A method for synthesizing 4'-chloro-2-aminobiphenyl

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing 4'-chloro-2-aminobiphenyl. The specific steps are: synthesizing 2,5-dichlorobenzenesulfonyl chloride, synthesizing 2,5-dichloro-N-phenylbenzenesulfonamide, synthesizing 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide, and synthesizing 4'-chloro-2-aminobiphenyl. The synthetic method is simple, does not require the use of noble metal catalysts and transition metals, is mild and green, and is simple and convenient to post-reaction, does not require complicated operations, and the raw materials used are basically all cheap and easily available basic chemical raw materials, the synthetic cost is low, the yield is high, and it is very suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing 4'-chloro-2-aminobiphenyl. Background Art

[0002] Boscalid is a nicotinamide fungicide developed by BASF of Germany. It is mainly used to prevent and treat powdery mildew, gray mold, various rot diseases, brown rot and root rot. It was registered as a pesticide fungicide in the UK, Germany and Switzerland in 2004. Boscalid is an inhibitor of succinate coenzyme Q reductase in the mitochondrial respiratory chain. It has a strong inhibitory ability on spore germination and has no cross-resistance with other fungicides. The preparation method of boscalid is mainly obtained by the reaction of 4'-chloro-2-aminobiphenyl and 2-chloronicotinyl chloride. The intermediate 2-chloronicotinyl chloride has been industrialized, so the preparation of 4'-chloro-2-aminobiphenyl is the key to the synthesis of boscalid and is also one of the current research difficulties.

[0003]

[0004] At present, palladium is generally used to catalyze the reaction of o-nitrochloro(bromo)benzene with p-chlorophenylboric acid to obtain 4'-chloro-2-nitrobiphenyl, and then Pd / C is used for reduction to prepare 4'-chloro-2-aminobiphenyl. However, this method uses expensive raw materials such as p-chlorophenylboric acid, palladium catalyst, Pd / C, etc., which will make the production cost too high.

[0005]

[0006] Chinese patents CN111662184, CN113831280 and CN115286514 use 9-fluorenone raw materials to synthesize 4'-chloro-2-nitrobiphenyl through organic synthesis methods such as ring opening, chlorination, and Hofmann degradation. In CN111662184, dangerous chemical antimony trichloride is used as a catalyst in the chlorination section, and the ring opening product 2-formic acid biphenyl is used as a raw material and sulfonyl chloride is used as a chlorinating agent for chlorination. This reaction has many side reactions, and the main product 4'-chloro-2-formic acid biphenyl is difficult to purify, which leads to a low yield of the target product. Patent CN113831280A also mentions that the prepared biphenyl-2-formamide is reacted with chlorine in the presence of a catalyst to generate 4'-chloro-2-amide biphenyl. Although the use of dangerous chemical antimony trichloride is avoided, toxic and dangerous chlorine is used as a chlorinating agent, and chlorine is introduced under heating conditions for chlorination. When repeated experiments were conducted, it was found that chlorinated isomers and polychlorinated products were generated, which made separation and purification difficult, and the actual separation yield was not high. Although CN115286514 did not use hazardous chemicals such as antimony trichloride and chlorine gas to obtain 4'-chloro-2-nitrobiphenyl with a higher yield, which reduced the cost, as 9-fluorenone, an important organic synthesis intermediate, is used not only in the field of pesticides, but also can be used to synthesize bisphenol fluorene, fluorenylbenzoxazine resin, acrylate resin, polyester, and epoxy resin modifier; it has also been found to have significant application value in the fields of medicine, dyes, and electronic materials. With the increase in the application of 9-fluorenone and the shortage of raw material supply, the price has increased significantly in recent years. The synthesis of 4'-chloro-2-aminobiphenyl using 9-fluorenone as a raw material no longer has the advantage of low cost.

[0007]

[0008] Synlett, 2011, 14, 2064-2068, reported the synthesis of l,4-dichlorobenzene Grignard reagent, which was prepared by lithium chloride catalysis. However, the reaction was not complete, the yield was low, and the expensive metal palladium was used as a catalyst, which was not suitable for large-scale production.

