CN104803949A - Method for preparing high-purity 4-hydroxyethyl piperazine ethane sulfonic acid - Google Patents
Method for preparing high-purity 4-hydroxyethyl piperazine ethane sulfonic acid Download PDFInfo
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- CN104803949A CN104803949A CN201510253865.3A CN201510253865A CN104803949A CN 104803949 A CN104803949 A CN 104803949A CN 201510253865 A CN201510253865 A CN 201510253865A CN 104803949 A CN104803949 A CN 104803949A
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- hydroxyethyl piperazine
- ethanesulfonic acid
- piperazine ethanesulfonic
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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Abstract
The invention belongs to the technical field of organic matter preparation, and particularly relates to a method for preparing high-purity 4-hydroxyethyl piperazine ethane sulfonic acid. The method comprises the following steps: carrying out addition reaction on vinylsulfonic acid or vinyl sulfonate and N-hydroxyethyl piperazine to prepare 4-hydroxyethylpiperazine ethane sulfonate; converting the 4-hydroxyethylpiperazine ethane sulfonate into 4-hydroxyethylpiperazine ethane sulfonic acid and corresponding salts of an acidifier by adopting the acidifier, thus obtaining acidifying mother liquor; then crystallizing to remove the corresponding salts of the acidifier to obtain processed acidifying mother liquor; adding soluble barium salt or calcium salt to the processed acidifying mother liquor to remove residual sulfate radicals, and carrying out evaporative concentration to obtain a primary purified product of the 4-hydroxyethylpiperazine ethane sulfonic acid; finally, washing the primary purified product by adopting small molecular weight alcohol and drying to obtain the high-purity 4-hydroxyethylpiperazine ethane sulfonic acid. The 4-hydroxyethylpiperazine ethane sulfonic acid prepared by the method disclosed by the invention is high in purity, simple and convenient in operation process, environment-friendly in production process, low in purification cost, high in yield and suitable for industrial batch production.
Description
Technical field
The invention belongs to technical field of organic matter preparation, particularly a kind of preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid.
Background technology
4-hydroxyethyl piperazine ethanesulfonic acid (HEPES) is a kind of hydrogen ion buffer reagent, and it has good surge capability in the pH value range of 6.8-8.2, the long period can control constant pH.Working concentration is about 10-50mmol/L, and general nutrient solution includes 20mmol/L HEPES can have good surge capability.
HEPES can be used for cell culture fluid, as application number be the patent of CN00109662.1, application number is that the patent of CN201010610401.0 adopts HEPES as the composition of cell culture fluid, effectively obtains a kind of simple, stability is high, culture effect is good cell culture system; HEPES also can be used for buffered soln, and the patent being CN201210171396.7 as application number adopts HEPES as the damping fluid detecting hypochlorite, serves good shock absorption.
Also find no the synthetic method that HEPES recorded by document at present.
In addition, the common method of separation and purification HEPES be first by the sodium salt of HEPES, sylvite or ammonium salt after acidifying transforms, on piperazine ring in recycling HEPES molecular structure the weakly alkaline of nitrogen-atoms by HEPES ion-exchange on Zeo-karb, then sulfate radical and sodium ion is removed with a large amount of water, and then with ammoniacal liquor, HEPES is exchanged, obtains HEPES finally by neutralization, concentrated, crystallization.The subject matter that the method exists is: produce a large amount of reluctant brine wastes in (1) production process, environmental pollution is serious; (2) ion exchange resin needs repeated regeneration, consumes a large amount of bronsted lowry acids and bases bronsted lowries; (3) obtain product purity not high enough, also need to do further isolation and purification; (4) the purifying amount of unit mass ion exchange resin is lower, and the life-span is shorter, and thus cost is high.
Summary of the invention
The object of this invention is to provide a kind of preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid, not only obtained HEPES purity is high, and purifying cost is low, technique simple, easy handling, pollution-free.
The preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid of the present invention, comprises the following steps:
(1) preparation of 4-hydroxyethyl piperazine ethanesulfonic acid salt: vinyl sulfonic acid or vinylsulfonate and N-hydroxyethyl piperazine are carried out addition reaction, obtained 4-hydroxyethyl piperazine ethanesulfonic acid salt;
(2) acidifying: adopt souring agent, 4-hydroxyethyl piperazine ethanesulfonic acid salt is converted into the salt of 4-hydroxyethyl piperazine ethanesulfonic acid and respective acids agent, obtains acidified mother liquor;
(3) crystallization desalination: the salt that acidified mother liquor removes respective acids agent through crystallization is obtained the acidified mother liquor after processing;
(4) sulfate radical removes: in the acidified mother liquor after process, adds the sulfate radical of soluble barium salt or calcium salt removing remnants, obtains the elementary purified product of 4-hydroxyethyl piperazine ethanesulfonic acid through evaporation concentration;
(5) purifying is washed: adopt small-molecular-weight alcohol to wash elementary purified product, drying obtains high purity 4-hydroxyethyl piperazine ethanesulfonic acid.
The reaction equation preparing HEPES in the present invention is as follows:
(1) N-hydroxyethyl piperazine and sodium vinyl sulfonate, vinyl sulfonic acid potassium or vinyl sulfonic acid ammonium generation addition reaction, its reaction equation is as shown in (I);
(2) 4-hydroxyethyl piperazine ethanesulfonic acid salt is converted into HEPES through acidification reaction, and its reaction equation is as shown in (II).
N-hydroxyethyl piperazine vinylsulfonate HEPES salt
M＝K、Na、NH
4
M=K, Na or NH
4
The feed ethylene base sulfonate of synthesis HEPES can contain a certain amount of sodium sulfate or potassium sulfate usually.The raw material of synthesis HEPES can also adopt vinyl sulfonic acid, but needs under the existence of potassium hydroxide, sodium hydroxide, ammonium hydroxide or ammoniacal liquor, carries out addition reaction.
In addition, in synthesis technique, when adopting the feed ratio of vinylsulfonate and N-hydroxyethyl piperazine equimolar amount, reaction is difficult to the carrying out of 100%, causes in reacted product containing unconverted vinylsulfonate and N-hydroxyethyl piperazine.In order to improve the utilization ratio of raw material, excessive vinylsulfonate can be adopted, but this also can cause in reacted product containing unconverted raw material.No matter be N-hydroxyethyl piperazine, vinyl sulfonic acid and salt thereof, or HEPES and salt thereof all have good water-soluble, thus make the isolation and purification of product very difficult.
The present invention is specific as follows:
(1) preparation of HEPES salt:
First vinylsulfonate is mixed with the certain density aqueous solution, then adds N-hydroxyethyl piperazine and carry out addition reaction, obtain the reaction mother liquor containing 4-hydroxyethyl piperazine ethanesulfonic acid salt.When adopting vinyl sulfonic acid to be raw material, addition reaction needs to carry out in the basic conditions, and preferred alkali comprises potassium hydroxide, sodium hydroxide, ammonium hydroxide and ammoniacal liquor etc.
The mol ratio of preferred vinylsulfonate and N-hydroxyethyl piperazine is 1.00 ~ 1.15:1.
Suitable temperature of reaction is 40 ~ 120 DEG C, reaction times 2 ~ 6h.Most preferred temperature of reaction is 60 ~ 110 DEG C.
Preferred vinylsulfonate is sodium vinyl sulfonate, vinyl sulfonic acid potassium or vinyl sulfonic acid ammonium.
(2) acidifying:
Described souring agent is the strong acid that pKa is less than 4.5, comprises sulfuric acid, hydrochloric acid, formic acid and oxalic acid, preferably sulfuric acid and oxalic acid.
The object of acidifying is converted into HEPES by reacting by N-hydroxyethyl piperazine and sodium vinyl sulfonate, potassium or ammonium salt the HEPES salt obtained.PKa value due to HEPES is 4.5 ~ 7.65, therefore, wants HEPES salt to be converted into HEPES, must adopt acid stronger acid, i.e. the pKa value acid that is less than 4.5.Under identical stoichiometric relation, have and HEPES salt (sodium, potassium or ammonium) can be converted into HEPES more up hill and dale compared with the souring agent of low pka values.
