阅读说明：本技术 一种苯并呋喃-2-(3h)-酮的制备方法 (Preparation method of benzofuran-2- (3H) -one ) 是由 孟庆伟 宋博 唐晓飞 赵静喃 于 2019-11-19 设计创作，主要内容包括：一种苯并呋喃-2-(3H)-酮的制备方法,属于有机合成技术领域。以苯酚为原料,与氯乙酰氯发生酯化反应,生成的α-氯乙酸苯酚酯在酸作催化剂的条件下发生Friedel-Crafts反应,自身环合生成苯并呋喃-2-(3H)-酮。本发明大大缩短了已有文献报道的反应途径,原材料苯酚简单易得,该方法不需要加入剧毒化合物氰化钠、大量的碱与酸,该方法反应条件温和,反应高效,原材料简单易得,极大的降低了反应成本,大大缩短了合成步骤,具有很高的工业应用价值。(The invention relates to a preparation method of benzofuran-2- (3H) -ketone, which belongs to the technical field of organic synthesis and takes phenol as a raw material to perform esterification reaction with chloroacetyl chloride, the generated α -chloroacetic acid phenolic ester performs Friedel-Crafts reaction under the condition of taking acid as a catalyst, and the benzofuran-2- (3H) -ketone is generated by self cyclization.)

1. A preparation method of benzofuran-2- (3H) -ketone is characterized in that phenol is used as a raw material and is subjected to esterification reaction with chloroacetyl chloride, so that α -chloroacetic acid phenolic ester is subjected to Friedel-Crafts reaction under the condition that acid is used as a catalyst, and is subjected to cyclization to generate the benzofuran-2- (3H) -ketone, and the preparation method comprises the following specific steps:

first step, α -chloroacetic acid phenol ester is synthesized

Reacting phenol and chloroacetyl chloride in a solvent under the action of alkali, wherein the reaction temperature is-20-100 ℃, the reaction time is 1-6 hours, evaporating the solvent in a rotary manner, and carrying out reduced pressure distillation to obtain α -chloroacetic acid phenolic ester with the content of not less than 98.5%, wherein the molar ratio of the alkali to the phenol is 1: 1-3, and the molar ratio of the phenol to the chloroacetyl chloride is 1: 1-3;

second, preparation of benzofuran-2- (3H) -ones

Adding α -chloroacetic acid phenolic ester generated in the first step into an organic solvent, and carrying out Friedel-Crafts reaction under the condition of an acid catalyst at the temperature of 20-120 ℃ for 3-12H to prepare benzofuran-2- (3H) -one, wherein the mass percent of the acid catalyst accounts for 0.1-20% of α -chloroacetic acid phenolic ester.

2. The process of claim 1, wherein the base in the first step is: sodium phenolate, sodium hydroxide, potassium hydroxide, triethylamine, trimethylamine, pyridine, sodium carbonate, potassium carbonate, methylethylamine and dimethylethanolamine.

3. A process according to claim 2, wherein the base in the first step is preferably triethylamine.

4. The process according to claim 1, wherein the solvent used in the first step comprises chlorinated hydrocarbons, naphthenic hydrocarbons, aliphatic and aromatic hydrocarbons and water.

5. The method of claim 4, wherein the solvent in the first step comprises dichloromethane, chloroform, carbon tetrachloride, petroleum ether, cyclohexane, ethyl acetate, toluene and water.

6. The process of claim 1, wherein the acid catalyst of the second step comprises a Lewis acid, a protonic acid, and a mixture of one or both of them.

7. The method of claim 6, wherein the Lewis acid in the second step is one or more of aluminum trichloride, ferric trichloride, zinc chloride, boron trifluoride diethyl etherate, copper triflate and scandium triflate.

8. The method according to claim 6, wherein the protonic acid in the second step is one or more of trifluoromethanesulfonic acid, methanesulfonic acid, hydrofluoric acid, polyphosphoric acid, p-toluenesulfonic acid, and concentrated sulfuric acid.

9. The process of claim 1, wherein the solvent of the second step comprises dichloromethane, 1, 2-dichloroethane, nitrobenzene, carbon tetrachloride, carbon disulfide.

10. The process of claim 9, wherein the solvent in the second step is preferably selected from the group consisting of carbon tetrachloride, 1,2, -dichloroethane.

Technical Field

The invention belongs to the technical field of organic synthesis, and relates to a preparation method of benzofuran-2- (3H) -one.

Background

The azoxystrobin serving as a bactericide has the advantages of wide bactericidal spectrum, disease resistance improvement, stress resistance improvement, crop senescence delay, long lasting period, high efficiency, safety and the like, and as the original drug and the compound of the azoxystrobin exceed the effective period of a patent, the domestic demand of the intermediate benzofuran-2- (3H) -ketone increases day by day.

Common methods for preparing benzofuran-2- (3H) -ones are: the method comprises the steps of taking o-chlorobenzyl chloride as a raw material, and carrying out cyanidation, hydrolysis and intramolecular esterification to obtain a product; the second method is that cyclohexanone and dimethoxy methyl acetate are used as raw materials and are prepared by condensation, cyclization and dehydrogenation; in the third method, phenol is used as a raw material to generate benzofuran-2- (3H) -ketone (EP,1481959A1[ P ].2004-12-01) through four steps of etherification, rearrangement, oxidation and esterification. Although the total yield of the first method is up to 87%, the method uses a highly toxic compound sodium cyanide and a large amount of alkali and acid in the reaction, and is not environment-friendly, so that the industrialization of the method is limited to a great extent. The second method has relatively complex process, more solvent consumption, complex treatment after reaction, serious pollution and low total yield, and is not an ideal preparation route. The third method has an overall yield of 64%, but uses a large amount of solvent in the reaction, is complicated in post-treatment, and uses an expensive catalyst, which prevents further industrialization of the method. Because the environmental pollution problem is increasingly prominent, the country pays more and more attention to environmental protection, and the green preparation of the compound becomes more and more important, so the green preparation of the benzofuran-2- (3H) -ketone has important practical significance.

Disclosure of Invention

The invention provides a novel preparation method of benzofuran-2- (3H) -ketone, which does not need to add a virulent compound of sodium cyanide, a large amount of alkali and acid, has mild reaction conditions, stable catalyst structure and high reaction efficiency, greatly reduces the reaction cost, greatly shortens the synthesis steps and has high industrial application value.

In order to achieve the purpose of the invention, the technical scheme of the invention is as follows:

a process for preparing benzofuran-2- (3H) -one includes such steps as esterifying phenol with chloroacetyl chloride to obtain α -chloroacetic phenol ester, Friedel-Crafts reaction in the presence of acid as catalyst, and self-cyclization to obtain benzofuran-2- (3H) -one:

first step, α -chloroacetic acid phenol ester is synthesized

Reacting phenol and chloroacetyl chloride in a solution under the action of organic base, wherein the reaction temperature is-20-100 ℃, the reaction time is 1-6h, evaporating the solvent in a rotary manner, and carrying out reduced pressure distillation to obtain α -chloroacetic acid phenolic ester with the content of not less than 98.5%, wherein the synthesis method of the α -chloroacetic acid phenolic ester comprises the following steps:

the molar ratio of phenol to chloroacetyl chloride is 1: 1-3. The molar ratio of the organic base to the phenol is 1: 1-3.

The organic base is one or a mixture of more than two of sodium phenolate, sodium hydroxide, potassium hydroxide, triethylamine, trimethylamine, pyridine, sodium carbonate, potassium carbonate, methylethylamine and dimethylethanolamine. Triethylamine is preferred.

The solvent comprises chlorohydrocarbon, cycloparaffin, aliphatic hydrocarbon, aromatic hydrocarbon and water, namely dichloromethane, chloroform, carbon tetrachloride, petroleum ether, cyclohexane, ethyl acetate, toluene and water.

Second step, synthesis of benzofuran-2- (3H) -ones

Adding α -chloroacetic acid phenolic ester generated in the first step into a solvent, and carrying out Friedel-Crafts reaction under the condition of an acid catalyst, wherein the mass percent of the acid catalyst accounts for 0.1-20% of that of α -chloroacetic acid phenolic ester, the reaction temperature is 20-120 ℃, the reaction time is 3-12H, and the synthetic method of benzofuran-2- (3H) -ketone comprises the following steps:

the acid catalyst comprises Lewis acid and protonic acid, wherein the Lewis acid comprises one or the mixture of more than two of aluminum trichloride, ferric trichloride, zinc chloride, boron trifluoride diethyl etherate, copper triflate and scandium triflate; the protonic acid comprises one or more of trifluoromethanesulfonic acid, methanesulfonic acid, hydrofluoric acid, polyphosphoric acid, p-toluenesulfonic acid and concentrated sulfuric acid.

The solvent comprises dichloromethane, 1, 2-dichloroethane, chloroform, carbon tetrachloride, DMSO, DMF, carbon disulfide, isopropyl ether and the like. Carbon tetrachloride, 1,2, -dichloroethane are preferred.

The invention has the beneficial effects that: the method greatly shortens the reaction path reported in the prior literature, the raw material phenol is simple and easy to obtain, the method does not need to add a highly toxic compound sodium cyanide, a large amount of alkali and acid, the method has mild reaction conditions, high reaction efficiency and simple and easy-to-obtain raw materials, greatly reduces the reaction cost, greatly shortens the synthesis steps and has high industrial application value.

Drawings

FIG. 1 is a schematic representation of the product α -chloroacetyl chloride of example 1¹H-NMR spectrum.

Detailed Description

Specific examples of the present invention will be described in detail below with reference to the technical solutions, but the process conditions are not limited to these examples.