A process for the preparation of 2-nitro-3-methyl-5-chlorobenzoic acid

Abstract

The application discloses a preparation method of 2-nitro-3-methyl-5-chlorobenzoic acid, which comprises the following steps: step (1), 2-nitro-3,5-dichlorotoluene is reacted with a compound of formula I in the presence of an alkali to prepare a compound of formula II, and step (2), the compound of formula II is directly oxidized with an oxidant in the presence of an alkali to obtain 2-nitro-3-methyl-5-chlorobenzoic acid, and a synthetic route is as follows: wherein X and Y can be same or different and are selected from hydrogen, -NO2, -COOR, CN, -CONH2, R1-CO- and pyridyl, R and R1 are H or an alkyl group respectively, and the condition is that X and Y are not nitro, pyridyl or hydrogen at the same time. The method has the characteristics of mild reaction condition, high yield, high product purity and less reaction waste, is suitable for industrial production and has a wide application prospect.

Description

Technical Field

[0001] This invention relates to the field of pesticide intermediate preparation, specifically to a method for preparing 2-nitro-3-methyl-5-chlorobenzoic acid. Background Technology

[0002] 2-Amino-3-alkyl-5-chlorobenzoic acid is an important pharmaceutical intermediate. In particular, 2-amino-3-methyl-5-chlorobenzoic acid is an important intermediate in the preparation of chlorantraniliprole (Kangkuan).

[0003] Reference 1 (CN103058993B) reports a method for preparing 2-amino-3-methyl-5-chlorobenzoic acid, which includes the following route:

[0004] Route 1: Hydrogen peroxide is added dropwise to an aqueous sodium hydroxide solution containing 7-methylindole-2,3-dione to obtain 2-amino-3-methylbenzoic acid. Then, NCS is added to a DMF solution containing 2-amino-3-methylbenzoic acid, and the reaction mixture is heated to 100°C and reacted for 40 minutes to obtain 2-amino-3-methyl-5-chlorobenzoic acid. This method uses relatively expensive 7-methylindole-2,3-dione and NCS, resulting in high costs.

[0005] The reaction equation is as follows:

[0006]

[0007] Route 2: Chlorine gas is passed through a mixture of 7-methylindole-2,3-dione and chloroform, and the mixture is refluxed for 24 hours. The mixture is then placed in an ice bath to obtain 5-chloro-7-methylindole-2,3-dione. This 5-chloro-7-methylindole-2,3-dione is then added to a sodium hydroxide solution and stirred for half an hour. A mixture of hydrogen peroxide and sodium hydroxide aqueous solution is then added dropwise, and the reaction is allowed to proceed for 1.5 hours to obtain 2-amino-3-methyl-5-chlorobenzoic acid. This method has an excessively long reaction time, and the handling of chlorine gas requires high precision and carries safety risks.

[0008] The reaction equation is as follows:

[0009]

[0010] Route 3: Dissolve 7-methylindole-2,3-dione (3) in glacial acetic acid. The solution is wine red. Slowly add 2.5 to 3.5 times the amount of 7-methylindole-2,3-dione (preferably 3 times the amount of sulfonyl chloride), stir magnetically and heat. The solid slowly dissolves completely. Reflux for 3 hours, stop the reaction and cool to room temperature. Pour the reaction solution into crushed ice and let it stand for 1 hour. Extract, dry with anhydrous sodium sulfate, and rotary evaporate to obtain a brick red precipitate of 5-chloro-7-methylindole-2,3-dione (4). The obtained 5-chloro-7-methylindole-2,3-dione (4) was placed in a 10% potassium hydroxide solution and stirred for ten minutes to obtain a brownish-black solution. Hydrogen peroxide with a 30% concentration was added dropwise at room temperature, wherein the molar ratio of 5-chloro-7-methylindole-2,3-dione to hydrogen peroxide was 1:2.5–3 (preferably 1:3). Bubbles were produced, and the solution gradually turned beige. After stirring for another 30 minutes, the reaction solution was poured into a certain amount of ice water to cool. The pH of the solution was adjusted to 3–4 with hydrochloric acid, and the solid was obtained by filtration. After washing with cold water and drying, 2-amino-3-methyl-5-chlorobenzoic acid (5) was obtained. In this reaction route, 7-methylindole-2,3-dione is expensive, and the route is long and generates a large amount of waste.

[0011] The reaction equation is as follows:

[0012] .

[0013] Reference 2 (CN112778147B, 2022-10-11) discloses a method for preparing 2-amino-3-methyl-5-chlorobenzoic acid, comprising the following steps: mixing m-methylbenzoic acid and nitric acid to carry out a nitration reaction to obtain 2-nitro-3-methylbenzoic acid, wherein the mass concentration of the nitric acid is 60-75%; mixing the 2-nitro-3-methylbenzoic acid, a hydrogenation reduction reaction solvent, and a hydrogenation catalyst, and carrying out a hydrogenation reduction reaction in a hydrogen atmosphere to obtain 2-amino-3-methylbenzoic acid; mixing the 2-amino-3-methylbenzoic acid, a chlorination reagent, benzoic acid peroxide, and a chlorination reaction solvent, and carrying out a chlorination reaction to obtain 2-amino-3-methyl-5-chlorobenzoic acid.

[0014] The reaction equation is as follows:

[0015] .

[0016] This method faces the problem of selectivity in the nitration reaction and the resulting product separation problem. The chlorination reaction uses N-chlorosuccinimide or dichlorohydantoin as the chlorination reagent, and the yield of the chlorination reaction is only about 85%, resulting in a low overall yield and increased synthesis cost. Summary of the Invention

[0017] To address the deficiencies in the preparation of 2-amino-3-methyl-5-chlorobenzoic acid in the prior art, this invention provides a method for synthesizing 2-amino-3-methyl-5-chlorobenzoic acid, the reaction steps of which include reducing 2-nitro-3-methyl-5-chlorobenzoic acid with a reducing agent to obtain 2-amino-3-methyl-5-chlorobenzoic acid.

[0018] The preparation of 2-nitro-3-methyl-5-chlorobenzoic acid in this invention is carried out through the following steps:

[0019] Step (1): 2-Nitro-3,5-dichlorotoluene reacts with compound I in the presence of a base to prepare compound II.

[0020] Step (2): Compound II is directly oxidized with an oxidizing agent in the presence of a base to give 2-nitro-3-methyl-5-chlorobenzoic acid. The synthetic route is as follows:

[0021] ,

[0022] Wherein, X and Y can be the same or different, and are selected from hydrogen, alkyl, -NO2, -COOR, CN, -CONH2, R1-CO- and pyridyl, respectively, and R and R1 are H or alkyl, respectively.

[0023] The condition is that X and Y are not simultaneously alkyl, nitro, pyridyl, or hydrogen.

[0024] Beneficial effects of the invention

[0025] The present invention has a simple reaction step, high product yield, low waste during production, and is a green and environmentally friendly process suitable for industrial production. Detailed Implementation

[0026] The specific embodiments of the present invention will be further described in detail below with reference to examples. To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprising of," etc., will be understood to include the stated components and steps, without excluding the presence of other substances or steps.

[0027] Furthermore, to better illustrate the present invention, numerous specific details are provided in the following detailed embodiments.

[0028] Those skilled in the art will understand that the present invention can be practiced even without certain specific details. In some embodiments, materials, methods, and means well known to those skilled in the art are not described in detail in order to highlight the spirit of the invention.

[0029] Embodiments of the invention are described in detail below. However, these embodiments are exemplary, and the invention is not limited thereto; rather, the invention is defined by the scope of the claims.

[0030] In this invention, percentage content generally refers to weight percentage unless otherwise specified.

[0031] In this invention, unless otherwise specified, room temperature refers to approximately 20°C-25°C.

[0032] As used herein, unless otherwise specifically defined, the following terms used in the specification and claims have the following meanings.

[0033] The NCS described in this invention is N-chlorosuccinimide.

[0034] In this invention, DMF is N,N-dimethylformamide.

[0035] In this invention, the solvent dmac refers to N,N-dimethylacetamide.

[0036] In this invention, the solvent nmp refers to N-methylpyrrolidone.

[0037] In this invention, the base DBU refers to 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0038] In this invention, DMSO refers to dimethyl sulfoxide.

[0039] The term "alkyl" as used in this invention (and in other groups containing alkyl, such as the alkyl portion of an alkoxy group, the alkyl portion of an arylalkyl group) in each case generally means a straight-chain or branched alkyl group having 1-20 carbon atoms, often 1-6 carbon atoms, preferably 1-4 carbon atoms, and especially 1-3 carbon atoms. Examples of C1-C4 alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), and 1,1-dimethylethyl (tert-butyl). Examples of C1-C6 alkyl groups, in addition to those mentioned for C1-C4 alkyl groups, include n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl. C1-C 10 Examples of alkyl groups, in addition to those mentioned for C1-C6 alkyl groups, include n-heptyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 1-ethylhexyl, 2-ethylhexyl, 1,2-dimethylhexyl, 1-propylpentyl, 2-propylpentyl, nonyl, decyl, 2-propylheptyl, and 3-propylheptyl, but are not limited to these. Alkyl groups can be substituted with halogens, cyano, nitro, aryl, cycloalkyl, heterocyclic, amide, ester, etc., but are not limited to these.

[0040] In this invention, "alkali metals or alkaline earth metals" has the conventional meaning in the art. Alkali metal elements refer to the six metallic elements in Group IA of the periodic table, excluding hydrogen (H), including lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr); alkaline earth metals refer to elements in Group IIA of the periodic table, adjacent to Group IA where alkali metals are located, including beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).

[0041] Exemplary compounds of the present invention, namely "inorganic bases being hydroxides of alkali metals or alkaline earth metals", include potassium hydroxide and sodium hydroxide, but are not limited thereto.

[0042] Exemplary compounds of the present invention’s “alkali metal or alkaline earth metal carbonates” include sodium carbonate, potassium carbonate, and calcium carbonate, but are not limited thereto.

[0043] Exemplary compounds of the present invention’s “alkali metal or alkaline earth metal bicarbonates” include sodium bicarbonate, potassium bicarbonate and calcium bicarbonate, but are not limited thereto.

[0044] The "metal reducing agent" of this invention refers to a substance containing a metal element that can be used in a reduction reaction. Exemplary compounds include, but are not limited to, stannous chloride, potassium borohydride, sodium borohydride, etc.

[0045] This invention provides a method for preparing 2-nitro-3-methyl-5-chlorobenzoic acid, which includes the following steps:

[0046] Step (1): 2-Nitro-3,5-dichlorotoluene reacts with compound I in the presence of a base to prepare compound II.

[0047] Step (2): Compound II is directly oxidized with an oxidizing agent in the presence of a base to give 2-nitro-3-methyl-5-chlorobenzoic acid. The synthetic route is as follows:

[0048] ,

[0049] Wherein, X and Y can be the same or different, and are selected from hydrogen, -NO2, -COOR, CN, -CONH2, R1-CO- and pyridinyl, respectively, and R and R1 are H or alkyl groups, respectively.

[0050] The condition is that X and Y are not simultaneously nitro, pyridyl, or hydrogen.

[0051] Preferably, the alkyl group is a C1-C6 alkyl group, more preferably methyl or ethyl.

[0052] Preferably, the compound of formula I is one of nitromethane, dimethyl malonate, diethyl malonate, methyl cyanoacetate, ethyl cyanoacetate, isopropyl cyanoacetate, malondiamide, monomethyl malonate, monoethyl malonate, methyl pyridineacetate, ethyl pyridineacetate, isopropyl pyridineacetate, methyl acetoacetate, ethyl acetoacetate, methyl formylacetate, and ethyl formylacetate.

[0053] Preferably, the reaction in step (1) of the above preparation method can be carried out in an organic solvent, which is a polar solvent or a non-polar solvent, preferably one or more of DMF, dmac, nmp, DMSO, dichloroethane, acetonitrile, dioxane, toluene and xylene.

[0054] Preferably, the bases in steps (1) and (2) of the above preparation method can be the same or different, and the bases are inorganic or organic bases; the inorganic bases are hydroxides of alkali metals or alkaline earth metals, carbonates of alkali metals or alkaline earth metals, and bicarbonates of alkali metals or alkaline earth metals, preferably one or more of potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, potassium bicarbonate, and sodium bicarbonate, and particularly preferably potassium carbonate; the organic bases are preferably one or more of triethylamine, pyridine, and DBU.

[0055] Preferably, the reaction temperature of the above reaction step (1) is 20-200℃; more preferably 50-120℃.

[0056] In a preferred embodiment, in step (1) of the above preparation method, the amount of compound I relative to 1 mol of 2-nitro-3,5-dichlorotoluene is 1-3 mol, preferably 1-1.2 mol, and the amount of base is 1-3 mol, preferably 1-1.5 mol.

[0057] In the above preparation method, in step (2), the oxidant is a peroxide or oxygen. Preferably, the peroxide is one of hydrogen peroxide, sodium percarbonate and potassium percarbonate, and hydrogen peroxide is particularly preferred.

[0058] In a preferred embodiment, in the above preparation method, in step (2), the amount of oxidant used relative to 1 mol of 2-nitro-3,5-dichlorotoluene is 1-10 mol, preferably 1-3 mol, and the amount of alkali used is 1-3 mol, preferably 1-1.5 mol.

[0059] This invention also provides a method for preparing 2-amino-3-methyl-5-chlorobenzoic acid, comprising the following steps: reducing 2-nitro-3-methyl-5-chlorobenzoic acid to obtain 2-amino-3-methyl-5-chlorobenzoic acid, wherein the 2-nitro-3-methyl-5-chlorobenzoic acid is obtained according to the above-described preparation method of this invention. The reducing agent is a metal reducing agent or hydrogen gas.

[0060] In this invention, the base or salt used to provide alkaline conditions in each step may be the same or different.

[0061] In this invention, unless otherwise specified, room temperature refers to "25°C".

[0062] In this invention, the left and right ranges have a positive and negative error of ±5. For example, "around 25°C" can be expressed as a range between 20-30°C.

[0063] The present invention will be described in detail below through embodiments.

[0064] In the following examples, unless otherwise specified, all raw materials used are commercially available products.

[0065] The content (purity) of reactants and products was determined by liquid chromatography (Agilent HPLC 1260).

[0066] The conversion rate and selectivity of the reaction are calculated using the following formulas:

[0067] Conversion rate = (molar amount of raw material input - molar amount of raw material remaining in the product) / molar amount of raw material input × 100%.

[0068] Selectivity = (Actual molar amount of target product / Theoretical molar amount of target product) × 100%

[0069] Example 1

[0070]

[0071] In a four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.1 mol of 2-nitro-3,5-dichlorotoluene, 100 g of DMF, 0.12 mol of methyl cyanoacetate, and 0.12 mol of potassium carbonate were added. The mixture was reacted at 80-90°C for 3 hours. After the liquid phase analysis showed that the reaction was satisfactory, the mixture was cooled to room temperature, filtered, and the solvent was removed. Then, 100 g of dichloroethane and 0.1 mol of potassium carbonate were added, and the mixture was heated to about 80°C. 0.2 mol of hydrogen peroxide was added dropwise over 2 hours. The mixture was kept at this temperature for another 2 hours. After the liquid phase analysis showed that the reaction was complete, 100 g of water was added, and the mixture was allowed to stand and separate into layers. After the organic phase was removed, the target product was obtained with a yield of 90% (based on 2-nitro-3,5-dichlorotoluene).

