Preparation method of 3-amino-2-fluorobenzoyl halide

Abstract

The invention discloses a preparation method of 3-amino-2-fluorobenzoyl halide (formula V). The method comprises two routes: a route I and # imgabs 0 # or a route II and # imgabs 1 #, wherein R, R1 and R2 are defined in the specification.

Description

Technical Field

[0001] The invention relates to the field of chemical synthesis, and in particular to a method for preparing 3-amino-2-fluorobenzoyl halide. Background Art

[0002] Isophthalamide insecticides were also discovered accidentally during the research of diamide insecticides. Their characteristic structures are similar to those of diamide insecticides, but their mechanisms of action are different (thus they are often classified as diamide insecticides). Currently, two varieties, bromofenac (codenamed MCI-8007 and MIE-1209FL) and cyprofenac (codenamed CAC-I-785), have been developed. Among them, bromofenac is the first isophthalamide insecticide obtained by Mitsui Agrochemicals (Mitsui) of Japan through structural optimization of flubendiamide lead compounds. It can be used for public health and the control of pests such as flies, termites, ants, cockroaches, armyworms, cotton bollworms, fall armyworms, cabbage borers, diamondback moths and yellow flea beetles in crops such as vegetables, beans and potatoes. BASF first obtained the sanitary insecticide registration of this product in Australia in 2019, and subsequently obtained pesticide registration in China, Japan and other countries, while registration in the United States, Brazil, Canada, Mexico, India and Australia is also in progress. Ciprofloxacin is an independently developed variety obtained by introducing cyclopropyl methyl into the lead compound bromiclanthamide. It has high insecticidal activity against sensitive and resistant lepidopteran pests of crops such as rice, corn, cotton, soybeans, fruit trees and vegetables. At present, this variety has become a blockbuster product of strategic cooperation with Syngenta, and pesticide registration in China is also in progress. Isophthalamide insecticides have good rapidity and persistence, and have no cross-resistance to existing varieties. They have become a hot spot in current research and development and have very broad market prospects. The chemical structures of bromiclanthamide and ciprofloxacin are as follows:

[0003]

[0004] 3-Amino-2-fluorobenzoyl halide is an important intermediate for the synthesis of bromobenzene and cyprodinil. In the prior art, 3-amino-2-fluorobenzoyl halide is mainly prepared by reacting an acid in thionyl chloride. The specific methods for preparing 3-amino-2-fluorobenzoic acid mainly include: 1) 2-fluoro-3-chloroaniline is hydrolyzed with sodium cyanide to obtain the target product, refer to WO202170124; this method has expensive raw materials, uses highly toxic sodium cyanide, and has harsh operating conditions, which is not suitable for industry Chemical production; 2) 2-fluorotoluene is nitrated, oxidized, and reductively dehalogenated to obtain the target product, refer to WO2009137391; this method has poor nitration selectivity, and the oxidizing reagent potassium permanganate has a high risk factor and serious environmental pollution, which is not suitable for large-scale production processes; 3) 2,6-dichlorobenzoic acid is nitrated, fluorinated and dehalogenated to prepare the target product, refer to CN111320548A; this method has poor fluorination selectivity, isomer impurities are difficult to remove, resulting in high costs, and is not suitable for industrial production.

[0005] In summary, the existing methods have the disadvantages of high cost, harsh production environment, and unsuitability for industrial production when preparing intermediates. Summary of the invention

[0006] Aiming at various defects in the synthesis of 3-amino-2-fluorobenzoyl halide compounds in the prior art, the present invention provides a method for preparing 3-amino-2-fluorobenzoyl chloride and its derivatives, which solves the problems in the prior art process.

[0007] The present invention discloses a method for preparing a compound of formula V, and the synthetic route thereof is as follows:

[0008]

[0009] Wherein, R1 is selected from chlorine, bromine or iodine; R is selected from fluorine and chlorine.

[0010] The present invention also provides a preparation method of formula III-a, and its synthetic route is as follows:

[0011] Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine.

[0012] The present invention also provides another method for preparing the compound of formula V, and the synthetic route thereof is as follows:

[0013]

[0014] Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine; R is selected from fluorine and chlorine.

