Method for efficiently preparing fluorene derivative by ball milling method
The ball milling method is used to carry out a one-pot cyclization reaction using common and easy-to-get biphenyl derivatives under the protection of inert gas, which successfully solved the complexity and low efficiency of the preparation of 9,9-disubstituted fluorene derivatives in the prior art, and achieved an efficient and environmentally friendly preparation method.
Patent Information
- Application Number
- CN202510069163.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-16
- Publication Date
- 2025-05-30
AI Technical Summary
In the prior art, the method for preparing 9,9-disubstituted fluorene derivatives has the problem that raw materials are difficult to obtain, many preparation steps, and inefficient.
By using the ball milling method, 2-amino-2'-iodibene, tert-butyl nitrite, 1,3-dicarbonyl derivatives, palladium trifluoroacetate and potassium carbonate were used as raw materials under the protection of an inert gas atmosphere, and a one-pot method was carried out to prepare 9,9-disubstituted fluorene derivatives.
It realizes the preparation of fluorene derivatives that are simple, efficient, green and environmentally friendly, avoids environmental pollution and solvent recovery problems, and improves the preparation efficiency.
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Figure CN120058516A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the technical field of chemical engineering, and particularly to a method for efficiently preparing fluorene derivatives by ball milling method. Background Art
[0002] The descriptions in this section only provide background information related to the present disclosure and do not constitute prior art. Fluorene is an important functional structure, widely present in various natural products and organic functional materials. In the pharmaceutical field, 9,9-disubstituted fluorene can be used to manufacture antispasmodics, sedatives, analgesics, antihypertensive drugs, etc. In the field of optoelectronic materials, 9,9-dimethylfluorene has strong fluorescence emission properties and is commonly used in organic synthesis and the preparation of optoelectronic materials, especially in important applications in optoelectronic devices and organic light-emitting diodes (OLEDs) and other fields.
[0003] Therefore, the synthesis of fluorene has attracted extensive research, including traditional Friedel-Crafts reactions, modification of existing fluorene core structures, and other methods. Although current methods can efficiently prepare various fluorenes, there are still problems such as the unavailability of starting materials and limited substrate scope. In related technologies, it is utilized that the 9-position proton of fluorene is acidic and can be removed by a base to generate an aromatic anion, which, as a nucleophile, can undergo a substitution reaction with an electrophile at the 9-position to obtain various 9,9-position modified fluorene derivatives. However, there are fewer methods for directly constructing 9,9-disubstituted fluorene through a cyclization reaction using biphenyl derivatives as raw materials. In related technologies, there is a method for directly constructing 9,9-disubstituted fluorene through a cyclization reaction. However, the raw material used in this method is diphenyliodonium salt, and from a synthetic perspective, the raw material is not easily available, the preparation steps are numerous, and the efficiency is reduced. Summary of the Invention
[0004] In view of this, this application provides a method for efficiently preparing fluorene derivatives by ball milling method, which uses common and easily available biphenyl derivatives as raw materials and directly and efficiently performs a cyclization reaction in one pot to prepare 9,9-disubstituted fluorene derivatives. It can solve the technical problems of multiple steps being cumbersome and complex in the preparation methods of organic optoelectronic materials containing fluorene units, and has the characteristics of simplicity, high efficiency, and environmental friendliness.
[0005] To achieve the above object, this application is realized through the following technical solutions:
[0006] A method for efficiently preparing fluorene derivatives by ball milling method, characterized in that: under the protection of an inert gas atmosphere, the raw materials are 2-amino-2'-iodobiphenyl, tert-butyl nitrite, 1,3-dicarbonyl derivatives, palladium trifluoroacetate, and potassium carbonate, and a ball milling reaction is carried out to obtain the 9,9-disubstituted fluorene derivatives shown in Formula I.
[0007]
[0008] A further technical solution includes the following steps:
[0009] S1: Put 2-amino-2'-iodobiphenyl and tert-butyl nitrite into a ball-milling container, and under the protection of an inert gas, grind them with a ball mill;
[0010] S2: Add 1,3-dicarbonyl derivatives, palladium trifluoroacetate and potassium carbonate to the above-mentioned mixed system, and under the protection of an inert gas, conduct secondary grinding with a ball mill.
[0011] A further technical solution is that a solubilizing solvent is also added in S1, and the solubilizing solvent is selected from one of dimethyl sulfoxide, N,N-dimethylformamide and N,N-dimethylacetamide or a mixed solvent of these solvents. Among them, when dimethyl sulfoxide is used as the solubilizing solvent, the yield is the best.
[0012] A further technical solution is that the grinding time of the ball mill in S1 is 0.5 - 1.5 hours, and the rotation speed of the ball mill is 300 - 900 rpm; the grinding time of the ball mill in S2 is 6 - 24 hours, and the rotation speed of the ball mill is 300 - 900 rpm. Preferably, the grinding time of the ball mill in S1 is 1 hour, and the rotation speed of the ball mill is 600 rpm; the grinding time of the ball mill in S2 is 12 hours, and the rotation speed of the ball mill is 600 rpm.
[0013] A further technical solution is that the molar ratio of the raw materials 2-amino-2'-iodobiphenyl and 1,3-dicarbonyl derivatives is 1:1 - 3 in sequence. Preferably 1:1.2.
[0014] In a further technical solution, the atmosphere is an argon atmosphere or a nitrogen atmosphere.
[0015] In a further technical solution, the 1,3-dicarbonyl derivative is one of ethyl acetoacetate, 1,3-cyclohexanedione, dibenzoylmethane and 1,3-indanedione.
[0016] From the above technical solutions, it can be seen that this application has at least the following advantages and positive effects:
[0017] In the related technology, the synthesis technology basically adopts the solution method. In the solution method, a large amount of solvent is required for the reaction, which may cause environmental pollution, and the solvent needs to be recovered and treated. This application is more environmentally friendly, does not use solvents or uses a small amount of solvents, avoiding the problems of environmental pollution and solvent recovery. In addition, the reaction route of this application has the characteristics of simplicity and high efficiency. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 It is the optimal synthesis route diagram for preparing 9,9-disubstituted fluorene derivatives in this application;
[0019] Figure 2 1H NMR spectrum of compound 1 prepared in Example 1 of this application;
[0020] Figure 3 1H NMR spectrum of compound 2 prepared in Example 2 of this application;
[0021] Figure 4 1H NMR spectrum of compound 3 prepared in Example 3 of this application;
[0022] Figure 5 1H NMR spectrum of compound 4 prepared in Example 4 of this application. Detailed implementation manners
[0023] In order to make the objectives, technical solutions and advantages of this application clearer, the following will further describe this application in detail with reference to the accompanying drawings.
[0024] Example 1: Preparation of compound 1 (ethyl 9-acetyl-9H-fluorene-9-carboxylate).
[0025] Refer to Figure 1 and Figure 2 , put dry silica gel powder (silicon dioxide) (3.0 g) into a stainless-steel grinding jar (25 mL), and add three zirconia grinding balls (diameter 5.0 mm). Then add 2-amino-2'-iodobiphenyl (0.5 mmol, 148 mg), tert-butyl nitrite (0.6 mmol, 62 mg), and dimethyl sulfoxide (1 mL) to the silicon dioxide. After closing the stainless-steel grinding jar under argon protection, place the jar in a ball mill (600 revolutions per minute) and grind for 1 hour. Open the stainless-steel grinding jar, and add the following materials to the above mixture system: ethyl acetoacetate (0.6 mmol, 78 mg), palladium(II) trifluoroacetate (0.2 mmol, 66 mg), and anhydrous potassium carbonate (1.5 mmol, 207 mg). After closing the stainless-steel grinding jar under argon protection, place the jar in a ball mill (600 revolutions per minute) and grind for 12 hours. After the ball milling is completed, open the stainless-steel grinding jar, and extract the organic matter with dichloromethane (20 mL). The solution is washed 2 times with deionized water (20 mL), dried with anhydrous sodium sulfate, and concentrated under vacuum. The residue is purified by silica gel column chromatography (eluent: from pure petroleum ether to ethyl acetate / petroleum ether = 1 / 100 volume ratio) to obtain yellow liquid ethyl 9-acetyl-9H-fluorene-9-carboxylate (85 mg, yield 61%).
[0026] 1H NMR spectrum 1 H NMR(400MHz, CDCl 3)δ 8.68 - 8.73 (m, 2H), 8.12 - 8.14 (m, 1H), 7.73 - 7.77 (m, 1H), 7.67 - 7.71 (m, 2H), 7.58 - 7.66 (m, 2H), 4.59 (q, 2H, J = 7.2), 2.71 (s, 3H), 1.49 (t, 3H, J = 7.2).
[0027] High resolution mass spectrometry ESI - HRMS for [C 18 H 16 O 3 + , calcd: 280.1099; found: 280.1102.
[0028] Example 2: Preparation of Compound 2 (spiro[cyclopentane - 1,9'-fluorene]-2,5-dione).
