CN1233634C - Chemical synthesis method of 3-phenyl-5-methylisoxazole-4-formyl chloride - Google Patents
Chemical synthesis method of 3-phenyl-5-methylisoxazole-4-formyl chloride Download PDFInfo
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- CN1233634C CN1233634C CN 03116220 CN03116220A CN1233634C CN 1233634 C CN1233634 C CN 1233634C CN 03116220 CN03116220 CN 03116220 CN 03116220 A CN03116220 A CN 03116220A CN 1233634 C CN1233634 C CN 1233634C
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- phenyl
- methyl
- isoxzzole
- formic acid
- trichloromethyl
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Abstract
The present invention relates to a chemical synthetic method of 3-phenyl-5-methyl-4-isoxazole formyl chloride. Bi (trichloromethyl) carbonate and 3-phenyl-5-methyl-4-isoxazole formic acid are used as raw material; in organic solvent, through acyl chloride reaction, 3-phenyl-5-methyl-4-isoxazole formyl chloride is prepared. The product of the present invention relates to a pivotal intermediate body of srafilpen. The synthetic method is a chemical synthetic method of 3-phenyl-5-methyl-4-isoxazole formyl chloride, which has the advantages of reasonable technology, safe and reliable preparation, high reaction yield, low preparation cost and almost no generation of waste water, waste gas and waste slag.
Description
Technical field
The present invention relates to the chemical synthesis process that two (trichloromethyl) carbonic ethers [bis (trichloromethyl) carbonate] of a kind of usefulness substitute sulfur oxychloride or phosphorus oxychloride or phosphorus pentachloride or phosphorus trichloride and 3-phenyl-5-methyl isoxzzole-4-formic acid prepared in reaction 3-phenyl-5-methyl isoxzzole-4-formyl chloride (3-phenyl-5-Methylisoxazole-4-carbonylChloride), 3-phenyl-5-methyl isoxzzole-4-formyl chloride is the key intermediate of Prostaphlin.
Background technology
Before the present invention made, the chemical synthesis process of prior art 3-phenyl-5-methyl-4-isoxzzole formyl chloride was to be that raw material reaction makes with sulfur oxychloride or phosphorus oxychloride or phosphorus pentachloride or phosphorus trichloride and 3-phenyl-5-methyl-4-isoxzzole formic acid.Propose as US 2996501 (1961), react with 0.1 mole 3-phenyl-5-methyl-4-isoxzzole formic acid and 0.48 mole sulfur oxychloride and synthesize 3-phenyl-5-methyl-4-isoxzzole formyl chloride.The shortcoming of this technology be use in the world that control uses than toxogen material sulfur oxychloride, equipment corrosion is serious, trouble is that quantity of three wastes is big, and difficult treatment, expense height.
Summary of the invention
Task of the present invention is the shortcoming that overcomes prior art, provides that a kind of technology is reasonable, production safety is reliable, reaction yield is high, production cost is low, does not have the 3-phenyl-5-methyl-4-isoxzzole formyl chloride chemical synthesis process of the three wastes substantially.
The chemical synthesis process of 3-phenyl-5-methyl isoxzzole-4-formyl chloride, it is characterized in that in organic solvent with two (trichloromethyl) carbonic ethers directly and 3-phenyl-5-methyl-4-isoxzzole formic acid make through acyl chloride reaction, its molar ratio is 3-phenyl-5-methyl-4-isoxzzole formic acid: two (trichloromethyl) carbonic ether: catalyzer=1: 0.34～0.5: 0.001～0.1, consumption of organic solvent is 5-15 a times of 3-(2-chloro-phenyl-)-5-methyl-4-isoxzzole formic acid quality, its temperature of reaction is 20～150 ℃, reaction times is 1～6 hour, and its reaction equation is:
5-Methyl-3-phenyl-isoxazole 5-Methyl-3-phenyl-isoxazole
-4-carboxylic?acid -4-carbonyl?chloride
Organic solvent can be benzene or toluene or dimethylbenzene or chlorobenzene or dichlorobenzene or tetrahydrofuran (THF) or methylene dichloride or trichloromethane or tetracol phenixin or ethylene dichloride.
Catalyzer can be tetrabutyl urea or triethylamine or pyridine or 3-picoline or N-methylpyrrole or N-methyl Pyrrolidine or N, dinethylformamide.
The present invention compared with prior art, the operational path advanced person, processing condition are reasonable, used raw material avoided that control in the world uses than toxogen material sulfur oxychloride or phosphorus oxychloride or phosphorus pentachloride or phosphorus trichloride, production safety is reliable, the reaction yield height, generally more than 95%, production cost is lower, and equipment corrosion is little, few and the easy processing of the three wastes has bigger implementary value and economic results in society.
