CN114560835A - Preparation method of tetrahydropyranone derivative - Google Patents
Preparation method of tetrahydropyranone derivative Download PDFInfo
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- CN114560835A CN114560835A CN202011351647.0A CN202011351647A CN114560835A CN 114560835 A CN114560835 A CN 114560835A CN 202011351647 A CN202011351647 A CN 202011351647A CN 114560835 A CN114560835 A CN 114560835A
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- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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 preparation method of a tetrahydropyranone derivative, which comprises the following steps: (1) reacting 1, 5-dihalogen-3-pentanone or a derivative thereof with an alkaline oxidant in an organic solvent in the presence of a metal catalyst to obtain a mixed solution; (2) adding an alkaline catalyst into the mixed solution for reaction to prepare tetrahydropyranone and derivatives thereof; among them, the halogen in 1, 5-dihalo-3-pentanone may include chlorine or bromine. The synthesis method is simple to operate, mild in condition, few in by-products, high in product purity and high in product yield.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of a tetrahydropyranone derivative.
Background
Pyran is an oxygen-containing six-membered heterocyclic ring system with an oxygen atom replacing one carbon atom in the six-membered ring, and is a very important heterocyclic compound. The pyran compounds have wide biological activity, and the synthesis of the compounds has important significance. Is an important structural kernel of natural products such as a plurality of carbohydrates, polyether antibiotics, marine toxins, pheromones and the like, and plays an important role in the biological activity of the natural products. Tetrahydropyran is also an important synthetic intermediate for constructing other heterocyclic compounds, and the heterocyclic compounds have good effects in the aspects of resisting cancer, resisting allergy, resisting aging, inhibiting cancer cells, resisting cytotoxin activity and the like according to the existing reports. Therefore, the synthesis method of tetrahydropyran compounds has received extensive attention from researchers, and has become a research hotspot of organic synthesis.
According to the current reports, the preparation method of the tetrahydropyranone derivatives mainly comprises the following steps: (1) under the conditions of normal temperature and normal pressure, pyran-4-ketone and hydrogen react in ethanol in the presence of Raney nickel to prepare tetrahydropyranone, and the method has low yield and is difficult to produce and use on a large scale; (2) the method for preparing the tetrahydropyranone by reacting pyran-4-ketone with hydrogen in a methanol environment under the catalysis of palladium/scandium carbonate in a high-pressure environment has the advantage of difficult adaptation to industrial production although the yield is improved. Therefore, the research and development of the preparation method of the tetrahydropyranone derivative with higher yield and simple operation has important practical significance.
Disclosure of Invention
The invention aims to provide a preparation method of a tetrahydropyranone derivative, which has the advantages of simple operation, mild conditions, less by-products, high product purity and high product yield.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for preparing a tetrahydropyranone derivative, comprising the steps of:
(1) reacting 1, 5-dihalogen-3-pentanone or a derivative thereof with an alkaline oxidant in an organic solvent in the presence of a metal catalyst to obtain a mixed solution;
(2) adding an alkaline catalyst into the mixed solution for reaction to prepare tetrahydropyranone and derivatives thereof;
among them, the halogen in 1, 5-dihalo-3-pentanone may include chlorine or bromine.
In an embodiment of the present application, the step (1) specifically includes:
mixing the 1, 5-dihalogen-3-pentanone or the derivative thereof, the metal catalyst and the organic solvent, then adding an alkaline oxidant under the condition of controlling the temperature to be 0-20 ℃, and reacting to obtain a mixed solution.
In one embodiment of the present application, the reaction temperature in step (1) is 5-10 ℃ and the reaction time is 4-8 h.
In one embodiment of the present application, the organic solvent is an alcohol, a ketone carbonyl compound, an ester, acetonitrile; ether, N-dialkyl amide, dialkyl sulfoxide.
In one embodiment of the present application, the 1, 5-dihalo-3-pentanone or its derivative, the metal catalyst and the basic oxidant in step (1) are used in a molar ratio of 1 (0.99-1.05): (2-5).
In an embodiment of the present application, the metal catalyst is at least one of palladium, platinum or nickel.
In one embodiment of the present application, the alkaline oxidizing agent is at least one of sodium hypochlorite, sodium percarbonate, sodium perborate, and potassium perborate.
In an embodiment of the present application, the step (2) is specifically:
adding an alkaline catalyst into the mixed solution, and reacting at 60-80 ℃ for 12-24h to obtain the tetrahydropyranone and the derivatives thereof.
In one embodiment of the present application, the basic catalyst is one or more of an alkali metal hydride, an alkaline earth metal hydride, an alkali metal alkoxide, and an alkaline earth metal alkoxide.
In one embodiment of the present application, the temperature of the reaction in the step (2) is 70-80 ℃, and the reaction time is 18-20 h.
The invention has the following beneficial effects that the application discloses a preparation method of a tetrahydropyranone derivative, which is characterized in that under the catalysis of a metal catalyst, a basic oxidant is utilized to oxidize halogen in 1, 5-dihalogen-3-pentanone or the derivative thereof. Because the metal catalyst is added, the oxidation process can be rapidly carried out under a mild condition, and the oxidation efficiency is high. And then, directly cyclizing the oxidized 1, 5-dihalo-3-pentanone or the derivative thereof by using a basic catalyst to prepare the tetrahydropyranone derivative. Under the catalysis of an alkaline catalyst, the cyclization reaction is mild and rapid, and the conversion rate of the reaction is higher. In addition, an intermediate purification step is not needed in the reaction process, the operation is simple, the product yield is high, and the method is very suitable for large-scale industrial production.
Detailed Description
In order to better understand the present invention, the following examples further illustrate the invention, the examples are only used for explaining the invention, not to constitute any limitation of the invention.
A process for preparing a tetrahydropyranone derivative, comprising the steps of:
(1) reacting 1, 5-dihalogen-3-pentanone or a derivative thereof with an alkaline oxidant in an organic solvent in the presence of a metal catalyst to obtain a mixed solution;
(2) adding an alkaline catalyst into the mixed solution for reaction to prepare tetrahydropyranone and derivatives thereof;
among them, the halogen in 1, 5-dihalo-3-pentanone may include chlorine or bromine.
In an embodiment of the present application, the step (1) specifically includes: mixing the 1, 5-dihalogen-3-pentanone or the derivative thereof, the metal catalyst and the organic solvent, then adding an alkaline oxidant under the condition of controlling the temperature to be 0-20 ℃, and obtaining a mixed solution after reaction. Preferably, the reaction temperature in the step (1) is 5-10 ℃, and the reaction time is 4-8 h.
In one embodiment of the present application, the organic solvent is an alcohol, a ketone carbonyl compound, an ester, acetonitrile; ether, N-dialkyl amide and dialkyl sulfoxide. Specifically, the organic solvent is alcohol, preferably C1-C5 alcohol, including C1-C4 alcohol such as methanol, ethanol, propan-1-ol, propan-2-ol, butan-1-ol and 2-methylpropan-1-ol; ketocarbonyls including acetone, methyl isobutyl ketone, and the like; esters, including ethyl acetate, n-butyl acetate, and the like; acetonitrile; ethers such as diethyl ether, methyl tert-butyl ether; n, N-dialkylamides such as N, N-dimethylformamide and N, N-dimethylacetamide; ketones such as acetone and butanone; dialkyl sulfoxides such as dimethyl sulfoxide, and the like.
In one embodiment of the present application, the 1, 5-dihalo-3-pentanone or its derivative, the metal catalyst and the basic oxidant in step (1) are used in a molar ratio of 1: (0.99-1.05): (2-5). Preferably, the molar ratio is 1: (1-1.02): (3-4). More preferably, the molar ratio is 1: 1.01: 3.
in an embodiment of the present application, the metal catalyst is at least one of palladium, platinum or nickel. Preferably, the metal catalyst is palladium.
In one embodiment of the present application, the alkaline oxidizing agent is at least one of sodium hypochlorite, sodium percarbonate, sodium perborate, and potassium perborate. Preferably, the alkaline oxidizing agent is sodium perborate.
In an embodiment of the present application, the step (2) is specifically: adding an alkaline catalyst into the mixed solution, and reacting at 60-80 ℃ for 12-24h to obtain the tetrahydropyranone and the derivatives thereof.
