CN102731334A - Method for preparing 5-aminosalicylic acid - Google Patents
Method for preparing 5-aminosalicylic acid Download PDFInfo
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Abstract
The invention discloses a method for preparing 5-aminosalicylic acid. The method comprises the following steps of: adding an ionic liquid 1-butyl-3-methylimidazolium chloride and a substrate sodium p-aminophenolate into a reaction kettle; dissolving the sodium p-aminophenolate into the 1-butyl-3-methylimidazolium chloride to form solution; inputting carbon dioxide gas into the solution and making the carbon dioxide gas and the sodium p-aminophenolate fully generate the gas phase carboxylation, wherein the reaction pressure of the gas phase carboxylation is between 0.5MPa and 3MPa and the reaction temperature of the gas phase carboxylation is between 120 DEG C and 200 DEG C; obtaining a reaction mixture with sodium 5-aminosalicylate; dissolving the reaction mixture with sodium 5-aminosalicylate in water to obtain the solution of the reaction mixture with sodium 5-aminosalicylate; and, acidifying the solution of the reaction mixture with sodium 5-aminosalicylate by dilute hydrochloric acid to form acidified solution, and reacting the hydrochloric acid and sodium 5-aminosalicylate to generate the 5-aminosalicylic acid and separate the 5-aminosalicylic acid from the acidified solution.
Description
[technical field]
The present invention relates generally to the preparation method of phenolic acid, particularly a kind of method for preparing 5-aminosalicylic acid.
[background technology]
5-aminosalicylic acid (5-Amino salicylic acid); Commodity are called the Mei Lasha piperazine; Because 5-aminosalicylic acid (5-ASA) possesses radical (DPPHL) reductive action, hydrogen peroxide cancellation effect, hypochlorite ion's cancellation effect, lipoperoxide restraining effect and leukotrienes B4 biosynthesizing restraining effect, is mainly used in industrial circles such as medicine, agricultural chemicals.
Ulcerative colitis is a kind of non-specific chronic intestinal tract disease, and this disease can not be cured so far fully.At present, 5-aminosalicylic acid and verivate thereof are the first-use drugs of this disease of treatment.The compound method of the 5-ASA of bibliographical information mainly contains four kinds of operational paths at present: aniline process, salicylic acid method, PARA AMINOPHENOL solid phase carboxylation synthesis method and PARACETAMOL BP98 solid phase carboxylation method.The external 5-aminosalicylic acid process method of producing still adopts traditional aniline synthesis method or Whitfield's ointment synthesis method mostly.(1997,28 (8): 341～342) " new synthetic method of mesalazine " literary composition report is a starting raw material with the PARA AMINOPHENOL to people such as Mo Fenzhu, and under high pressure and high temperature, gas phase condition descends and carbon dioxide reaction makes 5-ASA at Chinese Journal of Pharmaceuticals.The document is simply reported the 5-ASA with the preparation of this method, and total recovery surpasses 80%, and this method operational path is short, pollute little, but severe reaction conditions, the gas-solid carboxylation reaction carries out under HTHP, the very easily oxidized and polymerization of amino-phenol.
[summary of the invention]
The purpose of this invention is to provide a kind of novel method for preparing 5-aminosalicylic acid.
The objective of the invention is to realize through following technical scheme:
A kind of method for preparing 5-aminosalicylic acid; In reaction kettle, add ionic liquid chlorination 1-butyl-3-Methylimidazole and substrate PARA AMINOPHENOL sodium; This PARA AMINOPHENOL sodium is dissolved in this chlorination 1-butyl-3-Methylimidazole and forms solution; In this solution, feed dioxide gas, carbonic acid gas and PARA AMINOPHENOL sodium carry out abundant gas phase carboxylation reaction, and the reaction pressure of this gas phase carboxylation reaction is 0.5-3MPa; Temperature of reaction is 120 ℃-200 ℃, obtains containing the reaction mixture of 5-aminosalicylic acid sodium; This contains the reaction mixture of 5-aminosalicylic acid sodium with water dissolution, obtains the solution that this contains the reaction mixture of 5-aminosalicylic acid sodium; This contains the solution of the reaction mixture of 5-aminosalicylic acid sodium with the Hydrogen chloride acidifying, forms souring soln, and hydrochloric acid and the reaction of 5-aminosalicylic acid sodium generate 5-aminosalicylic acid and separate out from this souring soln;
Reaction formula is following:
Carboxylation reaction
The method for preparing 5-aminosalicylic acid of the present invention is compared with the method for preparing 5-aminosalicylic acid of prior art has following advantage:
(1) use ionic liquid chlorination 1-butyl-3-Methylimidazole as reaction solvent; Can not only dissolve substrate PARA AMINOPHENOL sodium, and, help the carrying out that reacts for carbonic acid gas provides good carboxylation reaction microenvironment; Making that the carboxylation reaction time short, is 5～10 hours.
(2) substrate PARA AMINOPHENOL sodium directly as gas phase carboxylation reaction raw material, has reduced oxidation and polymerization, and good positioning effect, and good reaction selectivity can directedly generate 5-aminosalicylic acid, and gas phase carboxylation reaction yield is high, and product purity is high.
(3) replace the solid state chemistry carboxylation reaction with the gas phase carboxylation reaction, reaction system is the gas-liquid system, is easy to feed in raw material, treating processess such as stirring, blowing, and energy consumption is low.
(4) technical process is simple, and reaction conditions is gentle, and production safety is fit to the large-scale industry serialization and produces.
For technique scheme:
Preferably, the reaction pressure of said gas phase carboxylation reaction is 1.0-2.5MPa, and temperature of reaction is 140 ℃-170 ℃.
Preferably, said when this contains the solution of reaction mixture of 5-aminosalicylic acid sodium with the Hydrogen chloride acidifying, this solution that contains the reaction mixture of 5-aminosalicylic acid sodium is acidified to the pH value between the 5.0-6.0.
Further; Carry out abundant gas phase carboxylation reaction at said carbonic acid gas and PARA AMINOPHENOL sodium; After generation contains the reaction mixture of 5-aminosalicylic acid sodium, cool off this autoclave, the temperature in this autoclave is quickly fallen to below 80 ℃; Discharge the dioxide gas in this autoclave simultaneously; Treat that dioxide gas puts the kettle cover of opening this autoclave after clean, carry out then that said this contains the reaction mixture of 5-aminosalicylic acid sodium with water dissolution, obtain the solution step of this reaction mixture that contains 5-aminosalicylic acid sodium.
Further, spinning goes out the 5-aminosalicylic acid solid from said souring soln; Dry 5-aminosalicylic acid solid 10-14 hour obtains 5-aminosalicylic acid black xln; 5-aminosalicylic acid black xln was placed the dry 10-14 of vacuum drying oven hour; Dried 5-aminosalicylic acid black xln is dissolved in the solution of hydrochloric acid and water composition; Hydrochloric acid is 1 to 3 with the volume ratio of water; Stirring heating is dissolved 5-aminosalicylic acid black xln fully, adds proper amount of active carbon in the solution and boils 8-12 minute, removes by filter gac then; Filtrating uses 30%NaOH solution adjusting pH value to be 5-6, separates out colourless 5-aminosalicylic acid solid; Cooling contains colourless 5-aminosalicylic acid solid filtrating; Spinning goes out the 5-aminosalicylic acid solid from filtrating; The 5-aminosalicylic acid solid that spinning is gone out about 90 ℃-110 ℃ dry 10-14 hour obtains having a little grayish white crystals 5-aminosalicylic acid.
[embodiment]
The present invention also will combine embodiment to do further detailed description.
The following stated embodiment has only expressed several kinds of embodiments of asking in the patent of the present invention, and it describes comparatively concrete and detailed, but can not therefore be interpreted as the restriction to patented claim protection domain of the present invention.Under the prerequisite that does not break away from the present invention's design, can also make some distortion and improvement, these all belong to the protection domain of patented claim of the present invention.Therefore, the protection domain of patented claim of the present invention should be as the criterion with accompanying claims.
The preparation of ionic liquid chlorination 1-butyl-3-Methylimidazole:
In the 250ml round-bottomed flask, add 8.2g (0.1mol) 1-Methylimidazole, 16.44g (0.12mol) bromination of n-butane and 50ml acetonitrile, under the normal pressure in 70 ℃; Under the N2 protection, stirring reaction 12 hours obtains flaxen bromination 1-butyl-3-Methylimidazole viscous solution; Underpressure distillation is removed acetonitrile and unreacted completely behind the raw material, adds the 13.3g anhydrous AlCl3, and room temperature N2 protection was stirred 12 hours down; Obtain faint yellow viscous solution, remove sodium chloride salt with ether (10ml * 3) washing, rotary evaporation is removed ether then; 80 ℃ of following vacuum-dryings 12 hours, obtain ionic liquid chlorination 1-butyl-3-Methylimidazole.
Synthesizing of substrate PARA AMINOPHENOL sodium:
In the 150mL round-bottomed flask, add the 5.4701g PARA AMINOPHENOL, then 50ml 0.5mol/L sodium hydroxide solution is added; Under normal pressure, N2 protection, stir while adding, add under the room temperature of back and continue to stir 30 minutes, be warmed up to 70 ℃ again; Underpressure distillation removes water; Become when thick to solution, transfer in the ceramic whiteware dish, place vacuum drying oven to carry out the drying under reduced pressure first time.Keep vacuum tightness 0.08MPa-0.09MPa, temperature is at 80 ℃-100 ℃, after dry 24 hours; Reduce to room temperature, take out solid p-aminophenyl sodium phenolate and in mortar, wear into fine powder, because sodium salt very easily absorbs water; So need put into the ceramic whiteware dish once more, place vacuum drying oven to carry out the drying second time, temperature is at 80 ℃-100 ℃; Keep 0.08MPa-0.09MPa, dry 12 hours, obtain the p-aminophenyl sodium phenolate.
Embodiment 1
Take by weighing 2.0g substrate PARA AMINOPHENOL sodium and put into the 50ml autoclave, add ionic liquid 13.54g chlorination 1-butyl-3-Methylimidazole, add kettle cover sealed high pressure reaction kettle; Feed CO2 gas and carry out carboxylation reaction; Temperature of reaction is 140 ℃, when reaction pressure is 2.5MPa, keeps this pressure and temperature; Continue carboxylation reaction 10 hours, and obtained containing the reaction mixture of 5-aminosalicylic acid sodium; Stop carboxylation reaction, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 80 ℃, open simultaneously air valve is discharged the dioxide gas in the autoclave, treats to open the autoclave kettle cover after dioxide gas is put only; Contain the reaction mixture of 5-aminosalicylic acid sodium with water dissolution, obtain containing the solution of the reaction mixture of 5-aminosalicylic acid sodium; Use solution to the pH value of reaction mixture that the Hydrogen chloride acidifying contains 5-aminosalicylic acid sodium as between the 5.0-6.0, form souring soln, hydrochloric acid is separated out with 5-aminosalicylic acid sodium reaction generation 5-aminosalicylic acid and from souring soln; Spinning goes out the 5-aminosalicylic acid solid from souring soln; Dry 5-aminosalicylic acid solid 12 hours obtains 5-aminosalicylic acid black xln; 5-aminosalicylic acid black xln was placed vacuum drying oven dry 12 hours; Dried 5-aminosalicylic acid black xln is dissolved in the solution of 5ml hydrochloric acid and 15ml water composition; Stirring heating is dissolved 5-aminosalicylic acid black xln fully; Add proper amount of active carbon in the solution and boiled 10 minutes; Remove by filter gac then, filtrating uses 30%NaOH solution adjusting pH value to be 5-6, separates out almost colourless 5-aminosalicylic acid solid; Cooling contains colourless 5-aminosalicylic acid solid filtrating; Spinning goes out the 5-aminosalicylic acid solid from filtrating; The 5-aminosalicylic acid solid that spinning is gone out about 100 ℃ dry 12 hours obtains having a little grayish white crystals 5-aminosalicylic acid.Purity is 98%, and once through yield is 81%.
Embodiment 2
Take by weighing 2.0g substrate PARA AMINOPHENOL sodium and put into the 50ml autoclave, add ionic liquid 13.54g chlorination 1-butyl-3-Methylimidazole, add kettle cover sealed high pressure reaction kettle; Feed CO2 gas and carry out carboxylation reaction; Temperature of reaction is 120 ℃, when reaction pressure is 3.0MPa, keeps this pressure and temperature; Continue carboxylation reaction 10 hours, and obtained containing the reaction mixture of 5-aminosalicylic acid sodium; Stop carboxylation reaction, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 80 ℃, open simultaneously air valve is discharged the dioxide gas in the autoclave, treats to open the autoclave kettle cover after dioxide gas is put only; Contain the reaction mixture of 5-aminosalicylic acid sodium with water dissolution, obtain containing the solution of the reaction mixture of 5-aminosalicylic acid sodium; Use solution to the pH value of reaction mixture that the Hydrogen chloride acidifying contains 5-aminosalicylic acid sodium as between the 5.0-6.0, form souring soln, hydrochloric acid is separated out with 5-aminosalicylic acid sodium reaction generation 5-aminosalicylic acid and from souring soln; Spinning goes out the 5-aminosalicylic acid solid from souring soln; Dry 5-aminosalicylic acid solid 10 hours obtains 5-aminosalicylic acid black xln; 5-aminosalicylic acid black xln was placed vacuum drying oven dry 12 hours; Dried 5-aminosalicylic acid black xln is dissolved in the solution of 5ml hydrochloric acid and 15ml water composition; Stirring heating is dissolved 5-aminosalicylic acid black xln fully; Add proper amount of active carbon in the solution and boiled 8 minutes; Remove by filter gac then, filtrating uses 30%NaOH solution adjusting pH value to be 5-6, separates out almost colourless 5-aminosalicylic acid solid; Cooling contains colourless 5-aminosalicylic acid solid filtrating; Spinning goes out the 5-aminosalicylic acid solid from filtrating; The 5-aminosalicylic acid solid that spinning is gone out about 100 ℃ dry 12 hours obtains having a little grayish white crystals 5-aminosalicylic acid.Purity is 34%, and once through yield is 27%.
Embodiment 3
Take by weighing 2.0g substrate PARA AMINOPHENOL sodium and put into the 50ml autoclave, add ionic liquid 13.54g chlorination 1-butyl-3-Methylimidazole, add kettle cover sealed high pressure reaction kettle; Feed CO2 gas and carry out carboxylation reaction; Temperature of reaction is 200 ℃, when reaction pressure is 0.5MPa, keeps this pressure and temperature; Continue carboxylation reaction 10 hours, and obtained containing the reaction mixture of 5-aminosalicylic acid sodium; Stop carboxylation reaction, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 80 ℃, open simultaneously air valve is discharged the dioxide gas in the autoclave, treats to open the autoclave kettle cover after dioxide gas is put only; Contain the reaction mixture of 5-aminosalicylic acid sodium with water dissolution, obtain containing the solution of the reaction mixture of 5-aminosalicylic acid sodium; Use solution to the pH value of reaction mixture that the Hydrogen chloride acidifying contains 5-aminosalicylic acid sodium as between the 5.0-6.0, form souring soln, hydrochloric acid is separated out with 5-aminosalicylic acid sodium reaction generation 5-aminosalicylic acid and from souring soln; Spinning goes out the 5-aminosalicylic acid solid from souring soln; Dry 5-aminosalicylic acid solid 14 hours obtains 5-aminosalicylic acid black xln; 5-aminosalicylic acid black xln was placed vacuum drying oven dry 12 hours; Dried 5-aminosalicylic acid black xln is dissolved in the solution of 5ml hydrochloric acid and 15ml water composition; Stirring heating is dissolved 5-aminosalicylic acid black xln fully; Add proper amount of active carbon in the solution and boiled 12 minutes; Remove by filter gac then, filtrating uses 30%NaOH solution adjusting pH value to be 5-6, separates out almost colourless 5-aminosalicylic acid solid; Cooling contains colourless 5-aminosalicylic acid solid filtrating; Spinning goes out the 5-aminosalicylic acid solid from filtrating; The 5-aminosalicylic acid solid that spinning is gone out about 100 ℃ dry 10 hours obtains having a little grayish white crystals 5-aminosalicylic acid.Purity is 9.81%, and once through yield is 7.66%.
Embodiment 4
Take by weighing 2.0g substrate PARA AMINOPHENOL sodium and put into the 50ml autoclave, add ionic liquid 13.54g chlorination 1-butyl-3-Methylimidazole, add kettle cover sealed high pressure reaction kettle; Feed CO2 gas and carry out carboxylation reaction; Temperature of reaction is 160 ℃, when reaction pressure is 2.0MPa, keeps this pressure and temperature; Continue carboxylation reaction 10 hours, and obtained containing the reaction mixture of 5-aminosalicylic acid sodium; Stop carboxylation reaction, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 80 ℃, open simultaneously air valve is discharged the dioxide gas in the autoclave, treats to open the autoclave kettle cover after dioxide gas is put only; Contain the reaction mixture of 5-aminosalicylic acid sodium with water dissolution, obtain containing the solution of the reaction mixture of 5-aminosalicylic acid sodium; Use solution to the pH value of reaction mixture that the Hydrogen chloride acidifying contains 5-aminosalicylic acid sodium as between the 5.0-6.0, form souring soln, hydrochloric acid is separated out with 5-aminosalicylic acid sodium reaction generation 5-aminosalicylic acid and from souring soln; Spinning goes out the 5-aminosalicylic acid solid from souring soln; Dry 5-aminosalicylic acid solid 12 hours obtains 5-aminosalicylic acid black xln; 5-aminosalicylic acid black xln was placed vacuum drying oven dry 10 hours; Dried 5-aminosalicylic acid black xln is dissolved in the solution of 5ml hydrochloric acid and 15ml water composition; Stirring heating is dissolved 5-aminosalicylic acid black xln fully; Add proper amount of active carbon in the solution and boiled 10 minutes; Remove by filter gac then, filtrating uses 30%NaOH solution adjusting pH value to be 5-6, separates out almost colourless 5-aminosalicylic acid solid; Cooling contains colourless 5-aminosalicylic acid solid filtrating; Spinning goes out the 5-aminosalicylic acid solid from filtrating; The 5-aminosalicylic acid solid that spinning is gone out about 100 ℃ dry 14 hours obtains having a little grayish white crystals 5-aminosalicylic acid.Purity is 53%, and once through yield is 49%.
Embodiment 5
Take by weighing 2.0g substrate PARA AMINOPHENOL sodium and put into the 50ml autoclave, add ionic liquid 13.54g chlorination 1-butyl-3-Methylimidazole, add kettle cover sealed high pressure reaction kettle; Feed CO2 gas and carry out carboxylation reaction; Temperature of reaction is 170 ℃, when reaction pressure is 1.0MPa, keeps this pressure and temperature; Continue carboxylation reaction 10 hours, and obtained containing the reaction mixture of 5-aminosalicylic acid sodium; Stop carboxylation reaction, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 80 ℃, open simultaneously air valve is discharged the dioxide gas in the autoclave, treats to open the autoclave kettle cover after dioxide gas is put only; Contain the reaction mixture of 5-aminosalicylic acid sodium with water dissolution, obtain containing the solution of the reaction mixture of 5-aminosalicylic acid sodium; Use solution to the pH value of reaction mixture that the Hydrogen chloride acidifying contains 5-aminosalicylic acid sodium as between the 5.0-6.0, form souring soln, hydrochloric acid is separated out with 5-aminosalicylic acid sodium reaction generation 5-aminosalicylic acid and from souring soln; Spinning goes out the 5-aminosalicylic acid solid from souring soln; Dry 5-aminosalicylic acid solid 12 hours obtains 5-aminosalicylic acid black xln; 5-aminosalicylic acid black xln was placed vacuum drying oven dry 14 hours; Dried 5-aminosalicylic acid black xln is dissolved in the solution of 5ml hydrochloric acid and 15ml water composition; Stirring heating is dissolved 5-aminosalicylic acid black xln fully; Add proper amount of active carbon in the solution and boiled 10 minutes; Remove by filter gac then, filtrating uses 30%NaOH solution adjusting pH value to be 5-6, separates out almost colourless 5-aminosalicylic acid solid; Cooling contains colourless 5-aminosalicylic acid solid filtrating; Spinning goes out the 5-aminosalicylic acid solid from filtrating; The 5-aminosalicylic acid solid that spinning is gone out about 100 ℃ dry 12 hours obtains having a little grayish white crystals 5-aminosalicylic acid.Purity is 15%, and once through yield is 12%.
Reference examples
Take by weighing 2.0g PARA AMINOPHENOL sodium and put into the 50ml autoclave, add kettle cover sealed high pressure reaction kettle, feed CO2 and carry out carboxylation reaction; Temperature of reaction is 140 ℃, when reaction pressure is 2.5MPa, keeps this pressure and temperature; After continuing to react 10 hours; Obtain containing the reaction mixture of 5-aminosalicylic acid sodium, stop carboxylation reaction, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 80 ℃; Open simultaneously air valve is discharged the dioxide gas in the autoclave, treats to open the autoclave kettle cover after dioxide gas is put only; Contain the reaction mixture of 5-aminosalicylic acid sodium with water dissolution, obtain containing the solution of the reaction mixture of 5-aminosalicylic acid sodium; Use solution to the pH value of reaction mixture that the Hydrogen chloride acidifying contains 5-aminosalicylic acid sodium as between the 5.0-6.0, form souring soln, hydrochloric acid is separated out with 5-aminosalicylic acid sodium reaction generation 5-aminosalicylic acid and from souring soln; Spinning goes out the 5-aminosalicylic acid solid from souring soln; Dry 5-aminosalicylic acid solid 12 hours obtains 5-aminosalicylic acid black xln; 5-aminosalicylic acid black xln was placed vacuum drying oven dry 12 hours; Dried 5-aminosalicylic acid black xln is dissolved in the solution of 5ml hydrochloric acid and 15ml water composition; Stirring heating is dissolved 5-aminosalicylic acid black xln fully; Add proper amount of active carbon in the solution and boiled 10 minutes; Remove by filter gac then, filtrating uses 30%NaOH solution adjusting pH value to be 5-6, separates out almost colourless 5-aminosalicylic acid solid; Cooling contains colourless 5-aminosalicylic acid solid filtrating; Spinning goes out the 5-aminosalicylic acid solid from filtrating; The 5-aminosalicylic acid solid that spinning is gone out about 100 ℃ dry 12 hours obtains having a little grayish white crystals 5-aminosalicylic acid.Purity is 28%, and once through yield is 34%.
For embodiment 1; Substrate PARA AMINOPHENOL sodium is dissolved in ionic liquid chlorination 1-butyl-3-Methylimidazole, carries out the gas phase carboxylation reaction with CO2 gas, for reference examples; PARA AMINOPHENOL sodium and CO2 gas carry out the solid state chemistry carboxylation reaction; The former is basic identical with other condition of the latter, and the result is that the former purity and once through yield all are much higher than the latter.
Purity is defined as: the ratio of the weight of the weight of 5-aminosalicylic acid and gained white crystals is purity in the gained white crystals.
Once through yield is defined as: carry out the 5-aminosalicylic acid sodium that the gas phase carboxylation reaction is generated with the carbonic acid gas of reacting weight and the chlorination 1-butyl-3-Methylimidazole of reacting weight; Make denominator through the 5-aminosalicylic acid of the theoretical amount that hcl acidifying generated of reacting weight again; 5-aminosalicylic acid with the actual amount that makes is made molecule, and the latter and the former ratio are once through yield.
Claims (5)
1. method for preparing 5-aminosalicylic acid; It is characterized in that; In reaction kettle, add ionic liquid chlorination 1-butyl-3-Methylimidazole and substrate PARA AMINOPHENOL sodium, this PARA AMINOPHENOL sodium is dissolved in this chlorination 1-butyl-3-Methylimidazole and forms solution, in this solution, feeds dioxide gas; Carbonic acid gas and PARA AMINOPHENOL sodium carry out abundant gas phase carboxylation reaction; The reaction pressure of this gas phase carboxylation reaction is 0.5-3MPa, and temperature of reaction is 120 ℃-200 ℃, obtains containing the reaction mixture of 5-aminosalicylic acid sodium; This contains the reaction mixture of 5-aminosalicylic acid sodium with water dissolution, obtains the solution that this contains the reaction mixture of 5-aminosalicylic acid sodium; This contains the solution of the reaction mixture of 5-aminosalicylic acid sodium with the Hydrogen chloride acidifying, forms souring soln, and hydrochloric acid and the reaction of 5-aminosalicylic acid sodium generate 5-aminosalicylic acid and separate out from this souring soln;
Reaction formula is following:
Carboxylation reaction
2. the method for preparing 5-aminosalicylic acid according to claim 1 is characterized in that, the reaction pressure of said gas phase carboxylation reaction is 1.0-2.5MPa, and temperature of reaction is 140 ℃-170 ℃.
3. the method for preparing 5-aminosalicylic acid according to claim 1; It is characterized in that; Said when this contains the solution of reaction mixture of 5-aminosalicylate with the Hydrogen chloride acidifying, this solution that contains the reaction mixture of 5-aminosalicylate is acidified to the pH value between the 5.0-6.0.
4. the method for preparing 5-aminosalicylic acid according to claim 1; It is characterized in that, carry out abundant gas phase carboxylation reaction, after generation contains the reaction mixture of 5-aminosalicylate at said carbonic acid gas and chlorination 1-butyl-3-Methylimidazole; Cool off this autoclave; Temperature in this autoclave is quickly fallen to below 80 ℃, discharge the dioxide gas in this autoclave simultaneously, treat to open after dioxide gas is put only the kettle cover of this autoclave; Carry out then that said this contains the reaction mixture of 5-aminosalicylate with water dissolution, obtain the solution step of this reaction mixture that contains 5-aminosalicylate.
5. according to claim 1 or the 4 described methods that prepare 5-aminosalicylic acid, it is characterized in that spinning goes out the 5-aminosalicylic acid solid from said souring soln; Dry 5-aminosalicylic acid solid 10-14 hour obtains 5-aminosalicylic acid black xln; 5-aminosalicylic acid black xln was placed the dry 10-14 of vacuum drying oven hour; Dried 5-aminosalicylic acid black xln is dissolved in the solution of hydrochloric acid and water composition; Hydrochloric acid is 1 to 3 with the volume ratio of water; Stirring heating is dissolved 5-aminosalicylic acid black xln fully, adds proper amount of active carbon in the solution and boils 8-12 minute, removes by filter gac then; Filtrating uses 30%NaOH solution adjusting pH value to be 5-6, separates out colourless 5-aminosalicylic acid solid; Cooling contains colourless 5-aminosalicylic acid solid filtrating; Spinning goes out the 5-aminosalicylic acid solid from filtrating; The 5-aminosalicylic acid solid that spinning is gone out about 90 ℃-110 ℃ dry 10-14 hour obtains having a little grayish white crystals 5-aminosalicylic acid.
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| CN109180513B (en) * | 2018-08-17 | 2021-02-09 | 浙江恒康药业股份有限公司 | Post-treatment process of mesalazine crude product |
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Application publication date: 20121017 |