阅读说明：本技术 一种制备对溴苯甲腈的方法 (Method for preparing p-bromobenzonitrile ) 是由 黄惠敏 刘嫚嫚 刘志飞 于高磊 徐波 孙国伟 梅迎华 孙晓川 张轲 于 2021-09-30 设计创作，主要内容包括：本发明公开一种制备对溴苯甲腈的方法,将4-溴-α-苯乙醇和碳酸铵加入有机溶剂中,然后加入铜盐作为催化剂,通入氧气至一定压力并密封反应器,于氧气中100～180℃反应15～60h,得到对溴苯甲腈,并通过柱色谱法分离提纯对溴苯甲腈产物。本方案以对溴苯乙酮和碳酸铵为反应试剂,污染小,生产成本低；通过对本方案所得对溴苯甲腈产物通过气相色谱内标法进行定量,产率最高达81%。(The invention discloses a method for preparing p-bromobenzonitrile, which comprises the steps of adding 4-bromo-alpha-phenethyl alcohol and ammonium carbonate into an organic solvent, then adding copper salt as a catalyst, introducing oxygen to a certain pressure, sealing a reactor, reacting for 15-60 hours at 100-180 ℃ in oxygen to obtain p-bromobenzonitrile, and separating and purifying a p-bromobenzonitrile product by column chromatography. The method takes the bromoacetophenone and the ammonium carbonate as reaction reagents, so that the pollution is low and the production cost is low; by quantifying the obtained p-bromobenzonitrile product by a gas chromatography internal standard method, the yield can reach 81 percent.)

1. A method for preparing p-bromobenzonitrile is characterized in that: adding 4-bromo-alpha-phenylethyl alcohol and ammonium carbonate into an organic solvent according to a certain proportion, then adding copper salt as a catalyst, introducing oxygen to a certain pressure, sealing the reactor, and reacting in oxygen at the reaction temperature of 100-180 ℃ for 15-60 h to obtain the p-bromobenzonitrile.

2. The method for preparing p-bromobenzonitrile as claimed in claim 1, characterized in that: the copper salt is any one of copper acetate, cuprous iodide, cuprous cyanide and copper acetylacetonate.

3. The method for preparing p-bromobenzonitrile as claimed in claim 1, characterized in that: the organic solvent is acetonitrile,N,N-any one of dimethylformamide, dimethylsulfoxide and tetrahydrofuran.

4. The method for preparing p-bromobenzonitrile as claimed in claim 1, characterized in that: in the reactor, the introduction pressure of oxygen is 0.5-8 MPa.

5. The method for preparing p-bromobenzonitrile as claimed in claim 1, characterized in that: adding 3-10 mL of organic solvent into each millimole of 4-bromo-alpha-phenylethyl alcohol.

6. The method for preparing p-bromobenzonitrile as claimed in claim 1, characterized in that: the molar ratio of the 4-bromo-alpha-phenylethyl alcohol to the ammonium carbonate to the copper salt is 1: 0.5-4: 0.2-1.

Technical Field

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

Background

The bromoxynil is also called 4-bromoxynil, is an important bromine fine chemical and is mainly applied to the fields of medicines and organic synthesis. Several new processes have been developed in the chemical industry, such as the reaction of bromoiodobenzene with cyanide to form p-bromobenzonitrile under transition metal catalysis. The other method is dehydrogenation of p-bromophenylethylamine, which is to perform oxidative dehydrogenation in the presence of a transition metal catalyst and an oxidant to obtain p-bromobenzonitrile. The p-bromobenzamide can also be used for synthesizing the p-bromobenzonitrile, and the method is to dehydrate under the action of a catalyst to obtain a target product. Under the catalysis of copper compound and in the presence of oxygen, the p-bromophenylacetic acid undergoes a series of reactions with urea after decarboxylation, and the p-bromophenylnitrile can also be obtained. However, these methods have drawbacks, such as expensive raw materials, high pollution, use of highly toxic reagents, and the like.

Disclosure of Invention

The invention aims to provide a method for preparing p-bromoxynil, which takes p-bromoacetophenone and ammonium carbonate as reaction reagents, and has the advantages of small pollution and low production cost.

The invention adopts the following technical scheme: a method for preparing p-bromobenzonitrile comprises the steps of adding 4-bromo-alpha-phenethyl alcohol and ammonium carbonate into an organic solvent according to a certain proportion, then adding copper salt as a catalyst, introducing oxygen to a certain pressure, sealing a reactor, and reacting in oxygen at the reaction temperature of 100-180 ℃ for 15-60 hours to obtain the p-bromobenzonitrile.

The structural formula of the 4-bromo-alpha-phenethyl alcohol is as follows:

the ammonium carbonate is: (NH)₄)₂CO₃；

The structural formula of the p-bromobenzonitrile is as follows:

the synthetic route of the scheme is as follows:

specifically, the copper salt is any one of copper acetate, cuprous iodide, cuprous cyanide and copper acetylacetonate. Preferably copper acetate.

Specifically, the organic solvent is any one of acetonitrile, N-dimethylformamide, dimethyl sulfoxide and tetrahydrofuran. Dimethyl sulfoxide is preferred.

Specifically, in the reactor, the introduction pressure of oxygen is 0.5-8 MPa. Preferably, the oxygen is introduced at a pressure of 4 MPa.

Specifically, 3-10 mL of organic solvent is added to each millimole of 4-bromo-alpha-phenylethyl alcohol. Preferably 4 mL.

Specifically, the molar ratio of the 4-bromo-alpha-phenylethyl alcohol to the ammonium carbonate to the copper salt is 1: 0.5-4: 0.2-1. Preferably, the molar ratio of the 4-bromo-alpha-phenylethyl alcohol, ammonium carbonate and copper salt is 1:1.5: 0.5.

Preferably, the reaction temperature is 120 ℃ and the reaction time is 40 h.

The basic principle of the invention is as follows: in the scheme, under the catalysis of copper salt, 4-bromine-alpha-phenethyl alcohol reacts with oxygen and undergoes carbon-carbon bond breakage to generate a 4-bromine-benzaldehyde intermediate; the 4-bromo-benzaldehyde intermediate reacts with ammonium carbonate to obtain an imine intermediate. The intermediate is subjected to oxidative dehydrogenation, so that the target product, namely the p-bromobenzonitrile, is obtained.

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

the method for preparing the p-bromobenzonitrile by using the 4-bromo-alpha-phenethyl alcohol as the reaction reagent has low production cost, does not use toxic reagents, and effectively reduces the pollution to the environment.

Secondly, the preparation method of the invention obtains the target product of the p-bromobenzonitrile, and the obtained p-bromobenzonitrile product is purified by using column chromatography (mobile phase: mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 15: 1), and the method utilizes¹³C-NMR and¹H-NMR confirmed the structure of the product as follows:

the obtained p-bromobenzonitrile product is quantified by a gas chromatography internal standard method, and the yield reaches up to 81 percent.

Drawings

FIG. 1 shows the preparation of p-bromobenzonitrile obtained in example 1¹An H-NMR spectrum;

FIG. 2 shows the preparation of p-bromobenzonitrile obtained in example 1¹³A C-NMR spectrum;

FIG. 3 is a reaction scheme of a synthetic route of the present invention;

Detailed Description

The present invention will be explained in more detail with reference to the following examples, but it should be noted that the present invention is not limited to the following examples.

The scheme provides a method for preparing p-bromobenzonitrile, which comprises the following steps of adding 4-bromo-alpha-phenylethyl alcohol, ammonium carbonate, copper salt and an organic solvent into a high-pressure reaction kettle, then filling oxygen and sealing the high-pressure reaction kettle, and reacting to obtain the p-bromobenzonitrile, wherein the specific operation method comprises the following steps: adding 3-10 mL of organic solvent into each millimole of 4-bromo-alpha-phenylethyl alcohol; adding 4-bromo-alpha-phenylethyl alcohol and ammonium carbonate into an organic solvent, wherein the organic solvent is any one of acetonitrile, N-dimethylformamide, dimethyl sulfoxide and tetrahydrofuran; then adding copper salt as a catalyst, wherein the copper salt is any one of copper acetate, cuprous iodide, cuprous cyanide and copper acetylacetonate; feeding the materials according to the molar ratio of the 4-bromo-alpha-phenethyl alcohol to the ammonium carbonate to the copper salt of 1: 0.5-4: 0.2-1. Introducing oxygen, sealing the reactor, reacting for 15-60 h in oxygen with the pressure of 0.5-8 MPa at the reaction temperature of 100-180 ℃ to obtain the p-bromobenzonitrile, and separating and purifying the obtained p-bromobenzonitrile product by column chromatography.

Preferably, the molar ratio of the 4-bromo-alpha-phenylethyl alcohol, ammonium carbonate and copper salt is 1:1.5: 0.5.

Preferably, the reaction temperature is 120 ℃ and the reaction time is 40 h.

Example 1

Adding 0.5mmol of 4-bromo-alpha-phenylethyl alcohol, 0.75mmol of ammonium carbonate, 0.25mmol of copper acetate and 2mL of dimethyl sulfoxide into a high-pressure reaction kettle, filling oxygen with 4MPa, sealing the reaction kettle, and reacting at 120 ℃ for 40 hours; after the reaction was completed, quantitative analysis was performed by gas chromatography internal standard method with a yield of 81%, and the p-bromobenzonitrile product (mobile phase: mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 15: 1) was isolated and purified by column chromatography using the same as shown in FIG. 1¹H-NMR and as shown in FIG. 2¹³C-NMR confirmed the structure of the product as follows:

as shown in fig. 1¹The H-NMR spectrum is matched with that of the compound, wherein delta-7.64 (d, J-8.7 Hz,2H) is the peak of two hydrogens on a benzene ring adjacent to bromine, and 7.53(d, J-8.6 Hz,2H) is the peak of two hydrogens on a benzene ring adjacent to a cyano group, and is matched with the structure of the compound;

as shown in fig. 2¹³The C-NMR spectrum corresponds to that of the compound, and δ is 133.6,132.8,128.2,118.2, 111.4, which corresponds to the structure of the compound.

Examples 2 to 4

The copper acetate in example 1 was replaced with equimolar amounts of cuprous iodide, cuprous cyanide and copper acetylacetonate, respectively, and the other conditions were the same as in example 1. The yields to bromobenzonitrile product were 72%, 63%, 37%, respectively.

Examples 5 to 7

The dimethyl sulfoxide in example 1 was replaced with equal volumes of acetonitrile, N-dimethylformamide, and tetrahydrofuran, respectively, and the other conditions were the same as in example 1. The yields of the product bromobenzonitrile were 67%, 52%, 55%, respectively.

Examples 8 to 11

The amount of dimethyl sulfoxide used in example 1 was changed to 1.5mL, 3mL, 4mL, and 5mL, respectively, and the other conditions were the same as in example 1. The yields to bromobenzonitrile product were 77%, 79%, 65%, 63%, respectively.

Examples 12 to 16

The oxygen pressure in example 1 was changed to 0.5MPa, 1MPa, 2MPa, 6MPa, and 8MPa, respectively, and the other conditions were the same as in example 1. The yields to bromobenzonitrile product were 57%, 69%, 75%, 80%, 79%, respectively.

Examples 17 to 21

The amounts of ammonium carbonate used in example 1 were changed to 0.25mmol, 0.5mmol, 1mmol, 1.5mmol and 2mmol, respectively, and the other conditions were the same as in example 1. The yields to bromobenzonitrile product were 51%, 67%, 77%, 73%, 80%, respectively.

Examples 22 to 26

The amount of copper acetate used in example 1 was changed to 0.1mmol, 0.2mmol, 0.3mmol, 0.4mmol and 0.5mmol, respectively, and the other conditions were the same as in example 1. The yields to bromobenzonitrile product were 59%, 75%, 78%, 72%, 81%, respectively.

Examples 36 to 40

The reaction temperature in example 1 was changed to 100 ℃, 130 ℃, 140 ℃, 150 ℃, 160 ℃, 170 ℃ and 180 ℃ respectively, and the other conditions were the same as in example 1. The yields to bromobenzonitrile product were 17%, 73%, 80%, 70%, 78%, 75%, 73%, respectively.

Examples 41 to 45

The reaction time in example 1 was changed to 15 hours, 25 hours, 35 hours, 50 hours, and 60 hours, respectively, and the other conditions were the same as in example 1. The yields to bromobenzonitrile product were 46%, 67%, 72%, 75%, 70%, respectively.

Although the present invention has been described with reference to a preferred embodiment, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.