[0009]

[0010] WO2013132006 reported that phenylhydrazine analogs and aniline analogs were used as starting materials. According to the method reported in the literature, 4'-chloro-2-aminobiphenyl was obtained with a yield of 41% by using p-chlorophenylhydrazine and excess aniline (20 times equivalent) in the presence of excess manganese dioxide. However, excessive manganese dioxide and aniline were used in the reaction and the yield was extremely low, which was not conducive to industrialization.

[0011]

[0012] Journal of the American Chemical 2007, 129, 4824-4833 reported that o-nitrobenzoic acid and 1,4-dichlorobenzene were coupled under the catalytic conditions of metallic palladium to give 4'-chloro-2-nitrobiphenyl. The reaction had a moderate yield (66%) and used an expensive palladium catalyst.

[0013]

[0014] Chinese patent CN114230433 uses aniline and p-chloroiodobenzene as raw materials, and uses cobalt chloride to generate 4'-chloro-2-aminobiphenyl through a photocatalyst coupling reaction, which has the advantages of high yield and less pollution. However, p-chloroiodobenzene and photocatalyst are expensive, and special light source equipment must be used to emit a light source of a special wavelength to obtain 4'-chloro-2-aminobiphenyl in high yield, which invisibly increases the production cost and is not suitable for industrial production.

[0015]

[0016] In summary, the reported synthesis processes of 4'-chloro-2-aminobiphenyl, the intermediate of boscalid, mostly use expensive catalysts. Expensive raw materials such as p-chlorophenylboronic acid, 9-fluorenone, and photocatalysts greatly increase the production cost and the difficulty of mass production. In addition, given that boscalid has the advantages of a broad bactericidal spectrum, environmental friendliness, and a large market demand, it is urgent to find a novel production process suitable for large-scale production. Summary of the invention

[0017] In order to solve the deficiencies in the prior art, the present invention provides a method for synthesizing 4'-chloro-2-aminobiphenyl. The method is simple, does not require the use of precious metal catalysts and transition metals, is mild and green, and has simple and convenient post-reaction treatment, does not require complicated operations, and the raw materials used are basically cheap and easily available basic chemical raw materials. The synthesis cost is low and the yield is high, which is very suitable for industrial production.

[0018] The technical solution of the present invention is as follows:

[0019] A synthetic method for 4'-chloro-2-aminobiphenyl, the reaction equation of the synthetic method is:

[0020]

[0021] Preferably, the synthesis method is as follows:

[0022] (1) Synthesis of 2,5-dichlorobenzenesulfonyl chloride: using dichlorobenzene and chlorosulfonic acid;

[0023] (2) Synthesis of 2,5-dichloro-N-phenylbenzenesulfonamide: using dichlorobenzenesulfonyl chloride and aniline;

[0024] (3) Synthesis of 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide: synthesized by reductive cyclization of 2,5-dichloro-N-phenylbenzenesulfonamide;

[0025] (4) Synthesis of 4'-chloro-2-aminobiphenyl: It was synthesized by cleavage of 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide using H2SO4.

[0026] Further preferably, the molar ratio of p-dichlorobenzene to chlorosulfonic acid in step (1) is 1:1 to 3. More preferably, the solvent used in step (1) is one or more of dichloromethane, dichloroethane, tetrachloroethane, chloroform, carbon tetrachloride, nitrobenzene, and methylnitrobenzene, and the mass of the solvent is 1 to 10 times the mass of p-dichlorobenzene.

[0027] Further preferably, in the synthesis of 2,5-dichloro-N-benzenesulfonamide in step (2), the base used is one or more of triethylamine, diisopropylethylamine, sodium carbonate, potassium carbonate, cesium fluoride, cesium carbonate, calcium carbonate, 1,8-diazabicycloundec-7-ene, 1,4-diazabicyclo[2.2.2]octane, and the amount of the base is 1 to 10 times the amount of the aniline. More preferably, in the synthesis of 2,5-dichloro-N-benzenesulfonamide in step (2), the solvent used is one or more of dichloromethane, dichloroethane, toluene, tetrahydrofuran, methyltetrahydrofuran, and cyclopentyl methyl ether, and the mass of the solvent is 5 to 25 times the mass of aniline.

[0028] Further preferably, the specific steps of synthesizing 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide in step (3) are: 2,5-dichloro-N-benzenesulfonamide, sodium formaldehyde sulfoxylate and potassium hydroxide are mixed to obtain a mixture, after nitrogen replacement, dimethyl sulfoxide is added to the mixture, and under nitrogen protection, the mixture is stirred at 80°C to 130°C, and after the reaction of the raw materials is completed, the mixture is slowly cooled to room temperature, and 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide is obtained after post-treatment. More preferably, in step (3), the ratio of the amount of sodium formaldehyde sulfoxylate to 2,5-dichloro-N-benzenesulfonamide is 1:2 to 1:8; the ratio of the amount of sodium formaldehyde sulfoxylate to potassium hydroxide is 1:1 to 1:9; the ratio of the mass of 2,5-dichloro-N-benzenesulfonamide to the volume of dimethyl sulfoxide is 1:5 to 1:50 g / ml.

[0029] Further preferably, the specific steps of synthesizing 4'-chloro-2-aminobiphenyl in step (4) are: adding 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide to sulfuric acid to obtain a mixture, boiling the mixture for 26-28 hours, and post-treating to obtain 4'-chloro-2-aminobiphenyl. More preferably, in step (4), the molar ratio of 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide to sulfuric acid is 1:3 to 1:20; further preferably, the mass fraction of the sulfuric acid is 50%-98%; most preferably, the mass fraction of the sulfuric acid is 70%.

[0030] The present invention provides a biphenyl synthesis method route, which is not limited to the synthesis of 4'-2-aminobiphenyl by this invention, but also includes the synthesis of other biphenyl compounds by this invention. The specific synthesis formula is as follows:

[0031]

[0032] X1 and X2 are independently CH, CF, CCH3 or N

[0033] R1, R2, R3, and R4 are any combination of the following (a), (b), (c), and (d).

[0034] (a) F, Cl, Br, I, H, CN, CF3, CHF2, CH2F, NO, NO2, NH2, COOH, COOMe, OH, OMe, SH, -SSMe, SO2Me, Se, CHO, COCH3, CS2H, COSH, -CH2CH3, PO3H, PO2OMe;

[0035] (b) C1-C6 alkyl optionally substituted by 1 to 3 fluorine groups;

[0036] (c) is phenyl which is optionally substituted with one or more substituents;

[0037] (d) is an aromatic heterocycle optionally substituted by one or more substituents;

[0038] The invention provides a method for synthesizing 4'-chloro-2-aminobiphenyl. The method is simple, does not require the use of noble metal catalysts and transition metals, has a mild and green reaction post-treatment, is simple and does not require complicated operations, and the raw materials used are basically cheap and easily available basic chemical raw materials. The synthesis cost is low and the yield is high, which is very suitable for industrial production. DETAILED DESCRIPTION

[0039] The present invention is further described by the following examples, but the following examples should not be construed as limiting the scope of protection of the present invention. Without departing from the technical scope of the present invention, any non-essential improvements and changes to the present invention should be included in the technical scope of the present invention.

[0040] Example 1: Synthesis of 2,5-dichlorobenzenesulfonyl chloride:

[0041]

[0042] In a 2L four-necked flask equipped with a dropping funnel, a thermometer and a reflux condenser, 500g of 1,2-dichloroethane was added, 147g (1mol) of p-dichlorobenzene was slowly added under magnetic stirring, and 291g (2.5mol) of chlorosulfonic acid was added dropwise over a period of 150min, and the temperature was maintained between 90 and 100°C. After the chlorosulfonic acid was completely added, the reaction mixture was stirred at room temperature for another 45 minutes, and the reaction mixture was mechanically stirred at 0°C in a frozen mixture bath containing ice and salt; the product was extracted with three 500ml portions of chloroform (extracted three times with 500ml chloroform each time), and after drying over anhydrous sodium sulfate overnight, the chloroform was distilled off under reduced pressure to obtain 196g (yield 80%) of 2,5-dichlorobenzenesulfonyl chloride, which was pure enough and did not require further purification, and it was directly used in the next reaction.

