Method for preparing 2, 6-dichloro-alpha-(4-chlorophenyl)-4-nitrophenylacetonitrile

Abstract

The invention discloses a method for preparing 2, 6-dichloro-alpha-(4-chlorophenyl)-4-nitrophenylacetonitrile, which comprises the following steps: S1, synthesizing 2, 6-dichloro-alpha-(4-chlorophenyl)-4-nitrophenylacetonitrile: reacting phenylacetonitrile with chlorine under the action of a chlorination catalyst; the 2, 6-dichlorobenzyl cyanide is obtained; s2, introducing a 4-chlorophenyl group: carrying out a cross-coupling reaction on the 2, 6-dichlorobenzyl cyanide obtained in the step 1 and 4-chlorophenylboronic acid or 4-chlorophenyl lithium in a solvent; and S3, introducing a nitro group into the intermediate obtained in the step 2. Carrying out nitration reaction on the intermediate and nitric acid under the catalytic action of sulfuric acid; and S4, purification: purifying the final product through a conventional separation and purification technology. The synthesis method provided by the invention has high reaction yield, can effectively reduce the waste of raw materials, improves the yield of the product, not only can reduce the production cost, but also can reduce the pollution to the environment, and has high economic and environmental benefits.

Description

Technical Field

[0001] The invention relates to the technical field of production of 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile, and in particular to a method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile. Background Art

[0002] 2,6-dichloro-α-(4-chlorophenyl)-4-nitrobenzeneacetonitrile is an important intermediate for the synthesis of triazine benzeneacetonitrile compounds, which is widely used and has a large market demand. Among them, the key intermediate reaction is that 1,2,3-trichloro-5-nitrobenzene and p-chlorobenzeneacetonitrile are subjected to condensation reaction under phase transfer catalysis in high concentration liquid alkali to obtain the product. In the reaction process, it is necessary to introduce an organic solvent to dissolve 1,2,3-trichloro-5-nitrobenzene, and form a two-phase liquid surface with a high concentration of alkali solution, and condense under phase transfer catalysis. Under the background of a sharp rise in raw materials, how to seek a production process with mild reaction and reduced cost is an important indicator of whether this product can be developed sustainably.

[0003] 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile is a compound with important chemical structure and biological activity. Its molecule contains multiple chloro groups and nitro groups, which makes it have strong electronic properties and can show special activity in chemical reactions, so it has important applications in organic synthesis. However, the current synthesis method of this compound is relatively limited, and the synthesis method in the prior art has certain disadvantages, such as harsh reaction conditions, low yield, high raw material cost, etc. Therefore, a more efficient and environmentally friendly synthesis method is urgently needed to improve yield, reduce cost and optimize reaction conditions. Summary of the invention

[0004] The present invention aims to solve one of the technical problems in the above-mentioned technology at least to some extent.

[0005] To achieve the above object, the first aspect of the present invention provides a method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile, comprising:

[0006] S1. Synthesis of 2,6-dichlorobenzeneacetonitrile: react benzyl cyanide with chlorine in the presence of a chlorination catalyst. Chlorine is gradually introduced into the reaction system, and proper stirring is required during the reaction to ensure sufficient reaction of the chlorine. After the reaction is completed, the mixture is cooled to room temperature, washed with water and extracted to obtain 2,6-dichlorobenzeneacetonitrile;

[0007] S2, introducing 4-chlorophenyl group: cross-coupling reaction of 2,6-dichlorobenzeneacetonitrile obtained in step 1 with 4-chlorophenylboronic acid or 4-chlorophenyllithium in a solvent. Through this reaction, 4-chlorophenyl group is successfully introduced into 2,6-dichlorobenzeneacetonitrile molecule to obtain intermediate 2,6-dichloro-α-(4-chlorophenyl)benzeneacetonitrile;

[0008] S3, nitration reaction: introducing a nitro group into the intermediate obtained in step 2. Specifically, the intermediate is subjected to a nitration reaction with nitric acid under the catalytic action of sulfuric acid. In this step, nitric acid reacts with the intermediate to introduce a nitro group at the 4-position of the benzene ring to obtain 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile;

[0009] S4, purification: The final product is purified by conventional separation and purification techniques (such as column chromatography, recrystallization, etc.) to obtain the target compound 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile. This step can remove residual impurities and ensure the high purity of the product.

[0010] In addition, the method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to the present invention can also have the following additional technical features:

[0011] Furthermore, the chlorination catalyst is one or a combination of aluminum chloride, ferric chloride, zinc chloride or titanium chloride.

[0012] Furthermore, the cross-coupling reaction catalyst is a palladium-based catalyst, and the palladium-based catalyst is palladium chloride, palladium dichloride or other palladium-containing compounds.

[0013] Furthermore, the cross-coupling reaction solvent is dichloromethane, tetrahydrofuran, diethyl ether or a mixture thereof.

[0014] Furthermore, the nitration reaction catalyst is concentrated sulfuric acid.

[0015] Furthermore, the reaction temperature in step 1 is 60° C. to 80° C., and the reaction time is 4 to 6 hours.

[0016] Furthermore, the cross-coupling reaction temperature in step 2 is 80° C. to 100° C., and the reaction time is 6 to 8 hours.

[0017] Furthermore, the nitration reaction temperature in step 3 is 60° C., and the reaction time is 3 hours.

[0018] According to the method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile of the present invention, the synthesis method has a high reaction yield, can effectively reduce the waste of raw materials, and improve the yield of the product, which can not only reduce the production cost, but also reduce the pollution to the environment, and has high economic and environmental benefits.

[0019] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. DETAILED DESCRIPTION

[0020] The embodiments of the present invention are described in detail below, which are intended to explain the present invention but should not be construed as limiting the present invention.

[0021] The method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to an embodiment of the present invention may include:

[0022] S1, synthesis of 2,6-dichlorobenzeneacetonitrile: benzyl cyanide and chlorine are reacted under the action of a chlorination catalyst. Chlorine is gradually introduced into the reaction system, and appropriate stirring is required to ensure sufficient reaction of chlorine during the reaction. After the reaction is completed, it is cooled to room temperature, washed with water and extracted to obtain 2,6-dichlorobenzeneacetonitrile.

[0023] It should be noted that the chlorination catalyst is one or a combination of aluminum chloride, ferric chloride, zinc chloride or titanium chloride, the reaction temperature in step 1 is 60° C. to 80° C., and the reaction time is 4 to 6 hours.

[0024] S2, introduction of 4-chlorophenyl group: cross-coupling reaction of 2,6-dichlorobenzeneacetonitrile obtained in step 1 with 4-chlorophenylboronic acid or 4-chlorophenyllithium in a solvent. Through this reaction, 4-chlorophenyl group is successfully introduced into 2,6-dichlorobenzeneacetonitrile molecule to obtain intermediate 2,6-dichloro-α-(4-chlorophenyl)benzeneacetonitrile.

[0025] It should be noted that the cross-coupling reaction catalyst is a palladium-based catalyst, and the palladium-based catalyst is palladium chloride, palladium dichloride or other palladium-containing compounds. The cross-coupling reaction solvent is dichloromethane, tetrahydrofuran, diethyl ether or a mixture thereof. The cross-coupling reaction temperature in step 2 is 80° C. to 100° C., and the reaction time is 6 to 8 hours.

[0026] S3, nitration reaction: introducing a nitro group into the intermediate obtained in step 2. Specifically, the intermediate is subjected to a nitration reaction with nitric acid under the catalytic action of sulfuric acid. In this step, nitric acid reacts with the intermediate to introduce a nitro group at the 4-position of the benzene ring to obtain 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile.

[0027] It should be noted that the nitration reaction catalyst is concentrated sulfuric acid, the nitration reaction temperature in step 3 is 60° C., and the reaction time is 3 hours.

[0028] S4, purification: The final product is purified by conventional separation and purification techniques (such as column chromatography, recrystallization, etc.) to obtain the target compound 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile. This step can remove residual impurities and ensure the high purity of the product.

[0029] It should be noted that the purity of the target compound obtained through the purification step is not less than 98%.

[0030] In summary, according to the method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to the embodiment of the present invention, the synthesis method has a high reaction yield, can effectively reduce the waste of raw materials, and improve the yield of the product, which can not only reduce the production cost, but also reduce the pollution to the environment, and has high economic and environmental benefits.

[0031] In the description of this specification, the terms "first" and "second" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In the description of this application, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0032] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0033] Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limitations on the present application. Ordinary technicians in this field can change, modify, replace and modify the above embodiments within the scope of the present application.

Claims

1. A method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile, characterized in that: include: S1. Synthesis of 2,6-dichlorobenzeneacetonitrile: react benzyl cyanide with chlorine in the presence of a chlorination catalyst. Chlorine is gradually introduced into the reaction system, and proper stirring is required during the reaction to ensure sufficient reaction of the chlorine. After the reaction is completed, the mixture is cooled to room temperature, washed with water and extracted to obtain 2,6-dichlorobenzeneacetonitrile; S2, introducing 4-chlorophenyl group: cross-coupling reaction of 2,6-dichlorobenzeneacetonitrile obtained in step 1 with 4-chlorophenylboronic acid or 4-chlorophenyllithium in a solvent. Through this reaction, 4-chlorophenyl group is successfully introduced into 2,6-dichlorobenzeneacetonitrile molecule to obtain intermediate 2,6-dichloro-α-(4-chlorophenyl)benzeneacetonitrile; S3, nitration reaction: introducing a nitro group into the intermediate obtained in step 2. Specifically, the intermediate is subjected to a nitration reaction with nitric acid under the catalytic action of sulfuric acid. In this step, nitric acid reacts with the intermediate to introduce a nitro group at the 4-position of the benzene ring to obtain 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile; S4, purification: The final product is purified by conventional separation and purification techniques (such as column chromatography, recrystallization, etc.) to obtain the target compound 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile. This step can remove residual impurities and ensure the high purity of the product.

2. The method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to claim 1, characterized in that: The chlorination catalyst is one of aluminum chloride, ferric chloride, zinc chloride or titanium chloride or a combination thereof.

3. The method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to claim 1, characterized in that: The cross-coupling reaction catalyst is a palladium-based catalyst, and the palladium-based catalyst is palladium chloride, palladium dichloride or other palladium-containing compounds.

4. The method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to claim 1, characterized in that: The cross-coupling reaction solvent is dichloromethane, tetrahydrofuran, diethyl ether or a mixture thereof.

5. The method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to claim 1, characterized in that: The nitration reaction catalyst is concentrated sulfuric acid.

6. The method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to claim 1, characterized in that: The reaction temperature in step 1 is 60° C. to 80° C., and the reaction time is 4 to 6 hours.

7. The method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to claim 1, characterized in that: The cross-coupling reaction temperature in step 2 is 80° C. to 100° C., and the reaction time is 6 to 8 hours.

8. The method for preparing 2,6-dichloro-α-(4-chlorophenyl)-4-nitrophenylacetonitrile according to claim 1, characterized in that: The nitration reaction temperature in step 3 is 60° C. and the reaction time is 3 hours.