CN1247512C - Process for preparing trifluoromethyl acetophenone compound - Google Patents
Process for preparing trifluoromethyl acetophenone compound Download PDFInfo
- Publication number
- CN1247512C CN1247512C CN 200410052696 CN200410052696A CN1247512C CN 1247512 C CN1247512 C CN 1247512C CN 200410052696 CN200410052696 CN 200410052696 CN 200410052696 A CN200410052696 A CN 200410052696A CN 1247512 C CN1247512 C CN 1247512C
- Authority
- CN
- China
- Prior art keywords
- trifluoromethyl
- mole
- grams
- preparation
- formula
- 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.)
- Expired - Fee Related
Links
Abstract
The present invention relates to a method for preparing a trifluoromethyl acetophenone compound, which comprises the following steps that: trifluoromethyl halogeno benzene and a vinyl ether compound are stirred and react for 1 to 20 hours at the temperature of 10DEG. C to 150DEG. C when a palladium catalyst, ligand and organic amine exist. After reactions are completed, acid is added to the mixture to acidify the mixture. The method has the advantages of novel preparation technology, low cost, easy operation and little environment pollution. A solvent can be recovered and utilized.
Description
(1) technical field
The present invention relates to a kind of preparation method of trifluoromethyl acetophenone compound, relating in particular to a kind of is medium with the ionic liquid, in palladium catalyst and 1, under two (phenylbenzene is seen) alkane catalysis of 3-, prepare the method for trifluoromethyl acetophenone compound by halogenated aryl hydrocarbon and Vinyl Ether compound reaction (Heck reaction).
(2) background technology
Trifluoromethyl acetophenone compound is the important pharmaceutical intermediate of a class, is widely used in fields such as medicine, agricultural chemicals, chemical industry.The preparation of current trifluoromethyl acetophenone compound mainly contains: 1, the grignard reaction of trifluoromethyl cyanobenzene and methyl iodide; 2, trifluoromethylbenzoic acid is after chloride, and the cadion with methyl iodide reacts again; 3, trifluoromethylated benzaldehyde and diazomethane reaction.The starting raw material price of three kinds of synthetic methods is expensive, source difficulty, and yield is low, and the cadion used of method 2 can increase the work of treatment of waste water, and the diazomethane of method 3 is explosive and hypertoxic, is difficult to carry out large-scale industrial production.
The Heck reaction is the important method of being synthesized the alkenyl substituted aromatic hydroxy compound under palladium catalyst catalysis by halogenated aryl hydrocarbon.And ionic liquid is expected to solve the pollution problem that chemical reaction process may occur as emerging Green Chemistry solvent.Different with typical organic solvent, ionic liquid is non-volatile, and is nonflammable explosive, and organism and inorganics are had good solubility, and reaction can be carried out at homogeneous phase, stable to water and air, is convenient to operation and processing, easily reclaims.In addition, but quicken the process of chemical reaction with ionic liquid catalysis.
In ion liquid medium, utilizing Heck prepared in reaction trifluoromethyl acetophenone compound is a kind of operational path novelty, and the green synthesis method of application prospect is arranged, and does not appear in the newspapers as yet.
(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 trifluoromethyl acetophenone compound of green synthesis techniques, utilizes Heck prepared in reaction trifluoromethyl acetophenone compound.
Trifluoromethyl acetophenone compound of the present invention is suc as formula shown in (I), described preparation method may further comprise the steps: suc as formula the trifluoromethyl halogeno-benzene shown in (II) with suc as formula the vinyl ethers compound shown in (III) in ionic liquid, in the presence of palladium catalyst, part, organic amine, in 10 ℃～150 ℃ following stirring reactions 1～20 hour, be acidified with acid after the reaction; Described trifluoromethyl halogeno-benzene is chloro or bromo or iodo trifluoromethylbenzene, and described part is 1, two (phenylbenzene is seen) propane (DPPP) or 1 of 3-, two (phenylbenzene is seen) butane of 3-;
In its Chinese style (I), trifluoromethyl be in ethanoyl the neighbour,, contraposition; In the formula (II), X is chlorine or bromine or iodine, trifluoromethyl be in X the neighbour,, contraposition; In the formula (III), R
1Expression C
1～C
4Alkyl.
Described palladium catalyst is the Heck catalysts, as palladium.
Ionic liquid described in the present invention is preferably 3-methyl imidazolium tetrafluoroborate or 1-alkyl-3-methyl imidazolium tetrafluoroborate, and wherein alkyl is the alkyl of carbon atom quantity n=1～18.As 1-butyl-3-methyl imidazolium tetrafluoroborate, 1-ethyl-3-methyl imidazolium tetrafluoroborate etc.
Above-mentioned organic amine is preferably triethylamine.
Described acid is preferably dilute hydrochloric acid or dilute sulphuric acid when being acidified with acid, and being acidified to pH is 1～3.
Above-mentioned vinyl ethers compound is preferably ethyl vinyl ether and vinyl-n-butyl ether.
Trifluoromethyl acetophenone compound of the present invention is preparation according to the following steps preferably:
With 0.1 mole of trifluoromethyl halogeno-benzene, 0.025 mole of palladium, 1, two (phenylbenzene is seen) propane (0.05 mole) of 3-, 0.2 mole of vinyl-n-butyl ether, 0.12 mole of triethylamine, 200 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 100 ℃ of reactions 15 hours.After reaction finishes, cooling, the dilute sulphuric acid of adding 10% is acidified to about pH=3.
The purity chromatographic determination of reaction product is further identified product with mass spectrum.
Present method preparation technology's novelty, 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-trifluoromethyl chlorobenzene 18.2 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, vinyl-n-butyl ether 20 grams (0.2 mole), triethylamine 11 grams (0.12 mole), 200 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 100 ℃ of reactions 15 hours.After reaction finishes, cooling, the dilute hydrochloric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 9.5 grams, yield 50%.198～202 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of embodiment 2 m-trifluoromethyl methyl phenyl ketones
With m-trifluoromethyl phenyl-bromide 22.4 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, vinyl-n-butyl ether 20 grams (0.2 mole), triethylamine 11 grams (0.12 mole), 200 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 100 ℃ of reactions 15 hours.After reaction finishes, cooling, the dilute sulphuric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 13 grams, yield 70%.198～202 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of embodiment 3 m-trifluoromethyl methyl phenyl ketones
With m-trifluoromethyl phenyl-bromide 22.4 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, ethyl vinyl ether 18 grams (0.2 mole), triethylamine 11 grams (0.12 mole), 200 milliliters of 1-ethyls-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 100 ℃ of reactions 15 hours.After reaction finishes, cooling, the dilute sulphuric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 18 grams, yield 92%.30～32 ℃ of fusing points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of embodiment 4 m-trifluoromethyl methyl phenyl ketones
With m-trifluoromethyl iodobenzene 27.2 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, ethyl vinyl ether 18 grams (0.2 mole), triethylamine (0.12 mole), 200 milliliters of 1-ethyls-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 100 ℃ of reactions 15 hours.After reaction finishes, cooling, the dilute sulphuric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 17 grams, yield 90%.30～32 ℃ of fusing points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of embodiment 5 m-trifluoromethyl methyl phenyl ketones
70 ℃ of stirring reactions 10 hours.Other is with embodiment 1.
Get product 8.5 grams, yield 45%.198～202 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of embodiment 6 m-trifluoromethyl methyl phenyl ketones
50 ℃ of stirring reactions 20 hours.Other is with embodiment 1.
Get product 7.5 grams, yield 40%.198～202 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of embodiment 7 m-trifluoromethyl methyl phenyl ketones
140 ℃ of stirring reactions 3 hours.Other is with embodiment 1.
Get product 7.4 grams, yield 39%.198～202 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of 8 pairs of trifluoromethyl acetophenones of embodiment
Will be to methyl bromobenzene trifluoride 22.4 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, vinyl-n-butyl ether 20 grams (0.2 mole), triethylamine 11 grams (0.12 mole), 200 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 100 ℃ of reactions 15 hours.After reaction finishes, cooling, the dilute hydrochloric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 15.5 grams, yield 80%.30～32 ℃ of fusing points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of 9 pairs of trifluoromethyl acetophenones of embodiment
Will be to trifluoromethyl chlorobenzene 18.2 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, vinyl-n-butyl ether 20 grams (0.2 mole), triethylamine 11 grams (0.12 mole), 200 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 100 ℃ of reactions 15 hours.After reaction finishes, cooling, the dilute sulphuric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 9.5 grams, yield 50%.198～202 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of 10 pairs of trifluoromethyl acetophenones of embodiment
Will be to methyl bromobenzene trifluoride 22.4 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, vinyl-n-butyl ether 20 grams (0.2 mole), triethylamine 11 grams (0.12 mole), 200 milliliters of 1-ethyls-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 50 ℃ of reactions 18 hours.After reaction finishes, cooling, the dilute sulphuric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 12 grams, yield 70%.162～165 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of 11 pairs of trifluoromethyl acetophenones of embodiment
Will be to trifluoromethyl iodobenzene 27.2 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, vinyl-n-butyl ether 20 grams (0.2 mole), triethylamine (0.12 mole), 200 milliliters of 1-ethyls-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 80 ℃ of reactions 18 hours.After reaction finishes, cooling, the dilute sulphuric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 17.4 grams, yield 91%.162～165 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of 12 pairs of trifluoromethyl acetophenones of embodiment
50 ℃ of stirring reactions 15 hours.Other is with embodiment 11.
Get product 16.1 grams, yield 85%.162～165 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of embodiment 13 o-trifluoromethyl methyl phenyl ketones
With o-trifluoromethyl phenyl-bromide 22.4 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, vinyl-n-butyl ether 20 grams (0.2 mole), triethylamine 11 grams (0.12 mole), 200 milliliters of 1-butyl-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 100 ℃ of reactions 15 hours.After reaction finishes, cooling, the dilute sulphuric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 17 grams, yield 90%.198～202 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
The preparation of embodiment 14 o-trifluoromethyl methyl phenyl ketones
With o-trifluoromethyl phenyl-bromide 22.4 grams (0.1 mole), palladium 8.2 grams (0.025 mole), 1, two (phenylbenzene is seen) propane 21 grams (0.05 mole) of 3-, ethyl vinyl ether 18 grams (0.2 mole), triethylamine 11 grams (0.12 mole), 200 milliliters of 1-ethyls-3-methyl imidazolium tetrafluoroborate, place 1000 milliliters of there-necked flasks, stirring heating was 100 ℃ of reactions 15 hours.After reaction finishes, cooling, the dilute sulphuric acid of adding 10% is acidified to pH=3, stirs 30 minutes, and aftertreatment gets product 15 grams, yield 88%.162～165 ℃ of boiling points, purity 〉=98%, MS (m/z): 188 (M
+).
Claims (9)
1, a kind of preparation method suc as formula the trifluoromethyl acetophenone compound shown in (I), it is characterized in that may further comprise the steps: suc as formula the trifluoromethyl halogeno-benzene shown in (II) with suc as formula the vinyl ethers compound shown in (III) in ionic liquid, in the presence of palladium catalyst, part, organic amine, in 10 ℃～150 ℃ following stirring reactions 1～20 hour, be acidified with acid after the reaction; Described trifluoromethyl halogeno-benzene is chloro or bromo or iodo trifluoromethylbenzene, and described part is 1, two (phenylbenzene is seen) propane or 1 of 3-, two (phenylbenzene is seen) butane of 3-;
In its Chinese style (I), trifluoromethyl be in ethanoyl the neighbour,, contraposition; In the formula (II), X is chlorine or bromine or iodine, trifluoromethyl be in X the neighbour,, contraposition; In the formula (III), R
1Expression C
1～C
4Alkyl.
2, by the described preparation method of claim 1, it is characterized in that described palladium catalyst is a palladium.
3, by the described preparation method of claim 2, it is characterized in that described ionic liquid is 3-methyl imidazolium tetrafluoroborate or 1-alkyl-3-methyl imidazolium tetrafluoroborate, described alkyl is the alkyl of carbon atom quantity n=1～18.
4, by the described preparation method of claim 3, it is characterized in that described ionic liquid is one of following: 1. 2. 1-ethyl-3-methyl imidazolium tetrafluoroborate of 1-butyl-3-methyl imidazolium tetrafluoroborate.
5, by the described preparation method of claim 2, it is characterized in that described organic amine is a triethylamine.
6, by the described preparation method of claim 2, it is characterized in that described acid is dilute hydrochloric acid or dilute sulphuric acid, being acidified to pH is 1～3.
7, by the described preparation method of claim 2, it is characterized in that described temperature of reaction is 100 ℃, the reaction times is 15 hours.
8, by one of claim 1～7 described preparation method, the mol ratio that it is characterized in that described trifluoromethyl halogeno-benzene, vinyl ethers compound, palladium catalyst, part is 4: 8: 1: 2.
9, by the described preparation method of claim 8, it is characterized in that: with 0.1 mole of trifluoromethyl halogeno-benzene is benchmark, and described organic amine consumption is 0.12 mole, and described ionic liquid consumption is 200 milliliters.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410052696 CN1247512C (en) | 2004-07-07 | 2004-07-07 | Process for preparing trifluoromethyl acetophenone compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410052696 CN1247512C (en) | 2004-07-07 | 2004-07-07 | Process for preparing trifluoromethyl acetophenone compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1587246A CN1587246A (en) | 2005-03-02 |
| CN1247512C true CN1247512C (en) | 2006-03-29 |
Family
ID=34602564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410052696 Expired - Fee Related CN1247512C (en) | 2004-07-07 | 2004-07-07 | Process for preparing trifluoromethyl acetophenone compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1247512C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101161621B (en) * | 2007-11-15 | 2010-06-09 | 浙江工业大学 | A method for preparing trifluoromethyl acetophenone compound |
| TWI455919B (en) * | 2008-04-09 | 2014-10-11 | Du Pont | Method for preparing 3-trifluoromethyl chalcones |
-
2004
- 2004-07-07 CN CN 200410052696 patent/CN1247512C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1587246A (en) | 2005-03-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Schneider et al. | Catalytic activation of pinacolyl allylboronate with indium (I): development of a general catalytic allylboration of ketones | |
| Takahashi et al. | Diborative reduction of alkynes to 1, 2-diboryl-1, 2-dimetalloalkanes: its application for the synthesis of diverse 1, 2-bis (boronate) s | |
| Kabalka et al. | Palladium-Catalyzed Cross-Coupling of Baylis− Hillman Acetate Adducts with Organosilanes | |
| Zhu et al. | Copper-catalyzed oxidative homo-and cross-coupling of Grignard reagents using diaziridinone | |
| CN1931804A (en) | Chloromethylation reaction process | |
| CN1247512C (en) | Process for preparing trifluoromethyl acetophenone compound | |
| CN100347177C (en) | Method for producing, via organometallic compounds, organic intermediate products | |
| CN111807938B (en) | (E) -1-chloro-2-iodoethylene compound and preparation method thereof | |
| JP2007230999A (en) | Substituted aromatic nitrile compound and method for producing the same | |
| CN1170804C (en) | Ortho-substituted benzaldehyde, its preparing method and use | |
| JP3541223B2 (en) | Heck reaction using Pd / C catalyst in ionic liquid | |
| CN1894180A (en) | Ecology-friendly bromo-benzene synthesizing method | |
| KR20110041561A (en) | Process for the preparation of 4-bromophenyl derivatives | |
| CN103242261A (en) | Synthetic method of alpha-amino aromatic ketone compound | |
| CN1847223A (en) | Production process of tetrabromobispheno S bis (2,3-dibromopropyl) ether | |
| CN101186566B (en) | Method for preparing acetylacetone by using D301 type alkalescent anion exchange resin as catalyst | |
| CN107235816A (en) | A kind of method that halogenated hydrocarbons hydrolysis prepares alcohol | |
| CN101161621B (en) | A method for preparing trifluoromethyl acetophenone compound | |
| CN1197836C (en) | Method for asymmetrically synthesizing secondary propiolic alcohol compound | |
| CN1284756C (en) | Process for preparing 2-aryl allyl alcohol | |
| CN1290839C (en) | Preparation method of 2-methyl-2-aryl-1,3-oxa amylcyclo compound | |
| Beaumont et al. | Synthesis of novel chiral quaternary phosphonium fluorides: reagents for simple asymmetric nucleophilic fluorination reactions | |
| CN109485550A (en) | The method for preparing styrene derivative with ionic liquid | |
| JP2007051079A (en) | Method for producing aromatic acetylene compound | |
| CN103012073B (en) | Preparation method of chloromethylated cardanol |
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 | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |