Double-site acylation method of 9-phenanthrene methyl ether
By controlling the Friedel-Crafts reaction conditions and utilizing Bronsted acid and Lewis acid catalysts, the selective alkylation reaction of 9-methoxybenzo[a]pyrene at the C3 and C10 positions was achieved, solving the problem of poor product selectivity in existing technologies and obtaining high-purity alkylated products.
Patent Information
- Application Number
- CN202411266156.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-03
- Publication Date
- 2024-12-13
AI Technical Summary
Existing technologies struggle to achieve highly selective alkylation of 9-hydroxybenzo[a]pyrene derivatives, particularly the distinct alkylation reactions at the C10 and C3 positions, which are difficult to control and result in poor product selectivity.
By using Bronsted acid and Lewis acid as catalysts and controlling the Friedel-Crafts reaction conditions, selective alkylation of 9-methoxybenzo[a]pyrene at the C3 and K positions was achieved by selecting appropriate solvents and reaction temperatures.
Highly selective alkylation products at the C3 and C10 positions were successfully obtained, improving the regioselectivity and purity of the reaction.
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Figure CN119118805A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic and polymer synthesis, and specifically relates to a double-site acylation reaction of a 9-hydroxyphenanthrene derivative. Background Art
[0002] Phenanthrene is one of the most abundant polycyclic aromatic hydrocarbons in coal tar, and has important application value in many fields, including: optoelectronic materials, synthesis of macrocyclic conjugated systems, synthesis of organic conductive materials, quantum channels, chiral separation, supramolecular self-assembly materials, etc. The functionalization reaction of phenanthrene and its important derivative 9-hydroxyphenanthrene plays an important role in the application of phenanthrene. Due to the unique structural characteristics of phenanthrene, the electron-rich sites of phenanthrene are concentrated in the K region (C9 and C10 positions). Therefore, whether it is phenanthrene or 9-hydroxyphenanthrene derivatives, their electrophilic reactions occur in the K region, such as bromination, nitrosylation, etc. Acylation of phenanthrene is an important method for introducing carbonyl groups. As early as the 1940s, the Friedel-Crafts acylation reaction of phenanthrene began to be studied and reported. However, the reaction usually produces mixed products with poor regioselectivity. One of the important reasons is that Friedel-Crafts acylation is reversible. Therefore, the preparation method of acylated phenanthrene is still lacking. Relatively speaking, 9-alkoxyphenanthrene, a derivative of 9-hydroxyphenanthrene, can obtain C10-formylation products with very clear C10-site selectivity due to the electron-donating effect of the alkoxy group, using POCl3 as a catalyst and DMF as a reactant. As for the direct introduction of acyl chloride, there is still no effective method for Friedel-Crafts reaction. So far, we still have to use the method of first lithiation and then introduction of acyl chloride. This method can also only introduce products with carbonyl substituents at the C10-position, and other sites cannot be achieved.
[0003] The present invention proposes a selective acylation reaction of 9-phenanthrene methyl ether. By controlling the conditions of the Friedel-Crafts reaction, under the action of Bronsted acid and Lewis acid, a C3-site preferential acylation reaction product and a C10-site preferential acylation reaction of 9-phenanthrene methyl ether are obtained respectively, thereby successfully solving the problem that phenanthrene compounds are difficult to be highly selectively acylated.
[0004] Summary of the invention
[0005] The object of the present invention is to provide a method for introducing acyl groups in C3- and K-regions of 9-methoxyphenanthrene. Figure 2 As shown:
[0006]
[0007] The specific steps are:
[0008] (1) Under nitrogen atmosphere, add 0.2 mmol 9-methoxyphenanthrene to a Schlenk tube, add 2 mL solvent, add 3.0 equivalents of newly sublimed aluminum chloride or 1 mL of anhydrous trifluoroacetic acid with stirring, then add 2.0 equivalents of acyl chloride or anhydride, and stir to completely dissolve the reactants, wherein the solvent is selected from any one of dichloromethane and 1,2-dichloroethane, and the acyl chloride or anhydride is selected from any one of alkyl acyl chloride, aryl acyl chloride, alkyl anhydride or aryl anhydride.
[0009] (2) stirring the reaction solution at any temperature between 25°C and 80°C for 4 to 25 hours,
[0010] (3) After the reaction is completed, water is added to the reaction in which aluminum chloride is involved, and a saturated sodium carbonate aqueous solution is added to the reaction in which trifluoroacetic acid is involved. The reaction solution is extracted and separated with dichloromethane, dried with sodium sulfate, and the solvent is evaporated under reduced pressure. The crude product is then separated by column chromatography, and the eluent is a mixed solvent of petroleum ether and ethyl acetate to obtain a pure product. BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Figure 1 :The product in Example 1 1 H-NMR spectrum;
[0012] Figure 2 :The product in Example 1 13 C-NMR spectrum;
[0013] Figure 3 : The product in Example 2 1 H-NMR spectrum;
[0014] Figure 4 : The product in Example 2 13 C-NMR spectrum;
[0015] Figure 5 : The product in Example 3 1 H-NMR spectrum;
[0016] Figure 6 : The product in Example 3 13 C-NMR spectrum;
[0017] Figure 7 : The product in Example 4 1 H-NMR spectrum;
[0018] Figure 8 : The product in Example 4 13 C-NMR spectrum;
[0019] Fig. 9 : The product in Example 5 1 H-NMR spectrum;
[0020] Fig.10 : The product in Example 5 13 C-NMR spectrum;
[0021] Fig.11 : The product in Example 6 1 H-NMR spectrum;
[0022] Fig.12 : The product in Example 6 13 C-NMR spectrum; DETAILED DESCRIPTION
[0023] The present invention is illustrated by way of examples. The specific material ratios, process conditions and results described in the examples are only used to illustrate the present invention, and the present invention should not and will not be limited by the examples.
[0024] Example 1
[0025] After the reaction of phenanthrene methyl ether was complete, 10 mL of water was added to hydrolyze the excess aluminum chloride, followed by extraction with 10 mL × 3 dichloromethane, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was separated by column chromatography and petroleum ether / ethyl acetate (V 石油醚 :V 乙酸乙酯 =15:1) as the eluent for elution, and the separated product was distilled under reduced pressure again to finally obtain 220.1 mg of pure product with a yield of 88% and a purity of >95% as determined by nuclear magnetic resonance.
[0026] Example 2
[0027] mmol, 400mg), p-methoxybenzoyl chloride (2mmol, 0.28mL), react at 50℃ for 4h. After the reaction of phenanthroline methyl ether was complete as detected by TLC, 10ml of water was added to hydrolyze the excess aluminum chloride, and then 10mL×3 dichloromethane was added for extraction. The solvent was distilled off under reduced pressure to obtain a crude product. The crude product was separated by column chromatography and petroleum ether / ethyl acetate (V 石油醚 :V 乙酸乙酯 =10:1) as the eluent for elution, and the separated product was distilled under reduced pressure again to finally obtain 266.8 mg of pure product with a yield of 78% and a purity of >95% as determined by nuclear magnetic resonance.
[0028] Example 3
[0029] Aluminum chloride (3mmol, 400mg), 4-tert-butylbenzoyl chloride (2mmol, 0.36mL), 50℃ for 4h. After the reaction of phenanthrene methyl ether was complete, 10mL of water was added to hydrolyze the excess aluminum chloride, followed by 10mL×3 dichloromethane extraction, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was separated by column chromatography, and petroleum ether / ethyl acetate (V 石油醚 :V 乙酸乙酯 =20:1) as the eluent for elution, and the separated product was distilled under reduced pressure again to finally obtain 305.6 mg of pure product with a yield of 83%. The purity detected by nuclear magnetic resonance was >95%.
[0030] Example 4
[0031] 10 mL of a mixed solvent of dichloroethane and trifluoroacetic acid = 2:1 was added to the tube, and then 3-chlorobenzoyl chloride (2 mmol, 0.26 mL) was added, and the mixture was reacted at room temperature for 25 h. After the reaction of phenanthroline methyl ether was completed by TLC, 10 ml of a saturated sodium carbonate solution was added to neutralize the trifluoroacetic acid, and then 10 mL × 3 of dichloromethane was added for extraction. The solvent was distilled off under reduced pressure to obtain a crude product. The crude product was separated by column chromatography, and petroleum ether / ethyl acetate (V 石油醚 :V 乙酸乙酯 =15:1) as the eluent for elution, and the separated product was distilled under reduced pressure again to finally obtain 280.4 mg of pure product with a yield of 81% and a purity of >95% as determined by nuclear magnetic resonance.
[0032] Example 5
[0033] In this state, 10 mL of a mixed solvent of dichloroethane and trifluoroacetic acid = 2:1 was added to the tube, and then 4-chlorobenzoyl chloride (2 mmol, 0.24 mL) was added, and the mixture was reacted at room temperature for 24 h. After the reaction of phenanthroline methyl ether was completed as detected by TLC, 10 mL of a saturated sodium carbonate solution was added to neutralize the trifluoroacetic acid, and then 10 mL × 3 of dichloromethane was added for extraction. The solvent was distilled off under reduced pressure to obtain a crude product. The crude product was separated by column chromatography, and petroleum ether / ethyl acetate (V 石油醚 :V 乙酸乙酯 =15:1) as the eluent for elution, and the separated product was distilled under reduced pressure again to finally obtain 263.02 mg of pure product with a yield of 76%. The purity detected by nuclear magnetic resonance was >95%.
[0034] Example 6
[0035] 10 mL of a mixed solvent of dichloroethane and trifluoroacetic acid = 2:1 was added to the tube, and then benzoic anhydride (2 mmol, 450 mg) was added, and the mixture was reacted at room temperature for 25 h. After the reaction of phenanthroline methyl ether was completed by TLC, 10 ml of a saturated sodium carbonate solution was added to neutralize the trifluoroacetic acid, and then 10 mL × 3 of dichloromethane was added for extraction. The solvent was distilled off under reduced pressure to obtain a crude product. The crude product was separated by column chromatography, and petroleum ether / ethyl acetate (V 石油醚 :V 乙酸乙酯 =17:1) as the eluent for elution, and the separated product was distilled under reduced pressure again to finally obtain 268.4 mg of pure product with a yield of 86%. The purity detected by nuclear magnetic resonance was >95%.
Claims
1. A double-site acylation method for 9-phenanthrene methyl ether, the reaction formula is shown in the figure below.
2. The double-site acylation method of 9-phenanthrene methyl ether according to claim 1, comprising the following steps: (1) Under nitrogen atmosphere, add 0.2 mmol 9-methoxyphenanthrene to a Schlenk tube, add 2 mL solvent, add 3.0 equivalents of newly sublimed aluminum chloride or 1 mL of anhydrous trifluoroacetic acid with stirring, then add 2.0 equivalents of acyl chloride or anhydride, and stir to completely dissolve the reactants, wherein the solvent is selected from any one of dichloromethane and 1,2-dichloroethane, and the acyl chloride or anhydride is selected from any one of alkyl acyl chloride, aryl acyl chloride, alkyl anhydride or aryl anhydride. (2) stirring the reaction solution at any temperature between 25°C and 80°C for 4 to 25 hours, (3) After the reaction is completed, water is added to the reaction in which aluminum chloride is involved, and a saturated sodium carbonate aqueous solution is added to the reaction in which trifluoroacetic acid is involved. The reaction solution is extracted and separated with dichloromethane, dried with sodium sulfate, and the solvent is evaporated under reduced pressure. The crude product is then separated by column chromatography, and the eluent is a mixed solvent of petroleum ether and ethyl acetate to obtain a pure product.
3. A double-site acylation method for 9-phenanthrene methyl ether as claimed in claim 2, Features: The acid type used in the reaction system of step (1) is aluminum chloride or trifluoroacetic acid.
4. A double-site acylation method for 9-phenanthrene methyl ether as claimed in claim 2, Features: The acylating agent used in the reaction system in step (1) is selected from any one of alkyl acyl chloride, aryl acyl chloride, alkyl anhydride or aryl anhydride.
5. A double-site acylation method for 9-phenanthrene methyl ether as claimed in claim 2, Features: The solvent used in the reaction system of step (1) is any one of dichloromethane or 1,2-dichloroethane.
6. A double-site acylation method for 9-phenanthrene methyl ether as claimed in claim 2, Features: The temperature of the reaction system in step (2) is between 25°C and 80°C.
7. A double-site acylation method for 9-phenanthrene methyl ether as claimed in claim 2, Features: When aluminum chloride is used as a catalyst in step (1), any acyl chloride or anhydride is used as an acylating agent to participate in the reaction to obtain the main product of compound 2.
8. A double-site acylation method for 9-phenanthrene methyl ether as claimed in claim 2, Features: When trifluoroacetic acid is used as a catalyst in step (1), aryl acid chloride or acid anhydride is used as an acylating agent to participate in the reaction to obtain compound 1 as the main product.
9. A double-site acylation method for 9-phenanthrene methyl ether as claimed in claim 2, Features: When an alkyl acyl chloride or anhydride is used as the acylating agent in step (2), the main product obtained by the reaction is compound 2 regardless of whether aluminum chloride or trifluoroacetic acid is used as the catalyst.