A new method for synthesizing 2-ethoxymethylchromone

Abstract

The invention discloses a novel method for synthesizing 2-ethoxymethyl chromone, relates to the technical field of organic synthesis, and specifically comprises the following steps: S1: in a microwave bottle, sodium metal is added to methanol, until sodium is completely dissolved; S2: o-hydroxyacetophenone is added, after the solution is light green, 2-ethoxyethyl acetate is added, the solution turns white and solid is precipitated; S3: 1,4-dioxane is added, and microwave reaction generates a yellow viscous liquid; S4: the yellow viscous liquid is transferred to a flask, concentrated hydrochloric acid is added to adjust pH to 1~2, and reacts 12h under reflux conditions, cools, and obtains a reaction solution; S5: water is added to the reaction solution, extracted 3 times with ethyl acetate, and the organic phase is dried with anhydrous sodium sulfate after liquid separation and concentrated; S6: column chromatography is performed to obtain light yellow crystals. The inventive method has the advantages of simple operation, high yield and few by-products, and can effectively avoid overreaction and complex side reactions in traditional methods, and improves the simplicity and efficiency of operation.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a new method for synthesizing 2-ethoxymethyl chromone. Background Art

[0002] Chromone compounds are a class of organic molecules with wide application value, and have attracted much attention due to their unique properties and functions in the fields of medicine, dyes and organic synthesis. In the field of medicine, chromone compounds are often used as active ingredients of antibacterial, anti-inflammatory, antiviral and anticancer drugs, which can significantly improve the efficacy and selectivity of drugs; in the dye industry, these compounds are widely used in the synthesis of various high-performance dyes and pigments due to their excellent color development properties and light stability; in addition, in the field of organic synthesis, chromone compounds are also an important class of synthetic intermediates, participating in a variety of organic reactions and used to construct complex organic molecular structures.

[0003] However, despite the broad application prospects of chromone compounds, existing chromone derivative synthesis methods generally have some problems that need to be solved. First, many traditional synthesis methods need to be carried out under harsh conditions such as high temperature and high pressure, strong acid and strong base or toxic and hazardous reagents, which not only puts higher requirements on the safety of experimental equipment and operators, but also limits the practical application scope of these methods. Secondly, existing methods are often accompanied by the problems of low yield and many by-products, which not only reduces the reaction efficiency, but also increases the difficulty and cost of subsequent separation and purification. In industrial production, low yield and complex separation process will also lead to waste of resources and environmental pollution, further weakening the sustainability and economy of these synthesis methods.

[0004] Based on this, developing a mild, efficient and green method for synthesizing chromone derivatives is of great significance for improving the synthesis efficiency and purity of chromone compounds, reducing the formation of by-products, and reducing industrial production costs and environmental burdens. Summary of the invention

[0005] In view of the above problems, the present invention provides a new method for synthesizing 2-ethoxymethyl chromone, which innovatively solves the common problems of harsh reaction conditions, cumbersome steps, and many by-products in the prior art. The present invention is suitable for introducing a methylene group at the 2-position of a chromone compound, and can be widely applied to a variety of different types of chromone substrates, providing an innovative synthetic strategy for the structural diversification and functionalization of chromone compounds.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] The present invention provides a novel method for synthesizing 2-ethoxymethylchromone, which specifically comprises the following steps:

[0008] S1: In a microwave vial, add sodium metal to methanol and wait until the sodium is completely dissolved;

[0009] S2: Add o-hydroxyacetophenone, and when the solution turns light green, add ethyl 2-ethoxylate, the solution turns white and solid precipitates;

[0010] S3: Add 1,4-dioxane and microwave for 30 min to generate a yellow viscous liquid;

[0011] S4: transfer the yellow viscous liquid to a flask, add concentrated hydrochloric acid to adjust the pH to 1-2, react under reflux for 12 h, and cool to obtain a reaction solution;

[0012] S5: adding water to the reaction solution, extracting with ethyl acetate three times, separating the liquids, drying the organic phase with anhydrous sodium sulfate and concentrating;

[0013] S6: Finally, column chromatography is performed to obtain light yellow crystals, namely 2-ethoxymethylchromone.

[0014] The synthetic route is as follows:

[0015]

[0016] Furthermore, in step S1, the mass of sodium is 253 mg, and the volume of methanol is 4 mL.

[0017] Furthermore, in step S2, the mass of o-hydroxyacetophenone is 272 mg, and the mass of ethyl 2-ethoxylate is 1.32 g.

[0018] Furthermore, in step S3, the volume of 1,4-dioxane is 4 mL; and the microwave reaction temperature is 120°C.

[0019] Furthermore, in step S5, the volume of water is 40 mL, and the volume of ethyl acetate is 40 mL.

[0020] Furthermore, in step S6, petroleum ether and ethyl acetate are used as mobile phases for column chromatography separation.

[0021] Furthermore, the volume ratio of petroleum ether to ethyl acetate in the mobile phase is 4:1.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The present invention proposes an innovative method, by using sodium methoxide as a dehydrogenation reagent, o-hydroxyacetophenone is effectively dehydrogenated, thereby promoting the smooth progress of two nucleophilic addition reactions. The reaction conditions of the method of the present invention are mild, and can be carried out in sodium alcoholate, without the need to use strong base sodium hydride or anhydrous and oxygen-free conditions, avoiding the harsh conditions commonly found in traditional methods. In addition, the method has the advantages of simple operation, high yield and few by-products, can effectively avoid overreaction and complex side reactions in traditional methods, improve the purity of the target product, greatly simplify the subsequent separation and purification steps, and improve the simplicity and efficiency of operation. At the same time, using sodium methoxide as a dehydrogenation reagent, it is easy to separate after the reaction, simplifies the post-processing steps, and makes the entire synthesis process more efficient and environmentally friendly. Through this innovative synthesis strategy, a methylene group can be successfully introduced at the 2-position of the chromone compound, significantly improving the synthesis efficiency and structural diversity of chromone derivatives, and providing a new approach for organic synthesis and drug development. DETAILED DESCRIPTION

[0024] In order to make the purpose and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0025] The instruments, reagents, materials, etc. involved in the following examples, unless otherwise specified, are all conventional instruments, reagents, materials, etc. in the prior art and can be obtained through regular commercial channels. The experimental methods, detection methods, etc. involved in the following examples, unless otherwise specified, are all conventional experimental methods, detection methods, etc. in the prior art.

[0026] Example 1

[0027] This embodiment provides a new method for synthesizing 2-ethoxymethylchromone, which specifically comprises the following steps:

[0028] S1: In a microwave vial, add 253 mg of sodium metal (11 mmol) to 4 mL of methanol until the sodium is completely dissolved;

[0029] S2: Add 272 mg of o-hydroxyacetophenone (2 mmol), and when the solution turns light green, add 1.32 g of ethyl 2-ethoxylate (10 mmol), the solution turns white and solid precipitates;

[0030] S3: Add 4 mL of 1,4-dioxane and microwave for 30 min at 120 °C to generate a yellow viscous liquid;

[0031] S4: transfer the yellow viscous liquid to a flask, add concentrated hydrochloric acid to adjust the pH to 1-2, react under reflux for 12 h, and cool to obtain a reaction solution;

[0032] S5: Add 40 mL of water to the reaction solution, extract with 40 mL of ethyl acetate three times, separate the liquids, dry the organic phase with anhydrous sodium sulfate and concentrate;

[0033] S6: Finally, column chromatography was performed using petroleum ether / ethyl acetate (4:1) as the mobile phase to obtain light yellow crystals, namely 2-ethoxymethylchromone.

[0034] The synthetic route is as follows:

[0035]

[0036] The yield of light yellow crystals obtained by column chromatography was 68.8%.

[0037] Traditional synthesis methods of chromone compounds often face the problems of harsh reaction conditions, low yield, many by-products, and great separation difficulty, which seriously restricts its promotion and use in practical applications. In the present embodiment, by optimizing reaction conditions, selecting suitable dehydrogenation reagents and reaction medium, and using unique catalytic system and reaction conditions, the selective introduction of methylene can be achieved under milder conditions, avoiding common overreactions and side reactions in traditional methods, and improving the yield and purity of the target product. In addition, the method also has the advantages of easy operation and wide application range, and can be effectively applied to various types of chromone substrates, providing a new strategy and means for the structural modification and functionalization of chromone compounds. This new method can not only meet the needs in basic scientific research, but also has potential industrial application value, and provides new possibilities for the large-scale production and application development of chromone compounds. Through the implementation of the present invention, researchers and producers will be able to synthesize target compounds more efficiently, thereby promoting the further development of chromone chemical research and application.

[0038] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing 2-ethoxymethylchromone, characterized in that: The specific steps include: S1: In a microwave vial, add sodium metal to methanol and wait until the sodium is completely dissolved; S2: Add o-hydroxyacetophenone, and when the solution turns light green, add ethyl 2-ethoxylate, the solution turns white and solid precipitates; S3: Add 1,4-dioxane and microwave for 30 min to generate a yellow viscous liquid; S4: transfer the yellow viscous liquid to a flask, add concentrated hydrochloric acid to adjust the pH to 1-2, react under reflux for 12 h, and cool to obtain a reaction solution; S5: adding water to the reaction solution, extracting with ethyl acetate three times, separating the liquids, drying the organic phase with anhydrous sodium sulfate and concentrating; S6: Finally, column chromatography is performed to obtain light yellow crystals, namely 2-ethoxymethylchromone.

2. A method for synthesizing 2-ethoxymethyl chromone according to claim 1, characterized in that: In step S1, the mass of sodium is 253 mg, and the volume of methanol is 4 mL.

3. A method for synthesizing 2-ethoxymethyl chromone according to claim 1, characterized in that: In the step S2, the mass of o-hydroxyacetophenone is 272 mg, and the mass of ethyl 2-ethoxylate is 1.32 g.

4. A method for synthesizing 2-ethoxymethyl chromone according to claim 1, characterized in that: In the step S3, the volume of 1,4-dioxane is 4 mL; and the microwave reaction temperature is 120°C.

5. A method for synthesizing 2-ethoxymethyl chromone according to claim 1, characterized in that: In step S5, the volume of water is 40 mL, and the volume of ethyl acetate is 40 mL.

6. A method for synthesizing 2-ethoxymethylchromone according to claim 1, characterized in that: In step S6, petroleum ether and ethyl acetate are used as mobile phases for column chromatography separation.

7. A method for synthesizing 2-ethoxymethylchromone according to claim 6, characterized in that: The volume ratio of petroleum ether to ethyl acetate in the mobile phase is 4:1.

Images