[0029] See Figure 1 and Figure 3 , put dry silica gel powder (silicon dioxide) (3.0 g) into a stainless - steel grinding jar (25 mL), and add three zirconia grinding balls (diameter 5.0 mm). Then add 2 - amino - 2'-iodobiphenyl (0.5 mmol, 148 mg), tert - butyl nitrite (0.6 mmol, 62 mg), and dimethyl sulfoxide (1 mL) to the silicon dioxide. After closing the stainless - steel grinding jar under argon protection, place the jar in a ball mill (600 revolutions per minute) and grind for 1 hour. Open the stainless - steel grinding jar, and add the following materials to the above mixture system: 1,3 - cyclohexanedione (0.6 mmol, 67 mg), palladium(II) trifluoroacetate (0.2 mmol, 66 mg), and anhydrous potassium carbonate (1.5 mmol, 207 mg). After closing the stainless - steel grinding jar under argon protection, place the jar in a ball mill (600 revolutions per minute) and grind for 12 hours. After finishing ball - milling, open the stainless - steel grinding jar, extract the organic matter with dichloromethane (20 mL). The solution is washed twice with deionized water (20 mL), dried with anhydrous sodium sulfate, and concentrated in vacuo. The residue is purified by silica gel column chromatography (eluent: from pure petroleum ether to ethyl acetate / petroleum ether = 1 / 100 volume ratio) to obtain the yellow solid spiro[cyclopentane - 1,9'-fluorene]-2,5-dione (73 mg, yield 56%).
[0030] Proton nuclear magnetic resonance 1 H NMR (400 MHz, CDCl 3 )δ9.25 - 9.27 (m, 1H), 8.74 (d, 1H, J = 8.4), 8.67 (dd, 1H, J = 8.4, J = 1.2), 8.61 (dd, 1H, J = 8.0, J = 1.2), 8.06 (d, 1H, J = 7.6), 7.77 - 7.81 (m, 1H), 7.70 - 7.75 (m, 1H), 7.64 - 7.69 (m, 3H), 7.50 (dt, 1H, J = 1.2, J = 7.6), 7.32 (dt, 1H, J = 0.8, J = 7.6).
[0031] High resolution mass spectrometry ESI - HRMS for [C 18 H 14 O 2 + , calcd: 262.0994; found: 262.1003.
[0032] Example 3: Preparation of compound 3 ((9H - Fluorene - 9,9 - diyl) bis (phenylmethanone)).
[0033] See Figure 1 and Figure 4 , put dry silica gel powder (silicon dioxide) (3.0 g) into a stainless - steel grinding jar (25 mL), and add three zirconia grinding balls (diameter 5.0 mm). Then add 2 - amino - 2'- iodobiphenyl (0.5 mmol, 148 mg), tert - butyl nitrite (0.6 mmol, 62 mg), and dimethyl sulfoxide (1 mL) to the silica gel. After closing the stainless - steel grinding jar under argon protection, put the jar into a ball mill (600 rpm) and grind for 1 hour. Open the stainless - steel grinding jar, and add the following materials to the above mixture system: dibenzoylmethane (0.6 mmol, 135 mg), palladium (II) trifluoroacetate (0.2 mmol, 66 mg), and anhydrous potassium carbonate (1.5 mmol, 207 mg). After closing the stainless - steel grinding jar under argon protection, put the jar into a ball mill (600 rpm) and grind for 12 hours. After finishing ball - milling, open the stainless - steel grinding jar, extract the organic matter with dichloromethane (20 mL). The solution is washed 2 times with deionized water (20 mL), dried with anhydrous sodium sulfate, and concentrated in vacuo. The residue is purified by silica gel column chromatography (eluent: from pure petroleum ether to ethyl acetate / petroleum ether = 1 / 100 volume ratio) to obtain a white solid (9H - Fluorene - 9,9 - diyl) bis (phenylmethanone) (118 mg, yield 63%).
[0034] 1H NMR spectrum 1 1H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, 2H, J = 7.2), 7.76 - 7.81 (m, 4H), 7.52 - 7.56 (m, 1H), 7.39 - 7.46 (m, 5H), 7.31 - 7.36 (m, 5H), 6.95 (s, 1H).
[0035] High resolution mass spectrometry ESI - HRMS for [C 27 H 18 O 2 + , calcd: 374.1307; found: 374.1311.
[0036] Example 4: Preparation of Compound 4 (spiro[fluorene - 9,2'-indene]-1',3'-dione).
