CN112979612A - Method for preparing 2-iodo-heterocyclic aromatic ether at room temperature - Google Patents
Method for preparing 2-iodo-heterocyclic aromatic ether at room temperature Download PDFInfo
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention discloses a method for preparing 2-iodo-heterocyclic aromatic ether at room temperature, which comprises the steps of adding alkali metal hydride and phenol into a solvent, then adding diiodo-heterocyclic aromatic hydrocarbon, and reacting at 0-100 ℃ to obtain a 2-iodo-heterocyclic aromatic ether product. The coupling process of the invention does not need to add a transition metal catalyst, and does not cause metal pollution to the product; the product of the invention can be used as an organic synthesis raw material for further reaction, and can also be used as an added flame retardant reagent for improving the flame retardant property of plastics.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing 2-iodo heterocyclic aryl ether by a coupling reaction of an aryne intermediate generated by ortho-iodine halide under the action of alkali metal hydride and phenol.
Background
The average concentration of oxygen in the air is 21 percent, the general oxygen index is below 21 and is flammable plastic, 22-27 is self-extinguishing plastic, the higher the oxygen index is, the plastic is difficult to burn, and pure plastic needs to be added with a flame retardant to be non-flammable. The halogen flame retardant refers to a flame retardant containing a halogen element. Because of the low C-X bond energy, the halogen flame retardant is easy to decompose under the action of high temperature, the reaction absorbs heat to reduce the surface temperature of the material, and meanwhile, the flame-retardant high-density gas HX can expel air to form a protective layer on the surface of the asphalt to prevent the combustion of the resin. Four elements in the halogen system: fluorine, chlorine, bromine and iodine have flame retardance, and the flame retardant effect is sequentially enhanced according to the arrangement sequence of fluorine, chlorine, bromine and iodine. Because the fluorine-containing flame retardant can not effectively capture free radicals and the iodine-containing flame retardant has poor stability, the halogen flame retardant used at present mainly comprises chlorine and bromine. Aiming at products with low flame-retardant requirements, the development of new iodine-containing compounds has industrial value.
Disclosure of Invention
The invention provides a method for synthesizing 2-iodo-heterocyclic aromatic ether by one-step reaction at room temperature; the method is characterized in that o-iodo halide is used for the first time to absorb halogen atoms of another molecule of o-iodo halide under the action of alkali metal hydride to form a 2-iodo heterocyclic aromatic ether product, and the obtained product can be used for flame retardance of resin.
The technical means of synthesizing the 2-iodo-heterocyclic aromatic ether is to mix alkali metal hydride, phenol and diiodo-heterocyclic aromatic hydrocarbon in a solvent and carry out conventional stirring reaction to obtain a product. The specific technical scheme is as follows:
a method for preparing 2-iodo-heterocyclic aromatic ether at room temperature comprises reacting diiodo-heterocyclic aromatic hydrocarbon with phenol in the presence of alkali metal hydride to obtain 2-iodo-heterocyclic aromatic ether; preferably, adding alkali metal hydride and phenol into a solvent, then adding diiodo heterocyclic aromatic hydrocarbon, and reacting at 0-100 ℃ to obtain the 2-iodo heterocyclic aromatic ether.
In the present invention, the phenol is phenol, substituted phenol or heterocyclic phenol.
In the present invention, the alkali metal hydride is sodium hydride, potassium hydride and calcium hydride, preferably sodium hydride and potassium hydride, more preferably sodium hydride.
In the present invention, the solvent is DMF (N,N-dimethylformamide), DMA (N,NDimethylacetamide), THF (tetrahydrofuran), 2-MeTHF (2-methyltetrahydrofuran), DME (ethylene glycol dimethyl ether), MTBE (methyl tert-butyl ether), diethyl ether, DMSO, NMP (R) ((R)N-methyl pyrrolidone), toluene, preferably DMA and THF, more preferably a mixture of DMA and THF.
In the invention, the molar ratio of the phenol to the diiodo heterocyclic aromatic hydrocarbon to the alkali metal hydride is 1 (0.1-10) to 1.2-10; preferably 1 (0.5-5) to 1.5-5; more preferably 1 (1-3) to 2-4; most preferably 1:1.5: 3.
In the technical scheme, the reaction temperature is 10-50 ℃, and room temperature is more preferable; the reaction time is 0.2-10 hours, preferably 0.5-2 hours.
The preparation method of the 2-iodo-heterocyclic aromatic ether has the following advantages: 1) transition metal catalysts are not needed to be added in the coupling process, so that metal pollution to products is avoided; 2) the method can be carried out at room temperature, has high functional group compatibility, and solves the problem that the coupling reaction of the existing metal catalysis into the aromatic ether needs to be carried out at higher temperature; 3) the reaction is simple, the reagent is cheap, and the required cost is low; 4) products which are not readily prepared by other methods, such as products containing iodine on both aromatic rings, can be prepared.
In the invention, the chemical structural formula of the diiodo heterocyclic aromatic hydrocarbon is as follows:
in the invention, the chemical structural formula of the phenol is Ar2OH。
In the invention, the chemical structural formula of the 2-iodo heterocyclic aromatic ether is as follows:
in the present invention, Ar2Is benzene, naphthalene, pyridine, quinolinePyrimidine, thiophene, and the like.
The coupling reaction of phenol and iodide does not need to add any catalyst, the operation is simple, the by-product of the reaction is only sodium iodide, and no toxic substances are generated; the 2-iodo-heterocyclic aromatic ether prepared by the method can be obtained by only one-step mild reaction, does not contain excessive coupling products, and is superior to all existing methods.
Drawings
FIG. 1 shows the nuclear magnetic spectrum of product 1 i.
Detailed Description
The technical scheme of the invention is as follows: suspending an alkali metal hydride in a solvent, adding phenol, adding diiodo heterocyclic aromatic hydrocarbon, reacting for 0.2-10 hours at room temperature, adding water to terminate the reaction, extracting with the solvent, evaporating to dryness, and purifying by column chromatography to obtain a product, namely 2-iodo heterocyclic aromatic ether; the reaction of the invention does not need inert atmosphere and catalyst, and the reaction can be carried out by covering after the material is added into the reaction bottle; the specific operation and purification are conventional techniques.
The raw materials involved in the invention are all commercial products, and the specific operation method and the test method are the prior art.
Synthesis example
Triphenylphosphine (39 mmol, 10.48 g) was dissolved in THF (80 mL), stirred at 0 deg.C, and diisopropyl azodicarboxylate (DIAD) (39 mmol, 7.9 mL) was added and stirred at 0 deg.C for 1 h. To this was added a solution of 1-phenyl-2-propyn-1-ol (30 mmol, 4.0 g) and thioacetic acid (39 mmol, 2.86 mL) in THF (20 mL), and the mixture was allowed to react at room temperature for 12 h. Evaporated to dryness and the residue diluted with hexane (80 mL), filtered, evaporated to dryness and purified by column chromatography to give the product 1ia as a black oil in 57% yield.
Zinc dibromide (702 mg, 2.7 mmol) was suspended in ether (81 mL) under nitrogen and 1ia (2.39 g, 12.5 mmol), diisopropylethylamine (4.15 mL, 27 mmol), benzaldehyde (2.7 mL, 27 mmol) and TMSOTf (2.93 mL, 16.2 mmol) were added dropwise in that order.The reaction mixture was stirred at room temperature for 12 hours. The solid was filtered through celite, and the filtrate was concentrated and then diluted with THF (30 mL). Adding 1.0M HCl (45 mL) and stirring for 1h, EA extraction, water and saturated NaHCO3And (6) washing. Evaporated to dryness and purified by column chromatography to give 1ib as a yellow oil in 51% yield.
Will I2 (9 mmol, 2.28 g) was added to a solution of 1ib (3 mmol, 888 mg) in dichloromethane (30 mL) and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane and washed with saturated sodium thiosulfate. Evaporated to dryness and purified by column chromatography to give 1ic as a yellow solid in 44% yield.
DDQ (3 mmol, 681 mg) was added to a solution of 1ic (1 mmol, 489 mg) in toluene (20 mL), and the resulting mixture was stirred at reflux temperature for 36 hours. Filtering, evaporating to dryness, purifying by column chromatography to obtain yellow solid product 1i with yield of 85%, and nuclear magnetic chromatogram shown in figure 1,1H NMR (400 MHz, CDCl3) δ 7.59-7.56 (m, 4H), 7.48-7.42 (m, 6H)。
example 1
Sodium hydride (60% in oil, 36 mg, 0.9 mmol, 3 eq.) was suspended in THF (1 mL), a solution of phenol 2a (28 mg, 0.3 mmol, 1 eq.) in DMA (0.3 mL) was added with regular stirring, after addition was stirred at room temperature for 10 minutes, then a solution of 1i (151mg, 0.45 mmol, 1.5 eq.) in THF (0.2 mL) was added, reaction was carried out at room temperature for 1 hour, reaction was complete, water was added and quenched, extraction was carried out three times with ethyl acetate, organic layers were combined, dried over sodium sulfate, evaporated to dryness and purified by column chromatography to give the product iodoaryl ether 3ia, yield 94%.1H NMR (400 MHz, CDCl3) δ 7.71 (m, 4H), 7.56-7.20 (m, 8H), 7.11-6.88 (m, 3H). LR-MS (ESI): m/z 455.1 [M+H]+。
Example 2
Sodium hydride (60% in oil, 36 mg, 0.9 mmol, 3 eq.) was suspended in THF (1 mL), a solution of phenol 2a (28 mg, 0.3 mmol, 1 eq.) in DMA (0.3 mL) was added with regular stirring, after addition was stirred at room temperature for 10 minutes, then a solution of 1i (151mg, 0.45 mmol, 1.5 eq.) in THF (0.2 mL) was added, the reaction was carried out in an ice-water bath for 1 hour, the reaction was complete, water was added and quenched, extracted three times with ethyl acetate, the organic layers were combined, dried over sodium sulfate, evaporated to dryness and purified by column chromatography to give the product iodoaryl ether 3ia in 54% yield.
Example 3
Sodium hydride (60% in oil, 36 mg, 0.9 mmol, 3 eq.) was suspended in THF (1 mL), a solution of phenol 2a (28 mg, 0.3 mmol, 1 eq.) in DMA (0.3 mL) was added with regular stirring, after addition was stirred at room temperature for 10 minutes, then a solution of 1i (151mg, 0.45 mmol, 1.5 eq.) in THF (0.2 mL) was added, reaction was carried out at 50 ℃ for 1 hour, reaction was complete, water was added and quenched, extraction was carried out three times with ethyl acetate, organic layers were combined, dried over sodium sulfate, evaporated to dryness and purified by column chromatography to give the product iodoaryl ether 3ia, yield 95%.
Example 4
Potassium hydride (0.9 mmol, 3 eq.) is suspended in THF (1 mL), a solution of phenol 2a (28 mg, 0.3 mmol, 1 eq.) in DMA (0.3 mL) is added with regular stirring, after addition is stirred at room temperature for 10 minutes, then a solution of 1i (151mg, 0.45 mmol, 1.5 eq.) in THF (0.2 mL) is added, the reaction is carried out at room temperature for 1 hour, the reaction is complete, water is added for quenching, extraction is carried out three times with ethyl acetate, the organic layers are combined, dried over sodium sulfate, evaporated to dryness and purified by column chromatography to give the product iodoaryl ether 3ia, yield 25%.
Example 5
Suspending calcium hydride (0.9 mmol, 3 eq.) in THF (1 mL), adding a solution of phenol 2a (28 mg, 0.3 mmol, 1 eq.) in DMA (0.3 mL) with regular stirring, stirring at room temperature for 10 minutes after addition is complete, then adding a solution of 1i (151mg, 0.45 mmol, 1.5 eq.) in THF (0.2 mL), reacting at room temperature for 1 hour, completing the reaction, adding water for quenching, extracting three times with ethyl acetate, combining the organic layers, drying with sodium sulfate, evaporating to dryness, purifying by column chromatography to give the product iodoaryl ether 3ia, yield 12%.
Application examples
Iodo-aromatic ether 3ia, epoxy resin E44 and ethylenediamine in a weight ratio of 0.5: 10: 1 are used as raw materials, a process of curing at room temperature for 12 hours and curing at 60 ℃ for 1.5 hours is adopted, and an oxygen index is 23.6 according to an ASTM D2863 sample preparation test; an epoxy resin E44, ethylene diamine in a weight ratio of 10: 1 was used as a comparison, and an oxygen index of 20.7 was also measured.
Compared with the prior art, the invention can obtain the 2-iodo heterocyclic aromatic ether only by stirring commercial o-dihalobenzene (at least one of which is iodine) and phenol for a period of time at room temperature under the action of alkali metal hydride, and is obviously superior to the prior method in terms of synthesis efficiency and cost; the product can be used as a non-reactive flame retardant to improve the flame retardant property of pure resin.
Claims (10)
1. A method for preparing 2-iodo-heterocyclic aromatic ether at room temperature comprises the following steps of reacting diiodo-heterocyclic aromatic hydrocarbon with phenol in the presence of alkali metal hydride to obtain 2-iodo-heterocyclic aromatic ether.
2. The method for preparing 2-iodo heterocyclic aromatic ether at room temperature according to claim 1, wherein the 2-iodo heterocyclic aromatic ether is obtained by adding an alkali metal hydride and a phenol to a solvent, and then adding a diiodo heterocyclic aromatic hydrocarbon to react.
3. The method for preparing 2-iodo heterocyclic aromatic ether at room temperature according to claim 2, wherein the solvent is one or more of DMF, DMA, THF, 2-MeTHF, DME, MTBE, diethyl ether, DMSO, NMP, and toluene.
4. The method for preparing 2-iodo heterocyclic aromatic ether at room temperature according to claim 1, wherein the alkali metal hydride is sodium hydride, potassium hydride or calcium hydride; the phenol is phenol, substituted phenol or heterocyclic phenol.
5. The method for preparing 2-iodo-heterocyclic aromatic ether at room temperature as claimed in claim 1, wherein the molar ratio of the phenol, the diiodo-heterocyclic aromatic hydrocarbon and the alkali metal hydride is 1 (0.1-10) to 1.2-10.
6. The method for preparing 2-iodo-heterocyclic aromatic ether at room temperature as claimed in claim 5, wherein the molar ratio of the phenol, the diiodo-heterocyclic aromatic hydrocarbon and the alkali metal hydride is 1 (0.5-5) to 1.5-5.
7. The method for preparing 2-iodo-heterocyclic aromatic ether at room temperature according to claim 1, wherein the reaction temperature is 10-50 ℃; the reaction time is 0.2-2 hours.
8. A diiodo heterocyclic aromatic hydrocarbon having the chemical formula:
9. the application of alkali metal hydride in preparing 2-iodo-heterocyclic aromatic ether by using diiodo-heterocyclic aromatic hydrocarbon and phenol as raw materials; the diiodo heterocyclic aromatic hydrocarbon is characterized in that the chemical structural formula of the diiodo heterocyclic aromatic hydrocarbon is as follows:
10. the 2-iodo heterocyclic aromatic ether prepared by the method for preparing a 2-iodo heterocyclic aromatic ether at room temperature according to claim 1, wherein the chemical structural formula of the 2-iodo heterocyclic aromatic ether is as follows:
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| WO2022174468A1 (en) * | 2021-02-22 | 2022-08-25 | 苏州大学 | Method for preparing 2-iodoheterocyclic aryl ether at room temperature |
Citations (3)
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|---|---|---|---|---|
| CN1911887A (en) * | 2006-08-23 | 2007-02-14 | 嘉兴学院 | Method of synthesizing aromatic ether without solvent |
| CN102344345A (en) * | 2011-07-28 | 2012-02-08 | 南京师范大学 | Preparation method of arylene ether compound |
| US20120214785A1 (en) * | 2010-09-02 | 2012-08-23 | Boehringer Ingelheim International Gmbh | New compounds, pharmaceutical compositions and uses thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1911887A (en) * | 2006-08-23 | 2007-02-14 | 嘉兴学院 | Method of synthesizing aromatic ether without solvent |
| US20120214785A1 (en) * | 2010-09-02 | 2012-08-23 | Boehringer Ingelheim International Gmbh | New compounds, pharmaceutical compositions and uses thereof |
| CN102344345A (en) * | 2011-07-28 | 2012-02-08 | 南京师范大学 | Preparation method of arylene ether compound |
Non-Patent Citations (3)
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| DEBABRATA MAITI等: "Cu-Catalyzed Arylation of Phenols: Synthesis of Sterically", 《J ORG CHEM.》 * |
| WANWAN SUN等: "A NaH-promoted N-detosylation reaction of diverse", 《TETRAHEDRON LETTERS》 * |
| YUNTONG ZHAI等: "Copper-Catalyzed Diaryl Ether Formation from (Hetero)aryl Halides", 《J. ORG. CHEM》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2022174468A1 (en) * | 2021-02-22 | 2022-08-25 | 苏州大学 | Method for preparing 2-iodoheterocyclic aryl ether at room temperature |
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