CN103172582A - Method for preparing isoxadifen - Google Patents
Method for preparing isoxadifen Download PDFInfo
- Publication number
- CN103172582A CN103172582A CN2013100986514A CN201310098651A CN103172582A CN 103172582 A CN103172582 A CN 103172582A CN 2013100986514 A CN2013100986514 A CN 2013100986514A CN 201310098651 A CN201310098651 A CN 201310098651A CN 103172582 A CN103172582 A CN 103172582A
- Authority
- CN
- China
- Prior art keywords
- acid
- organic bases
- ethyl ester
- preparation
- mixing solutions
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
The invention discloses a method for preparing isoxadifen. The method comprises a step of reacting with each other by utilizing 1, 1-diphenylethlene and ethyl chlorooximidoacetate in the presence of organic alkali and an organic solvent, wherein the organic alkali is N, N-dimethylethanolamine or N, N-diethylethylenediamine, the molar ratio of the 1, 1-diphenylethlene to the ethyl chlorooximidoacetate to the organic alkali is 1:(1-4):(1-4), preferably 1:(1.5-2.5):(1.5-2.5). According to the method, the N, N-dimethylethanolamine or N, N-diethylethylenediamine is served as the organic alkali, so that the reaction yield is obviously increased.
Description
Technical field
The present invention relates to a kind of preparation method of herbicide-safener, particularly relate to the preparation method of a kind of Shuan Ben oxazole acid.
Background technology
The chemical name of Shuan Ben oxazole acid is 4,5-dihydro-5,5-phenylbenzene-1, and 2-oxazole-3-carboxylic acid, ethyl ester, it is to research and develop De isoxazole safener by Sanofi-Aventis.
Chinese patent literature CN1133038A discloses the preparation method of a kind of Shuan Ben oxazole acid: under 0 ℃ with 13.52g(0.075mol) 1,1-diphenylethlene and 5.06g(0.05mol) triethylamine is dissolved in the 200mL ether, then through approximately being dissolved in the 7.58g(0.05mol of 100mL ether in two hours) 2-chloro-2-glyoxylic acid oxime ethyl ester dropwise add, at room temperature after continuously stirring 1 hour, add 100mL water, then use the extracted with diethyl ether mixture, through MgSO
4After drying, steam except ether, resistates is purified on silicagel column, obtains the 12.7g product.The deficiency of the document is: adopt the excessive mode of 1，1-diphenylethylene to prepare the acid of Shuan Ben oxazole, and 1，1-diphenylethylene is higher with respect to 2-chloro-2-glyoxylic acid oxime ethyl ester cost, causes the method preparation cost higher, is not suitable for suitability for industrialized production.
As its improvement, " agricultural chemicals " o. 11th in 2012 discloses the preparation method of a kind of Shuan Ben oxazole acid: in the 250mL four-necked bottle, add chloro glyoxylic acid oxime ethyl ester 24.6g(0.16mol), hexanaphthene 80mL, slowly drip diphenylethlene 16.2g(0.09mol under room temperature), triethylamine 16.4g(0.16mol), the mixed solution of hexanaphthene 30mL, dropwise, continue to stir 1h, add 80mL water to stir, standing, layering, organic layer washing 3 times, anhydrous MgSO
4Drying, precipitation, column chromatography get white solid 17g, yield 64%(comes in diphenylethlene), purity 99%.The deficiency of the method is: adopt triethylamine to have the part by product as organic bases and generate, cause yield lower.
Summary of the invention
The object of the invention is to address the above problem, the preparation method of the Shuan Ben oxazole acid that a kind of not only production cost is lower but also yield is higher is provided.
The technical scheme that realizes the object of the invention is: the preparation method of a kind of Shuan Ben oxazole acid, reacted under the existence of organic bases and organic solvent by 1，1-diphenylethylene and chloro glyoxylic acid oxime ethyl ester and obtain; Described organic bases is N, N-dimethylethanolamine or N, N-diethylethanolamine.
The mol ratio of described 1，1-diphenylethylene, chloro glyoxylic acid oxime ethyl ester and organic bases is 1: (1～4): (1～4), preferred 1: (1.5～2.5): (1.5～2.5).
Described organic solvent is hexanaphthene, ethyl acetate, sherwood oil or ether; Preferred hexanaphthene or ethyl acetate; More select ethyl acetate.
Detailed process can be with reference to the method for prior art:
With 1,1-diphenylethlene and organic bases and a part of organic solvent are mixed to get mixed solution C, chloro glyoxylic acid oxime ethyl ester and another part organic solvent are mixed to get mixing solutions D, slowly be added drop-wise to mixed solution C in mixing solutions D under stirring or slowly be added drop-wise to mixing solutions D in mixed solution C, drip off and continue to be stirred to the reaction end, obtain the acid of Shuan Ben oxazole through aftertreatment.
But, in order further to improve yield, preferred following method:
Organic bases and a part of organic solvent are mixed to get mixed solution A, with 1,1-diphenylethlene and chloro glyoxylic acid oxime ethyl ester and another part organic solvent are mixed to get mixing solutions B, slowly be added drop-wise to mixed solution A in mixing solutions B under stirring or slowly be added drop-wise to mixing solutions B in mixed solution A, drip off and continue to be stirred to the reaction end, obtain the acid of Shuan Ben oxazole through aftertreatment.
The positively effect that the present invention has: (1) the present invention adopts N, and N-diethylethanolamine or N, N-dimethylethanolamine can obviously reduce the generation of by product like this as organic bases, improves the selectivity of reaction, and then obviously improves yield.(2) the present invention finds to adopt the mixing solutions and 1 with organic bases and a part of organic solvent composition, the mode that the mixing solutions that 1-diphenylethlene and chloro glyoxylic acid oxime ethyl ester and another part organic solvent form mixes, than adopting prior art with 1, the mixing solutions that 1-diphenylethlene and organic bases and a part of organic solvent form forms with chloro glyoxylic acid oxime ethyl ester and another part organic solvent the mode that mixing solutions mixes, and can further improve yield.
Embodiment
(embodiment 1)
The preparation method of the Shuan Ben oxazole acid of the present embodiment has following steps:
1. with the 1，1-diphenylethylene (0.09mol) of 16.2g and the N of 18.7g, N-diethylethanolamine (0.16mol) joins in the hexanaphthene of 30mL, obtains mixed solution C.
2. add the chloro glyoxylic acid oxime ethyl ester (0.16mol) of 24.6g and the hexanaphthene of 80mL in the four-necked bottle of 250mL, obtain mixing solutions D.
3. in room temperature (15 ℃～25 ℃, lower same) and under stirring, slowly drip mixed solution C in four-necked bottle, drip off and continue stirring 1h.
4. after reaction finishes, add the water of 80mL and stir, standing demix, organic layer washing three times, anhydrous MgSO
4Drying, precipitation, column chromatography get white solid Shuan Ben oxazole acid 19.5g, and yield is that 72%(comes in diphenylethlene), purity is 98%.
(embodiment 2)
1. with the N of 25.7g, N-diethylethanolamine (0.22mol) joins in the hexanaphthene of 30mL, obtains mixed solution A.
2. add the 1，1-diphenylethylene (0.09mol) of 16.2g, the chloro glyoxylic acid oxime ethyl ester (0.22mol) of 33.2g and the hexanaphthene of 80mL in the four-necked bottle of 250mL, obtain mixing solutions B.
3. in room temperature and under stirring, slowly drip mixed solution A in four-necked bottle, drip off and continue to stir 1h.
4. after reaction finishes, add the water of 80mL and stir, standing demix, organic layer washing three times, anhydrous MgSO
4Drying, precipitation, column chromatography get white solid Shuan Ben oxazole acid 20.9g, and yield is that 78%(comes in diphenylethlene), purity is 99%.
(embodiment 3～embodiment 4)
The preparation method of each embodiment is substantially the same manner as Example 2, and difference sees Table 1.
Table 1
By embodiment 1 and embodiment 2 as can be known: adopt the mixing solutions and 1 that organic bases and a part of organic solvent are formed, the mode that the mixing solutions that 1-diphenylethlene and chloro glyoxylic acid oxime ethyl ester and another part organic solvent form mixes, than adopting 1, the mixing solutions that 1-diphenylethlene and organic bases and a part of organic solvent form forms with chloro glyoxylic acid oxime ethyl ester and another part organic solvent the mode that mixing solutions mixes, and can further improve yield.
By embodiment 2 and embodiment 3 as can be known: select N, than N, the N-dimethylethanolamine is as organic bases as organic bases for the N-diethylethanolamine, and yield is slightly higher.
By embodiment 3 and embodiment 4 as can be known: selecting ethyl acetate is organic solvent as organic solvent than cyclohexane give, and yield is slightly higher.
(Comparative Examples 1)
The preparation method of Comparative Examples 1 is substantially the same manner as Example 1, and difference sees Table 2.
(Comparative Examples 2)
The preparation method of Comparative Examples 2 is substantially the same manner as Example 2, and difference sees Table 2.
Table 2
| ? | Comparative Examples 1 | Comparative Examples 2 |
| Four-necked bottle | 250mL | 250mL |
| Chloro glyoxylic acid oxime ethyl ester | 24.6g(0.16mol) | 33.2g(0.22mol) |
| 1，1-diphenylethylene | 16.2g(0.09mol) | 16.2g(0.09mo1) |
| Organic bases | 16.4g triethylamine (0.16mol) | 22.6g triethylamine (0.22mol) |
| Solvent | Hexanaphthene 80mL+30mL | Hexanaphthene 80mL+30mL |
| Water | 80mL | 80mL |
| Product weight | 17g | 18.2g |
| Yield | 64％ | 68％ |
| Purity | 99％ | 99％ |
.
By embodiment 1 and Comparative Examples 1 as can be known: select N, the N-diethylethanolamine as organic bases than triethylamine as organic bases, yield is significantly improved (surpassing 10%).
By embodiment 1 and Comparative Examples 2 as can be known: the organic bases kind for the impact of yield obviously greater than the impact of hybrid mode.
Claims (4)
1. the preparation method of two benzene oxazole acid is reacted under the existence of organic bases and organic solvent by 1，1-diphenylethylene and chloro glyoxylic acid oxime ethyl ester and obtains; It is characterized in that: described organic bases is N, N-dimethylethanolamine or N, N-diethylethanolamine.
2. the preparation method of Shuan Ben oxazole according to claim 1 acid, it is characterized in that: the mol ratio of described 1，1-diphenylethylene, chloro glyoxylic acid oxime ethyl ester and organic bases is 1: (1～4): (1～4).
3. the preparation method of Shuan Ben oxazole according to claim 2 acid, it is characterized in that: the mol ratio of described 1，1-diphenylethylene, chloro glyoxylic acid oxime ethyl ester and organic bases is 1: (1.5～2.5): (1.5～2.5).
4. the preparation method of described Shuan Ben of one of according to claim 1 to 3 oxazole acid, it is characterized in that: organic bases and a part of organic solvent are mixed to get mixed solution A, with 1,1-diphenylethlene and chloro glyoxylic acid oxime ethyl ester and another part organic solvent are mixed to get mixing solutions B, slowly be added drop-wise to mixed solution A in mixing solutions B under stirring or slowly be added drop-wise to mixing solutions B in mixed solution A, drip off and continue to be stirred to the reaction end, obtain the acid of Shuan Ben oxazole through aftertreatment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310098651.4A CN103172582B (en) | 2013-03-25 | 2013-03-25 | Method for preparing isoxadifen |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310098651.4A CN103172582B (en) | 2013-03-25 | 2013-03-25 | Method for preparing isoxadifen |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103172582A true CN103172582A (en) | 2013-06-26 |
| CN103172582B CN103172582B (en) | 2015-04-08 |
Family
ID=48632840
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310098651.4A Active CN103172582B (en) | 2013-03-25 | 2013-03-25 | Method for preparing isoxadifen |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103172582B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103709113A (en) * | 2013-11-14 | 2014-04-09 | 江苏中旗作物保护股份有限公司 | Synthetic method of herbicide safener isoxadifen-ethyl |
| US20170118988A1 (en) * | 2015-10-29 | 2017-05-04 | Rotam Agrochem International Company Limited | Novel form of isoxadifen-ethyl, a process for its preparation and use of the same |
| CN107652245A (en) * | 2017-08-24 | 2018-02-02 | 郑州手性药物研究院有限公司 | Chiral isoxadifen ethyl ester compound and its preparation method and application |
| CN108440435A (en) * | 2018-03-21 | 2018-08-24 | 重庆化工职业学院 | A kind of synthetic method of the isoxadifen of suitable industrialized production |
| CN112979494A (en) * | 2021-02-02 | 2021-06-18 | 河南佰研生物科技有限公司 | Method for synthesizing bisbenzoxazole acid intermediate chlorooximido ethyl acetate |
| CN113135866A (en) * | 2020-01-17 | 2021-07-20 | 河北谷之润科技有限公司 | Ethyl bisbenzoxazolate with few impurities and preparation method thereof |
| CN115806531A (en) * | 2021-09-14 | 2023-03-17 | 新发药业有限公司 | Preparation method of 4, 5-dihydro-5, 5-diphenyl isoxazole-3-formic acid and derivatives thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1133038A (en) * | 1993-09-16 | 1996-10-09 | 赫彻斯特-舍林农业发展有限公司 | Substituted isoxazolines, process for producing them, agents containing them and their use as safeners |
-
2013
- 2013-03-25 CN CN201310098651.4A patent/CN103172582B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1133038A (en) * | 1993-09-16 | 1996-10-09 | 赫彻斯特-舍林农业发展有限公司 | Substituted isoxazolines, process for producing them, agents containing them and their use as safeners |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103709113A (en) * | 2013-11-14 | 2014-04-09 | 江苏中旗作物保护股份有限公司 | Synthetic method of herbicide safener isoxadifen-ethyl |
| US20170118988A1 (en) * | 2015-10-29 | 2017-05-04 | Rotam Agrochem International Company Limited | Novel form of isoxadifen-ethyl, a process for its preparation and use of the same |
| WO2017071411A1 (en) * | 2015-10-29 | 2017-05-04 | Rotam Agrochem International Company Limited | Novel form of isoxadifen-ethyl, process for preparation and use thereof |
| GB2555748A (en) * | 2015-10-29 | 2018-05-09 | Jiangsu Rotam Chemistry Co Ltd | Novel form of isoxadifen-ethyl, process for preparation and use thereof |
| US10015967B2 (en) * | 2015-10-29 | 2018-07-10 | Rotam Agrochem International Company Limited | Form of isoxadifen-ethyl, a process for its preparation and use of the same |
| GB2555748B (en) * | 2015-10-29 | 2020-03-11 | Jiangsu Rotam Chemistry Co Ltd | Novel form of isoxadifen-ethyl, process for preparation and use thereof |
| CN107652245A (en) * | 2017-08-24 | 2018-02-02 | 郑州手性药物研究院有限公司 | Chiral isoxadifen ethyl ester compound and its preparation method and application |
| CN108440435A (en) * | 2018-03-21 | 2018-08-24 | 重庆化工职业学院 | A kind of synthetic method of the isoxadifen of suitable industrialized production |
| CN113135866A (en) * | 2020-01-17 | 2021-07-20 | 河北谷之润科技有限公司 | Ethyl bisbenzoxazolate with few impurities and preparation method thereof |
| CN112979494A (en) * | 2021-02-02 | 2021-06-18 | 河南佰研生物科技有限公司 | Method for synthesizing bisbenzoxazole acid intermediate chlorooximido ethyl acetate |
| CN115806531A (en) * | 2021-09-14 | 2023-03-17 | 新发药业有限公司 | Preparation method of 4, 5-dihydro-5, 5-diphenyl isoxazole-3-formic acid and derivatives thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103172582B (en) | 2015-04-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103172582B (en) | Method for preparing isoxadifen | |
| CN103755603B (en) | Preparation method for 2-amino sulfonyl-4-methylsalfonamido methyl benzoic acid methyl ester | |
| CN102850325A (en) | Preparation method of Dabigatran etexilate key intermediate | |
| CN105218329B (en) | Intermediate of liflozin analogues and preparation method of intermediate | |
| CN103725279B (en) | A kind of Anacardol dimeric surfactant and preparation method thereof | |
| CN102942444B (en) | Synthesis method of 2,2'-dibromo-9,9'-spirobifluorene | |
| CN104892418A (en) | Synthesis method of citric acid tributyl citrate | |
| CN109704971B (en) | Preparation method of ethyl 4-chloroacetoacetate | |
| CN102351749B (en) | Benzenesulphonate anionic gemini surfactant and preparation method thereof | |
| WO2014203270A2 (en) | Process for the preparation of acrylate derivatives | |
| EP3119741B1 (en) | An improved process for the synthesis of dimethyl fumarate | |
| CN108707067B (en) | Preparation method of 1-aryl-4, 4, 4-trifluoro-1-butanone compound | |
| JP2017071554A (en) | Fluorene-based compound and method of producing fluorene-based compound | |
| EP3309142A1 (en) | Method for preparing citalopram glycol intermediate | |
| CN101967075A (en) | Method for synthesizing terminal alkyne compound by using 3-aryl-2,3-dibromopropionic acid | |
| CN104672179B (en) | Preparation method of [(1S)-3-methyl-1-[[(2R)-2-methylepoxyethyl]carbonyl]butyl]tert-butyl carbamate | |
| CN103880740A (en) | Synthesis of 4-nitro-3-hydroxy-2-picolinic acid | |
| RU2568439C1 (en) | Method of producing terephthalic aldehyde | |
| CN109912396B (en) | Synthetic method of 3-bromo-4-fluorobenzaldehyde | |
| CN110407787A (en) | A method of regulation chlorination-hydrolysis prepares maltol and its homologue | |
| CN104418735A (en) | Preparation method of adamantine monoester | |
| CN104591939B (en) | A kind of method preparing xenyl acrylic acid ether compound | |
| WO2019069321A1 (en) | An improved process for the preparation of a key intermediate of gemfibrozil | |
| CN104151161B (en) | A kind of 2-(2-allyl group) preparation method of amylene-4-acid methyl esters | |
| CN106892806B (en) | Method for preparing 1-p-methylphenyl-4, 4, 4-trifluoro-1, 3-butanedione |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |