method according to claim 2, characterized in that: 1.1) and 1.2) in the preparation method are replaced by the following steps: 1.3) Under light, add bromide salt, water and concentrated sulfuric acid to the electrolytic cell, and turn on the electrochemical workstation; under stirring, add p-chlorotoluene and a phase transfer catalyst, and continue the reaction until p-chlorotoluene reacts completely to obtain a brominated intermediate; turn off the electrochemical workstation, continue to illuminate until the brominated intermediate reacts completely, and cool to room temperature; then adjust the pH value to a weak alkaline state, extract with an organic solvent, and remove the solvent to obtain p-chlorobenzaldehyde as a white solid.

4. The preparation method according to claim 2 or 3, characterized in that: The bromide salt is one or more of NaBr, KBr, NH4Br, MgBr2, and CsBr.

5. The preparation method according to claim 2 or 3, characterized in that: In 1.1) and 1.3), the molar ratio of p-chlorotoluene: bromide salt: concentrated sulfuric acid: phase transfer catalyst is 1:2-10:1-3:0.01-0.

15.

6. The preparation method according to claim 2, characterized in that: The molar ratio of p-chlorobenzaldehyde: sodium methyl mercaptan: oxidant: concentrated sulfuric acid: sodium tungstate, phase transfer catalyst in 2.1) and 2.2) is 1:1-2:2-4:0.01-0.4:0.005-0.05:0.01-0.

1.

7. The preparation method according to claim 2 or 3, characterized in that: The molar ratio of p-chlorobenzaldehyde to sodium methyl mercaptan is 1:1-1.5; and / or The phase transfer catalyst is tetrabutylammonium bromide; and / or The lighting used in 1.3) is an incandescent lamp or an LED lamp.

8. The preparation method according to claim 2 or 3, characterized in that: When using the electrochemical workstation, a three-electrode system is used, and the current is output and the reaction is controlled through it; and / or The output voltage of the electrochemical workstation is 0.2-0.5V, the interval time is 0.1s, the running time is 1-24h, and the sensitivity is 0.1-0.0001.

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