CN103664761A - Preparation method of 4-pyridol - Google Patents
Preparation method of 4-pyridol Download PDFInfo
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- CN103664761A CN103664761A CN201310646586.4A CN201310646586A CN103664761A CN 103664761 A CN103664761 A CN 103664761A CN 201310646586 A CN201310646586 A CN 201310646586A CN 103664761 A CN103664761 A CN 103664761A
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- pyridol
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- pyridyl
- microwave
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/68—One oxygen atom attached in position 4
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of 4-pyridol. The method comprises the following steps: mixing pyridine and ethyl acetate, treating the mixture with microwave in a microwave oven, dropwise adding thionyl chloride into the reactants during the reaction process, taking out the reactants and conducting posttreatment to obtain N-(4-pyridyl) pyridine hydrochloride; and mixing and heating N-(4-pyridyl) pyridine hydrochloride with water, adding alkaline substances to adjust the pH value to 7.5-8.5, precipitating precipitate, filtering the precipitate, adjusting the pH value to 4.5-5 with acidic substances and conducting posttreatment to obtain 4-pyridol. Through the above way, the preparation method of 4-pyridol provided by the invention employs a microwave method for synthesis, has simple synthetic process, greatly shortens the reaction time and saves the cost of production. The obtained 4-pyridol has high purity, almost contains no by-product, does not need other treatment process, and can be directly applied to the subsequent production.
Description
Technical field
The present invention relates to Minute Organic Synthesis field, particularly relate to a kind of preparation method of 4-pyridol.
Background technology
The molecular formula of 4-pyridol is C
5h
5nO, molecular weight is 95.1, has certain pungency, and eyes, respiratory system and skin are had to very large hormesis.4-pyridol is a kind of important organic synthesis intermediate, at aspects such as medicine, agricultural chemicals, has been widely used, and can be used in synthetic diuretic torasemide, treatment congestive heart failure medicine support Luo Sai meter or other drug intermediate.In the process of the synthetic 4-pyridol of tradition, can produce a large amount of by products, long reaction time.
Summary of the invention
The technical problem that the present invention mainly solves is to provide a kind of preparation method of 4-pyridol, and the method is simple to operate and safe and reliable.
For solving the problems of the technologies described above, the technical scheme that the present invention adopts is: a kind of preparation method of 4-pyridol is provided, comprises that step is:
(1) pyridine and ethyl acetate are mixed to put in microwave oven carry out microwave, in reaction process, in reactant, drip thionyl chloride, reaction is taken out aftertreatment and is obtained N-(4-pyridyl) pyridine hydrochloride;
(2) by N-(4-pyridyl) pyridine hydrochloride and water Hybrid Heating, add alkaline matter to regulate pH value for 7.5-8.5, there is Precipitation, filtering and with acidic substance, regulating pH value is again 4.5-5, aftertreatment obtains 4-pyridol.
In a preferred embodiment of the present invention, step is set to 70-80 ℃ by the temperature setting of described microwave oven in (1).
In a preferred embodiment of the present invention, the reaction times described in step (1) is 20-30 ℃.
In a preferred embodiment of the present invention, described in step (2), alkaline matter is potassium hydroxide or sodium hydroxide, and described acidic substance are hydrochloric acid or sulfuric acid.
The invention has the beneficial effects as follows: the preparation method of 4-pyridol of the present invention, by microwave method, synthesize, building-up process is simple to operate, energy is Reaction time shorten greatly, save production cost, the 4-pyridol purity obtaining is high, and by product does not almost have, do not need to carry out other treating processes, can be applied directly in follow-up production.
Embodiment
Below the technical scheme in the embodiment of the present invention is clearly and completely described, obviously, described embodiment is only a part of embodiment of the present invention, rather than whole embodiment.Embodiment based in the present invention, those of ordinary skills, not making all other embodiment that obtain under creative work prerequisite, belong to the scope of protection of the invention.
Embodiment mono-:
A kind of preparation method of 4-pyridol is provided, comprises that step is:
(1) pyridine and ethyl acetate are mixed put into and in microwave oven, carry out microwave, the temperature setting of described microwave oven is set to 76 ℃, in reaction process, in reactant, drip thionyl chloride, the described reaction times is 20 ℃, and reaction is taken out aftertreatment and obtained N-(4-pyridyl) pyridine hydrochloride;
(2) by N-(4-pyridyl) pyridine hydrochloride and water Hybrid Heating, adding potassium hydroxide or sodium hydroxide to regulate pH value is 8.5, has Precipitation, and filtering is 4.5 with sulphur acid for adjusting pH value again, and aftertreatment obtains 4-pyridol.
Embodiment bis-:
A kind of preparation method of 4-pyridol is provided, comprises that step is:
(1) pyridine and ethyl acetate are mixed put into and in microwave oven, carry out microwave, the temperature setting of described microwave oven is set to 70 ℃, in reaction process, in reactant, drip thionyl chloride, the described reaction times is 30 ℃, and reaction is taken out aftertreatment and obtained N-(4-pyridyl) pyridine hydrochloride;
(2) by N-(4-pyridyl) pyridine hydrochloride and water Hybrid Heating, adding potassium hydroxide or sodium hydroxide to regulate pH value is 8, has Precipitation, and filtering is 4.8 with sulphur acid for adjusting pH value again, and aftertreatment obtains 4-pyridol.
Embodiment tri-:
A kind of preparation method of 4-pyridol is provided, comprises that step is:
(1) pyridine and ethyl acetate are mixed put into and in microwave oven, carry out microwave, the temperature setting of described microwave oven is set to 80 ℃, in reaction process, in reactant, drip thionyl chloride, the described reaction times is 27 ℃, and reaction is taken out aftertreatment and obtained N-(4-pyridyl) pyridine hydrochloride;
(2) by N-(4-pyridyl) pyridine hydrochloride and water Hybrid Heating, adding potassium hydroxide or sodium hydroxide to regulate pH value is 7.5, has Precipitation, and filtering is 5 with salt acid for adjusting pH value again, and aftertreatment obtains 4-pyridol.
The foregoing is only embodiments of the invention; not thereby limit the scope of the claims of the present invention; every equivalent structure or conversion of equivalent flow process that utilizes description of the present invention to do; or be directly or indirectly used in other relevant technical field, be all in like manner included in scope of patent protection of the present invention.
Claims (4)
1. a preparation method for 4-pyridol, is characterized in that, comprises that step is:
(1) pyridine and ethyl acetate are mixed to put in microwave oven carry out microwave, in reaction process, in reactant, drip thionyl chloride, reaction is taken out aftertreatment and is obtained N-(4-pyridyl) pyridine hydrochloride;
(2) by N-(4-pyridyl) pyridine hydrochloride and water Hybrid Heating, add alkaline matter to regulate pH value for 7.5-8.5, there is Precipitation, filtering and with acidic substance, regulating pH value is again 4.5-5, aftertreatment obtains 4-pyridol.
2. the preparation method of 4-pyridol according to claim 1, is characterized in that, step is set to 70-80 ℃ by the temperature setting of described microwave oven in (1).
3. the preparation method of 4-pyridol according to claim 1, is characterized in that, the reaction times described in step (1) is 20-30 ℃.
4. the preparation method of 4-pyridol according to claim 1, is characterized in that, described in step (2), alkaline matter is potassium hydroxide or sodium hydroxide, and described acidic substance are hydrochloric acid or sulfuric acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310646586.4A CN103664761A (en) | 2013-12-06 | 2013-12-06 | Preparation method of 4-pyridol |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310646586.4A CN103664761A (en) | 2013-12-06 | 2013-12-06 | Preparation method of 4-pyridol |
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| CN103664761A true CN103664761A (en) | 2014-03-26 |
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| CN201310646586.4A Pending CN103664761A (en) | 2013-12-06 | 2013-12-06 | Preparation method of 4-pyridol |
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| CN (1) | CN103664761A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995007892A1 (en) * | 1993-09-14 | 1995-03-23 | Hoechst Schering Agrevo Gmbh | Substituted pyridines, process for producing them and their use as pesticides and fungicides |
| CN1130902A (en) * | 1993-09-14 | 1996-09-11 | 赫彻斯特-舍林农业发展有限公司 | Substituted pyridines, process for producing them and their use as pesticides and fungicides |
| US5723450A (en) * | 1993-09-14 | 1998-03-03 | Hoechst Schering Agrevo Gmbh | Substituted pyridines, their preparation, and their use as pesticides and fungicides |
| CN1468055A (en) * | 2000-10-03 | 2004-01-14 | �����ɷ� | Phenylpropynyloxypyridine herbicides |
| CN1560036A (en) * | 2004-03-12 | 2005-01-05 | 南通市东昌化工有限公司 | 4-hydroxylic pyridine and production process thereof |
| CN102947270A (en) * | 2010-06-22 | 2013-02-27 | 巴斯夫欧洲公司 | Process for preparing 4-hydroxypyridines |
-
2013
- 2013-12-06 CN CN201310646586.4A patent/CN103664761A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995007892A1 (en) * | 1993-09-14 | 1995-03-23 | Hoechst Schering Agrevo Gmbh | Substituted pyridines, process for producing them and their use as pesticides and fungicides |
| CN1130902A (en) * | 1993-09-14 | 1996-09-11 | 赫彻斯特-舍林农业发展有限公司 | Substituted pyridines, process for producing them and their use as pesticides and fungicides |
| US5723450A (en) * | 1993-09-14 | 1998-03-03 | Hoechst Schering Agrevo Gmbh | Substituted pyridines, their preparation, and their use as pesticides and fungicides |
| CN1468055A (en) * | 2000-10-03 | 2004-01-14 | �����ɷ� | Phenylpropynyloxypyridine herbicides |
| CN1560036A (en) * | 2004-03-12 | 2005-01-05 | 南通市东昌化工有限公司 | 4-hydroxylic pyridine and production process thereof |
| CN102947270A (en) * | 2010-06-22 | 2013-02-27 | 巴斯夫欧洲公司 | Process for preparing 4-hydroxypyridines |
Non-Patent Citations (6)
| Title |
|---|
| DR.K.THOMAS,等: "Neuere Methoden der praparativen organischen Chemie II 12. Die Einführung von Substituenten in den Pyridin-Ring", 《ANGEWANDTE CHEMIE》, vol. 70, no. 24, 21 December 1958 (1958-12-21), pages 719 - 737 * |
| RUSSELL F. EVANS,等: "The Sulfonic Acids Derived from Pyridine and 2,6-Lutidine and the Corresponding N-Oxides", 《J.ORG.CHEM.》, vol. 27, no. 4, 30 April 1962 (1962-04-30), pages 1329 - 1336 * |
| 施永兵,等: "4-羟基吡啶的合成工艺进展", 《浙江化工》, vol. 35, no. 05, 31 May 2004 (2004-05-31), pages 15 - 16 * |
| 熊振湖,等: "4-羟基吡啶合成方法的改进", 《化学研究》, vol. 12, no. 04, 31 December 2001 (2001-12-31), pages 37 - 38 * |
| 王富山,等: "4-苯氧基吡啶的合成", 《辽宁化工》, vol. 30, no. 01, 31 January 2001 (2001-01-31), pages 31 - 33 * |
| 陈毅平,等: "4-羟基吡啶的合成", 《精细化工中间体》, vol. 32, no. 05, 31 October 2002 (2002-10-31), pages 15 - 16 * |
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Application publication date: 20140326 |