CN116640064A - Synthesis method of 4' -chloro-2-aminobiphenyl - Google Patents

Synthesis method of 4' -chloro-2-aminobiphenyl Download PDF

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CN116640064A
CN116640064A CN202310534156.7A CN202310534156A CN116640064A CN 116640064 A CN116640064 A CN 116640064A CN 202310534156 A CN202310534156 A CN 202310534156A CN 116640064 A CN116640064 A CN 116640064A
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chloro
aminobiphenyl
synthesizing
synthesis
dichloro
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贾永林
成道泉
王祥传
李珂
张力伟
刘玲玲
马淼
张帆
杨丽君
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Shandong Jingbo Agrochemical Technology Co ltd
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Shandong Jingbo Agrochemical Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/62—Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
    • C07C303/04—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by substitution of hydrogen atoms by sulfo or halosulfonyl groups
    • C07C303/08—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by substitution of hydrogen atoms by sulfo or halosulfonyl groups by reaction with halogenosulfonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/38—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/02—1,2-Thiazines; Hydrogenated 1,2-thiazines

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of 4' -chloro-2-aminobiphenyl, which comprises the following specific steps of: the synthesis method is simple, does not need noble metal catalyst, transition metal, mild and green reaction post-treatment, does not need complex operation, and the used raw materials are basically cheap and easily obtained basic chemical raw materials, the synthesis cost is lower, the yield is high, and the method is very suitable for industrial production.

Description

Synthesis method of 4' -chloro-2-aminobiphenyl
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of 4' -chloro-2-aminobiphenyl.
Background
Boscalid is a nicotinamide fungicide developed by basf corporation in germany and is mainly used for controlling powdery mildew, gray mold, various rot diseases, brown rot and root rot, etc., and is registered as a pesticide fungicide in the united kingdom, germany and switzerland in 2004. Boscalid belongs to a succinate coenzyme Q reductase inhibitor in the mitochondrial respiratory chain, has strong inhibition capability on spore germination, and has no cross resistance with other bactericides. The boscalid is prepared by reacting 4' -chloro-2-aminobiphenyl with 2-chloronicotinyl chloride. The intermediate 2-chloronicotinyl chloride has been industrialized, so the preparation of 4' -chloro-2-aminobiphenyl is the key for synthesizing boscalid and is one of the current research difficulties.
At present, palladium is generally adopted to catalyze o-nitrochloro (bromo) benzene to react with p-chlorobenzeneboronic 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 of p-chlorophenylboronic acid, palladium catalyst, pd/C, etc., which makes the production cost excessively large.
Chinese patent CN111662184 and CN113831280 and CN115286514 use 9-fluorenone as raw material to synthesize 4' -chloro-2-nitro biphenyl by ring opening, chlorination, huffman degradation and other organic synthesis means. In CN111662184, dangerous chemical antimony trichloride is used as a catalyst in a chlorination section, ring-opening product 2-diphenyl formate is used as a raw material, sulfonyl chloride is used as a chlorinating agent to carry out chlorination, so that the reaction has a plurality of side reactions, and the main product 4' -chloro-2-diphenyl formate is difficult to purify, so that the yield of a target product is low. Patent CN113831280a also mentions that the prepared biphenyl-2-carboxamide reacts with chlorine gas in the presence of a catalyst to produce 4' -chloro-2-amidebiphenyl, which avoids the use of the dangerous chemical antimony trichloride, but uses toxic dangerous chlorine gas as a chlorinating agent, and is chlorinated by introducing chlorine gas under heating. When repeated experiments are carried out on the compound, the generation of chlorinated isomer and polychlorinated product is found, the separation and purification are difficult, and the actual separation yield is low. Although the critical chemicals such as antimony trichloride and chlorine are not used in CN115286514 to obtain 4' -chloro-2-nitrobiphenyl with higher yield, the cost is reduced, the application range of the important organic synthesis intermediate of 9-fluorenone is not only used in the pesticide field, but also used for synthesizing modifiers of bisphenol fluorene, fluorenyl benzoxazine resin, acrylic ester resin, polyester and epoxy resin; has great application value in the fields of medicine, dye, electronic material and the like. The application of 9-fluorenone is increased, the raw material supply is insufficient, the price is greatly improved in recent years, and the synthesis of 4' -chloro-2-aminobiphenyl by taking 9-fluorenone as the raw material has no advantage of low cost.
