A method for synthesizing pinacol dibenzo[B,D]furan-4-boronic acid ester

Abstract

This invention discloses a method for synthesizing dibenzo[B,D]furan-4-boronic acid pinacol ester. Using dibenzofuran and 4,4,5,5-tetramethyl-2-(trimethylsilyl)-1,3,2-dioxacyclopentaborane as raw materials, the final product dibenzo[B,D]furan-4-boronic acid pinacol ester is obtained through a one-step reaction. This method has the advantages of simple synthesis, convenient production, and easy purification, and can be developed into an industrial production method.

Description

Technical Field

[0001] This invention relates to the field of organic compound synthesis technology, specifically to a method for synthesizing dibenzo[B,D]furan-4-boronic acid pinacol ester. Background Technology

[0002] Pinaryl dibenzo[B,D]furan-4-boronate is a key intermediate frequently used in drug development, chemical engineering, and optoelectronic materials. Currently, the main synthetic method for pinaryl dibenzo[B,D]furan-4-boronate is through coupling. However, coupling requires expensive palladium metal catalysts, and the borate ester and halogenated raw materials are relatively costly, making it unsuitable for industrial-scale production.

[0003] Therefore, developing a new synthetic method for dibenzo[B,D]furan-4-boronic acid pinacol ester to achieve its industrial production is of great significance. Summary of the Invention

[0004] The technical problem solved by this invention is to provide a method for synthesizing pinacol dibenzo[B,D]furan-4-boronic acid ester. The method of this invention has the advantages of simple synthesis, convenient production, environmental protection and safety, and easy purification, and can be used for industrial production.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0006] A method for synthesizing dibenzo[B,D]furan-4-boronic acid pinacol ester, wherein the reaction formula of the synthesis method is as follows:

[0007]

[0008] Includes the following steps:

[0009] Add reactant 1 to the solvent, cool to below 0°C, then add Lewis acid and base, then heat to 20-30°C, stir and mix to obtain a mixture;

[0010] The mixture is cooled to below 0°C, reactant 2 is added, and the temperature is raised after the addition is complete to react and obtain the target product, dibenzo[B,D]furan-4-boronic acid pinacol ester.

[0011] Among them, reactant 1 is dibenzofuran; reactant 2 is 4,4,5,5-tetramethyl-2-(trimethylsilyl)-1,3,2-dioxacyclopentaborane.

[0012] In one embodiment of the present invention, the reaction is carried out under the protection of an inert gas.

[0013] As one embodiment of the present invention, the synthesis method includes the following steps:

[0014] Under inert gas protection, reactant 1 is added to the solvent and cooled to below 0°C. Then, Lewis acid and base are added sequentially, and the temperature is raised to 20-30°C. The mixture is stirred for 20-40 minutes until homogeneous, and a mixed solution is obtained.

[0015] The mixture is cooled to below 0°C, and a tetrahydrofuran solution containing reactant 2 is added dropwise. After the addition is complete, the temperature is first raised to 20-30°C and stirred for 20-40 minutes. Then, the temperature is raised to reflux and the reflux reaction is carried out for 10-15 hours to prepare the target product, dibenzo[B,D]furan-4-boronic acid pinacol ester.

[0016] In one embodiment of the present invention, the Lewis acid is selected from zinc chloride, boron trifluoride ether, and aluminum trichloride.

[0017] In one embodiment of the present invention, the alkali is selected from potassium fluoride, cesium fluoride, cesium carbonate, potassium carbonate, diisopropylaminolithium, and n-butyllithium.

[0018] In one embodiment of the present invention, the solvent is selected from tetrahydrofuran, 1,4-dioxane, and ethylene glycol dimethyl ether.

[0019] In one embodiment of the present invention, the feed equivalent ratio of reactant 1, reactant 2, Lewis acid, and base is 1:(2-3):(2-3):(1-3). The feed equivalent ratio is the molar ratio of the feeds.

[0020] In one embodiment of the present invention, the Lewis acid is boron trifluoride ethyl ether; the base is selected from cesium fluoride, diisopropylaminolithium, and n-butyllithium; and the solvent is selected from tetrahydrofuran and ethylene glycol dimethyl ether.

[0021] In one embodiment of the present invention, the feed equivalent ratio of reactant 1, reactant 2, Lewis acid, and base is 1:2.5:2:2.5.

[0022] In one embodiment of the present invention, the inert gas is selected from nitrogen and argon.

[0023] Preferably, the inert gas is nitrogen.

[0024] The present invention also provides a dibenzo[B,D]furan-4-boronic acid pinacol ester prepared by the synthesis method described in the present invention.

[0025] The beneficial effects of this invention are as follows: This invention provides a novel method for synthesizing dibenzo[B,D]furan-4-boronic acid pinacol ester. It uses readily available and inexpensive dibenzofuran and 4,4,5,5-tetramethyl-2-(trimethylsilyl)-1,3,2-dioxane as raw materials, and obtains the final product dibenzo[B,D]furan-4-boronic acid pinacol ester through a one-step reaction. This method has the advantages of readily available and inexpensive raw materials, simple synthesis, convenient production, and easy purification, and can be developed into an industrial production method. Detailed Implementation

[0026] The technical solution of the present invention will be described in detail below through embodiments.