[0072] Example 2

[0073]

[0074] In a four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.1 mol of 2-nitro-3,5-dichlorotoluene, 100 g of DMF, 0.12 mol of nitromethane, and 0.12 mol of potassium carbonate were added. The mixture was reacted at 80-90°C for 3 hours. After the liquid phase analysis showed that the reaction was satisfactory, the mixture was cooled to room temperature, filtered, and the solvent was removed. Then, 100 g of dichloroethane and 0.1 mol of potassium carbonate were added, and the mixture was heated to about 80°C. 0.2 mol of hydrogen peroxide was added dropwise over 2 hours. The mixture was then kept at this temperature for another 2 hours. After the liquid phase analysis showed that the reaction was complete, 100 g of water was added, and the mixture was allowed to stand and separate into layers. After the organic phase was removed, the target product was obtained with a yield of 88% (based on 2-nitro-3,5-dichlorotoluene).

[0075] Example 3

[0076]

[0077] In a four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.1 mol of 2-nitro-3,5-dichlorotoluene, 100 g of DMF, 0.12 mol of dimethyl malonate, and 0.12 mol of potassium carbonate were added. The mixture was reacted at 90-100℃ for 3 h. After the liquid phase analysis showed that the reaction was satisfactory, the mixture was cooled to room temperature, filtered, and the solvent was removed. Then, 100 g of dichloroethane and 0.12 mol of potassium carbonate were added, and the mixture was heated to about 80℃. 0.2 mol of hydrogen peroxide was added dropwise over 2 h. The mixture was then kept at this temperature for another 2 h. After the liquid phase analysis showed that the reaction was complete, 100 g of water was added, and the mixture was allowed to stand and separate into layers. After the organic phase was removed, the target product was obtained with a yield of 80% (calculated based on 2-nitro-3,5-dichlorotoluene).

[0078] Example 4

[0079]

[0080] In a four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.1 mol of 2-nitro-3,5-dichlorotoluene, 100 g of dichloroethane, 0.12 mol of ethyl cyanoacetate, and 0.12 mol of potassium carbonate were added. The mixture was reacted at 90-100℃ for 3 h. After the liquid phase analysis showed that the reaction was satisfactory, the mixture was cooled to room temperature, filtered, and the solvent was removed. Then, 100 g of dichloroethane and 0.12 mol of potassium carbonate were added, and the mixture was heated to about 80℃. 0.3 mol of hydrogen peroxide was added dropwise over 2 h. The mixture was then kept at this temperature for another 2 h. After the liquid phase analysis showed that the reaction was complete, 100 g of water was added, and the mixture was allowed to stand and separate into layers. After the organic phase was removed, the target product was obtained with a yield of 85% (calculated based on 2-nitro-3,5-dichlorotoluene).

[0081] Example 5

[0082]

[0083] In a four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.1 mol of 2-nitro-3,5-dichlorotoluene, 100 g of dichloroethane, 0.12 mol of ethyl cyanoacetate, and 0.12 mol of potassium carbonate were added. The mixture was reacted at 90-100℃ for 3 h. After the liquid phase analysis showed that the reaction was satisfactory, the mixture was cooled to room temperature, filtered, and the solvent was removed. Then, 100 g of dichloroethane and 0.12 mol of sodium carbonate were added, and the mixture was heated to about 80℃. 0.5 mol of hydrogen peroxide was added dropwise over 2 h. The mixture was then kept at this temperature for another 2 h. After the liquid phase analysis showed that the reaction was complete, 100 g of water was added, and the mixture was allowed to stand and separate into layers. After the organic phase was removed, the target product was obtained with a yield of 70% (based on 2-nitro-3,5-dichlorotoluene).

[0084] Example 6

[0085] 0.1 mol of 2-nitro-3-methyl-5-chlorobenzoic acid, 100 ml of methanol, and 1 g of nickel were added to a 250 ml autoclave. After the autoclave was assembled and purged with nitrogen three times, 2 kg of hydrogen was introduced. The mixture was heated to 60 °C and reacted for 4 h. After the liquid phase test showed that the reaction was qualified, the mixture was filtered, the catalyst was recovered and reused, and the mother liquor was desolventized to obtain 2-amino-3-methyl-5-chlorobenzoic acid with a yield of 95% and a purity of 98%.

[0086] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for preparing 2-nitro-3-methyl-5-chlorobenzoic acid, characterized in that, Includes the following steps, Step (1): 2-Nitro-3,5-dichlorotoluene reacts with compound I in the presence of a base to prepare compound II. Step (2): Compound II is directly oxidized with an oxidant in the presence of a base to give 2-nitro-3-methyl-5-chlorobenzoic acid. The synthetic route is as follows: ， Wherein, X and Y can be the same or different, and are selected from hydrogen, -NO2, -COOR, CN, -CONH2, R1-CO- and pyridinyl, respectively, and R and R1 are H or alkyl groups, respectively. The condition is that X and Y are not simultaneously nitro, pyridyl, or hydrogen.

2. The method according to claim 1, characterized in that, The reaction in step (1) can be carried out in an organic solvent, which can be a polar solvent or a non-polar solvent.

3. The method according to claim 2, characterized in that, The organic solvent is one or more of DMF, dmac, nmp, DMSO, dichloroethane, acetonitrile, dioxane, toluene, and xylene.

4. The preparation method according to any one of claims 1-3, characterized in that, The bases in steps (1) and (2) may be the same or different, and the bases may be inorganic or organic; the inorganic bases may be hydroxides of alkali metals or alkaline earth metals, carbonates of alkali metals or alkaline earth metals, bicarbonates of alkali metals or alkaline earth metals, and sodium hydrogen; the organic bases may be one or more of triethylamine, pyridine, and DBU.

5. The preparation method according to claim 4, characterized in that, The inorganic base is one or more of potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, potassium bicarbonate, and sodium bicarbonate.

6. The preparation method according to claim 5, characterized in that, The inorganic base mentioned is potassium carbonate.

7. The preparation method according to claim 1, characterized in that, The reaction temperature in step (1) is 20-200℃.

8. The preparation method according to claim 7, characterized in that, The reaction temperature in step (1) is 50-120℃.

9. The preparation method according to claim 1, characterized in that, In step (1), the amount of compound I used in the reaction is 1-3 mol relative to 1 mol of 2-nitro-3,5-dichlorotoluene, and the amount of base used is 1-3 mol.

10. The preparation method according to claim 9, characterized in that, In step (1), the amount of compound I used in the reaction is 1-1.2 mol relative to 1 mol of 2-nitro-3,5-dichlorotoluene, and the amount of base used is 1-1.5 mol.

11. The preparation method according to claim 1, characterized in that, In step (2), the oxidant is a peroxide or oxygen.

12. The preparation method according to claim 11, characterized in that, The peroxide is one of hydrogen peroxide, sodium percarbonate, and potassium percarbonate.

13. The preparation method according to claim 12, characterized in that, The peroxide mentioned is hydrogen peroxide.

14. The preparation method according to claim 11, characterized in that, In step (2), the amount of oxidant used is 1-10 mol relative to 1 mol 2-nitro-3,5-dichlorotoluene, and the amount of base used is 1-3 mol.

15. The preparation method according to claim 14, characterized in that, In step (2), the amount of oxidant used is 1-3 mol relative to 1 mol of 2-nitro-3,5-dichlorotoluene, and the amount of base used is 1-1.5 mol.

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