Synthesis method of 4-alkyl bromobenzene

Abstract

The invention relates to the technical field of organic synthesis, and particularly discloses a synthetic method of 4-alkyl bromobenzene. The invention provides a synthetic method of 4-alkyl bromobenzene, which specifically comprises the following steps in sequence: sequentially adding raw materials, namely 4-alkylaniline, a bromide and a catalyst into a solvent acetonitrile, then reacting under a reflux or closed condition, and after the reaction is finished, carrying out post-treatment to obtain the 4-alkyl bromobenzene, the brominated substance is selected from one of bromoethane and 1, 2-dibromoethane; the catalyst is composed of potassium nitrate and sodium thiosulfate in a molar ratio of (0.5-1.5): (0.5-1.5); the molar ratio of the catalyst to the 4-alkylaniline is (0.01-0.1): 1. According to the technical scheme provided by the invention, 4-alkylbromobenzene is synthesized by adopting a one-step method, and the synthesis method is safe, environmentally friendly, low in cost and relatively high in yield of finished products.

Description

Technical Field

[0001] This application relates to the technical field of organic synthesis, and specifically relates to a method for synthesizing 4-alkylbromobenzene. Background Art

[0002] 4-alkylbromobenzene is a product formed by replacing the para hydrogen atom in the molecular structure of alkylbenzene compounds with a bromine atom, and belongs to basic chemical products. There are various types of 4-alkylbromobenzenes, including but not limited to 4-methylbromobenzene, 4-ethylbromobenzene, 4-n-propylbromobenzene, 4-n-butylbromobenzene, etc. The synthesis or use of 4-alkylbromobenzene is indispensable in fields such as medicine, pesticides, chemical additives, resin rubber, biochemistry, coatings and printing, and display materials.

[0003] The synthesis methods of 4-alkylbromobenzene generally fall into two categories: Some researchers directly use halogens or halogenating reagents for halogenation; the reaction selectivity of direct halogenation with halogens is poor, and it is easy to produce ortho or meta isomeric impurities, and polysubstituted products will also appear. It requires strict temperature and reaction rate control, and the direct use of bromine is dangerous and not environmentally friendly, which does not conform to the concept of safe and environmentally friendly production; the use of halogenating reagents such as N-bromosuccinimide (NBS) also needs to consider cost and safety issues, and the substitution reaction effect is also not very ideal.

[0004] Some researchers have also made improvements on this basis: using hydrobromic acid to provide bromine elements and cooperating with oxidants to generate bromine for bromination reactions; however, the reaction selectivity in the reaction process of this method is still poor, and it is easy to produce ortho or meta isomeric impurities. Polybrominated products are inevitably produced, and a large amount of bromine is also generated. The volatilization of bromine will have an adverse impact on safety and the environment, and the use of a large amount of oxidants also has safety problems.

[0005] In addition, some researchers, based on the Sandmeyer diazotization halogenation reaction, use 4-alkylarylamine to form diazonium salts and then carry out halogenation; the Sandmeyer reaction perfectly solves the reaction selectivity problem, but a large amount of diazonium salts as reaction intermediates needs to be used. Diazonium salts belong to dangerous chemicals and are prone to decomposition and explosion under conditions such as heat, friction or impact. Diazonium salts are more unstable in the dry state and cannot be stored normally, which additionally increases the production cost and also does not conform to the concept of safe production. Summary of the Invention

[0006] In order to solve the above technical problems, this application provides a method for synthesizing 4-alkylbromobenzene.

[0007] This application provides a method for synthesizing 4-alkylbromobenzene, which specifically includes the following steps carried out in sequence: In acetonitrile as the solvent, the raw material 4-alkyl aniline, the bromide, and the catalyst are added in sequence, and then the reaction is carried out under reflux or closed conditions. After the reaction is completed, 4-alkyl bromobenzene is obtained through post-treatment. The bromide is selected from one of bromoethane and 1,2-dibromoethane. The catalyst is composed of potassium nitrate and sodium thiosulfate with a molar ratio of 0.5 - 1.5:0.5 - 1.5; the molar ratio of the catalyst to the 4-alkyl aniline is 0.01 - 0.1:1.

[0008] To solve the selectivity problem in the synthesis of 4-alkyl bromobenzene, improve the safety of the synthesis of 4-alkyl bromobenzene, and reduce costs, this application provides a relatively safe and low-cost method for synthesizing 4-alkyl bromobenzene. The technical solution provided by this application synthesizes 4-alkyl bromobenzene by a one-step method, and the yield of the finished product is relatively high.

[0009] Among them, the alkyl group in 4-alkyl bromobenzene can be an alkyl group such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, hexyl, isopropyl, cycloalkyl, etc.

[0010] During the reaction process, potassium nitrate activates the C-Br bond of 1,2-dibromoethane or bromoethane, reducing the electron cloud density of the carbocation and increasing its electropositivity; sodium thiosulfate activates the C-N bond of 4-alkyl aniline, increasing the electron cloud density of the nitrogen anion and its electronegativity. The nitrogen anion attacks the carbocation of the C-Br bond of 1,2-dibromoethane or bromoethane, and the bromide anion leaves and attacks the carbocation of the C-N bond of 4-alkyl aniline to obtain 4-alkyl bromobenzene.

[0011] Preferably, the 4-alkyl aniline is selected from any one of 4-methyl aniline, 4-ethyl aniline, 4-n-propyl aniline, 4-n-butyl aniline, and 4-n-pentyl aniline.

[0012] Preferably, the weight ratio of the solvent to the 4-alkyl aniline is 0.5 - 2:1.

[0013] In a specific embodiment, the weight ratio of the solvent to the 4-alkyl aniline can be 0.5:1, 1:1, 1.5:1, 1.7:1, or 2:1.

[0014] Preferably, the molar ratio of the bromide to the 4-alkyl aniline is 1 - 2:1.

[0015] Preferably, the molar ratio of the bromide to the 4-alkyl aniline is 1 - 1.2:1.

[0016] In a specific embodiment, the molar ratio of the bromide to the 4-alkyl aniline can be 1:1, 1.1:1, 1.2:1, 1.3:1, 1.5:1, 1.7:1, 1.8:1, 2:1.

[0017] Preferably, the molar ratio of the catalyst to the 4-alkyl aniline is 0.02 - 0.04:1.

[0018] In a specific embodiment, the molar ratio of the catalyst to the 4-alkyl aniline can be 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.1:1.

[0019] Preferably, the catalyst is composed of potassium nitrate and sodium thiosulfate with a molar ratio of 0.8 - 1.2:0.8 - 1.2.

[0020] In a specific embodiment, in the catalyst, the molar ratio of potassium nitrate to sodium thiosulfate can be 0.5:1, 0.8:1, 1:1, 1.2:1, 1.5:1, 0.8:0.5, 1:0.5, 1.2:0.5, 1.5:0.5, 0.5:0.8, 1:0.8, 1.2:0.8, 1.5:0.8, 0.5:1.2, 0.8:1.2, 1:1.2, 1.5:1.2, 0.5:1.5, 0.8:1.5, 1:1.5, 1.2:1.5.

[0021] Through experimental analysis, it can be known that using the catalyst composed of potassium nitrate and sodium thiosulfate with the above molar ratio in this application can further improve the reaction yield of the synthesis method of 4-alkyl bromobenzene.

[0022] Preferably, the temperature of the reaction is 40 - 100 °C.

[0023] Preferably, the temperature of the reaction is 60 - 70 °C.

[0024] In a specific embodiment, the temperature of the reaction can be 40 °C, 50 °C, 60 °C, 65 °C, 70 °C, 75 °C, 80 °C, 85 °C, 90 °C, 95 °C, 100 °C.

