2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid compound and synthesis method thereof

Abstract

A 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid compound and a synthesis method thereof. The method comprises the following steps: introducing a nitro group on the benzene ring in the first reaction step, wherein no triazolinone ring structure is present in this reaction step; then reducing the compound to an amino group, etc., wherein no triazolinone ring structure is present in this reduction reaction step; and finally using the compound to form sulfentrazone containing a triazolinone ring structure. Using the intermediate to synthesize sulfentrazone avoids the problem of partial decomposition of the triazolinone ring, thereby reducing by-products and improving the synthesis yield of sulfentrazone. The specific structural formula of the compound is as follows: #imgabs0#

Description

Technical Field

[0001] The present invention relates to the technical field of synthesis of an important intermediate of sulfentrazone, and in particular to an intermediate for preparing sulfentrazone, namely, a 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid compound and a synthesis method thereof. Background Art

[0002] Sulfonamide, its chemical structure is as follows:

[0003]

[0004] It is a difluoromethyltriazolinone herbicide, and its chemical name is N-(2,4-dichloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide. Due to its good effect, many reports on its synthesis methods have been published, among which the most basic one is as follows:

[0005]

[0006] (Zhang Yuanyuan, Sun Yonghui, Shi Yueping, etc., Pesticides, 2013, 52(4), 260-262.); This method uses 2,4-dichloroaniline as raw material, and obtains the final sulfentrazone through the steps of diazotization, hydrazone formation, cyclization, N-difluoromethylation, nitration, reduction, and mesylation, with an overall yield of 26.8%. In addition, Liang Kai et al. also reported a method for synthesizing sulfentrazone using the same route (Liang Kai, Xu Gang, Yang Lirong, Wu Jianping, Chemical Reaction Engineering and Technology, 2012, 28(5), 412-417.), with an overall yield of 30.7%. In other documents such as CN103951627B, the preparation method of sulfentrazone is also disclosed, but the contents disclosed in these patent documents are all improvements to individual steps in the above-mentioned basic method for synthesizing sulfentrazone. However, these existing technologies inevitably first obtain the N-difluoromethyl substituted triazolinone ring—— This structure is then used as a basis for subsequent nitration and reduction reactions to obtain the final sulfentrazone. However, since the total yield of these two steps is only approximately 70%, the production cost of sulfentrazone using this technical solution is high. Furthermore, since the N-difluoromethyl-substituted triazolinone ring is unstable under certain conditions (possibly instability occurs under complex reaction conditions), the stability of this group limits the range of methods available for nitration and reduction of the benzene ring in the presence of the N-difluoromethyl-substituted triazolinone ring, hindering the continued improvement of this technical solution. Summary of the Invention

[0007] In view of the above-mentioned deficiencies in the prior art, the present invention provides an intermediate for synthesizing sulfentrazone: a 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid compound. The 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid is prepared by first introducing a nitro group on the benzene ring in the first step (no N-difluoromethyl substituted triazolinone ring structure is present in this step), then reducing it to an amino group (no N-difluoromethyl substituted triazolinone ring structure is present in this step), and then using it to finally form sulfentrazone containing an N-difluoromethyl substituted triazolinone ring structure. The intermediate is used to synthesize sulfentrazone, which can avoid the problem of the above-mentioned problems. The problem of a narrow range of reaction conditions due to the N-difluoromethyl-substituted triazolinone ring structure is avoided. Furthermore, the intermediate of the present application undergoes nitration and nitroreduction reactions on the benzene ring before the N-difluoromethyl-substituted triazolinone ring is formed, thereby reducing the production cost of sulfentrazone. Furthermore, since the nitration and nitroreduction reactions are performed on the benzene ring before the N-difluoromethyl-substituted triazolinone ring is formed, the instability of the N-difluoromethyl-substituted triazolinone ring need not be considered. Therefore, a wider range of methods can be selected without considering the impact of these methods on the N-difluoromethyl-substituted triazolinone ring, thereby facilitating the continuous improvement of sulfentrazone synthesis technology. Furthermore, the use of this intermediate in the synthesis of sulfentrazone can achieve higher yields than previously disclosed technical solutions.

[0008] In order to solve the above technical problems, the technical solution adopted by the present invention is: a 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid compound, the structure of which is:

[0009]

[0010] Furthermore, the present invention discloses a method for synthesizing the above-mentioned 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid compound, wherein the specific synthesis path of the method is as follows:

[0011]

[0012] Preferably, the synthesis method of the 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid compound mentioned above in the present application comprises the following specific synthesis steps:

[0013] (1) Add 2,4-dichloroaniline and concentrated sulfuric acid to a reaction vessel and cool in an ice-water bath; then add dropwise a mixture of concentrated sulfuric acid and concentrated nitric acid at 0°C or below, and continue the reaction at the same temperature after the addition is complete; after the reaction is complete, add the reaction mixture to an ice-water mixture, filter out the precipitate, and crystallize it in an isopropyl alcohol / water mixed solvent to obtain 2,4-dichloro-5-nitroaniline;

[0014] (2) adding 2,4-dichloro-5-nitroaniline prepared by the method of step (1) and a base to a reaction vessel containing a solvent and stirring uniformly; adding acetyl chloride dropwise to the reaction vessel at room temperature, and continuing the reaction at room temperature after the addition is complete; after the reaction is complete, adding the reaction mixture to ice water, separating the liquids, washing the solvent layer with saturated brine 2-4 times, then washing with water 1-2 times, drying over anhydrous sodium sulfate, filtering, removing the solvent, and crystallizing the resulting crude product in ethanol / water to obtain N-(2,4-dichloro-5-nitrophenyl)acetamide;

[0015] (3) Adding N-(2,4-dichloro-5-nitrophenyl)acetamide prepared by the method of step (2) and the material for nitro group reduction into a reaction vessel, stirring evenly and then slowly heating to 80-90° C. for reaction; after the reaction is completed, neutralizing the reaction mixture to pH = 7.5-8.5, extracting with ethyl acetate 2-5 times respectively, combining the ethyl acetate, drying over anhydrous sodium sulfate, filtering, removing the ethyl acetate, and crystallizing the resulting crude product in ethanol / water to obtain N-(5-amino-2,4-dichlorophenyl)acetamide;

[0016] (4) adding N-(5-amino-2,4-dichlorophenyl)acetamide prepared by the method of step (3) and concentrated hydrochloric acid to a reaction vessel, stirring for 0.5-1.5 hours, then cooling to below -10°C, adding dropwise a solution of sodium nitrite dissolved in water under nitrogen protection, and continuing the reaction at the same temperature for 1.5-2.5 hours after the addition is complete; adding stannous chloride in batches to the above reaction mixture at -10°C or below, stirring and reacting for 0.5-2 hours after the addition is complete, then heating to room temperature and continuing the reaction for 2-4 hours; adding saturated sodium hydroxide solution, adjusting to pH = 8-9, extracting, drying, filtering, and removing the extraction solvent to obtain N-(2,4-dichloro-5-hydrazinophenyl)acetamide;

[0017] (5) Adding N-(2,4-dichloro-5-hydrazinylphenyl)acetamide prepared by the method of step (4) and hydrochloric acid to a reaction vessel and stirring evenly at room temperature; adding dropwise a solution of pyruvic acid dissolved in water; continuing to stir the reaction for 20-40 minutes after the addition is complete, filtering to obtain a precipitate, and then rinsing the precipitate with ice water 2-5 times. The obtained solid is dried in a vacuum environment to obtain the target product 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid.

[0018] Preferably, the ratio of the amount of 2,4-dichloroaniline to concentrated sulfuric acid (the concentrated sulfuric acid here refers to the concentrated sulfuric acid added separately for the first time) added in step (1) is 0.1-0.2 mol:100 ml (i.e., 0.1-0.2 mol of 2,4-dichloroaniline is added for every 100 ml of concentrated sulfuric acid); and the volume ratio of concentrated sulfuric acid to concentrated nitric acid in the mixture of concentrated sulfuric acid and concentrated nitric acid is 9-12:1.

[0019] Preferably, the ratio of the amount of 2,4-dichloroaniline added to the mixture of concentrated sulfuric acid and concentrated nitric acid in step (1) is 0.2-0.25 mol:100 ml (i.e., 0.2-0.25 mol of 2,4-dichloroaniline is added to every 100 ml of the mixture of concentrated sulfuric acid and concentrated nitric acid).

[0020] Preferably, the molar ratio of 2,4-dichloro-5-nitroaniline to the base in step (2) is 1:2-3.