Synlett,2011,14,2064-2068 reports the synthesis of l, 4-dichlorobenzene as a grignard reagent, which is prepared by lithium chloride catalysis, but the scheme is not thorough in reaction, low in yield, and unsuitable for mass production due to the use of expensive metallic palladium as a catalyst.
WO2013132006 reports that p-chlorophenylhydrazine and an excess of aniline (20-fold equivalent) are obtained as 4' -chloro-2-aminobiphenyl in 41% yield under the condition of excess manganese dioxide using phenylhydrazine analogue and aniline analogue as starting materials according to the method reported in the literature, but the reaction uses an excess of manganese dioxide and aniline and the yield is extremely low, thus being unfavorable for industrialization.
Journal of the American Chemical 2007,129,4824-4833 it is reported that o-nitrobenzoic acid and 1, 4-p-dichlorobenzene are coupled under palladium metal catalysis to give 4' -chloro-2-nitrobiphenyl in moderate yields (66%) and using expensive palladium catalysts.
In Chinese patent CN114230433, aniline and p-chloroiodobenzene are adopted as raw materials, cobalt chloride is used for generating 4 '-chloro-2-aminobiphenyl through a photocatalyst coupling reaction, the yield is high, pollution is less and the like, but the p-chloroiodobenzene and the photocatalyst are relatively expensive, and the 4' -chloro-2-aminobiphenyl can be obtained in high yield only by using special light source equipment to emit a light source with a special wavelength, so that the production cost is improved intangibly, and the method is not suitable for industrial production.
In conclusion, most of reported boscalid intermediate 4' -chloro-2-aminobiphenyl synthesis processes use expensive catalysts, and raw materials such as p-chlorophenylboronic acid, 9-fluorenone and photocatalyst with high price greatly improve the production cost and increase the difficulty of mass production. In addition, in view of the advantages of wide sterilization spectrum, environmental friendliness and the like of boscalid and the characteristics of large market demand, it is not enough to find a novel production process suitable for mass production.
Disclosure of Invention
In order to solve the defects existing in the prior art, the invention provides a synthesis method of 4' -chloro-2-aminobiphenyl, which is simple, does not need to use a noble metal catalyst, transition metal, is mild and green, has simple and convenient reaction post-treatment, does not need complex operation, adopts the raw materials which are basic chemical raw materials with low cost and easy obtainment, has lower synthesis cost and high yield, and is very suitable for industrial production.
The technical scheme of the invention is as follows:
a synthetic method of 4' -chloro-2-aminobiphenyl comprises the following steps:
preferably, the synthesis method is specifically as follows:
(1) Synthesis of 2, 5-dichlorobenzenesulfonyl chloride: synthesizing by dichlorobenzene and chlorosulfonic acid;
(2) Synthesis of 2, 5-dichloro-N-benzenesulfonamide: synthesizing with dichlorobenzenesulfonyl chloride and aniline;
(3) Synthesis of 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide: is synthesized by reduction cyclization of 2, 5-dichloro-N-benzene sulfonamide;
(4) Synthesis of 4' -chloro-2-aminobiphenyl: by H 2 SO 4 Cleavage of 2-chloro-6H-dibenzo [ c, e][1，2]Thiazine 5, 5-dioxide synthesis.
Further preferably, the molar ratio of paradichlorobenzene to chlorosulfonic acid in the step (1) is 1:1-3. More preferably, the solvent adopted in the step (1) is one or more of dichloromethane, dichloroethane, tetrachloroethane, trichloromethane, carbon tetrachloride, nitrobenzene and methyl nitrobenzene, and the mass of the solvent is 1 to 10 times of that of p-dichlorobenzene.
Further preferably, in the synthesis of 2, 5-dichloro-N-benzenesulfonamide in the step (2), the base is one or more of triethylamine, diisopropylethylamine, sodium carbonate, potassium carbonate, cesium fluoride, cesium carbonate, calcium carbonate, 1, 8-diazabicyclo undec-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 substance. More preferably, in the synthesis of the 2, 5-dichloro-N-benzene sulfonamide in the step (2), the solvent is one or more of dichloromethane, dichloroethane, toluene, tetrahydrofuran, methyltetrahydrofuran and cyclopentyl methyl ether, and the mass of the solvent is 5-25 times of that of aniline.
