CN100398510C - Method for preparing beta-diketo-ester - Google Patents
Method for preparing beta-diketo-ester Download PDFInfo
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- CN100398510C CN100398510C CNB2003101090365A CN200310109036A CN100398510C CN 100398510 C CN100398510 C CN 100398510C CN B2003101090365 A CNB2003101090365 A CN B2003101090365A CN 200310109036 A CN200310109036 A CN 200310109036A CN 100398510 C CN100398510 C CN 100398510C
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Abstract
The present invention discloses a preparation method of beta-diketo-ester. The present invention takes acetoacetic ester sodium methoxide as a raw material to carry out condensation agent reaction in a reaction solvent, a condensation product is muriatic, a hydrolysis reaction is carried out for extract and ammonia water, and the destination product of the present invention is obtained. The purity of the beta-diketo-ester obtained by the preparation method reaches more than 98%. Compared with the prior art, the present invention has simple operation, easy control and stable product quality, and the present invention is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of beta-diketon ester.
Background technology
The beta-diketon ester is a kind of important organic synthesis intermediate, can be used as the intermediate of synthetic anti-inflammatory type medicine especially, has a wide range of applications, and its structural formula is as follows:
In the prior art, US3142692 discloses a kind of method for preparing the beta-diketon ester: be raw material with the methyl aceto acetate, in the mixed solvent of tetrahydrofuran (THF) and methyl alcohol, react with the magnesium powder, generate methyl aceto acetate magnesium methylate solution, the pressure reducing and steaming solvent carries out addition reaction with acyl chlorides then, hydrolysis obtains the beta-diketon ester.In this preparation method, use the magnesium powder, reaction process produces a large amount of hydrogen, needs to protect with nitrogen, has unsafe factor; Because the magnesium powder is excessive, the magnesium methylate of generation remains in the reaction system, and next step reaction is produced detrimentally affect; Reaction system adopts tetrahydrofuran (THF) and methanol solvate, after the dissolving fully of magnesium powder, is difficult to boil off fully solvent, and residual methyl alcohol enters next step reaction, and by product is more in the products therefrom, purification difficult, and industrial prospect is undesirable.
Summary of the invention
The technical problem that the present invention solves provides a kind of preparation method of beta-diketon ester, overcoming the unsafe factor that uses the magnesium powder to exist in the prior art, and complex operation, by product is many, the unfavorable shortcoming of industrial prospect.
Technical conceive of the present invention is such: with the methyl aceto acetate magnesium methylate is raw material, in reaction solvent, react with condensing agent, and the acidifying of condensation product salt, the reaction that is hydrolyzed of extract and ammoniacal liquor obtains target product of the present invention.
Technical scheme of the present invention:
The methyl aceto acetate magnesium methylate is added in the reaction solvent, and 20-30 ℃ drips condensing agent acyl chlorides, backflow 1-4 hour, 20-30 ℃ adds 3-10% hydrochloric acid, extraction phase adds 5-20% ammoniacal liquor, and reaction is 1-3 hour under 20-30 ℃ the condition, collects target product beta-diketon ester from reaction product.
Reaction expression is:
Wherein R is C
2-C
5Alkyl is worked as R=C
3The time, product beta-diketon ester is an ethyl butyrylacetate, by that analogy.
Said reaction solvent is a tetrahydrofuran (THF), 1,4-dioxane, toluene, one or more in the dimethyl formamide, preferred tetrahydrofuran (THF).
According to the present invention, the weightmeasurement ratio of reactant and reaction solvent is 1.0: 4.0-8.0, and the add-on of acyl chlorides and the mol ratio of reactant are 1.0-1.1: 1.0;
The consumption of hydrochloric acid is a reactant: hydrochloric acid=1.0: 10.0-15.0 (weightmeasurement ratio)
According to the present invention, adopt extraction agent from acidizing fluid, to collect condensation product, said extraction agent is a tetracol phenixin, trichloromethane, methylene dichloride, 1,2-ethylene dichloride, 1,1, the 1-trichloroethane, ethyl acetate, one or more in the methyl acetate, preferred tetracol phenixin; The consumption of extraction agent is a reactant: extraction agent=1.0: 8.0-15.0 (mass ratio).
Ratio of components is a reactant: ammoniacal liquor=1.0: 1.0-1.5 (mass ratio);
Collect target product beta-diketon ester and can comprise the steps: to tell organic phase from reaction product, washing boils off organic solvent, and rectification under vacuum is target product of the present invention.The beta-diketon ester purity that is obtained reaches more than 98%, identifies the structure of product with nucleus magnetic resonance.
Raw material methyl aceto acetate magnesium methylate used in the present invention can prepare as follows:
Magnesium methylate 19.7 grams (0.2291mol) add 1: 1 methyl alcohol/tetrahydrofuran solvent 500ml, methyl aceto acetate 28.5 grams (0.2190mol), and back flow reaction, the white crystal that obtains is the raw material that the present invention uses.
The present invention compared with prior art, and is easy and simple to handle, is easy to control, and constant product quality is suitable for suitability for industrialized production.
Embodiment
The invention will be further described below by embodiment, but embodiment does not limit protection scope of the present invention.
Embodiment
Having heating, stir, in the reactor of thermometer, add exsiccant tetrahydrofuran (THF) 150ml respectively, methyl aceto acetate magnesium methylate crystal 33 grams (0.179mol), stirring and dissolving, holding temperature 20-30 ℃ drips butyryl chloride 19.7 grams (0.185mol), reflux was reacted the pressure reducing and steaming solvent 2 hours, condensation product adds 5% hydrochloric acid 400ml acidifying, 100ml/ extraction of tetracol phenixin 3 times, organic phase adds 20% ammoniacal liquor 160ml, room temperature reaction 2 hours, extraction phase after the separation is used 10% salt acid elution respectively, the washing of 5% yellow soda ash, water washing boils off organic solvent, rectification under vacuum, obtain ethyl butyrylacetate 19.2 grams, productive rate 67.7%, purity 98.4% (GC).
Isobutyryl chloride substitutes butyryl chloride, and is identical with above-mentioned preparation method, obtains ethyl isobutyryl product 20.7 grams, productive rate 73%, purity 98.3% (GC).
Claims (9)
1. the preparation method of a beta-diketon ester is characterized in that comprising the steps:
The methyl aceto acetate magnesium methylate is added in the reaction solvent, and 20-30 ℃ drips condensing agent acyl chlorides, backflow 1-4 hour, 20-30 ℃ adds 3-10% hydrochloric acid, and extraction phase adds 5-20% ammoniacal liquor, and reaction is 1-3 hour under 20-30 ℃ the condition, from reaction product, collect target product beta-diketon ester
Reaction expression is:
R is C
2-C
5Alkyl.
2. method according to claim 1 is characterized in that said reaction solvent is a tetrahydrofuran (THF), 1, one or more in 4-dioxane, toluene, the dimethyl formamide.
3. method according to claim 2 is characterized in that said reaction solvent is a tetrahydrofuran (THF).
4. according to each described method of claim 1-3, the weightmeasurement ratio that it is characterized in that reactant and reaction solvent is 1.0: 4.0-8.0.
5. method according to claim 1 is characterized in that the add-on of acyl chlorides and the mol ratio of reactant are 1.0-1.1: 1.0.
6. method according to claim 1, the add-on weightmeasurement ratio that it is characterized in that hydrochloric acid is a reactant: hydrochloric acid=1.0: 10.0-15.0.
7. method according to claim 1 is characterized in that adopting extraction agent to collect condensation product from acidizing fluid, and said extraction agent is tetracol phenixin, trichloromethane, methylene dichloride, 1, the 2-ethylene dichloride, 1,1,1-trichloroethane, ethyl acetate, one or more in the methyl acetate.
8. method according to claim 7 is characterized in that said extraction agent is a tetracol phenixin, and the consumption mass ratio of extraction agent is a reactant: extraction agent=1.0: 8.0-15.0.
9. method according to claim 1 is characterized in that said ratio of components mass ratio is a reactant: ammoniacal liquor=1.0: 1.0-1.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101090365A CN100398510C (en) | 2003-12-03 | 2003-12-03 | Method for preparing beta-diketo-ester |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2003101090365A CN100398510C (en) | 2003-12-03 | 2003-12-03 | Method for preparing beta-diketo-ester |
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| CN1623973A CN1623973A (en) | 2005-06-08 |
| CN100398510C true CN100398510C (en) | 2008-07-02 |
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| CNB2003101090365A Expired - Fee Related CN100398510C (en) | 2003-12-03 | 2003-12-03 | Method for preparing beta-diketo-ester |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115246772B (en) * | 2021-12-07 | 2024-02-02 | 浙江科技学院 | Preparation method of isobutyryl methyl acetate |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3142692A (en) * | 1961-03-29 | 1964-07-28 | Eastman Kodak Co | Preparation of beta-keto esters |
| US5144057A (en) * | 1990-10-15 | 1992-09-01 | Lonza Ltd. | Process for the production of 3-oxocarboxylic acid esters |
| US5194671A (en) * | 1991-05-23 | 1993-03-16 | Wacker-Chemie Gmbh | Process for the preparation of β-ketocarboxylic acid esters |
| US5945559A (en) * | 1996-05-24 | 1999-08-31 | Takasago International Corporation | Process for producing 3-oxocarboxylic acid esters |
-
2003
- 2003-12-03 CN CNB2003101090365A patent/CN100398510C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3142692A (en) * | 1961-03-29 | 1964-07-28 | Eastman Kodak Co | Preparation of beta-keto esters |
| US5144057A (en) * | 1990-10-15 | 1992-09-01 | Lonza Ltd. | Process for the production of 3-oxocarboxylic acid esters |
| US5194671A (en) * | 1991-05-23 | 1993-03-16 | Wacker-Chemie Gmbh | Process for the preparation of β-ketocarboxylic acid esters |
| US5945559A (en) * | 1996-05-24 | 1999-08-31 | Takasago International Corporation | Process for producing 3-oxocarboxylic acid esters |
Non-Patent Citations (8)
| Title |
|---|
| b-酮酸酯合成法的改进. 吴安心等.化学试剂，第20卷第6期. 1998 |
| b-酮酸酯合成法的改进. 吴安心等.化学试剂，第20卷第6期. 1998 * |
| procedures for the acylations of diethyl malonateandethylacetoacetate with acid chlorides using tertiaryaminebase andmagnesium chloride. Michael W et al.J. Org. Chem.,Vol.50 . 1985 |
| procedures for the acylations of diethyl malonateandethylacetoacetate with acid chlorides using tertiaryaminebase andmagnesium chloride. Michael W et al.J. Org. Chem.,Vol.50 . 1985 * |
| 依托度酸合成工艺的实验研究. 张治柳等.中国药业，第10卷第10期. 2001 |
| 依托度酸合成工艺的实验研究. 张治柳等.中国药业，第10卷第10期. 2001 * |
| 苯甲酰乙酸乙酯的合成. 王钦军等.山东化工. 1999 |
| 苯甲酰乙酸乙酯的合成. 王钦军等.山东化工. 1999 * |
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