[0021] Preferably, the molar ratio of acetyl chloride to base in step (2) is 1:1.8-2.2.

[0022] Preferably, the solvent in step (2) is at least one organic solvent selected from dichloromethane, chloroform, and dichloroethane, and the base is one selected from triethylamine, pyridine, or diisopropylethylamine.

[0023] Preferably, the material for nitro reduction in step (3) is one of concentrated hydrochloric acid and stannous chloride, or Fe and acetic acid, or sodium sulfide or catalytic hydrogenation.

[0024] Further preferably, the materials for nitro reduction in step (3) are concentrated hydrochloric acid and stannous chloride, wherein the molar ratio of stannous chloride to N-(5-nitro-2,4-dichlorophenyl)acetamide is 2.5-3.5:1.

[0025] Preferably, the molar ratio of N-(5-amino-2,4-dichlorophenyl)acetamide to sodium nitrite and stannous chloride in step (4) is 1:1:2.5-3.5.

[0026] Preferably, the concentration of the hydrochloric acid in step (5) is 4-6 mol / l.

[0027] Preferably, the reaction ratio of N-(2,4-dichloro-5-hydrazinophenyl)acetamide and 4-6 mol / l hydrochloric acid in step (5) is: 0.15-0.3 mol: 100 ml.

[0028] Preferably, in the solution formed by pyruvic acid and water in step (5), the ratio of pyruvic acid to water is 0.15-0.3 mol:100 ml.

[0029] Advantages and beneficial effects of the present invention:

[0030] 1. This application provides a new intermediate for the preparation of sulfentrazone, the structure of which is as follows: This is the first time that this structure has been used as an intermediate in the synthesis of sulfentrazone, thus providing more options for the preparation of sulfentrazone.

[0031] 2. The present invention still uses 2,4-dichloroaniline as a starting material. However, unlike the prior art, the present invention directly uses 2,4-dichloroaniline as a starting material. In the first step, a nitro group is introduced into the benzene ring of the aniline by mixed acid nitration. The intermediate is then synthesized by reactions such as acetyl protection of the amino group, reduction of the nitro group by stannous chloride, diazotization, reduction of the diazo group, and hydrazone formation. These reactions are easy to carry out and do not change the starting materials of the prior art. The raw materials are cheap and readily available, the reaction conditions are mild, and the reaction yield is high. 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono) can be synthesized efficiently and economically. The intermediate propionic acid; and the present invention, in the first mixed acid step, does not contain an N-difluoromethyl-substituted triazolinone ring structure, but rather a 2,4-dichloroaniline structure. Therefore, when performing nitration and nitroreduction reactions on the benzene ring, the absence of an N-difluoromethyl-substituted triazolinone ring allows for a variety of benzene ring nitration and nitroreduction methods and conditions to be selected without having to consider the stability of the N-difluoromethyl-substituted triazolinone ring under these methods and conditions. This provides more options and development ideas for the development of more advanced sulfentrazone synthesis processes, which is of great significance to the synthesis of sulfentrazone. Furthermore, the use of this intermediate in the synthesis of sulfentrazone can achieve higher yields than previously disclosed technical solutions. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 H NMR spectrum of N-(2,4-dichloro-5-hydrazinophenyl)acetamide prepared in Example 1.

[0033] Figure 2 The carbon NMR spectrum of N-(2,4-dichloro-5-hydrazinophenyl)acetamide prepared in Example 1.

[0034] Figure 3 Mass spectrum of N-(2,4-dichloro-5-hydrazinophenyl)acetamide prepared in Example 1.

[0035] Figure 4 H NMR spectrum of 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid prepared in Example 1.

[0036] Figure 5 The carbon NMR spectrum of 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid prepared in Example 1.

[0037] Figure 6 Mass spectrum of 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid prepared in Example 1. DETAILED DESCRIPTION

[0038] The present invention is further described in detail below by way of examples, but the present invention is not limited to the following examples.

[0039] The specific amounts of each material used in the examples of this application are quantified by rounding; the raw materials are conventional raw materials or commercially available products unless otherwise specified. The intermediate structures involved in the following examples of this application are all materials synthesized in the previous step and used as starting materials for the next step; other conventional auxiliary materials are conventional commercially available chemical materials unless otherwise specified.

[0040] Example 1

[0041] 1. To a 500ml round-bottom flask, 64.80g (0.40mol) of 2,4-dichloroaniline and 300ml of concentrated sulfuric acid were added and cooled in an ice-water bath. A mixture of 160ml of concentrated sulfuric acid and 16ml of concentrated nitric acid was added dropwise at 0°C. After completion of the addition, the reaction was continued at the same temperature for 2 hours. The reaction mixture was then added to 1500ml of ice-water, the precipitate was filtered out, and crystallized from an isopropyl alcohol / water mixture (the volume ratio of the isopropyl alcohol / water mixture was 3:1, the same as in Example 2) to give 66.24g (0.32mol) of 2,4-dichloro-5-nitroaniline in an 80% yield.

[0042] 2. Add 200 ml of dichloromethane, 62.10 g (0.30 mol) of 2,4-dichloro-5-nitroaniline, and 66.79 g (0.66 mol) of triethylamine to a 500 ml round-bottom flask and stir until uniform. Add 86.35 g (0.33 mol) of acetyl chloride dropwise to the flask at room temperature. After the addition is complete, continue the reaction at room temperature for 5 hours. After completion of the reaction, the reaction mixture was added to 200 ml of ice water, the layers were separated, the dichloromethane layer was washed twice with 100 ml of saturated brine and once with 100 ml of water, dried over anhydrous sodium sulfate, filtered, and the dichloromethane was removed. The crude product was crystallized from ethanol / water (the volume ratio of ethanol / water was 2:1, the same as in Example 2) to obtain 70.97 g (0.285 mol) of N-(2,4-dichloro-5-nitrophenyl)acetamide (N-(5-nitro-2,4-dichlorophenyl)acetamide) with a yield of 95%.

[0043] 3. To a 500 ml round-bottom flask, 200 ml of concentrated hydrochloric acid, 113.77 g (0.6 mol) of stannous chloride, and 49.80 g (0.20 mol) of N-(5-nitro-2,4-dichlorophenyl)acetamide were added. The mixture was stirred evenly and then slowly heated to 85° C. for 8 hours. After completion of the reaction, the reaction mixture was neutralized with sodium hydroxide solution to a pH of 8 and extracted three times with 300 ml of ethyl acetate. The ethyl acetate was combined, dried over anhydrous sodium sulfate, filtered, and the ethyl acetate was removed. The resulting crude product was crystallized from ethanol / water (the volume ratio of ethanol / water was 3:1, the same as in Example 2) to obtain 42.05 g (0.192 mol) of N-(5-amino-2,4-dichlorophenyl)acetamide, with a yield of 96%.

[0044] 4. In a 1000ml round-bottomed flask, add N-(5-amino-2,4-dichlorophenyl) ethanamide 65.72 grams (0.30mol) and 200ml concentrated hydrochloric acid, stir and cool to-10 ℃ after 1 hour, drip the solution that sodium nitrite 20.7 grams (0.30mol) is dissolved in 120ml water under nitrogen protection, and continue reaction under the same temperature after dropwising for 2 hours. Under-10 ℃, 170.65 grams (0.90mol) of stannous chloride are joined in the above-mentioned reaction mixture in batches, add the back stirring reaction 1 hour, then be warmed up to room temperature and continue reaction for another 3 hours. Add saturated sodium hydroxide solution, be adjusted to pH=9, dichloromethane extraction (dichloromethane is as extraction solvent), anhydrous sodium sulfate drying, filter, remove after dichloromethane and obtain product N-(2,4-dichloro-5-hydrazinophenyl) ethanamide 56.16 grams (0.24mol), productive rate 80%.

[0045] The obtained product N-(2,4-dichloro-5-hydrazinophenyl)acetamide was detected by hydrogen spectrum and carbon spectrum: 1 H NMR (500 MHz, CDCl3) δ8.45 (1H, s, -NH-CO-), 7.95 (1H, s, -NH-NH2), 7.50 (1H, s, -C6H-), 7.23 (1H, s, -C6H-), 4.12 (2H, s, -NH2-), 2.23 (3H, s, -CH3CO-) (see Appendix for details) Figure 1 ).

[0046] 13 C NMR (500 MHz, CD3OD) δ170.60 (-CO-), 108.10~142.71 (-C6H2-), 22.08 (-CH3-) (see attached Figure 2 ).

[0047] ESI-MS C8H9Cl2N3O[M+HCOOH] +, calculated value: 279.02, found 279.10 (see attached Figure 3 ).

[0048] 5. 46.82 g (0.20 mol) of N-(2,4-dichloro-5-hydrazinylphenyl)acetamide and 100 ml of 5.0 mol / l hydrochloric acid were added to a 250 ml round-bottom flask and stirred at room temperature. A solution of 17.61 g (0.20 mol) of pyruvic acid dissolved in 100 ml of water was added dropwise, and the reaction mixture gradually became turbid during the addition. After the addition was complete, the reaction mixture was stirred for half an hour. The precipitate was filtered and rinsed three times with 70 ml of ice water. The resulting solid was vacuum-dried at 50°C to yield 54.72 g of 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid, with a yield of 90%.

[0049] As attached Figure 4-6 As shown, the obtained product 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid was subjected to spectrum detection:

[0050] 1 H NMR (500MHz, CDCl3) δ8.03 (s, 1H), 7.42 (s, 1H), 2.19 (s, 3H), 2.15 (s, 3H) ( Figure 4 1H spectrum).

[0051] 13 C NMR (500MHz, CD3OD) δ170.66, 154.09, 145.69, 139.50, 134.27, 128.92, 118.00, 114.26, 110.12, 21.98, 18.91 ( Figure 5 carbon spectrum).

[0052] ESI-MS C 11 H 11 Cl2N3O3[MH] - , calculated values: 303.0177, 305.0148, measured values: 302.0185, 304.0141( Figure 6 mass spectrometry).

[0053] The above examples show that the method of the present application indeed obtains a new intermediate for preparing sulfentrazone, and the yield of the intermediate is high (yield 90%). In addition, the use of this intermediate to synthesize sulfentrazone can avoid the risk of subsequent destabilization of the triazolinone ring under complex reaction conditions such as mixed acid and reduction, thereby reducing the production of by-products and thereby improving the synthesis yield of sulfentrazone.

[0054] Example 2

[0055] 1. Add 81.00 g (0.50 mol) of 2,4-dichloroaniline and 330 ml of concentrated sulfuric acid to a 500 ml round-bottom flask and cool in an ice-water bath. Add a mixture of 180 ml of concentrated sulfuric acid and 18 ml of concentrated nitric acid dropwise at 0°C. After the addition is complete, continue the reaction at the same temperature for 2 hours. Add the reaction mixture to 1600 ml of ice-water, filter the precipitate, and crystallize it from an isopropanol / water mixture to obtain 80.73 g (0.39 mol) of 2,4-dichloro-5-nitroaniline (78% yield).

[0056] 2. Add 220 ml of chloroform, 62.10 g (0.30 mol) of 2,4-dichloro-5-nitroaniline, and 54.51 g (0.69 mol) of pyridine to a 250 ml round-bottom flask and stir evenly at room temperature. Add 94.2 g (0.36 mol) of acetyl chloride dropwise to the flask at room temperature. After the addition is complete, continue the reaction at room temperature for 5 hours. After the reaction is complete, add the reaction mixture to 220 ml of ice water, separate the layers, wash the chloroform layer twice with 120 ml of saturated brine, then once with 120 ml of water, dry over anhydrous sodium sulfate, filter, remove the chloroform, and crystallize the resulting crude product in ethanol / water to obtain 70.22 g (0.282 mol) of N-(2,4-dichloro-5-nitrophenyl)acetamide (N-(5-nitro-2,4-dichlorophenyl)acetamide) with a yield of 94%.

[0057] 3. To a 500 ml round-bottom flask, add 230 ml of concentrated hydrochloric acid, 132.73 g (0.7 mol) of stannous chloride, and 56.03 g (0.225 mol) of N-(5-nitro-2,4-dichlorophenyl)acetamide. Stir thoroughly, then slowly heat to 85°C and react for 8.5 hours. After completion of the reaction, neutralize the reaction mixture with sodium hydroxide solution to pH 8 and extract three times with 320 ml of ethyl acetate, respectively. The ethyl acetate is combined, dried over anhydrous sodium sulfate, filtered, and the ethyl acetate removed. The resulting crude product is crystallized from ethanol / water to yield 46.87 g (0.214 mol) of N-(5-amino-2,4-dichlorophenyl)acetamide, in a yield of 95%.