[0037] See Figure 1 and Figure 5 , put dry silica gel powder (silicon dioxide) (3.0 g) into a stainless - steel grinding jar (25 mL), and add three zirconia grinding balls (diameter 5.0 mm). Then add 2 - amino - 2'-iodobiphenyl (0.5 mmol, 148 mg), tert - butyl nitrite (0.6 mmol, 62 mg), and dimethyl sulfoxide (1 mL) to the silica. After closing the stainless - steel grinding jar under argon protection, put the jar into a ball mill (600 rpm) and grind for 1 hour. Open the stainless - steel grinding jar, and add the following materials to the above mixture system: 1,3 - indanedione (0.6 mmol, 88 mg), palladium (II) trifluoroacetate (0.2 mmol, 66 mg), and anhydrous potassium carbonate (1.5 mmol, 207 mg). After closing the stainless - steel grinding jar under argon protection, put the jar into a ball mill (600 rpm) and grind for 12 hours. After the ball - milling is completed, open the stainless - steel grinding jar, and extract the organic matter with dichloromethane (20 mL). The solution is washed twice with deionized water (20 mL), dried with anhydrous sodium sulfate, and concentrated in vacuo. The residue is purified by silica gel column chromatography (eluent: from pure petroleum ether to ethyl acetate / petroleum ether = 1 / 100 volume ratio) to obtain the red solid spiro[fluorene - 9,2'-indene]-1',3'-dione (86 mg, yield 58%).
[0038] 1H NMR 1 1H NMR (400 MHz, CDCl 3 ) δ 8.42 (d, 1H, J = 6.0), 7.79 (d, 1H, J = 7.2), 7.73 - 7.75 (m, 1H), 7.60 (d, 1H, J = 7.6), 7.28 - 7.40 (m, 4H), 3.29 (t, 2H, J = 6.8), 2.75 (t, 2H, J = 6.8), 2.13 - 2.20 (m, 2H).
[0039] High-resolution mass spectrometry ESI-HRMS was [C21H12O2] + , calcd: 296.0837; found: 296.0842.
[0040] Finally, it should be noted that: The above embodiments are only used to illustrate the technical solutions of the embodiments of the present application, and are not intended to limit them; Although the embodiments of the present application have been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: They can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; And these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application.
Claims
1. A method for efficiently preparing fluorene derivatives by ball milling, characterized in that: Under the protection of an inert gas atmosphere, the raw materials are 2-amino-2'-iodobiphenyl, tert-butyl nitrite, 1,3-dicarbonyl derivatives, palladium trifluoroacetate and potassium carbonate, and ball milling reaction is performed to obtain a 9,9-disubstituted fluorene derivative shown in formula I.
2. The method for efficiently preparing fluorene derivatives by ball milling according to claim 1, characterized in that: The following steps are involved: S1: putting 2-amino-2'-iodobiphenyl and tert-butyl nitrite into a ball mill container, and grinding them by a ball mill under the protection of inert gas; S2: Add 1,3-dicarbonyl derivatives, palladium trifluoroacetate and potassium carbonate to the above mixed system, and perform secondary grinding in a ball mill under the protection of inert gas.
3. The method for efficiently preparing fluorene derivatives by ball milling according to claim 2, characterized in that: A dissolving solvent is also added to S1, and the dissolving solvent is selected from one of dimethyl sulfoxide, N,N-dimethylformamide and N,N-dimethylacetamide, or a mixed solvent of these solvents.
4. The method for efficiently preparing fluorene derivatives by ball milling according to claim 2, characterized in that: The grinding time of the ball mill in S1 is 0.5-1.5 hours, and the rotation speed of the ball mill is 300-900 rpm; the grinding time of the ball mill in S2 is 6-24 hours, and the rotation speed of the ball mill is 300-900 rpm.
5. The method for efficiently preparing fluorene derivatives by ball milling according to any one of claims 1 to 2, characterized in that: The molar ratio of the raw materials 2-amino-2'-iodobiphenyl and 1,3-dicarbonyl derivatives is 1:1-3 respectively.
6. The method for efficiently preparing fluorene derivatives by ball milling according to any one of claims 1 to 2, characterized in that: The atmosphere is an argon atmosphere or a nitrogen atmosphere.
7. A method for efficiently preparing fluorene derivatives by ball milling according to any one of claims 1 to 2, characterized in that: The 1,3-dicarbonyl derivative is one of ethyl acetoacetate, 1,3-cyclohexanedione, dibenzoylmethane and 1,3-indandione.