CN101121649A - Method for preparing functional acetophenone compound - Google Patents
Method for preparing functional acetophenone compound Download PDFInfo
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- CN101121649A CN101121649A CNA2007100704387A CN200710070438A CN101121649A CN 101121649 A CN101121649 A CN 101121649A CN A2007100704387 A CNA2007100704387 A CN A2007100704387A CN 200710070438 A CN200710070438 A CN 200710070438A CN 101121649 A CN101121649 A CN 101121649A
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Abstract
The present invention relates to a preparation method for a functioned hypnone compound listed in the equation (I): in the ion liquid, the functioned acidum benzoicum listed in the equation (II) is taken esterifying reaction with C1-16 ester to obtain the functioned benzoic ether listed in the equation (III). The functioned benzoic ether is mixed with C1-16 ester under natrium alcohol catalyzer with benzoic ether to obtain the functioned benzoyl acetic ester listed in the equation (IV) after being condensed and then to be extracted by toluene or acetic ester or dichloromethane; after being extracted and condensed, under the acid condition, the material is to be hydrolyzed to obtain the purposed product (I); the molar ratio between alcohol and ether of acidum benzoicum is 1:1 to 3:1 to 3; R listed in the equation (I) and (II) is neighboring, near, contraposition any atom, C1-10 fatty group substituent and C1-16 aromatic series substituent. The technical scheme in the present invention has the advantages of strong composing selectivity, novel process, low cost and easy operation. The solution can be recycled so as not to pollute the environment.
Description
(1) technical field
The present invention relates to a kind of preparation method of functional acetophenone compound.
(2) background technology
Functional acetophenone compound is the important pharmaceutical intermediate of a class, is widely used in fields such as medicine, agricultural chemicals, chemical industry.The preparation method of current functional acetophenone compound mainly contains: 1, the grignard reaction of substituted benzene formonitrile HCN and methyl iodide; 2, substituted benzoic acid is after chloride, and the cadion with methyl iodide reacts again; 3, substituted benzaldehyde and diazomethane reaction; 4, substituted benzene friedel-crafts reaction etc.These synthetic method complicated operations, yield is low, and the three wastes are many.Grignard reaction, cadion, diazomethane potential safety hazard are more, and large-scale industrial is produced difficult.
In recent years, we just are being devoted to utilize the improvement research of green synthesis techniques to traditional technology, in the present invention, with functionalized phenylformic acid is raw material, in the ionic liquid reaction system, through esterification, condensation and three step of hydrolysis cascade reaction, studied the new synthetic method of preparation functional acetophenone compound.Enlarge the source of raw material, simplified technological operation, reduced raw materials cost, improved product yield, reduced the generation of the three wastes.
(3) summary of the invention
The object of the invention is to provide a kind of operational path novelty, meets the preparation method of the functional acetophenone compound of green synthesis techniques.
For reaching goal of the invention, benzene is invented by the following technical solutions:
A kind of preparation method: in ionic liquid suc as formula functional acetophenone compound shown in (I), carrying out esterification suc as formula the alcohol of functionalized phenylformic acid shown in (II) and C1～6 must be suc as formula the functionalized benzoic ether shown in (III), described functionalized benzoic ether makes suc as formula the functionalized Benzoylacetic acid ester shown in (IV) through condensation in the presence of the catalyzer sodium alkoxide with the ester of C1～6 again, hydrolysis under acidic conditions again makes target product (I); Described phenylformic acid is 1: 1～3: 1～3 with alcohol and ester amount of substance ratio, R shown in formula (I), (II) be adjacent,, contraposition arbitrary atom, the aliphatics substituting group of C1～10 and the aromatic substituents of C1～16.
Ionic liquid of the present invention is 1-alkyl-3-Methylimidazole hexafluorophosphate or 1-alkyl-3-methyl imidazolium tetrafluoroborate, and the alkyl described in 1-alkyl-3-Methylimidazole hexafluorophosphate and the 1-alkyl-3-methyl imidazolium tetrafluoroborate is the alkyl of C1～C18.
The method of the invention may further comprise the steps:
1) esterification: the alcohol of functionalized phenylformic acid shown in the adding formula (II) and C1～6 in ionic liquid, in 60～200 ℃ of reactions 1～20 hour reaction solution, described ion liquid consumption is a functionalized phenylformic acid shown in every mole of formula (II) with 100～1000 milliliters of ionic liquids;
2) condensation reaction: in step 1) gained reaction solution, add the ester and the catalyzer sodium alkoxide of C1～6, reacted 1～20 hour, concentrate concentrated solution;
3) hydrolysis reaction: in step 2) add diluted acid in the gained concentrated solution, reaction is hydrolyzed, use organic solvent extraction after the hydrolysis, described organic solvent is toluene or ethyl acetate or methylene dichloride, gets functional acetophenone compound shown in the formula (I) behind the organic layer extraction liquid concentrate drying.
Step 1) of the present invention and step 2) described reaction carries out under 60～200 ℃ of temperature separately, is preferably 100～160 ℃.Described reaction time of esterification is preferably 5～10 hours.The preferred alcohol of described step 1) esterification is ethanol.
Described step of condensation 2) ester of Jia Ruing is an ethyl acetate.
The described diluted acid of described step 3) hydrolysis reaction is recommended as hydrochloric acid or sulfuric acid, and the consumption of described diluted acid is generally 10～30% diluted acid.The recommendation consumption of organic solvent be the same volume consumption of reaction system.
Present method is strong to target compound synthetic selectivity, preparation technology's novelty, and cost is low, and is easy to operate, the recyclable utilization of solvent, environmental pollution is little.
(4) embodiment
The invention will be further described below in conjunction with specific embodiment, but protection scope of the present invention is not limited to this.
The preparation of embodiment .1 m-trifluoromethyl methyl phenyl ketone
With m-trifluoromethylbenzoic acid 19 grams (0.1 mole), ethanol 14 grams (0.3 mole), 50 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 500 milliliters of there-necked flasks, stirring heating, 60 ℃ of reactions 20 hours, add the sodium ethylate of ethyl acetate 18 grams (0.2 mole) and catalytic amount, continue reaction 20 hours.After reaction finishes, cooling, with toluene 50 milliliters * 3 extractions, the toluene layer extraction liquid concentrates, and adds 30% dilute hydrochloric acid hydrolysis, uses 20 milliliters of extractions of toluene again, and the dry extraction in the dense place of toluene layer extraction liquid makes product 17 grams, yield 90%.198～202 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
Embodiment .2 is to the preparation of trifluoromethyl acetophenone
Will be to trifluoromethylbenzoic acid 19 grams (0.1 mole), ethanol 14 grams (0.3 mole), 50 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 500 milliliters of there-necked flasks, stir, reflux, reacted 1 hour, add the sodium ethylate of ethyl acetate 18 grams (0.2 mole) and catalytic amount, continue reaction 1 hour.After reaction finishes, cooling, toluene 50 milliliters * 3 extractions concentrate, and add 30% dilute hydrochloric acid hydrolysis, and 30 milliliters of extractions of toluene make product 17.1 grams, yield 91%.30～32 ℃ of fusing points, purity 〉=98%, MS (m/z): 188 (M
+).
Embodiment .3 3, the preparation of 5-two (trifluoromethyl) methyl phenyl ketone
With 3,5-two (trifluoromethyl) phenylformic acid 25.8 grams (0.1 mole), ethanol 14 grams (0.3 mole), 50 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 500 milliliters of there-necked flasks, stirring heating 100 ℃ of reactions 4 hours, adds the sodium ethylate of ethyl acetate 18 grams (0.2 mole) and catalytic amount, continue reaction 4 hours, after reaction finishes, cooling, ethyl acetate 50 milliliters * 3 extractions, concentrate, the dilute sulphuric acid hydrolysis of adding 30%, 20 milliliters of extractions of ethyl acetate make product 20.7 grams, yield 82%.185～188 ℃ of boiling points, purity 〉=98%, MS (m/z): 256 (M
+).
Embodiment .4 2, the preparation of 4-two chloro-5-fluoro acetophenones
With 2,4-two chloro-5-fluorobenzoic acids 20.9 grams (0.1 mole), ethanol 14 grams (0.3 mole), 50 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 500 milliliters of there-necked flasks, stirring heating was 60 ℃ of reactions 4 hours, add the sodium ethylate of ethyl acetate 18 grams (0.2 mole) and catalytic amount, continue reaction 4 hours.After reaction finishes, cooling, methylene dichloride 50 milliliters * 3 extractions concentrate, and add 30% dilute sulphuric acid hydrolysis, and 20 milliliters of extractions of methylene dichloride make product 18.2 grams, yield 88%.30 ℃ of fusing points, purity 〉=98%, MS (m/z): 207 (M
+).
The preparation of embodiment .5 o-hydroxyacetophenone
With salicylic acid 13.8 grams (0.1 mole), ethanol 14 grams (0.3 mole), 50 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 500 milliliters of there-necked flasks, stirring heating, 120 ℃ of reactions 6 hours, add the sodium ethylate of ethyl acetate 18 grams (0.2 mole) and catalytic amount, continue reaction 4 hours.After reaction finishes, cooling, toluene 50 milliliters * 3 extractions concentrate, and add 30% dilute sulphuric acid hydrolysis, and 20 milliliters of extractions of toluene make product 12.2 grams, yield 90%.109～110 ℃ of fusing points, purity 〉=98%, MS (m/z): 136 (M
+).
The preparation of the adjacent thiophenyl methyl phenyl ketone of embodiment .6
With adjacent thiophenyl phenylformic acid 23 grams (0.1 mole), ethanol 14 grams (0.3 mole), 100 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 500 milliliters of there-necked flasks, stirring heating, 200 ℃ of reactions 1 hour, add the sodium ethylate of ethyl acetate 18 grams (0.2 mole) and catalytic amount, continue reaction 4 hours.After reaction finishes, cooling, toluene 50 milliliters * 3 extractions concentrate, and add 30% dilute sulphuric acid hydrolysis, and 20 milliliters of extractions of toluene make product 19.6 grams, yield 84%.70～72 ℃ of fusing points, purity 〉=98%, MS (m/z): 228 (M
+).
The preparation of embodiment .7 p-methoxy-acetophenone
With anisic acid 15.2 grams (0.1 mole), ethanol 14 grams (0.3 mole), 50 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 500 milliliters of there-necked flasks, stirring heating, 120 ℃ of reactions 10 hours, add the sodium ethylate of ethyl acetate 18 grams (0.2 mole) and catalytic amount, continue reaction 4 hours.After reaction finishes, cooling, methylene dichloride 50 milliliters * 3 extractions concentrate, and add 30% dilute sulphuric acid hydrolysis, and 20 milliliters of extractions of methylene dichloride make product 13.6 grams, yield 89%.36～38 ℃ of fusing points, purity 〉=98%, MS (m/z): 150 (M
+).
The preparation of embodiment .8 3-fluoro-4-methoxyacetophenone
With 3-fluoro-4-methoxybenzoic acid 17 grams (0.1 mole), ethanol 14 grams (0.3 mole), 100 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 500 milliliters of there-necked flasks, stirring heating, 100 ℃ of reactions 20 hours, add the sodium ethylate of ethyl acetate 18 grams (0.2 mole) and catalytic amount, continue reaction 4 hours.After reaction finishes, cooling, toluene 50 milliliters * 3 extractions concentrate, and add 30% dilute sulphuric acid hydrolysis, and 20 milliliters of extractions of toluene make product 15 grams, yield 90%.90～91 ℃ of fusing points, purity 〉=98%, MS (m/z): 168 (M
+).
Claims (7)
1. preparation method suc as formula functional acetophenone compound shown in (I), it is characterized in that described method is in ionic liquid, carrying out esterification suc as formula the alcohol of functionalized phenylformic acid shown in (II) and C1～6 must be suc as formula the functionalized benzoic ether shown in (III), described functionalized benzoic ether makes suc as formula the functionalized Benzoylacetic acid ester shown in (IV) through condensation in the presence of the catalyzer sodium alkoxide with the ester of C1～6 again, use organic solvent extraction again, described organic solvent is toluene or ethyl acetate or methylene dichloride, after the organic solvent layer extraction liquid concentrates, hydrolysis under acidic conditions makes target product (I); Described phenylformic acid is 1: 1～3: 1～3 with the alcohol of C1～6 and the ester amount of substance ratio of C1～6, R shown in the formula respectively do for oneself the neighbour,, contraposition arbitrary atom or the aliphatics substituting group of C1～10 or the aromatic substituents of C1～16.
2. the preparation method of functional acetophenone compound as claimed in claim 1, it is characterized in that described ionic liquid is 1-alkyl-3-Methylimidazole hexafluorophosphate or 1-alkyl-3-methyl imidazolium tetrafluoroborate, the alkyl described in 1-alkyl-3-Methylimidazole hexafluorophosphate and the 1-alkyl-3-methyl imidazolium tetrafluoroborate is the alkyl of C1～C18.
3. the preparation method of functional acetophenone compound as claimed in claim 1, it is characterized in that said method comprising the steps of: 1) esterification: the alcohol of functionalized phenylformic acid shown in the adding formula (II) and C1～6 in ionic liquid, stir, in 60～200 ℃ of reactions 1～20 hour reaction solution, described ion liquid consumption is a functionalized phenylformic acid shown in every mole of formula (II) with 100～1000 milliliters of ionic liquids;
2) condensation reaction: the ester and the catalyzer sodium alkoxide that in step 1) gained reaction solution, add C1～6, stir, in 60～200 ℃ of reactions 1～20 hour, cooling back organic solvent extraction, described organic solvent is toluene or ethyl acetate or methylene dichloride, the organic solvent layer extraction liquid concentrate concentrated solution;
3) hydrolysis reaction: in step 2) add 30% dilute hydrochloric acid or sulfuric acid in the gained concentrated solution, reaction is hydrolyzed, use organic solvent extraction after the hydrolysis again, described organic solvent is toluene or ethyl acetate or methylene dichloride, gets functional acetophenone compound shown in the formula (I) behind the organic layer extraction liquid concentrate drying.
4. as the preparation method of functional acetophenone compound as described in the claim 3, it is characterized in that the described reaction time of esterification of step 1) is 5～10 hours.
5. as the preparation method of functional acetophenone compound as described in the claim 3, it is characterized in that the alcohol that the step 1) esterification adds C1～6 is ethanol.
6. as the preparation method of functional acetophenone compound as described in the claim 3, it is characterized in that the ester that the step 1) condensation reaction adds C1～6 is an ethyl acetate.
7. as the preparation method of functional acetophenone compound as described in the claim 3, it is characterized in that described step 2) the consumption of organic solvent be 150 milliliters.
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| CN200710070438A CN101121649B (en) | 2007-08-01 | 2007-08-01 | Method for preparing functional acetophenone compound |
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| CN200710070438A CN101121649B (en) | 2007-08-01 | 2007-08-01 | Method for preparing functional acetophenone compound |
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| CN101121649A true CN101121649A (en) | 2008-02-13 |
| CN101121649B CN101121649B (en) | 2010-05-26 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044231A (en) * | 2011-10-15 | 2013-04-17 | 徐州师范大学 | Preparation method of 3, 5-dibromo-2, 4-dihydroxyacetophenone |
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2007
- 2007-08-01 CN CN200710070438A patent/CN101121649B/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044231A (en) * | 2011-10-15 | 2013-04-17 | 徐州师范大学 | Preparation method of 3, 5-dibromo-2, 4-dihydroxyacetophenone |
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