[0058] 4. Add 76.65 g (0.35 mol) of N-(5-amino-2,4-dichlorophenyl)acetamide and 210 ml of concentrated hydrochloric acid to a 1000 ml round-bottom flask, stir for 1 hour, then cool to -10°C. Add 24.15 g (0.35 mol) of sodium nitrite dissolved in 125 ml of water dropwise under nitrogen. After the addition is complete, continue the reaction at the same temperature for 2 hours. Add 205.73 g (1.085 mol) of stannous chloride in batches to the reaction mixture at -10°C. After the addition is complete, stir and react for 1 hour, then warm to room temperature and continue the reaction for another 3 hours. Add saturated sodium hydroxide solution and adjust to pH = 9. Extract with dichloromethane, dry over anhydrous sodium sulfate, filter, and remove dichloromethane to obtain 66.46 g (0.284 mol) of N-(2,4-dichloro-5-hydrazinophenyl)acetamide, with a yield of 81%.

[0059] 5. Add 42.13 g (0.18 mol) of N-(2,4-dichloro-5-hydrazinylphenyl)acetamide and 120 ml of 4.8 mol / l hydrochloric acid to a 250 ml round-bottom flask and stir at room temperature. Add 15.85 g (0.18 mol) of pyruvic acid dissolved in 90 ml of water dropwise. The reaction mixture gradually becomes turbid during the addition. After the addition is complete, continue stirring for 25 minutes. Filter the precipitate and rinse it three times with 65 ml of ice water. Dry the resulting solid under vacuum at 50°C to obtain 48.97 g of 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid, with a yield of 89.5%.

[0060] The above examples show that the 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid of the present application, as an important intermediate for the synthesis of sulfentrazone, can effectively avoid the risk of ring instability that may exist when the triazolinone ring structure is subjected to strongly acidic reaction conditions such as mixed acid nitration during the synthesis of sulfentrazone; and the target product obtained by the method for synthesizing 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid of the present application has a high yield.

[0061] The intermediate used in the synthesis of sulfentrazone in the present application is a brand-new compound that has not appeared in the existing synthesis of sulfentrazone. The other intermediate structures before and after the intermediate involved in the present application are also brand-new intermediates for the synthesis of sulfentrazone. Each intermediate can be used as an important raw material for the synthesis of sulfentrazone. Therefore, it has very important protection significance for the applicant and provides more options for the synthesis route of sulfentrazone. More importantly, the intermediate of the present application and the other intermediates for the synthesis of sulfentrazone before and after the intermediate can achieve: when the nitration and nitroreduction reactions are carried out on the benzene ring, due to the absence of N-difluoromethyl substituted trifluoromethyl, the intermediate can be used as a new intermediate for the synthesis of sulfentrazone. Due to the presence of the oxazolinone ring, a variety of methods and conditions for nitration and nitro reduction of the benzene ring can be selected without considering the stability of the N-difluoromethyl-substituted triazolinone ring under these methods and conditions. This can provide more options and development ideas for the development of more advanced sulfentrazone synthesis processes, which is of great significance to the synthesis of sulfentrazone. The use of the intermediate structures of the present application or subsequent intermediates to synthesize sulfentrazone effectively improves the yield of the final target product and the yield and purity of other intermediates. Therefore, the applicant has applied for patent protection for various intermediates involved in the specific synthesis process of sulfentrazone in this application.