Embodiment
Embodiment 1
3-phenyl-5-methyl-4-isoxzzole formic acid: two (trichloromethyl) carbonic ether: N, dinethylformamide=1: 0.34: 0.01 (mol ratio), chlorobenzene consumption are 8 times of 3-(2-chloro-phenyl-)-5-methyl-4-isoxzzole formic acid quality.
In thermometer, reflux condensing tube and churned mechanically 500 milliliters of four-hole boiling flasks are housed, add 100 milliliters of chlorobenzenes, 22 gram 99.2%3-phenyl-5-methyl-4-isoxzzole formic acid, open and stir, add N in proportion, the chlorobenzene solution of dinethylformamide and two (trichloromethyl) carbonic ethers.Be warming up to 130 ℃ under stirring, held stationary back flow reaction 2 hours, reaction finishes the back underpressure distillation and reclaims chlorobenzene, the last cut of collecting 153-155 ℃ under 0.667KPa.Yield is 93.6%.Through the high-performance liquid chromatogram determination product purity is 99.5%.
Embodiment 2
3-phenyl-5-methyl-4-isoxzzole formic acid: two (trichloromethyl) carbonic ether: N, dinethylformamide=1: 0.34: 0.005 (mol ratio), chlorobenzene consumption are 8 times of 3-(2-chloro-phenyl-)-5-methyl-4-isoxzzole formic acid quality.
In thermometer, reflux condensing tube and churned mechanically 500 milliliters of four-hole boiling flasks are housed, add 100 milliliters and reclaim chlorobenzene, 22 gram 99.2%3-phenyl-5-methyl-4-isoxzzole formic acid, open and stir, add N in proportion, the chlorobenzene solution of dinethylformamide and two (trichloromethyl) carbonic ethers.Be warming up to 130 ℃ under stirring, held stationary back flow reaction 5 hours, reaction finishes the back underpressure distillation and reclaims chlorobenzene, the last cut of collecting 153-155 ℃ under 0.667KPa.Yield is 95.1%.Through the high-performance liquid chromatogram determination product purity is 99.8%.
Embodiment 3
3-phenyl-5-methyl-4-isoxzzole formic acid: two (trichloromethyl) carbonic ether: N, dinethylformamide=1: 0.5: 0.01 (mol ratio), chlorobenzene consumption are 8 times of 3-(2-chloro-phenyl-)-5-methyl-4-isoxzzole formic acid quality.
In thermometer, reflux condensing tube and churned mechanically 500 milliliters of four-hole boiling flasks are housed, add 100 milliliters of chlorobenzenes, 22 gram content are 3-phenyl-5-methyl-4-isoxzzole formic acid of 99.2%, open and stir, add N in proportion, behind the dinethylformamide, drip the chlorobenzene solution of two (trichloromethyl) carbonic ethers at room temperature 30 minutes.Be warming up to 130 ℃ under stirring, held stationary back flow reaction 3 hours, reaction finishes the back underpressure distillation and reclaims chlorobenzene, the last cut of collecting 153-155 ℃ under 0.667KPa.Yield is 96.0%.Through the high-performance liquid chromatogram determination product purity is 99.5%.
Embodiment 4
3-phenyl-5-methyl-4-isoxzzole formic acid: two (trichloromethyl) carbonic ether: tetrabutyl urea=1: 0.50: 0.05 (mol ratio), toluene consumption are 12 times of 3-(2-chloro-phenyl-)-5-methyl-4-isoxzzole formic acid quality.
In thermometer, reflux condensing tube and churned mechanically 500 milliliters of four-hole boiling flasks are housed, add 100 milliliters of toluene, 22 gram 99.2%3-phenyl-5-methyl-4-isoxzzole formic acid, open and stir, add the toluene solution of tetrabutyl urea and two (trichloromethyl) carbonic ethers in proportion.Be warming up to 110 ℃ under stirring, held stationary back flow reaction 3 hours, reaction finishes the back underpressure distillation and reclaims toluene, the last cut of collecting 153-155 ℃ under 0.667KPa.Yield is 96.2%.Through the high-performance liquid chromatogram determination product purity is 99.7%.
Embodiment 5
3-phenyl-5-methyl-4-isoxzzole formic acid: two (trichloromethyl) carbonic ether: tetrabutyl urea=1: 0.50: 0.02 (mol ratio), recovery toluene consumption are 10 times of 3-(2-chloro-phenyl-)-5-methyl-4-isoxzzole formic acid quality.
In thermometer, reflux condensing tube and churned mechanically 500 milliliters of four-hole boiling flasks are housed, add 100 milliliters and reclaim toluene, 22 gram 99.2%3-phenyl-5-methyl-4-isoxzzole formic acid, open and stir, add the toluene solution of tetrabutyl urea and two (trichloromethyl) carbonic ethers in proportion.Be warming up to 110 ℃ under stirring, held stationary back flow reaction 5 hours, reaction finishes the back underpressure distillation and reclaims toluene, the last cut of collecting 153-155 ℃ under 0.667KPa.Yield is 97.3%.Through the high-performance liquid chromatogram determination product purity is 99.8%.
Embodiment 6
3-phenyl-5-methyl-4-isoxzzole formic acid: two (trichloromethyl) carbonic ether: tetrabutyl urea=1: 0.50: 0.02 (mol ratio), benzene consumption are 12 times of 3-(2-chloro-phenyl-)-5-methyl-4-isoxzzole formic acid quality.
In thermometer, reflux condensing tube and churned mechanically 500 milliliters of four-hole boiling flasks are housed, add 100 milliliters of benzene, 22 gram 99.2%3-phenyl-5-methyl-4-isoxzzole formic acid, open and stir, add the toluene solution of tetrabutyl urea and two (trichloromethyl) carbonic ethers in proportion.Be warming up to 80 ℃ under stirring, held stationary back flow reaction 6 hours, reaction finishes the back underpressure distillation and reclaims benzene, the last cut of collecting 153-155 ℃ under 0.667KPa.Yield is 95.8%.Through the high-performance liquid chromatogram determination product purity is 99.6%.
Embodiment 7
3-phenyl-5-methyl-4-isoxzzole formic acid: two (trichloromethyl) carbonic ether: tetrabutyl urea=1: 0.50: 0.02 (mol ratio), tetrahydrofuran (THF) consumption are 10 times of 3-(2-chloro-phenyl-)-5-methyl-4-isoxzzole formic acid quality.
In thermometer, reflux condensing tube and churned mechanically 500 milliliters of four-hole boiling flasks are housed, add 100 milliliters and reclaim tetrahydrofuran (THF), 22 gram 99.2%3-phenyl-5-methyl-4-isoxzzole formic acid, open and stir, add the tetrahydrofuran solution of tetrabutyl urea and two (trichloromethyl) carbonic ethers in proportion.Be warming up to 30 ℃ under stirring, held stationary back flow reaction 8 hours, reaction finishes the back underpressure distillation and reclaims tetrahydrofuran (THF), the last cut of collecting 153-155 ℃ under 0.667KPa.Yield is 95.0%.Through the high-performance liquid chromatogram determination product purity is 99.1%.
The present invention compares with existing processes, has production safety, and equipment corrosion is little, and is easy to operate, the reaction yield height, and the few and easy processing of the three wastes, advantages such as good product quality are methods that is suitable for suitability for industrialized production.
Claims (3)
1, the chemical synthesis process of 3-phenyl-5-methyl isoxzzole-4-formyl chloride, it is characterized in that with two (trichloromethyl) carbonic ethers and 3-phenyl-5-methyl-4-isoxzzole formic acid being to react under the effect of raw material catalyzer in organic solvent to make, its molar ratio is 3-phenyl-5-methyl-4-isoxzzole formic acid: two (trichloromethyl) carbonic ether: catalyzer is 1: 0.34～0.5: 0.001-0.1; Its consumption of organic solvent is 3-15 a times of 3-phenyl-5-methyl-4-isoxzzole formic acid quality; Its temperature of reaction is 20-150 ℃; Its reaction times is 1～10 hour.
2,, it is characterized in that organic solvent can be tetrahydrofuran (THF) or ethyl acetate or benzene or toluene or dimethylbenzene or chlorobenzene or orthodichlorobenzene or Meta Dichlorobenzene or santochlor or trichloromethane or tetracol phenixin or ethylene dichloride as the said chemical synthesis process of claim 1.
3,, it is characterized in that catalyzer can be triethylamine or pyridine or 3-picoline or N-methylpyrrole or N-methyl Pyrrolidine or N, dinethylformamide or tetrabutyl urea as the said chemical synthesis process of claim 1.
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| CN 03116220 CN1233634C (en) | 2003-04-03 | 2003-04-03 | Chemical synthesis method of 3-phenyl-5-methylisoxazole-4-formyl chloride |
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| CN1233634C true CN1233634C (en) | 2005-12-28 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100500633C (en) * | 2006-09-29 | 2009-06-17 | 浙江工业大学 | Acetoxy acetyl chloride chemical synthesizing method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100537510C (en) * | 2006-08-04 | 2009-09-09 | 浙江工业大学 | Chemical method for synthesizing palmitoyl chloride |
| CN100467455C (en) * | 2007-02-14 | 2009-03-11 | 浙江工业大学 | Synthetic method for 3-(2'-chloro-6'-fluorophenyl)-5-methyl-4-isooxazole formyl chloride |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100500633C (en) * | 2006-09-29 | 2009-06-17 | 浙江工业大学 | Acetoxy acetyl chloride chemical synthesizing method |
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