A method for preparing 3-organoselenium functionalized chromone compounds by three-component series catalysis
Through the reaction of components such as oxygen, silver nitrate and SDS at 130°C, the problems of rare reagents, difficult separation of products and high cost in the prior art are solved, and economical and efficient synthesis of 3-organic selenium chromone is achieved. Wide practical application prospects.
Patent Information
- Application Number
- CN202310607022.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-05-26
- Publication Date
- 2025-02-14
- Estimated Expiration
- 2043-05-26
AI Technical Summary
The existing method for preparing 3-organoselenecone from 1-(2-methoxyphenyl)-3-phenylpropyl-2-ynyl-1-one has mild reaction conditions but rare reagents and difficult to separate reaction products. , the use of expensive oxidants and other problems have led to high production costs and limited product diversity.
Oxygen is used as the oxidant, silver nitrate is the catalyst, sodium dodecyl sulfate (SDS) is the additive, 1-(2-methoxyaryl)-3-arylpropyl-2-ynyl-1-one, selenium The three-component powder and aryl boric acid react in series, and react at 130°C for several hours to directly prepare 3-organic selenium chromoketone compounds.
The economical, efficient and simple synthesis of 3-organic selenose chromone is achieved, reducing the cost of reagents, shortening the reaction time, and improving the diversity and yield of products.
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Abstract
Description
Technical Field
[0001] The invention relates to a method for preparing 3-organoselenium functionalized chromone compounds, and specifically relates to a method for preparing 3-organoselenium chromone compounds by using oxygen as a terminal oxidant, silver nitrate as a catalyst, sodium dodecyl sulfate (SDS) as an additive, and 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one, selenium powder and aryl boric acid as three components in series. Background Art
[0002] 3-Organoselenium functionalized chromones are a class of novel functionalized molecules with potential practical application value in the fields of medicine, pesticides and materials. In particular, recent studies have shown that these compounds have physiological activities such as antioxidant, antifungal, anti-inflammatory, anti-HIV and anti-tumor. In view of the important application value of 3-Organoselenium functionalized chromones, in the past few years, the academic community has reported many methods for the synthesis of this class of compounds. Among them, the intramolecular cyclization of 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one and diorgano diselenide under the action of an oxidant is one of the most common methods (see the following formula).
[0003]
[0004] So far, four reaction systems have been reported, such as: Document 1 (Adv.Synth.Catal.2011,353(11-12),2042-2050) reported that 1.5 equivalents of ferric chloride were used as the oxidant, dichloromethane was used as the reaction medium, and the reaction was carried out at room temperature for 15-24 hours to prepare 27 3-organoselenones, and the yield of most products was between 60-87%. Document 2 (Org.Chem.Front.2020,7(23),3935-3940) reported that 0.6 equivalents of bis(trifluoroacetoxy)iodobenzene (PIFA) were used as the oxidant, acetonitrile was used as the reaction medium, and the reaction was carried out at room temperature for 30 minutes to prepare 19 3-organoselenones with a yield of 80-96%. Document 3 (New J.Chem.2023,47(3),1076-1080) reported that 0.5 equivalents of selective fluorine were used to prepare 19 3-organoselenones. As a fluorination reagent, acetonitrile is the reaction medium, and the reaction is carried out at room temperature for 20 hours to prepare 20 3-organoselenones with a yield of 25-90%. Considering that most diorganodiselenides are not commercially available, they can be prepared by boric acid and selenium powder. Document 4 (Org. Biomol. Chem. 2022, 20 (25), 5104-5114) reports a two-step one-pot method for preparing 3-organoselenones. First, under air conditions, with 20% AgNO2 as a catalyst and DMSO as a reaction medium, 2 equivalents of arylboronic acid and 2 equivalents of selenium powder are reacted at 120 ° C for 1 hour to obtain diaryl diselenide. Then, 1-(2-methoxyaryl)-3-arylpropyl-2-alkyne-1-one and 1 equivalent of PIFA are added, and the reaction is continued for 12 hours under the same conditions until the reaction ends. 37 3-organoselenones were synthesized by this method with a yield of 42-83%.
[0005] In summary, it can be found that the existing methods for preparing 3-organoselenone from 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one have many disadvantages. Although the reaction conditions of documents 1-3 are mild, they use diorgano diselenide as the selenium source, most of which are commercially unavailable and require a cumbersome synthesis process. In addition, the reaction uses stoichiometric oxidants (FeCl3, PIFA and ), not only a large amount of oxidation by-products are produced, but also separation of the target product from these wastes is a thorny problem. Document 4 uses commercially available aryl boronic acid and selenoether to replace diselenide, simplifying the reaction process and increasing the diversity of products. However, this method still requires the use of equivalent expensive PIFA as a chemical oxidant. In addition, there are also disadvantages such as large amounts of aryl boronic acid and selenium powder (2.0 equivalents) and long reaction time (12h). Summary of the invention
[0006] The invention aims to provide a novel method for synthesizing 3-organoselenium chromone compounds which is economical, efficient, simple and has wide substrate applicability.
[0007] The reaction of the present invention uses 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1), selenium powder and arylboronic acid (2) as raw materials, oxygen as an oxidant, silver salt as a catalyst, and a common surfactant as an additive. The reaction is carried out at 130° C. for several hours in a common solvent to directly synthesize 3-organoselenium chromone compounds in series. Compared with the reported methods, the present invention has significant advantages and has broad practical application prospects.
[0008] Reaction formula of the present invention is as follows:
[0009]
[0010] The technical solution of the present invention is as follows:
[0011] A method for preparing 3-organoselenium functionalized chromone compounds by three-component series catalysis of silver, the method comprising:
[0012] Mixing 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1), aryl boronic acid (2), selenium powder, silver salt, additives and reaction solvent, reacting at 120-140° C. (preferably 130° C.) for 5-8 h (preferably 6 h) under an oxygen atmosphere, and monitoring by GC until the raw material (1) is completely converted, the reaction solution is post-treated to obtain a product 3-organoselenium functionalized chromone compound (3);
[0013] The silver salt is selected from the group consisting of silver nitrite, silver nitrate, silver carbonate, silver sulfate, silver trifluoromethanesulfonate or silver oxide, preferably silver nitrate; the amount of the silver salt is 10-30 mol %, preferably 20 mol %, of the molar amount of 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1);
[0014] The additive is selected from the group consisting of dodecylammonium bromide (CTAB), tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetraethylene glycol monolauryl ether (Brij-30), Triton X-100, Tween 40, sodium dodecyl sulfate (SDS), sodium dodecyl sulfonate (SDSO3Na) or sodium dodecylbenzene sulfonate (SDBS), preferably SDS or CTAB; the amount of the additive is 5-15 mol%, preferably 10 mol%, of the molar amount of 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1);
[0015] The amount of selenium powder used is 1.0-2.0 equivalents of the molar amount of 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1), preferably 1.2 equivalents;
[0016] The amount of arylboronic acid (2) used is 1.0-2.0 equivalents, preferably 1.2 equivalents, of the molar amount of 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1);
[0017] The reaction solvent is selected from the group consisting of toluene, tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethylene glycol dimethyl ether, 1,4-dioxane, acetonitrile, N,N-dimethylformamide (DMF) or dimethyl sulfoxide (DMSO), preferably 1,4-dioxane; the volume molar ratio of the reaction solvent to 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1) is 1.0-5.0:1, mL / mmol, preferably 3.3:1, mL / mmol;
[0018] The specific post-treatment method is as follows: after the reaction is completed, ammonia water is added to the reaction solution, extracted with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, filtered, and the organic solvent is recovered under reduced pressure and vacuum. The residue is separated and purified by column chromatography, using petroleum ether / ethyl acetate as eluent and 200 mesh silica gel as column filler to obtain the product 3-organoselenium functionalized chromone compound (3);
[0019]
[0020] In formula (1), formula (2) or formula (3),
[0021] R' is H, C1-C4 alkyl, C1-C4 alkoxy or halogen; preferably R' is H, 2-methyl, 3-methoxy, 4-chloro or 3-bromo;
[0022] R" is aryl, substituted aryl, cycloalkyl or heteroaryl; preferably R" is phenyl, 2-methoxyphenyl, 4-methylphenyl, 4-fluorophenyl, 3-chlorophenyl, 2-bromophenyl, 4-trifluoromethylphenyl, naphthyl, thienyl or cyclopropyl;
[0023] Ar is an aryl group or a substituted aryl group; preferably, Ar is a phenyl group, a 4-methylphenyl group, a 4-tert-butylphenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-trifluoromethylphenyl group, a 4-formylphenyl group, a 4-methoxycarbonylphenyl group, a 4-cyanophenyl group, a 2-methylphenyl group, a 2-fluorophenyl group, a 3-methylphenyl group, a 3-fluorophenyl group, a 2,6-dimethylphenyl group or a 2-naphthyl group.
[0024] Compared with the prior art, the beneficial effects of the present invention are mainly reflected in:
[0025] (1) This method uses oxygen as an oxidant, 20 mol% AgNO3 as a catalyst, and 10 mol% SDS as an additive. It is green, economical, and produces little waste.
[0026] (2) This method uses 1.2 equivalents of arylboronic acid and 1.2 equivalents of selenium powder as an organic selenium source, which saves reaction reagents and reduces production costs.
[0027] (3) This method has wide substrate applicability, and 32 3-arylselenylchromone compounds were synthesized.
[0028] (4) The reaction time is short and the reaction can be completed in 6 hours. DETAILED DESCRIPTION
[0029] The present invention is further described below by means of specific embodiments, but the protection scope of the present invention is not limited thereto.
[0030] Example 1: Preparation of 3-phenylseleno-2-phenylchromone
[0031] Silver nitrate (204 mg, 0.12 mmol), SDS (173 mg, 0.06 mmol), selenium powder (569 mg, 0.72 mmol), phenylboric acid (878 mg, 0.72 mmol), 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one (142 mg, 0.6 mmol) and 1,4-dioxane (2 mL) were added to a 30 mL stainless steel pressure reactor with a PTFE liner, and the reaction mixture was sealed after replacing oxygen three times. The reactor was placed in an oil pan preheated to 130°C, stirred for 6 hours, then stopped heating and cooled to room temperature. TLC detected that the raw materials reacted completely. Post-treatment: add ammonia water (10 mL), extract with dichloromethane three times (5 mL each time), combine the organic phases, dry over anhydrous sodium sulfate, filter, recover the solvent under reduced pressure, and purify the residue by column chromatography (petroleum ether / ethyl acetate) to obtain 202 mg of 3-phenylselenyl-2-phenylchromone, with a yield of 89%. The product is a yellow solid with a melting point of 130-132°C. 1 H NMR (CDCl3, 400MHz): δ8.27 (dd, J=8.0, 1.7Hz, 1H), 7.70-7.66 (m, 3H), 7.51-7.40 (m, 5H), 7.36-7.32 (m, 2H), 7.17-7.12 (m, 3H)ppm; 13 C NMR(CDCl3,100MHz): δ175.99,167.83,156.00,134.20,134.04,131.40,131.04,13 0.80,129.29,129.10,128.04,126.77,126.70,125.65,122.43,117.96,114.12ppm; 77 Se NMR (CDCl3, 95.5MHz): δ304.56ppm.
[0032] Example 2: Preparation of 3-phenylseleno-2-phenylchromone
[0033] The silver salt used was silver nitrite (20 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one), and the other operations and reaction conditions were the same as those in Example 1 to obtain 188 mg of 3-phenylseleno-2-phenylchromone with a yield of 83%.
[0034] Example 3: Preparation of 3-phenylseleno-2-phenylchromone
[0035] The additive used was dodecylammonium bromide (CTAB) (10 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one), and the other operations and reaction conditions were the same as those in Example 1 to obtain 202 mg of 3-phenylseleno-2-phenylchromone with a yield of 89%.
[0036] Example 4: Preparation of 3-phenylseleno-2-phenylchromone
[0037] The additive used was Triton X-100 (10 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one), and the other operations and reaction conditions were the same as those in Example 1 to obtain 81 mg of 3-phenylseleno-2-phenylchromone with a yield of 36%.
[0038] Example 5: Preparation of 3-phenylseleno-2-phenylchromone
[0039] The additive used was Tween 40 (10 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one), and the other operations and reaction conditions were the same as those in Example 1 to obtain 79 mg of 3-phenylseleno-2-phenylchromone with a yield of 35%.
[0040] Example 6: Preparation of 3-phenylseleno-2-phenylchromone
[0041] The additive used was sodium dodecylsulfonate SDSO3Na (10 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one), and the other operations and reaction conditions were the same as those in Example 1 to obtain 102 mg of 3-phenylselenyl-2-phenylchromone with a yield of 45%.
[0042] Example 7: Preparation of 3-phenylseleno-2-phenylchromone
[0043] The additive used was sodium dodecylbenzenesulfonate (SDBS) (10 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one), and the other operations and reaction conditions were the same as those in Example 1 to obtain 149 mg of 3-phenylseleno-2-phenylchromone with a yield of 66%.
[0044] Example 8: Preparation of 3-phenylseleno-2-phenylchromone
[0045] The organic solvent used was diethylene glycol dimethyl ether (2 mL) (based on 0.6 mmol 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one). Other operations and reaction conditions were the same as those in Example 1 to obtain 136 mg of 3-phenylseleno-2-phenylchromone with a yield of 60%.
[0046] Example 9: Preparation of 3-phenylseleno-2-phenylchromone
[0047] The organic solvent used was toluene (2 mL) (based on 0.6 mmol 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one). Other operations and reaction conditions were the same as those in Example 1. 106 mg of 3-phenylseleno-2-phenylchromone was obtained with a yield of 47%.
[0048] Example 10: Preparation of 3-phenylseleno-2-phenylchromone
[0049] Silver nitrate (10 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one) was used, and other operations and reaction conditions were the same as those in Example 1 to obtain 129 mg of 3-phenylseleno-2-phenylchromone with a yield of 57%.
[0050] Example 11: Preparation of 3-phenylseleno-2-phenylchromone
[0051] Silver nitrate (30 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one) was used, and other operations and reaction conditions were the same as those in Example 1 to obtain 202 mg of 3-phenylseleno-2-phenylchromone with a yield of 89%.
[0052] Example 12: Preparation of 3-phenylseleno-2-phenylchromone
[0053] Sodium dodecyl sulfate (SDS) (5 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one) was used, and other operations and reaction conditions were the same as those in Example 1 to obtain 147 mg of 3-phenylseleno-2-phenylchromone with a yield of 65%.
[0054] Example 13: Preparation of 3-phenylseleno-2-phenylchromone
[0055] Sodium dodecyl sulfate (SDS) (15 mol%) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one) was used, and other operations and reaction conditions were the same as those in Example 1 to obtain 202 mg of 3-phenylselenyl-2-phenylchromone with a yield of 89%.
[0056] Example 14: Preparation of 3-phenylseleno-2-phenylchromone
[0057] The selenium powder and aromatic boronic acid (1.0 equiv) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one) used, and other operation and reaction conditions were the same as those in Example 1, to obtain 170 mg of 3-phenylselenyl-2-phenylchromone with a yield of 75%.
[0058] Example 15: Preparation of 3-phenylseleno-2-phenylchromone
[0059] The selenium powder and aromatic boronic acid (1.5 equiv) (based on the amount of 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one) used, and other operation and reaction conditions were the same as those in Example 1, to obtain 202 mg of 3-phenylselenyl-2-phenylchromone with a yield of 89%.
[0060] Example 16: Preparation of 3-phenylseleno-2-phenylchromone
[0061] The organic solvent used was dioxane (1.67 mL / mmol) (0.6 mmol 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one), and other operation and reaction conditions were the same as those in Example 1 to obtain 158 mg of 3-phenylseleno-2-phenylchromone with a yield of 70%.
[0062] Example 17: Preparation of 3-phenylseleno-2-phenylchromone
[0063] The organic solvent used was dioxane (5 mL / mmol) (0.6 mmol 1-(2-methoxyphenyl)-3-phenylpropyl-2-yn-1-one), and other operation and reaction conditions were the same as those in Example 1 to obtain 197 mg of 3-phenylseleno-2-phenylchromone with a yield of 87%.
[0064] Example 18: Preparation of 3-phenylseleno-2-phenylchromone
[0065] The reaction temperature was 120° C., and other operation and reaction conditions were the same as those in Example 1, to obtain 158 mg of 3-phenylseleno-2-phenylchromone with a yield of 70%.
[0066] Example 19: Preparation of 3-phenylseleno-2-phenylchromone
[0067] The reaction temperature was 140° C., and other operation and reaction conditions were the same as those in Example 1, to obtain 188 mg of 3-phenylseleno-2-phenylchromone with a yield of 83%.
[0068] Example 20: Preparation of 3-phenylseleno-2-phenylchromone
[0069] The reaction time was 5 h, and other operation and reaction conditions were the same as those in Example 1, to obtain 190 mg of 3-phenylseleno-2-phenylchromone with a yield of 84%.
[0070] Example 21: Preparation of 3-phenylseleno-2-phenylchromone
[0071] The reaction time was 8 h, and other operation and reaction conditions were the same as those in Example 1, to obtain 202 mg of 3-phenylseleno-2-phenylchromone with a yield of 89%.
[0072] Example 22-52: Preparation of 3-organoselenium chromone
[0073] Silver nitrate (204 mg, 0.12 mmol), SDS (173 mg, 0.06 mmol), selenium powder (569 mg, 0.72 mmol), arylboronic acid (0.72 mmol), alkynone (1) (0.6 mmol) and 1,4-dioxane (2 mL) were added to a 30 mL stainless steel pressure reactor with a PTFE liner. The oxygen was replaced three times and then sealed. The reactor was placed in an oil pan preheated to 130 ° C. After stirring for 6 hours, the heating was stopped and cooled to room temperature. The same post-treatment and purification were performed to obtain the 3-organoselenone product, and the yield was calculated. The structure of the product is shown in FIG. 1 H NMR, 13 CNMR, 77 Se NMR and HRMS characterization, the experimental results are shown in Table 1.
[0074]
[0075]
[0076]
[0077]
[0078]
[0079]
[0080]
Claims
1. A method for preparing 3-organoselenium functionalized chromone compounds by three-component tandem reaction catalyzed by silver, characterized in that: The method is: Mix 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1), aryl boronic acid (2), selenium powder, silver salt, additives and reaction solvent, react at 120-140° C. for 5-8 hours under oxygen atmosphere, monitor by GC until the raw material (1) is completely converted, and then post-treat the reaction solution to obtain the product 3-organoselenium functionalized chromone compound (3); Wherein, the silver salt is selected from: silver nitrite or silver nitrate; the additive is selected from: dodecyl ammonium bromide or sodium dodecyl sulfate; In formula (1), formula (2) or formula (3), R′ is H, C1-C4 alkyl, C1-C4 alkoxy or halogen; R″ is phenyl, 2-methoxyphenyl, 4-methylphenyl, 4-fluorophenyl, 3-chlorophenyl, 2-bromophenyl, 4-trifluoromethylphenyl, naphthyl, thienyl or cyclopropyl; Ar is phenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-formylphenyl, 4-methoxycarbonylphenyl, 4-cyanophenyl, 2-methylphenyl, 2-fluorophenyl, 3-methylphenyl, 3-fluorophenyl, 2,6-dimethylphenyl or 2-naphthyl.
2. The method for preparing 3-organoselenium functionalized chromone compounds by series connection of three components catalyzed by silver as claimed in claim 1, characterized in that: The amount of the silver salt used is 10-30 mol% of the molar amount of 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1).
3. The method for preparing 3-organoselenium functionalized chromone compounds by three-component tandem reaction of silver catalysts as claimed in claim 1, characterized in that: The amount of the additive used is 5-15 mol% of the molar amount of 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1).
4. The method for preparing 3-organoselenium functionalized chromone compounds by three-component tandem reaction of silver catalysts as claimed in claim 1, characterized in that: The amount of selenium powder used is 1.0-2.0 equivalents to the molar amount of 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1).
5. The method for preparing 3-organoselenium functionalized chromone compounds by series connection of three components catalyzed by silver as claimed in claim 1, characterized in that: The amount of arylboronic acid (2) used is 1.0 to 2.0 equivalents to the molar amount of 1-(2-methoxyaryl)-3-arylpropyl-2-yn-1-one (1).
6. The method for preparing 3-organoselenium functionalized chromone compounds by series connection of three components catalyzed by silver as claimed in claim 1, characterized in that: The reaction solvent is selected from: toluene, tetrahydrofuran, 2-methyltetrahydrofuran, diethylene glycol dimethyl ether, 1,4-dioxane, acetonitrile, N,N-dimethylformamide or dimethyl sulfoxide.
7. The method for preparing 3-organoselenium functionalized chromone compounds by three-component tandem reaction of silver catalysts as claimed in claim 1, characterized in that: The post-treatment method is as follows: after the reaction is completed, ammonia water is added to the reaction solution, extracted with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, filtered, and the organic solvent is recovered under reduced pressure and vacuum. The residue is separated and purified by column chromatography, using petroleum ether / ethyl acetate as eluent and 200 mesh silica gel as column filler to obtain the product 3-organoselenium functionalized chromone compound (3).
8. The method for preparing 3-organoselenium functionalized chromone compounds by three-component tandem reaction of silver catalysts as claimed in claim 1, characterized in that: In formula (1) or formula (3): R' is H, 2-methyl, 3-methoxy, 4-chloro or 3-bromo.