[0027] Example 1

[0028] The method for synthesizing dibenzo[B,D]furan-4-boronic acid pinacol ester provided in this embodiment includes the following steps:

[0029] Under nitrogen atmosphere, 1.68 g of dibenzofuran was added to a freshly dried three-necked flask, followed by 50 mL of ultra-dry tetrahydrofuran, and then the temperature was lowered to 0°C. 2.84 g of boron trifluoride diethyl ether (2 equivalents) was added to the three-necked flask, and the mixture was stirred at 0°C for 1 hour. After maintaining the temperature at 0°C, 3.80 g of cesium fluoride (2.5 equivalents) was added, and the temperature was raised to room temperature (approximately 25°C) and stirred for 30 minutes.

[0030] The mixture was cooled to 0°C, and 5.00 g of 4,4,5,5-tetramethyl-2-(trimethylsilyl)-1,3,2-dioxane (prepared as a 50 mL tetrahydrofuran solution) was added dropwise. After the addition was complete, the temperature was slowly raised to room temperature (approximately 25°C), and the mixture was stirred for 30 minutes. Then, the temperature was slowly raised to reflux, and the reaction was maintained at reflux for 12 hours. The reaction was monitored by TLC until complete, and then the reaction system was cooled to room temperature. Post-treatment was then initiated, and the mixture was filtered. The resulting filtrate was concentrated to 20 mL and poured into 250 mL of ice water, causing solids to precipitate. The solids were then filtered, and the filter cake was washed with water. The solids were then filtered to near dryness and recrystallized in 10 mL of petroleum ether to obtain 2.68 g of product, with a yield of 91.0%.

[0031] The product's NMR data are as follows: 1 ¹H NMR (400MHz, CDCl₃): δ 8.07 (d, J = 7.6Hz, 1H), 7.92 (d, J = 7.7Hz, 1H), 7.89 (d, J = 7.2Hz, 1H), 7.67 (d, J = 8.2Hz, 2H), 7.46 (t, J = 7.7Hz, 1H), 7.39–7.30 (m, 2H), 1.45 (s, 12H), indicating the target product is dibenzo[B,D]furan-4-boronic acid pinacol ester.

[0032] Referring to Example 1, Examples 2-9 were performed as follows, as detailed in Table 1.

[0033] Table 1

[0034]

[0035] As can be seen from the above examples, the method for synthesizing dibenzo[B,D]furan-4-boronic acid pinacol ester provided by the present invention can successfully synthesize the target product. However, the product yield varies significantly depending on the choice of different reaction reagents, such as different Lewis acids, bases, and solvents. The preferred reaction conditions are boron trifluoride diethyl ether as the Lewis acid, cesium fluoride as the base, and tetrahydrofuran as the solvent. The reaction of dibenzofuran (reactant 1), 4,4,5,5-tetramethyl-2-(trimethylsilyl)-1,3,2-dioxacyclopentaborane (reactant 2), Lewis acid, and base in a molar ratio of 1:2.5:2:2.5 can yield the target product in high yield and can be developed into an industrial production method.

[0036] 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 synthesizing dibenzo[B,D]furan-4-boronic acid pinacol ester, characterized in that, The reaction formula for the synthesis method is: ； Reactant 1, Reactant 2, Target Product Includes the following steps: Add reactant 1 to the solvent, cool to below 0°C, then add Lewis acid and base in sequence, then heat to 20-30°C, stir and mix to obtain a mixture; The mixture is cooled to below 0°C, reactant 2 is added, and the temperature is raised after the addition is complete to react and obtain the target product, dibenzo[B,D]furan-4-boronic acid pinacol ester. The Lewis acid is boron trifluoride diethyl ether; the base is selected from cesium fluoride, diisopropylaminolithium, and n-butyllithium; the solvent is selected from tetrahydrofuran and ethylene glycol dimethyl ether. The feed equivalent ratio of reactant 1, reactant 2, Lewis acid, and base is 1:(2-3):(2-3):(1-3).

2. The synthesis method according to claim 1, characterized in that, The reaction is carried out under the protection of an inert gas.

3. The synthesis method according to claim 1 or 2, characterized in that, The synthesis method includes the following steps: Under inert gas protection, reactant 1 is added to the solvent and cooled to below 0°C. Then, Lewis acid and base are added sequentially, and the temperature is raised to 20-30°C. The mixture is stirred for 20-40 minutes until homogeneous, and a mixed solution is obtained. The mixture is cooled to below 0°C, and a tetrahydrofuran solution containing reactant 2 is added dropwise. After the addition is complete, the temperature is first raised to 20-30°C and stirred for 20-40 minutes. Then, the temperature is raised to reflux and the reflux reaction is carried out for 10-15 hours to prepare the target product, dibenzo[B,D]furan-4-boronic acid pinacol ester.

4. The synthesis method according to claim 1, characterized in that, The feed equivalent ratio of reactant 1, reactant 2, Lewis acid, and base is 1:2.5:2:2.

5.

5. The synthesis method according to claim 2, characterized in that, The inert gas is selected from nitrogen and argon.

6. The synthesis method according to claim 5, characterized in that, The inert gas is nitrogen.

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