[0025] Through experimental analysis, it can be known that controlling the reaction temperature within the above range in this application can further improve the reaction yield of the synthesis method of 4-alkyl bromobenzene.

[0026] Preferably, the specific steps of the post-treatment are: filtering the reaction solution; removing the solvent after column chromatography to obtain 4-alkyl bromobenzene.

[0027] Preferably, the elution solvent used for column chromatography is petroleum ether.

[0028] In summary, the technical solution of the present application has the following effects: In the present application, 4-alkylbromobenzene is directly prepared from 4-alkyl aniline by a one-step method, avoiding the direct use of hazardous chemicals such as bromine and diazonium salts. The process is simple and direct, avoiding the generation of isomeric impurities and polybrominated impurities, and the product is easy to purify, suitable for large-scale production. Detailed Description of the Invention

[0029] The present application will be further described in detail below in conjunction with examples, comparative examples and performance detection tests. These examples should not be construed as limiting the scope claimed in the present application.

[0030] Examples

[0031] Example 1

[0032] Example 1 provides a method for synthesizing 4-alkylbromobenzene.

[0033] The method for synthesizing 4-alkylbromobenzene in this example is specifically as follows.

[0034] 107 g of acetonitrile, 107 g of 1 mol of 4-methylaniline, 114.5 g of 1.05 mol of bromoethane, and 0.02 mol of a catalyst (1 g of 0.01 mol of potassium nitrate and 1.58 g of 0.01 mol of sodium thiosulfate) were added to a 1 L autoclave. After the system was sealed, the temperature was raised to 65 °C for reaction. After the reaction was completed, the material was filtered, the filtrate was passed through a column, and the solvent was removed by petroleum ether column chromatography to obtain 145.3 g of 4-methylbromobenzene product with a purity of 99.5% and a yield of 85.0%.

[0035] Examples 2-5 Examples 2-5 respectively provide a method for synthesizing 4-alkylbromobenzene.

[0036] The differences between the above examples and Example 1 are as follows: the types of the raw material 4-alkyl aniline are different, which are specifically as follows.

[0037] In Example 2: 121 g of acetonitrile, 121 g of 4-ethylaniline, 114.5 g of bromoethane, 1 g of potassium nitrate, and 1.6 g of sodium thiosulfate were added to a 1 L autoclave. After the system was sealed, the temperature was raised to 65 °C for reaction. After the reaction was completed, the material was filtered, the filtrate was passed through a column, and the solvent was removed by column chromatography to obtain a 4-ethylbromobenzene product.

[0038] In Example 3: 135 g of acetonitrile, 135 g of 4-propylaniline, 114.5 g of bromoethane, 1 g of potassium nitrate, and 1.6 g of sodium thiosulfate were added to a 1 L autoclave. After sealing the system, the temperature was raised to 65 °C for reaction. After the reaction ended, the material was filtered, and the filtrate was passed through a column and the solvent was removed by column chromatography to obtain the 4-propylbromobenzene product.

[0039] In Example 4: 149.2 g of acetonitrile, 149.2 g of 4-butylaniline, 114.5 g of bromoethane, 1 g of potassium nitrate, and 1.6 g of sodium thiosulfate were added to a 1 L three-necked glass flask. The temperature was raised to 65 °C for reflux reaction. After the reaction ended, the material was filtered, and the filtrate was passed through a column and the solvent was removed by column chromatography to obtain the 4-propylbromobenzene product.

[0040] In Example 5: 163 g of acetonitrile, 163 g of 4-pentylaniline, 114.5 g of bromoethane, 1 g of potassium nitrate, and 1.6 g of sodium thiosulfate were added to a 1 L autoclave. After sealing the system, the temperature was raised to 65 °C for reaction. After the reaction ended, the material was filtered, and the filtrate was passed through a column and the solvent was removed by column chromatography to obtain the 4-pentylbromobenzene product.

[0041] Examples 6-14 Examples 6-14 respectively provide a method for synthesizing 4-alkylbromobenzene.

[0042] The differences from Example 1 in the above examples are specifically as follows.

[0043] In Example 6: 1,2-dibromoethane in an equimolar amount was used instead of bromoethane as the brominating agent.

[0044] In Example 7: The amount of the catalyst used was 0.01 mol, specifically 0.005 mol of potassium nitrate and 0.005 mol of sodium thiosulfate.

[0045] In Example 8: The amount of the catalyst used was 0.03 mol, specifically 0.015 mol of potassium nitrate and 0.015 mol of sodium thiosulfate.

[0046] In Example 9: The amount of the catalyst used was 0.04 mol, specifically 0.02 mol of potassium nitrate and 0.02 mol of sodium thiosulfate.

[0047] In Example 10: The amount of the catalyst used was 0.1 mol, specifically 0.05 mol of potassium nitrate and 0.05 mol of sodium thiosulfate.

[0048] In Example 11: The amount of the catalyst used was 0.02 mol, specifically 0.005 mol of potassium nitrate and 0.015 mol of sodium thiosulfate (the molar ratio of potassium nitrate to sodium thiosulfate was 0.5:1.5).

[0049] In Example 12: The dosage of the catalyst is 0.02 mol, specifically 0.015 mol of potassium nitrate and 0.005 mol of sodium thiosulfate (the molar ratio of potassium nitrate to sodium thiosulfate is 1.5:0.5).

[0050] In Example 13: The dosage of the catalyst is 0.02 mol, specifically 0.008 mol of potassium nitrate and 0.012 mol of sodium thiosulfate (the molar ratio of potassium nitrate to sodium thiosulfate is 0.8:1.2).

[0051] In Example 14: The dosage of the catalyst is 0.02 mol, specifically 0.012 mol of potassium nitrate and 0.008 mol of sodium thiosulfate (the molar ratio of potassium nitrate to sodium thiosulfate is 1.2:0.8).

[0052] In the above examples, other process parameters are the same as those in Example 1.

[0053] Examples 15 - 18 Examples 15 - 18 respectively provide a method for synthesizing 4-alkylbromobenzene.

[0054] The differences between the above examples and Example 1 are specifically as follows.

[0055] In Example 15: The reaction temperature is 40 °C.

[0056] In Example 16: The reaction temperature is 60 °C.

[0057] In Example 17: The reaction temperature is 70 °C.

[0058] In Example 18: The reaction temperature is 100 °C.

[0059] In the above examples, other process parameters are the same as those in Example 1.

[0060] Comparative Examples Comparative Examples 1 - 5

[0061] Comparative Examples 1 - 5 respectively provide a method for synthesizing 4-alkylbromobenzene.

[0062] The differences between the above comparative examples and the examples are specifically as follows.

[0063] In Comparative Example 1: HBr in an equimolar amount is used instead of bromoethane as the brominating agent.

[0064] In Comparative Example 2: N-bromosuccinimide in an equimolar amount is used instead of bromoethane as the brominating agent.

[0065] In Comparative Example 3: Sodium nitrate in an equimolar amount is used instead of potassium nitrate in the catalyst.

[0066] In Comparative Example 4: Sodium sulfite was used in an equimolar amount instead of sodium thiosulfate in the catalyst.

[0067] In Comparative Example 5: The amount of the catalyst used was 0.02 mol, specifically 0.002 mol of potassium nitrate and 0.018 mol of sodium thiosulfate (the molar ratio of potassium nitrate to sodium thiosulfate was 1:9).

[0068] Other process parameters in the above comparative examples were the same as those in Example 1.

[0069] Performance detection test Record the reaction time, reaction purity, and yield of the synthesis method of 4-alkylbromobenzene in the examples and comparative examples.

[0070] Detection results: As shown in Table 1.

[0071] Table 1 Performance detection results of the synthesis method of 4-alkylbromobenzene in the examples and comparative examples.

[0072]

[0073] From the detection results in the above table, it can be seen that the technical solution provided by this application synthesizes 4-alkylbromobenzene by a one-step method, and this synthesis method is safe, environmentally friendly, low-cost, and has a relatively high yield of the finished product.

[0074] By comparing the detection results of Example 1, Example 6, and Comparative Examples 1-2, it can be seen that in Comparative Example 1, HBr was used as the bromide, and in Comparative Example 2, N-bromosuccinimide was used as the bromide, resulting in a relatively low yield of the finished product. In contrast, this application uses 1,2-dibromoethane or bromoethane as the bromide, and the yield of the finished product is relatively high.

[0075] By comparing the detection results of Example 1, Examples 7-14, and Comparative Examples 3-5, it can be seen that in Comparative Example 3, the catalyst was composed of sodium nitrate and sodium thiosulfate, in Comparative Example 4, the catalyst was composed of potassium nitrate and sodium sulfite, and in Comparative Example 5, the catalyst was composed of potassium nitrate and sodium thiosulfate with a molar ratio of 1:9, resulting in a relatively low yield of the finished product. In contrast, this application uses a catalyst composed of potassium nitrate and sodium thiosulfate with a molar ratio of 0.5-1.5:0.5-1.5, and the yield of the finished product is relatively high.

[0076] Although the present invention has been described in detail above with general descriptions and specific embodiments, based on the present invention, some modifications or improvements can be made, which are obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection required by the present invention.

Claims

1. A method for synthesizing 4-alkylbromobenzene, characterized in that, Specifically, it includes the following steps in sequence: In acetonitrile solvent, successively add raw material 4-alkyl aniline, bromide, and catalyst, and then carry out the reaction under reflux or closed conditions. After the reaction is completed, 4-alkyl bromobenzene is obtained through post-treatment. The bromide is selected from one of bromoethane and 1,2-dibromoethane. The catalyst is composed of potassium nitrate and sodium thiosulfate with a molar ratio of 0.5-1.5:0.5-1.5; the molar ratio of the catalyst to the 4-alkyl aniline is 0.01-0.1:

1.

2. The synthesis method of 4-alkyl bromobenzene according to claim 1, characterized in that, The 4-alkyl aniline is selected from any one of 4-methyl aniline, 4-ethyl aniline, 4-n-propyl aniline, 4-n-butyl aniline, and 4-n-pentyl aniline.

3. The synthesis method of 4-alkyl bromobenzene according to claim 1, wherein The weight ratio of the solvent to the 4-alkyl aniline is 0.5-2:

1.

4. The synthesis method of 4-alkyl bromobenzene according to claim 1, characterized in that, The molar ratio of the bromide to the 4-alkyl aniline is 1-2:

1.

5. The synthesis method of 4-alkylbromobenzene according to claim 4, wherein The molar ratio of the bromide to the 4-alkyl aniline is 1-1.2:

1.

6. The synthesis method of 4-alkyl bromobenzene according to claim 1, wherein The molar ratio of the catalyst to the 4-alkyl aniline is 0.02-0.04:

1.

7. The synthesis method of 4-alkyl bromobenzene according to claim 1, characterized in that, The catalyst is composed of potassium nitrate and sodium thiosulfate with a molar ratio of 0.8-1.2:0.8-1.

2.

8. The synthesis method of 4-alkylbromobenzene according to claim 1, characterized in that, The temperature of the reaction is 40-100 °C.

9. The synthesis method of 4-alkylbromobenzene according to claim 8, characterized in that, The temperature of the reaction is 60-70 °C.

10. The synthesis method of 4-alkyl bromobenzene according to claim 1, wherein The specific steps of the post-treatment are: filtering the reaction solution; removing the solvent after column chromatography to obtain 4-alkyl bromobenzene.

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