Claims

1. A method for synthesizing a 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid compound, characterized in that: The structure of this compound is: ； The specific synthetic route of this method is: ； The specific synthesis steps include: (1) Add 2,4-dichloroaniline and concentrated sulfuric acid to a reaction vessel and cool in an ice-water bath; then add dropwise a mixture of concentrated sulfuric acid and concentrated nitric acid at 0°C or below, and continue the reaction at the same temperature after the addition is complete; after the reaction is complete, add the reaction mixture to an ice-water mixture, filter out the precipitate, and crystallize it in an isopropyl alcohol / water mixed solvent to obtain 2,4-dichloro-5-nitroaniline; (2) adding 2,4-dichloro-5-nitroaniline prepared by the method of step (1) and a base to a reaction vessel containing a solvent and stirring uniformly; adding acetyl chloride dropwise to the reaction vessel at room temperature, and continuing the reaction at room temperature after the addition is complete; after the reaction is complete, adding the reaction mixture to ice water, separating the liquids, washing the solvent layer with saturated brine 2-4 times, then washing with water 1-2 times, drying over anhydrous sodium sulfate, filtering, removing the solvent, and crystallizing the resulting crude product in ethanol / water to obtain N-(2,4-dichloro-5-nitrophenyl)acetamide; (3) Adding N-(2,4-dichloro-5-nitrophenyl)acetamide prepared by the method of step (2) and the material for nitro group reduction into a reaction vessel, stirring evenly and then slowly heating to 80-90° C. for reaction; after the reaction is completed, neutralizing the reaction mixture to pH = 7.5-8.5, extracting with ethyl acetate 2-5 times respectively, combining the ethyl acetate, drying over anhydrous sodium sulfate, filtering, removing the ethyl acetate, and crystallizing the resulting crude product in ethanol / water to obtain N-(5-amino-2,4-dichlorophenyl)acetamide; (4) adding N-(5-amino-2,4-dichlorophenyl)acetamide prepared by the method of step (3) and concentrated hydrochloric acid to a reaction vessel, stirring for 0.5-1.5 hours, then cooling to below -10°C, adding dropwise a solution of sodium nitrite dissolved in water under nitrogen protection, and continuing the reaction at the same temperature for 1.5-2.5 hours after the addition is complete; adding stannous chloride in batches to the above reaction mixture at -10°C or below, stirring and reacting for 0.5-2 hours after the addition is complete, then heating to room temperature and continuing the reaction for 2-4 hours; adding saturated sodium hydroxide solution, adjusting to pH = 8-9, extracting, drying, filtering, and removing the extraction solvent to obtain N-(2,4-dichloro-5-hydrazinophenyl)acetamide; (5) Add N-(2,4-dichloro-5-hydrazinylphenyl)acetamide prepared by the method of step (4) and hydrochloric acid to a reaction vessel and stir evenly at room temperature; add dropwise a solution of pyruvic acid dissolved in water, continue stirring and reacting for 20-40 minutes after the addition is complete, and then filter to obtain a precipitate, and then rinse the precipitate with ice water 2-5 times. The obtained solid is dried in a vacuum environment to obtain the target product 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid.

2. The method for synthesizing 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid according to claim 1, wherein: The ratio of the addition amount of 2,4-dichloroaniline to concentrated sulfuric acid in step (1) is 0.1-0.2 mol:100 ml; and the volume ratio of concentrated sulfuric acid to concentrated nitric acid in the mixture of concentrated sulfuric acid and concentrated nitric acid is 9-12:

1.

3. The method for synthesizing 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid according to claim 1, wherein: The addition ratio of the mixture of 2,4-dichloroaniline, concentrated sulfuric acid and concentrated nitric acid in step (1) is 0.2-0.25 mol:100 ml.

4. The method for synthesizing 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid according to claim 1, wherein: The molar ratio of 2,4-dichloro-5-nitroaniline to the base in step (2) is 1:2-3; the molar ratio of acetyl chloride to the base in step (2) is 1:1.8-2.

2.

5. The method for synthesizing 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid according to claim 1, wherein: The solvent in step (2) is at least one organic solvent selected from dichloromethane, chloroform and dichloroethane, and the base is one selected from triethylamine, pyridine or diisopropylethylamine.

6. The method for synthesizing 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid according to claim 1, wherein: The material for nitro reduction in step (3) is one of concentrated hydrochloric acid and stannous chloride, or Fe and acetic acid, or sodium sulfide.

7. The method for synthesizing 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid according to claim 1, wherein: The materials for nitro reduction in step (3) are concentrated hydrochloric acid and stannous chloride, wherein the molar ratio of stannous chloride to N-(5-nitro-2,4-dichlorophenyl)acetamide is 2.5-3.5:

1.

8. The method for synthesizing 2-(2-(5-acetylamino-2,4-dichlorophenyl)hydrazono)propionic acid according to claim 1, wherein: The molar ratio of N-(5-amino-2,4-dichlorophenyl)acetamide to sodium nitrite and stannous chloride in step (4) is 1:1:2.5-3.5; the concentration of hydrochloric acid in step (5) is 4-6 mol / l, and the reaction ratio of N-(2,4-dichloro-5-hydrazinophenyl)acetamide to 4-6 mol / l hydrochloric acid in step (5) is 0.15-0.3 mol:100 ml; in the solution formed by pyruvic acid and water in step (5), the ratio of pyruvic acid to water is 0.15-0.3 mol:100 ml.

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