CN118166369A - A method for electrochemical synthesis of E-type styrene derivatives - Google Patents

Abstract

The present invention provides an electrochemical synthesis method of an E-type styrene derivative. The present invention utilizes an electrochemically initiated free radical chain reaction to isomerize an aromatic compound with an allyl structure into an E-type styrene derivative. The method comprises the following steps: in an electrochemical reaction cell, an aromatic compound with an allyl structure is used as a substrate, and a solvent and an electrolyte are added; the substrate generates free radical active species under electrode activation, which induces chain isomerization, thereby obtaining an E-type styrene derivative. The method does not require a metal catalyst and a ligand, has mild conditions, is green and safe, is easy to scale up, has a high product yield, is easy to separate and purify, and is suitable for industrial green production.

Description

A method for electrochemical synthesis of E-type styrene derivatives

Technical Field

The invention belongs to the field of organic synthesis and relates to an electrochemical synthesis method of E-type styrene derivatives.

Background technique

Styrene derivatives are widely found in various natural products, drug molecules and spices, such as the natural products (-)-Polysphorin and Fumimycin, rosuvastatin calcium which can be used as a lipid-lowering drug, and anethole which is a food additive. At present, a large number of methods for preparing styrene derivatives have been developed, among which the method of preparing styrene derivatives by isomerization using allyl aromatic compounds as raw materials is highly favored. Because allyl aromatic compounds have a wide range of sources, the isomerization methods are also diverse. At present, the isomerization methods can be roughly divided into base catalysis and metal catalysis. However, base catalysis requires very high temperatures, high energy consumption, and a large amount of base, and the configuration of the product is difficult to control. Although metal catalysis can well regulate the selectivity of the configuration, it usually requires precious metals, or complexes of non-precious metals and ligands as catalysts, which are difficult to recycle. Moreover, the reaction conditions are usually harsh, the production cost is high, and it is not conducive to industrial production. For example, in 2022, Phil S.Baran reported cobalt-catalyzed double bond isomerization. Patent document CN 110878012 A also reports an isomerization process in the presence of a metal nickel salt, a bipyridine ligand and an additive. Both processes require a catalytic system composed of complex ligands to proceed smoothly.

In view of this, there is an urgent need to develop a method for synthesizing styrene derivatives with low reaction condition requirements, convenient operation, good production safety, good environmental friendliness, low cost and high product yield.

Summary of the invention

In view of the above problems existing in the prior art of synthesizing styrene derivatives, the present invention provides a new concept for synthesizing E-type styrene derivatives, which utilizes an electrochemically initiated free radical chain reaction to isomerize aromatic compounds with an allyl structure into E-type styrene derivatives. Specifically, the present invention includes the following technical solutions:

An electrochemical synthesis method of an E-type styrene derivative, characterized in that an aromatic compound having an allyl structure such as formula I isomerizes to an E-type styrene derivative such as formula II.

An electrochemical synthesis method of an E-type styrene derivative, characterized in that it comprises the following steps:

In an electrochemical reaction cell, an electrolyte solution is added, and in a normal pressure atmosphere, an aromatic compound having an allyl structure shown in formula I is used as a substrate, the temperature of the solution is kept constant, and electrolysis is performed in a constant current mode or a constant voltage mode. The substrate generates free radical active species under electrode activation, which triggers chain isomerization, thereby obtaining an E-formula styrene derivative II.

Wherein, substrate I is an aromatic compound with an allyl structure, and its aromatic structure includes a benzene ring structure, and also includes other aromatic groups such as furanyl, thienyl, pyridyl, naphthyl, etc.; the aromatic structure may have electron-withdrawing groups such as ester groups, amide groups, acyl groups, halogen groups; or electron-donating groups such as methoxy groups and amino groups; ^R1 , ^R2 , ^R3 may be alkyl groups with a chain length between _C1 and _C10 , or ester groups, amide groups, acyl groups.

The electrochemical reaction cell is a single cell or a double cell. When the electrochemical reaction cell is a double cell, the cathode cell and the anode cell are separated by a cation exchange membrane or a glass sand core, preferably a single cell.

The electrode is selected from metal sheets such as iron, copper, nickel, cobalt, zinc, aluminum, magnesium, lead, silver, platinum, or any one of glassy carbon, stainless steel, and graphite, preferably an iron electrode.

Wherein, the electrolyte solution is selected from organic solvent/electrolyte or water/electrolyte, wherein the organic solvent is selected from acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, tetrahydrofuran, dichloromethane, ethylene glycol dimethyl ether or a mixture of two or more thereof; the electrolyte is selected from tetraalkylammonium salts such as tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium perchlorate, tetrabutylammonium hexafluorophosphate, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetraethylammonium perchlorate, tetramethylammonium tetrafluoroborate or inorganic salts such as sodium iodide, potassium sulfate, sodium chloride, sodium trifluoromethanesulfonate, etc., preferably an acetonitrile solution of sodium iodide.

The reaction temperature in the steps is between -30 and 200°C, preferably between 20 and 40°C.

The reaction atmosphere in the step is air atmosphere or inert gas atmosphere, and the inert gas is selected from nitrogen and argon, preferably argon.

The current density in the step is between 0.01 and 1000 mA cm ^-2 , and the operating voltage is between 0.1 and 220 V, preferably 50 to 100 mA cm ^-2 and 20 to 30 V.

The substrate concentration in the step is between 0.01 and 7 mol L ^-1 , preferably 0.5 and 1 mol L ^-1 .

The concentration of the electrolyte solution in the step is between 0.001 and 1 mol L ^-1 , preferably between 0.5 and 1 mol L ^-1 .

The electrochemical synthesis method of an E-type styrene derivative provided by the present invention has the following beneficial effects:

(1) An aromatic compound with an allyl structure is used as a substrate to generate free radical active species under electrode activation, which triggers chain isomerization to obtain an E-type styrene derivative II. The process is simple, the reaction conditions are mild, and the operability is strong.

(2) In the preparation of E-type styrene derivative II, an electro-initiated free radical chain isomerization synthesis strategy is adopted, which avoids the use of a large number of metal catalysts and complex ligands, and can well control the configuration of the product. The solvent and electrode used in the preparation method are recyclable, no hazardous reagents are used, no harmful substances are generated, and it is environmentally friendly.

(3) In the preparation of E-type styrene derivative II, the substrate concentration is high, the reaction is fast, the post-treatment is simple, the yield is high (up to 99%), the Z/E ratio is as high as 1/99, the product purity is high, and it is easy to scale up.

The present invention utilizes an electrochemically initiated free radical chain reaction to isomerize an aromatic compound having an allyl structure into an E-type styrene derivative. The reaction raw materials are readily available, the conditions are mild, and the Faraday efficiency is high. The present invention can perform rapid isomerization under room temperature and high concentration conditions, which is conducive to amplification reaction, and the product is easy to separate, the obtained product has high purity, and high configuration selectivity. Therefore, whether from the perspective of production safety or the economic perspective of reducing production costs, the method is a reasonable optimization scheme and has a prospect for promotion and application.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a gas chromatogram of (E)-β-methylstyrene in Example 1;

FIG. 2 is a hydrogen spectrum of (E)-β-methylstyrene in Example 1.

Detailed ways

In order to develop a method for preparing an E-type styrene derivative with low reaction condition requirements, convenient operation, good production safety, environmental friendliness, low cost and high product yield, the present invention uses an aromatic compound with an allyl structure shown in formula I as a substrate, generates free radical active species under electrode activation, and induces chain isomerization, thereby obtaining an E-type styrene derivative II:

Herein, the term "compound represented by formula X" is sometimes expressed as "formula X" or "compound X", which is understandable to those skilled in the art. For example, the compound represented by formula I and compound I both refer to the same compound.

In a preferred embodiment, after the reaction of each of the above steps is completed, post-treatment operations such as filtration, washing, decolorization, purification, crystallization, and drying can be performed according to common sense in the art. On the basis of conforming to common sense in the art, the above preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

The examples involve the addition amounts, contents and concentrations of various substances, wherein the percentages described therein, unless otherwise specified, are all by mass percentages.

In the examples herein, if no specific description is given for the reaction temperature or the operating temperature, the temperature generally refers to room temperature (15 to 30° C.).

The raw materials used in the examples of the present invention are: allylbenzene, p-methoxyallylbenzene, p-bromoallylbenzene, 1,4-dihydroxynaphthalene; tetrabutylammonium iodide, ammonium chloride, sodium iodide, potassium sulfate; nickel electrode, iron electrode, platinum electrode, graphite electrode, tetrahydrofuran, N,N-dimethylformamide, acetonitrile, dichloromethane, water, nitrogen with a purity of 99.99% and argon with a purity of 99.99%. Organic solvents and the like are all analytically pure and used directly. Reagents were purchased from China Pharmaceutical (Group) Shanghai Chemical Reagent Company.

Equipment used: constant current electrolyzer, electrochemical reaction cell, magnetic stirrer.

Detection instrument: Nuclear magnetic resonance instrument: Bruker superconducting nuclear magnetic resonance spectrometer; resonance frequency is 500MHz; CDCl ₃ is used as solvent and TMS is used as internal standard. Gas chromatograph: model is 7890A, and the chromatographic column used is HP-5 gas chromatographic column.

Example 1

In a single-cell reaction cell, a reaction cell with a volume of 150 mL is first filled with nitrogen gas, and 3.69 g (10 mmol) of tetrabutylammonium iodide, 1.18 g (10 mmol) of allylbenzene, and 100 mL of tetrahydrofuran are added; after stirring until they are dissolved, nitrogen gas is continued to be introduced; a nickel sheet with a surface area of ¹⁰ cm2 is used as the cathode and anode, a current of 20 mA is introduced, and electrolysis is continued for 3 hours at a temperature of 20°C; after the reaction is completed, the solvent is removed under vacuum conditions, 100 mL of water is added, and 100 mL of ethyl acetate is used for extraction three times, the organic phases are combined, the solvent is removed under vacuum conditions, and (E)-β-methylstyrene is obtained by purification by distillation.

After testing, the mass of the isomerized product (E)-β-methylstyrene is 1.21 g, the yield is 95%, and the Z/E is 1/99; (E)-β-methylstyrene is subjected to gas phase detection, as shown in Figure 1, and the retention time is 9.27 min; (E)-β-methylstyrene is subjected to nuclear magnetic resonance detection, and the hydrogen spectrum of (E)-β-methylstyrene is shown in Figure 2. As shown in Figure 2:

¹ H-NMR (CDCl ₃ , 500 Hz) δ ppm: 1.90-1.92 (d, 3H), 6.23-6.30 (m, 1H), 6.42-6.45 (d, 1H), 7.20-7.23 (t, 1H), 7.30-7.37 (m, 4H).

δ=1.90-1.92ppm: hydrogen in -CH ₃ , a single peak, number 3; 6.23-6.30ppm: hydrogen on the alkenyl carbon adjacent to the methyl group, a multiple peak, number 1; 6.42-6.45ppm: hydrogen on the alkenyl carbon in the benzyl position, a double peak, number 1; 7.20-7.37ppm: hydrogen on the benzene ring, number 5.

Example 2

In a single-cell reaction cell, first, a reaction cell with a volume of 200 mL is filled with argon gas, and 1.07 g (20 mmol) of ammonium chloride, 2.96 g (20 mmol) of p-methoxyallylbenzene, and 150 mL of N,N-dimethylformamide are added; after stirring until they are dissolved, argon gas is continued to be introduced; an iron sheet with a surface area of ²⁰ cm2 is used as the cathode and anode, a current of 100 mA is introduced, and electrolysis is continued for 4 hours at a temperature of 50°C; after the reaction is completed, the solvent is removed under vacuum conditions, 200 mL of water is added, and ethyl acetate is used for extraction three times, the organic phases are combined, the solvent is removed under vacuum conditions, and (E)-1-methoxy-4-(1-propenyl)benzene is purified by distillation.

After detection, the mass of the isomeric product (E)-1-methoxy-4-(1-propenyl)benzene was 2.87 g, the yield was 97%, and the Z/E was 1/99.

Example 3

In a single-cell reaction cell, 1.50 g (10 mmol) of sodium iodide, 3.94 g (20 mmol) of p-bromoallylbenzene, 50 mL of acetonitrile and 50 mL of water were added to the reaction cell with a volume of 200 mL; the mixture was stirred until dissolved; a platinum sheet with a surface area of ¹⁵ cm2 was used as the cathode and anode, a current of 60 mA was passed, and electrolysis was continued for 2 hours at a temperature of 30°C; after the reaction was completed, the solvent was removed under vacuum conditions, 200 mL of water was added, and the mixture was extracted three times with 200 mL of ethyl acetate, the organic phases were combined, the solvent was removed under vacuum conditions, and (E)-1-bromo-4-(1-propenyl)benzene was obtained by purification by distillation.

After testing, the mass of the isomeric product (E)-1-bromo-4-(1-propenyl)benzene was 3.86 g, the yield was 98%, and the Z/E ratio was 1/99.

Example 4

In a single-cell reaction cell, 1.74 g (10 mmol) of potassium sulfate, 1.30 g (10 mmol) of 1,4-dihydroxynaphthalene, 50 mL of dichloromethane and 50 mL of water were added to the reaction cell with a volume of 200 mL; after stirring until they were dissolved; a graphite sheet with a surface area of ²⁰ cm2 was used as the cathode and anode, a voltage of 20 V was connected, and electrolysis was continued for 4 hours at a temperature of 0°C; after the reaction was completed, the solvent was removed under vacuum conditions, 200 mL of water was added, and 200 mL of ethyl acetate was used for extraction three times, the organic phases were combined, the solvent was removed under vacuum conditions, and 1,2-dihydronaphthalene was obtained by purification by distillation.

After testing, the mass of the isomeric product 1,2-dihydronaphthalene was 1.22 g, and the yield was 94%.

It can be seen from the above Examples 1 to 4 that the method of the present invention has mild reaction conditions, simple process, strong operability, good production safety, and good environmental friendliness; the raw materials are cheap and easy to obtain, and the cost is low; and the product has high purity, high yield, stable quality, and is suitable for industrial production.

The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents, and these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (10)

1. An electrochemical synthesis method of E-type styrene derivatives is characterized in that an aromatic compound with an allyl structure is isomerised into E-type styrene derivatives shown as formula II;

2. the method for electrochemical synthesis of an E-type styrene derivative according to claim 1, comprising the steps of:

And (3) adding an electrolyte solution into an electrochemical reaction tank, and electrolyzing by using an aromatic compound with an allyl structure shown in the formula I as a substrate in a constant-current mode or a constant-voltage mode while keeping the temperature of the solution constant, wherein the substrate generates free radical active species under the activation of an electrode to trigger chain isomerization, so that the E-type styrene derivative II is obtained.

3. The method for electrochemical synthesis of E-type styrene derivatives according to claim 2, wherein the substrate I is an aromatic compound having an allyl structure, the aromatic structure of which comprises a benzene ring structure or a group having aromaticity; the aromatic group comprises at least one of furyl, thienyl, pyridyl and naphthyl; the aromatic structure is provided with an electron withdrawing group or an electron donating group; the electron withdrawing group comprises at least one of an ester group, an amide group, an acyl group and halogen; the electron donating group comprises at least one of methoxy and amino; the R ¹,R²,R³ may be alkyl, ester, amide, acyl with chain length between C ₁～C₁₀.

4. The method for electrochemical synthesis of E-type styrene derivatives according to claim 2, wherein the electrochemical reaction cell is a single cell or a double cell, and when the electrochemical reaction cell is a double cell, the cathode cell and the anode cell are separated by a cation exchange membrane or a glass sand core.

5. The method for electrochemical synthesis of E-styrene derivatives according to claim 2, wherein the electrodes in the step comprise at least one of metal sheet, glassy carbon, stainless steel or graphite; the metal sheet comprises at least one of iron, copper, nickel, cobalt, zinc, aluminum, magnesium, lead, silver and platinum.

6. The method for electrochemical synthesis of E-styrene derivatives according to claim 2, wherein the electrolyte solution in the step is selected from an organic solvent/electrolyte or water/electrolyte, wherein the organic solvent is selected from acetonitrile, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, tetrahydrofuran, dichloromethane, ethylene glycol dimethyl ether or a mixture of two or more thereof; the electrolyte is selected from tetraalkylammonium salt inorganic salt; the tetraalkylammonium salt comprises tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium perchlorate, tetrabutyltetrafluoroboric acid, tetrabutylammonium hexafluorophosphate, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetraethylammonium perchlorate, tetramethyltetrafluoroboric acid or at least one of sodium iodide, potassium sulfate, sodium chloride and sodium triflate.

7. The method according to claim 2, wherein the reaction temperature in the step is selected from any temperature between-30 and 200 ℃.

8. The method according to claim 2, wherein the current density in the step is between 0.01 and 1000mA cm ^-2 and the operating voltage is between 0.1 and 220V.

9. The method according to claim 2, wherein the substrate concentration in the step is between 0.01 and 7mol L ^-1.

10. The method of claim 2, wherein the concentration of the electrolyte solution in the step is between 0.001 and 1mol L ^-1.