[0015] The present invention also provides a preparation method of formula III-b, and its synthetic route is as follows:

[0016] Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine; R is selected from fluorine and chlorine.

[0017] The present invention also provides the following compounds:

[0018] Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine.

[0019] Beneficial Effects

[0020] The route used in the method provided by the present invention is firstly a new route with low raw material cost, less three wastes and high reaction yield; secondly, the acylation reaction in the reaction process realizes the green industrial use between acid and acyl chloride; thirdly, a new intermediate compound is synthesized in the synthesis process of the new route, which improves the competitiveness of the product and overcomes the problems of low yield and difficulty in removing isomeric impurities in the fluorination process. DETAILED DESCRIPTION

[0021] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0022] The specific embodiments of the present invention are described in detail below. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0023] In the present invention, the organic acid includes a monoprotic acid or a diprotic acid, and the exemplified organic acid is Q-COOH, QCOOH QCOOH or T-SO3H. Wherein, when it is a diprotic acid, Q can be the same or different, Q is an optionally substituted alkyl, an optionally substituted aryl, or an optionally substituted heteroaryl, and T is a substituted alkyl, an optionally substituted aryl, or an optionally substituted heteroaryl. Preferably, the organic acid is selected from at least one of formic acid, acetic acid, propionic acid, oxalic acid, benzoic acid, methanesulfonic acid, and p-toluenesulfonic acid, and oxalic acid is particularly preferred.

[0024] In the present invention, C n -C m The subscripts n and m in each case indicate the number of carbon atoms in the group. For example, C1-C6 means containing 1 to 6 carbon atoms. The alkyl group appearing in the definition of the substituent may be straight-chain or branched, preferably C1-C6 alkyl, such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, sec-butyl, isobutyl or tert-butyl.

[0025] In the present invention, halogen means fluorine, chlorine, bromine and iodine.

[0026] The aryl group in the present invention refers to a monovalent monocyclic or bicyclic aromatic hydrocarbon group of 6 to 10 ring atoms, such as phenyl or naphthyl, but is not limited thereto.

[0027] In the present invention, heteroaryl refers to a 5- to 10-membered aromatic monocyclic ring or an aromatic condensed ring, wherein the aromatic monocyclic ring contains one or more (e.g., 1 to 4, or in some embodiments, 1 to 3) heteroatoms selected from N, O and S and the remaining atoms are carbon; an aromatic condensed ring, which contains one or more (e.g., 1 to 4, or in some embodiments, 1 to 3) heteroatoms selected from N, O and S and the remaining ring atoms are carbon, and at least one heteroatom is present in the aromatic ring. For example, heteroaryl includes a 5- to 10-membered heterocycloalkyl aromatic ring fused to a 5- to 10-membered cycloalkyl or heterocycloalkyl ring. For the fused, bicyclic heteroaromatic ring system in which only one ring contains one or more heteroatoms, the connection point can be on either ring. When the total number of S and O atoms in the heteroaryl group exceeds 1, these heteroatoms are not adjacent to each other. In some embodiments, the total number of S and O atoms in the heteroaryl group does not exceed 2. In some embodiments, the total number of S and O atoms in the aromatic heterocycle does not exceed 1. Examples of heteroaryl groups include, but are not limited to (numbering from the attachment position as 1), 2-pyridyl, 3-pyridyl, 4-pyridyl, 2,3-pyridazinyl, 3,4-pyridazinyl, 2,4-pyrimidinyl, 3,5-pyrimidinyl, 2,3-pyrazolinyl, 2,4-imidazolinyl, isoxazolinyl, oxazolinyl, thiazolinyl, thiadiazolinyl, tetrazolyl, thienyl, benzothiophenyl, furanyl, benzofuranyl, benzimidazolinyl, indolyl, pyrazinyl, triazolyl, quinolinyl, pyrazolyl, and 5,6,7,8-tetrahydroisoquinolinyl. Divalent radicals derived from a monovalent heteroaryl radical whose name ends in "radical" by removing a hydrogen atom from a carbon with a free valence are named by adding "sub" to the name of the corresponding monovalent radical, such as a pyridyl radical with two points of attachment is a pyridylene radical. Heteroaryl does not encompass or overlap with aryl, cycloalkyl, or heterocycloalkyl, which are defined herein.

[0028] In the present invention, optionally substituted means that it may be substituted or unsubstituted. When substituted, the substituent may be alkyl, halogen, hydroxyl, nitro, cyano, etc., but is not limited thereto.

[0029] The present invention first provides a method for preparing a compound of formula V, and the synthetic route thereof is as follows:

[0030]

[0031] Wherein, R1 is selected from chlorine, bromine or iodine; R is selected from fluorine and chlorine.

[0032] In the above preparation method, formula III-a reacts under the action of a reducing and dehalogenating agent to generate a compound of formula IV-a. The reducing and dehalogenating agent is hydrogen, and the reaction temperature of formula III-a under the action of the reducing and dehalogenating agent is 30-100°C, preferably 40-60°C; the hydrogen pressure is 1-3MPa, preferably 1.5-1.8MPa, and the catalyst is preferably added to the reaction of the formula III-a under the action of the reducing and dehalogenating agent, and the catalyst is preferably palladium carbon or Raney nickel, more preferably palladium carbon. In the process of generating the compound of formula IV-a from the formula III-a under the action of the reducing and dehalogenating agent, an acid binding agent is preferably added, and the acid binding agent is selected from an organic base or an inorganic base. The organic base or inorganic base is at least one of triethylamine, pyridine, potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen, sodium acetate, sodium methoxide and sodium ethoxide; preferably triethylamine and / or potassium carbonate. The molar ratio of the compound III-a, the catalyst and the acidifying agent is 1:0.02-0.05:1.0-1.5. Preferably, the reaction is carried out in an organic solvent, and the organic solvent is preferably an alcohol or ether solvent, the alcohol solvent is preferably methanol and ethanol, and the ether solvent is preferably tetrahydrofuran and dioxane.

[0033] Preferably, the compound of formula IV-a undergoes an acylation reaction with an organic acid under the catalysis of a Lewis acid; the Lewis acid is ferric chloride, zinc chloride, aluminum chloride, preferably ferric chloride; the reaction temperature is -20-100°C, preferably 5-25°C; the organic acid is preferably at least one of formic acid, acetic acid, propionic acid, oxalic acid, benzoic acid, methanesulfonic acid, and p-toluenesulfonic acid, particularly preferably oxalic acid; the molar ratio of the compound of formula IV-a to the organic acid is 1:1.0-2.5. Preferably, the acylation reaction of the compound of formula IV-a with an organic acid under the catalysis of a Lewis acid is carried out in an organic solvent or without a solvent, and the organic solvent is a halogenated alkane or a benzene solvent, preferably dichloromethane, dichloroethane and chloroform.

[0034] In the above preparation method, the synthesis of formula III-a can adopt the following synthetic route:

[0035] Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine.

[0036] In the above preparation method, the compound of formula I is nitrated with a nitrating agent to generate a compound of formula II. The nitration reaction temperature is -20-30°C, preferably -5-5°C; the nitration time is 2-6h, preferably 3-4h; the nitration agent is nitric acid, preferably concentrated nitric acid with a concentration of 65-68wt%, and the molar ratio of the compound of formula I to nitric acid is 1:1-1.5, preferably 1:1.1-1.2. Preferably, the nitration reaction is carried out in an organic solvent, and the organic solvent is preferably a halogenated alkane, and more preferably one of dichloromethane, dichloroethane and chloroform.

[0037] In the above preparation method, the compound of formula II is subjected to fluorination reaction to generate compound III-a, and the fluorination reaction is carried out under solvent conditions, the reaction temperature is 60°C to 260°C, preferably 80°C to 140°C; the reaction time is 6-12h, preferably 8-10h. The fluorinating agent is selected from potassium fluoride, and the molar ratio of compound II to the fluorinating agent is 1:(1-2.5). The solvent is preferably one or a combination of two of DMF, DMAC, NMP, toluene, xylene and cyclohexane.

