Synthesis method of 1, 9-bit dihalogenated dibenzothiophene derivative

Abstract

The invention belongs to the technical field of organic compound synthesis processes, and discloses a synthesis method of a 1, 9-bit dihalogenated dibenzothiophene derivative. The preparation method comprises the following steps: by taking a substrate simultaneously containing methylene sulfonyl and amino, namely 2 '-halo-6'-(methyl sulfinyl)-[1, 1 '-biphenyl]-2-amine as a raw material, diazotizing the 2'-halo-6 '-(methyl sulfinyl)-[1, 1'-biphenyl]-2-amine to form halogen atoms through a one-step method, carrying out ring closure on the product in an acid environment, and simultaneously carrying out the two steps of reactions to obtain the 1, 2, 3, 4-triazole-2-amine. The invention relates to a 9-bit dihalogenated dibenzothiophene derivative. The synthesis method provided by the invention has the advantages of simple operation, mature reaction, easily available raw materials and catalyst, and high reaction yield.

Description

Technical Field

[0001] The invention relates to the technical field of organic compound synthesis technology, in particular to a method for synthesizing 1,9-dihalogenated dibenzothiophene derivatives. Background Art

[0002] Dibenzothiophene and its halogenated derivatives are a class of organic compounds with many advantages. They are widely used in technical fields such as superconducting materials, liquid crystal materials, OLED materials, and chemical raw materials.

[0003] At present, the common methods for the ring closure of dibenzothiophene include the following: First, diphenyl sulfide and its derivatives are used as raw materials to obtain dibenzothiophene derivatives through n-butyl lithium. The synthetic route is: Second, dibenzothiophene compounds are synthesized by activating the CH bond. 2-(methylsulfinyl)-1,1'-biphenyl is used as a raw material, which is protonated in a proton acid and then neutralized and alkalized with a potassium carbonate solution to synthesize dibenzothiophene compounds. The synthetic route is as follows: Third, the CS bond is formed by transition metal catalysis: 2,2'-diiodobiphenyl is used as raw material, cuprous iodide is used as catalyst, potassium sulfide is used as additive, and acetonitrile is used as solvent to synthesize dibenzothiophene compounds. The synthesis route is: Alternatively, dibenzothiophene compounds are synthesized using 2-iodo-diphenyl sulfide as a raw material, Pd2(dba)3 as a catalyst, copper acetate as an additive, and DMF as a solvent. The synthetic route is: The synthesis method of the above-mentioned dibenzothiophene compound provides a basic synthesis idea for the synthesis of its derivatives, but the synthesis methods of the three dibenzothiophene compounds disclosed above have the following problems: the first synthesis method uses a highly active lithium reagent (tert-butyl lithium) that needs to react under ultra-low temperature conditions. The ultra-low temperature reaction involves production safety issues, and the selectivity for other alkyl halides is low, and it is not easy to introduce commonly used functional groups such as bromine and chlorine into dibenzothiophene; the reaction substrate range is narrow, and the biphenyl substrate needs to carry both fluorine atoms and iodine atoms to react, which increases the difficulty of obtaining the substrate and thereby narrows the range of the reaction substrate. The second synthesis process is relatively mild, requiring multiple extractions and washings, and it is difficult to easily obtain high-purity products. In addition, due to the influence of the sulfinyl group, it is not easy to introduce different functional groups into the two rings at the same time when introducing functional groups. The third synthesis method requires the use of transition metals to catalyze the corresponding 2-iodide or 2-bromide to close the ring at high temperature to form a CS bond. The catalyst is expensive, has low selectivity for other functional groups, and is difficult to introduce different functional groups. At the same time, additives need to be added to assist the catalytic reaction, which complicates the reaction system. The common pain point of the above schemes is that it is difficult to introduce halogenated functional groups into the 1 and 9 positions at the same time.

[0004] In order to introduce different functional groups into dibenzothiophene at the 1,9 positions, the current synthesis methods include the following three methods. The first synthesis route is: First, the reaction material 4-iododibenzothiophene is not easy to obtain. Secondly, the synthesis process requires secondary transformation through related functional groups, which cannot effectively streamline the ring-closing process. At the same time, peroxide m-CPBA and strong acid trifluoromethanesulfonic acid have certain safety hazards in the reaction process. The second synthesis route is This synthesis process draws on the closed-loop process of the second dibenzothiophene compound synthesis method mentioned above. The raw material polyhalogenated compound in the first step of preparation is not easy to obtain, and the selectivity of the synthesis process is low. The third synthesis route is This synthesis process draws on the ring-closing process of the first dibenzothiophene compound synthesis method mentioned above. Since the reaction conditions in the ring-closing and bromination processes are harsh and require low-temperature reactions, the operation process is complicated.

[0005] In summary, the traditional method of synthesizing 1,9-disubstituted dibenzothiophene derivatives requires step-by-step synthesis or secondary conversion through other functional groups. Due to their steric hindrance, the conversion rate is generally very low and the operation process is complicated. Summary of the invention

[0006] In order to solve the above technical problems, the present invention provides a method for synthesizing 1,9-dihalogenated dibenzothiophene derivatives, which can efficiently synthesize 1,9-dihalogenated dibenzothiophene through a one-time feeding process, has the advantages of fewer synthetic operation steps, simple process operation, cheap and easy-to-obtain reagents, and has technical advantages such as being suitable for industrial-scale production.

[0007] The present invention discloses a method for synthesizing a 1,9-dihalogenated dibenzothiophene derivative, comprising the following steps:

[0008] Using 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5 as a raw material, adding a protonic acid, under the action of nitrite and cuprous halide, a Sandmeyer reaction occurs, the methylsulfinyl group is protonated, and a positively charged intermediate is generated. The positively charged intermediate undergoes an electrocyclization reaction to form a five-membered ring structure, and the intermediate in the five-membered ring structure loses a proton to obtain a 1,9-position dihalogenated dibenzothiophene derivative of formula 6. The synthesis route is:

[0009] Here, X and Z are each a halogen atom.