Further preferably, the specific steps of the synthesis of 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide in step (3) are: mixing 2, 5-dichloro-N-benzene sulfonamide, sodium formaldehyde sulfoxylate and potassium hydroxide to obtain a mixture, adding dimethyl sulfoxide into the mixture after nitrogen replacement, stirring at 80-130 ℃ under the protection of nitrogen, slowly cooling to room temperature after the reaction of the raw materials is finished, and obtaining the 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide after post treatment. More preferably, in step (3), the ratio of the amount of sodium formaldehyde sulfoxylate to the amount of 2, 5-dichloro-N-benzenesulfonamide material is 1: 2-1: 8, 8; ratio of the amount of sodium formaldehyde sulfoxylate to the amount of potassium hydroxide material 1:1 to 1:9, a step of performing the process; the ratio of the mass of the 2, 5-dichloro-N-benzene sulfonamide to the volume of the dimethyl sulfoxide is 1:5 to 1:50g/ml.
Further preferably, the specific steps of the synthesis of 4' -chloro-2-aminobiphenyl in step (4) are: adding 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide into sulfuric acid to obtain a mixture, boiling the mixture for 26-28H, and performing post-treatment to obtain 4' -chloro-2-aminobiphenyl. More preferably, the mass ratio of 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide to sulfuric acid in step (4) is 1: 3-1: 20, a step of; further preferably, the mass fraction of the sulfuric acid is 50% -98%; most preferably, the sulfuric acid has a mass fraction of 70%.
The invention provides a biphenyl synthesizing method route, which is not only limited to synthesizing 4' -2-amino biphenyl by the invention, but also comprises synthesizing other biphenyl compounds by the invention, and the specific synthetic general formula is as follows:
x1, X2 are independently CH, CF, CCH 3 Or N
R1, R2, R3 and R4 are any combination of the following (a), (b), (c) and (d).
(a)F、Cl、Br、I、H、CN、CF 3 、CHF 2 、CH 2 F、NO、NO 2 、NH 2 、COOH、COOMe、OH、OMe、SH、-SSMe、SO 2 Me、Se、CHO、COCH 3 、CS 2 H、COSH、-CH 2 CH 3 、PO 3 H、PO 2 OMe；
(b) C1-C6 alkyl optionally substituted with 1-3 fluoro;
(c) Is phenyl optionally substituted with one or more substituents;
(d) Is an aromatic heterocycle optionally substituted with one or more substituents;
the synthesis method of the 4' -chloro-2-aminobiphenyl provided by the invention is simple, does not need to use noble metal catalysts and transition metals, is mild and green, has simple and convenient reaction post-treatment, does not need complex operation, adopts the raw materials which are basic chemical raw materials and are cheap and easy to obtain, has lower synthesis cost and high yield, and is very suitable for industrial production.
Detailed Description
The present invention is further illustrated by the following examples, which are not to be construed as limiting the scope of the invention. Any modifications and variations which are not essential to the present invention, without departing from the technical scope of the present invention, should be included in the technical scope of the present invention.
Example 1: synthesis of 2, 5-dichlorobenzenesulfonyl chloride:
1, 2-dichloroethane 500g was added to a 2L four-necked flask equipped with a dropping funnel, a thermometer and a reflux condenser, p-dichlorobenzene 147g (1 mol) was slowly added under magnetic stirring, chlorosulfonic acid 291g (2.5 mol) was added dropwise over 150 minutes, the temperature was maintained at 90 to 100 ℃, after complete addition of chlorosulfonic acid, the reaction mixture was stirred at room temperature for another 45 minutes, and the reaction mixture was mechanically stirred at 0 ℃ in a frozen mixture bath containing ice and salt; the product was extracted with three 500ml portions of chloroform (three times each with 500ml of chloroform), dried over anhydrous sodium sulfate and distilled off under reduced pressure to give 196g (80% yield) of 2, 5-dichlorobenzenesulfonyl chloride, which was sufficiently pure that no further purification was required and was used directly in the next reaction.
Example 2: synthesis of 2, 5-dichloro-N-benzenesulfonamide
1kg of dichloroethane, 81.8g (0.88 mol) of aniline, 127.2g (1.2 mol) of anhydrous sodium carbonate and cooling to 0℃with an ice bath were added to a 3L flask equipped with a dropping funnel, a thermometer and a stirring rod, 196g (0.8 mol) of 2, 5-dichlorobenzenesulfonyl chloride prepared in example 1 above was dissolved in 500ml of dichloroethane and added to the dropping funnel, the temperature was kept between 0 and 5℃and slowly dropped (to the contents of the flask), after the dropping was completed, the ice bath was removed and slowly warmed to room temperature, and the mixture was stirred overnight; adding 1L distilled water to extract to obtain an organic phase, discarding a water layer, and washing the organic phase with 500ml saturated saline water and 500ml distilled water; the organic phase was concentrated to give an off-white solid which was recrystallized from dichloroethane and petroleum ether to give 217g of 2, 5-dichloro-N-benzenesulfonamide as a white solid in yield: 90%.1H NMR (400 MHz, chloroform-d): delta 7.98 (dd, J=1.9, 1.0Hz, 1H), 7.43 (d, J=1.8 Hz, 2H), 7.26 (dd, J=8.8, 6.9Hz, 2H), 7.18-7.10 (m, 3H), 7.04 (s, 1H)
Example 3: synthesis of 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide
30.2g (0.1 mol) of 2, 5-dichloro-N-benzenesulfonamide synthesized in example 2 above and rongalite [ sodium hydrosulfite (sodium formaldehyde sulfoxylate)](0.3 mol) and powdered KOH (0.3 mol) were charged into a 2L four-necked round bottom flask equipped with a magnetic stirring bar, replaced three times with nitrogen, DMSO (250 mL) was added to the mixture with a syringe, the resulting reaction mixture was stirred in an oil bath at 80℃for 24 hours under nitrogen protection, and the reaction mixture was cooled to room temperature by liquid phase HPLC following completion of the starting material reaction (disappearance of starting material); slowly dropwise adding 2L of water to the reaction solution, extracting the mixture with methyl tert-butyl ether (20 mL. Times.3), and using Na 2 SO 4 The organic layer was dried, concentrated under reduced pressure, and recrystallized and purified by beating with ethyl acetate/petroleum ether (30/70) to give 2-chloro-6H-dibenzo [ c, e ]][1，2]Thiazine 5, 5-dioxide 19.4g, yield: 73.2%.1H NMR (400 MHz, DMSO-d6, rt): δ11.56 (br.s, 1H), 8.36 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H), 7.51 (t, J=7.7 Hz, 1H), 7.30 (t, J=7.7 Hz, 1H), 7.23 (d, J=8.0 Hz, 1H); 13C NMR (100 MHz, DMSO-d6, rt): delta 137.6,136.9,133.8,133.0,131.1,128.5,125.9,125.4,124.0,123.3,120.5,119.7.H
Comparative example 1: synthesis of 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide
30.2g (0.1 mol) of 2, 5-dichloro-N-benzenesulfonamide synthesized in example 2 above and sodium formate dihydrate (8.16 g,0.12 mol) were dissolved in 280mL of dimethyl sulfoxide, the resulting mixture was reacted at 120℃for 8 hours, then 500mL of water was added, the mixture was transferred to a separating funnel, extracted with methylene chloride (500 mL. Times.2), the organic phases were combined, washed successively with 100mL of water and 100mL of saturated aqueous sodium chloride, and after washing, 5g of anhydrous sodium sulfate was added to dry, and the solvent was removed under reduced pressure to obtain a crude white solid; separating and purifying by column chromatography of dichloromethane/petroleum ether (volume ratio of 2:1) to obtain white solid refined product 10.6g with 40% yield. 1HNMR (400 MHz, DMSO-d6, rt): δ11.56 (br.s, 1H), 8.36 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H), 7.51 (t, J=7.7 Hz, 1H), 7.30 (t, J=7.7 Hz, 1H), 7.23 (d, J=8.0 Hz, 1H).
The yield of example 3 is significantly improved over that of comparative example 1 by comparing example 3 with comparative example 1.
Example 4: synthesis of 4' -chloro-2-aminobiphenyl
19.4g (0.073 mol) of 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide synthesized in example 3 was added to 97ml (5 ml/g) of 70% sulfuric acid (50 ml of concentrated acid, diluted with 31ml of water) (0.9 mol) in 500ml, and the mixture was gently boiled for 26 hours, the heat being supplied from an oil bath maintained at 165-195 °; then pouring the reaction mixture into 1 liter of ice water under the stirring action, adding 200ml of toluene, extracting, discarding the organic phase, neutralizing the water phase to be neutral by using 10% sodium hydroxide solution, washing three times by using 100ml of x water, extracting by using 500ml of x2 toluene to obtain the organic phase, and removing the toluene under vacuum condition under reduced pressure to obtain 11.8g of pure 4' -chloro-2-aminobiphenyl, wherein the yield is: 80%.1HNMR (500 MHz, DMSO-d 6) δ:7.47 (d, J=8.4 Hz,2H, arH '-3',5 '), 7.42 (d, J=8.4 Hz,2H, arH' -2', 6'), 7.04 (td, J=7.4, 1.1Hz,1H, arH-5), 6.96 (d, J=7.5 Hz,1H, arH-6), 6.75 (d, J=8.1 Hz,1H, arH-3), 6.62 (t, J=7.5 Hz,1H, arH-4), 4.80 (s, 2H, NH 2-2)
Comparative example 2: synthesis of 4' -chloro-2-aminobiphenyl
19.4g (0.073 mol) of the 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide synthesized in example 3 was added to 0.9mol of 97ml (5 ml/g) 80% sulfuric acid (50 ml of concentrated acid, diluted with 23ml of water) in 500 ml. The mixture was gently boiled for 26 hours, heat being supplied by an oil bath maintained at 165-195 °; then pouring the reaction mixture into 1 liter of ice water under the stirring action, adding 200ml of toluene, extracting the organic phase, discarding, neutralizing the aqueous phase with 10% sodium hydroxide solution to be neutral, washing with 100ml of x water three times, extracting with 500ml of x2 toluene to obtain the organic phase, and removing the toluene under vacuum condition under reduced pressure to obtain 9.42g of pure 4' -chloro-2-aminobiphenyl, wherein the yield is: 63%.
Comparative example 3: synthesis of 4' -chloro-2-aminobiphenyl
To a mixture of 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide 2.65g (10 mmol) and Mg powder (1.2 g,50 mmol) synthesized in example 3 in THF (5.0 mL) was added an atmosphere of Ti (O-i-Pr) 4 (2.9 mL,10 mmol) and Me3SiCl (2.0 mL,15 mmol) argon; after the resultant mixture was stirred at 50℃for 12 hours, it was monitored by TLC that the starting materials had been completely converted, 4mL of 3mol/L aqueous NaOH solution, methyl t-butyl ether (150 mL) in sodium fluoride (1 g) and diatomaceous earth (1 g) were added to the reaction solution at room temperature, after 30 minutes after stirring, the mixture was filtered through filter paper (a layer of diatomaceous earth was laid on the filter paper at the time of filtration), 3mol/L aqueous NaOH solution (150 mL) was added to the obtained filtrate, the mixture was extracted with methyl t-butyl ether (150 mL), the organic phase was washed with 3M 3mol/L aqueous NaOH solution, dried with anhydrous Na2SO4, filtered and concentrated, and the residue was purified by separation by methyl t-butyl ether/petroleum ether column chromatography to give 1.02g of 4' -chloro-2-aminobiphenyl, yield: 50%.
The yield of the product obtained by the method of example 4 was 80%, whereas by the methods of comparative examples 2 and 3, the yield of the product was only 63% and 50%, the yield was significantly lower than that of example 4, and the post-treatment operation of example 4 was simple, the synthetic method of the present invention has significant advantages over other prior art conventional methods.
The synthesis method of the 4' -chloro-2-aminobiphenyl provided by the invention is simple, does not need to use noble metal catalysts and transition metals, is mild and green, has simple and convenient reaction post-treatment, does not need complex operation, adopts the raw materials which are basic chemical raw materials and are cheap and easy to obtain, has lower synthesis cost and high yield, and is very suitable for industrial production.

