阅读说明：本技术 一种制备大茴香腈的方法 (Method for preparing anisyl nitrile ) 是由 徐波 孙国伟 张轲 于高磊 刘嫚嫚 刘志飞 黄惠敏 梅迎华 孙晓川 于 2021-09-30 设计创作，主要内容包括：本发明公开一种制备大茴香腈的方法,将4-甲氧基苄氯和三水合亚铁氰化钾按照一定比例加入有机溶剂中,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,于氧气中在反应温度为120～160℃条件下,进行反应10～50h,得到大茴香腈；本方案以三水合亚铁氰化钾为反应试剂,生产成本低,没有使用有毒试剂,不会造成环境污染。(The invention discloses a method for preparing anisyl nitrile, which comprises the steps of adding 4-methoxybenzyl chloride and potassium ferrocyanide trihydrate 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 120-160 ℃ for 10-50 h to obtain the anisyl nitrile; the scheme takes potassium ferrocyanide trihydrate as a reaction reagent, has low production cost, does not use toxic reagents, and does not cause environmental pollution.)

1. A method for preparing anisyl nitrile, which is characterized by comprising the following steps: adding 4-methoxybenzyl chloride and potassium ferrocyanide trihydrate 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 for 10-50 h in oxygen at the reaction temperature of 120-160 ℃ to obtain the anisic nitrile.

2. The process for producing anisidine of claim 1 wherein: the copper salt is any one of copper trifluoromethanesulfonate, cuprous bromide, copper nitrate, cuprous iodide, cupric chloride, cupric acetate, copper acetylacetonate, cuprous chloride and copper sulfate.

3. The process for producing anisidine of claim 1 wherein: the organic solvent is any one of N, N-dimethylformamide, N-methylpyrrolidone, tetrahydrofuran and dimethyl sulfoxide.

4. The process for producing anisidine of claim 3 wherein: the dosage of the organic solvent is 2-8 mL of the organic solvent added into every millimole of 4-methoxybenzyl chloride.

5. The process for producing anisidine of claim 3 wherein: and introducing oxygen into the reactor under the pressure of 1-10 MPa.

6. The process for producing anisidine of claim 3 wherein: the molar ratio of the 4-methoxybenzyl chloride to the potassium ferrocyanide trihydrate to the copper salt is 1: 1-6: 0.3-6.

Technical Field

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

Background

The anisic nitrile is also called 4-methoxybenzonitrile, is an artificial synthetic spice with excellent performance, and has wider and wider market prospect. In industry, anisic aldehyde is mainly used as a raw material to synthesize anisic nitrile, namely, the intermediate anisic aldehyde oxime is obtained through the reaction of the anisic aldehyde and hydroxylamine hydrochloride; the intermediate is dehydrated under the action of acetic anhydride to obtain the anisyl nitrile. The method has low conversion rate of raw materials, troublesome purification treatment and large consumption of acetic anhydride. Several new processes have been developed in the chemical industry, such as the conversion of 4-methoxy halobenzenes with cyanides to anisyl nitriles under transition metal catalysis. Under the catalysis of transition metal, 4-methoxyaniline is subjected to oxidative dehydrogenation to obtain the anisyl nitrile product. Under the catalysis of transition metal, 4-methoxyphenylboronic acid reacts with cyanide to obtain the anisyl nitrile.

Disclosure of Invention

The invention aims to provide a method for preparing anisic nitrile, which takes 4-methoxybenzyl chloride and potassium ferrocyanide trihydrate as reaction reagents, and has the advantages of little pollution and low production cost.

The invention adopts the following technical scheme: a method for preparing anisic nitrile comprises the steps of adding 4-methoxybenzyl chloride and potassium ferrocyanide trihydrate 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 120-160 ℃ for 10-50 hours to obtain the anisic nitrile;

the structural formula of the 4-methoxybenzyl chloride is as follows:

the potassium ferrocyanide trihydrate is: k₄[Fe(CN)₆]·3H₂O；

The structural formula of the anisic nitrile is as follows:

the synthetic route of the scheme is as follows:

specifically, the copper salt is any one of copper trifluoromethanesulfonate, cuprous bromide, cupric nitrate, cuprous iodide, cupric chloride, cupric acetate, copper acetylacetonate, cuprous chloride and cupric sulfate. Preferably cuprous chloride.

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

Specifically, the amount of the organic solvent is 2-8 mL of the organic solvent per millimole of 4-methoxybenzyl chloride, and preferably 3mL of the organic solvent per millimole of 4-methoxybenzyl chloride.

Specifically, the pressure range of the introduced oxygen in the reactor is 1-10 MPa. Preferably 2 MPa.

Specifically, the molar ratio of the 4-methoxybenzyl chloride to the potassium ferrocyanide trihydrate to the copper salt is 1: 1-6: 0.3-6. Most preferably, the molar ratio of 4-methoxybenzyl chloride, potassium ferrocyanide trihydrate and copper salt is 1:1.5: 1.2.

Preferably, the scheme is carried out for 30 hours in oxygen at the reaction temperature of 140 ℃ to obtain the anisyl nitrile;

the working principle of the scheme is as follows: in the scheme, under the catalysis of copper salt, 4-methoxybenzyl chloride can react with oxygen to generate acyl free radicals; the free radical reacts with potassium ferrocyanide and oxygen to generate a benzoyl isocyanate reactive intermediate; removing a molecule of carbon dioxide from the intermediate under the action of a catalyst to obtain an anisidine product.

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

the method for preparing the anisidine by using the 4-methoxybenzyl chloride as the reaction reagent does not use toxic reagents such as ammonia gas or sodium azide, does not cause environmental pollution, and has low production cost.

Secondly, the invention quantifies the obtained anisidine product by a gas chromatography internal standard method, the yield can reach 92 percent, and the product is purified by column chromatography (mobile phase: mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 12: 1) by utilizing¹³C-NMR and¹H-NMR confirmed the structure of the product as follows:

drawings

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

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

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

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 anisyl nitrile, which comprises the following steps of adding 4-methoxybenzyl chloride, potassium ferrocyanide trihydrate, copper salt and an organic solvent into a high-pressure reaction kettle, introducing oxygen to a certain pressure, sealing the reaction kettle, and reacting to obtain the anisyl nitrile, wherein the specific operation method comprises the following steps: adding 4-methoxybenzyl chloride and potassium ferrocyanide trihydrate into an organic solvent according to the proportion that 2-8 mL of the organic solvent is added into 4-methoxybenzyl chloride per millimole, wherein the organic solvent is any one of N, N-dimethylformamide, N-methylpyrrolidone, tetrahydrofuran and dimethyl sulfoxide. Then adding copper salt as a catalyst, wherein the copper salt is any one of copper trifluoromethanesulfonate, cuprous bromide, cupric nitrate, cuprous iodide, cupric chloride, cupric acetate, cupric acetylacetonate, cuprous chloride and cupric sulfate. The materials are fed according to the molar ratio of 4-methoxybenzyl chloride to potassium ferrocyanide trihydrate to copper salt of 1: 1-6: 0.3-6. And introducing oxygen, sealing the reactor, and reacting for 10-50 hours in oxygen with the pressure of 1-10 MP at the reaction temperature of 120-160 ℃ to obtain the anisic nitrile.

Preferably, the amount of organic solvent used is 3mL of organic solvent per millimole of 4-methoxybenzyl chloride.

Preferably, the pressure of the oxygen is in the range of 2 MPa.

Preferably, the molar ratio of the 4-methoxybenzyl chloride, potassium ferrocyanide trihydrate and copper salt is 1:1.5: 1.2.

Example 1

Adding 0.5mmol of 4-methoxybenzyl chloride, 0.75mmol of potassium ferrocyanide trihydrate, 0.6mmol of cuprous chloride and 1.5mL of dimethyl sulfoxide into a high-pressure reaction kettle, filling 2MPa of oxygen, sealing the reaction kettle, and reacting at the reaction temperature of 140 ℃ for 30 hours; after the reaction was completed, quantitative analysis was performed by gas chromatography internal standard method with a yield of 92%, and the anisonitrile product was separated and purified by column chromatography (mobile phase: mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 12: 1) 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 is 3.87(s,3H) as a peak of methyl, 6.96(d, J is 8.9Hz,2H) as a peak of methoxy ortho-position hydrogen on a benzene ring, and 7.60(d, J is 8.9Hz,2H) as a peak of cyano ortho-position hydrogen on the benzene ring, and the structure of the compound is matched;

as shown in fig. 2¹³The C-NMR spectrum matches the spectrum of the compound, where δ is 162.9,134.0,119.2,114.8,104.0,55.6, matching the structure of the compound.

Examples 2 to 9

The cuprous chloride in example 1 was replaced with equimolar amounts of copper trifluoromethanesulfonate, cuprous bromide, copper nitrate, cuprous iodide, copper chloride, copper acetate, copper acetylacetonate, and copper sulfate, respectively, and the other conditions were the same as in example 1. The yields of the anisonitrile product were 87%, 64%, 46%, 89%, 71%, 55%, 64%, 40%, respectively.

Examples 10 to 12

The dimethyl sulfoxide in example 1 was replaced with equal volumes of N, N-dimethylformamide, N-methylpyrrolidone and tetrahydrofuran, respectively, and the other conditions were the same as in example 1. The yields of the anisonitrile product were 83%, 57%, 30%, respectively.

Examples 13 to 16

The amount of dimethyl sulfoxide used in example 1 was changed to 1mL, 1.5mL, 3mL, and 4mL, respectively, and the other conditions were the same as in example 1. The yields of the anisidine product were 80%, 92%, 87%, 81%, respectively.

Examples 17 to 22

The oxygen pressure in example 1 was changed to 1MPa, 2MPa, 3MPa, 5MPa, 8MPa, and 10MPa, respectively, and the other conditions were the same as in example 1. The yields of the anisonitrile product were 56%, 92%, 83%, 90%, 80%, 88%, respectively.

Examples 23 to 29

The amount of potassium ferrocyanide trihydrate used in example 1 was changed to 0.5mmol, 0.75mmol, 1mmol, 1.5mmol, 2mmol, 2.5mmol, and 3mmol, respectively, and the other conditions were the same as in example 1. The yields of the anisonitrile product were 63%, 92%, 85%, 77%, 82%, 81%, 86%, respectively.

Examples 30 to 35

The amounts of cuprous chloride used in example 1 were changed to 0.15mmol, 0.3mmol, 0.6mmol, 1mmol, 2mmol, and 3mmol, respectively, and the other conditions were the same as in example 1. The yields of the anisonitrile product were 67%, 71%, 92%, 89%, 87%, 63%, respectively.

Examples 36 to 40

The reaction temperature in example 1 was changed to 120 ℃, 130 ℃, 140 ℃, 150 ℃ and 160 ℃, respectively, and the other conditions were the same as in example 1. The yields of the anisonitrile product were 55%, 81%, 92%, 80%, 82%, respectively.

Examples 41 to 45

The reaction time in example 1 was changed to 10 hours, 20 hours, 30 hours, 40 hours, and 50 hours, respectively, and the other conditions were the same as in example 1. The yields of the anisonitrile product were 34%, 78%, 92%, 90%, 87%, 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.