[0038] The present invention also provides a method for preparing a compound of formula V, and the synthetic route thereof is as follows:

[0039]

[0040] Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine; R is selected from fluorine and chlorine.

[0041] In the above preparation method, the compound of formula III-b is fluorinated with a fluorinating agent to generate a compound IV-b, and the fluorination reaction is carried out under solvent conditions, the reaction temperature is 60°C to 260°C, preferably 80°C to 140°C; the reaction time is 6-12h, preferably 8-10h. The fluorinating agent is selected from potassium fluoride, and the molar ratio of compound II to the fluorinating agent is 1: (1-2.5). The solvent is preferably one or a combination of two of DMF, DMAC, NMP, toluene, xylene and cyclohexane.

[0042] In the above preparation method, formula IV-b reacts under the action of a reducing and dehalogenating agent to generate a compound of formula V, the reducing and dehalogenating agent is hydrogen, and the reaction temperature of formula IV-b under the action of a reducing and dehalogenating agent is 30-100°C, preferably 40-60°C; the hydrogen pressure is 1-3MPa, preferably 1.5-1.8MPa. Preferably, a catalyst is added during the reaction of formula IV-b under the action of a reducing and dehalogenating agent, and the catalyst is selected from palladium carbon or Raney nickel, more preferably palladium carbon. Preferably, an acid binding agent is preferably added during the reaction of formula IV-b under the action of a reducing and dehalogenating agent to generate a compound of formula V, and the acid binding agent is selected from an organic base or an inorganic base. The organic base is at least one of triethylamine, pyridine, potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen, sodium methoxide, sodium acetate, and sodium ethoxide; preferably triethylamine and / or potassium carbonate. The molar ratio of the compound III-a, the catalyst and the acidifying agent is 1:0.02-0.05:1.0-1.5. Preferably, the reaction is carried out in an organic solvent, and the organic solvent is preferably an alcohol or ether solvent, the alcohol solvent is preferably methanol and ethanol, and the ether solvent is preferably tetrahydrofuran and dioxane.

[0043] The synthesis method of formula III-b in the above preparation method of the present invention can adopt the following synthesis route:

[0044] Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine; R is selected from fluorine and chlorine.

[0045] In the above synthetic route, the compound of formula I is subjected to a nitration reaction with a nitrating agent to generate a compound of formula II, the nitration reaction temperature is -20-30°C, preferably -5-5°C; the nitration time is 2-6h, preferably 3-4h; the nitration agent is nitric acid, preferably concentrated nitric acid with a concentration of 65-68wt%, and the molar ratio of the compound of formula I to nitric acid is 1:1-1.5, preferably 1:1.1-1.2. Preferably, the nitration reaction is carried out in an organic solvent, and the organic solvent is preferably a halogenated alkane, more preferably one of dichloromethane, dichloroethane and chloroform.

[0046] Preferably, in the above synthetic route, the compound of formula II undergoes an acylation reaction with an organic acid under the catalysis of a Lewis acid; the Lewis acid is ferric chloride, zinc chloride, aluminum chloride, preferably ferric chloride; the reaction temperature is -20-100°C, preferably 5-25°C; the organic acid is an organic acid, preferably at least one of formic acid, acetic acid, propionic acid, oxalic acid, benzoic acid, methanesulfonic acid, and p-toluenesulfonic acid, particularly preferably oxalic acid; the molar ratio of the compound of formula II to the organic acid is 1:1.0-2.5. Preferably, the acylation reaction is carried out in an organic solvent or without a solvent, and the organic solvent is a halogenated alkane or a benzene solvent, preferably dichloromethane or dichloroethane.

[0047] The present invention discloses the following compounds,

[0048] Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine. The route for preparing the product of the present invention through the above compounds is more optimal and has better effect, and can overcome the problem of poor selectivity of fluorination reaction in the prior art.

[0049] The present invention will be described in detail below by way of examples. In the following examples:

[0050] The amounts of reactants and products were measured by liquid chromatography (Agilent HPLC1260).

[0051] The conversion and selectivity of the reaction were calculated by the following formula:

[0052] Conversion rate = (molar amount of raw material input - molar amount of raw material remaining in the product) / molar amount of raw material input × 100%.

[0053] Selectivity = actual molar amount of target product / theoretical molar amount of target product × 100%

[0054] Yield = actual mass of target product / theoretical mass of target product × 100%

[0055] Unless otherwise specified, all raw materials used were commercially available products.

[0056] Example 1

[0057] In a four-necked bottle equipped with a mechanical stirrer, a thermometer, and a condenser, add 26g of dichloroethane and 26.4g of 2,5-dichlorotrichlorotoluene (0.1mol, 99%, purchased from Aladdin), keep warm at 0°C, drop 11.6g of 65% nitric acid for nitration, stir and react for 3h, HPLC detects that the raw materials are complete, add dichloroethane and water for extraction, then add alkali solution to adjust the pH to neutral, separate the liquids, separate the water and desolventize, and obtain 29.6g of the compound 3-nitro-2,5-dichloro-trichlorotoluene, with a yield of 96%;

[0058] The NMR data are as follows: 1 HNMR(500MHz,DMSO-d6)δ8.01(1H,s,ArH),7.98(1H,s,ArH);

[0059] The 3-nitro-2,5-dichloro-trichlorotoluene obtained in the previous step was added to a four-necked bottle, and 81 g of DMF and 10 g of xylene and 8.4 g of potassium fluoride were added. The mixture was kept at 90°C for 9 h. After the reaction of the raw materials was completed, the mixture was cooled to room temperature, the salt was filtered out, and the solvent was removed to obtain the compound 3-nitro-2-fluoro-5-chloro-trichlorotoluene, with a yield of 90%.

[0060] The NMR data are as follows: 1 H NMR(500MHz,DMSO-d6)δ8.22(1H,s,ArH),7.80(1H,s,ArH);

[0061] Then the crude product 3-nitro-2-fluoro-5-chloro-trichlorotoluene was added to the autoclave, and 76 g methanol, 0.5 g palladium carbon, and 17.8 g potassium carbonate were added. The autoclave was kept at 50°C and filled with 1.5 MPa of hydrogen. The reaction was continued for 5 h. HPLC detected that the raw material was complete. The solvent was removed by filtration to obtain 18.6 g of the compound 3-amino-2-fluorotrichlorotoluene, with a yield of 94.5%.

[0062] The NMR data are as follows: 1 H NMR(500MHz,DMSO-d6)δ7.89(2H,m,ArH),7.67(1H,dd,J=7.9Hz,1.4Hz,ArH),5.27(2H,s,N H 2);

[0063] Then add all the 3-amino-2-fluorotrichlorotoluene obtained in the previous step into a four-necked bottle, add 60g of dichloroethane and 1g of ferric chloride, keep warm at 5°C, add 11.0g of oxalic acid in batches, react for 2h, wait for the reaction of the raw materials, desolventize and recover the by-product oxalyl chloride, and obtain 12.7g of the compound 3-amino-2-fluorobenzoyl chloride, with a yield of 90%;

[0064] Example 2

[0065] The difference from Example 1 is that the compound 2-chloro-5-bromo-trichlorotoluene is used to replace 2,5-dichloro-trichlorotoluene, and the other molar ratios remain unchanged. The reaction produces 13.2 g of the compound 3-amino-2-fluorobenzoyl chloride with a total yield of 76%.

[0066] Example 3

[0067] The synthesized compound 3-nitro-2,5-dichlorotrichlorotoluene (0.96 mol) was added into a four-necked bottle, and 60 g of ethylene dichloride and 1 g of ferric chloride were added. The temperature was kept at 5°C, and 9.5 g of oxalic acid was added in batches. The reaction was continued for 2 h. After the reaction of the raw materials was completed, the by-product oxalyl chloride was recovered by desolventization to obtain 22.5 g of the compound 3-nitro-2,5-dichlorobenzoyl chloride, with a yield of 92%.

[0068] Then add 60g xylene and 10.8g potassium fluoride, separate water and keep warm at 140℃ for 9h. After the raw materials react, cool to room temperature and filter out the salt. After removing the solvent, transfer to an autoclave, add 65g methanol, 0.6g palladium carbon, and 13.1g potassium carbonate to the autoclave, keep warm at 60℃, fill with hydrogen at 1.8MPa, and react for 8h. HPLC detects that the raw materials are complete, filter and remove the solvent to obtain 11.5g of compound 3-amino-2-fluorobenzoyl fluoride, with a two-step yield of 83%;

[0069] Example 4

[0070] The difference from Example 3 is that acetic acid replaces oxalic acid, and the other molar ratios remain unchanged. The reaction produces 18.3 g of compound 3-nitro-2,5-dichlorobenzoyl chloride with a yield of 75%;

[0071] Example 5

[0072] The difference from Example 3 is that oxalic acid is replaced by benzoic acid, and the other molar ratios remain unchanged. The reaction produces 21.7 g of compound 3-nitro-2,5-dichlorobenzoyl chloride with a yield of 89%;

[0073] Example 6

[0074] The difference from Example 3 is that aluminum chloride replaces ferric chloride, and the other molar ratios remain unchanged. The reaction produces 15.1 g of compound 3-nitro-2,5-dichlorobenzoyl chloride with a yield of 62%;

[0075] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A method for preparing 3-amino-2-fluorobenzoyl halide (Formula V), characterized in that: Its synthetic route is as follows: Wherein, R1 is selected from chlorine, bromine or iodine; R is selected from fluorine and chlorine.

2. The preparation method according to claim 1, characterized in that: The compound of formula III-a is reacted under the action of a reducing and dehalogenating agent to generate a compound of formula IV-a.

3. The preparation method according to claim 2, characterized in that: The reducing and dehalogenating agent is hydrogen. Preferably, a catalyst and an acid-binding agent are added during the reaction of formula III-a under the action of the reducing and dehalogenating agent to generate a compound of formula IV-a. The catalyst is selected from palladium carbon or Raney nickel; the acid-binding agent is an organic base or an inorganic base.

4. The preparation method according to claim 1, characterized in that: The compound of formula IV-a undergoes acylation reaction with an organic acid under the catalysis of a Lewis acid to prepare a compound of formula V.

5. The preparation method according to claim 1, characterized in that: The synthetic route of formula III-a is as follows: Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine.

6. The preparation method according to claim 5, characterized in that: The compound of formula I is subjected to a nitration reaction with a nitrating agent to generate a compound of formula II.

7. The preparation method according to claim 5, characterized in that: The compound of formula II is subjected to fluorination reaction with a fluorination agent to generate compound III-a.

8. A method for preparing a 3-amino-2-fluorobenzoyl halide (Formula V) compound, characterized in that: Its synthetic route is as follows: Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine; R is selected from fluorine and chlorine.

9. The preparation method according to claim 8, characterized in that: The compound of formula III-b is fluorinated with a fluorination agent to generate a compound of formula IV-b.

10. The preparation method according to claim 8, characterized in that: Formula IV-b reacts under the action of a reducing and dehalogenating agent to generate a compound of formula V, wherein the reducing and dehalogenating agent is hydrogen. Preferably, a catalyst and an acid-binding agent are added during the reaction of formula IV-b under the action of a reducing and dehalogenating agent to generate a compound of formula V, wherein the catalyst is selected from palladium carbon or Raney nickel; and the acid-binding agent is an organic base or an inorganic base.

11. The preparation method according to claim 8, characterized in that: The synthetic route of formula III-b is as follows: Wherein, R1 and R2 are independently selected from chlorine, bromine or iodine; R is selected from fluorine and chlorine.

12. The preparation method according to claim 11, characterized in that: The compound of formula I is nitrated with a nitrating agent to generate a compound of formula II.

13. The preparation method according to claim 11, characterized in that: The compound of formula II undergoes acylation reaction with an organic acid under the catalysis of a Lewis acid to prepare a compound of formula III-b.

14. Compounds, in, R1 and R2 are independently selected from chlorine, bromine or iodine.

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