CN101538255A - Preparing method of 2-methoxy imino group 2-furan ammonium acetate - Google Patents
Preparing method of 2-methoxy imino group 2-furan ammonium acetate Download PDFInfo
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- CN101538255A CN101538255A CN200910097425A CN200910097425A CN101538255A CN 101538255 A CN101538255 A CN 101538255A CN 200910097425 A CN200910097425 A CN 200910097425A CN 200910097425 A CN200910097425 A CN 200910097425A CN 101538255 A CN101538255 A CN 101538255A
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Abstract
The invention relates to a preparing method of 2-methoxy imino group 2-furan ammonium acetate which comprises the following steps: (1) sodium nitrite reacts with acetate furan to generate furan keto acid by oximation, rearrangement and hydrolysis; (2) the furan keto acid is extracted; (3) condensation reaction is carried out on the furan keto and methoxy ammonium hydrochloride to generate 2-imino group 2-furan acetic acid; (4) the 2-imino group 2-furan acetic acid is extracted; (5) ammonia is introduced for salt formation to generate the 2-methoxy imino group 2-furan ammonium acetate; wherein, solvent adopted in the furan keto extraction of step (2) is butyl acetate. Under the same condition, the dissolution loss of the ethyl acetate in water is four times larger than that of the butyl acetate. With the butyl acetate being adopted as the solvent, the unit consumption is lowered by 50 percent, and the production cost is lowered. Furthermore, 58-60 DEG C of the reaction temperature for oximation is adopted by the invention, the production rate of furoic acid is smaller than 1 percent, and the product yield is improved greatly.
Description
Technical field
The present invention relates to a kind of preparation method of 2-methoxy imino group 2-furan ammonium acetate.
Background technology
2-methoxy imino group 2-furan ammonium acetate (SMIA) is 7 side chains of cephalofruxin, is synthetic cynnematin medicine---the important intermediate of cefuroxime axetil.Its main synthetic route has: with the 2-furancarboxylic acid is raw material, generates 2 furoyl chloride through chloro, or is raw material with the 2-acetofuran, generates 2 furoyl chloride through chlorination, and then makes through cyanogen generation, hydrolysis, oximate.As " synthesizing of 2-methoxy imino 2-furans ammonium acetate " (2003 the 43rd the 3rd phases of volume of Jiangxi Medical College's journal), above-mentioned route yield is not high, uses the sulfur oxychloride of severe corrosive and the prussiate of severe toxicity in building-up process, so is not suitable for suitability for industrialized production.
" (S)-2-methoxy imino-2-furans acetate synthetic " (Chinese microbiotic magazine the 30th the 5th phase of volume of May in 2005) discloses carries out acetyl furan oximate, resets synthetic furans oxoethanoic acid, generate the route of 2-imino-2-furans acetate again with the condensation of methoxy ammonium salt hydrochlorate, its chemical equation is as follows:
The temperature of oximate, rearrangement is controlled at 65～70 ℃, regulates pH to 1.5～2, extracts and adopts methylene dichloride; Synthetic pH to 4～5 of regulating of 2-imino-2-furans acetate are extracted and are adopted ethyl acetate.Adopt this route, raw material supply is guaranteed, and processing condition are not high, and total recovery reaches 34%, relatively is fit to suitability for industrialized production.But the solvent kind is many in the process of producing, and solvent consumption is big.Simultaneously, it is many that the temperature of oximate, rearrangement causes reaction to make by product furancarboxylic acid amount, and about 5～15%.
Summary of the invention
In order to solve the technological deficiency of above-mentioned existence, the purpose of this invention is to provide the preparation method of the few 2-methoxy imino group 2-furan ammonium acetate of a kind of solvent consumption amount.Further, the invention solves the many technological deficiencies of by product furancarboxylic acid amount.
In order to realize above-mentioned technical purpose, the present invention has adopted following technical scheme:
1. the preparation method of 2-methoxy imino group 2-furan ammonium acetate, this method comprise the steps:, are reacted by Sodium Nitrite and acetate furans, generate the furans ketone acid through oximate, rearrangement, hydrolysis; 2., extract and extract the furans ketone acid; 3., the furans ketone acid generates 2-imino-2-furans acetate with the condensation of methoxy ammonium salt hydrochlorate again; 4. extract 2-imino-2-furans acetate; 5. logical then ammonia salify generates the 2-methoxy imino group 2-furan ammonium acetate; Wherein: the solvent that 2. step extracts the employing of furans ketone acid is a butylacetate.
Above-mentioned preparation method's chemical equation is as follows:
As preferably, the temperature of reaction of above-mentioned oximate is 53 ℃～65 ℃.
Temperature of reaction as preferred again, above-mentioned oximate is 58 ℃～60 ℃.Adopt 58 ℃～60 ℃ above-mentioned temperature of reaction, the furancarboxylic acid growing amount will be less than 1%, has improved the yield of product greatly.
As preferably, 2. above-mentioned step extracts furans ketone acid control pH value is 0.2.
As preferably, 4. above-mentioned step extracts the solvent that 2-imino-2-furans acetate adopts is butylacetate.
As preferably, 4. above-mentioned step extracts 2-imino-2-furans acetate control pH value is 0.5.
As preferably, the solvent that the 5. logical ammonia salify of above-mentioned step adopts is butylacetate and methyl alcohol mixed liquor or butylacetate and DMF mixed solution.
The solvent that adopts as the 5. logical ammonia salify of preferred again, above-mentioned step is butylacetate and methyl alcohol mixed liquor, wherein methyl alcohol by volume the per-cent meter account for 5～10%.Adopting above-mentioned solvent is that the crystalline structure of product is good, has improved the quality of product.
The present invention is owing to adopted above-mentioned technical scheme, and the dissolving loss ratio butylacetate of ethyl acetate in water is big 4 times under identical condition, adopts butylacetate unit consumption can be descended 50% as solvent, has reduced production cost.Further, the present invention has adopted the temperature of reaction of 58 ℃～60 ℃ oximate, and the production rate of furancarboxylic acid has improved the yield of product greatly less than 1%.
Embodiment
The following specific embodiments of the present invention is to make a detailed explanation.
The preparation method of 2-methoxy imino group 2-furan ammonium acetate, this method comprises the steps:
1., by the reaction of Sodium Nitrite and acetate furans, the temperature of reaction is 59 ℃ ± 1 ℃, generates the furans ketone acid through oximate, rearrangement, hydrolysis;
2., add hydrochloric acid, regulating PH is 0.2, adopts butylacetate to extract, and then adds Na
2CO
3The solution back extraction obtains the furans ketone acid;
3., furans ketone acid and the condensation of methoxy ammonium salt hydrochlorate generate 2-imino-2-furans acetate;
4., to regulate PH be 0.5, adopts butylacetate to extract 2-imino-2-furans acetate, adds gac dehydration, decolouring;
5., in reaction solution, add the methyl alcohol of solvent volume 5～10%, logical then ammonia salify generates the 2-methoxy imino group 2-furan ammonium acetate.
Claims (8)
1.2-1. the preparation method of methoxy imino group 2-furan ammonium acetate, this method comprise the steps:, by the reaction of Sodium Nitrite and acetate furans, generate the furans ketone acid through oximate, rearrangement, hydrolysis; 2., extract and extract the furans ketone acid; 3., the furans ketone acid generates 2-imino-2-furans acetate with the condensation of methoxy ammonium salt hydrochlorate again; 4. extract 2-imino-2-furans acetate; 5. logical then ammonia salify generates the 2-methoxy imino group 2-furan ammonium acetate; It is characterized in that: the solvent that 2. step extracts the employing of furans ketone acid is a butylacetate.
2. the preparation method of 2-methoxy imino group 2-furan ammonium acetate according to claim 1 is characterized in that: the temperature of reaction of oximate is 53 ℃～65 ℃.
3. the preparation method of 2-methoxy imino group 2-furan ammonium acetate according to claim 2 is characterized in that: the temperature of reaction of oximate is 58 ℃～60 ℃.
4. according to the preparation method of claim 1 or 2 or 3 described 2-methoxy imino group 2-furan ammonium acetates, it is characterized in that: 2. step extracts furans ketone acid control pH value is 0.2.
5. the preparation method of 2-methoxy imino group 2-furan ammonium acetate according to claim 1 is characterized in that: the solvent that 4. step extracts the employing of 2-imino-2-furans acetate is a butylacetate.
6. the preparation method of 2-methoxy imino group 2-furan ammonium acetate according to claim 1 or 5, it is characterized in that: 4. step extracts 2-imino-2-furans acetate control pH value is 0.5.
7. the preparation method of 2-methoxy imino group 2-furan ammonium acetate according to claim 1 is characterized in that: the solvent that the 5. logical ammonia salify of step adopts is butylacetate and methyl alcohol mixed liquor or butylacetate and DMF mixed solution.
8. the preparation method of 2-methoxy imino group 2-furan ammonium acetate according to claim 7 is characterized in that: the solvent that the 5. logical ammonia salify of step adopts is butylacetate and methyl alcohol mixed liquor, wherein methyl alcohol by volume the per-cent meter account for 5～10%.
