A process for the preparation of 8-chloronaphtho[1,2-b]benzofuran
By using sodium chloride and sodium hypochlorite as chlorine sources and combining the reaction of sodium hydroxide in water and ethanol solvents, the problems of high cost and complex operation in the prior art are solved, and the efficient synthesis of 8-chloronaphtho[1,2-b]benzofuran is realized, which is suitable for industrial production.
Patent Information
- Application Number
- CN202512043478.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-31
- Publication Date
- 2026-05-26
AI Technical Summary
Existing methods for synthesizing 8-chloronaphtho[1,2-b]benzofuran use expensive and dangerous reagents, resulting in high costs, complex operations, and lengthy reaction steps, making industrial-scale production difficult.
Sodium chloride and sodium hypochlorite were used as chlorine sources, and sodium hydroxide was used as a base. The reaction temperature was controlled in water and ethanol solvents. Compound 1 was reacted by adding sodium hypochlorite aqueous solution dropwise to generate 8-chloronaphtho[1,2-b]benzofuran. The product was purified by utilizing its precipitation characteristics.
It reduces reaction costs, simplifies operation steps, and improves product purity and yield, making it suitable for industrial production.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of compound synthesis technology, and in particular to a method for preparing 8-chloronaphtho[1,2-b]benzofuran. Background Technology
[0002] 8-Chloronaphtho[1,2-b]benzofuran compounds and their derivatives are very important pharmaceutical and optoelectronic material intermediates, and are core structures that are frequently used in drug and optoelectronic material research and development.
[0003] While some literature reports a synthetic method for the direct chlorination of dibenzofuran to prepare 2-chlorodibenzofuran, this method requires the use of expensive [bis(trifluoroacetoxy)iodo]benzene as a reagent, significantly increasing costs. Furthermore, the high price of this iodine reagent poses significant safety risks when used in large quantities. Additionally, this reaction utilizes the strong Lewis acid aluminum trichloride and anhydrous reagents. Aluminum trichloride's hygroscopic nature presents a considerable challenge to the reaction operation, and the use of anhydrous reagents further increases production costs. Currently, there are limited reports of related synthetic methods, and many involve lengthy reaction steps or expensive raw materials, necessitating the development of superior synthetic routes.
[0004] Therefore, developing new synthetic methods for 8-chloronaphtho[1,2-b]benzofuran is of great significance for realizing its industrial production. Summary of the Invention
[0005] The main technical problem solved by this invention is to provide a method for preparing 8-chloronaphtho[1,2-b]benzofuran.
[0006] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is: a method for preparing 8-chloronaphtho[1,2-b]benzofuran, involving the following reaction formula: The preparation method includes the following steps: mixing compound 1 (naphtho[1,2-b]benzofuran) with a solvent, then adding sodium hydroxide and sodium chloride, followed by adding sodium hypochlorite aqueous solution dropwise, stirring the reaction, and obtaining the target compound 8-chloronaphtho[1,2-b]benzofuran.
[0007] In one embodiment of the present invention, the solvent is water and ethanol.
[0008] As one embodiment of the present invention, the volume ratio of water to ethanol is: water:ethanol = 1:(5-10). For example, water and ethanol can be mixed in volume ratios of 1:5, 1:6, 1:7, 1:8, 1:9, 1:10 or any other ratio within the range of 1:(5-10).
[0009] In a preferred embodiment of the present invention, the volume ratio of water to ethanol is: water:ethanol = 1:8.
[0010] In one embodiment of the present invention, the amounts of compound 1 and ethanol are as follows: 0.01 mol of compound 1 corresponds to 20-50 mL of ethanol. Preferably, 0.01 mol of compound 1 corresponds to 30-50 mL of ethanol. More preferably, 0.01 mol of compound 1 corresponds to 40 mL of ethanol.
[0011] In one embodiment of the present invention, the molar ratio of compound 1 to sodium hydroxide is 1:(1-3). For example, the molar ratio of compound 1 to sodium hydroxide can be 1:1, 1:2, 1:3, or any other ratio within the range of 1:(1-3).
[0012] In a preferred embodiment of the present invention, the molar ratio of compound 1 to sodium hydroxide is 1:2.
[0013] In one embodiment of the present invention, the molar ratio of compound 1 to sodium chloride is 1:(0.8-1.2). For example, the molar ratio of compound 1 to sodium chloride can be 1:0.8, 1:0.9, 1:1.0, 1:1.1, 1:1.2, or any other ratio within the range of 1:(0.8-1.2).
[0014] In a preferred embodiment of the present invention, the molar ratio of compound 1 to sodium chloride is 1:1.1.
[0015] In one embodiment of the present invention, the molar ratio of compound 1 to sodium hypochlorite is 1:(2-4). For example, the molar ratio of compound 1 to sodium hypochlorite can be 1:2, 1:3, 1:4, or any other ratio within the range of 1:(2-4).
[0016] In a preferred embodiment of the present invention, the molar ratio of compound 1 to sodium hypochlorite is 1:3.
[0017] In one embodiment of the present invention, the volume ratio of water to ethanol in the sodium hypochlorite aqueous solution is 1:(1-3).
[0018] Preferably, the volume ratio of water to ethanol in the sodium hypochlorite aqueous solution is 1:2.
[0019] In one embodiment of the present invention, the reaction is carried out at -5 to 5°C.
[0020] As one embodiment of the present invention, the preparation method includes the following steps: S1: Mix compound 1 with water and ethanol, then add sodium chloride, stir and cool down to -5 to 5°C, add sodium hydroxide, maintain the reaction system temperature at -5 to 5°C, add sodium hypochlorite aqueous solution dropwise, and then stir the reaction at -5 to 5°C. S2: After the reaction is complete, water is added to the reaction system, then the mixture is filtered, the resulting filter cake is washed with water, and then recrystallized and purified to obtain the target compound 8-chloronaphtho[1,2-b]benzofuran.
[0021] In one embodiment of the present invention, the recrystallization purifying agent is a mixture of ethanol and water. Preferably, the volume ratio of ethanol to water is 4:1.
[0022] The method for preparing 8-chloronaphtho[1,2-b]benzofuran provided by this invention uses sodium chloride and sodium hypochlorite as the chlorine source and sodium hydroxide as the alkali. By adjusting the amount of solvent and aqueous solution added during the reaction, the quantitative generation of the chlorine source is controlled. Furthermore, by utilizing the characteristic that the product precipitates immediately upon formation in the system, the generation of polychlorinated products is greatly reduced, thus significantly ensuring the purity and quality of the product. This method significantly reduces reaction costs, uses inexpensive raw materials, has a short reaction step, mild reaction conditions, simple operation, and high yield, making it suitable for large-scale production. Attached Figure Description
[0023] Figure 1 This is the 8-chloronaphtho[1,2-b]benzofuran prepared in Example 1 of this invention. 1 H-NMR spectrum. Detailed Implementation
[0024] The technical solution of the present invention will be described in detail below through specific embodiments. These embodiments are intended to further illustrate the content of the present invention, but are not intended to limit the scope of protection of the claims of the present invention.
[0025] Unless otherwise specified, the pharmaceutical agents used in the following embodiments are all commercially available products.
[0026] The technical solution of the present invention will be described below with reference to specific embodiments.
[0027] Example 1 This embodiment provides a method for preparing 8-chloronaphtho[1,2-b]benzofuran, involving the following reaction formula: The synthesis process is as follows: Compound 1, naphtho[1,2-b]benzofuran (2.18 g, 0.01 mol), was added to ethanol (40 mL), followed by 5 mL of water, and then sodium chloride (0.64 g, 0.011 mol). The mixture was stirred and slowly cooled to about 0 degrees Celsius. Sodium hydroxide (0.8 g, 0.02 mol) was added in portions, with the temperature controlled below 5 degrees Celsius. After the addition was complete, when the system temperature dropped to about 0 degrees Celsius, sodium hypochlorite (2.23 g, 0.03 mol) aqueous solution (with 20 mL of water) was slowly added dropwise. During the dropwise addition, the reaction temperature was controlled below 0 degrees Celsius. During the dropwise addition, the reaction system will precipitate and become viscous. The stirring speed was controlled to ensure uniform stirring. After the sodium hypochlorite aqueous solution was added, the reaction was stirred at 0 degrees Celsius until the reaction of compound 1 was complete.
[0028] To end the reaction, 30 mL of water was added to the reaction system, and then the mixture was filtered. The filter cake was washed with water and recrystallized from the filter cake with ethanol / water (ethanol / water volume ratio of 4:1) to obtain 2.20 g of 8-chloronaphtho[1,2-b]benzofuran, with a yield of 87%.
[0029] Example 2 This embodiment provides a method for preparing 8-chloronaphtho[1,2-b]benzofuran, involving the same reaction formula as in Example 1, and the synthesis process is as follows: Compound 1, naphtho[1,2-b]benzofuran (2.18 g, 0.01 mol), was added to ethanol (40 mL), followed by 5 mL of water, and then sodium chloride (0.58 g, 0.01 mol). The mixture was stirred and slowly cooled to about 0 degrees Celsius. Sodium hydroxide (0.4 g, 0.01 mol) was added in portions, with the temperature controlled below 5 degrees Celsius. After the addition was complete, when the system temperature dropped to about 0 degrees Celsius, sodium hypochlorite (1.49 g, 0.02 mol) aqueous solution (with 20 mL of water) was slowly added dropwise. During the dropwise addition, the reaction temperature was controlled below 0 degrees Celsius. During the dropwise addition, the reaction system will precipitate and become viscous. The stirring speed was controlled to ensure uniform stirring. After the sodium hypochlorite aqueous solution was added, the reaction was stirred at 0 degrees Celsius until the reaction of compound 1 was complete.
[0030] To end the reaction, 30 mL of water was added to the reaction system, and then the mixture was filtered. The filter cake was washed with water and recrystallized from the filter cake with ethanol / water (ethanol / water volume ratio of 4:1) to obtain 2.07 g of 8-chloronaphtho[1,2-b]benzofuran, with a yield of 82%.
[0031] Example 3 This embodiment provides a method for preparing 8-chloronaphtho[1,2-b]benzofuran, involving the same reaction formula as in Example 1, and the synthesis process is as follows: Compound 1, naphtho[1,2-b]benzofuran (2.18 g, 0.01 mol), was added to ethanol (40 mL), followed by 5 mL of water, and then sodium chloride (0.47 g, 0.008 mol). The mixture was stirred and slowly cooled to about 0 degrees Celsius. Sodium hydroxide (1.2 g, 0.03 mol) was added in portions, with the temperature controlled below 5 degrees Celsius. After the addition was complete, when the system temperature dropped to about 0 degrees Celsius, sodium hypochlorite (2.98 g, 0.04 mol) aqueous solution (with 20 mL of water) was slowly added dropwise. During the dropwise addition, the reaction temperature was controlled below 0 degrees Celsius. During the dropwise addition, the reaction system will precipitate and become viscous. The stirring speed was controlled to ensure uniform stirring. After the sodium hypochlorite aqueous solution was added, the reaction was stirred at 0 degrees Celsius until the reaction of compound 1 was complete.
[0032] The reaction was terminated, 50 mL of water was added to the reaction system, and then the mixture was filtered. The filter cake was washed with water and recrystallized from the filter cake with ethanol / water (ethanol / water volume ratio of 4:1) to obtain 2.11 g of 8-chloronaphtho[1,2-b]benzofuran, with a yield of 83%.
[0033] Referring to Example 1, two more batches of experiments were conducted, with yields of 89% and 87%, respectively.
[0034] The 8-chloronaphtho[1,2-b]benzofuran prepared in Example 1 was analyzed by nuclear magnetic resonance. 1 H-NMR spectrum as follows Figure 1 As shown, LCMS analysis indicates the product purity is greater than 95%.
[0035] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent transformations made based on the content of the present invention specification, or direct or indirect applications in other related technical fields, are included within the patent protection scope of the present invention.
Claims
1. A method for preparing 8-chloronaphtho[1,2-b]benzofuran, characterized in that, The reaction formulas involved are: The preparation method includes the following steps: mixing compound 1 with a solvent, then adding sodium hydroxide and sodium chloride, followed by adding sodium hypochlorite aqueous solution dropwise, stirring the reaction, and obtaining the target compound 8-chloronaphtho[1,2-b]benzofuran.
2. The preparation method according to claim 1, characterized in that, The solvents are water and ethanol.
3. The preparation method according to claim 2, characterized in that, The volume ratio of water to ethanol is: water:ethanol = 1:(5-10).
4. The preparation method according to claim 1, characterized in that, The molar ratio of compound 1 to sodium hydroxide is 1:(1-3).
5. The preparation method according to claim 1, characterized in that, The molar ratio of compound 1 to sodium chloride is 1:(0.8-1.2).
6. The preparation method according to claim 1, characterized in that, The molar ratio of compound 1 to sodium hypochlorite is 1:(2-4).
7. The preparation method according to claim 1, characterized in that, The volume ratio of water to ethanol in the sodium hypochlorite aqueous solution is 1:(1-3).
8. The preparation method according to claim 1, characterized in that, The reaction was carried out at -5 to 5°C.
9. The preparation method according to any one of claims 1-8, characterized in that, The method steps include: S1: Mix compound 1 with water and ethanol, then add sodium chloride, stir and cool down to -5 to 5°C, add sodium hydroxide, maintain the reaction system temperature at -5 to 5°C, add sodium hypochlorite aqueous solution dropwise, and then stir the reaction at -5 to 5°C. S2: After the reaction is complete, water is added to the reaction system, then the mixture is filtered, the resulting filter cake is washed with water, and then recrystallized and purified to obtain the target compound 8-chloronaphtho[1,2-b]benzofuran.
10. The preparation method according to claim 9, characterized in that, The recrystallization purifying agent is a mixture of ethanol and water, with a volume ratio of ethanol to water of 4:1.