Synthesis method of 2-bromo-4 '-chloro-1, 1'-biphenyl

Abstract

The invention belongs to the technical field of synthesis of compounds, and particularly discloses a synthesis method of 2-bromo-4 '-chloro-1, 1'-biphenyl. According to the method, aniline and parachloroiodobenzene are adopted as raw materials, an intermediate 1 is generated through a photocatalytic coupling reaction, and then the intermediate 1 is brominated through diazotization to obtain a final product. According to the method, expensive raw materials such as boric acid needed in the prior art are replaced with low-cost raw materials, the production cost is greatly reduced, and the method is energy-saving, environment-friendly, high in reaction yield in each step, simple in technological operation and suitable for technological amplification production.

Description

technical field

[0001] The invention relates to the technical field of compound synthesis, in particular to a synthesis method of 2-bromo-4'-chloro-1,1'-biphenyl. Background technique

[0002] 2-Bromo-4'-chloro-1,1'-biphenyl compound is a very important intermediate of medicine, pesticide and optoelectronic material, and is a key core structure frequently used in the research and development of medicine, pesticide and optoelectronic material. But its synthetic method has only following synthetic method at present:

[0003] Using o-dibromobenzene and p-chlorophenylboronic acid as raw materials, it is synthesized by Suzuki coupling reaction, and the route is as follows:

[0004]

[0005] In the synthesis method reported above, the raw materials o-dibromobenzene and p-chlorophenylboronic acid are expensive, and an expensive palladium catalyst is required, so the synthesis cost is very high. At the same time, due to containing two bromine atoms, the selectivity of the coupl...

Examples

Embodiment 1

[0026] This example provides a synthesis method of 2-bromo-4'-chloro-1,1'-biphenyl, the synthesis process is as follows:

[0027] (1) Synthesis of intermediate 1

[0028] Aniline (9.3g, 0.1mol) and p-chloroiodobenzene (28.6g, 0.12mol) were added to a mixed solvent of acetonitrile and water (90mL / 10mL), and then cobalt chloride (CoCl 2 ) (0.26g, 0.002mol), fluorescein (2.65g, 0.008mol), and finally the reaction was irradiated with 525nM LED green light at 70°C for 21 hours. TLC monitors that the aniline reaction is complete, then cool down, add 250mL of ethyl acetate, wash with saturated aqueous sodium chloride solution, combine the organic phases, dry and spin dry, and the obtained crude product is dissolved in a small amount of ethyl acetate, and then beaten in petroleum ether to obtain The product of intermediate 1 is 18.4 g in total, and the yield is 90.4%.

[0029] (2) Synthesis of product 2-bromo-4'-chloro-1,1'-biphenyl

[0030] Dissolve Intermediate 1 (2.0g, 0.01mol) ...

Embodiment 2

[0032] This example provides a synthesis method of 2-bromo-4'-chloro-1,1'-biphenyl, the synthesis process is as follows:

[0033] (1) Synthesis of intermediate 1

[0034] Aniline (9.3g, 0.1mol) and p-chloroiodobenzene (28.6g, 0.12mol) were added to a mixed solvent of acetonitrile and water (90mL / 10mL), and then cobalt chloride (CoCl 2 ) (0.26g, 0.002mol), rhodamine (3.8g, 0.008mol), and finally the reaction was irradiated with 525nM LED green light at 70°C for 36 hours. TLC monitors that the aniline reaction is complete, then cool down, add 250mL of ethyl acetate, wash with saturated aqueous sodium chloride solution, combine the organic phases, dry and spin dry, and the obtained crude product is dissolved in a small amount of ethyl acetate, and then beaten in petroleum ether to obtain The product of intermediate 1 is 16.6g in total, and the yield is 81.6%.

[0035] (2) Synthesis of product 2-bromo-4'-chloro-1,1'-biphenyl

[0036] Intermediate 1 (2.0g, 0.01mol) was dissolved...

Embodiment 3

[0038] This example provides a synthesis method of 2-bromo-4'-chloro-1,1'-biphenyl, the synthesis process is as follows:

[0039] (1) Synthesis of intermediate 1

[0040] Aniline (930g, 10mol) and p-chloroiodobenzene (2860g, 12mol) were added to a mixed solvent of acetonitrile and water (9L / 1L), and then cobalt chloride (CoCl 2 ) (26g, 0.2mol), fluorescein (265g, 0.8mol), and finally the reaction was irradiated with 525nM LED green light at 70°C for 36 hours. TLC monitors that the aniline reaction is complete, then lowers the temperature, adds 20L of ethyl acetate, washes with saturated aqueous sodium chloride solution, combines the organic phases, dries and spins to dry, and dissolves the obtained crude product in ethyl acetate, then beats in petroleum ether to obtain intermediate The product of body 1 is 1821g in total, and the yield is 89.5%.

[0041] (2) Synthesis of product 2-bromo-4'-chloro-1,1'-biphenyl

[0042] Intermediate 1 (200g, 1mol) was dissolved in 0.5mol / L h...

technical field

[0001] The invention relates to the technical field of compound synthesis, in particular to a synthesis method of 2-bromo-4'-chloro-1,1'-biphenyl. Background technique

[0002] 2-Bromo-4'-chloro-1,1'-biphenyl compound is a very important intermediate of medicine, pesticide and optoelectronic material, and is a key core structure frequently used in the research and development of medicine, pesticide and optoelectronic material. But its synthetic method has only following synthetic method at present:

[0003] Using o-dibromobenzene and p-chlorophenylboronic acid as raw materials, it is synthesized by Suzuki coupling reaction, and the route is as follows:

[0004]

[0005] In the synthesis method reported above, the raw materials o-dibromobenzene and p-chlorophenylboronic acid are expensive, and an expensive palladium catalyst is required, so the synthesis cost is very high. At the same time, due to containing two bromine atoms, the selectivity of the coupl...

Examples

Embodiment 1

[0026] This example provides a synthesis method of 2-bromo-4'-chloro-1,1'-biphenyl, the synthesis process is as follows:

[0027] (1) Synthesis of intermediate 1

[0028] Aniline (9.3g, 0.1mol) and p-chloroiodobenzene (28.6g, 0.12mol) were added to a mixed solvent of acetonitrile and water (90mL / 10mL), and then cobalt chloride (CoCl 2 ) (0.26g, 0.002mol), fluorescein (2.65g, 0.008mol), and finally the reaction was irradiated with 525nM LED green light at 70°C for 21 hours. TLC monitors that the aniline reaction is complete, then cool down, add 250mL of ethyl acetate, wash with saturated aqueous sodium chloride solution, combine the organic phases, dry and spin dry, and the obtained crude product is dissolved in a small amount of ethyl acetate, and then beaten in petroleum ether to obtain The product of intermediate 1 is 18.4 g in total, and the yield is 90.4%.

[0029] (2) Synthesis of product 2-bromo-4'-chloro-1,1'-biphenyl

[0030] Dissolve Intermediate 1 (2.0g, 0.01mol) ...

Embodiment 2

[0032] This example provides a synthesis method of 2-bromo-4'-chloro-1,1'-biphenyl, the synthesis process is as follows:

[0033] (1) Synthesis of intermediate 1

[0034] Aniline (9.3g, 0.1mol) and p-chloroiodobenzene (28.6g, 0.12mol) were added to a mixed solvent of acetonitrile and water (90mL / 10mL), and then cobalt chloride (CoCl 2 ) (0.26g, 0.002mol), rhodamine (3.8g, 0.008mol), and finally the reaction was irradiated with 525nM LED green light at 70°C for 36 hours. TLC monitors that the aniline reaction is complete, then cool down, add 250mL of ethyl acetate, wash with saturated aqueous sodium chloride solution, combine the organic phases, dry and spin dry, and the obtained crude product is dissolved in a small amount of ethyl acetate, and then beaten in petroleum ether to obtain The product of intermediate 1 is 16.6g in total, and the yield is 81.6%.

[0035] (2) Synthesis of product 2-bromo-4'-chloro-1,1'-biphenyl

[0036] Intermediate 1 (2.0g, 0.01mol) was dissolved...

Embodiment 3

[0038] This example provides a synthesis method of 2-bromo-4'-chloro-1,1'-biphenyl, the synthesis process is as follows:

[0039] (1) Synthesis of intermediate 1

[0040] Aniline (930g, 10mol) and p-chloroiodobenzene (2860g, 12mol) were added to a mixed solvent of acetonitrile and water (9L / 1L), and then cobalt chloride (CoCl 2 ) (26g, 0.2mol), fluorescein (265g, 0.8mol), and finally the reaction was irradiated with 525nM LED green light at 70°C for 36 hours. TLC monitors that the aniline reaction is complete, then lowers the temperature, adds 20L of ethyl acetate, washes with saturated aqueous sodium chloride solution, combines the organic phases, dries and spins to dry, and dissolves the obtained crude product in ethyl acetate, then beats in petroleum ether to obtain intermediate The product of body 1 is 1821g in total, and the yield is 89.5%.

[0041] (2) Synthesis of product 2-bromo-4'-chloro-1,1'-biphenyl

[0042] Intermediate 1 (200g, 1mol) was dissolved in 0.5mol / L h...

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