CN102351805A - Method for preparing, separating and refining 5-amino-1H-tetrazol-1-ylacetic acid - Google Patents
Method for preparing, separating and refining 5-amino-1H-tetrazol-1-ylacetic acid Download PDFInfo
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Abstract
The invention discloses a method for preparing, separating and refining 5-amino-1H-tetrazol-1-ylacetic acid. The method comprises the following steps of: 1, adding 5-amino-1H-tetrazol, chloroacetic acid and an alkaline substance into a solvent in turn, and performing reflux reaction for 20 hours; performing acidification treatment on reaction liquid to make reaction liquid precipitate, and performing suction filtration, washing and drying to obtain a first part of crude product; evaporating filtrate until dryness, extracting and washing a solid by using an organic solvent for many times, and evaporating an organic phase until dryness to obtain a light yellow solid; dissolving the light yellow solid in water, discoloring by using active carbon, and evaporating filtrate until dryness to obtain a second part of crude product; and mixing the obtained crude products, and recrystallizing to obtain the product. The method has mild conditions and is easy and convenient to implement; and by optimizing reaction conditions and subsequent extraction and refining conditions, the product loss is greatly reduced, the yield and the purity are obviously improved and reach 82.5 percent and 96-99 percent, the production cost is greatly reduced and the economic benefit is obvious.
Description
Technical field
The present invention relates to preparation, segregation and the process for purification of a kind of 5-amino-1H-tetrazoleacetic acid, be specifically related to the preparation technology of the good 5-amino-1H-tetrazoleacetic acid of a kind of yield height and purity, belong to technical field of medicine synthesis.
Background technology
5-amino-1H-tetrazoleacetic acid, English name: 5-amino-1H-tetrazole-1-acetic acid, CAS number: [21743-62-4], molecular formula: C
3H
5N
5O
2, molecular weight: 143.11, white crystal, water-soluble, methyl alcohol, ethanol etc., fusing point: 212-213 ℃ (decomposition).Main as chemical reagent, medicine intermediate, material intermediate etc., of many uses, the market requirement increases year by year.
So far, the preparation method of 5-amino-1H-tetrazoleacetic acid only have one piece of bibliographical information (
J. Org. Chem. 1970,
35 (10)3978-3980); This method is under the sodium hydroxide effect; With 5-amino-1H-tetrazole and chloroacetate reaction; The acidifying that refluxes after 20 hours is spent the night, and separates out product, and yield only is 53.1%; And high performance liquid chromatography (HPLC) analyze to show that this product is mixed with a large amount of organic impuritys, and purity is lower than 80%.Its reaction equation is following:
Special needs to be pointed out is that this process recovery ratio is low, product purity is poor, big limitations this Products Development and application.Therefore, be badly in need of improving its manufacturing condition, improve the yield and the purity of 5-amino-1H-tetrazoleacetic acid, to meet the need of market.
Summary of the invention
The present invention is directed to the deficiency of above-mentioned background technical matters, preparation, segregation and the process for purification of a kind of 5-amino-1H-tetrazoleacetic acid is provided.Present method has not only been carried out deep optimization to original technology, and has improved the follow-up purification step of product, and the yield of product and purity all are greatly improved.
The present invention realizes through following technical scheme:
(1) 5-amino-1H-tetrazole, Mono Chloro Acetic Acid and alkaline matter are added in the solvent successively back flow reaction 20h;
(2) above-mentioned reaction solution is carried out acidification, make reaction solution separate out deposition, through suction filtration, washing, the drying part crude product of winning;
(3) with step (2) gained filtrating evaporate to dryness, add organic solvent extracting and wash repeatedly, merge organic phase, evaporate to dryness gets light yellow solid; Said organic solvent is alcohol, ketone or ester class;
(4) step (3) gained light yellow solid is soluble in water, use activated carbon decolorizing, filter, evaporate to dryness filtrate the second section crude product;
(5) the gained crude product is merged, recrystallization gets product.
In the above-mentioned steps (1), solvent for use is water, tetrahydrofuran (THF) or toluene, considers reaction yield, preferably water or tetrahydrofuran (THF); Used alkaline matter is sodium hydrogencarbonate, yellow soda ash or sodium methylate.In use, solvent and alkaline matter will be used and just can reach the purpose that improves yield and purity.Generally speaking, when alkaline matter was yellow soda ash or sodium hydrogencarbonate, used solvent can be water; When alkaline matter was sodium methylate, solvent can be tetrahydrofuran (THF) or toluene.Solvent only for reaction environment is provided, can regulate voluntarily by its consumption.
In the above-mentioned steps (1), 5-amino-1H-tetrazole: Mono Chloro Acetic Acid: the mol ratio of sodium hydrogencarbonate/sodium methylate is 1:1～2:2～5, and preferred molar ratio is 1:1～1.2:2～3; 5-amino-1H-tetrazole: Mono Chloro Acetic Acid: the mol ratio of yellow soda ash is 1:1～2:1～3, and preferred molar ratio is 1:1～1.2:1～1.5.
In the above-mentioned steps (2), the last handling process of the reaction solution difference because of solvent there are differences, when solvent was water, last handling process was: with the reaction solution cooling, add hydrochloric acid, regulate pH to 1～3 to separating out deposition; When solvent was tetrahydrofuran (THF) or toluene, last handling process was: with the reaction solution evaporate to dryness, the gained solid is made into the aqueous solution, regulates pH to 1～3 then to separating out deposition.
In the above-mentioned steps (3), said alcohol is C
1-C
4Alcohol, said ketone is acetone, butanone, said ester is an ethyl acetate.
In the above-mentioned steps (3), organic solvent adds in the solid, under 45～55 ℃ of water-baths, stirs 2h, solid is come together wash.
In the above-mentioned steps (4), under 100 ℃, decolour, the add-on of gac is 5～7% of a solid masses.
In the above-mentioned steps (5); Used recrystallization solvent is that water, volume ratio are the mixed solution or the ethyl acetate of dehydrated alcohol and the water of 2～4:1, and every 100g crude product uses mixed solution or 140～160ml ethyl acetate of 75～85ml water, 110～125ml dehydrated alcohol and water.
In the present invention, at first reaction process is optimized.Reaction is investigated experiment with the screening of alkali and is shown that yellow soda ash, sodium hydrogencarbonate or sodium methylate are better than triethylamine or sodium hydroxide as the effect of reacting with alkali, and its yield is significantly improved.
In addition, when choosing the medium that reacts required, also to consider the type of used alkaline matter; The particularly important is, through adjusting Mono Chloro Acetic Acid, reacting the material proportion with alkali and 5-amino-1H-tetrazole, obtained optimum response material proportion condition, product yield is apparently higher than bibliographical information.
Moreover, to yield of product and the not high shortcoming of purity, increased product separation, purification step, particularly wash the solid organic solvent through the screening collection, from filtrating, extract crude product to greatest extent, the yield of product is greatly improved; And carried out a large amount of experiments to recrystallization solvent, product gas purity is further improved.
The improvement of novel process; Not only from reaction system, extract product (yield can reach 82.5%) to greatest extent; And improved product purity (purity can reach 96～99%), and the production cost of 5-amino-1H-tetrazoleacetic acid is greatly reduced, application prospect is more wide.
Preparing method's mild condition of the present invention, easy and simple to handle, through to the purification in reaction conditions and later stage, the selection of purification condition, product loss is obviously reduced, yield and purity all are significantly improved, and greatly reduce production cost, and economic benefit is very significantly.
Embodiment
Through specific embodiment scheme of the present invention is further set forth below, should be understood that, following embodiment only plays the effect of explanation, does not limit the invention.
Embodiment 1
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 11.3 grams (0.12mol), water 30 grams successively, stir, slowly add yellow soda ash 15.9 grams (0.15 mol).Under reflux temperature, reacted 20 hours then.
Under the room temperature, add 15 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 8.9 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 4.3 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 11.8 grams, yield 82.5%, purity 99.0% (HPLC).
Embodiment 2
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 9.5 grams (0.1mol), water 30 grams successively, stir, slowly add yellow soda ash 10.6 grams (0.1 mol).Under reflux temperature, reacted 20 hours then.
Under the room temperature, add 10 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 8.9 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 4.1 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 11.7 grams, yield 81.8%, purity 96.0% (HPLC).
Embodiment 3
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 11.3 grams (0.12mol), water 30 grams successively, stir, slowly add yellow soda ash 15.9 grams (0.15 mol).Under reflux temperature, reacted 20 hours then.
Under the room temperature, add 15 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 8.8 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of dehydrated alcohols, 50
oC stirred in water bath 2 hours is crossed and is filtered the ethanol phase.Ethanol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 4.0 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 11.2 grams, yield 78.3%, purity 99.2% (HPLC).
Embodiment 4
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 11.3 grams (0.12mol), water 30 grams successively, stir, slowly add yellow soda ash 15.9 grams (0.15 mol).Under reflux temperature, reacted 20 hours then.
Under the room temperature, add 15 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 8.9 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous ethyl acetates, 50
oC stirred in water bath 2 hours is crossed and is filtered the ethyl acetate phase.Ethyl acetate merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 3.8 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 11.4 grams, yield 79.7%, purity 98.2% (HPLC).
Embodiment 5
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 11.3 grams (0.12mol), water 30 grams successively, stir, slowly add yellow soda ash 15.9 grams (0.15 mol).Under reflux temperature, reacted 20 hours then.
Under the room temperature, add 15 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 8.8 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 4.5 grams.
The thick product of two portions merges, and uses 11 ml water recrystallizations, gets white 5-amino-1H-tetrazoleacetic acid product 11.5 grams, yield 80.5%, purity 99.0% (HPLC).
Embodiment 6
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 11.3 grams (0.12mol), water 30 grams successively, stir, slowly add yellow soda ash 15.9 grams (0.15 mol).Under reflux temperature, reacted 20 hours then.
Under the room temperature, add 15 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 8.7 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of acetone, 50
oC stirred in water bath 2 hours is crossed and is filtered the acetone phase.Acetone merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 2.0 grams.
The thick product of two portions merges, and uses 17 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 8.8 grams, yield 61.4%, purity 98.0% (HPLC).
Embodiment 7
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 11.3 grams (0.12mol), water 30 grams successively, stir, slowly add yellow soda ash 15.9 grams (0.15 mol).Under reflux temperature, reacted 20 hours then.
Under the room temperature, add 15 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 9.0 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 4.3 grams.
The thick product of two portions merges, and uses 12 ml waters and 4 milliliters of ethanol mixed system recrystallizations, gets white 5-amino-1H-tetrazoleacetic acid product 10.9 grams, yield 76.5%, purity 98.5% (HPLC).
Embodiment 8
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 9.5 grams (0.1mol), water 30 grams successively, stir, slowly add sodium hydrogencarbonate 16.8 grams (0.2 mol).Under reflux temperature, reacted 20 hours then.
Under the room temperature, add 10 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 8.8 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 3.8 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 11.5 grams, yield 80.4%, purity 96.3% (HPLC).
Embodiment 9
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 11.3 grams (0.12mol), water 30 grams successively, stir, slowly add sodium hydrogencarbonate 25.2 grams (0.3 mol).Under reflux temperature, reacted 20 hours then.
Under the room temperature, add 15 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 9.1 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 4.3 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 11.4 grams, yield 79.6%, purity 98.9% (HPLC).
Embodiment 10
In reaction flask, add 150 milliliters of 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 9.5 grams (0.1mol), sodium methylate 10.8 grams (0.2 mol), tetrahydrofuran (THF) successively, under reflux temperature, reacted 20 hours.
The reaction solvent evaporate to dryness, add 60 ml waters then.
Under the room temperature, add 10 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 8.7 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 4.2 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 11.2 grams, yield 78.3%, purity 97.3% (HPLC).
Embodiment 11
In reaction flask, add 150 milliliters of 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 11.3 grams (0.12mol), sodium methylate 16.2 grams (0.3 mol), tetrahydrofuran (THF) successively, under reflux temperature, reacted 20 hours.
The reaction solvent evaporate to dryness, add 60 ml waters then.
Under the room temperature, add 15 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 8.8 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 4.3 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 11.6 grams, yield 81.1%, purity 97.0% (HPLC).
Comparative Examples 1
In reaction flask, add 150 milliliters of 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 9.5 grams (0.1mol), triethylamine 20.2 grams (0.2 mol), toluene successively, under reflux temperature, reacted 20 hours.
The reaction solvent evaporate to dryness, add 60 ml waters then.
Under the room temperature, add 10 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 6.3 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 3.0 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 7.8 grams, yield 54.5%, purity 96.7% (HPLC).
Comparative Examples 2
In reaction flask, add 5-amino-1H-tetrazole 8.5 grams (0.1mol), Mono Chloro Acetic Acid 9.5 grams (0.1mol) and water 30 grams successively; Slowly add sodium hydroxide solution (8 gram sodium hydroxide; 0.2mol, add 80 gram water dissolution), reaction is 20 hours under reflux temperature.
The reaction solvent evaporate to dryness, add 60 ml waters then.
Under the room temperature, add 10 milliliters of concentrated hydrochloric acid acidifyings, separate out deposition, suction filtration, drying obtains thick product 5.3 grams of part.
The filtrating evaporate to dryness, get the off-white color solid, successively add three batches of 60 milliliters of anhydrous methanols, 50
oC stirred in water bath 2 hours is crossed and is filtered the methyl alcohol phase.Methyl alcohol merges mutually, and evaporate to dryness gets light yellow solid, adds entry and gac (5%), and 100 ℃ are stirred decolouring 30 minutes, filters, and the filtrating evaporate to dryness gets the second section crude product, weighs 2.3 grams.
