CN102558055A - Preparation method of 1-(2- formaldehyde base phenyl) pyrazol - Google Patents
Preparation method of 1-(2- formaldehyde base phenyl) pyrazol Download PDFInfo
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- CN102558055A CN102558055A CN2012100026318A CN201210002631A CN102558055A CN 102558055 A CN102558055 A CN 102558055A CN 2012100026318 A CN2012100026318 A CN 2012100026318A CN 201210002631 A CN201210002631 A CN 201210002631A CN 102558055 A CN102558055 A CN 102558055A
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- pyrazoles
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- 0 CC(c(cccc1)c1N(C)C=*)=O Chemical compound CC(c(cccc1)c1N(C)C=*)=O 0.000 description 1
Abstract
The invention discloses a preparation method of 1-(2-formaldehyde base phenyl) pyrazol, which aims at resolving the problem that bromobenzaldehyde is utilized to react with pyrazol under the existence of alkali in the prior art, the 1-(2-formaldehyde base phenyl) pyrazol is not stable, easy to go bad in the processing purification process after reaction, low in yield accordingly and difficult in production enlargement. The preparation method mainly improves the prior process route, avoids the aldehyde group from gene exposure and damage by conducting protection and deprotection on the aldehyde group, and enables each step of the reaction to be controllable and easy to operate, thereby facilitating production enlargement and improving efficiency.
Description
Technical field
The synthesis technology that the present invention relates to a kind of 1-(2-carboxaldehyde radicals phenyl) pyrazoles improves, and belongs to the medicine bioengineering chemical technology field.Also relate to some midbody that obtains through this method.
Background technology
1-(2-carboxaldehyde radicals phenyl) pyrazoles is a kind of pale solid, is a kind of medicine bioengineering chemical intermediate.
The synthesis technique of existing 1-(2-carboxaldehyde radicals phenyl) pyrazoles mainly adopts adjacent bromobenzaldehyde and pyrazoles is reacted in the presence of alkali.Because 1-(2-carboxaldehyde radicals phenyl) pyrazoles less stable be prone to degenerate in the post-reaction treatment purge process, so yield is very low.Be difficult to amplify and produce.
Summary of the invention
Not enough to prior art, the present invention mainly improves former operational path, through to aldehyde radical protection and deprotection, avoids aldehyde radical to degenerate because of exposed, makes per step react controlled easy to operate, is convenient to amplify and produces, and improve yield.
The present invention provides formula (1) compound
The present invention also provides by formula (4) compound
Hydrolysis prepares the method for formula (1) compound
This method comprises mineral acid example hydrochloric acid, Hydrogen bromide, hydroiodic acid HI, nitric acid, sulfuric acid, organic acid such as acetate, trifluoroacetic acid, tosic acid in suitable acid.Preferred hydrochloric acid.
The present invention provides by formula (3) compound
The method for preparing formula (4) compound
This method is passed through sodium hydrogen, pyrazoles, copper powder, 2-(2-bromophenyl)-1,3-dioxolane and N, and dinethylformamide reacts the some time in certain temperature.Alkali such as sodium hydrogen, sodium hydroxide, yellow soda ash, sodium hydrogencarbonate, salt of wormwood, saleratus, 4-Dimethylamino pyridine, preferred sodium hydrogen.Reaction solvent such as N, dinethylformamide, DMAC N,N, chloroform, methylene dichloride, acetone, acetonitrile, THF, preferred N, dinethylformamide.Certain temperature is the 20-180 degree, preferred 160 degree.Some time is 2-48 hour, preferred 15-20 hour.
The present invention provides by formula (2) compound
The method for preparing formula (3) compound
This method is carried out under acid catalyst and appropriate solvent certain temperature.Acid example hydrochloric acid, sulfuric acid, trifluoroacetic acid, tosic acid, preferred tosic acid.Protective material such as methyl alcohol, ethanol, terepthaloyl moietie, USP Kosher, preferred terepthaloyl moietie.Solvent such as benzene, toluene, chlorobenzene, YLENE, preferred toluene.Temperature of reaction 20-160 degree, preferred 110-120 degree, reaction times 5-72 hour, preferred 48 hours.
Embodiment
Embodiment 1
3 liters there-necked flask adds 300 gram formula (2) compounds, 102 gram terepthaloyl moietie, 27.8 gram tosic acid and 2 liters of toluene, the tool water trap, and electronic stirring, being heated to refluxes spends the night.Be cooled to room temperature, pour in the water separatory into.Organic layer is water and saturated common salt water washing respectively, anhydrous sodium sulfate drying.Concentrating under reduced pressure gets formula 370 gram formula (3) compounds
Embodiment 2
3 liters there-necked flask adds 77 gram sodium hydrogen, 120 gram pyrazoles and 1500 milliliters of N, dinethylformamide, and stirring at room 1 hour adds 10.3 gram copper powder and 370 gram formula (3) compounds, and reflux is spent the night.Be cooled to room temperature, pour in the water ethyl acetate extraction into.Merge organic layer, water and saturated common salt water washing respectively, anhydrous sodium sulfate drying.Pressurization concentrates, and column chromatography purification gets 250 gram formula (4) compounds
Embodiment 3
1 liter there-necked flask adds 250 gram formula (4) compounds and 400 milliliters of 1N hydrochloric acid, stirred overnight at room temperature.Transfer pH7～8 with sodium carbonate solution, cross and filter 200 gram formula (1) compounds.
