CN1041198C - Method for synthesizing 5-[1-hydroxy-2-(isopropylamino)ethyl] aminobenzonitrile - Google Patents
Method for synthesizing 5-[1-hydroxy-2-(isopropylamino)ethyl] aminobenzonitrile Download PDFInfo
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- CN1041198C CN1041198C CN95103024A CN95103024A CN1041198C CN 1041198 C CN1041198 C CN 1041198C CN 95103024 A CN95103024 A CN 95103024A CN 95103024 A CN95103024 A CN 95103024A CN 1041198 C CN1041198 C CN 1041198C
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Abstract
The present invention belongs to a method for synthesizing 5-[1-hydroxy-2-(isopropylamino) ethyl] aminobenzonitrile as shown in the specification. The present invention mainly solves the problems of many side reactions in the process of synthesis, difficult separation and purification between a midbody and products, low yield and inconvenient treatment of waste gas, waste water and waste residue. Since the present invention improves the reaction conditions of the synthesis method, uses phase-transfer catalysts, simplifies the operating steps of postprocessing and establishes a method for recycling solvents and a part of byproducts, the total yield of aminoacetophenone is increased by 15 to 18% from the original yield of 9%, the production cost is reduced, a quantity of byproducts and solvents can be recycled, and pollution is reduced. The present invention is mainly used for making increasing agents for the fowl of breeding livestock and poultry.
Description
The invention belongs to the method for synthetic 5-(1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile.
The method of synthetic 5-(1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile is more, and state-of-the-art in the world is the U.S., but its synthetic method exists that productive rate is low, by product and solvent can not reclaim contaminate environment, the problem that cost is high.
Task of the present invention is that the side reaction of the existing synthetic method existence of solution is many, and intermediate and separation and purification of products be difficulty relatively, and productive rate is low, and by product and solvent can not reclaim, cost height, problem of environment pollution caused.Can provide a kind of improved synthetic method to reach and reduce cost, improve yield, reduce the purpose of polluting.
The present invention includes following steps:
1.4 '-amino-3 '-preparation of bromoacetophenone
Para-aminoacetophenone is dissolved in the methyl alcohol, in the time of stirring, adds bromo-succinimide in 30-40 ℃, stirring reaction 2 hours is poured in the water, and the separation of methylbenzene layer washes with water, use anhydrous sodium sulfate drying, desolventize and promptly get product, be dissolved in the dimethyl formamide standby;
2.5-the preparation of acetylamino cyanobenzene
With 4 '-amino-3 '-bromoacetophenone is dissolved in the solution of dimethyl formamide, stir the inferior ketone of adding cyaniding down, stirring reaction 6 hours, underpressure distillation goes out solvent then, the weight that dimethylformamide is reclaimed in underpressure distillation is the 40-80% of usage quantity, adds FeCl in 60-70 ℃
3The aqueous solution continue to stir half an hour, pours in water and ethyl acetate or water and the chloroform mixed solution, separates water layer with ethyl acetate or chloroform extraction, merges organic phase, steam desolventize the back with ethanol wash the yellow solid product, fusing point 160-162 ℃;
3.5-the preparation of acetyl bromide anthranilo nitrile
5-acetylamino cyanobenzene is dissolved in the tetrahydrofuran (THF), add Tetrabutyl amonium bromide and cupric bromide, reaction is carried out in tetrahydrofuran (THF), chloroform, acetone, methyl alcohol or mixed solvent, reflux 3-5 hour, filter and use tetrahydrofuran (THF), merging filtrate, desolventize solid phase prod, fusing point 168-170 ℃;
The preparation of (4.5-1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile
5-acetyl bromide anthranilo nitrile is dissolved in the ethanol; under nitrogen protection is stirred; in about 5 ℃, add Isopropylamine; 20-25 ℃ react to reaction solution transparent after; in about 10 ℃, add benzyltriethylammoinium chloride; benzyl triethyl ammonium bromide; a kind of salt phase-transfer catalyst and sodium borohydride in 4-butyl ammonium hydrogen sulfate and the Tetrabutyl amonium bromide; stir; room temperature reaction 6 hours removes ethanol and remaining Isopropylamine under reduced pressure, washing, filtration, drying; get solid phase prod with recrystallizing methanol, fusing point 164-166 ℃.