The thick product of two portions merges, and uses 20 milliliters of re-crystallizing in ethyl acetate, gets white 5-amino-1H-tetrazoleacetic acid product 7.6 grams, yield 52.8%, HPLC content 78.4%.
Can find out that from top embodiment technological method of the present invention has improved the productive rate and the purity of 5-amino-1H-tetrazoleacetic acid greatly, helps industrialized production more.
Claims (10)
1. preparation, segregation and the process for purification of 5-amino-1H-tetrazoleacetic acid is characterized in that may further comprise the steps:
(1) 5-amino-1H-tetrazole, Mono Chloro Acetic Acid and alkaline matter are added in the solvent successively back flow reaction 20h;
(2) above-mentioned reaction solution is carried out acidification, make reaction solution separate out deposition, through suction filtration, washing, the drying part crude product of winning;
(3) with the filtrating evaporate to dryness of step (2), the gained solid with an organic solvent comes together and washes repeatedly, merges organic phase, and evaporate to dryness gets light yellow solid; Said organic solvent is alcohol, ketone or ester class;
(4) step (3) gained light yellow solid is soluble in water, use activated carbon decolorizing, filter, evaporate to dryness filtrate the second section crude product;
(5) the gained crude product is merged, recrystallization gets product.
2. preparation according to claim 1, segregation and process for purification is characterized in that: in the step (1), said solvent is water, tetrahydrofuran (THF) or toluene.
3. preparation according to claim 2, segregation and process for purification is characterized in that: in the step (1), said solvent is water or tetrahydrofuran (THF).
4. preparation according to claim 1, segregation and process for purification is characterized in that: in the step (1), said alkaline matter is sodium hydrogencarbonate, yellow soda ash or sodium methylate; 5-amino-1H-tetrazole: Mono Chloro Acetic Acid: the mol ratio of sodium hydrogencarbonate/sodium methylate is 1:1～2:2～5; 5-amino-1H-tetrazole: Mono Chloro Acetic Acid: the mol ratio of yellow soda ash is 1:1～2:1～3.
5. preparation according to claim 4, segregation and process for purification is characterized in that: in the step (1), 5-amino-1H-tetrazole: Mono Chloro Acetic Acid: the mol ratio of sodium hydrogencarbonate/sodium methylate is 1:1～1.2:2～3; 5-amino-1H-tetrazole: Mono Chloro Acetic Acid: the mol ratio of yellow soda ash is 1:1～1.2:1～1.5.
6. preparation according to claim 2, segregation and process for purification is characterized in that: when solvent was water in the step (1), reaction afterreaction liquid acidification process was: with the reaction solution cooling, add hydrochloric acid, regulate pH to 1～3, make reaction solution separate out deposition; When solvent was tetrahydrofuran (THF) or toluene in the step (1), reaction afterreaction liquid acidification process is: with the reaction solution solvent evaporated, the gained solid was made into the aqueous solution, adds hydrochloric acid then, regulates pH to 1～3, makes reaction solution separate out deposition.
7. preparation according to claim 1, segregation and process for purification is characterized in that: in the step (3), said alcohol is C
1-C
4Alcohol, said ketone is acetone or butanone, said ester is an ethyl acetate.
8. preparation according to claim 1, segregation and process for purification is characterized in that: in the step (3), organic solvent adds in the solid, under 45～55 ℃ of water-baths, stirs 2h, solid is come together wash.
9. preparation according to claim 1, segregation and process for purification is characterized in that: in the step (4), under 100 ℃, decolour, the add-on of gac is 5～7% of a solid masses.
10. preparation according to claim 1, segregation and process for purification; It is characterized in that: in the step (5); Used recrystallization solvent is that water, volume ratio are the mixed solution or the ethyl acetate of dehydrated alcohol and the water of 2～4:1, and every 100g crude product uses mixed solution or 140～160ml ethyl acetate of 75～85ml water, 110～125ml dehydrated alcohol and water.
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| CN111393382A (en) * | 2020-04-03 | 2020-07-10 | 杭州盛弗泰新材料科技有限公司 | Preparation method of 1-tetrazole acetate |
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Assignee: Jinan IFT Science & Technology Co., Ltd. Assignor: Chemical Inst., Shandong Prov. Contract record no.: 2012370000145 Denomination of invention: Method for preparing, separating and refining 5-amino-1H-tetrazol-1-ylacetic acid License type: Exclusive License Open date: 20120215 Record date: 20120504 |
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