A kind of synthetic method of 4-alkyl bromobenzene

Abstract

The present application relates to the technical field of organic synthesis, and specifically discloses a method for synthesizing 4-alkylbromobenzenes. The method for synthesizing a kind of 4-alkylbromobenzenes provided by the present application, specifically includes sequentially carrying out the following steps: in solvent acetonitrile, raw material 4-alkylaniline, bromide, catalyst are added sequentially, then reacted under reflux or closed conditions, after the reaction is completed, 4-alkylbromobenzenes are obtained through post-processing; bromide is selected from one of bromoethane, 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 catalyst to the 4-alkylaniline is 0.01-0.1: 1. The technical solution provided by the present application synthesizes 4-alkylbromobenzenes by adopting a one-step method, and the synthetic method is safe, environmentally friendly, low cost, and has a high finished product yield.

Description

Technical Field

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

[0002] 4-Alkylbromobenzenes are formed when bromine replaces the para-hydrogen atom in the molecular structure of an alkylbenzene compound. They are considered basic chemical products. There are numerous varieties of 4-alkylbromobenzenes, including but not limited to 4-methylbromobenzene, 4-ethylbromobenzene, 4-n-propylbromobenzene, and 4-n-butylbromobenzene. Their synthesis and use are essential in fields such as pharmaceuticals, pesticides, chemical additives, resins and rubbers, biochemicals, coatings and dyeing, and display materials.

[0003] The synthesis methods of 4-alkylbromobenzenes are generally divided into two categories: some researchers directly use halogens or halogenating agents for direct halogenation; direct halogenation using halogens has poor reaction selectivity, easily produces ortho- or meta-isomer impurities, and may also produce multiple substitutions, requiring strict temperature and reaction rate control. In addition, the direct use of bromine is dangerous and environmentally unfriendly, and does not conform to the production concept of safety and environmental protection; the use of halogenating agents such as N-bromosuccinimide (NBS) also needs to consider cost and safety issues, and the substitution reaction effect is also less than 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 reaction; however, the reaction selectivity of this method is still poor during the reaction process, and it is easy to produce ortho- or meta-isomer impurities, and polybrominated products are inevitable, and a large amount of bromine will also be produced. The volatilization of bromine will have adverse effects on safety and the environment, and the large-scale use of oxidants also has safety issues.

[0005] Alternatively, researchers have developed a Sandmeyer diazotization halogenation reaction, using 4-alkylarylamines to produce diazonium salts, followed by halogenation. While the Sandmeyer reaction effectively addresses the issue of reaction selectivity, it requires the use of large quantities of diazonium salts as reaction intermediates. Diazonium salts are hazardous chemicals prone to decomposition and explosion under conditions such as heat, friction, or impact. They are also more unstable in a dry state and cannot be properly stored, increasing production costs and incompatible with safety standards. Summary of the Invention

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

[0007] The present application provides a method for synthesizing 4-alkylbromobenzene, which specifically comprises the following steps in sequence:

[0008] In the solvent acetonitrile, the raw material 4-alkylaniline, 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-alkylbromobenzene is obtained through post-treatment;

[0009] The bromide is selected from one of bromoethane and 1,2-dibromoethane;

[0010] The catalyst consists of potassium nitrate and sodium thiosulfate in a molar ratio of 0.5-1.5:0.5-1.5; and the molar ratio of the catalyst to the 4-alkylaniline is 0.01-0.1:1.

[0011] To address the selectivity issues in the synthesis of 4-alkylbromobenzenes, while also improving safety and reducing costs, this application provides a relatively safe and low-cost method for synthesizing 4-alkylbromobenzenes. The technical solution provided in this application utilizes a one-step process to synthesize 4-alkylbromobenzenes, resulting in a high yield of the finished product.

[0012] The alkyl group in 4-alkylbromobenzene can be methyl, ethyl, n-propyl, n-butyl, n-pentyl, hexyl, isopropyl, cycloalkyl or other alkyl groups.

[0013] During the reaction, potassium nitrate activates the C-Br bond of 1,2-dibromoethane or bromoethane, reducing the electron cloud density of the carbon cation and increasing its electropositivity; sodium thiosulfate activates the CN bond of 4-alkylaniline, increasing the electron cloud density of the nitrogen anion and increasing its electronegativity. The nitrogen anion attacks the carbon cation of the C-Br bond of 1,2-dibromoethane or bromoethane, and the bromine anion leaves and attacks the carbon cation of the CN bond of 4-alkylaniline to obtain 4-alkylbromobenzene.

[0014] Preferably, the 4-alkylaniline is selected from any one of 4-methylaniline, 4-ethylaniline, 4-n-propylaniline, 4-n-butylaniline and 4-n-pentylaniline.

[0015] Preferably, the weight ratio of the solvent to the 4-alkylaniline is 0.5-2:1.

[0016] In a specific embodiment, the weight ratio of the solvent to the 4-alkylaniline can be 0.5:1, 1:1, 1.5:1, 1.7:1, or 2:1.

[0017] Preferably, the molar ratio of the bromide to the 4-alkylaniline is 1-2:1.

[0018] Preferably, the molar ratio of the bromide to the 4-alkylaniline is 1-1.2:1.

[0019] In a specific embodiment, the molar ratio of the bromide to the 4-alkylaniline can be 1:1, 1.1:1, 1.2:1, 1.3:1, 1.5:1, 1.7:1, 1.8:1, or 2:1.

[0020] Preferably, the molar ratio of the catalyst to the 4-alkylaniline is 0.02-0.04:1.

[0021] In a specific embodiment, the molar ratio of the catalyst to the 4-alkylaniline 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, or 0.1:1.

[0022] Preferably, the catalyst is composed of potassium nitrate and sodium thiosulfate in a molar ratio of 0.8-1.2:0.8-1.2.

[0023] 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, and 1.2:1.5.

[0024] Through experimental analysis, it can be seen that the present application uses potassium nitrate and sodium thiosulfate in the above molar ratio to form a catalyst, which can further improve the reaction yield of the synthesis method of 4-alkylbromobenzene.

[0025] Preferably, the reaction temperature is 40-100°C.

[0026] Preferably, the reaction temperature is 60-70°C.

[0027] In a specific embodiment, the reaction temperature can be 40°C, 50°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, or 100°C.

[0028] Through experimental analysis, it is known that the reaction yield of the method for synthesizing 4-alkylbromobenzene can be further improved by controlling the reaction temperature within the above range.

[0029] Preferably, the specific steps of the post-treatment are: filtering the reaction solution; and removing the solvent after column chromatography to obtain 4-alkylbromobenzene.

[0030] Preferably, the elution solvent used in the column chromatography is petroleum ether.

[0031] In summary, the technical solution of this application has the following effects:

[0032] The present application directly prepares 4-alkylbromobenzene from 4-alkylaniline 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 and suitable for large-scale production. DETAILED DESCRIPTION

[0033] The present application is further described in detail below in conjunction with examples, comparative examples and performance testing experiments. These examples should not be construed as limiting the scope of protection claimed in this application.

[0034] Example

[0035] Example 1

[0036] Example 1 provides a method for synthesizing 4-alkylbromobenzene.

[0037] The synthesis method of 4-alkyl bromobenzene in this embodiment is specifically as follows.

[0038] To a 1L autoclave, add 107g of acetonitrile, 107g of 1mol of 4-methylaniline, 114.5g of 1.05mol of ethyl bromide, and 0.02mol of a catalyst (1g of 0.01mol of potassium nitrate and 1.58g of 0.01mol of sodium thiosulfate). The system was sealed and the temperature was raised to 65°C for reaction. After completion of the reaction, the product was filtered, and the filtrate was purified by column chromatography and desolvation using petroleum ether to obtain 145.3g of 4-methylbromobenzene with a purity of 99.5% and a yield of 85.0%.

[0039] Examples 2-5

[0040] Examples 2-5 respectively provide a method for synthesizing 4-alkylbromobenzene.

[0041] The difference between the above embodiment and embodiment 1 is that the type of raw material 4-alkylaniline is different, as shown below.

[0042] In Example 2, 121 g of acetonitrile, 121 g of 4-ethylaniline, 114.5 g of ethyl bromide, 1 g of potassium nitrate, and 1.6 g of sodium thiosulfate were added to a 1 L autoclave. The system was sealed and the temperature was raised to 65°C for reaction. After the reaction, the material was filtered, and the filtrate was passed through a column and subjected to column chromatography for solvent removal to obtain 4-ethylbromobenzene product.

[0043] In Example 3, 135 g of acetonitrile, 135 g of 4-n-propylaniline, 114.5 g of ethyl bromide, 1 g of potassium nitrate, and 1.6 g of sodium thiosulfate were added to a 1 L autoclave. The system was sealed and the temperature was raised to 65°C for reaction. After the reaction, the material was filtered, and the filtrate was passed through a column and subjected to column chromatography for solvent removal to obtain 4-propyl bromobenzene product.

[0044] In Example 4, 149.2 g of acetonitrile, 149.2 g of 4-n-butylaniline, 114.5 g of ethyl bromide, 1 g of potassium nitrate, and 1.6 g of sodium thiosulfate were added to a 1 L glass three-necked flask, and the mixture was heated to 65°C for reflux reaction. After the reaction, the material was filtered, and the filtrate was passed through a column and subjected to column chromatography for solvent removal to obtain 4-propyl bromobenzene product.

[0045] In Example 5, 163 g of acetonitrile, 163 g of 4-n-pentylaniline, 114.5 g of ethyl bromide, 1 g of potassium nitrate, and 1.6 g of sodium thiosulfate were added to a 1 L autoclave. The system was sealed and the temperature was raised to 65°C for reaction. After the reaction, the material was filtered, and the filtrate was passed through a column and subjected to column chromatography for solvent removal to obtain 4-pentylbromobenzene product.

[0046] Examples 6-14

[0047] Examples 6-14 respectively provide a method for synthesizing 4-alkylbromobenzene.

[0048] The differences between the above embodiment and embodiment 1 are specifically as follows.

[0049] In Example 6, 1,2-dibromoethane was used in an equimolar amount instead of bromoethane as the bromide.

[0050] In Example 7, the amount of catalyst used is 0.01 mol, specifically 0.005 mol of potassium nitrate and 0.005 mol of sodium thiosulfate.

[0051] In Example 8, the amount of catalyst used is 0.03 mol, specifically 0.015 mol of potassium nitrate and 0.015 mol of sodium thiosulfate.

[0052] In Example 9, the amount of catalyst used is 0.04 mol, specifically 0.02 mol of potassium nitrate and 0.02 mol of sodium thiosulfate.

[0053] In Example 10, the amount of catalyst used is 0.1 mol, specifically 0.05 mol of potassium nitrate and 0.05 mol of sodium thiosulfate.

[0054] In Example 11, the amount of catalyst used is 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 is 0.5:1.5).

[0055] In Example 12, the amount of catalyst used 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).

[0056] In Example 13, the amount of catalyst used was 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 was 0.8:1.2).

[0057] In Example 14, the amount of catalyst used 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).

[0058] The other process parameters in the above embodiment are the same as those in Example 1.

[0059] Examples 15-18

[0060] Examples 15-18 respectively provide a method for synthesizing 4-alkylbromobenzene.

[0061] The differences between the above embodiment and embodiment 1 are specifically as follows.

[0062] In Example 15: the reaction temperature is 40°C.

[0063] In Example 16: the reaction temperature is 60°C.

[0064] In Example 17: the reaction temperature is 70°C.

[0065] In Example 18: the reaction temperature is 100°C.

[0066] The other process parameters in the above embodiment are the same as those in Example 1.

[0067] Comparative Example

[0068] Comparative Examples 1-5

[0069] Comparative Examples 1-5 respectively provide a method for synthesizing 4-alkylbromobenzene.

[0070] The differences between the comparative example and the embodiment are specifically as follows.

[0071] In Comparative Example 1, an equimolar amount of HBr was used instead of ethyl bromide as the bromide.

[0072] In Comparative Example 2, an equimolar amount of N-bromosuccinimide was used instead of bromoethane as the brominated compound.

[0073] In Comparative Example 3: an equimolar amount of sodium nitrate was used instead of potassium nitrate in the catalyst.

[0074] In Comparative Example 4, sodium thiosulfate was replaced by an equimolar amount of sodium sulfite in the catalyst.

[0075] In Comparative Example 5, the amount of 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).

[0076] The other process parameters in the above comparative example are the same as those in Example 1.

[0077] Performance testing

[0078] Record the reaction time, reaction purity and yield of the 4-alkylbromobenzene synthesis method in the examples and comparative examples.

[0079] Test results: as shown in Table 1.

[0080] Table 1 Performance test results of the synthesis methods of 4-alkylbromobenzenes in Examples and Comparative Examples.

[0081]

[0082] From the test results in the above table, it can be seen that the technical solution provided by the present application synthesizes 4-alkylbromobenzene by a one-step method, and the synthesis method is safe, environmentally friendly, low-cost, and has a high yield of finished products.

[0083] By comparing the test results of Example 1, Example 6, and Comparative Examples 1-2, it can be seen that the yield of the finished product is low when HBr is used as the bromide in Comparative Example 1 and N-bromosuccinimide is used as the bromide in Comparative Example 2. In contrast, the yield of the finished product is higher when 1,2-dibromoethane or bromoethane is used as the bromide in this application.

[0084] By comparing the test results of Example 1, Examples 7-14, and Comparative Examples 3-5, it can be seen that the catalyst in Comparative Example 3 is composed of sodium nitrate and sodium thiosulfate, the catalyst in Comparative Example 4 is composed of potassium nitrate and sodium sulfite, and the catalyst in Comparative Example 5 is composed of potassium nitrate and sodium thiosulfate in a molar ratio of 1:9, and the finished product yield is low. In contrast, the present application uses a catalyst composed of potassium nitrate and sodium thiosulfate in a molar ratio of 0.5-1.5:0.5-1.5, and the finished product yield is higher.

[0085] Although the present invention has been described in detail above using general descriptions and specific embodiments, it will be apparent to those skilled in the art that modifications and improvements may be made based on the present invention. Therefore, such modifications and improvements, which do not depart from the spirit of the present invention, are intended to be within the scope of protection claimed herein.

Claims

1. A method for synthesizing 4-alkylbromobenzene, characterized in that: Specifically, the following steps are performed in sequence: In the solvent acetonitrile, the raw material 4-alkylaniline, 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-alkylbromobenzene 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 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; The 4-alkylaniline is selected from any one of 4-methylaniline, 4-ethylaniline, 4-n-propylaniline, 4-n-butylaniline and 4-n-pentylaniline.

2. The method for synthesizing 4-alkylbromobenzene according to claim 1, wherein The weight ratio of the solvent to the 4-alkylaniline is 0.5-2:

1.

3. The method for synthesizing 4-alkylbromobenzene according to claim 1, characterized in that: The molar ratio of the bromide to the 4-alkylaniline is 1-2:

1.

4. The method for synthesizing 4-alkylbromobenzene according to claim 3, wherein The molar ratio of the bromide to the 4-alkylaniline is 1-1.2:

1.

5. The method for synthesizing 4-alkylbromobenzene according to claim 1, wherein The molar ratio of the catalyst to the 4-alkylaniline is 0.02-0.04:

1.

6. The method for synthesizing 4-alkylbromobenzene according to claim 1, characterized in that: The catalyst consists of potassium nitrate and sodium thiosulfate in a molar ratio of 0.8-1.2:0.8-1.

2.

7. The method for synthesizing 4-alkylbromobenzene according to claim 1, characterized in that: The reaction temperature is 40-100°C.

8. The method for synthesizing 4-alkylbromobenzene according to claim 7, characterized in that: The reaction temperature is 60-70°C.

9. The method for synthesizing 4-alkylbromobenzene according to claim 1, characterized in that: The specific steps of the post-treatment are: filtering the reaction solution; and removing the solvent after column chromatography to obtain 4-alkyl bromobenzene.

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