5. the weight of underpressure distillation recovery dimethyl formamide is 60% of usage quantity.The solvent that is used to extract the acetylamino cyanobenzene is an ethyl acetate.
6.5-the reaction solvent of acetylamino cyanobenzene and cupric bromide is to carry out in tetrahydrofuran solvent, the reaction times is 4 hours.
7. be to prepare that used phase-transfer catalyst is benzyltriethylammoinium chloride or Tetrabutyl amonium bromide in 5-acetyl bromide anthranilo nitrile and 5-(1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile.
The structure of 5-(1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile is as follows:
Advantage of the present invention:
The U.S. synthesizes the method for 5-(1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile, it is more to exist side reaction, intermediate and separation and purification of products be difficulty relatively, productive rate is low, in building-up process, by product and solvent can not reclaim, not only the cost height, and the bad processing of the three wastes, pollute etc.The present invention is owing to improved the reaction conditions of synthetic method, used phase-transfer catalyst, set up method to solvent and the utilization of part by-product recovery, make para-aminoacetophenone meter total recovery be increased to 15-18%, reduce pollution, simplified operation, reduced production cost, and U.S.'s total recovery has only 9%, and can not recycle by product and solvent.
The invention is further described below with reference to accompanying drawing.
Fig. 1 is the schema of 5-of the present invention (1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile.
With reference to Fig. 1:
Para aminoacetophenone is raw material, 4 '-amino-3 '-bromoacetophenone, 5-acetyl-amino benzonitrile and 5-bromine second The acyl amino benzonitrile is intermediate, and 5-(1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile is last product Product.
Embodiments of the invention:
1.4 '-amino-3 '-preparation of bromoacetophenone:
The 500g para-aminoacetophenone is dissolved in the 3000ml methyl alcohol, stir down and add the 650g bromo-succinimide in 30-40 ℃, stirring reaction 2 hours, pour in the water, the separation of methylbenzene layer washes with water, uses anhydrous sodium sulfate drying, desolventizes and promptly gets the 680g product, y=85.8% is dissolved in the dimethyl formamide standby;
2.5-the preparation of acetylamino cyanobenzene:
With 700g4 '-amino-3 '-bromoacetophenone is dissolved in the solution of 3000ml dimethyl formamide, stir to add the inferior ketone of cyaniding down, stirring reaction 6 hours, underpressure distillation goes out about 1800ml solvent, in 60-70 ℃ of adding 3600mlFeCl
3The aqueous solution continue to stir half an hour, pours in the mixed solution of 4000ml water and 4000ml ethyl acetate, separates water layer and extracts with ethyl acetate, merges organic phase, steam desolventize the back with ethanol wash yellow solid product 320g, y=61.1, fusing point 160-162 ℃;
3.5-the preparation of acetyl bromide anthranilo nitrile:
350g5-acetylamino cyanobenzene is dissolved in the 350g tetrahydrofuran (THF), adds 20g Tetrabutyl amonium bromide and 950g cupric bromide, reflux 4 hours is filtered, wash with tetrahydrofuran (THF), merging filtrate, desolventize solid phase prod 370g, fusing point 168-170 ℃;
The preparation of (4.5-1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile
500g5-acetyl bromide anthranilo nitrile is dissolved in the 2000ml ethanol; under nitrogen protection is stirred, in about 5 ℃, add the 500ml Isopropylamine, 20-25 ℃ react to reaction solution transparent after; in about 10 ℃, add 15g Tetrabutyl amonium bromide and 150g sodium borohydride; stir, room temperature reaction 6 hours removes ethanol and remaining Isopropylamine under reduced pressure; washing, filtration, drying; get solid phase prod 230g with recrystallizing methanol, y=50.4%, fusing point 164-166 ℃.
Claims (4)
1. the method for a synthetic 5-(1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile,
It is characterized in that:
A.4 '-amino-3 '-preparation of bromoacetophenone:
Para-aminoacetophenone is dissolved in the methyl alcohol, in the time of stirring, adds bromo-succinimide in 30-40 ℃, stirring reaction 2 hours is poured in the water, and the separation of methylbenzene layer washes with water, use anhydrous sodium sulfate drying, desolventize and promptly get product, be dissolved in the dimethyl formamide standby;
B.5-the preparation of acetylamino cyanobenzene:
With 4 '-amino-3 '-bromoacetophenone is dissolved in the solution of dimethyl formamide, stir the inferior ketone of adding cyaniding down, stirring reaction 6 hours, underpressure distillation goes out solvent then, the weight that dimethylformamide is reclaimed in underpressure distillation is the 40-80% of usage quantity, adds FeCl in 60-70 ℃
3The aqueous solution continue to stir half an hour, pours in water and ethyl acetate or water and the chloroform mixed solution, separates water layer and merges organic phase with ethyl acetate or chloroform extraction, steam desolventize the back with ethanol wash the yellow solid product, fusing point 160-162 ℃;
C.5-the preparation of acetyl bromide anthranilo nitrile:
5-acetylamino cyanobenzene is dissolved in the tetrahydrofuran (THF), add Tetrabutyl amonium bromide and cupric bromide, reaction is carried out in tetrahydrofuran (THF), chloroform, acetone, methanol solvate, reflux 3-5 hour, filtration is washed with tetrahydrofuran (THF), merging filtrate, desolventize solid phase prod, fusing point 168-170 ℃;
D.5-the preparation of (1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile
5-acetyl bromide anthranilo nitrile is dissolved in the ethanol; under nitrogen protection is stirred; in about 5 ℃, add Isopropylamine; 20-25 ℃ react to reaction solution transparent after; in about 10 ℃, add benzyltriethylammoinium chloride; benzyl triethyl ammonium bromide; a kind of salt phase-transfer catalyst and sodium borohydride in 4-butyl ammonium hydrogen sulfate and the Tetrabutyl amonium bromide; stir; room temperature reaction 6 hours removes ethanol and remaining Isopropylamine under reduced pressure, washing, filtration, drying; get solid phase prod with recrystallizing methanol, fusing point 164-166 ℃.
2. method according to claim 1 is characterized in that it is 60% of usage quantity that the weight of dimethyl formamide is reclaimed in underpressure distillation; The solvent that is used to extract 5-acetylamino cyanobenzene is an ethyl acetate.
3. method according to claim 1 is characterized in that the reaction of 5-acetylamino cyanobenzene and cupric bromide is carried out in tetrahydrofuran solvent, the time is 4 hours.
4. method according to claim 1 is characterized in that preparing that used phase-transfer catalyst is benzyltriethylammoinium chloride or Tetrabutyl amonium bromide in 5-acetyl bromide anthranilo nitrile and 5-(1-hydroxyl-2-(isopropylamine base) ethyl) anthranilo nitrile.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95103024A CN1041198C (en) | 1995-04-03 | 1995-04-03 | Method for synthesizing 5-[1-hydroxy-2-(isopropylamino)ethyl] aminobenzonitrile |
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| CN95103024A CN1041198C (en) | 1995-04-03 | 1995-04-03 | Method for synthesizing 5-[1-hydroxy-2-(isopropylamino)ethyl] aminobenzonitrile |
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| CN1120535A CN1120535A (en) | 1996-04-17 |
| CN1041198C true CN1041198C (en) | 1998-12-16 |
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| CN109912434B (en) * | 2017-12-13 | 2022-07-12 | 上海安谱实验科技股份有限公司 | Synthesis method of phenylethanolamine beta receptor agonist |
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