Method for synthesizing 3, 5-dichloronitrobenzene

Abstract

The invention discloses a method for synthesizing 3, 5-dichloronitrobenzene, which comprises the following steps of: a, adding 2, 6-dichloro-4-nitroaniline into concentrated sulfuric acid and nitrososulfuric acid to carry out diazotization reaction to obtain diazo liquid; b, adding the diazotization liquid in the step a into a mixture of a reducing agent and a catalyst copper salt, and carrying out a deamination reaction; c, a solvent is added for extraction, and a 3, 5-dichloronitrobenzene solution is obtained. The method for synthesizing the 3, 5-dichloronitrobenzene is simple in process operation, low in production cost, high in yield and suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing 3,5-dichloronitrobenzene. Background Art

[0002] Iprodione is a highly effective, broad-spectrum, contact fungicide from the dicarboximide class. It is suitable for controlling diseases such as early leaf drop, gray mold, and early blight in a variety of fruit trees, vegetables, and melons. The key intermediate 3,5-dichloroaniline in iprodione is derived from 3,5-dichloronitrobenzene, which is synthesized by diazotization-deamination of 2,6-dichloro-4-nitroaniline in a reducing medium.

[0003] The prior art method for synthesizing 3,5-dichloronitrobenzene is to use an inorganic acid or acidic ion for a diazotization reaction and an alcohol compound as a reducing agent to carry out the reaction.

[0004] For example, the article by Zhao Hui, Cai Chun et al. (Improvement of the Synthesis Process of 3,5-Dichloronitrobenzene [J]. Fine Chemicals, 2003, 20(9): 3. DOI: 10.3321 / j.issn: 1003-5214.2003.09.017.) discloses a scheme using sodium nitrite as a diazotizing agent and ethanol as a reducing agent, with the highest yield of 3,5-dichloronitrobenzene being 77.0%.

[0005] For another example, in Chinese patent CN117402065A, an alcohol compound is used as a reducing agent, and the yield is about 88%.

[0006] For another example, Chinese patent CN116444376B emphasizes the use of acidic ionic liquids instead of inorganic acids for diazotization reactions, and the reducing agent used is an alcohol organic solvent, with a claimed yield of 85.8% to 92.5%.

[0007] However, the yield of this reaction pathway in the prior art is difficult to improve, mainly due to the high amount of tar and incomplete reduction. Summary of the Invention

[0008] The technical problem to be solved by the present invention is how to improve the synthesis yield of 3,5-dichloronitrobenzene. In view of the above technical problem to be solved, a method for synthesizing 3,5-dichloronitrobenzene is now proposed.

[0009] To achieve the above object, the present invention provides the following technical solution: a method for synthesizing 3,5-dichloronitrobenzene, comprising the following steps:

[0010] a: Add compound 1: 2,6-dichloro-4-nitroaniline to concentrated sulfuric acid and nitrosylsulfuric acid to carry out diazotization reaction to obtain diazo liquid;

[0011] b: adding the diazotization solution in step a to the mixture of the reducing agent and the copper salt catalyst to carry out a deamination reaction;

[0012] c: Add solvent for extraction to obtain a solution of compound 2: 3,5-dichloronitrobenzene.

[0013] Furthermore, in step a, the nitrosylsulfuric acid is nitrosylsulfuric acid with a concentration of 40% solution, wherein the solution is sulfuric acid.

[0014] Furthermore, the diazotization reaction in step a is carried out at a temperature of 0°C to 40°C.

[0015] Furthermore, the diazotization reaction in step a is carried out at a temperature of 10°C to 18°C.

[0016] Furthermore, in step b, the reducing agent is formaldehyde or formic acid.

[0017] Furthermore, in step b, the catalyst copper salt is copper sulfate pentahydrate.

[0018] Furthermore, the deamination reaction in step b is carried out at a temperature of 40°C-75°C.

[0019] Furthermore, the deamination reaction in step b is carried out at a temperature of 55°C-65°C.

[0020] Furthermore, the molar ratio of 2,6-dichloro-4-nitroaniline, 98% concentrated sulfuric acid (calculated as H2SO4), 40% nitrosylsulfuric acid (calculated as nitrous acid), reducing agent, and copper sulfate pentahydrate (calculated as copper sulfate) in step a and step b is 1:4-6:1.0-1.4:4-6:0.005-0.010.

[0021] Furthermore, in step c, the extraction solvent is one or more of toluene, dichloroethane, and cyclohexane.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The present invention uses formaldehyde and formic acid as reducing agents instead of the traditional alcohol, thereby greatly improving output efficiency and reducing costs. At the same time, formaldehyde is decomposed into CO and formic acid is decomposed into CO2 and leave the reaction system, making post-reaction processing simpler. Among them, 37% formaldehyde is preferably used as the reducing agent system, and the reaction yield can be as high as 94.56%. DETAILED DESCRIPTION

[0024] The technical scheme in the embodiment of the present invention will be clearly and completely described below. Obviously, the described embodiment is only a part of the present invention, rather than all embodiments. Based on the embodiment in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work premise belong to the scope of protection of the present invention. In the following examples, the content of the raw materials and reagents involved refers to the percentage by mass.

[0025] Example 1

[0026] This specific embodiment provides a method for synthesizing 3,5-dichloronitrobenzene, which is implemented under laboratory conditions.

[0027] First, 50.04 g (0.5 mol) of 98% concentrated sulfuric acid and 38.12 g (0.12 mol) of 40% nitrosylsulfuric acid were added to a 500 mL four-necked flask. Compound 1 (21.79 g, 0.1 mol, 95%) was added in batches at a temperature of 10-18°C. The addition was complete over 10 minutes and the mixture was incubated for 30 minutes. Separately, 2.25 g (0.0009 mol) of copper sulfate pentahydrate and 24.30 g (0.5 mol) of 37% formaldehyde solution were added to a 500 mL flask. The reaction mixture was added dropwise at a temperature of 55-65°C over a period of 1 hour. After completion, the mixture was incubated for 3 hours. 160 g of toluene was added, and the upper layer was separated to obtain 179.58 g of a toluene solution of Compound 2. Analysis revealed an external standard content of 10.11%, yielding 94.56%.

[0028] Among them, compound 1 is 2,6-dichloro-4-nitroaniline, and compound 2 is 3,5-dichloronitrobenzene.

[0029] Example 2

[0030] This specific example provides a method for synthesizing 3,5-dichloronitrobenzene, which differs from Example 1 only in that the reducing agent is 50% formic acid. HPLC analysis and calculation show that the yield of compound 2 is 85.25%.

[0031] Example 3

[0032] This specific example provides a method for synthesizing 3,5-dichloronitrobenzene, which differs from Example 1 only in that the reducing agent is methanol. HPLC analysis and calculation show that the yield of compound 2 is 87.62%.

[0033] Example 4

[0034] This specific example provides a method for synthesizing 3,5-dichloronitrobenzene. The method differs from Example 1 only in that the molar ratios of Compound 1, 98% concentrated sulfuric acid, 40% nitrosylsulfuric acid, reducing agent, and copper sulfate pentahydrate are 1:4:1.2:6:0.006, and the diazotization deamination temperature is 20°C to 30°C. HPLC analysis and calculation show a yield of 92.86% for Compound 2.

[0035] Example 5

[0036] This specific example provides a method for synthesizing 3,5-dichloronitrobenzene. The method differs from Example 1 only in that the molar ratio of Compound 1, 98% concentrated sulfuric acid, 40% nitrosylsulfuric acid, reducing agent, and copper sulfate pentahydrate is 1:6:1.2:5:0.009, and the reduction temperature is 45°C to 55°C. HPLC analysis and calculation show that the yield of Compound 2 is 93.25%.

[0037] Example 6

[0038] This specific example provides a method for synthesizing 3,5-dichloronitrobenzene. The method differs from Example 1 only in that the molar ratio of Compound 1, 98% concentrated sulfuric acid, 40% nitrosylsulfuric acid, reducing agent, and copper sulfate pentahydrate is 1:5.5:1.4:4:0.010, the diazotization deamination temperature is 20°C to 30°C, and the reduction temperature is 45°C to 55°C. HPLC analysis and calculation show a yield of 91.56% for Compound 2.

[0039] Comparative Example 1

[0040] A method for synthesizing 3,5-dichloronitrobenzene is disclosed. As a control group, the method differs from Example 1 only in that the reducing agent is ethanol. HPLC analysis and calculation show that the yield of compound 2 is 81.65%.

[0041] Comparative Example 2

[0042] A method for synthesizing 3,5-dichloronitrobenzene is disclosed. As a control group, the method differs from Example 1 only in that the reducing agent is isopropanol. HPLC analysis and calculation show that the yield of compound 2 is 82.38%.

[0043] Comparative Example 3

[0044] A method for synthesizing 3,5-dichloronitrobenzene is disclosed. As a control group, the method differs from Example 1 only in the order of adding the ingredients. Specifically, 21.79 g (95%, 0.1 mol) of compound 1 is added to a 500 mL four-necked flask. 50.04 g (0.5 mol) of 98% concentrated sulfuric acid is added dropwise starting at 10°C-18°C over 15 minutes. The temperature is then controlled at 10°C-18°C and 38.12 g (0.12 mol) of 40% nitrosylsulfuric acid is added dropwise over 20 minutes, followed by a 30-minute incubation. Separately, 2.25 g (0.0009 mol) of copper sulfate pentahydrate is added to a 500 mL flask. The temperature is then controlled at 55°C-65°C. 24.30 g (0.5 mol) of 37% formaldehyde solution is added dropwise over 1 hour, followed by a 3-hour incubation. 160 g of toluene was added, and the upper layer was separated to obtain 179.2 g of toluene solution of compound 2. Analysis showed that the external standard content was 9.27% ​​and the yield was 86.52%.

[0045] Comparative Example 4

[0046] Disclosed is a method for synthesizing 3,5-dichloronitrobenzene. As a control group, the only difference between it and comparative example 2 is the order of feeding. The order and reaction conditions are the same as those of comparative example 3. Finally, after HPLC analysis and calculation, the yield of compound 2 is 81.34%.

[0047] In addition, the amount of each substance in Examples 1-6 and Comparative Examples 1-2, the reducing agent / solvent system, the diazotization deamination temperature, the reduction temperature, and the yield of Compound 2 are shown in Table 1 below.

[0048] The order of adding materials in Table 1 is: adding 98% concentrated sulfuric acid and 40% nitrosylsulfuric acid, adding compound 1: 2,6-dichloro-4-nitroaniline in batches, adding a reducing agent and a catalyst copper sulfate pentahydrate, and then dripping the materials after the above reaction.

[0049] Table 1:

[0050]

[0051] The amounts of the substances, reducing agent / solvent systems, diazotization deamination temperature, reduction temperature, and yield of Compound 2 in Comparative Examples 3-4 are shown in Table 2 below.

[0052] The order of adding materials in Table 2 is: adding compound 1: 2,6-dichloro-4-nitroaniline, adding 98% concentrated sulfuric acid dropwise, adding 40% nitrosylsulfuric acid dropwise, adding catalyst copper sulfate pentahydrate and reducing agent, and then adding the materials after the above reaction dropwise.

[0053] Table 2:

[0054]

[0055] As can be seen from Table 1, when ethanol and isopropanol were used as reducing agent systems, the yield of compound 2 was relatively low; when 37% formaldehyde, 50% formic acid, and methanol were used as reducing agent systems, the yield was significantly improved, among which 37% formaldehyde was the best, followed by methanol, and then 50% formic acid.

[0056] As can be seen from Table 2, the order of feeding will also affect the reaction yield, and the feeding order described in this patent is more advantageous.

[0057] In addition, the percentages of the above substances are expressed as abbreviations of the percentage concentrations of the solutions, wherein the solvent for formaldehyde and formic acid solutions is water, and the solvent for nitrosylsulfuric acid is sulfuric acid.

[0058] The present invention uses formaldehyde and formic acid as reducing agents instead of the traditional alcohol, thereby greatly improving output efficiency and reducing costs. At the same time, formaldehyde is decomposed into CO and formic acid is decomposed into CO2 and leave the reaction system, making post-reaction processing simpler. When 37% formaldehyde is preferably used as the reducing agent system, the reaction yield can be as high as 94.56%.

[0059] While the present invention is described through the above-described embodiments, the present invention is not limited to the above-described detailed methods, and implementation of the present invention is not necessarily dependent on the above-described detailed methods. Those skilled in the art will appreciate that any improvements to the present invention, equivalent replacements for raw materials in the products of the present invention, addition of auxiliary ingredients, and specific method selection, etc., fall within the scope of protection and disclosure of the present invention.

Claims

1. A method for synthesizing 3,5-dichloronitrobenzene, characterized in that: The following steps are involved: a: Add 2,6-dichloro-4-nitroaniline to concentrated sulfuric acid and nitrosylsulfuric acid to carry out diazotization reaction to obtain diazo liquid; b: adding the diazotization solution in step a to the mixture of the reducing agent and the copper salt catalyst to carry out a deamination reaction; c: Add solvent for extraction to obtain a solution of 3,5-dichloronitrobenzene.

2. The method for preparing 3,5-dichloronitrobenzene according to claim 1, wherein: In step a, the nitrosylsulfuric acid is nitrosylsulfuric acid with a concentration of 40% solution, wherein the solution is sulfuric acid.

3. A method for synthesizing 3,5-dichloronitrobenzene according to claim 1, characterized in that, The diazotization reaction in step a is carried out at a temperature of 0°C to 40°C.

4. A method for synthesizing 3,5-dichloronitrobenzene according to claim 3, characterized in that, The diazotization reaction in step a is carried out at a temperature of 10°C to 18°C.

5. A method for synthesizing 3,5-dichloronitrobenzene according to claim 1, characterized in that, In step b, the reducing agent is formaldehyde or formic acid.

6. A method for synthesizing 3,5-dichloronitrobenzene according to claim 1, characterized in that, In step b, the catalyst copper salt is copper sulfate pentahydrate.

7. A method for synthesizing 3,5-dichloronitrobenzene according to claim 1, characterized in that, The deamination reaction in step b is carried out at a temperature of 40°C-75°C.

8. A method for synthesizing 3,5-dichloronitrobenzene according to claim 7, characterized in that, The deamination reaction in step b is carried out at a temperature of 55°C-65°C.

9. The method for synthesizing 3,5-dichloronitrobenzene according to claim 1, wherein: The molar ratio of 2,6-dichloro-4-nitroaniline, 98% concentrated sulfuric acid (calculated as H2SO4), 40% nitrosylsulfuric acid (calculated as nitrous acid), reducing agent, and copper sulfate pentahydrate (calculated as copper sulfate) in step a and step b is 1:4-6:1.0-1.4:4-6:0.005-0.

010.

10. The method for synthesizing 3,5-dichloronitrobenzene according to claim 1, characterized in that: In the step c, the extraction solvent is one or more of toluene, dichloroethane, and cyclohexane.

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