Preparation method of substituted biphenyl

Abstract

The invention discloses a preparation method of substituted biphenyl. The preparation method comprises the following step of performing a coupling reaction on a compound 2 and a compound 3 under anhydrous conditions in a solvent in the presence of Ni salt and ZnX<3>X<4>, so as to obtain the substituted biphenyl, wherein the Ni salt is one or more of NiX<5>X<6> (PPh3)2, NiX<7>X<8>(dppp), NiX<9>X<10>(dppf), NiX<11>X<12>(dppe) and acetylacetone nickel, and the mole ratio of the ZnX<3>X<4> to the compound 3 is less than 1. The method has the advantages of mild reaction conditions, simple process, safety in operation, low equipment requirement, simplicity in postprocessing, less environmental pollution, easiness in industrial production, low zinc halide consumption, low cost, high yield and high product purity.

Description

technical field

[0001] The invention relates to a preparation method of substituted biphenyl. Background technique

[0002] 4-cyanobiphenyls are an important intermediate of liquid crystal materials, which are widely used in the fields of medicine, pesticides, spices and dyes. Due to regioselectivity, the traditional synthesis method has low atom utilization rate, high toxicity of raw materials, long steps, heavy environmental pollution, many wastes, high requirements for equipment, and low yield, which lead to increased industrial production costs.

[0003] The most commonly used method for the synthesis of 4-cyanobiphenyl reported both at home and abroad is:

[0004] 1. Biphenyl method 1: This method uses biphenyl as raw material, reacts with bromine to obtain 4-bromobiphenyl, and then reacts with copper cyanide or cuprous cyanide to obtain the product; the reaction formula is as follows:

[0005]

[0006] 2. Biphenyl method 2: This method uses biphenyl as a raw mater...

Examples

Embodiment 14

[0073] The preparation of embodiment 14-cyanobiphenyl

[0074] The preparation of step 1 phenylmagnesium chloride Grignard reagent

[0075] In the 1L reaction flask, add 283.32g tetrahydrofuran, 22.18g (0.924mol) magnesium chips, add 94.44g (0.84mol) chlorobenzene, 94.44g tetrahydrofuran in the dropping funnel, after adding, drop a small amount of chlorobenzene into the reaction flask , start stirring, and after the reaction is initiated, raise the temperature of the system to 45-50°C, start adding the remaining chlorobenzene solution dropwise, and keep the temperature of the reaction system between 45-50°C. After the reaction of the raw materials is detected, the temperature of the reaction bottle is lowered to 20-25° C., and it is stored under nitrogen protection for later use. Yield 95%.

[0076] Step 24 - Preparation of cyanobiphenyl

[0077] In another 1L four-necked reaction flask, under nitrogen protection, 219.54g tetrahydrofuran, 73.18g (0.532mol) p-chlorobenzonitr...

Embodiment 2

[0079] The preparation of step 1 phenylmagnesium chloride Grignard reagent

[0080] In the 1L reaction flask, add 283.32g tetrahydrofuran, 22.18g (0.924mol) magnesium chips, add 94.44g (0.84mol) chlorobenzene, 94.44g tetrahydrofuran in the dropping funnel, after adding, drop a small amount of chlorobenzene into the reaction flask , start stirring, and after the reaction is initiated, raise the temperature of the system to 45-50°C, start adding the remaining chlorobenzene solution dropwise, and keep the temperature of the reaction system between 45-50°C. After the reaction of the raw materials is detected, the temperature of the reaction bottle is lowered to 20-25° C., and under the protection of nitrogen, 0.73 g (0.00532 mol) of zinc chloride is added therein and stored for later use. Yield 95%.

[0081] Step 24 - Preparation of cyanobiphenyl

[0082] In another 1L four-necked reaction flask, under nitrogen protection, 219.54g tetrahydrofuran, 73.18g (0.532mol) p-chlorobenzo...

Embodiment 34

[0083] The preparation of embodiment 34-cyanobiphenyl

[0084] The preparation of step 1 phenylmagnesium chloride Grignard reagent

[0085] With embodiment 1.

[0086] Step 24 - Preparation of cyanobiphenyl

[0087] In another 1L four-necked reaction flask, under nitrogen protection, 219.54g tetrahydrofuran, 73.18g (0.532mol) p-chlorobenzonitrile, 0.73g (0.00532mol) zinc chloride, 0.29g (0.000532mol) (dppp) were successively added NiCl 2 , start stirring, lower the temperature of the reaction system to 10-15°C, dropwise add the phenylmagnesium chloride Grignard reagent produced in step 1 to the system, keep the temperature at 10-15°C, add the time for 3 hours, after the addition is complete, keep the temperature for 4h , take a sample to detect that the reaction is complete, add dilute hydrochloric acid dropwise to the reaction solution, quench the reaction, stir for 10 min, leave it to stand, and separate layers, wash the organic layer with 5% sodium chloride solution, lea...

technical field

[0001] The invention relates to a preparation method of substituted biphenyl. Background technique

[0002] 4-cyanobiphenyls are an important intermediate of liquid crystal materials, which are widely used in the fields of medicine, pesticides, spices and dyes. Due to regioselectivity, the traditional synthesis method has low atom utilization rate, high toxicity of raw materials, long steps, heavy environmental pollution, many wastes, high requirements for equipment, and low yield, which lead to increased industrial production costs.

[0003] The most commonly used method for the synthesis of 4-cyanobiphenyl reported both at home and abroad is:

[0004] 1. Biphenyl method 1: This method uses biphenyl as raw material, reacts with bromine to obtain 4-bromobiphenyl, and then reacts with copper cyanide or cuprous cyanide to obtain the product; the reaction formula is as follows:

[0005]

[0006] 2. Biphenyl method 2: This method uses biphenyl as a raw mater...

Examples

Embodiment 14

[0073] The preparation of embodiment 14-cyanobiphenyl

[0074] The preparation of step 1 phenylmagnesium chloride Grignard reagent

[0075] In the 1L reaction flask, add 283.32g tetrahydrofuran, 22.18g (0.924mol) magnesium chips, add 94.44g (0.84mol) chlorobenzene, 94.44g tetrahydrofuran in the dropping funnel, after adding, drop a small amount of chlorobenzene into the reaction flask , start stirring, and after the reaction is initiated, raise the temperature of the system to 45-50°C, start adding the remaining chlorobenzene solution dropwise, and keep the temperature of the reaction system between 45-50°C. After the reaction of the raw materials is detected, the temperature of the reaction bottle is lowered to 20-25° C., and it is stored under nitrogen protection for later use. Yield 95%.

[0076] Step 24 - Preparation of cyanobiphenyl

[0077] In another 1L four-necked reaction flask, under nitrogen protection, 219.54g tetrahydrofuran, 73.18g (0.532mol) p-chlorobenzonitr...

Embodiment 2

[0079] The preparation of step 1 phenylmagnesium chloride Grignard reagent

[0080] In the 1L reaction flask, add 283.32g tetrahydrofuran, 22.18g (0.924mol) magnesium chips, add 94.44g (0.84mol) chlorobenzene, 94.44g tetrahydrofuran in the dropping funnel, after adding, drop a small amount of chlorobenzene into the reaction flask , start stirring, and after the reaction is initiated, raise the temperature of the system to 45-50°C, start adding the remaining chlorobenzene solution dropwise, and keep the temperature of the reaction system between 45-50°C. After the reaction of the raw materials is detected, the temperature of the reaction bottle is lowered to 20-25° C., and under the protection of nitrogen, 0.73 g (0.00532 mol) of zinc chloride is added therein and stored for later use. Yield 95%.

[0081] Step 24 - Preparation of cyanobiphenyl

[0082] In another 1L four-necked reaction flask, under nitrogen protection, 219.54g tetrahydrofuran, 73.18g (0.532mol) p-chlorobenzo...

Embodiment 34

[0083] The preparation of embodiment 34-cyanobiphenyl

[0084] The preparation of step 1 phenylmagnesium chloride Grignard reagent

[0085] With embodiment 1.

[0086] Step 24 - Preparation of cyanobiphenyl

[0087] In another 1L four-necked reaction flask, under nitrogen protection, 219.54g tetrahydrofuran, 73.18g (0.532mol) p-chlorobenzonitrile, 0.73g (0.00532mol) zinc chloride, 0.29g (0.000532mol) (dppp) were successively added NiCl 2 , start stirring, lower the temperature of the reaction system to 10-15°C, dropwise add the phenylmagnesium chloride Grignard reagent produced in step 1 to the system, keep the temperature at 10-15°C, add the time for 3 hours, after the addition is complete, keep the temperature for 4h , take a sample to detect that the reaction is complete, add dilute hydrochloric acid dropwise to the reaction solution, quench the reaction, stir for 10 min, leave it to stand, and separate layers, wash the organic layer with 5% sodium chloride solution, lea...

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