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102010390A (en) * | 2010-12-10 | 2011-04-13 | 湖北楚阳科技股份有限公司 | Method for producing furan ammonium salt by using furoic acid |
| CN102070572A (en) * | 2010-12-17 | 2011-05-25 | 山东金城医药化工股份有限公司 | Method for recovering and preparing furanone acid from syn-2-methoxyimino-2-(2-furayl)-acetic acid-ammonia salt waste residue |
| CN102863407A (en) * | 2012-10-10 | 2013-01-09 | 山东金城医药化工股份有限公司 | Preparation method of 2-methoxyiminofurylacetic acid amonium salt |
| CN103145656A (en) * | 2013-03-01 | 2013-06-12 | 江苏清泉化学有限公司 | Method for improving yield of synthesized 2-furanyloxoacetic acid |
| CN105503792A (en) * | 2015-12-21 | 2016-04-20 | 山东金城医药化工股份有限公司 | Method for synthesizing (Z)-2-(alpha-methoxyimino)furanylacetic acid ammonium |
| CN105712959A (en) * | 2014-12-01 | 2016-06-29 | 王志训 | Furan derivative industrial production process |
| CN106032366A (en) * | 2015-03-16 | 2016-10-19 | 王志训 | Industrial production method of furan derivative |
| CN109160908A (en) * | 2018-10-30 | 2019-01-08 | 四平市精细化学品有限公司 | A kind of synthetic method of 2- methoxy imino -2- furans acetic acid |
| CN112876436A (en) * | 2021-03-01 | 2021-06-01 | 安徽金轩科技有限公司 | Method for preparing furan ammonium salt with high selectivity |
| CN112979591A (en) * | 2021-03-01 | 2021-06-18 | 安徽金轩科技有限公司 | Oxidation extraction process for recycling dichloromethane in preparation of furan ammonium salt |
-
2009
- 2009-04-02 CN CN2009100974258A patent/CN101538255B/en not_active Expired - Fee Related
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102010390A (en) * | 2010-12-10 | 2011-04-13 | 湖北楚阳科技股份有限公司 | Method for producing furan ammonium salt by using furoic acid |
| CN102010390B (en) * | 2010-12-10 | 2012-07-04 | 湖北楚阳科技股份有限公司 | Method for producing furan ammonium salt by using furoic acid |
| CN102070572A (en) * | 2010-12-17 | 2011-05-25 | 山东金城医药化工股份有限公司 | Method for recovering and preparing furanone acid from syn-2-methoxyimino-2-(2-furayl)-acetic acid-ammonia salt waste residue |
| CN102070572B (en) * | 2010-12-17 | 2012-10-03 | 山东金城医药化工股份有限公司 | Method for recovering and preparing furanone acid from syn-2-methoxyimino-2-(2-furayl)-acetic acid-ammonia salt waste residue |
| CN102863407B (en) * | 2012-10-10 | 2014-07-23 | 山东金城医药化工股份有限公司 | Preparation method of 2-methoxyiminofurylacetic acid amonium salt |
| CN102863407A (en) * | 2012-10-10 | 2013-01-09 | 山东金城医药化工股份有限公司 | Preparation method of 2-methoxyiminofurylacetic acid amonium salt |
| CN103145656A (en) * | 2013-03-01 | 2013-06-12 | 江苏清泉化学有限公司 | Method for improving yield of synthesized 2-furanyloxoacetic acid |
| CN103145656B (en) * | 2013-03-01 | 2015-11-25 | 江苏清泉化学股份有限公司 | A kind of method improving synthesis 2-oxo-2-furans acetic acid yield |
| CN105712959A (en) * | 2014-12-01 | 2016-06-29 | 王志训 | Furan derivative industrial production process |
| CN106032366A (en) * | 2015-03-16 | 2016-10-19 | 王志训 | Industrial production method of furan derivative |
| CN105503792A (en) * | 2015-12-21 | 2016-04-20 | 山东金城医药化工股份有限公司 | Method for synthesizing (Z)-2-(alpha-methoxyimino)furanylacetic acid ammonium |
| CN109160908A (en) * | 2018-10-30 | 2019-01-08 | 四平市精细化学品有限公司 | A kind of synthetic method of 2- methoxy imino -2- furans acetic acid |
| CN112876436A (en) * | 2021-03-01 | 2021-06-01 | 安徽金轩科技有限公司 | Method for preparing furan ammonium salt with high selectivity |
| CN112979591A (en) * | 2021-03-01 | 2021-06-18 | 安徽金轩科技有限公司 | Oxidation extraction process for recycling dichloromethane in preparation of furan ammonium salt |
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| CN101538255B (en) | 2011-07-20 |
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Denomination of invention: Preparing method of 2-methoxy imino group 2-furan ammonium acetate Effective date of registration: 20130910 Granted publication date: 20110720 Pledgee: Zhejiang Deqing rural commercial bank Limited by Share Ltd. Pledgor: ZHEJIANG TOP MEDICINE Co.,Ltd. Registration number: 2013990000665 |
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