Claims (4)
- The preparation method of (1.1-2-carboxaldehyde radicals phenyl) pyrazoles, with adjacent bromobenzaldehyde, terepthaloyl moietie, tosic acid and toluene, reflux is spent the night, through fraction water device water-dividing.Be cooled to room temperature then, pour in the water separatory into.Organic layer is water and saturated common salt water washing respectively, anhydrous sodium sulfate drying.Concentrating under reduced pressure obtains 2-(2-bromophenyl)-1, the 3-dioxolane.With sodium hydrogen, pyrazoles and N, dinethylformamide, stirring at room 2 hours adds copper powder and 2-(2-bromophenyl)-1, the 3-dioxolane, reflux is spent the night.Be cooled to room temperature, pour in the water ethyl acetate extraction into.Merge organic layer, water and saturated common salt water washing respectively, anhydrous sodium sulfate drying.Pressurization concentrates, and column chromatography purification gets 1-(2-[1,3]-dioxolane-2-phenyl)-1H-pyrazoles.Mixed 1-(2-[1,3]-dioxolane-2-phenyl)-1H-pyrazoles and hydrochloric acid, stirred overnight at room temperature.Transfer pH7-8 with sodium carbonate solution, cross and filter 1-(2 carboxaldehyde radicals phenyl) pyrazoles
- 2. the preparation method of 1-(2-carboxaldehyde radicals phenyl) pyrazoles as claimed in claim, it is characterized in that: aldehyde radical protection under the suitable acid catalysis of the first step, acid includes but not limited to hydrochloric acid, sulfuric acid, trifluoroacetic acid, tosic acid.Protective material includes but not limited to methyl alcohol, ethanol, terepthaloyl moietie, USP Kosher.Reaction solvent includes but not limited to benzene, toluene, chlorobenzene, YLENE.Temperature of reaction 20-160 degree, reaction times 5-72 hour.
- 3. the preparation method of 1-(2-carboxaldehyde radicals phenyl) pyrazoles as claimed in claim is characterized in that: the second step sodium hydrogen, pyrazoles, copper powder, 2-(2-bromophenyl)-1, and 3-dioxolane and N, dinethylformamide reacts the some time in certain temperature.Alkali includes but not limited to sodium hydrogen, sodium hydroxide, yellow soda ash, sodium hydrogencarbonate, salt of wormwood, saleratus, 4-Dimethylamino pyridine.Reaction solvent includes but not limited to N, dinethylformamide, DMAC N,N, chloroform, methylene dichloride, acetone, acetonitrile, THF.Certain temperature is the 20-180 degree, and the some time is 2-48 hour.
- 4. the preparation method of 1-(2-carboxaldehyde radicals phenyl) pyrazoles as claimed in claim, it is characterized in that: deprotection under the 3rd step acidic conditions, used acid includes but not limited to hydrochloric acid, sulfuric acid, tosic acid.Temperature of reaction 0-120 degree, reaction times 4-40 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100026318A CN102558055A (en) | 2012-01-06 | 2012-01-06 | Preparation method of 1-(2- formaldehyde base phenyl) pyrazol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100026318A CN102558055A (en) | 2012-01-06 | 2012-01-06 | Preparation method of 1-(2- formaldehyde base phenyl) pyrazol |
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| CN102558055A true CN102558055A (en) | 2012-07-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN2012100026318A Pending CN102558055A (en) | 2012-01-06 | 2012-01-06 | Preparation method of 1-(2- formaldehyde base phenyl) pyrazol |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5426247A (en) * | 1992-12-07 | 1995-06-20 | Rhone-Poulenc Nutrition Animale | Process for the preparation of vitamin A and intermediate compounds which are useful for this process |
| US20100222598A1 (en) * | 2005-12-28 | 2010-09-02 | Daikin Industries, Ltd. | PROCESS FOR PREPARING HETEROAROMATIC RING COMPOUND HAVING N-Rf GROUP |
-
2012
- 2012-01-06 CN CN2012100026318A patent/CN102558055A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5426247A (en) * | 1992-12-07 | 1995-06-20 | Rhone-Poulenc Nutrition Animale | Process for the preparation of vitamin A and intermediate compounds which are useful for this process |
| US20100222598A1 (en) * | 2005-12-28 | 2010-09-02 | Daikin Industries, Ltd. | PROCESS FOR PREPARING HETEROAROMATIC RING COMPOUND HAVING N-Rf GROUP |
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Application publication date: 20120711 |