Preparation method for iminoaryl compound and preparation method for intermediate
By optimizing the preparation method of iminoaryl compounds, using catalysts and solvents such as zinc-copper alloys, and simplifying the process flow, the problems of complex processes and low yields in existing technologies have been solved, and efficient industrial production has been achieved.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- SHANDONG KINGAGROOT CROPSCIENCE CO LTD
- Filing Date
- 2025-12-19
- Publication Date
- 2026-06-25
AI Technical Summary
Existing synthetic processes for iminoaryl compounds are complex, generate a lot of wastewater, and have low yields, making them unsuitable for industrial production.
By employing novel reduction, substitution, and chlorination reaction steps, and utilizing catalysts and solvents such as zinc-copper alloys and hydroxylamine hydrochloride, the intermediate preparation process is simplified, the chlorination step is reduced, and the reaction yield is improved.
By simplifying the process flow and reducing wastewater generation, the yield of each step and the overall yield are significantly improved, making it suitable for industrial production.
Smart Images
Figure CN2025143717_25062026_PF_FP_ABST
Abstract
Description
Preparation methods of iminoaryl compounds and intermediates Technical Field
[0001] This invention belongs to the field of organic chemical synthesis, specifically relating to a method for preparing iminoaryl compounds and intermediates. Background Technology
[0002] In recent years, my country's pesticide innovation has developed rapidly, and the variety of herbicides has also increased. Iminoaryl compounds are a new type of herbicide disclosed in CN113105405A, which has the characteristics of broad-spectrum weed control, high activity, fast weed control, and environmental friendliness. Although the synthesis of an intermediate compound of this compound is disclosed in CN115124476A, the synthesis process still has problems such as complex reaction steps, large amounts of wastewater, and low yield. Scientists still need to further develop a synthesis process more suitable for industrial production. Summary of the Invention
[0003] To address the aforementioned problems in the prior art, this invention provides a method for preparing iminoaryl compounds and intermediates.
[0004] The technical solution adopted in this invention is as follows:
[0005] This invention also provides a method for preparing iminoaryl compound intermediate IX, which includes the following steps:
[0006] Compound VIII is reduced to give compound IX, as shown in the following reaction formula:
[0007] This invention also provides a method for preparing iminoaryl compounds, comprising the following steps:
[0008] (1) Compound VIII was reduced to give compound IX;
[0009] (2) Compound IX reacts with hydroxylamine hydrochloride to give compound X, and then compound X reacts with... The substitution reaction yielded iminoaryl compound XI;
[0010] Or (3) Compound IX reacts with IX-B or its salt (such as hydrochloride) to obtain iminoaryl compound XI;
[0011] The synthesis route is as follows:
[0012] Where L represents halogen.
[0013] In one specific embodiment, the reduction reaction is carried out in the presence of a solvent, a catalyst, and an additive; preferably, the catalyst is selected from at least one of zinc-copper alloys; the solvent is selected from at least one of acetonitrile, DME, dichloromethane, 1,2-dichloroethane, toluene, or xylene; and / or the additive is selected from at least one of tributylphosphine / methanesulfonic acid or triphenylphosphine / methanesulfonic acid.
[0014] In another specific embodiment, the reaction of compound IX with hydroxylamine hydrochloride in step (2) is carried out in the presence of a solvent; preferably, the solvent is an alcohol (such as methanol, ethanol, n-propanol or isopropanol, etc.).
[0015] In another specific embodiment, the substitution reaction in step (2) is carried out in the presence of a base and a polar solvent; preferably, the base is selected from at least one of sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, potassium carbonate, potassium bicarbonate, sodium ethoxide, or sodium tert-butoxide; and / or the polar solvent is selected from at least one of acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, sulfolane, or N-methylpyrrolidone.
[0016] In another specific embodiment, step (3) is carried out in the presence of a solvent; preferably, the solvent is an alcohol (such as methanol, ethanol, n-propanol or isopropanol, etc.).
[0017] In another specific embodiment, compound VIII is obtained from compound VII via a chlorination reaction, as shown in the following reaction formula:
[0018] Preferably, the chlorination reaction is carried out in the presence of a chlorinating agent and a solvent; more preferably, the chlorinating agent is selected from at least one of thionyl chloride or oxalyl chloride; and / or the solvent is selected from at least one of dichloromethane, dichloroethane or chloroform.
[0019] In another specific embodiment, compound VII is obtained from compound VI via hydrolysis, as shown in the following reaction formula:
[0020] Preferably, the hydrolysis reaction is carried out in the presence of an acid; more preferably, the acid is selected from at least one of sulfuric acid or Lewis acids (such as ferric chloride, zinc chloride, aluminum chloride, etc.).
[0021] In another specific embodiment, the preparation method of compound VI includes the following steps: after reacting compound IV with chloroformate compound IV-a to obtain compound V, compound V first forms a ring with V-a1 and then undergoes a methylation reaction to obtain compound VI, or compound V forms a ring with V-a2 to obtain compound VI; the reaction formula is as follows:
[0022] Wherein, R1 is selected from alkyl or aryl, and R2 is selected from alkyl or aryl; the aforementioned "aryl" is optionally replaced by at least one group selected from hydroxyl, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkylthio or alkylsulfonyl.
[0023] Preferably, R1 is selected from C1-C8 alkyl or aryl, and R2 is selected from C1-C8 alkyl or aryl; the aforementioned "aryl" is optionally substituted by at least one group selected from hydroxyl, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, C1-C8 alkoxy, halo-C1-C8 alkoxy, C1-C8 alkoxy carbonyl, C1-C8 alkylthio or C1-C8 alkylsulfonyl.
[0024] More preferably, R1 is selected from C1-C4 alkyl or phenyl, and R2 is selected from methyl, ethyl, isopropyl or phenyl; the aforementioned "phenyl" is optionally substituted by at least one group selected from hydroxyl, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, C1-C6 alkoxy carbonyl, C1-C6 alkylthio or C1-C6 alkylsulfonyl.
[0025] In another specific embodiment, the reaction for preparing compound V is carried out in the presence of a solvent; preferably, the solvent is selected from at least one of acetonitrile, tetrahydrofuran, ethyl acetate, dichloromethane, 1,2-dichloroethane, toluene, xylene, chlorobenzene, or dichlorobenzene.
[0026] In another specific embodiment, the cyclization reaction is carried out in the presence of a solvent and a base; preferably, the solvent is selected from at least one of acetonitrile, tetrahydrofuran, toluene, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolinone, sulfolane, or N-methylpyrrolidone; and / or the base is selected from at least one of inorganic bases (such as K2CO3, Na2CO3, Cs2CO3, NaHCO3, KF, CsF, K3PO4, NaOH, KOH, NaH, KH, etc.) or organic bases (such as AcOK, AcONa, t-BuONa, MeONa, EtONa, DMAP, pyrazole, triethylamine, DIEA, etc.).
[0027] In another specific embodiment, the reagent required for the methylation reaction is selected from at least one of iodomethane, chloromethane, bromomethane, dimethyl sulfate, or dimethyl carbonate.
[0028] In another specific embodiment, compound IV is obtained by hydrogenation of compound III, as shown in the following reaction formula:
[0029] Preferably, the hydrogenation reaction is carried out in the presence of a catalyst, a solvent, and an anti-dehalogenation agent; more preferably, the catalyst is selected from at least one of palladium on carbon, platinum on carbon, Raney nickel, sodium hydrosulfite, ferric chloride, copper powder, or iron powder, the solvent is an alcohol (such as methanol, ethanol, n-propanol, or isopropanol), and / or the anti-dehalogenation agent is zinc bromide or dicyandiamide.
[0030] In another specific embodiment, compound III is obtained by nitration of compound II with nitric acid, as shown in the following reaction formula: Preferably, the nitration reaction is carried out in the presence of a solvent and a catalyst; more preferably, the solvent is selected from at least one of dichloromethane, dichloroethane, chloroform, water, acetic acid, or trifluoroacetic acid; and / or the catalyst is selected from at least one of concentrated sulfuric acid, acetic anhydride, or trifluoroacetic anhydride.
[0031] In another specific embodiment, compound II is obtained from compound I via a chlorination reaction, as shown in the following reaction formula:
[0032] Preferably, the chlorination reaction is carried out in the presence of a chlorinating agent; more preferably, a catalyst is added during the reaction; even more preferably, the chlorinating agent is selected from at least one of chlorine gas or hydrogen peroxide / concentrated hydrochloric acid; and / or the catalyst is selected from at least one of azobisisobutyronitrile, benzoyl peroxide, m-chloroperoxybenzoic acid or tert-butanol peroxide.
[0033] In another specific embodiment, the carbon atom at * in the iminoaryl compound has an R configuration, and its reaction formula is as follows:
[0034] This application has the following superior effects: Compared with the prior art, this application does not require the intermediate of 4-chloro-2-fluoro-5-trifluoromethylaniline, and can directly prepare compound V through the intermediate of 4-chloro-2-fluoro-5-trichloromethylaniline, which can reduce the intermediate chlorination process and wastewater, and the reaction yield of each step and the overall yield are also significantly improved. Detailed Implementation
[0035] The following examples are for illustrative purposes only and should not be construed as limiting the invention in any way. The scope of protection of this invention is defined by the claims.
[0036] For experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.
[0037] Example 1
[0038] A method for preparing a compound XI(R) includes the following steps:
[0039] 1) Preparation of compound II
[0040] Compound I (MW 144.57, 144.57 g) was added to a 500 mL chlorination reactor, along with 8.2 g of azobisisobutyronitrile (AIBN). Chlorine gas was slowly introduced, and the temperature control device was adjusted to maintain the reaction temperature at 80-110 °C. 2-Chloro-4-fluoromonochlorotoluene was initially produced. Continuing to introduce chlorine gas yielded 2-Chloro-4-fluorodichlorotoluene, and finally 2-Chloro-4-fluorotrichlorotoluene. When the content of 2-Chloro-4-fluorodichlorotoluene in the reaction system was less than 0.5%, the chlorination was stopped, and residual chlorine dissolved in the material was removed with nitrogen gas. The crude product was transferred to a distillation apparatus for vacuum distillation, and the distillate was collected as 223.11 g of the target product II, with a yield of 90%.
[0041] 2) Preparation of Compound III
[0042] In a 1000 mL four-necked flask equipped with a mechanical stirrer and thermometer, compound II (MW 247.90, 111.55 g), 333 g concentrated sulfuric acid, and 220 g dichloromethane were added. The mixture was stirred and cooled to 0-5 °C, and 48.14 g of 65% nitric acid was added dropwise over 2 hours. After the addition was completed, the mixture was brought to room temperature and stirred at room temperature for 2 hours until the reaction was complete. The reaction solution was poured into an ice-water mixture, separated, and the aqueous phase was extracted with 200 g of dichloromethane. The two organic phases were combined and washed successively with saturated sodium bicarbonate solution and purified water. The organic phases were dried and concentrated to give compound III 118.62 g, with a yield of 90%.
[0043] 3) Preparation of compound IV
[0044] Compound III (MW 292.90, 59.31 g) was added to a 500 mL hydrogenation reactor, along with 125 g of methanol, 0.55 g of 5% platinum-carbon, and 0.05 g of zinc bromide. The reactor was sealed, purged with nitrogen and hydrogen, and the reaction was maintained at 30 °C and 0.5 MPa for 3 h. The catalyst was filtered off, and the mixture was distilled under reduced pressure. After removing the fore-fraction, 51.11 g of compound IV was obtained, with a yield of 96%.
[0045] 4) Preparation of compound V
[0046] Compound IV (MW 262.91, 99.66 g) obtained in the previous step was added to a 500 mL reaction flask, along with 200 g of 1,2-dichloroethane. The mixture was heated to reflux, and phenyl chloroformate (MW 156.57, 71.22 g) was added dropwise over 4 hours. The reaction was then maintained at this temperature with stirring for 2 hours until completion. The mixture was cooled to room temperature, quenched with 10% hydrochloric acid, and separated into liquid and liquid phases. The organic phase was washed with purified water and concentrated to give intermediate V 136.61 g, with a yield of 97%.
[0047] 5) Preparation of compound VI
[0048] Add 228 g of N,N-dimethylformamide and ethyl 3-amino-4,4,4-trifluorobutenoate (MW 183.13, 78.38 g) to a 1000 mL reaction flask. Cool to 0-15 °C, add sodium hydroxide (25.5 g), stir for 1 h, then add dropwise a 30% solution of intermediate V in N,N-dimethylformamide (MW 383.02, containing 136.61 g of V). After the addition is complete, maintain the temperature and stir for 1 h. The reaction is confirmed by HPLC. Raise to room temperature, add 74 g of potassium carbonate, and then add dropwise dimethyl sulfate (MW 126.13, 67.48 g). Maintain the temperature at 20-30 °C for 2 h. Slowly pour the reaction solution into water to quench the reaction, extract with toluene, stir for 1 h, separate the layers, wash with the organic phase, concentrate, and give 145.95 g of pale yellow solid VI, yield 93%.
[0049] 6) Preparation of compound VII
[0050] 500 g of 80% sulfuric acid aqueous solution was added to a 1000 mL reaction flask equipped with a mechanical stirrer and thermometer. The temperature was raised to 70 °C, and compound VI (MW 440.0, 145.95 g) was added in batches. The reaction temperature was then adjusted to 100-110 °C and stirred for 3-5 hours. A large amount of white solid gradually precipitated from the system. After the reaction was completed, the reaction solution was cooled to 50 °C and diluted with 200 g of water. Then, 300 g of ethyl acetate was added for extraction. The mixture was separated, and the organic phase was washed with 300 g of water. The solution was concentrated to give 103.36 g of white solid VII, with a yield of 85%.
[0051] 7) Preparation of compound VIII
[0052] Compound VII (MW 366.65, 115.53 g) was dissolved in 300 g of 1,2-dichloroethane, heated to reflux, and 51.03 g of thionyl chloride was added dropwise. The mixture was refluxed for 1 h. After the liquid phase analysis showed that the reaction was satisfactory, the mixture was cooled to remove 1,2-dichloroethane, yielding compound VIII 116.49 g, with a yield of 96%.
[0053] 8) Preparation of compound IX
[0054] Compound VIII (MW 385.10, 116.49 g) was dissolved in acetonitrile, degassed with nitrogen, and cooled to 0 °C. 73.44 g of tributylphosphine was added, and the mixture was stirred at this temperature for 0.5 h. Then, 58.14 g of methanesulfonic acid and 78 g of zinc-copper alloy were added, and the reaction mixture was slowly heated to room temperature and stirred for 1 h. After the reaction was complete, the mixture was poured into a 10% hydrochloric acid aqueous solution, extracted twice with 800 g of 1,2-dichloroethane, and washed with a 10% sodium carbonate aqueous solution. The organic phase was dried over anhydrous sodium sulfate, concentrated, and yielded 99.7 g of a white solid IX, with a yield of 94%.
[0055] 9) Preparation of compound X
[0056] The compound IX (MW 350.65, 74.26 g) obtained in the previous step was added to a 500 mL reaction flask, along with 210 g of ethanol. The mixture was heated to 50 °C, and 18.4 g of hydroxylamine hydrochloride was added to the reaction flask in three batches. The mixture was kept warm and stirred for 6 h until the reaction was complete. The mixture was then cooled to room temperature, and 5% sodium hydroxide aqueous solution was added dropwise to adjust the pH of the system to 7.0-7.5. The mixture was kept warm and stirred for 0.5 h, filtered, and dried to obtain 73.96 g of white solid X with a purity of 97% and a yield of 95.5%.
[0057] 10) Preparation of compound XI(R)
[0058] Compound X (MW 365.67, 73.96 g) was added to a 1000 mL reaction flask, along with 296 g of N,N-dimethylformamide, 35.6 g of anhydrous potassium carbonate powder, and 96.66 g of methyl s-2-chloropropionate. The mixture was stirred at 25-30 °C for 8 h. The reaction was considered complete when the starting material disappeared as detected by HPLC. The reaction solution was quenched in water, extracted with toluene, and the organic phase was washed with purified water and concentrated under reduced pressure to obtain 87.64 g of compound XI(R), with a purity of 98.0% and a yield of 97%.
[0059] Example 2
[0060] The difference from Example 1 lies in the different synthetic steps of compound IX to compound XI(R). The synthetic route is as follows:
[0061] The compound IX (MW 350.65, 35.61 g) obtained in the previous step was added to a 500 mL reaction flask, along with 100 g of ethanol. The mixture was heated to 50 °C, and compound IX-B(R) hydrochloride (MW 155.58, 15.56 g) was added to the reaction flask in five batches. The mixture was kept at this temperature and stirred for 5 h until the reaction was complete. The mixture was then cooled to room temperature, and 5% sodium carbonate aqueous solution was added dropwise to adjust the pH of the system to 7.0-7.5. The ethanol was removed under reduced pressure, and 100 g of toluene was added. The mixture was stirred, allowed to stand, and separated. The organic phase was dried over anhydrous magnesium sulfate and concentrated to obtain 45.18 g of product XI(R), with a purity of 98.0% and a yield of 98%.
[0062] Example 3
[0063] The difference from Example 1 lies in the preparation steps of compound II:
[0064] Compound I (MW 144.57, 144.57 g) was added to a 500 mL chlorination reactor. The temperature was adjusted to 110 °C, and a UV lamp (365 nm) was turned on. Chlorine gas was slowly introduced, initially producing 2-chloro-4-fluoromonochlorotoluene. Continuing to introduce chlorine gas yielded 2-chloro-4-fluorodichlorotoluene, and finally 2-chloro-4-fluorotrichlorotoluene. When the content of 2-chloro-4-fluorodichlorotoluene in the reaction system was less than 0.5%, chlorination was stopped, and residual chlorine dissolved in the material was removed with nitrogen. The crude product was transferred to a distillation unit for vacuum distillation, and the distillate was collected as target product II, 215.67 g, with a yield of 87%.
[0065] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.
Claims
1. A method for preparing an imino aryl class intermediate IX, characterized in that, Includes the following steps: Compound VIII is reduced to give compound IX, as shown in the following reaction scheme:
2. A method for producing an imino aryl compound, characterized by, Includes the following steps: (1) Compound VIII was reduced to give compound IX; (2) Compound IX is reacted with hydroxylamine hydrochloride to obtain compound X, and then compound X is reacted with The substitution reaction yielded iminoaryl compound XI; Or (3) Compound IX reacts with IX-B or its salt to give iminoaryl compound XI; The synthetic route is as follows: Where L represents halogen.
3. The production method according to claim 1 or 2, characterized by, The reduction reaction is carried out in the presence of a solvent, a catalyst, and an additive; preferably, the catalyst is selected from at least one of zinc-copper alloys; the solvent is selected from at least one of acetonitrile, DME, dichloromethane, 1,2-dichloroethane, toluene, or xylene; and / or the additive is selected from at least one of tributylphosphine / methanesulfonic acid or triphenylphosphine / methanesulfonic acid.
4. The production method according to claim 2, characterized by, The reaction of compound IX with hydroxylamine hydrochloride in step (2) is carried out in the presence of a solvent; preferably, the solvent is an alcohol; and / or the substitution reaction in step (2) is carried out in the presence of a base and a polar solvent; preferably, the base is selected from at least one of sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, potassium carbonate, potassium bicarbonate, sodium ethoxide or sodium tert-butoxide; and / or the polar solvent is selected from at least one of acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, sulfolane or N-methylpyrrolidone.
5. The preparation method according to claim 2, characterized in that, The reaction in step (3) takes place in the presence of a solvent; preferably, the solvent is an alcohol.
6. The production method according to claim 1 or 2, characterized by, Compound VIII is obtained from compound VII by chlorination reaction, and the reaction formula is as follows: Preferably, the chlorination reaction is carried out in the presence of a chlorinating agent and a solvent; preferably, the chlorinating agent is selected from at least one of thionyl chloride or oxalyl chloride; and / or the solvent is selected from at least one of dichloromethane, dichloroethane or chloroform.
7. The preparation method according to claim 6, characterized in that, Compound VII is obtained from compound VI by a hydrolysis reaction, as shown in the following reaction scheme: Preferably, the hydrolysis reaction is carried out in the presence of an acid; more preferably, the acid is selected from at least one of sulfuric acid or Lewis acid.
8. The preparation method according to claim 7, characterized in that, The preparation method of the compound VI comprises the following steps: after compound IV is reacted with a chloroformate compound IV-a to obtain compound V, compound V is first ring-formed and then subjected to a methylation reaction to obtain compound VI, or compound V is ring-formed with V-a2 to obtain compound VI; the reaction formula is as follows: Wherein, R1 is selected from alkyl or aryl, and R2 is selected from alkyl or aryl; the aforementioned "aryl" is optionally replaced by at least one group selected from hydroxyl, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkylthio or alkylsulfonyl. Preferably, R1 is selected from C1-C8 alkyl or aryl, and R2 is selected from C1-C8 alkyl or aryl; the aforementioned "aryl" is optionally substituted by at least one group selected from hydroxyl, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, C1-C8 alkoxy, halo-C1-C8 alkoxy, C1-C8 alkoxy carbonyl, C1-C8 alkylthio or C1-C8 alkylsulfonyl. More preferably, R1 is selected from C1-C4 alkyl or phenyl, and R2 is selected from methyl, ethyl, isopropyl or phenyl; the aforementioned "phenyl" is optionally substituted by at least one group selected from hydroxyl, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, C1-C6 alkoxy carbonyl, C1-C6 alkylthio or C1-C6 alkylsulfonyl. Preferably, the reaction for preparing compound V is carried out in the presence of a solvent; more preferably, the solvent is selected from at least one of acetonitrile, tetrahydrofuran, ethyl acetate, dichloromethane, 1,2-dichloroethane, toluene, xylene, chlorobenzene, or dichlorobenzene. Preferably, the cyclization reaction is carried out in the presence of a solvent and a base; more preferably, the solvent is selected from at least one of acetonitrile, tetrahydrofuran, toluene, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolinone, sulfolane, or N-methylpyrrolidone; and / or the base is selected from at least one of an inorganic base or an organic base; And / or preferably, the reagent required for the methylation reaction is selected from at least one of iodomethane, chloromethane, bromomethane, dimethyl sulfate, or dimethyl carbonate.
9. The production method according to claim 8, characterized by, The compound IV is obtained from the compound III by hydrogenation reaction, and the reaction formula is as follows: Preferably, the hydrogenation reaction is carried out in the presence of a catalyst, a solvent, and an anti-dehalogenation agent; more preferably, the catalyst is selected from at least one of palladium on carbon, platinum on carbon, Raney nickel, sodium hydrosulfite, ferric chloride, copper powder, or iron powder, the solvent is an alcohol, and / or the anti-dehalogenation agent is zinc bromide or dicyandiamide.
10. The method of claim 9, wherein, The compound III is obtained by nitration of compound II with nitric acid, and the reaction formula is as follows: Preferably, the nitration reaction is carried out in the presence of a solvent and a catalyst; more preferably, the solvent is selected from at least one of dichloromethane, dichloroethane, chloroform, water, acetic acid, or trifluoroacetic acid; and / or the catalyst is selected from at least one of concentrated sulfuric acid, acetic anhydride, or trifluoroacetic anhydride.
11. The method of claim 10, wherein, The compound II is obtained from compound I by chlorination reaction, and the reaction formula is as follows: Preferably, the chlorination reaction is carried out in the presence of a chlorinating agent; more preferably, a catalyst is added during the reaction; even more preferably, the chlorinating agent is selected from at least one of chlorine gas or hydrogen peroxide / concentrated hydrochloric acid; and / or the catalyst is selected from at least one of azobisisobutyronitrile, benzoyl peroxide, m-chloroperoxybenzoic acid or tert-butanol peroxide.
12. The method of any one of claims 2-11, wherein, The imino aryl compound has R configuration at the carbon atom, and the reaction formula is as follows: