阅读说明：本技术 一种苯乙烯双氧化产物的制备方法 (Preparation method of styrene double oxidation product ) 是由 李栋 郝小松 张谦 于 2021-09-29 设计创作，主要内容包括：本发明公开一种苯乙烯双氧化产物的制备方法,包括以下步骤：将钴催化剂、苯乙烯类化合物、N-羟基邻苯二甲酰亚胺和有机溶剂混合均匀后,在氧气条件下进行搅拌反应,反应结束后经分离纯化,得到苯乙烯双氧化产物；钴催化剂为氯化钴或六水合氯化钴中的至少一种。本发明以苯乙烯类化合物和N-羟基邻苯二甲酰亚胺为原料,在过渡金属钴催化下实现苯乙烯双氧化,本发明工艺过程简单、反应条件温和、选择性高、产率高而且催化剂成本低廉,对环境非常友好,降低了成本提高了经济利益；本发明的产物是一种重要的合成中间体,可以用来制备苯基乙二醇、α-氧代苯乙酮等产物,进一步应用到香料、医药合成、农药化学以及涂料染料合成等领域。(The invention discloses a preparation method of a styrene double oxidation product, which comprises the following steps: uniformly mixing a cobalt catalyst, a styrene compound, N-hydroxyphthalimide and an organic solvent, stirring and reacting under the condition of oxygen, and separating and purifying after the reaction is finished to obtain a styrene double oxidation product; the cobalt catalyst is at least one of cobalt chloride or cobalt chloride hexahydrate. The method takes the styrene compound and the N-hydroxyphthalimide as raw materials, and realizes styrene dual oxidation under the catalysis of the transition metal cobalt, and the method has the advantages of simple process, mild reaction conditions, high selectivity, high yield, low catalyst cost, environmental friendliness, reduced cost and improved economic benefit; the product of the invention is an important synthetic intermediate, can be used for preparing products such as phenyl glycol, alpha-oxoacetophenone and the like, and is further applied to the fields of spice, medicine synthesis, pesticide chemistry, paint dye synthesis and the like.)

1. A preparation method of styrene double oxidation products is characterized by comprising the following steps:

uniformly mixing a cobalt catalyst, a styrene compound, N-hydroxyphthalimide and an organic solvent, stirring and reacting under the condition of oxygen, and separating and purifying after the reaction is finished to obtain a styrene double oxidation product; the cobalt catalyst is at least one of cobalt chloride or cobalt chloride hexahydrate.

2. The method for preparing styrene double oxidation product according to claim 1, wherein the styrenic compound has the following structural formula:

wherein R is₁Is H, alkyl or halogen, R₂Is H, alkyl or phenyl, R₃Is H or alkyl.

3. The method for producing styrene dioxide product according to claim 1, wherein R is₁Is H orC₁～C₃Alkyl of R₂Is H, R₃Is H or methyl.

4. The method for producing styrene dioxide according to claim 1, wherein the styrene-based compound is at least one of styrene, 4-methylstyrene, α -methylstyrene, 3-methylstyrene, and 2, 5-dimethylstyrene.

5. The method for preparing styrene double oxidation product according to claim 1, wherein the molar ratio of the styrene compound to the N-hydroxyphthalimide is 1: (0.1-10), wherein the molar ratio of the styrene compound to the catalyst is 1: (0.01-0.3).

6. The method for preparing styrene double oxidation product according to claim 5, wherein the molar ratio of the styrene compound to the N-hydroxyphthalimide is 1: (0.3-2), wherein the molar ratio of the styrene compound to the catalyst is 1: (0.025 to 0.1).

7. The method for producing styrene dioxide according to claim 1, wherein the organic solvent is at least one of 1, 2-dichloroethane, acetonitrile, dichloromethane, and acetone.

8. The method for preparing styrene double oxidation products as claimed in claim 7, wherein the amount ratio of the styrene compound to the organic solvent is (10-100) mg: 1 mL.

9. The method for preparing styrene dioxide according to claim 1, wherein the stirring reaction temperature is 20-60 ℃ and the stirring reaction time is 8-12 h.

10. The method for preparing styrene dioxide according to claim 1, wherein the steps of separating and purifying are specifically as follows: after the stirring reaction is finished, pouring the reaction liquid into a separating funnel, adding water, extracting by using ethyl acetate, distilling an organic phase under reduced pressure to obtain a crude product, and separating and purifying by using column chromatography to obtain a product of styrene double oxidation.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a preparation method of a styrene double oxidation product.

Background

Olefins are cheap, readily available and versatile building blocks that can be converted into a variety of multifunctional compounds. Among them, the double oxidation of olefins has been the focus of research because it can provide different oxygen-containing molecules, such as 1, 2-diols, α -hydroxyketones and 1, 2-dicarbonyl compounds, which have a wide range of uses in synthetic chemistry. For example: 1, 2-dihydroxy compounds are important synthetic intermediates that are widely used in the fields of pesticides, pharmaceuticals, fragrances, and fine chemicals. The 2-phenoxy-1-phenyl ethanol is commonly used for preparing common medical intermediate aniline and the like through selective catalytic conversion of lignin.

Conventional olefin double oxidation processes include: the Pr vost-Woodward reaction, Sharpless double hydroxylation reaction and the like are widely applied to organic synthesis. However, the process often uses expensive heavy metals and stoichiometric amounts of oxidizing agents which make it environmentally hazardous and which also limit its further use. Therefore, it is necessary to develop a new method for the double oxidation of olefins, which is simple, efficient, environmentally friendly, and suitable for industrial production. Metallic cobalt is an inexpensive and environmentally friendly catalyst, but its reports on double oxidation of olefins are very lacking. The oxygen is a sustainable natural resource, has the advantages of large reserve, low cost, environmental protection and the like, and the molecular oxygen selective olefin oxidation reaction conforms to the concept of green chemistry, thereby being a very meaningful clean production technology. The product of styrene double oxidation prepared by the method is a synthesis intermediate with wide application. It can synthesize the alpha-oxo acetophenone compound simply and efficiently in one step. The method can also be used for synthesizing phenyl glycol compounds widely applied to the fields of liquid crystal materials, perfumes, medicine synthesis and the like, and provides a new high-efficiency green and clean synthetic method for industrial preparation of the phenyl glycol compounds.

Disclosure of Invention

In view of the above, there is a need to provide a method for preparing a styrene double oxidation product, so as to solve the technical problems of high cost of the catalyst used for preparing the styrene double oxidation product and complex preparation process in the prior art.

The invention provides a preparation method of a styrene double oxidation product, which comprises the following steps:

uniformly mixing a cobalt catalyst, a styrene compound, N-hydroxyphthalimide and an organic solvent, stirring and reacting under the condition of oxygen, and separating and purifying after the reaction is finished to obtain a styrene double oxidation product; the catalyst is at least one of cobalt chloride or cobalt chloride hexahydrate.

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

the method takes the styrene compound and the N-hydroxyphthalimide as raw materials, and realizes styrene dual oxidation under the catalysis of the transition metal cobalt, and the method has the advantages of simple process, mild reaction conditions, high selectivity, high yield, low catalyst cost, environmental friendliness, reduced cost and improved economic benefit;

the product of the invention is an important synthetic intermediate, can be used for preparing products such as phenyl glycol, alpha-oxoacetophenone and the like, and is further applied to the fields of spice, medicine synthesis, pesticide chemistry, paint dye synthesis and the like.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

The invention provides a preparation method of a styrene double oxidation product, which comprises the following steps:

uniformly mixing a cobalt catalyst, a styrene compound, N-hydroxyphthalimide and an organic solvent, stirring and reacting under the condition of oxygen, and separating and purifying after the reaction is finished to obtain a styrene double-oxidation product.

In the present invention, the cobalt catalyst is at least one of cobalt chloride or cobalt chloride hexahydrate, and preferably cobalt chloride hexahydrate. The styrene compound and N-hydroxyphthalimide (NHPI) generate a product of alcohol of styrene double oxidation under the combined action of cobalt chloride catalysts and oxygen, the product can not react with the cobalt chloride catalysts further, and the final product of styrene double oxidation has good selectivity and high yield.

In the present invention, the styrenic compound has the following structural formula:

wherein R is₁Is H, alkyl or halogen, R₂Is H, alkyl or phenyl, R₃Is H or alkyl.

In some embodiments of the invention, R₁Is H or C₁～C₃Alkyl of R₂Is H, R₃Is H or methyl.

In some embodiments of the invention, the styrenic compound is at least one of styrene (A-a), 4-methylstyrene (A-b), alpha-methylstyrene (A-c), 3-methylstyrene (A-d), 2, 5-dimethylstyrene (A-e).

In the invention, the molar ratio of the styrene compound to the N-hydroxyphthalimide is 1: (0.1-10), further 1: (0.3-2), further 1: 0.5.

in the present invention, the molar ratio of the styrenic compound to the catalyst is 1: (0.01 to 0.3), further 1: (0.025 to 0.1), further 1: 0.05.

in the present invention, the organic solvent is at least one of 1, 2-dichloroethane, acetonitrile, dichloromethane, and acetone, and preferably 1, 2-dichloroethane. In the present invention, the inventors found in the experimental process that the highest yield of the product was obtained when the organic solvent was 1, 2-dichloroethane.

In the invention, the dosage ratio of the styrene compound to the organic solvent is (10-100) mg: 1mL, further (20-50) mg: 1 mL.

In the invention, the stirring reaction temperature is 20-60 ℃, and preferably 40 ℃; the stirring reaction time is 8-12 h, preferably 12 h.

In the invention, the steps of separation and purification are specifically as follows: after the stirring reaction is finished, pouring the reaction liquid into a separating funnel, adding water, extracting by using ethyl acetate, distilling an organic phase under reduced pressure to obtain a crude product, and separating and purifying by using column chromatography to obtain a product of styrene double oxidation.

The general reaction formula of the invention is:

in some embodiments of the present invention, a process for preparing a styrene double oxidation product comprises the steps of:

adding a cobalt catalyst, a styrene compound, N-hydroxyphthalimide and an organic solvent into a reactor, then introducing oxygen, introducing condensed water into a condenser pipe from bottom to top, and then placing the reactor into an oil bath kettle at the temperature of 20-60 ℃ for heating and reacting for 8-12 hours; pouring the reaction liquid into a separating funnel, adding distilled water, extracting by ethyl acetate, distilling the organic phase under reduced pressure to obtain a crude product, and separating and purifying by column chromatography to obtain a product of styrene double oxidation.

Example 1

In this example, styrene and N-hydroxyphthalimide were used as raw materials to prepare 2- (2-hydroxy-2-phenylethoxy) isoindole-1, 3-dione (C-aa), and the influence of the catalyst type, the catalyst amount, the reaction raw material amount, the reaction temperature, the reaction time, the solvent and other factors on the reaction was examined, and the specific reaction conditions and yield are shown in table 1.

Wherein, the structural formula of the styrene double oxidation product is as follows:

the preparation method comprises the following steps:

the cobalt catalyst, styrene, N-hydroxyphthalimide, 2mL of organic solvent and one of the No. 5 magnetons are added into a reactor. Then 1atm oxygen was introduced. And (3) introducing condensed water into the condensation pipe from bottom to top, and then placing the reactor into an oil bath for heating reaction. After the reaction is finished, pouring the reaction liquid into a separating funnel, adding 15mL of distilled water, extracting for 3 times by using 10mL of ethyl acetate, carrying out reduced pressure distillation on an organic phase to obtain a crude product, and carrying out column chromatography separation and purification to obtain a styrene double oxidation product 2- (2-hydroxy-2-phenethyloxy) isoindole-1, 3-diketone (C-aa) which is a white solid.

TABLE 1

The nuclear magnetic resonance hydrogen spectrum and carbon spectrum of the product 2- (2-hydroxy-2-phenethyloxy) isoindole-1, 3-dione (C-aa) of the example determine that the structure is as follows:¹H NMR(400MHz,CDCl₃):δ9.55(s,1H),7.88-7.81(m,2H),7.80-7.74(m,2H),7.41-7.32(m,5H),5.43–5.40(m,1H),4.55–5.45(m,2H)；¹³C NMR(100MHz,CDCl₃):δ163.8,135.7,134.8,128.9,128.8,128.7,127.1,123.9,85.5,79.0。

example 2

This example prepared 2- (2-hydroxy-2-p-tolylethoxy) isoindole-1, 3-dione (C-ba) starting from 4-methylstyrene and N-hydroxyphthalimide, which has the following structural formula:

the preparation method comprises the following steps:

to the reactor was added 0.02mmol of cobalt chloride hexahydrate, 0.4mmol of 4-methylstyrene, 0.2mmol of N-hydroxyphthalimide, 2mL of 1, 2-dichloroethane, and one of magnetons # 5. Then 1atm oxygen was introduced. After the condensation pipe is filled with condensed water from bottom to top, the reactor is placed in an oil bath kettle at 40 ℃ for heating reaction for 12 hours. Pouring the reaction liquid into a separating funnel, adding 15mL of distilled water, extracting for 3 times by using 10mL of ethyl acetate, distilling an organic phase under reduced pressure to obtain a crude product, and separating and purifying by column chromatography to obtain 50.8mg of a styrene double oxidation product 2- (2-hydroxy-2-p-tolylethoxy) isoindole-1, 3-diketone (C-ba) which is a white solid and has the yield of 85%.

The product was structurally determined via nuclear magnetic resonance hydrogen and carbon spectra:¹H NMR(400MHz,CDCl₃):δ9.54(s,1H),7.86-7.80(m,2H),7.77-7.74(m,2H),7.29-7.26(m,2H),7.16(d,J＝7.96Hz,2H),5.40-5.40(m,1H),4.49(d,J＝5.76Hz,2H),2.32(s,3H)；¹³C NMR(100MHz,CDCl₃):δ162.8,137.7,133.7,131.7,128.4,127.7,126.1,122.8,84.2,77.9,20.1。

example 3

This example prepared 2- (2-hydroxy-2-phenylpropoxy) isoindole-1, 3-dione (C-ca) starting from α -methylstyrene and N-hydroxyphthalimide, which has the following structural formula:

the preparation method comprises the following steps:

to the reactor was added 0.02mmol of cobalt chloride hexahydrate, 0.4mmol of alpha-methylstyrene, 0.2mmol of N-hydroxyphthalimide, 2mL of 1, 2-dichloroethane, and one of magnetons # 5. Then 1atm oxygen was introduced. After the condensation pipe is filled with condensed water from bottom to top, the reactor is placed in an oil bath kettle at 40 ℃ for heating reaction for 12 hours. Pouring the reaction liquid into a separating funnel, adding 15mL of distilled water, extracting for 3 times by using 10mL of ethyl acetate, distilling an organic phase under reduced pressure to obtain a crude product, and separating and purifying by column chromatography to obtain 48.9mg of a styrene double oxidation product 2- (2-hydroxy-2-phenylpropoxy) isoindole-1, 3-diketone (C-ca) which is a white solid, wherein the yield is 83%.

The product was structurally determined via nuclear magnetic resonance hydrogen and carbon spectra:¹H NMR(400MHz,CDCl₃):δ9.80(s,1H),7.89-7.82(m,2H),7.81–7.74(m,2H),7.633-7.48(m,2H),7.41-7.35(m,2H),7.33-7.27(m,1H),4.73-4.62(m,2H),1.66(s,3H)；¹³C NMR(100MHz,CDCl₃):δ163.8,140.8,134.9,128.7,128.6,127.9,125.4,123.9,84.4,79.8,22.9。

example 4

This example prepared 2- (2-hydroxy-2- (m-tolyl) ethoxy) isoindole-1, 3-dione (C-da) starting from 3-methylstyrene and N-hydroxyphthalimide, which has the following structural formula:

the preparation method comprises the following steps:

to the reactor was added 0.02mmol of cobalt chloride hexahydrate, 0.4mmol of 3-methylstyrene, 0.2mmol of N-hydroxyphthalimide, 2mL of 1, 2-dichloroethane, and one of magnetons # 5. Then 1atm oxygen was introduced. After the condensation pipe is filled with condensed water from bottom to top, the reactor is placed in an oil bath kettle at 40 ℃ for heating reaction for 12 hours. The reaction solution was poured into a separatory funnel, 15mL of distilled water was added, extraction was carried out 3 times with 10mL of ethyl acetate, and the organic phase was distilled under reduced pressure to give a crude product, which was purified by column chromatography to give 47.8mg of styrene bis-oxide 2- (2-hydroxy-2- (m-tolyl) ethoxy) isoindole-1, 3-dione (C-da) as a white solid with a yield of 81%.

The product was structurally determined via nuclear magnetic resonance hydrogen and carbon spectra:¹H NMR(400MHz,CDCl₃):δ9.54(s,1H),7.88-7.83(m,2H),7.80–7.73(m,2H),7.27-7.12(m,4H),5.41-5.37(m,1H),4.53-4.44(m,2H),2.34(s,3H)；¹³C NMR(100MHz,CDCl₃):δ163.8,138.5,135.7,134.8,129.6,128.7,128.6,127.8,124.1,123.8,85.6,79.1,21.4。

example 5

This example uses 2, 5-dimethylstyrene and N-hydroxyphthalimide as starting materials to produce 2- (2- (2, 5-dimethylphenyl) -2-hydroxyethoxy) isoindole-1, 3-dione (C-ea), which has the following structural formula:

the preparation method comprises the following steps:

to the reactor was added 0.02mmol of cobalt chloride hexahydrate, 0.4mmol of 2, 5-dimethylstyrene, 0.2mmol of N-hydroxyphthalimide, 2mL of 1, 2-dichloroethane, and one of magnetons 5. Then 1atm oxygen was introduced. After the condensation pipe is filled with condensed water from bottom to top, the reactor is placed in an oil bath kettle at 40 ℃ for heating reaction for 12 hours. Pouring the reaction liquid into a separating funnel, adding 15mL of distilled water, extracting for 3 times by using 10mL of ethyl acetate, distilling an organic phase under reduced pressure to obtain a crude product, and separating and purifying by column chromatography to obtain 51.4mg of a styrene double oxidation product 2- (2- (2, 5-dimethylphenyl) -2-hydroxyethoxy) isoindole-1, 3-diketone (C-ea) which is a white solid and has the yield of 82%.

The product was structurally determined via nuclear magnetic resonance hydrogen and carbon spectra:¹H NMR(400MHz,CDCl₃):δ9.64(s,1H),7.88–7.84(m,2H),7.81–7.76(m,2H),7.18(s,1H),7.08–7.01(m,2H),5.67–5.63(m,2H),4.49–4.39(m,2H),2.36(s,3H),2.28(s,3H)；¹³C NMR(100MHz,CDCl₃):δ162.8,134.8,133.8,132.4,131.7,129.7,128.4,127.6,125.9,122.8,81.7,78.0,20.0,17.6。

the above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention.