CN101519379A - Method for preparing 5-methylprazine-2-carboxylic acid - Google Patents
Method for preparing 5-methylprazine-2-carboxylic acid Download PDFInfo
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- CN101519379A CN101519379A CN200910068469A CN200910068469A CN101519379A CN 101519379 A CN101519379 A CN 101519379A CN 200910068469 A CN200910068469 A CN 200910068469A CN 200910068469 A CN200910068469 A CN 200910068469A CN 101519379 A CN101519379 A CN 101519379A
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Abstract
The invention provides a method for preparing 5-methylprazine-2-carboxylic acid. The preparation method comprises the steps: using 5-methyl-2and3- pyrazine 2-carboxylic acid as raw material, carrying out photophobism reaction in a saturated saline solution, and obtaining 5-methylprazine-2-carboxylic acid as a final product. The preparation method optimizes the process from the source on the basis of the principle of water decarboxylation, thereby being a method for effective decarboxylation in a saline solution at lower temperature. Moreover, in the preparation method, no organic solvent is added in the chemical reaction, no pollution is generated, the condition is mild, the reaction in the whole technological process has no high temperature, high selectivity and few by-products, thus the preparation method is a simple and available pollution-free method which has the capability of large-scale production.
Description
(1) technical field:
The present invention relates to the preparation method of a kind of 5-methylpyrazine-2-carboxylic acid.
(2) background technology:
Decarboxylic reaction generally is to utilize the unstable of compound to heat, and by the vacuum decarboxylation, methods such as solvent decarboxylation and the decarboxylation of water medium mesohigh are finished.
The vacuum decompression decarboxylation is to utilize vacuum to take out the carbonic acid gas that generates after the dereaction, thereby reaction is carried out to positive dirction.This method need add joins specific apparatus, and the early stage input of producing is bigger.
The solvent decarboxylation is to select higher solvent of boiling point such as dimethylbenzene for use, and trimethylbenzene carries out decarboxylation about 140～180 ℃.The shortcoming of this kind method is that cost is higher, need expend a large amount of organic solvents, and by product is more and be difficult to remove, and carbonization phenomenon is comparatively serious because temperature of reaction is very high.
Decarboxylation in the water report among the patent EP0194671 that pH need be strict controlled in 0.7～2.2 in the decarboxylation procedure, and temperature of reaction is 155～170 ℃ because its green characteristics have more research in recent years.Reporting too among the CN96100260 needs strict control pH 3.5～8, and temperature of reaction is 100～160 ℃ reacts down, and this method can be in decompression, and normal pressure adds to depress and carries out.This kind method condition harshness, though be but that the water react temperature is higher, be unfavorable for large-scale production.
(3) summary of the invention:
Technical problem to be solved by this invention is to provide the preparation method of a kind of 5-methylpyrazine-2-carboxylic acid.
For solving the problems of the technologies described above, technical scheme of the present invention is:
The preparation method of a kind of 5-methylpyrazine-2-carboxylic acid, with 5-methyl-2,3-pyrazine dioctyl phthalate is raw material lucifuge reaction in saturated aqueous common salt, obtains finished product 5-methylpyrazine-2-carboxylic acid, concrete preparation process is as follows:
(1) with the saturated aqueous common salt is solvent, adds main raw material 5-methyl-2,3-pyrazine dioctyl phthalate
Add a little salt again and make the salt solution supersaturation, heat temperature raising is to 105-115 ℃, and back flow reaction 8-15 hour to main raw material 5-methyl-2,3-pyrazine dioctyl phthalate
Disappear; Wherein the consumption of saturated aqueous common salt is at every gram
5ml-10ml;
(2) question response is finished, and reduces to room temperature, suction filtration, and filtrate extracts with butanone, and organic phase merges the back and concentrates, and cooling crystallization in ice-water bath, suction filtration promptly get product; Wherein butanone consumption at every gram
15-25ml.
The preparation method of above-mentioned a kind of 5-methylpyrazine-2-carboxylic acid, wherein the consumption of step (1) saturated aqueous common salt is at every gram
5ml～8ml; Step (2) butanone consumption at every gram
15～18mL.
The preparation method of above-mentioned a kind of 5-methylpyrazine-2-carboxylic acid, wherein the consumption of step (1) saturated aqueous common salt is at every gram
8ml; Step (2) butanone consumption at every gram
18mL.
Superiority of the present invention:
1, preparation method of the present invention is based on the principle of decarboxylation in the water, from the source, technology is optimized, be under a kind of lesser temps in salt solution the effective method of decarboxylation, by in supersaturated brine in 110 ℃ of decarboxylations, obtain end product 5-methylpyrazine-2-carboxylic acid through aftertreatment again, purity can reach 98%; 2, aforesaid method chemical reaction organic solvent-free; the environmental protection mild condition; reaction in the whole technological process, no pyroreaction, and ripe on this Technology; because selectivity height; so isomer impurities can be controlled at 0.5%～3%, cost is low, and by product is few; be the method for simple environmental protection, possess the ability of large-scale production.
(4) description of drawings:
Fig. 1: synthetic
Chemical reaction process.
(5) embodiment:
Embodiment 1:
In the 2L four-hole bottle, add 80g 5-methyl-2,3-pyrazine dioctyl phthalate
(1eq), be warmed up to 110oC back flow reaction 10h with 0.96kg saturated aqueous common salt (10ml/g).When question response proceeds to HPLC demonstration transformation efficiency 91%, reduce to room temperature, suction filtration, filtrate merges the back and concentrates with 1.6kg butanone (25mL/g), organic phase, and cooling crystallization in ice-water bath, suction filtration promptly get product 33.5g.HPLC purity: 98%, isomer impurities content: 1.1%, productive rate: 55%.
Embodiment 2:
In the 2L four-hole bottle, add 36g 5-methyl-2,3-pyrazine dioctyl phthalate
(1eq), be warmed up to 108oC back flow reaction 8h with 349g saturated aqueous common salt (8ml/g).When question response proceeds to HPLC demonstration transformation efficiency 92%, reduce to room temperature, suction filtration, filtrate merges the back and concentrates with 524g butanone (18mL/g), organic phase, and cooling crystallization in ice-water bath, suction filtration promptly get product 15.3g.HPLC purity: 98%, isomer impurities content: 0.7%, productive rate: 56.2%.
Embodiment 3:
In the 2L four-hole bottle, add 54g 5-methyl-2,3-pyrazine dioctyl phthalate
(1eq), be warmed up to 105oC back flow reaction 8h with 327g saturated aqueous common salt (5ml/g).When question response proceeds to HPLC demonstration transformation efficiency 90%, reduce to room temperature, suction filtration, filtrate merges the back and concentrates with 655g butanone (15mL/g), organic phase, and cooling crystallization in ice-water bath, suction filtration promptly get product 22.5g.HPLC purity: 98%, isomer impurities content: 2.0%, productive rate: 55%.
Embodiment 4:
In the 2L four-hole bottle, add 100g 5-methyl-2,3-pyrazine dioctyl phthalate
(1eq), be warmed up to 115 ℃ of back flow reaction 15h with 1.2kg saturated aqueous common salt (10ml/g).When question response proceeds to HPLC demonstration transformation efficiency 94%, reduce to room temperature, suction filtration, filtrate merges the back and concentrates with 2.0kg butanone (25mL/g), organic phase, and cooling crystallization in ice-water bath, suction filtration promptly get product 40.2g.HPLC purity: 98%, isomer impurities content: 1.6%, productive rate: 53%.
Claims (3)
1, the preparation method of a kind of 5-methylpyrazine-2-carboxylic acid is characterized in that concrete preparation process is as follows:
(1) with the saturated aqueous common salt is solvent, adds main raw material 5-methyl-2,3-pyrazine dioctyl phthalate
Add a little salt again and make the salt solution supersaturation, heat temperature raising is to 105-115 ℃, and back flow reaction 8-15 hour to main raw material 5-methyl-2,3-pyrazine dioctyl phthalate
Disappear; Wherein the consumption of saturated aqueous common salt is at every gram
5ml-10ml;
(2) question response is finished, and reduces to room temperature, suction filtration, and filtrate extracts with butanone, and organic phase merges the back and concentrates, and cooling crystallization in ice-water bath, suction filtration promptly get product; Wherein butanone consumption at every gram
15-25ml.
2, according to the preparation method of the described a kind of 5-methylpyrazine of claim 1-2-carboxylic acid, the consumption that it is characterized in that step (1) saturated aqueous common salt wherein is at every gram
5ml～8ml; Step (2) butanone consumption at every gram
15～18mL.
3, according to the preparation method of claim 1 or 2 described a kind of 5-methylpyrazine-2-carboxylic acids, the consumption that it is characterized in that step (1) saturated aqueous common salt wherein is at every gram
8ml; Step (2) butanone consumption at every gram
18mL.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009100684698A CN101519379B (en) | 2009-04-14 | 2009-04-14 | Method for preparing 5-methylprazine-2-carboxylic acid |
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| CN2009100684698A CN101519379B (en) | 2009-04-14 | 2009-04-14 | Method for preparing 5-methylprazine-2-carboxylic acid |
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| CN101519379A true CN101519379A (en) | 2009-09-02 |
| CN101519379B CN101519379B (en) | 2011-02-02 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664805A (en) * | 2013-12-05 | 2014-03-26 | 华北水利水电大学 | Method for preparing acipimox |
| CN105418342A (en) * | 2015-11-09 | 2016-03-23 | 贝利化学（张家港）有限公司 | High-temperature decarboxylation method |
| CN108059621A (en) * | 2018-01-26 | 2018-05-22 | 常州工程职业技术学院 | A kind of process for purification of high-purity 5-Methylpyrazine-2-carboxylic acid |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4769492A (en) * | 1985-03-13 | 1988-09-06 | Nippon Shokubai Kagaku Kogyo Co., Ltd. | Method for production of 2,3,4,5-tetrafluorobenzoic acid |
| CN1155581C (en) * | 2002-07-17 | 2004-06-30 | 常州市康瑞化工有限公司 | Process for preparing 5-methyl pyrazine-2-carboxylic acid |
-
2009
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664805A (en) * | 2013-12-05 | 2014-03-26 | 华北水利水电大学 | Method for preparing acipimox |
| CN103664805B (en) * | 2013-12-05 | 2016-05-11 | 华北水利水电大学 | A kind of method of preparing Acipimox |
| CN105418342A (en) * | 2015-11-09 | 2016-03-23 | 贝利化学（张家港）有限公司 | High-temperature decarboxylation method |
| CN108059621A (en) * | 2018-01-26 | 2018-05-22 | 常州工程职业技术学院 | A kind of process for purification of high-purity 5-Methylpyrazine-2-carboxylic acid |
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| CN101519379B (en) | 2011-02-02 |
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Address after: 300457 No. seventh, 71 Avenue, Tianjin economic and Technological Development Zone Co-patentee after: Asymchem Medical Group (Tianjin) Inc. Patentee after: Asymchem Life Science and Tecnology (Tianjin) Co., Ltd. Co-patentee after: Asymchem Medical Chemical (Fuxin) Technology Co., Ltd. Co-patentee after: Jilin Asymchem Medicinal and Pharmaceutical Chemistry Co., Ltd. Address before: 300457 No. seventh, 71 Avenue, Tianjin economic and Technological Development Zone Co-patentee before: Kailaiying Medical Chemical (Tianjin) Co., Ltd. Patentee before: Asymchem Life Science and Tecnology (Tianjin) Co., Ltd. Co-patentee before: Asymchem Medical Chemical (Fuxin) Technology Co., Ltd. Co-patentee before: Jilin Asymchem Medicinal and Pharmaceutical Chemistry Co., Ltd. |
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Effective date of registration: 20180704 Address after: 123129 Yi Mo Tu village (fluorinated Industrial Park), Yi Tu Town, Fumeng County, Fuxin, Liaoning Patentee after: Liaoning kailaiying Medical Chemical Co. Ltd. Address before: 300457 No. 71 Seventh Avenue, Tianjin economic and Technological Development Zone Co-patentee before: Asymchem Medical Group (Tianjin) Inc. Patentee before: Asymchem Life Science and Tecnology (Tianjin) Co., Ltd. Co-patentee before: Asymchem Medical Chemical (Fuxin) Technology Co., Ltd. Co-patentee before: Jilin Asymchem Medicinal and Pharmaceutical Chemistry Co., Ltd. |
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