[0010] As a preferred embodiment, the ratio of the amount of 2'-halogeno-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of Formula 5 to the amount of protonic acid is 1:3.5-4.5, and the ratio of the amount of 2'-halogeno-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of Formula 5, nitrite and cuprous halide is 1:1-2:1-1.5.

[0011] As a preferred embodiment, the protonic acid is sulfuric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydroiodic acid.

[0012] As a preferred embodiment, the 2'-halo-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5 is added to a protonic acid aqueous solution, and then a solvent is added, and the mixture is kept warm at 45°C to 55°C for 0.5h to 1h under stirring, and then the temperature is lowered to -5°C to 0°C, and a nitrite-containing compound and water are added, and the mixture is kept warm, and then cuprous halide and a protonic acid solution are added, and the mixture is kept warm at 25°C to 35°C for 0.5h to 1h, and then the temperature is naturally raised and the reaction is carried out for 9h to 10h to obtain a 1,9-dihalogenated dibenzothiophene derivative of formula 6.

[0013] As a preferred embodiment, after the reaction is completed, sodium bisulfite aqueous solution is added to quench, and water and ethyl acetate are used for extraction. The organic phase after extraction is washed with brine, and the solvent is removed by distillation under reduced pressure. Column chromatography is performed with petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a 1,9-dihalogenated dibenzothiophene derivative of formula 6.

[0014] As a preferred embodiment, the synthesis method of 2'-halo-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5 comprises the following steps:

[0015] Using 4-halogenated-2-aminobenzothiazole of formula 1 as a raw material, adding an inorganic strong base, heating to 140° C. to 160° C. in an ethylene glycol solvent, a ring-opening reaction occurs to generate a thiolate, cooling to room temperature, adding potassium iodide to perform a methylation reaction, and obtaining 2-halogenated-6-(methylthio)aniline of formula 2;

[0016] Using 2-halogenated-6-(methylthio)aniline of formula 2 as a raw material, a Sandmeyer reaction is carried out with nitrite and potassium halide in a strong acid environment to convert the amino group in formula 2 into a halogen to obtain 2-halogenated-6-(methylthio)halobenzene of formula 3;

[0017] Using 2-halogenated-6-(methylthio)halobenzene of formula 3 and 2-aminophenylboronic acid pinacol ester as raw materials, Suzuki reaction occurs under alkaline environment and palladium catalyst to obtain 2'-halogenated-6'-(methylthio)-[1,1'-biphenyl]-2-amine of formula 4;

[0018] Using 2'-halogenated-6'-(methylthio)-[1,1'-biphenyl]-2-amine of formula 4 as a raw material, an oxidation reaction occurs under the action of an oxidant to oxidize the thioether to obtain 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5. The synthetic route is:

[0019] wherein X and Y are each a halogen atom.

[0020] As a preferred embodiment, the ratio of the amount of 4-halogenated-2-aminobenzothiazole of Formula 1 to the inorganic strong base is 1:10-20, and the ratio of the amount of 4-halogenated-2-aminobenzothiazole of Formula 1 to ethylene glycol is 1:8-15.

[0021] As a preferred embodiment, the ratio of the amount of 2-halogenated-6-(methylthio)aniline of formula 2 to the inorganic strong acid is 1:3.5-4.5, the ratio of the amount of 2-halogenated-6-(methylthio)aniline of formula 2 to potassium iodide is 1:1-1.5, and the nitrite is one or both of sodium nitrite and tert-butyl nitrite.

[0022] As a preferred embodiment, the ratio of the amount of 2-halogenated-6-(methylthio)halobenzene of formula 3, 2-aminophenylboronic acid pinacol ester and the base used in the alkaline environment is 1:1 to 2:2 to 4. The ratio of the amount of 2-halogenated-6-(methylthio)halobenzene of formula 3 and the palladium catalyst is 1:0.01 to 0.05; the base used in the alkaline environment is potassium carbonate, sodium carbonate, potassium phosphate or triethylamine; the palladium catalyst is Pd2(dba)3, Pd132, Pd(pph3)4 or Pd(OAc)2.

[0023] As a preferred embodiment, the oxidant is hydrogen peroxide or an organic peroxide, and the molar ratio of the 2'-halo-6'-(methylthio)-[1,1'-biphenyl]-2-amine of Formula 4 to the oxidant is 1:1-2.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The invention provides a method for synthesizing a 1,9-dihalogenated dibenzothiophene derivative. 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine is used as a raw material, a protonic acid is added, and a Sandmeyer reaction occurs under the joint action of nitrite and cuprous halide, so that a methylsulfinyl group in the raw material structure is protonated to generate a positively charged intermediate, and the positively charged intermediate undergoes an electrocyclization reaction to form a five-membered ring structure, and the intermediate in the five-membered ring structure loses a proton, that is, 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine is first diazotized with a halogen atom, and the product is then ring-closed in an acidic environment to obtain a 1,9-dihalogenated dibenzothiophene derivative. Since the diazotization and ring-closing reactions are carried out simultaneously, the operation of the feeding process and the use of related auxiliary materials are reduced. The invention uses a substrate containing both methanesulfonyl and amino groups, namely 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine as a raw material, and synthesizes 1,9-dihalogenated dibenzothiophene derivatives through a one-step method. The invention has the advantages of simple operation, mature reaction and high yield, and effectively solves the technical problems that the traditional method of synthesizing 1,9-disubstituted dibenzothiophene derivatives needs to be synthesized step by step or converted twice through other functional groups, and the conversion rate is generally low and the operation process is complicated due to steric hindrance problems. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the hydrogen spectrum of 1-bromo-9-chlorodibenzothiophene prepared in Example 1 of the present invention.

[0027] Figure 2 This is the hydrogen spectrum of 1,9-dibromodibenzothiophene prepared in Example 2 of the present invention.

[0028] Figure 3 This is the hydrogen spectrum of 1,9-dichlorodibenzothiophene prepared in Example 3 of the present invention. DETAILED DESCRIPTION

[0029] In order to enable those skilled in the art to better understand the technical solution of the present invention and implement it, the present invention is further described below in conjunction with specific examples, but the examples are not intended to limit the present invention. The following test methods and detection methods, unless otherwise specified, are conventional methods; the reagents and raw materials, unless otherwise specified, are commercially available.

[0030] The following technical problems exist in the synthesis method of the existing 1,9-dihalogenated dibenzothiophene derivatives: for the preparation method of dibenzothiophene ring closure, the synthesis process requires ultra-low temperature, which involves production safety issues, and it is not easy to introduce commonly used functional groups into dibenzothiophene; the reaction substrate range is narrow, and it is difficult to simply obtain a high-purity product after the reaction. Due to the influence of the sulfinyl group, it is not easy to introduce different functional groups into the two rings at the same time when introducing functional groups. During the synthesis, it is necessary to use transition metals to catalyze the corresponding 2-iodide or 2-bromide to close the ring at high temperature to form a CS bond. The catalyst is expensive, and additives need to be added to assist the catalytic reaction, which complicates the reaction system. The traditional method of synthesizing 1,9-disubstituted dibenzothiophene derivatives requires step-by-step synthesis or secondary conversion of other functional groups, and due to its steric hindrance, the conversion rate is generally very low, and the operation process is complicated. Based on the above technical problems, the present invention provides a synthesis method of 1,9-dihalogenated dibenzothiophene derivatives.

[0031] The technical solution of the present invention is described clearly and completely below.

[0032] The present invention provides a method for synthesizing a 1,9-dihalogenated dibenzothiophene derivative, comprising the following steps:

[0033] Using 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5 as a raw material, adding a protonic acid, under the joint action of nitrite and cuprous halide, a Sandmeyer reaction occurs, the methylsulfinyl group is protonated, and a positively charged intermediate is generated. The positively charged intermediate undergoes an electrocyclization reaction to form a five-membered ring structure, and the intermediate in the five-membered ring structure loses a proton to obtain a 1,9-position dihalogenated dibenzothiophene derivative of formula 6. The synthesis route is:

[0034] Wherein, X and Z are each a halogen atom, X is a halogen atom F, Cl or Br; Z is a halogen atom Cl, Br or I.

[0035] For the above reaction process, specifically, first add 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5 to a protonic acid aqueous solution, then add a solvent, keep warm at 45°C to 55°C for 0.5h to 1h under stirring, then cool to -5°C to 0°C, add a nitrite-containing compound and water, keep warm for 0.5h, then add cuprous halide and a protonic acid solution to the system, keep warm at 25°C to 35°C for 0.5h to 1h, then naturally heat up, react for 10h, monitor by TLC that there is no residue of raw materials, add a sodium bisulfite aqueous solution to quench, extract with water and ethyl acetate, wash the organic phase with brine, remove the solvent by reduced pressure distillation, and obtain a 1,9-dihalogenated dibenzothiophene derivative by column chromatography.

[0036] In the technical scheme for synthesizing 1,9-dihalogenated dibenzothiophene derivatives, a substrate containing both methanesulfonyl and amino groups, namely 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine, is used as a raw material to synthesize 1,9-dihalogenated dibenzothiophene derivatives by a one-step method. During the synthesis process, 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine is first diazotized with a halogen atom, and the product is then ring-closed in an acidic environment to obtain a 1,9-dihalogenated dibenzothiophene derivative. Since the diazotization and ring-closure reactions are carried out simultaneously, the feeding process operation and related auxiliary materials are reduced. The method of the present invention has the advantages of simple operation, mature reaction, easy availability of raw materials and catalysts, and high reaction yield.

[0037] It should be noted that the ratio of the amount of 2'-halogeno-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of Formula 5 to the amount of protonic acid is 1:3.5-4.5, and the ratio of the amount of 2'-halogeno-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of Formula 5, nitrite and cuprous halide is 1:1-2:1-1.5.

[0038] In order to achieve the protonation of 2'-halo-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5, the proton acid is sulfuric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydroiodic acid. Under the action of the proton acid, the methylsulfinyl group is protonated to generate a positively charged intermediate.

[0039] In order to prepare the 1,9-dihalogenated dibenzothiophene derivative by one step, the 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5 is added to a protonic acid aqueous solution, and then a solvent is added, and the mixture is kept at 45°C to 55°C for 0.5h to 1h under stirring, and then the temperature is lowered to -5°C to 0°C, and a nitrite-containing compound and water are added, and the mixture is kept warm, and then cuprous halide and a protonic acid solution are added, and the mixture is kept warm at 25°C to 35°C for 0.5h to 1h, and then the temperature is naturally raised and the reaction is carried out for 9h to 10h to obtain the 1,9-dihalogenated dibenzothiophene derivative of formula 6.

[0040] In order to obtain a 1,9-dihalogenated dibenzothiophene derivative with higher purity, after the reaction is completed, sodium bisulfite aqueous solution is added to quench, and water and ethyl acetate are used for extraction. The organic phase after extraction is washed with brine, and the solvent is removed by distillation under reduced pressure. Column chromatography is performed using petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a 1,9-dihalogenated dibenzothiophene derivative of formula 6.

[0041] The raw material used in the present invention, i.e., 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of the above formula 5, can be obtained by a variety of preparation methods. The present invention provides a preferred synthesis method of 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5, which is specifically as follows:

[0042] The present invention provides a method for synthesizing 2'-halo-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5, comprising the following steps:

[0043] S1, using 4-halogenated-2-aminobenzothiazole of formula 1 as a raw material, adding an inorganic strong base, heating to 140°C to 160°C in ethylene glycol solvent, causing a ring-opening reaction, cooling to room temperature, adding potassium iodide, reacting at room temperature, and obtaining 2-halogenated-6-(methylthio)aniline of formula 2. Specifically, adding an inorganic strong base and ethylene glycol to 4-halogenated-2-aminobenzothiazole, stirring is started, heating the system to 140 to 160°C and reacting for 16 to 20 hours, and monitoring by TLC that there is no residual raw material, the reaction solution is naturally cooled to room temperature, iodomethane is added, stirring is continued, and after the reaction is completed, water and toluene are added for extraction, the organic phase is washed with water, and the solvent is removed by distillation under reduced pressure to obtain 2-halogenated-6-(methylthio)aniline of formula 2.

[0044] S2, using 2-halogenated-6-(methylthio)aniline of formula 2 as a raw material, adding an inorganic strong acid, and under the action of a catalyst, a Sandmeyer reaction occurs to convert the amino group in formula 2 into a halogen to obtain 2-halogenated-6-(methylthio)halobenzene of formula 3. Specifically, an inorganic strong acid aqueous solution is added to 2-halogenated-6-(methylthio)aniline and a solvent, stirring is started, the system is kept at 45 to 55° C. for 0.5 to 1 h, the system is cooled to -5° C. to 0° C., a nitrite-containing compound and water are slowly added and kept warm for 0.5 to 1 h, and then potassium halide and water are slowly added and kept warm for 0.5 h. The temperature is naturally raised to react for 14 to 20 h. TLC monitoring shows that there is no residue of the raw material, sodium bisulfite aqueous solution is added to quench, water and ethyl acetate are added for extraction, the organic phase is washed with brine, the solvent is distilled off under reduced pressure, n-heptane is added for pulping, and filtration is performed to obtain 2-halogenated-6-(methylthio)halobenzene of formula 3.

[0045] S3, using 2-halogenated-6-(methylthio)halobenzene and 2-aminophenylboronic acid pinacol ester of formula 3 as raw materials, adding a base, and carrying out Suzuki coupling reaction under the action of a palladium catalyst to obtain 2'-halogenated-6'-(methylthio)-[1,1'-biphenyl]-2-amine of formula 4. Specifically, 2-halogenated-6-(methylthio)halobenzene, 2-aminophenylboronic acid pinacol ester, a base, a palladium catalyst, Am-phos, a solvent and water are mixed, stirring is started, the system is heated to 90°C and kept warm for 16 to 20 hours, TLC monitoring shows that no raw materials remain, water and toluene are added for extraction, the organic phase is washed with brine, and the solvent is removed by distillation under reduced pressure to obtain 2'-halogenated-6'-(methylthio)-[1,1'-biphenyl]-2-amine of formula 4.

[0046] S4, using 2'-halogenated-6'-(methylthio)-[1,1'-biphenyl]-2-amine of formula 4 as a raw material, an oxidation reaction occurs under the action of an oxidant to obtain 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5. Specifically, acetic acid and dichloroethane are added to 2'-halogenated-6'-(methylthio)-[1,1'-biphenyl]-2-amine, stirring is started and the system is cooled to -5 to 0°C, an aqueous solution of the oxidant is added dropwise, the temperature is naturally raised to react for 10 to 16 hours, and the raw material is monitored to be free of residue, sodium bisulfite aqueous solution is added to quench, ethyl acetate and water are added to extract, and water is used for washing. The solvent is removed by distillation under reduced pressure to obtain 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5.

[0047] The reaction synthesis route of the above S1 to S4 is:

[0048] wherein X and Y are each a halogen atom.

[0049] In the process of synthesizing 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of the above-mentioned formula 5, the raw materials used, namely 2-amino-4-halogenated benzothiazole of formula 1) are easy to prepare, the market supply is sufficient, and they have been commercially sold, so they have the advantages of low cost and easy availability of raw materials. The reaction types involved in the present invention include ring-opening reaction, Sandmeyer reaction, and Suzuki reaction, so they have the advantages of high reaction success rate and high yield.

[0050] In order to improve the yield and purity of 2-halogenated-6-(methylthio)aniline of formula 2 and prevent side reactions, the ratio of the amount of 4-halogenated-2-aminobenzothiazole of formula 1 to the amount of inorganic strong base is 1:10-20, and the inorganic strong base is sodium hydroxide. If the amount is too much, the side reactions will increase, such as multiple positions on benzothiophene being attacked by nucleophilic reagents to generate complex by-products; at the same time, if there is too much sodium hydroxide, methyl iodide will undergo hydrolysis reaction under strong alkaline conditions to generate methanol and sodium iodide, resulting in a decrease in the effective concentration of methyl iodide, reducing its chance of reacting with benzothiophene, thereby affecting the ring-opening reaction process of benzothiophene, slowing down the reaction rate and reducing the yield. Furthermore, too much sodium hydroxide will corrode the equipment and shorten the service life of the equipment. If the amount of sodium hydroxide is insufficient, the reaction is incomplete and the yield is low. The ratio of the amount of 4-halogenated-2-aminobenzothiazole of Formula 1 to ethylene glycol is 1:8-15. If the amount of solvent ethylene glycol is too little, the reactants are not well dissolved; if the solvent is too much, the effective concentration of the reactants will be reduced, which is not conducive to the reaction moving in the positive direction.

[0051] In order to improve the yield and purity of 2-halogenated-6-(methylthio)halobenzene of formula 3, the ratio of the amount of substance of 2-halogenated-6-(methylthio)aniline of formula 2 to the inorganic strong acid is 1:3.5-4.5, and the inorganic strong acid is sulfuric acid. If it is excessive, it will affect the balance of diazotization reaction. Diazotization reaction is a reversible reaction. Excessive sulfuric acid will make the solution too acidic, which may affect the stability of diazonium salt; excessive sulfuric acid may react with potassium iodide, so that the concentration of iodide ions in the system is reduced, thereby reducing the yield of iodide in the product; excessive sulfuric acid will corrode equipment, shorten the service life of equipment, and increase equipment maintenance costs. If sulfuric acid is insufficient, the reaction is incomplete and the yield is low.

[0052] In addition, the ratio of the amount of 2-halogenated-6-(methylthio)aniline of formula 2 to potassium iodide is 1:1-1.5. If the amount of potassium iodide is excessive, it will lead to the formation of iodine, increase the difficulty of separation, and affect the purity of the product; if the amount of potassium iodide is insufficient, the reaction is incomplete and the yield is low. It should be noted that the catalyst is one or two of sodium nitrite and tert-butyl nitrite.

[0053] In order to improve the yield and purity of 2'-halogenated-6'-(methylthio)-[1,1'-biphenyl]-2-amine of formula 4, the ratio of the amount of substance of 2-halogenated-6-(methylthio)halobenzene, 2-aminophenylboronic acid pinacol ester and base of formula 3 is 1:1.0-2.0:2-4. The ratio of the amount of substance of 2-halogenated-6-(methylthio)halobenzene of formula 3 and palladium catalyst is 1:0.01-0.05. If the palladium catalyst is excessive, the difficulty of post-reaction treatment is increased, and the cost is wasted; if the palladium catalyst is insufficient, the reaction is incomplete and the yield is low.

[0054] The base used in the present invention is selected from potassium carbonate, sodium carbonate, potassium phosphate or triethylamine; the palladium catalyst is selected from Pd2(dba)3, Pd132, Pd(pph3)4 or Pd(OAc)2.

[0055] In order to improve the yield and purity of 2'-halogeno-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5, the oxidant is hydrogen peroxide or sulfuric acid, and the ratio of the amount of 2'-halogeno-6'-(methylthio)-[1,1'-biphenyl]-2-amine of formula 4 to the oxidant is 1:1 to 2. If the oxidant is excessive, the by-products increase, increasing the difficulty of post-reaction treatment; if the amount of the oxidant is insufficient, the reaction is incomplete and the yield is reduced.

[0056] The present invention expands the substrates for the synthesis of dibenzothiophene derivatives for the first time, and synthesizes 1,9-dihalogenated dibenzothiophene through a one-step method through the methanesulfonyl group and the amino group in the biphenyl group. The method of the present invention has easy-to-obtain raw materials and catalysts, a high reaction yield, and can realize large-scale production.

[0057] The technical effects of the present invention are described below through specific embodiments.

[0058] Example 1

[0059] A method for synthesizing 1-bromo-9-chlorodibenzothiophene, wherein the synthetic route is:

[0060]

[0061] The synthesis process includes the following steps:

[0062] Step 1: Synthesis of 2-chloro-6-(methylthio)aniline (1-2)

[0063] Add 10g (0.05mol) of 4-chloro-2-aminobenzothiazole, 100mL of ethylene glycol, and 32g (0.80mol) of solid sodium hydroxide to a 250mL round-bottom flask, start stirring, heat the system to 150°C and react for 16h. After TLC monitoring shows that there is no residual raw material, the reaction liquid naturally cools to room temperature, and 14.2g (0.10mol) of iodomethane is added and continued to stir for 2h. After the reaction is completed, add 100mL of water, extract 3 times with 50mL of toluene, wash the organic phase with 100mL of water 3 times, and remove the solvent by vacuum distillation to obtain 7.98g of light gray liquid with a purity of 98% and a yield of 92%.

[0064] Step 2: Synthesis of 2-chloro-6-(methylthio)iodobenzene (1-3)

[0065] In a 250mL two-necked flask, 21g (0.21mol) of sulfuric acid, 25mL of water, 10.4g (0.06mol) of 2-chloro-6-(methylthio)aniline and 100mL of acetonitrile were added, stirring was started, the system was kept at 50°C for 0.5 hours, then the system was cooled to -5°C-0°C, 4.83g (0.07mol) of sodium nitrite and 30mL of water were slowly added and kept warm for 0.5 hours, then 10.96g (0.066mol) of potassium iodide and 10mL of water were slowly added, kept warm for 0.5 hours, and the temperature was naturally raised to react for 14h. After TLC monitoring, there was no residue of raw materials, and sodium bisulfite aqueous solution was added to quench, 200mL of water and 200mL of ethyl acetate were added to extract 3 times, the organic phase was washed 3 times with 200mL of brine, the solvent was distilled off under reduced pressure, 10mL of n-heptane was added for pulping, and 9.38g of green solid was obtained after filtration, with a purity of 98% and a yield of 55%.

[0066] Step 3: Synthesis of 2'-chloro-6'-(methylthio)-[1,1'-biphenyl]-2-amine (1-4) In a 250 mL two-necked flask, add: 2-chloro-6-(methylthio)iodobenzene 11.38 g (0.04 mol), 2-aminophenylboronic acid pinacol ester 10.95 g (0.05 mol), potassium phosphate 16.98 g (0.08 mol), Pd2(dba) 30.46 g (0.5 mmol), Am-ph os([(4-(N,N-dimethylamino)phenyl]di-tert-butylphosphine)0.21g (0.8mmol), dioxane 100mL and water 20mL, start stirring, heat the system to 90°C and keep warm for 16h, after TLC monitoring no raw material remaining, add 200mL of water and 150mL of toluene to extract 3 times, wash the organic phase with 200mL of brine three times, and distill under reduced pressure to remove the solvent to obtain 8.59g of white solid with a purity of 99% and a yield of 86%.

[0067] Step 4: Synthesis of 2'-chloro-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine (1-5)

[0068] In a 250 mL round-bottom flask, 10 g (0.04 mol) of 2'-chloro-6'-(methylthio)-[1,1'-biphenyl]-2-amine, 50 mL of acetic acid, and 50 mL of dichloroethane were added. Stirring was started and the system was cooled to 0°C. 9.06 g (0.08 mol) of 30% aqueous hydrogen peroxide solution was added dropwise. The temperature was naturally raised to react for 10 h. After monitoring that there was no residual raw material, sodium bisulfite aqueous solution was added to quench. 100 mL of ethyl acetate and 100 mL of water were added to extract 3 times, and 100 mL of water was used to wash 3 times. The solvent was removed by distillation under reduced pressure to obtain 9.46 g of a white solid with a purity of 98% and a yield of 89%.

[0069] Step 5: Synthesis of 1-bromo-9-chlorodibenzothiophene (1-6)

[0070] In a 250mL two-necked flask, add 15g (0.15mol) of sulfuric acid and 15mL of water, then add 10.63g (0.04mol) of 2'-chloro-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine and 100mL of ethyl acetate, start stirring, keep the system at 50℃ for 0.5 hours, then cool the system to -5-0℃, slowly add 3.45g (0.05mol) of sodium nitrite and 30mL of water and keep the temperature for 0.5 hours, then slowly add 5.5g (0.05mol) of copper bromide to the system. 74g (0.04mol), 40mL hydrobromic acid solution, keep warm at 30℃ for 0.5h, then naturally raise the temperature to react for 10h, add sodium bisulfite aqueous solution to quench after TLC monitoring shows that there is no residual raw material, add 200mL water and 200mL ethyl acetate to extract 3 times, the organic phase is washed 3 times with 200mL brine, and the solvent is distilled off under reduced pressure. Column chromatography is performed with petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain 1-bromo-9-chlorodibenzothiophene, 9.28g, purity 99%, yield 78%, white solid.

[0071] The hydrogen spectrum of 1-bromo-9-chlorodibenzothiophene prepared in Example 1 is as follows Figure 1 As shown, 1H NMR (500 MHz, CD3OD) δ 7.82-7.72 (m, 2H), 7.52-7.44 (m, 3H), 7.20 (t, J=7.5 Hz, 1H).

[0072] Example 2

[0073] A method for synthesizing 1,9-dibromodibenzothiophene, wherein the synthetic route is:

[0074]

[0075] The synthesis process includes the following steps:

[0076] Step 1: Synthesis of 2-bromo-6-(methylthio)aniline (2-2)

[0077] 9.16g (0.04mol) of 4-bromo-2-aminobenzothiazole, 100mL of ethylene glycol, and 16g (0.40mol) of solid sodium hydroxide were added to a 250mL round-bottom flask, stirring was started, the system was heated to 150°C for 18h, and after TLC monitoring, no residual raw materials were found, the reaction liquid was naturally cooled to room temperature, 11.36g (0.08mol) of iodomethane was added, and stirring was continued for 1h. After the reaction was completed, 100mL of water was added, and 50mL of toluene was extracted 3 times. The organic phase was washed with 100mL of water for 3 times, and the solvent was removed by distillation under reduced pressure to obtain 7.59g of light gray liquid with a purity of 98% and a yield of 87%.

[0078] Step 2: Synthesis of 2-bromo-6-(methylthio)iodobenzene (2-3)

[0079] In a 250mL two-necked flask, 22.5g (0.225mol) of sulfuric acid, 20mL of water, 10.9g (0.05mol) of 2-bromo-6-(methylthio)aniline and 100mL of acetonitrile were added, stirring was started, the system was kept at 50°C for 0.5 hours, then the system was cooled to -5-0°C, 5.18g (0.075mol) of sodium nitrite and 30mL of water were slowly added and kept warm for 0.5 hours, then 12.45g (0.075mol) of potassium iodide and 10mL of water were slowly added, kept warm for 0.5 hours, and the temperature was naturally raised to react for 16 hours. After TLC monitoring showed that there was no residue of raw materials, sodium bisulfite aqueous solution was added to quench, 200mL of water and 200mL of ethyl acetate were added to extract 3 times, the organic phase was washed 3 times with 200mL of brine, the solvent was removed by distillation under reduced pressure, 10mL of n-heptane was added for pulping, and 8.88g of green solid was obtained after filtration, with a purity of 98% and a yield of 54%.

[0080] Step 3: Synthesis of 2'-bromo-6'-(methylthio)-[1,1'-biphenyl]-2-amine (2-4)

[0081] In a 250 mL two-necked flask were added: 2-bromo-6-(methylthio)iodobenzene 9.86 g (0.03 mol), 2-aminophenylboronic acid pinacol ester 10.95 g (0.05 mol), potassium phosphate 19.1 g (0.09 mol), Pd2(dba)31.1 (1.2 mmol), Am-phos 0.16 g (0.6 mmol), dioxane 100 mL and water 20 mL. Stirring was started, the system was heated to 90° C. and kept warm for 20 h. After TLC monitoring showed that no raw material remained, 200 mL of water and 150 mL of toluene were added for extraction 3 times. The organic phase was washed three times with 200 mL of brine, and the solvent was distilled off under reduced pressure to obtain 6.8 g of a white solid with a purity of 98% and a yield of 77%.

[0082] Step 4: Synthesis of 2'-bromo-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine (2-5)

[0083] In a 250 mL round-bottom flask, 8.83 g (0.03 mol) of 2'-bromo-6'-(methylthio)-[1,1'-biphenyl]-2-amine, 50 mL of acetic acid, and 50 mL of dichloroethane were added. Stirring was started and the system was cooled to 0°C. 4.4 g (0.045 mol) of 30% aqueous hydrogen peroxide solution was added dropwise. The temperature was naturally raised to react for 10 h. After monitoring that there was no residual raw material, sodium bisulfite aqueous solution was added to quench. 100 mL of ethyl acetate and 100 mL of water were added to extract 3 times, and 100 mL of water was used to wash 3 times. The solvent was removed by distillation under reduced pressure to obtain 8.19 g of a white solid with a purity of 99% and a yield of 88%.

[0084] Step 5: Synthesis of 1,9-dibromodibenzothiophene (2-6)

[0085] In a 250mL two-necked flask, add 13g (0.13mol) of sulfuric acid and 15mL of water, then add 9.31g (0.03mol) of 2'-bromo-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine and 100mL of ethyl acetate, start stirring, keep the system at 50℃ for 0.5 hours, then cool the system to -5-0℃, slowly add 4.14g (0.06mol) of sodium nitrite and 30mL of water and keep the temperature for 0.5 hours, then slowly add 6.04g (0.06mol) of copper bromide to the system. 45g (0.45mol), 40mL of hydrobromic acid solution, keep warm at 30℃ for 0.5h, then naturally raise the temperature to react for 14h. After TLC monitoring shows that there is no residual raw material, add sodium bisulfite aqueous solution to quench, add 200mL of water and 200mL of ethyl acetate to extract 3 times, wash the organic phase with 200mL of brine 3 times, distill under reduced pressure to remove the solvent, and perform column chromatography with petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain 1,9-dibromodibenzothiophene, 7.9g, purity 99%, yield 77%, white solid.

[0086] The hydrogen spectrum of 1,9-dibromodibenzothiophene prepared in Example 2 is as follows Figure 2 As shown, 1HNMR (500MHz, CD3OD) δ7.80 (dd, J = 14.9, 3.0 Hz, 2H), 7.47 (dd, J = 15.0, 3.1 Hz, 2H), 7.20 (t, J = 14.9 Hz, 2H).

[0087] Example 3

[0088] A method for synthesizing 1,9-dichlorodibenzothiophene, wherein the synthetic route is:

[0089]

[0090] The synthesis process includes the following steps:

[0091] Step 1: Synthesis of 2-chloro-6-(methylthio)aniline (3-2)

[0092] Add 10g (0.05mol) of 4-chloro-2-aminobenzothiazole, 100mL of ethylene glycol, and 32g (0.80mol) of solid sodium hydroxide to a 250mL round-bottom flask, start stirring, heat the system to 150°C and react for 16h. After TLC monitoring shows that there is no residual raw material, the reaction liquid naturally cools to room temperature, and 14.2g (0.10mol) of iodomethane is added and continued to stir for 2h. After the reaction is completed, add 100mL of water, extract 3 times with 50mL of toluene, wash the organic phase with 100mL of water 3 times, and remove the solvent by vacuum distillation to obtain 7.98g of light gray liquid with a purity of 98% and a yield of 92%.

[0093] Step 2: Synthesis of 2-chloro-6-(methylthio)iodobenzene (3-3)

[0094] In a 250mL two-necked flask, 21g (0.21mol) of sulfuric acid, 25mL of water, 10.4g (0.06mol) of 2-chloro-6-(methylthio)aniline and 100mL of acetonitrile were added, stirring was started, the system was kept at 50°C for 0.5 hours, then the system was cooled to -5°C-0°C, 4.83g (0.07mol) of sodium nitrite and 30mL of water were slowly added and kept warm for 0.5 hours, then 10.96g (0.066mol) of potassium iodide and 10mL of water were slowly added, kept warm for 0.5 hours, and the temperature was naturally raised to react for 14h. After TLC monitoring, there was no residue of raw materials, and sodium bisulfite aqueous solution was added to quench, 200mL of water and 200mL of ethyl acetate were added to extract 3 times, the organic phase was washed 3 times with 200mL of brine, the solvent was distilled off under reduced pressure, 10mL of n-heptane was added for pulping, and 9.38g of green solid was obtained after filtration, with a purity of 98% and a yield of 55%.

[0095] Step 3: Synthesis of 2'-chloro-6'-(methylthio)-[1,1'-biphenyl]-2-amine (3-4) In a 250 mL two-necked flask, add: 2-chloro-6-(methylthio)iodobenzene 11.38 g (0.04 mol), 2-aminophenylboronic acid pinacol ester 10.95 g (0.05 mol), potassium phosphate 16.98 g (0.08 mol), Pd2(dba) 30.46 g (0.5 mmol), Am-ph os([(4-(N,N-dimethylamino)phenyl]di-tert-butylphosphine)0.21g (0.8mmol), dioxane 100mL and water 20mL, start stirring, heat the system to 90°C and keep warm for 16h, after TLC monitoring no raw material remaining, add 200mL of water and 150mL of toluene to extract 3 times, wash the organic phase with 200mL of brine three times, and distill under reduced pressure to remove the solvent to obtain 8.59g of white solid with a purity of 99% and a yield of 86%.

[0096] Step 4: Synthesis of 2'-chloro-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine (3-5)

[0097] In a 250 mL round-bottom flask, 10 g (0.04 mol) of 2'-chloro-6'-(methylthio)-[1,1'-biphenyl]-2-amine, 50 mL of acetic acid, and 50 mL of dichloroethane were added. Stirring was started and the system was cooled to 0°C. 9.06 g (0.08 mol) of 30% aqueous hydrogen peroxide solution was added dropwise. The temperature was naturally raised to react for 10 h. After monitoring that there was no residual raw material, sodium bisulfite aqueous solution was added to quench. 100 mL of ethyl acetate and 100 mL of water were added to extract 3 times, and 100 mL of water was used to wash 3 times. The solvent was removed by distillation under reduced pressure to obtain 9.46 g of a white solid with a purity of 98% and a yield of 89%.

[0098] Step 5: Synthesis of 1,9-dichlorodibenzothiophene (3-6)

[0099] In a 250mL two-necked flask, add 15g (0.15mol) of sulfuric acid and 15mL of water, then add 10.63g (0.04mol) of 2'-chloro-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine (i.e., intermediate 1-5) and 100mL of ethyl acetate, start stirring, keep the system at 50°C for 0.5 hours, then cool the system to -5-0°C, slowly add 3.45g (0.05mol) of sodium nitrite and 30mL of water and keep the temperature for 0.5 hours, then slowly add 5.94 g (0.06 mol) of cuprous chloride and 40 mL of hydrochloric acid solution were kept at 30 ° C for 0.5 hour and then naturally heated to react for 10 hours. After TLC monitoring showed that there was no residual raw material, sodium bisulfite aqueous solution was added to quench, and 200 mL of water and 200 mL of ethyl acetate were added to extract 3 times. The organic phase was washed 3 times with 200 mL of brine, and the solvent was distilled off under reduced pressure. Column chromatography was performed with petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain 1,9-dichlorodibenzothiophene, 8.0 g, purity 99%, yield 79%, white solid.

[0100] The hydrogen spectrum of 1,9-dichlorodibenzothiophene prepared in Example 3 is as follows Figure 3 As shown, 1H NMR (500 MHz, CDCl3) δ 7.80-7.68 (m, 2H), 7.54-7.41 (m, 4H).

[0101] In summary, the present invention uses a substrate containing both methanesulfonyl and amino groups, namely 2'-halo-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine as a raw material to synthesize 1,9-dihalogenated dibenzothiophene derivatives through a one-step method, which has the advantages of simple operation, mature reaction and high yield.

[0102] Obviously, the above embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

Claims

1. A method for synthesizing a 1,9-dihalogenated dibenzothiophene derivative, characterized in that: Using 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5 as a raw material, a Sandmeyer reaction occurs under the action of nitrite and cuprous halide in a protonic acid environment, 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine is first diazotized with a halogen atom, and the product is ring-closed in an acidic environment. A 1,9-dihalogenated dibenzothiophene derivative of formula 6 is synthesized by a one-step method, and the synthesis route is as follows: Here, X and Z are each a halogen atom.

2. The synthesis method according to claim 1, characterized in that The ratio of the amount of 2'-halogeno-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of Formula 5 to the amount of protonic acid is 1:3.5-4.5, and the ratio of the amount of 2'-halogeno-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of Formula 5, nitrite and cuprous halide is 1:1-2:1-1.

5.

3. The synthesis method according to claim 1, characterized in that The protonic acid is sulfuric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydroiodic acid.

4. The synthesis method according to claim 1, characterized in that The 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5 is added to a protonic acid aqueous solution, and then a solvent is added, and the mixture is kept warm at 45°C to 55°C for 0.5h to 1h under stirring, and then the temperature is lowered to -5°C to 0°C, and a nitrite-containing compound and water are added, and the mixture is kept warm, and then cuprous halide and a protonic acid solution are added, and the mixture is kept warm at 25°C to 35°C for 0.5h to 1h, and then the temperature is naturally raised and the reaction is carried out for 9h to 10h to obtain a 1,9-dihalogenated dibenzothiophene derivative of formula 6.

5. The synthesis method according to claim 4, characterized in that After the reaction is completed, sodium bisulfite aqueous solution is added to quench, and extraction is carried out with water and ethyl acetate. The organic phase after extraction is washed with brine, and the solvent is removed by distillation under reduced pressure. Column chromatography is performed with petroleum ether and ethyl acetate to obtain a 1,9-dihalogenated dibenzothiophene derivative of formula 6.

6. The synthesis method according to claim 1, characterized in that The synthesis method of 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of Formula 5 comprises the following steps: Using 4-halogenated-2-aminobenzothiazole of formula 1 as a raw material, adding an inorganic strong base, heating to 140° C. to 160° C. in an ethylene glycol solvent, a ring-opening reaction occurs to generate a thiolate, cooling to room temperature, adding potassium iodide to perform a methylation reaction, and obtaining 2-halogenated-6-(methylthio)aniline of formula 2; Using 2-halogenated-6-(methylthio)aniline of formula 2 as a raw material, a Sandmeyer reaction is carried out with nitrite and potassium halide in a strong acid environment to convert the amino group in formula 2 into a halogen to obtain 2-halogenated-6-(methylthio)halobenzene of formula 3; Using 2-halogenated-6-(methylthio)halobenzene of formula 3 and 2-aminophenylboronic acid pinacol ester as raw materials, Suzuki reaction occurs under alkaline environment and palladium catalyst to obtain 2'-halogenated-6'-(methylthio)-[1,1'-biphenyl]-2-amine of formula 4; Using 2'-halogenated-6'-(methylthio)-[1,1'-biphenyl]-2-amine of formula 4 as a raw material, an oxidation reaction occurs under the action of an oxidant to oxidize the thioether to obtain 2'-halogenated-6'-(methylsulfinyl)-[1,1'-biphenyl]-2-amine of formula 5. The synthetic route is: Here, X and Y are each a halogen atom.

7. The synthesis method according to claim 6, characterized in that The molar ratio of the 4-halogenated 2-aminobenzothiazole of Formula 1 to the inorganic strong base is 1:10-20, and the molar ratio of the 4-halogenated 2-aminobenzothiazole of Formula 1 to ethylene glycol is 1:8-15.

8. The synthesis method according to claim 6, characterized in that The molar ratio of the 2-halogenated-6-(methylthio)aniline of formula 2 to the inorganic strong acid is 1:3.5-4.5, the molar ratio of the 2-halogenated-6-(methylthio)aniline of formula 2 to potassium iodide is 1:1-1.5, and the nitrite is one or both of sodium nitrite and tert-butyl nitrite.

9. The synthesis method according to claim 6, characterized in that: The ratio of the amount of the 2-halogeno-6-(methylthio)halobenzene of formula 3, 2-aminophenylboronic acid pinacol ester and the base used in the alkaline environment is 1:1 to 2:2 to 4. The ratio of the amount of the 2-halogeno-6-(methylthio)halobenzene of formula 3 and the palladium catalyst is 1:0.01 to 0.05; the base used in the alkaline environment is potassium carbonate, sodium carbonate, potassium phosphate or triethylamine; the palladium catalyst is Pd2(dba)3, Pd132, Pd(pph3)4 or Pd(OAc)2.

10. The synthesis method according to claim 6, characterized in that: The oxidant is hydrogen peroxide or an organic peroxide, and the molar ratio of the 2'-halogeno-6'-(methylthio)-[1,1'-biphenyl]-2-amine of Formula 4 to the oxidant is 1:1-2.

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