CN113636952B

CN113636952B - Method for preparing 4-bromobenzamide

Info

Publication number: CN113636952B
Application number: CN202110811796.9A
Authority: CN
Inventors: 田欣哲; 任运来; 刘文波; 郭莹港
Original assignee: Henan Agricultural University
Current assignee: Henan Agricultural University
Priority date: 2021-07-19
Filing date: 2021-07-19
Publication date: 2023-07-21
Anticipated expiration: 2041-07-19
Also published as: CN113636952A

Abstract

The invention relates to a method for preparing 4-bromobenzamide, which comprises the steps of mixing 4-bromobenzyl chloride and potassium ferrocyanide trihydrate with an organic solvent, and reacting for 10-60 hours at 120-160 ℃ in oxygen in the presence of a catalyst 1, 10-phenanthroline/copper salt to prepare the 4-bromobenzamide. The method uses potassium ferrocyanide trihydrate as a reaction reagent, and has the advantages of simple synthesis method, low production cost and little pollution.

Description

Method for preparing 4-bromobenzamide

Technical Field

The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a method for preparing 4-bromobenzamide.

Background

4-bromobenzamide is an important organic synthesis intermediate and can be used for synthesizing medicines or dyes such as methyl anthranilate, bifenthrin, procainamide hydrochloride, cisapride and the like (Chinese medical biotechnology, 2020, volume 15, pages 603-607). There are a number of methods for synthesizing 4-bromobenzamide. The method mainly comprises the following steps: (1) 4-bromobenzylamine is used as a raw material, and 4-bromobenzamide is generated through the reaction of benzyl carbon-hydrogen bond and oxygen under the catalysis of transition metal (ChemCatChem, 2019, volume 11, pages 401-406). (2) 4-bromobenzaldehyde is used as a raw material, and a 4-bromobenzamide product is obtained through the reaction of hydroxylamine hydrochloride and aldehyde groups under the catalysis of transition metal (Journal of Organometallic Chemistry, 2019, 894 and 67-77). (3) 4-bromobenzamide products were obtained by selective hydrolysis of cyano groups under transition metal catalysis starting from 4-bromobenzonitrile (Chemical Science, 2019, volume 10, pages 10647-10652). (4) 4-bromobenzyl chloride is used as a raw material, and is reacted with reagents such as hydrazine, ammonia molecules/oxidizing agent, azide salts/oxidizing agent and the like to obtain a 4-bromobenzamide product (Tetrahedron Letters, 2010, volume 51, pages 5328-5332). However, the existing synthesis method has the defects of harsh synthesis conditions, high cost, serious environmental pollution and the like.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a method for preparing 4-bromobenzamide, which takes potassium ferrocyanide trihydrate as a reaction reagent, and has the advantages of simple synthesis method, low production cost and little pollution.

In order to achieve the aim of the invention, the invention adopts the following technical scheme:

the preparation method of the 4-bromobenzamide comprises the steps of mixing 4-bromobenzyl chloride, potassium ferrocyanide trihydrate and an organic solvent, and reacting for 10-60 hours at 120-160 ℃ in oxygen in the presence of a catalyst 1, 10-phenanthroline/copper salt to obtain the 4-bromobenzamide.

The structural formula of the 4-bromobenzyl chloride is as follows:；

the structural formula of the 4-bromobenzamide is as follows:；

the potassium ferrocyanide trihydrate is: k (K) ₄ [Fe(CN) ₆ ]·3H ₂ O 。

Further, the copper salt is any one of cuprous chloride, cupric nitrate, cuprous bromide, copper trifluoromethane sulfonate, cuprous iodide, cupric chloride, cupric acetate, cupric acetylacetonate and cupric sulfate, preferably cuprous chloride.

Further, the organic solvent is any one of dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone and tetrahydrofuran, preferably dimethyl sulfoxide.

Specifically, the molar ratio of the 4-bromobenzyl chloride, the potassium ferrocyanide trihydrate, the 1, 10-phenanthroline and the copper salt is 1: (0.5 to 6): (0.5 to 6): (0.4 to 4).

Further preferably, the molar ratio of the 4-bromobenzyl chloride, the potassium ferrocyanide trihydrate, the 1, 10-phenanthroline and the copper salt is 1:1.5:1:1.

further, the amount of the organic solvent is 2-16 mL, preferably 4mL, of the organic solvent per millimole of 4-bromobenzyl chloride.

In the method for preparing 4-bromobenzamide, the pressure of the oxygen is 0.5-8 MPa, preferably 1.5MPa.

Preferably, in the preparation process, the reaction temperature is 120-160 ℃, the reaction time is 10-60 h, and optimally, the reaction temperature is 140 ℃ and the reaction time is 30h.

Compared with the prior art, the invention has the following beneficial effects:

the basic principle of the invention is as follows: under the catalysis of 1, 10-phenanthroline/copper salt, 4-bromobenzyl chloride reacts with oxygen to generate 4-bromobenzoyl free radical; the free radical reacts with potassium ferrocyanide and oxygen to generate benzoyl isocyanate intermediate; the intermediate is hydrolyzed under the catalysis of copper salt to generate 4-bromobenzamide. Specifically, 4-bromobenzyl chloride, potassium ferrocyanide trihydrate, 1, 10-phenanthroline, copper salt and an organic solvent are added into a high-pressure reaction kettle, then oxygen is filled into the high-pressure reaction kettle, and the reaction kettle is sealed, so that 4-bromobenzamide is prepared by the reaction, wherein the reaction formula is as follows:

。

the obtained product 4-bromobenzamide is quantified by a gas chromatography internal standard method, the yield is up to 87%, the product is purified by column chromatography (mobile phase: mixed solvent of petroleum ether and ethyl acetate with volume ratio of 10:1), and the product is utilized ¹³ C-NMR ¹ H-NMR confirmed the product structure as follows:

。

the invention takes 4-bromobenzyl chloride as a reaction reagent, and provides a method for preparing 4-bromobenzamide, which is simple and convenient, has low production cost, does not use toxic reagents, and reduces environmental pollution.

Drawings

FIG. 1 shows the 4-bromobenzamide prepared in example 1 ¹ H-NMR spectrum;

FIG. 2 shows the 4-bromobenzamide prepared in example 1 ¹³ C-NMR spectrum.

Detailed Description

In order to make the technical objects, technical solutions and advantageous effects of the present invention more apparent, the technical solutions of the present invention will be further described with reference to the accompanying drawings and specific examples, but the examples are intended to illustrate the present invention and should not be construed as limiting the present invention, and specific techniques or conditions are not specified in the examples, and the reagents or apparatuses used are conventional products which are commercially available according to the techniques or conditions described in the literature in the art or according to the specifications of the products.

Example 1

A method for preparing 4-bromobenzamide, which comprises the following steps:

adding 0.5mmol of 4-bromobenzyl chloride, 0.75mmol of potassium ferrocyanide trihydrate, 0.5mmol of 1, 10-phenanthroline, 0.5mmol of cuprous chloride and 2mL of dimethyl sulfoxide into a high-pressure reaction kettle, filling 1.5MPa of oxygen, sealing the reaction kettle, and reacting at 140 ℃ for 30h; after the reaction was completed, quantitative analysis was performed by using a gas chromatography internal standard method, the yield was 87%, and the 4-bromobenzamide product was separated and purified by column chromatography (mobile phase: mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1) using a solution as shown in FIG. 1 ¹ H-NMR and As shown in FIG. 2 ¹³ The structure of the product was determined by C-NMR as follows:

。

shown in FIG. 1 ¹ The H-NMR spectrum corresponds to that of the compound described in the literature (Inorg. Chem. 2020, 59, 16582-16590): wherein the method comprises the steps ofδPeaks at=2.35 and 2.51 for solvent DMSO and water respectively,δat=8.05 (s, 1H) and 7.46 (s, 1H) are peaks of two hydrogens on the amido group, 7.82 (d,Jat 8.5 Hz, 2H) is the peak of amido ortho-hydrogen on the benzene ring, 7.67 (d,J=8.5 Hz, 2H) is the peak of bromo ortho-hydrogen on the benzene ring,is consistent with the structure of the compound.

Shown in FIG. 2 ¹³ The C-NMR spectrum corresponds to that of the compound described in the literature (Inorg. Chem. 2020, 59, 16582-16590):δ=167.4, 133.9, 131.7, 130.1, 125.5, in agreement with the structure of the compound.

Examples 2 to 9

The copper chloride in example 1 was replaced with copper nitrate, copper bromide, copper trifluoromethane sulfonate, copper iodide, copper chloride, copper acetate, copper acetylacetonate, and copper sulfate in equimolar amounts, respectively, and the other conditions were the same as in example 1. The yields of the 4-bromobenzamide products were 71%, 68%, 76%, 82%, 67%, 51%, 57%, 39%, respectively.

Examples 10 to 12

The dimethyl sulfoxide of example 1 was replaced with equal volumes of N, N-dimethylformamide, N-methylpyrrolidone and tetrahydrofuran, respectively, with the other conditions being the same as in example 1. The yields of the 4-bromobenzamide products were 72%, 64%, 39%, respectively.

Examples 13 to 16

The amounts of dimethyl sulfoxide in example 1 were 1mL, 3mL, 4mL and 8mL, respectively, and the other conditions were the same as in example 1. The yields of the 4-bromobenzamide products were 73%, 82%, 70%, 51%, respectively.

Examples 17 to 21

The oxygen pressure in example 1 was changed to 0.5 MPa, 1 MPa, 3 MPa, 5MPa, 8MPa, respectively, and the other conditions were the same as in example 1. The yields of the 4-bromobenzamide products were 31%, 70%, 82%, 85%, 82%, respectively.

Examples 22 to 26

The amounts of potassium ferrocyanide trihydrate in example 1 were changed to 0.25mmol, 0.5mmol, 1mmol, 1.5mmol and 3mmol, respectively, and the other conditions were the same as in example 1. The yields of the 4-bromobenzamide products were 37%, 66%, 82%, 85%, 81%, respectively.

Examples 27 to 31

The amount of 1, 10-phenanthroline in example 1 was changed to 0.25mmol, 1mmol, 1.5mmol, 2mmol and 3mmol, respectively, and the other conditions were the same as in example 1. The yields of the 4-bromobenzamide products were 64%, 80%, 85%, 83%, 77%, respectively.

Examples 32 to 36

The amounts of cuprous chloride used in example 1 were changed to 0.2mmol, 0.4mmol, 0.8mmol, 1mmol and 2mmol, respectively, and the other conditions were the same as in example 1. The yields of the 4-bromobenzamide products were 22%, 72%, 85%, 83%, 80%, respectively.

Examples 37 to 40

The reaction temperature in example 1 was changed to 120℃and 130℃and 150℃and 160℃respectively, and the other conditions were the same as in example 1. The yields of the 4-bromobenzamide products were 63%, 79%, 82%, 87%, respectively.

Examples 41 to 50

The reaction times in example 1 were changed to 10h, 15h, 20h, 25h, 35h, 40h, 45h, 50h, 55h, 60h, respectively, and the other conditions were the same as in example 1. The yields of the 4-bromobenzamide products were 44%, 73%, 83%, 85%, 80%, 83%, 81%, 80%, 86%, 83%, respectively.

Finally, what should be said is: the above embodiments are only for illustrating the technical solution of the present invention, and any equivalent replacement of the present invention and modification or partial replacement without departing from the spirit and scope of the present invention should be covered in the scope of the claims of the present invention.

Claims

1. The method for preparing the 4-bromobenzamide is characterized in that 4-bromobenzyl chloride and potassium ferrocyanide trihydrate are mixed with an organic solvent and then react for 10-60 hours at 120-160 ℃ in oxygen in the presence of a catalyst 1, 10-phenanthroline/copper salt to prepare the 4-bromobenzamide;

the copper salt is any one of cuprous chloride, cupric nitrate, cuprous bromide, copper trifluoromethane sulfonate, cuprous iodide, cupric chloride, cupric acetate, cupric acetylacetonate and cupric sulfate;

the organic solvent is any one of dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone and tetrahydrofuran.

2. The method for preparing 4-bromobenzamide according to claim 1, wherein the molar ratio of 4-bromobenzyl chloride, potassium ferrocyanide trihydrate, 1, 10-phenanthroline and copper salt is 1: (0.5 to 6): (0.5 to 6): (0.4 to 4).

3. The method for preparing 4-bromobenzamide according to claim 2, wherein the molar ratio of 4-bromobenzyl chloride, potassium ferrocyanide trihydrate, 1, 10-phenanthroline and copper salt is 1:1.5:1:1.

4. the method for preparing 4-bromobenzamide according to claim 1, wherein the amount of the organic solvent is 2-16 ml of the organic solvent per millimole of 4-bromobenzyl chloride.

5. The method for preparing 4-bromobenzamide according to claim 1, wherein the oxygen gas has a pressure of 0.5-8 mpa.