CN103664803A - Novel synthesis method of 2, 3, 5, 6-tetramethylpyrazine - Google Patents
Novel synthesis method of 2, 3, 5, 6-tetramethylpyrazine Download PDFInfo
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- CN103664803A CN103664803A CN201210341607.7A CN201210341607A CN103664803A CN 103664803 A CN103664803 A CN 103664803A CN 201210341607 A CN201210341607 A CN 201210341607A CN 103664803 A CN103664803 A CN 103664803A
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- tetramethylpyrazine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Abstract
The invention discloses a novel synthesis method of 2, 3, 5, 6-tetramethylpyrazine and belongs to the technical field of synthesis of perfumes, medicines and pesticides. The reaction comprises addition, rearrangement, condensation and oxidation, which are performed in a reaction and sublimation route device, and a qualified product is obtained by steam distillation. According to the synthesis method disclosed by the invention, the process steps are simplified, material resources are fully utilized, and the synthesis method further has the advantages of low energy consumption, high product yield, environmental friendliness, low production cost, and simplicity and rapidness in operation, and is further conductive to industrial mass production. The synthesis method disclosed by the invention can be widely applied to industrial production of 2, 3, 5, 6-tetramethylpyrazine. By adopting the novel synthesis process disclosed by the invention, the 2, 3, 5, 6-tetramethylpyrazine product can be produced, and the 2, 3, 5, 6-tetramethylpyrazine product can be widely used as the perfume, a food additive, a photosensitizer, the medicine, the pesticide and the like.
Description
Technical field
The invention belongs to spices, foodstuff additive, photosensitizers, medicine and pesticide synthesis technical field, the present invention has simplified processing step, makes the most of material resources; and it is low to have energy consumption, product yield is high, utilizes environment protection; production cost is low, and method is simple to operation, utilizes industrialized production.The present invention can be widely used in suitability for industrialized production 2，3，5，6-tetramethylpyrazine.
Background technology
According to what study for many years 2，3，5，6-tetramethylpyrazine product, syntheticly there is a following methods:
1. this compound comes from Mei Ladaode reaction at first, and Amrani-Hemaimi reaction mechanism, thinks that pyrazine compound is to be formed by the condensation of alpha-amino group ketone.Agric?Food?Chem，1995，43：2818～2822。
2.1959 years Shu and Lawrencc 3-hydroxy-2-butanone and ammonium sulfide reaction mechanisms:
3. domestic and international industrialized 2，3，5，6-tetramethylpyrazine synthetic method has two classes at present, and a class is biological synthesis process, mainly take glucose as raw material, the natural product that make via microorganism fermentation; One class is chemical synthesis, greatly mainly with 2,3-dimethyl diketone, and 2,3-butanediamine or be that raw material is synthetic with butanone and ethyl nitrite.Result is undesirable.
4. several units such as Third Military Medical University are with 3-hydroxy-2-butanone, Ammoniom-Acetate, ethanol, N
2protection, with Manganse Dioxide and zinc chloride oxidation, yield is low, pollutes greatly, and cost is high.
5. Henan chemical industry is with 3-hydroxy-2-butanone, and Ammoniom-Acetate and water reaction, then pay and press oxidation by vacuum, due to product distillation, obtains product yield low, pollutes also greatly, and cost is high.
6. the patent CN1238344C of the Li Zhu of Guangdong Province group, Tetramethylpyrazine production methods, operational path is long, pollutes greatly, and yield is low, and cost is high.
Embodiment
One, Tetramethylpyrazine
1500L reactor adds 240Kg 3-hydroxy-2-butanone, 360Kg Ammoniom-Acetate, 95% ethanol 240Kg.Stir and heat up 90 ℃～93 ℃, react 10 hours; Reactant is cooled to 60 ℃, with in 20% liquid caustic soda and PH=7～8.Forward reactant to 1500L reactor and be warmed up to 82 ℃～99 ℃ recovery 95% ethanol (recycling), then add 600Kg water, intensification distillage, when temperature reaches 105 ℃ of limits (600Kg) limit distillage that drips, within approximately 10 hours, complete, 2000L reactor, 400Kg pure water receives product and is cooled to 4 ℃～5 ℃ centrifugal products (Centrifugal Effluent Treatment recycles), obtains Tetramethylpyrazine 160Kg.
Two. phosphoric acid Ligustrazine
Salify: 100kg dehydrated alcohol is sucked to 500L reactor, then 100kg Tetramethylpyrazine is dropped into reactor successively, open agitator.20 ℃ of left and right drip phosphoric acid 50kg, and test PH=2～3 drip off and continue to stir 20 minutes, centrifugal, and heat-wind circulate drying between temperature 60 C～70 ℃, completes, obtain 110Kg for approximately 6 hours.
Three. ligustrazine hydrochloride
Salify: 100kg dehydrated alcohol is sucked to 500L reactor, then 100kg Tetramethylpyrazine is dropped into reactor successively, open agitator.20 ℃ of left and right drip 33% acidic alcohol 31kg, test PH=2～3, drip off continuation stirring and add after 20 minutes, then reclaim ethanol 120Kg, a small amount of water of rear pressure reducing and steaming, be cooled to 60 ℃ to add the crystallization of 250kg ethyl acetate, centrifugal, at 40 ℃, carry out below heat-wind circulate drying, pulverize, via hole diameter sieve on the 40th, takes approximately 12 hours.Obtain 85Kg.
Claims (8)
1. the synthetic method of a synthetic following formula: compound I:
Formula (I)
2. the synthetic method of a synthetic following formula: compound II:
Formula (II)
3. the synthetic method of a synthetic following formula: compound III:
Formula (III)
4. according to the method described in claim 1, three kinds of material rates are 3-hydroxy-2-butanone: 95% ethanol: Ammoniom-Acetate=1: 1: 1～2.
Solvent comprises dehydrated alcohol, methyl alcohol, acetone, butanone and DMF.
5. according to the method described in claim 1, in and pH value scope 6～12.
6. according to the method described in claim 1, temperature of reaction is 80 ℃～105 ℃.
7. according to the method described in claim 1, the reaction times is 4～20 hours.
8. according to the method described in claim 1, water distillation water is 1: 20～100.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210341607.7A CN103664803A (en) | 2012-09-17 | 2012-09-17 | Novel synthesis method of 2, 3, 5, 6-tetramethylpyrazine |
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| CN201210341607.7A CN103664803A (en) | 2012-09-17 | 2012-09-17 | Novel synthesis method of 2, 3, 5, 6-tetramethylpyrazine |
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| CN103664803A true CN103664803A (en) | 2014-03-26 |
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| CN201210341607.7A Pending CN103664803A (en) | 2012-09-17 | 2012-09-17 | Novel synthesis method of 2, 3, 5, 6-tetramethylpyrazine |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015163090A1 (en) * | 2014-04-21 | 2015-10-29 | 株式会社Adeka | Alkoxide compound, raw material for forming thin film, method for producing thin film, and alcohol compound |
| CN107384728A (en) * | 2017-07-17 | 2017-11-24 | 福建农林大学 | A kind of method of the content of Tetramethylpyrazine in raising vinegar |
| CN107460106A (en) * | 2017-07-17 | 2017-12-12 | 福建农林大学 | A kind of method of the content of alkyl pyrazine compound in raising vinegar |
| CN107556251A (en) * | 2017-08-23 | 2018-01-09 | 广东昊邦医药健康有限责任公司 | A kind of ligustrazine phosphat derivative compound and its pharmaceutical composition |
| CN107879987A (en) * | 2017-12-23 | 2018-04-06 | 山东吉田香料股份有限公司 | A kind of preparation method of 2,3,5,6 Tetramethylpyrazine |
| CN108863954A (en) * | 2018-08-03 | 2018-11-23 | 滕州市悟通香料有限责任公司 | A kind of synthetic method and device of 2,3,5,6- Tetramethylpyrazine |
| CN108892645A (en) * | 2018-09-15 | 2018-11-27 | 广州方中化工有限公司 | A method of preparing Tetramethylpyrazine |
| JP2020514390A (en) * | 2017-03-24 | 2020-05-21 | アール・ジエイ・レイノルズ・タバコ・カンパニー | Method for selective formation of substituted pyrazines |
Citations (6)
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|---|---|---|---|---|
| JPS6058756B2 (en) * | 1976-02-13 | 1985-12-21 | 高砂香料工業株式会社 | Method for producing alkylpyrazine |
| US4865599A (en) * | 1986-08-18 | 1989-09-12 | Houston Biotechnology, Inc. | Ophthalmic compositions for treating nerve degeneration |
| CA2062149A1 (en) * | 1991-03-26 | 1992-09-27 | Teh-Kuei Chen | Preparation of pyrazines |
| CN1253134A (en) * | 1998-11-11 | 2000-05-17 | 浙江省应用化学重点研究实验室 | Process for preparing tetramethyl pyrazine |
| CN1546474A (en) * | 2003-10-27 | 2004-11-17 | 丽珠集团利民制药厂 | Method for preparing tetramethyl pyrazine |
| CN102391192A (en) * | 2011-10-09 | 2012-03-28 | 湖南中医药大学 | Preparation method and application of shikimic acid ligustrazine |
-
2012
- 2012-09-17 CN CN201210341607.7A patent/CN103664803A/en active Pending
Patent Citations (6)
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|---|---|---|---|---|
| JPS6058756B2 (en) * | 1976-02-13 | 1985-12-21 | 高砂香料工業株式会社 | Method for producing alkylpyrazine |
| US4865599A (en) * | 1986-08-18 | 1989-09-12 | Houston Biotechnology, Inc. | Ophthalmic compositions for treating nerve degeneration |
| CA2062149A1 (en) * | 1991-03-26 | 1992-09-27 | Teh-Kuei Chen | Preparation of pyrazines |
| CN1253134A (en) * | 1998-11-11 | 2000-05-17 | 浙江省应用化学重点研究实验室 | Process for preparing tetramethyl pyrazine |
| CN1546474A (en) * | 2003-10-27 | 2004-11-17 | 丽珠集团利民制药厂 | Method for preparing tetramethyl pyrazine |
| CN102391192A (en) * | 2011-10-09 | 2012-03-28 | 湖南中医药大学 | Preparation method and application of shikimic acid ligustrazine |
Non-Patent Citations (1)
| Title |
|---|
| 杜宇，等: "3-羟基-2-丁酮合成2，3，5，6-四甲基吡嗪的研究", 《河南化工》, no. 2, 31 December 2011 (2011-12-31), pages 35 - 38 * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015163090A1 (en) * | 2014-04-21 | 2015-10-29 | 株式会社Adeka | Alkoxide compound, raw material for forming thin film, method for producing thin film, and alcohol compound |
| JP2015205837A (en) * | 2014-04-21 | 2015-11-19 | 株式会社Adeka | Alkoxide compound, raw material for forming thin film, manufacturing method for thin film and alcohol compound |
| US10351584B2 (en) | 2014-04-21 | 2019-07-16 | Adeka Corporation | Alkoxide compound, raw material for forming thin film, method for manufacturing thin film, and alcohol compound |
| JP2020514390A (en) * | 2017-03-24 | 2020-05-21 | アール・ジエイ・レイノルズ・タバコ・カンパニー | Method for selective formation of substituted pyrazines |
| JP7278958B2 (en) | 2017-03-24 | 2023-05-22 | アール・ジエイ・レイノルズ・タバコ・カンパニー | Method for Selective Formation of Substituted Pyrazines |
| CN107384728A (en) * | 2017-07-17 | 2017-11-24 | 福建农林大学 | A kind of method of the content of Tetramethylpyrazine in raising vinegar |
| CN107460106A (en) * | 2017-07-17 | 2017-12-12 | 福建农林大学 | A kind of method of the content of alkyl pyrazine compound in raising vinegar |
| CN107556251A (en) * | 2017-08-23 | 2018-01-09 | 广东昊邦医药健康有限责任公司 | A kind of ligustrazine phosphat derivative compound and its pharmaceutical composition |
| CN107879987A (en) * | 2017-12-23 | 2018-04-06 | 山东吉田香料股份有限公司 | A kind of preparation method of 2,3,5,6 Tetramethylpyrazine |
| CN108863954A (en) * | 2018-08-03 | 2018-11-23 | 滕州市悟通香料有限责任公司 | A kind of synthetic method and device of 2,3,5,6- Tetramethylpyrazine |
| CN108892645A (en) * | 2018-09-15 | 2018-11-27 | 广州方中化工有限公司 | A method of preparing Tetramethylpyrazine |
| CN108892645B (en) * | 2018-09-15 | 2021-07-13 | 广州方中化工有限公司 | Method for preparing tetramethylpyrazine |
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Application publication date: 20140326 |