Synthesis method of 4, 4-dibromo diphenyl sulfoxide

Abstract

The invention provides a synthesis method of 4, 4-dibromo diphenyl sulfoxide, which is characterized by comprising the following steps: (1) a reaction step: dissolving phenyl sulfide in a non-polar solvent, dropwise adding liquid bromine, stirring at the temperature of more than 25 DEG C to react for more than 3 hours, controlling the molar ratio of the phenyl sulfide to the liquid bromine to be 1: (3-5), and reacting for 1-2 hours at the temperature of more than 25 DEG C to obtain 4, 4-dibromo diphenyl sulfoxide; and (2) a post-treatment step: carrying out organic solvent extraction on the reaction liquid obtained in the reaction step (1), and carrying out silica gel column chromatography on the obtained organic phase to obtain the target product 4, 4-dibromo diphenyl sulfoxide.

Description

Technical Field

[0001] The invention relates to a method for synthesizing 4,4-dibromodiphenyl sulfoxide. Background Art

[0002] 4,4'-Dibromodiphenyl sulfoxide is an important organic compound intermediate that can be used to construct other organic compounds, expand the research field of organic chemistry, and can also be used to study the mechanism and kinetics of chemical reactions, providing experimental support for the development of chemical theory. It is widely used in compounds in the pharmaceutical field.

[0003] At present, in the existing synthesis methods of 4,4-dibromodiphenyl sulfoxide, for example, in the synthesis method of 4,4-dibromodiphenyl sulfoxide in European Journal of Organic Chemistry; vol. 2021; b. 26; (2021); P. 3743–3747, p-bromophenyl sulfide is reacted with oxygen to generate 4,4-dibromodiphenyl sulfoxide. In this synthesis method, since a large amount of pure oxygen is used in the synthesis method and light needs to be controlled during the reaction, there are great safety hazards in the production scale, the production conditions are complex to control, and the price of p-bromophenyl sulfide as a raw material is expensive, which is costly in industrial production. Therefore, a safe, easy to control and low-cost synthesis method is expected in the industrial industry. Summary of the invention

[0004] Problems to be Solved by the Invention

[0005] In view of the above problems in the prior art, the purpose of the present invention is to provide a method for synthesizing 4,4'-dibromodiphenyl sulfoxide, which has cheaper starting materials, safe reaction process, simple reaction conditions and easy control, and further provides a method for synthesizing 4,4'-dibromodiphenyl sulfoxide with higher yield.

[0006] Methods for solving problems

[0007] In order to solve the above technical problems, the present invention provides the following method for synthesizing 4,4'-dibromodiphenyl sulfoxide.

[0008] [1] A method for synthesizing 4,4-dibromodiphenyl sulfoxide, characterized by comprising:

[0009] (1) Reaction step: dissolving phenylene sulfide in a non-polar solvent, adding liquid bromine dropwise, stirring and reacting for more than 3 hours at a temperature above 25° C. in the presence of oxygen, wherein the molar ratio of phenylene sulfide to liquid bromine is 1:3-5.

[0010] (2) Post-treatment step: extracting the reaction solution obtained in the reaction step (1) with an organic solvent, and subjecting the obtained organic phase to silica gel column chromatography to obtain the target product 4,4-dibromodiphenyl sulfoxide.

[0011] [2] The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to [1] is characterized in that, in the post-treatment step, the developing solvent of the silica gel column chromatography is petroleum ether:ethyl acetate = 10:1.

[0012] [3] The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to [1], characterized in that in the reaction step, the non-polar solvent is carbon tetrachloride.

[0013] [4] The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to [1], characterized in that in the reaction step, after dissolving phenylene sulfide in a non-polar solvent, an inorganic base or an organic base is further added before adding liquid bromine dropwise.

[0014] [5] The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to [4], characterized in that the inorganic base is any one selected from sodium hydrogen sulfide, potassium carbonate, and sodium carbonate.

[0015] [6] The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to [4], characterized in that the organic base is 4-dimethylaminopyridine or triethylamine.

[0016] [7] The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to [3], characterized in that the molar ratio of the phenylene sulfide to the base is 1:2.

[0017] [8] The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to [1] is characterized in that the ratio of the non-polar solvent to diphenyl sulfide is 15-20 mL: 1 g.

[0018] [9] The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to [1], characterized in that in the reaction step, the reaction temperature is below 80° C. and the stirring reaction time is below 16 hours.

[0019]

[10] The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to [1] is characterized in that, in the post-treatment step, the alkaline solution added to the reaction solution is a sodium bicarbonate solution or a sodium hydroxide solution.

[0020] Effects of the Invention

[0021] The invention provides a method for synthesizing 4,4-dibromodiphenyl sulfoxide. The method can obtain a target compound with a high yield under simple reaction conditions, and the synthesis process is mild, stable and safe. The starting raw material of the reaction, phenylene sulfide, is economical and easily available, and the cost is saved by 99% compared with p-bromophenyl sulfide used in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is the H NMR spectrum of 4,4-dibromodiphenyl sulfoxide obtained in Example 1.

[0023] Figure 2 is the mass spectrum of 4,4-dibromodiphenyl sulfoxide obtained in Example 1, wherein: Figure 2 a is measured by measuring the mass-to-charge ratio (m / z) of the molecular ion of the compound and the information of the fragment ions. Figure 2 b is a purity analysis that detects the presence of impurities in the sample and the relative content of the impurities, thereby evaluating the purity of the sample. DETAILED DESCRIPTION

[0024] The specific implementation of the present invention will be further explained and illustrated below in conjunction with specific examples, but the explanation and illustration do not limit the technical solution of the present invention. In the present invention, the target product is 4,4-dibromodiphenyl sulfoxide.

[0025] The synthesis method of 4,4-dibromodiphenyl sulfoxide of the present invention is characterized by comprising:

[0026] (1) Reaction steps: dissolving phenylene sulfide in a non-polar solvent, adding liquid bromine dropwise, stirring and reacting at 25°C to 80°C in the presence of oxygen, wherein the molar ratio of phenylene sulfide to liquid bromine is 1:3 to 5.

[0027] (2) Post-treatment step: extract the reaction solution obtained in the reaction step (1) with an organic solvent, and perform silica gel column chromatography on the obtained organic phase to obtain the target product 4,4-dibromodiphenyl sulfoxide.

[0028] In the synthesis method of 4,4-dibromodiphenyl sulfoxide of the present invention, phenylene sulfide is dissolved in a non-polar solvent and liquid bromine is added dropwise, the system turns reddish brown, and the reaction is carried out under stirring at 25°C to 80°C in the presence of oxygen. From the perspective of easy post-treatment and high yield after the raw material product phenylene sulfide and liquid bromine are fully reacted, the molar ratio of phenylene sulfide to liquid bromine is 1:3 to 5.

[0029] In the synthesis method of 4,4-dibromodiphenyl sulfoxide of the present invention, a non-polar solvent is used to dissolve phenylene sulfide. The type and amount of the non-polar solvent can be used as long as phenylene sulfide can be fully dissolved. Examples of the non-polar solvent include carbon tetrachloride and benzene. Carbon tetrachloride is preferred in terms of stability of the reaction and ease of post-treatment. In terms of being able to fully dissolve phenylene sulfide, the amount ratio of the non-polar solvent to phenylene sulfide is 15 to 20 mL: 1 g.

[0030] In the method for synthesizing 4,4-dibromodiphenyl sulfoxide of the present invention, a higher yield can be stably obtained when the stirring temperature is 25°C or higher after the dropwise addition of liquid bromine in the reaction step. From the perspective of easy control of the reaction conditions, the temperature is preferably 25°C to 80°C, and more preferably 25°C to 30°C (room temperature).

[0031] In the method for synthesizing 4,4-dibromodiphenyl sulfoxide of the present invention, in the reaction step, after the dropwise addition of liquid bromine, stirring is preferably performed for 3 hours or more to ensure sufficient reaction. From the perspective of reaction cost and reaction time control, the reaction time may be 16 hours or less.

[0032] In the synthesis method of 4,4-dibromodiphenyl sulfoxide of the present invention, after the reaction is completed, a post-treatment step is performed. In order to remove the unreacted liquid bromine, an alkaline solution is added to the reaction solution. The alkaline solvent can remove the unreacted liquid bromine and has no effect on the reaction. Alkaline solutions such as sodium bicarbonate or sodium hydroxide solution can be cited. From the perspective of easy availability and short reaction time, sodium hydroxide solution is preferred.

[0033] After adding the alkaline solution, the aqueous phase is extracted with an organic solvent, and the organic phase is taken. In order to remove water-soluble impurities, it is washed with water or saturated brine, and after drying, silica gel column chromatography is performed. The developing solvent can be listed as dichloromethane: methanol = 50: 1 and petroleum ether: ethyl acetate = 10: 1. From the perspective of better development effect, petroleum ether: ethyl acetate = 10: 1 is preferred. After silica gel column chromatography, the obtained solution is spin-dried. The above-mentioned organic solvent can be used as long as it can extract the aqueous phase, but dichloromethane is preferred from the perspective of low toxicity, environmental friendliness, low boiling point and easy separation. Organic matter in saturated brine can reduce the solubility of organic matter in water, prevent emulsification, wash away inorganic matter, and use osmotic pressure to reduce the water content of the organic layer.

[0034] Theoretically, liquid bromine is a strong electrophilic reagent. When phenyl sulfide reacts with liquid bromine, the liquid bromine molecule approaches the phenyl sulfide molecule. The sulfur atom in phenyl sulfide has a certain electron cloud density. After the bromine molecule is polarized, its positively charged part (Br δ+ ) attacks the sulfur atom to form a sulfur-bromine bond. The reaction mechanism is speculated to be as follows.

[0035]

[0036] However, in the present invention, phenylene sulfide reacts with liquid bromine to generate 4,4-dibromodiphenyl sulfoxide of the present invention during actual experiments. The reaction mechanism is not clear, but it is speculated as follows. Liquid bromine is a strong electrophilic reagent. At the beginning of the reaction, the liquid bromine molecule approaches the phenylene sulfide molecule. The sulfur atom in phenylene sulfide has a certain electron cloud density. After the bromine molecule is polarized, its positively charged part (Br δ+ ) attacks the sulfur atom to form an unstable sulfur-bromine bond. This step causes the electron cloud of the sulfur atom to shift, and the sulfur atom carries a partial positive charge. Next, the benzene ring in the phenylene sulfide molecule will produce a certain electron conjugation effect on the partially positively charged sulfur atom, causing the electron cloud to redistribute and further stabilize the reaction intermediate state. Then, another bromine molecule attacks the sulfur atom again, replacing the hydrogen atom on the sulfur to form a preliminary reaction product. Finally, after a series of intramolecular electron rearrangements and bond adjustments, 4,4-dibromodiphenyl sulfoxide is generated. The driving force of the entire reaction is the affinity of the electrophile (bromine) for the sulfur atom and the relatively stable intermediate and transition states formed during the reaction.

[0037] Specifically, liquid bromine dissociates to a certain extent in the reaction system to form bromide ions (Br + ) and bromide anion (Br - ). Then, the bromide ion acts as an electrophilic reagent to attack the sulfur atom in phenylene sulfide. The sulfur atom has a lone pair of electrons and can undergo an electrophilic substitution reaction with the bromide ion. One of the bromine atoms replaces a phenyl group on the sulfur atom to form a bromophenyl sulfide intermediate (Ph-Br-S-Ph), and hydrogen bromide (HBr) is produced at the same time. Next, the key step of the reaction is the formation of a sulfur-oxygen double bond. In this process, the oxygen in the system may participate in the reaction. Oxygen can oxidize the sulfur atom in the bromophenyl sulfide intermediate, converting it from a divalent sulfur (S 2- ) is oxidized to tetravalent sulfur (S 4+ ), and forms a sulfur-oxygen double bond with the oxygen atom to obtain 4,4-dibromodiphenyl sulfoxide. In this reaction, liquid bromine acts as an electrophilic reagent to attack the benzene ring in phenyl sulfide to form a bromophenyl sulfide intermediate. Then, the intermediate is oxidized, and the lone pair of electrons of the sulfur atom forms a double bond with the oxygen atom to generate 4,4-dibromodiphenyl sulfoxide.

[0038] In order to obtain a higher yield, the present invention preferably further adds a base after dissolving the diphenyl sulfide in the non-polar solvent and before adding the liquid bromine. After stirring evenly, the liquid bromine is added dropwise. By further adding a base after dissolving the diphenyl sulfide in the non-polar solvent, the yield can be further improved.

[0039] The mechanism is not clear yet, but it is speculated that the addition of alkali will make the charge in the phenylene sulfide molecule more active, making it easier for the bromine molecule to attack the sulfur atom.

[0040] The molar ratio of the phenylene sulfide to the base is 1:2. The base can be an organic base or an inorganic base. The inventors of the present invention have found that after adding an organic base, although the target product of the present invention can be obtained, solid agglomerates will be generated in the reaction system, which will make industrial production and processing difficult. Therefore, from the perspective of simple reaction processing and more suitable for industrial production, inorganic bases are preferred. From the perspective of being able to obtain a higher yield, sodium hydrogen, potassium carbonate, and sodium carbonate are preferred. From the perspective of being more stable, safer, and having a higher yield, the base is more preferably potassium carbonate.

[0041] The method for synthesizing 4,4-dibromodiphenyl sulfoxide of the present invention can obtain the target compound with a high yield under simple reaction conditions, and the synthesis process is mild, stable and safe. The starting raw material of the reaction, phenylene sulfide, is economical and easily available, and the cost is saved by 99% compared with the p-bromophenyl sulfide used in the prior art. The post-treatment has good operability, is suitable for scale-up production, and has broad application prospects.

[0042] Example

[0043] In the reaction system of the present invention, whether the reaction is carried out or not is completely controlled by TLC (thin layer chromatography) spot plate. The specific steps include:

[0044] 1. Prepare thin plate: HSGF254 thin layer chromatography silica gel plate;

[0045] 2. Prepare the developing agent: Pour 3 to 5 ml of the selected solvent system of petroleum ether: ethyl acetate = 10:1 into the developing cell and place a large piece of filter paper in the developing cell;

[0046] 3. Sampling: Use a 3ml rubber-tipped dropper to take 0.5ml of the reaction solution into a 10ml test tube, add 1ml of 5% sodium hydroxide solution to quench, let stand, separate the layers, the lower layer is the sample, sample after 3 hours of reaction time, and sample every 1 hour after the reaction is completed.

[0047] 4. Spot samples at the marked baseline: Use a purchased capillary to take samples and spot them on the HSGF254 thin layer chromatography silica gel plate with marked lines. While tracking the reaction, spot the starting reactants, the reaction liquid mixture, and the mixture of the two. When the depth of the raw material and product spots no longer changes, the reaction is over.

[0048] 6. Expand: Allow the solvent to expand upwards to about 90% of the sheet length;

[0049] 7. Remove the sheet and immediately mark with a pencil the position of the front where the solvent reaches, and calculate the RF value accordingly;

[0050] 8. Allow the solvent on the sheet to evaporate;

[0051] 9. Observe the thin plate: Observe it under the model: WFH-203B three-purpose UV analyzer, and mark all UV-active points with a pencil.

[0052] 10. Make TLC marks and calculate the R of each spot f value, and draw a graph in the experimental record, R f =l / l0, l is the distance from the sample baseline to the center of the developed spot (center of mass), l0 is the distance from the baseline to the front of the developing agent, R f Smaller values ​​indicate greater polarity.

[0053] Judging criteria:

[0054] The raw material phenylene sulfide spots of the present invention appear in R f The value is around 0.79. Therefore, through R f The depth and shape of the spots of the raw material with a value of 0.79 on the silica gel plate determine the progress of the reaction. f When the raw material spot with a value of 0.79 (the raw material spot area is set to 1 at this time) changes from an initial dark dot to almost an arc, it can be determined that the reaction is complete. If the dark dot becomes smaller or lighter in color, the reaction is in progress but not complete.

[0055] In addition, the product spots of the present invention appear in R f The value is around 0.20. Therefore, from R f Whether a product is generated is determined by whether there is a product spot near the value of 0.20, and the depth or size of the product spot on the silica gel plate is used to determine the generation of the product.

[0056] According to the change in the size of the raw material phenyl sulfide spot after the reaction, the TLC spot plate central control is evaluated according to the following levels (visual inspection by the test personnel):

[0057] ○○: All reactions (the raw material spot becomes almost an arc, and the area of ​​the product spot is set to 1)

[0058] ○: Most reactions (0≤area of ​​raw material spot≤0.5, 0.5≤area of ​​product spot≤1)

[0059] △: Minor reaction (0.5<area of ​​raw material spot<1, 0<area of ​​product spot<0.5)

[0060] ×: No reaction at all (no change in the raw material spots, no product spots generated).

[0061] Example 1

[0062] In a 100 ml reaction bottle, dissolve phenyl sulfide (1.5 g, 8.1 mmol) in 30 ml carbon tetrachloride, and add liquid bromine (3.88 g, 24.2 mmol) dropwise at room temperature. The system turns red-brown. After the addition is completed, stir at room temperature for 3 hours.

[0063] Perform TLC point plate central control, the result is R f The raw material spot with a value of 0.79 becomes a very small spot, which means that most of the raw materials have reacted, but some raw materials have not reacted completely. f A new point with greater polarity appears at a value of 0.19, which indicates that a product with greater polarity is generated.

[0064] 50 ml of 5% sodium hydroxide solution was added to the reaction solution to remove the unreacted liquid bromine, and then 50 ml of dichloromethane was added to stir and extract the aqueous phase. After separation, the aqueous phase was extracted with 100 ml of dichloromethane, and the organic phases were combined. The organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and the dichloromethane was dried by spin drying. The residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1). The obtained solution was spin dried to obtain 1.80 g of white solid 1.

[0065] The white solid 1 was analyzed using a nuclear magnetic resonance spectrometer (Braker 400 MHZ, Switzerland) and a mass spectrometer (LC Agilent 1260ⅡMS Agilent 96160A). The obtained spectra are shown in Figure 1 , Figure 2 middle.

[0066] White solid 1:

[0067] 1 H NMR (400MHz, Chloroform-d) δ7.71–7.60(m,4H),7.58–7.46(m,4H).

[0068] LC-MS(UV214): 360.9(M+H)+; RT=1.914min; 95% purity.

[0069] It can be seen that the white solid is the target compound 4,4-dibromodiphenyl sulfoxide.

[0070] The theoretical yield of 4,4-dibromodiphenyl sulfoxide was calculated to be 2.92 g. Therefore, the yield of 4,4-dibromodiphenyl sulfoxide in Example 1 was 62.1%.

[0071] The method for synthesizing 4,4-dibromodiphenyl sulfoxide in Example 1 has the following synthesis route:

[0072]

[0073] Example 2

[0074] In Example 2, the same procedure as in Example 1 was followed except that the stirring at room temperature was changed to stirring under reflux at 80°C for 3 hours, to obtain 1.85 g of a white solid 2. The results of TLC spot plate control showed that R f The raw material spot with a value of 0.79 becomes a very small spot, which means that most of the raw materials have reacted, but some raw materials have not reacted completely. f A new point with greater polarity appears at a value of 0.19, which indicates that a product with greater polarity is generated.

[0075] The white solid 2 was analyzed in the same manner as in Example 1, and was confirmed to be 4,4-dibromodiphenyl sulfoxide.

[0076] By calculation, the yield of 4,4-dibromodiphenyl sulfoxide in Example 2 was 63.36%.

[0077] Example 3

[0078] In Example 3, the reaction was carried out in the same manner as in Example 1 except that the reaction time was changed to 16 hours, and 1.82 g of white solid 3 was obtained. The results of TLC spot plate control showed that R f The raw material spot with a value of 0.79 becomes a very small spot, which means that most of the raw materials have reacted, but some raw materials have not reacted completely. f A new point with greater polarity appears at a value of 0.19, which indicates that a product with greater polarity is generated.

[0079] The white solid 3 was analyzed in the same manner as in Example 1, and was confirmed to be 4,4-dibromodiphenyl sulfoxide.

[0080] By calculation, the yield of 4,4-dibromodiphenyl sulfoxide in Example 3 was 62.33%.

[0081] Example 4

[0082] In Example 4, except that liquid bromine (6.44 g, 40.5 mmol) was used and the molar ratio of phenyl sulfide to liquid bromine was changed to 1:5, the same method as in Example 1 was used to obtain 1.88 g of white solid 4. The results of TLC spot plate control showed that R f The raw material spot with a value of 0.79 becomes a very small spot, which means that most of the raw materials have reacted, but some raw materials have not reacted completely. f A new point with greater polarity appears at a value of 0.19, which indicates that a product with greater polarity is generated.

[0083] The white solid 4 was analyzed in the same manner as in Example 1, and was confirmed to be 4,4-dibromodiphenyl sulfoxide.

[0084] By calculation, the yield of 4,4-dibromodiphenyl sulfoxide in Example 4 was 64.38%.

[0085] Example 5

[0086] In a 100ml reaction bottle, dissolve phenyl sulfide (1.5g, 8.1mmol) in 30ml carbon tetrachloride, and add 60% sodium hydrogen (0.648g, 16.2mmol) in batches. The system changes from a clear state to a gray turbid state, and stir at room temperature for 1h. Add liquid bromine (3.88g, 24.2mmol) dropwise, and the system turns reddish brown. Stir at room temperature for 3 hours after the addition is completed.

[0087] The results of TLC spot plate central control, R f The raw material spot with a value of 0.79 becomes a very small spot, which means that most of the raw materials have reacted, but some raw materials have not reacted completely, and the R f A new point with greater polarity appears at a value of 0.19, which indicates that a product with greater polarity is generated.

[0088] After the reaction solution was placed in an ice bath, 50 ml of 5% sodium hydroxide solution was added to the reaction solution to remove the unreacted liquid bromine, and then 50 ml of dichloromethane was added to stir and extract the aqueous phase. After stratification, the aqueous phase was extracted with 100 ml of dichloromethane, and the organic phases were combined. The organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and the dichloromethane was dried by spin drying. The residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1). The obtained solution was spin dried to obtain 2.14 g of white solid 5.

[0089] The white solid 5 was analyzed in the same manner as in Example 1, and was confirmed to be 4,4-dibromodiphenyl sulfoxide.

[0090] By calculation, the yield of 4,4-dibromodiphenyl sulfoxide in Example 5 was 73.29%.

[0091] Example 6

[0092] In a 100ml reaction bottle, phenyl sulfide (1.5g, 8.1mmol) was dissolved in 30ml carbon tetrachloride, potassium carbonate (3.35g, 24.3mmol) was added, and liquid bromine (3.88g, 24.2mmol) was added dropwise, and the system turned dark red-brown. After the addition was completed, the system was stirred at room temperature for 3 hours, and the system turned dark red-brown.

[0093] The results of TLC spot plate central control, R f The raw material spot with a value of 0.79 turns into a very thin arc, which can be judged as the raw material reaction is complete and f A new point with large polarity appears at a value of 0.19, which indicates that a product with large polarity is generated.

[0094] 50 ml of 5% sodium hydroxide solution was added to the reaction solution to remove the unreacted liquid bromine, and then 50 ml of dichloromethane was added to stir and extract the aqueous phase. After stratification, the aqueous phase was extracted with 100 ml of dichloromethane, and the organic phases were combined. The organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and the dichloromethane was spin-dried. The residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1). The obtained solution was spin-dried to obtain 2.55 g of white solid 6.

[0095] The white solid 6 was analyzed in the same manner as in Example 1, and was confirmed to be 4,4-dibromodiphenyl sulfoxide.

[0096] According to calculation, the yield of 4,4-dibromodiphenyl sulfoxide in Example 6 is 87.33%.

[0097] Example 7

[0098] In a 100ml reaction bottle, phenyl sulfide (1.5g, 8.1mmol) was dissolved in 30ml carbon tetrachloride, and DMAP (4-dimethylaminopyridine) (2.9g, 24.3mmol) was added. Liquid bromine (3.88g, 24.2mmol) was added dropwise, and the system turned light reddish brown. After the addition was completed, the system was stirred at room temperature for 3 hours, and the system turned light yellow and clear, with a large amount of solid lumps at the bottom, making it difficult to stir.

[0099] The results of TLC spot plate central control, R f The raw material spot with a value of 0.79 becomes a dot with a missing part, which can be judged as a small amount of raw material reaction, and in R f At a value of 0.19, a very thin elliptical polar new point appears, which indicates that a small amount of product with a relatively high polarity is generated.

[0100] 50 ml of 5% sodium hydroxide solution was added to the reaction solution to remove the unreacted liquid bromine, and then 50 ml of dichloromethane was added to stir and extract the aqueous phase. After separation, the aqueous phase was extracted with 100 ml of dichloromethane, and the organic phases were combined. The organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and the dichloromethane was spin-dried. The residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1), and the obtained liquid was spin-dried to obtain 1.59 g of white solid 7.

[0101] The white solid 7 was analyzed in the same manner as in Example 1, and was confirmed to be 4,4-dibromodiphenyl sulfoxide.

[0102] According to calculation, the yield of 4,4-dibromodiphenyl sulfoxide in Example 7 is 54.45%.

[0103] Example 8

[0104] In a 100ml reaction bottle, phenyl sulfide (1.5g, 8.1mmol) was dissolved in 30ml carbon tetrachloride, and triethylamine (2.46g, 24.3mmol) was added. Liquid bromine (3.88g, 24.2mmol) was added dropwise, and the system turned light yellow and a large amount of white smoke was generated. After the addition was completed, the system was stirred at room temperature for 3 hours, and the system turned light yellow and clear, with a large amount of solid lumps at the bottom, making it difficult to stir.

[0105] The results of TLC spot plate central control, R f The raw material spot with a value of 0.79 changes to a dot with a missing part, which indicates that most of the raw materials have reacted. f At a value of 0.19, a new elliptical polar point appears, which indicates that a product with greater polarity is generated.

[0106] 50 ml of 5% sodium hydroxide solution was added to the reaction solution to remove the unreacted liquid bromine, and then 50 ml of dichloromethane was added to stir and extract the aqueous phase. After separation, the aqueous phase was extracted with 100 ml of dichloromethane, and the organic phases were combined, washed with saturated brine, dried with anhydrous sodium sulfate, and the dichloromethane was dried by spin drying. The residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1). Purification gave 1.93 g of white solid 8.

[0107] The white solid 8 was analyzed in the same manner as in Example 1, and was confirmed to be 4,4-dibromodiphenyl sulfoxide.

[0108] According to calculation, the yield of 4,4-dibromodiphenyl sulfoxide in Example 8 was 66.10%.

[0109] Comparative Example 1

[0110] Comparative Example 1 was carried out in the same manner as Example 1 except that the stirring at room temperature was changed to -15°C. As a result of the TLC spot plate central control, the raw material spot did not change, which can be judged as the raw material did not react, and no new spots appeared except the raw material spot, which can be judged as no reaction. Then, the reaction was kept at 0°C overnight, and the result of the TLC spot plate central control was that the raw material spot still did not change, which can be judged as the raw material still did not react, and no new spots appeared except the raw material spot, which can be judged as no reaction. Since the raw material did not react, no post-treatment step was performed.

[0111] Comparative Example 2

[0112] Comparative Example 2 was carried out in the same manner as Example 1 except that the stirring at room temperature was changed to stirring at 10°C for 3 hours, a TLC spot plate control was performed, and then the reaction was kept at 10°C overnight, and a TLC spot plate control was performed again. The same procedure as Example 1 was performed to obtain 0.62 g of a white solid 2'. The result of the first TLC spot plate control was R fThe dots of the raw material spots with a value of 0.79 become slightly smaller dots, which can be judged as a very small part of the raw material reaction, and in R f A very thin elliptical polar new point appeared at the value of 0.19, which can be judged that a very small amount of a product with a large polarity was generated. The results of the second TLC spot plate control were unchanged compared to the results of the first TLC spot plate control, which can be judged that the raw material reaction did not undergo further changes.

[0113] The white solid 2' was analyzed in the same manner as in Example 1, and was confirmed to be 4,4-dibromodiphenyl sulfoxide.

[0114] According to calculation, the yield of 4,4-dibromodiphenyl sulfoxide in Comparative Example 2 was 21.23%.

[0115] Comparative Example 3

[0116] In Comparative Example 3, the same method as in Example 1 was used except that liquid bromine (2.58 g, 16.2 mmol) was used and the molar ratio of phenyl sulfide to liquid bromine was changed to 1:2 to obtain 0.53 g of white solid 3'. The results of TLC spot plate control showed that R f The dots of the raw material spots with a value of 0.79 become slightly smaller dots, which can be judged as a very small part of the raw material reaction, and in R f At a value of 0.19, a very fine elliptical polar new point appears, which indicates that a very small amount of a product with a relatively high polarity is generated.

[0117] The white solid 3' was analyzed in the same manner as in Example 1, and was confirmed to be 4,4-dibromodiphenyl sulfoxide.

[0118] According to calculation, the yield of 4,4-dibromodiphenyl sulfoxide in Comparative Example 3 was 18.15%.

[0119] The raw materials, reaction processes and results used in the above examples and comparative examples are listed in Table 1.

[0120] Comparative Example 4

[0121] In Comparative Example 4, except that iron was used as a catalyst in the reaction step, the same procedure as Example 1 was followed, and the reaction was stirred at room temperature for three hours. The results of the TLC spot control showed that the raw material spot did not change, which indicated that the raw material had not reacted, and no new spots appeared except the raw material spots, which indicated that no reaction had occurred. The reaction was then maintained overnight, and the raw material still did not react, and no new spots were generated, as shown in the TLC spot control.

[0122] [Table 1]

[0123]

[0124] It can be seen from Example 1 of the present invention that after adding liquid bromine, the reaction conversion rate can be greatly improved under the condition of stirring for 3 hours at room temperature (25°C to 30°C), but there are still raw materials that have not reacted completely. After adding liquid bromine in Example 2, stirring at reflux for 3 hours at 80°C, the yield is slightly increased, but the stirring temperature at reflux at 80°C does not significantly promote the reaction. In Comparative Example 1, after adding liquid bromine and stirring at -15°C for 3 hours, the reaction cannot proceed. After stirring at 0°C overnight, the reaction also fails to proceed. It can be seen that the reaction of the present invention cannot proceed under -15°C-0°C conditions. In Comparative Example 2, after stirring at 10°C for 3 hours, very few raw materials reacted. After continuing to stir overnight, no further reaction was carried out. It can be seen that the synthesis reaction of the present invention can be carried out at 10°C, but the yield is low.

[0125] In Example 3, the only difference between the stirring time and that in Example 1 is that the stirring time is changed to 16 hours, and the yield is slightly increased. However, extending the stirring time to 16 hours has less effect on the reaction progress than stirring for 3 hours.

[0126] Compared with Example 1, Example 4 changes the molar ratio of benzene sulfide: liquid bromine to 1:5, and Comparative Example 3 changes the molar ratio of benzene sulfide: liquid bromine to 1:2 in Comparative Example 3. The yield of Example 4 is slightly higher than that of Example 1. The yield of Comparative Example 3 is significantly lower than that of Example 1. It can be seen that when the molar ratio of benzene sulfide: liquid bromine is less than 3, the raw material conversion rate is low and the yield is low. When the molar ratio of benzene sulfide: liquid bromine is between 1:3 and 5, a relatively stable conversion rate and yield can be obtained.

[0127] In Examples 5 and 6, sodium hydrogen and potassium carbonate as inorganic bases were further added before adding liquid bromine, respectively. In particular, after adding potassium carbonate, the yield was greatly improved compared to Example 1. Therefore, it is believed that the addition of sodium hydrogen and potassium carbonate as inorganic bases is conducive to the forward progress of the reaction of the present invention and has a certain promoting effect on the improvement of the yield of the reaction product.

[0128] In Examples 7 and 8, DMAP and triethylamine were further added as organic bases before adding liquid bromine. The yield in Example 7 was slightly lower than that in Example 1, and the yield in Example 8 was higher than that in Example 1. However, in Examples 7 and 8, a large amount of solid agglomerates appeared during the stirring process, and stirring was difficult, which is disadvantageous for industrial production.

[0129] In the general method of bromination on the benzene ring, benzene is usually mixed with liquid bromine, and iron powder is added as a catalyst. In Comparative Example 4, the iron powder used in the general method of bromination on the benzene ring is used as a catalyst. However, phenylene sulfide and night bromine do not react after adding iron powder as a catalyst.

[0130] As can be seen from the above, the synthesis method of 4,4-dibromodiphenyl sulfoxide of the present invention can obtain the target compound with a high yield under simple reaction conditions, and the synthesis process is mild, stable and safe. The starting raw material of the reaction is phenylene sulfide, which is economical and easy to obtain, and saves 99% of the cost compared with the p-bromophenyl sulfide used in the prior art. The post-treatment has good operability, is suitable for scale-up production, and has broad application prospects.

[0131] It should be noted that the existing technologies in the protection scope of the present invention are not limited to the embodiments given in the present application documents. All existing technologies that do not contradict the solutions of the present invention, including but not limited to prior patent documents, prior public publications, prior public uses, etc., can be included in the protection scope of the present invention. In addition, the combination of various technical features in this case is not limited to the combination described in the claims of this case or the combination described in the specific embodiments. All technical features recorded in this case can be freely combined or combined in any way unless there is a contradiction between them.

[0132] It should also be noted that the above-listed embodiments are only specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments, and similar changes or modifications made therewith can be directly derived or easily associated with the contents disclosed by those skilled in the art from the present invention, and all should belong to the protection scope of the present invention.

Claims

1. A method for synthesizing 4,4-dibromodiphenyl sulfoxide, characterized in that: include: (1) Reaction step: dissolving phenylene sulfide in a non-polar solvent, adding liquid bromine dropwise, stirring and reacting for more than 3 hours at a temperature above 25° C. in the presence of oxygen, wherein the molar ratio of phenylene sulfide to liquid bromine is 1:3-5. (2) Post-treatment step: extracting the reaction solution obtained in the reaction step (1) with an organic solvent, and subjecting the obtained organic phase to silica gel column chromatography to obtain the target product 4,4-dibromodiphenyl sulfoxide.

2. The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to claim 1, characterized in that: In the post-treatment step, the developing solvent of the silica gel column chromatography is petroleum ether:ethyl acetate=10:

1.

3. The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to claim 1, characterized in that: In the reaction step, the non-polar solvent is carbon tetrachloride.

4. The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to claim 1, characterized in that: In the reaction step, after dissolving diphenyl sulfide in a nonpolar solvent, an inorganic base or an organic base is further added before adding liquid bromine dropwise.

5. The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to claim 4, characterized in that: The inorganic base is any one selected from sodium hydrogen phosphate, potassium carbonate and sodium carbonate.

6. The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to claim 4, characterized in that: The organic base is 4-dimethylaminopyridine or triethylamine.

7. The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to claim 3, characterized in that: The molar ratio of the phenylene sulfide to the inorganic base or the organic base is 1:

2.

8. The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to claim 1, characterized in that: The usage ratio of the non-polar solvent to diphenyl sulfide is 15-20 mL: 1 g.

9. The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to claim 1, characterized in that: In the reaction step, the reaction temperature is below 80° C., and the stirring reaction time is below 16 hours.

10. The method for synthesizing 4,4-dibromodiphenyl sulfoxide according to claim 1, characterized in that: In the post-treatment step, the alkaline solution added to the reaction solution is a sodium bicarbonate solution or a sodium hydroxide solution.

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