Claims (10)

1. The synthesis method of the 4' -chloro-2-aminobiphenyl is characterized in that the reaction equation of the synthesis method is as follows:
2. the method for synthesizing 4' -chloro-2-aminobiphenyl according to claim 1, which is characterized in that the method comprises the following steps:
(1) Synthesis of 2, 5-dichlorobenzenesulfonyl chloride: synthesizing by dichlorobenzene and chlorosulfonic acid;
(2) Synthesis of 2, 5-dichloro-N-benzenesulfonamide: synthesizing with dichlorobenzenesulfonyl chloride and aniline;
(3) Synthesis of 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide: is synthesized by reduction cyclization of 2, 5-dichloro-N-benzene sulfonamide;
(4) Synthesis of 4' -chloro-2-aminobiphenyl: by H 2 SO 4 Cleavage of 2-chloro-6H-dibenzo [ c, e][1，2]Thiazine 5, 5-dioxide synthesis.
3. The method for synthesizing 4' -chloro-2-aminobiphenyl according to claim 2, wherein the molar ratio of paradichlorobenzene to chlorosulfonic acid in the step (1) is 1:1-3.
4. The method for synthesizing 4' -chloro-2-aminobiphenyl according to claim 3, wherein the solvent used in the step (1) is one or more of dichloromethane, dichloroethane, tetrachloroethane, chloroform, carbon tetrachloride, nitrobenzene and methyl nitrobenzene, and the mass of the solvent is 1 to 10 times that of p-dichlorobenzene.
5. The method for synthesizing 4' -chloro-2-aminobiphenyl according to claim 2, wherein in the step (2), 2, 5-dichloro-N-benzenesulfonamide, the base is one or more of triethylamine, diisopropylethylamine, sodium carbonate, potassium carbonate, cesium fluoride, cesium carbonate, calcium carbonate, 1, 8-diazabicyclo undec-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.
6. The method for synthesizing 4' -chloro-2-aminobiphenyl according to claim 5, wherein in the step (2), the solvent used in the synthesis of 2, 5-dichloro-N-phenylsulfonamide is one or more of dichloromethane, dichloroethane, toluene, tetrahydrofuran, methyltetrahydrofuran and cyclopentylmethyl ether, and the mass of the solvent is 5-25 times that of aniline.
7. The method for synthesizing 4' -chloro-2-aminobiphenyl according to claim 2, wherein the specific steps of synthesizing 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide in step (3) are as follows: mixing 2, 5-dichloro-N-benzene sulfonamide, sodium formaldehyde sulfoxylate and potassium hydroxide to obtain a mixture, adding dimethyl sulfoxide into the mixture after nitrogen replacement, stirring at 80-130 ℃ under the protection of nitrogen, slowly cooling to room temperature after the reaction of the raw materials is finished, and obtaining the 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide after post treatment.
8. The method for synthesizing 4' -chloro-2-aminobiphenyl according to claim 7, wherein in the step (3), the ratio of the amount of sodium formaldehyde sulfoxylate to the amount of 2, 5-dichloro-N-benzenesulfonamide material is 1: 2-1: 8, 8; ratio of the amount of sodium formaldehyde sulfoxylate to the amount of potassium hydroxide material 1:1 to 1:9, a step of performing the process; the ratio of the mass of the 2, 5-dichloro-N-benzene sulfonamide to the volume of the dimethyl sulfoxide is 1:5 to 1:50g/ml.
9. The method for synthesizing 4 '-chloro-2-aminobiphenyl according to claim 2, wherein the specific steps of synthesizing 4' -chloro-2-aminobiphenyl in step (4) are as follows: adding 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide into sulfuric acid to obtain a mixture, boiling the mixture for 26-28H, and performing post-treatment to obtain 4' -chloro-2-aminobiphenyl.
10. The method for synthesizing 4' -chloro-2-aminobiphenyl according to claim 9, wherein the mass ratio of 2-chloro-6H-dibenzo [ c, e ] [1,2] thiazine 5, 5-dioxide to sulfuric acid in step (4) is 1: 3-1: 20, a step of; further preferably, the mass fraction of the sulfuric acid is 50% -98%; most preferably, the sulfuric acid has a mass fraction of 70%.
CN202310534156.7A 2023-05-10 2023-05-10 Synthesis method of 4' -chloro-2-aminobiphenyl Pending CN116640064A (en)

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