The kind of the basic catalyst is not particularly limited as long as it is known to those skilled in the art, and in the present invention, one or more of alkali metal hydride, alkaline earth metal hydride, alkali metal alkoxide and alkaline earth metal alkoxide is preferable; wherein the alkali metal is preferably sodium or potassium; the alcohol in the alkali metal alkoxide and the alkaline earth metal alkoxide is preferably methanol, ethanol, n-propanol, isopropanol, n-butanol or tert-butanol; in the present invention, it is most preferable that the first basic catalyst is sodium methoxide or potassium tert-butoxide.
In one embodiment of the present application, the temperature of the reaction in the step (2) is 70-80 ℃, and the reaction time is 18-20 h. Preferably, the temperature of the reaction in the step (2) is 75 ℃, and the reaction time is 19 h.
Example 1
A process for preparing a tetrahydropyranone derivative, comprising the steps of:
(1) mixing the 1, 5-dichloro-3-pentanone or the derivative thereof, palladium and N, N-dimethylformamide, and then adding an alkaline oxidant under the condition of controlling the temperature to be 5 ℃ to react for 8 hours to obtain a mixed solution; the molar ratio is 1: 1.01: 3;
(2) and adding sodium methoxide into the mixed solution, and reacting at 75 ℃ for 20h to obtain the tetrahydropyranone and the derivatives thereof.
The purity of the prepared tetrahydropyranone derivative is 99.8%, and the product yield is 93.6%.
Example 2
A process for preparing a tetrahydropyranone derivative, comprising the steps of:
(1) mixing the 1, 5-dichloro-3-pentanone or the derivative thereof, palladium and N, N-dimethylformamide, and then adding an alkaline oxidant under the condition of controlling the temperature to be 10 ℃ to react for 8 hours to obtain a mixed solution; the molar ratio is 1: 1.01: 3;
(2) and adding sodium methoxide into the mixed solution, and reacting at 80 ℃ for 20h to obtain the tetrahydropyranone and the derivatives thereof.
The purity of the obtained tetrahydropyran derivative was 99.8%, and the product yield was 94.1%.
Example 3
A process for preparing a tetrahydropyranone derivative, comprising the steps of:
(1) mixing the 1, 5-dichloro-3-pentanone or the derivative thereof, palladium and N, N-dimethylformamide, and then adding an alkaline oxidant under the condition of controlling the temperature to be 10 ℃ to react for 6 hours to obtain a mixed solution; the molar ratio is 1: 1.01: 3;
(2) and adding sodium methoxide into the mixed solution, and reacting at 75 ℃ for 19h to obtain the tetrahydropyranone and the derivatives thereof.
The purity of the obtained tetrahydropyranone derivative was 99.9%, and the product yield was 94.5%.
Example 4
A process for preparing a tetrahydropyranone derivative, comprising the steps of:
(1) mixing the 1, 5-dichloro-3-pentanone or the derivative thereof, palladium and N, N-dimethylformamide, and then adding an alkaline oxidant under the condition of controlling the temperature to be 8 ℃ to react for 4 hours to obtain a mixed solution; the molar ratio is 1: 1.01: 3;
(2) and adding sodium methoxide into the mixed solution, and reacting at 80 ℃ for 19h to obtain the tetrahydropyranone and the derivatives thereof.
The purity of the obtained tetrahydropyranone derivative was 99.9%, and the product yield was 93.7%.
Claims (10)
1. A process for producing a tetrahydropyranone derivative, characterized by comprising: the method comprises the following steps:
(1) reacting 1, 5-dihalogen-3-pentanone or a derivative thereof with an alkaline oxidant in an organic solvent in the presence of a metal catalyst to obtain a mixed solution;
(2) adding an alkaline catalyst into the mixed solution, and reacting to obtain tetrahydropyranone and derivatives thereof;
among them, the halogen in 1, 5-dihalo-3-pentanone may include chlorine or bromine.
2. The process for producing a tetrahydropyranone derivative according to claim 1, characterized in that: the step (1) is specifically as follows:
mixing the 1, 5-dichloro-3-pentanone or the derivative thereof, the metal catalyst and the organic solvent, then adding an alkaline oxidant under the condition of controlling the temperature to be 0-20 ℃, and obtaining a mixed solution after reaction.
3. The process for producing a tetrahydropyranone derivative according to claim 1, characterized in that: the reaction temperature in the step (1) is 5-10 ℃, and the reaction time is 4-8 h.
4. The process for producing a tetrahydropyranone derivative according to claim 1, characterized in that: the organic solvent is alcohols, ketone type carbonyls, esters and acetonitrile; ether, N-dialkyl amide and dialkyl sulfoxide.
5. The process for producing a tetrahydropyranone derivative according to claim 1, characterized in that: the molar ratio of the 1, 5-dichloro-3-pentanone or the derivative thereof, the metal catalyst and the alkaline oxidant in the step (1) is 1 (0.99-1.05): (2-5).
6. The process for producing a tetrahydropyranone derivative according to claim 1, characterized in that: the metal catalyst is at least one of palladium, platinum or nickel.
7. The process for producing a tetrahydropyranone derivative according to claim 1, characterized in that: the alkaline oxidant is at least one of sodium hypochlorite, sodium percarbonate, sodium perborate and potassium perborate.
8. The process for producing a tetrahydropyranone derivative according to claim 1, characterized in that: the step (2) is specifically as follows:
adding an alkaline catalyst into the mixed solution, and reacting at 60-80 ℃ for 12-24h to obtain the tetrahydropyranone and the derivatives thereof.
9. The process for producing a tetrahydropyranone derivative according to claim 1, characterized in that: the alkaline catalyst is one or more of alkali metal hydride, alkaline earth metal hydride, alkali metal alkoxide and alkaline earth metal alkoxide.
10. The process for producing a tetrahydropyranone derivative according to claim 1, characterized in that: the reaction temperature in the step (2) is 70-80 ℃, and the reaction time is 18-20 h.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0912567A (en) * | 1995-06-23 | 1997-01-14 | Ube Ind Ltd | Production of tetrahydro-4h-pyrane-4-one |
| CN1285835A (en) * | 1997-11-11 | 2001-02-28 | 拜尔公司 | Novel substituted phenyl keto enols |
| CN1898229A (en) * | 2003-12-19 | 2007-01-17 | 宇部兴产株式会社 | Processes for producing tetrahydropyran-4-one and pyran-4-one |
| CN102770414A (en) * | 2010-04-28 | 2012-11-07 | 第一三共株式会社 | [5,6] heterocyclic compound |
| CN108047181A (en) * | 2017-12-29 | 2018-05-18 | 东莞市联洲知识产权运营管理有限公司 | A kind of synthetic method of tetrahydro pyrone |
-
2020
- 2020-11-27 CN CN202011351647.0A patent/CN114560835A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0912567A (en) * | 1995-06-23 | 1997-01-14 | Ube Ind Ltd | Production of tetrahydro-4h-pyrane-4-one |
| CN1285835A (en) * | 1997-11-11 | 2001-02-28 | 拜尔公司 | Novel substituted phenyl keto enols |
| CN1898229A (en) * | 2003-12-19 | 2007-01-17 | 宇部兴产株式会社 | Processes for producing tetrahydropyran-4-one and pyran-4-one |
| CN102770414A (en) * | 2010-04-28 | 2012-11-07 | 第一三共株式会社 | [5,6] heterocyclic compound |
| CN108047181A (en) * | 2017-12-29 | 2018-05-18 | 东莞市联洲知识产权运营管理有限公司 | A kind of synthetic method of tetrahydro pyrone |
Non-Patent Citations (3)
| Title |
|---|
| G. R. OWEN ET AL.: "A convenient preparation of tetrahydro-4H-pyran-4-one", 《J.CHEM.SOC.》, pages 2401 - 2403 * |
| 侯薇等: "合成环氧化合物的新途径", 《化学工业与工程》, vol. 13, no. 3, pages 47 - 50 * |
| 王小飞等: "过硼酸钠对高碳烯烃的环氧化", 《应用化工》, vol. 43, no. 12, pages 2234 - 2236 * |
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