[0043] Example 2: Synthesis of 2,5-dichloro-N-phenylbenzenesulfonamide

[0044]

[0045] In a 3L flask equipped with a dropping funnel, a thermometer and a stirring rod, 1kg of dichloroethane, 81.8g (0.88mol) of aniline and 127.2g (1.2mol) of anhydrous sodium carbonate were added, stirring was started and the mixture was cooled to 0°C with an ice bath. 196g (0.8mol) of 2,5-dichlorobenzenesulfonyl chloride prepared in Example 1 was dissolved in 500ml of dichloroethane and added to the dropping funnel. The mixture was slowly added dropwise (to the substance in the flask) while maintaining the temperature between 0-5°C. After the addition was completed, the ice bath was removed and the mixture was slowly heated to room temperature and stirred overnight. 1L of distilled water was added to extract the organic phase, the water layer was discarded, and the organic phase was washed with 500ml of saturated brine and 500ml of distilled water. The organic phase was concentrated to obtain an off-white solid, which was recrystallized with dichloroethane and petroleum ether to obtain 217g of white solid 2,5-dichloro-N-benzenesulfonamide, with a yield of 90%. 1H NMR (400MHz, chloroform-d): δ7.98(dd,J=1.9,1.0Hz,1H),7.43(d,J=1.8Hz,2H),7.26(dd,J=8.8,6.9Hz,2H),7.18-7.10(m,3H),7.04(s,1H)

[0046] Example 3: Synthesis of 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide

[0047]

[0048] 30.2 g (0.1 mol) of 2,5-dichloro-N-benzenesulfonamide synthesized in Example 2, rongalite [hydrocarbon powder (sodium formaldehyde sulfoxylate)] (0.3 mol) and powdered KOH (0.3 mol) were placed in a 2L four-necked round-bottom flask equipped with a magnetic stirring bar, replaced with nitrogen three times, DMSO (250 mL) was added to the mixture with a syringe, and the resulting reaction mixture was stirred in an oil bath at 80°C for 24 hours under nitrogen protection. The reaction mixture was cooled to room temperature after the raw material reaction was complete (the raw material disappeared) as tracked by liquid HPLC; 2L of water was slowly added dropwise to the above reaction solution, the mixture was extracted with methyl tert-butyl ether (20 mL x 3), the organic layer was dried with Na2SO4, concentrated under reduced pressure, and purified by slurrying and recrystallization with ethyl acetate / petroleum ether (30 / 70) to obtain 19.4 g of 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide with a yield of 73.2%. 1H NMR (400MHz, DMSO-d6, rt): δ11.56(br.s,1H),8.36(s,1H),8.28(d,J=8.0Hz,1H),7.95(d,J=8.4Hz ,1H),7.72(d,J=8.4Hz,1H),7.51(t,J=7.7Hz,1H),7.30(t,J=7.7Hz,1H),7.23(d,J=8.0Hz,1H); 13C NMR(100MHz,DMSO-d6,rt): δ137.6,136.9,133.8,133.0,131.1,128.5,125.9,125.4,124.0,123.3,120.5,119.7.H

[0049] Comparative Example 1: Synthesis of 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide

[0050]

[0051] 30.2 g (0.1 mol) of 2,5-dichloro-N-benzenesulfonamide synthesized in Example 2 and sodium formate dihydrate (8.16 g, 0.12 mol) were dissolved in 280 mL of dimethyl sulfoxide, and the resulting mixture was reacted at 120° C. for 8 hours, then 500 mL of water was added, the mixture was transferred to a separatory funnel, extracted with dichloromethane (500 mL×2), the organic phases were combined, washed with 100 mL of water and 100 mL of saturated sodium chloride solution in sequence, and after washing, 5 g of anhydrous sodium sulfate was added for drying, and the solvent was removed under reduced pressure to obtain a white solid crude product; the product was separated and purified by column chromatography using dichloromethane / petroleum ether (volume ratio 2:1) to obtain 10.6 g of a white solid fine product with a yield of 40%. 1HNMR (400MHz, DMSO-d6, rt): δ11.56(br.s,1H),8.36(s,1H),8.28(d,J=8.0Hz,1H),7.95(d,J=8.4 Hz, 1H), 7.72 (d, J = 8.4Hz, 1H), 7.51 (t, J = 7.7Hz, 1H), 7.30 (t, J = 7.7Hz, 1H), 7.23 (d, J = 8.0Hz, 1H).

[0052] By comparing Example 3 with Comparative Example 1, the yield of Example 3 is significantly improved relative to that of Comparative Example 1.

[0053] Example 4: Synthesis of 4'-chloro-2-aminobiphenyl

[0054]

[0055] 19.4 g (0.073 mol) of 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide synthesized in Example 3 was added to 97 ml (5 ml / g) 70% sulfuric acid (50 ml concentrated acid, diluted with 31 ml water) (0.9 mol) in 500 ml, and the mixture was gently boiled for 26 hours, with heat provided by an oil bath maintained at 165-195°; then the reaction mixture was poured into 1 liter of ice water with stirring, and 200 ml x 2 of toluene was added for extraction, the organic phase was discarded, the aqueous phase was neutralized to neutrality with 10% sodium hydroxide solution, washed three times with 100 ml x water, and the organic phase was extracted with 500 ml x 2 toluene, and the toluene was removed under reduced pressure under vacuum conditions to obtain 11.8 g of pure 4'-chloro-2-aminobiphenyl, with a yield of 80%. 1HNMR(500MHz,DMSO-d6)δ:7.47(d,J=8.4Hz,2H,ArH′-3′,5′),7.42(d,J=8.4Hz,2H,ArH′-2′,6′),7.04(td,J=7.4,1.1Hz ,1H,ArH-5),6.96(d,J=7.5Hz,1H,ArH-6),6.75(d,J=8.1Hz,1H,ArH-3),6.62(t,J=7.5Hz,1H,ArH-4),4.80(s,2H,NH2-2)

[0056] Comparative Example 2: Synthesis of 4'-chloro-2-aminobiphenyl

[0057] 19.4 g (0.073 mol) of 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide synthesized in Example 3 was added to 97 ml (5 ml / g) 80% sulfuric acid (50 ml concentrated acid, diluted with 23 ml water) 0.9 mol) in 500 ml. The mixture was gently boiled for 26 hours, and the heat was provided by an oil bath maintained at 165-195°; then the reaction mixture was poured into 1 liter of ice water under stirring, and 200 ml x 2 of toluene was added to extract the organic phase and discarded, the aqueous phase was neutralized with 10% sodium hydroxide solution to neutrality, washed three times with 100 ml x water, and the organic phase was extracted with 500 ml x 2 toluene to obtain the organic phase, and the toluene was removed under reduced pressure under vacuum conditions to obtain 9.42 g of pure 4'-chloro-2-aminobiphenyl, with a yield of 63%.

[0058] Comparative Example 3: Synthesis of 4'-chloro-2-aminobiphenyl

[0059]

[0060] To a mixture of 2.65 g (10 mmol) of 2-chloro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide synthesized in Example 3 and Mg powder (1.2 g, 50 mmol) in THF (5.0 mL) was added Ti(Oi-Pr)4 (2.9 mL, 10 mmol) and Me3SiCl (2.0 mL, 15 mmol) in an argon atmosphere; the resulting mixture was stirred at 50°C for 12 hours. After monitoring by TLC that the raw materials had been completely converted, 4 mL of a 3 mol / L NaOH aqueous solution, methyl tert-butyl ether (150 mL), sodium fluoride (1 g) and diatomaceous earth (1 g) were added to the reaction solution at room temperature. After stirring for 30 minutes, the mixture was filtered through filter paper (a layer of diatomaceous earth was spread on the filter paper during filtration), and a 3 mol / L NaOH aqueous solution (150 mL) was added to the resulting filtrate. The mixture was extracted with methyl tert-butyl ether (150 ml), and the organic phase was 3M The residue was washed with 3 mol / L NaOH aqueous solution, dried with anhydrous Na2SO4, filtered and concentrated. The residue was separated and purified by methyl tert-butyl ether / petroleum ether column chromatography to obtain 1.02 g of 4'-chloro-2-aminobiphenyl. The yield was 50%.

[0061] The yield of the product obtained by the method of Example 4 is 80%, while the yields of the product obtained by the methods of Comparative Examples 2 and 3 are only 63% and 50%, which are significantly lower than those of Example 4. In addition, the post-processing operation of Example 4 is simple. The synthesis method of the present invention has obvious advantages over other conventional methods in the prior art.

[0062] The invention provides a method for synthesizing 4'-chloro-2-aminobiphenyl. The method is simple, does not require the use of precious metal catalysts and transition metals, has a mild and green reaction post-treatment, is simple and does not require complicated operations, and the raw materials used are basically cheap and easily available basic chemical raw materials. The synthesis cost is low and the yield is high, which is very suitable for industrial production.

Claims

1. A method for synthesizing 4'-chloro-2-aminobiphenyl, characterized in that: The reaction equation of the synthetic method is: ， The synthesis method is specifically as follows: (1) Synthesis of 2,5-dichlorobenzenesulfonyl chloride: using p-dichlorobenzene and chlorosulfonic acid; (2) Synthesis of 2,5-dichloro-N-phenylbenzenesulfonamide: using 2,5-dichlorobenzenesulfonyl chloride and aniline, adding a base; (3) Synthesis of 2-chloro-6H-dibenzo[c,e][1,2]thiazine-5,5-dioxide: synthesized by reduction cyclization of 2,5-dichloro-N-benzenesulfonamide, the specific steps are: 2,5-dichloro-N-benzenesulfonamide, sodium formaldehyde sulfoxylate and potassium hydroxide are mixed to obtain a mixture, after nitrogen replacement, dimethyl sulfoxide is added to the mixture, and under nitrogen protection, the mixture is stirred at 80°C to 130°C, after the reaction of the raw materials is completed, it is slowly cooled to room temperature, and after post-treatment, 2-chloro-6H-dibenzo[c,e][1,2]thiazine-5,5-dioxide is obtained; (4) Synthesis of 4'-chloro-2-aminobiphenyl: The synthesis is carried out by cleaving 2-chloro-6H-dibenzo[c,e][1,2]thiazine-5,5-dioxide using H2SO4. The specific steps are as follows: 2-chloro-6H-dibenzo[c,e][1,2]thiazine-5,5-dioxide is added to sulfuric acid to obtain a mixture, the mixture is boiled for 26-28 hours, and 4'-chloro-2-aminobiphenyl is obtained by post-treatment.

2. The method for synthesizing 4'-chloro-2-aminobiphenyl according to claim 1, characterized in that: In step (1), the molar ratio of p-dichlorobenzene to chlorosulfonic acid is 1:1-3.

3. The method for synthesizing 4'-chloro-2-aminobiphenyl according to claim 1, characterized in that: The solvent used in step (1) is one or more of dichloromethane, dichloroethane, tetrachloroethane, chloroform, and carbon tetrachloride, and the mass of the solvent is 1 to 10 times the mass of p-dichlorobenzene.

4. The method for synthesizing 4'-chloro-2-aminobiphenyl according to claim 1, characterized in that: In the synthesis of 2,5-dichloro-N-phenylbenzenesulfonamide in step (2), the base used is one or more of triethylamine, diisopropylethylamine, sodium carbonate, potassium carbonate, cesium fluoride, cesium carbonate, 1,8-diazabicycloundec-7-ene, and 1,4-diazabicyclo[2.2.2]octane, and the amount of the base is 1 to 10 times the amount of the aniline.

5. The method for synthesizing 4'-chloro-2-aminobiphenyl according to claim 1, characterized in that: In the synthesis of 2,5-dichloro-N-benzenesulfonamide in step (2), the solvent used is one or more of dichloromethane, dichloroethane, toluene, tetrahydrofuran, methyltetrahydrofuran, and cyclopentyl methyl ether, and the mass of the solvent is 5 to 25 times the mass of aniline.

6. The method for synthesizing 4'-chloro-2-aminobiphenyl according to claim 1, characterized in that: In step (3), the ratio of the amount of sodium formaldehyde sulfoxylate to 2,5-dichloro-N-phenylbenzenesulfonamide is 1:2 to 1:8; the ratio of the amount of sodium formaldehyde sulfoxylate to potassium hydroxide is 1:1 to 1:9; and the ratio of the mass of 2,5-dichloro-N-phenylbenzenesulfonamide to the volume of dimethyl sulfoxide is 1:5 to 1:50 g / ml.

7. The method for synthesizing 4'-chloro-2-aminobiphenyl according to claim 1, characterized in that: In step (4), the molar ratio of 2-chloro-6H-dibenzo[c,e][1,2]thiazine-5,5-dioxide to sulfuric acid is 1:3 to 1:20; and the mass fraction of the sulfuric acid is 50% to 98%.

8. The method for synthesizing 4'-chloro-2-aminobiphenyl according to claim 7, characterized in that: The mass fraction of the sulfuric acid is 70%.

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