When selecting souring agent, except the pKa value will considering souring agent, also to take into account the salt of generation and the easy separation of HEPES.Such as, when with sulfuric acid being souring agent, reaction generates HEPES and vitriol, and when being souring agent with hydrochloric acid, then generates HEPES and hydrochloride.Because vitriol and hydrochloride all have water-soluble preferably, comparatively difficult when this makes it be separated with HEPES.Utilize the change of solubleness along with temperature of vitriol, can obtain part by low temperature crystallization and remove; And utilize hydrochloride to be insoluble in the characteristic of concentrated hydrochloric acid, then by passing into the method for HCl in HEPES salt brine solution, hydrochloride can be removed.When taking organic acid as souring agent, the salt of generation is then soluble in the mother liquor after acidifying, but can by small molecular alcohol washing removing.
Described souring agent and 4-hydroxyethyl piperazine ethanesulfonic acid salt consumption mol ratio are 0.9 ~ 1.2:1, preferably 0.95 ~ 1.05:1.
Due to acidification reaction normally thermopositive reaction, therefore acidification reaction needs to carry out under lower temperature condition.Suitable souring temperature is 0 ~ 40 DEG C, acidification reaction time 1 ~ 2h.And keep being uniformly mixed fully.Too high temperature of reaction can cause product colourity darker.
(3) crystallization desalination:
Make the salt of souring agent by crystallization acidified mother liquor cooling, then remove after filtration.Suitable Tc is-20 ~ 10 DEG C, and preferably-10 ~ 5 DEG C, crystallization time is 0.5 ~ 1h.When taking sulfuric acid as souring agent, the salt of about 90% can be removed; When selecting hydrochloric acid or hydrogenchloride is souring agent, because the solubility with temperature change of hydrochloride in water generated is less, first reduction vaporization is needed to concentrate, and then the hydrochloride that decrease temperature crystalline removing is separated out; When taking organic acid as souring agent, decrease temperature crystalline remove portion organic acid salt again after also needing reduction vaporization concentrated, remainder then because of being soluble in small molecular alcohol, and is removed by recrystallization or washing.
(3) sulfate radical removes:
Still a certain amount of sulfate ion can be contained in the HEPES mother liquor that part is removed after sodium salt or sylvite.Feature that insoluble precipitates can effectively be removed to utilize soluble barium salt or calcium salt and sulfate ion to generate.Suitable soluble barium salt or calcium salt comprise bariumchloride, barium formate, barium acetate, hydrated barta, calcium chloride, calcium formiate, lime acetate, calcium hydroxide, and preferred precipitation agent is bariumchloride, barium acetate or hydrated barta.When removing sulfate radical, need first soluble barium salt or calcium salt to be mixed with the certain density aqueous solution, then according to the content of sulfate radical in HEPES masterbatch, add barium salt or the calcium salt soln of chemical reaction quantitative relation.Suitable barium salt or calcium salt feed postition are under fully stirring, and slowly join HEPES mother liquor in 0 ~ 40 DEG C, reinforced complete and stirring reaction more than 0.5 hour, are then filtered or centrifugal disgorging by mixed solution.The last concentrated obtained elementary purified product of 4-hydroxyethyl piperazine ethanesulfonic acid of HEPES solution will obtained again.
(5) purifying is washed:
May containing micro-4-hydroxyethyl piperazine ethanesulfonic acid sodium (HEPES-Na), 4-hydroxyethyl piperazine ethanesulfonic acid potassium (HEPES-K) or 4-hydroxyethyl piperazine ethanesulfonic acid ammonium (HEPES-NH in elementary purified product obtained above
4), vinylsulfonate or N-hydroxyethyl piperazine etc.Itself and the HEPES dissolubility difference in small molecular alcohol can be utilized to remove.
During washing purifying, add in small molecular alcohol by elementary for HEPES obtained above purified product, abundant agitator treating repeatedly; Then filtering separation, filter cake is the HEPES product after improving; Filtrate is reclaimed after small molecular alcohol through evaporation, returns acidizing process and applies mechanically.HEPES product sterling can reach 99.9%.
Suitable small molecular alcohol comprises at least one in methyl alcohol, ethanol, propyl alcohol; Also can be their aqueous solution certain density.Preferred small molecular alcohol is methyl alcohol and/or ethanol.
Beneficial effect of the present invention is as follows:
Not only purity is high for the 4-hydroxyethyl piperazine ethanesulfonic acid that the present invention obtains, operating procedure is easy, and purifying cost is low, technique is simple, easy handling, pollution-free.
Embodiment
Below in conjunction with embodiment, the invention will be further described.
Embodiment 1-5 is HEPES salt synthetic example.
Embodiment 1
By 131.5g N-hydroxyethyl piperazine, (purity is 99%, about 1mol) and the sodium vinylsulphonate solution (containing 1.05mol sodium vinyl sulfonate) of 30% (mass concentration) add in the 1000mL four-hole boiling flask of band return line, under fully stirring, carry out addition reaction; First react 1.0 hours at 60 DEG C, be then warming up to boiling reflux (about 100 ~ 120 DEG C, visual response liquid forms and changes) gradually, and continue reaction 2.0 hours; Then, cooling obtains the reaction mother liquor containing 4-hydroxyethyl piperazine ethanesulfonic acid sodium.Through efficient liquid phase chromatographic analysis, the productive rate calculating 4-hydroxyethyl piperazine ethanesulfonic acid sodium is 95.2%.
Embodiment 2
The sodium vinylsulphonate solution (containing 1.15mol sodium vinyl sulfonate) of 1mol N-hydroxyethyl piperazine and 35% (mass concentration) is added in the 1000mL four-hole boiling flask of band return line, under fully stirring, carry out addition reaction; First react 2.0 hours at 50 DEG C, then heat up boiling reflux gradually, and continue reaction 3.0 hours; Then, cooling obtains the reaction mother liquor containing 4-hydroxyethyl piperazine ethanesulfonic acid sodium.Through efficient liquid phase chromatographic analysis, the productive rate calculating 4-hydroxyethyl piperazine ethanesulfonic acid sodium is 96.4%.
Embodiment 3
The vinyl sulfonic acid aqueous solution (containing 1.00mol vinyl sulfonic acid) of 1mol N-hydroxyethyl piperazine and 30% (mass concentration) is added in the 1000mL four-hole boiling flask of band return line, then under fully stirring, aqueous sodium hydroxide solution (mass concentration is 30%, containing 1.1mol sodium hydroxide) is slowly added dropwise to; Then react 2.0 hours at 40 DEG C, then heat up boiling reflux gradually, and continue reaction 1.5 hours; Then, cooling obtains the reaction mother liquor containing 4-hydroxyethyl piperazine ethanesulfonic acid sodium.Through efficient liquid phase chromatographic analysis, the productive rate calculating 4-hydroxyethyl piperazine ethanesulfonic acid sodium is 87.7%.
Embodiment 4
The vinyl sulfonic acid aqueous solutions of potassium (containing 1.05mol vinyl sulfonic acid potassium) of 1mol N-hydroxyethyl piperazine and 40% (mass concentration) is added in the 1000mL four-hole boiling flask of band return line, under fully stirring, carry out addition reaction; First react 1.5 hours at 50 DEG C, then heat up boiling reflux gradually, and continue reaction 2.0 hours; Then, cooling obtains the reaction mother liquor containing 4-hydroxyethyl piperazine ethanesulfonic acid potassium.Through efficient liquid phase chromatographic analysis, the productive rate calculating 4-hydroxyethyl piperazine ethanesulfonic acid potassium is 95.1%.
Embodiment 5
The vinyl sulfonic acid aqueous ammonium (containing 1.10mol vinyl sulfonic acid ammonium) of 1mol N-hydroxyethyl piperazine and 25% (mass concentration) is added in the 1000mL four-hole boiling flask of band return line, under fully stirring, carry out addition reaction; First react 1.5 hours at 60 DEG C, then heat up boiling reflux gradually, and continue reaction 2.5 hours; Then, cooling obtains the reaction mother liquor containing 4-hydroxyethyl piperazine ethanesulfonic acid ammonium.Through efficient liquid phase chromatographic analysis, the productive rate calculating 4-hydroxyethyl piperazine ethanesulfonic acid ammonium is 89.4%.
Embodiment 6-12 is the specific embodiment of separation and purification HEPES.
Embodiment 6
By the mass concentration containing 0.5mol HEPES-Na be 40% reaction mother liquor be placed in 500mL beaker, under stirring, slowly drip the 23.5g vitriol oil (98wt%) in room temperature, then stir, under room temperature, acidifying 1 hour.Put into low temperature thermostat bath, cool to-10 DEG C, crystallisation by cooling 0.5 hour, suction filtration removing sodium sulfate.Filtrate is put into beaker, constantly stirs, slowly add 3.5g Ba (OH)
2, react 1 hour, the sulfate radical that removing is residual.Obtain filtrate through suction filtration after adding 5g activated carbon decolorizing, through rotary evaporation to anhydrous, obtain solid primary purified product.Solids is used respectively 500ml methanol wash 3 times, then through vacuum-drying, obtain high purity HEPES.
Embodiment 7
Be that the reaction mother liquor of 40wt% is placed in 500mL beaker by the mass concentration containing 0.5mol HEPES-Na, under stirring, under room temperature, slowly add 27.3g oxalic acid (99wt%), then stir, at 20 DEG C, acidifying 1 hour.Put into low temperature thermostat bath, cool to 10 DEG C, crystallisation by cooling 0.5 hour, the sodium oxalate that suction filtration removing is separated out.Filtrate is put into beaker, constantly stirs, slowly add 1.0g Ba (OH)
2, react 1 hour, removing sulfate radical.Obtain filtrate through suction filtration after adding 5g activated carbon decolorizing, through rotary evaporation to anhydrous, obtain solid primary purified product.Solid is used respectively 500ml washing with alcohol 3 times, then through vacuum-drying, obtain high purity HEPES.
Embodiment 8
The reaction mother liquor being 50wt% by the mass concentration containing 0.5mol HEPES-Na is placed in 500mL beaker, under stirring, under room temperature, slowly drips the dense HCl of 52.2.0g (37wt%), then stirs, at 25 DEG C, and acidifying 1.5 hours.Reduction vaporization concentrates, and puts into low temperature thermostat bath, cools to-12 DEG C, crystallisation by cooling 0.5 hour, suction filtration removing sodium-chlor.Filtrate is put into beaker, slowly adds 2.0g BaCl
2, react 1 hour, removing sulfate radical, passes into HCl under then constantly stirring, removing residue NaCl.Obtain filtrate through suction filtration after adding 5g activated carbon decolorizing, through rotary evaporation to anhydrous, obtain solid primary purified product.Solid is used respectively 500ml washing with alcohol 3 times, then through vacuum-drying, obtain high purity HEPES.
Embodiment 9
The reaction mother liquor being 35wt% by the mass concentration containing 0.5mol HEPES-K is placed in 500mL beaker, under stirring, slowly drips the 25.0g vitriol oil (98wt%), then stir under room temperature, at 40 DEG C, and acidifying 1 hour.Put into low temperature thermostat bath, cool to-20 DEG C, crystallisation by cooling 0.5 hour, suction filtration removing potassium sulfate.Filtrate is put into beaker, constantly stirs, slowly add 4.0g Ca (OH)
2, react 1 hour, the sulfate radical that removing is residual.Obtain filtrate through suction filtration after adding 5g activated carbon decolorizing, through rotary evaporation to anhydrous, obtain solid primary purified product.Solid is used respectively 500ml methanol wash 2 times, 500ml washing with alcohol once, then through vacuum-drying, obtains high purity HEPES.
Embodiment 10
Be that the reaction mother liquor of 40wt% is placed in 500mL beaker by the mass concentration containing 0.5mol HEPES-Na, under stirring, under room temperature, slowly drip 28.2g formic acid (85wt%), then fully stir, acidifying 2 hours at 15 DEG C.Reduction vaporization concentrates, and puts into low temperature thermostat bath, cools to-8 DEG C, crystallisation by cooling 0.5 hour, suction filtration removing sodium formiate.Filtrate is put into beaker, constantly stirs, slowly add 0.5g barium formate, react 1 hour, the sulfate radical that removing is residual.Obtain filtrate through suction filtration after adding 5g activated carbon decolorizing, through rotary evaporation to anhydrous, obtain solid primary purified product.Divided by solid and use 500ml methanol wash 2 times, 500ml washing with alcohol once, then through vacuum-drying, obtains high purity HEPES.
Embodiment 11
The reaction mother liquor containing 0.5mol HEPES-Na being 40wt% is placed in 500mL beaker, under stirring, under room temperature, slowly drips 23.9g oxalic acid (99wt%), then fully stir, acidifying 1 hour at 5 DEG C.Reduction vaporization concentrates, and puts into low temperature thermostat bath, cools to-12 DEG C, crystallisation by cooling 0.5 hour, suction filtration removing sodium oxalate.Filtrate is put into beaker, constantly stirs, slowly add 0.5g barium acetate, react 1 hour, the sulfate radical that removing is residual.Obtain filtrate through suction filtration after adding 5g activated carbon decolorizing, through rotary evaporation to anhydrous, obtain solid primary purified product.Solid is used respectively 500ml methanol wash 2 times, 500ml washing with alcohol once, then through vacuum-drying, obtains high purity HEPES.
Embodiment 12
Will containing 0.5mol HEPES-NH
4reaction mother liquor be placed in 500mL beaker, under stirring, slowly drip the 27.5g vitriol oil (98wt%) in room temperature, then stir, at 0 DEG C, acidifying 1 hour.Put into low temperature thermostat bath, cool to-15 DEG C, crystallisation by cooling 0.5 hour, suction filtration removing sodium sulfate.Filtrate is put into beaker, constantly stirs, slowly add 3.0gBa (OH)
2, react 1 hour, the sulfate radical that removing is residual.Obtain filtrate through suction filtration after adding 5g activated carbon decolorizing, through rotary evaporation to anhydrous, obtain solid primary purified product.Divided by solid and use 500ml methanol wash 2 times, 500ml washing with alcohol once, then through vacuum-drying, obtains high purity HEPES.
High purity HEPES is surveyed HEPES content, yield, pH value, sulfate ion and colourity respectively, the results are shown in Table 1.
The purity of table 1 HEPES, yield and quality index
In embodiment, the Product Quality Evaluation method of HEPES is as follows:
The purity detecting of HEPES adopts electropotential volumetry.
The yield of HEPES is calculated as follows
Wherein, m
0and m
1be respectively the quality of HEPES mother liquor quality and rear HEPES solids of purifying before purifying, g;
C
0for the mass percent of the HEPES salt in front HEPES masterbatch of purifying;
C
1for the purity of HEPES product after purifying, wt%;
238.3 is molecular weight of HEPES;
M
wit is the molecular weight of HEPES salt.
The pH value of HEPES sample measures the pH value adopting pH acidometer to measure the 5wt%HEPES aqueous solution and represents.
In HEPES sample, the content of sulfate radical adopts complexometric titration.
The colorimetric detection of HEPES adopts ultraviolet spectrophotometer method.The thick cuvette with 1cm at a wavelength of 280 nm, measures the absorbancy of the HEPES aqueous solution of 1mol/L concentration.
Claims (10)
1. a preparation method for high purity 4-hydroxyethyl piperazine ethanesulfonic acid, is characterized in that comprising the following steps:
(1) preparation of 4-hydroxyethyl piperazine ethanesulfonic acid salt: vinyl sulfonic acid or vinylsulfonate and N-hydroxyethyl piperazine are carried out addition reaction, obtained 4-hydroxyethyl piperazine ethanesulfonic acid salt;
(2) acidifying: adopt souring agent, 4-hydroxyethyl piperazine ethanesulfonic acid salt is converted into the salt of 4-hydroxyethyl piperazine ethanesulfonic acid and respective acids agent, obtains acidified mother liquor;
(3) crystallization desalination: the salt that acidified mother liquor removes respective acids agent through crystallization is obtained the acidified mother liquor after processing;
(4) sulfate radical removes: in the acidified mother liquor after process, adds the sulfate radical of soluble barium salt or calcium salt removing remnants, obtains the elementary purified product of 4-hydroxyethyl piperazine ethanesulfonic acid through evaporation concentration;
(5) purifying is washed: adopt small-molecular-weight alcohol to wash elementary purified product, drying obtains high purity 4-hydroxyethyl piperazine ethanesulfonic acid.
2. the preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid according to claim 1, is characterized in that: described vinylsulfonate is sodium vinyl sulfonate, vinyl sulfonic acid potassium or vinyl sulfonic acid ammonium.
3. the preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid according to claim 1, is characterized in that: the mol ratio of described vinylsulfonate and N-hydroxyethyl piperazine is 1.00 ~ 1.15:1.
4. the preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid according to claim 1, is characterized in that: the temperature of described addition reaction is 40 ~ 120 DEG C, reaction times 2 ~ 6h.
5. the preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid according to claim 1, is characterized in that: described souring agent is the strong acid that pKa is less than 4.5.
6. the preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid according to claim 5, is characterized in that: described souring agent comprises sulfuric acid, hydrochloric acid, formic acid and oxalic acid.
7. the preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid according to claim 1, is characterized in that: the mol ratio of described souring agent and 4-hydroxyethyl piperazine ethanesulfonic acid salt is 0.9 ~ 1.2:1; Described acidification reaction temperature is 0 ~ 40 DEG C, acidification reaction time 1 ~ 2h.
8. the preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid according to claim 1, is characterized in that: described Tc is-20 ~ 10 DEG C, and crystallization time is 0.5 ~ 1h.
9. the preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid according to claim 1, is characterized in that: described soluble barium salt comprises bariumchloride, barium formate, barium acetate, hydrated barta; Described soluble calcium salt comprises calcium chloride, calcium formiate, lime acetate, calcium hydroxide.
10. the preparation method of high purity 4-hydroxyethyl piperazine ethanesulfonic acid according to claim 1, is characterized in that: described small-molecular-weight alcohol is at least one in methyl alcohol, ethanol or propyl alcohol.
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|---|---|---|---|---|
| CN109836398A (en) * | 2017-11-27 | 2019-06-04 | 荆楚理工学院 | A kind of preparation method of two ethanesulfonic acid 1.5Na salt of special biological buffer-piperazine |
| CN109836361A (en) * | 2017-11-27 | 2019-06-04 | 荆楚理工学院 | A kind of preparation method of highly purified biogenic buffer HEPES-Na salt |
| CN110283144A (en) * | 2019-06-12 | 2019-09-27 | 山东星之联生物科技股份有限公司 | A kind of preparation method of morpholino b acid |
| CN110526883A (en) * | 2019-07-22 | 2019-12-03 | 苏州农业职业技术学院 | A method of it is pungent to extract bubble manaca from sugar apple seed |
| CN110683995A (en) * | 2019-09-17 | 2020-01-14 | 苏州亚科科技股份有限公司 | Piperazine ethanesulfonic acid derivative preparation method |
| CN114591266A (en) * | 2022-01-28 | 2022-06-07 | 苏州亚科科技股份有限公司 | Preparation process of compound containing sulfonic group |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060089509A1 (en) * | 2003-09-16 | 2006-04-27 | Carroll Glenn T | Preparation of substituted alkanesulfonates from 2-hydroxyalkanesulfonates |
-
2015
- 2015-05-19 CN CN201510253865.3A patent/CN104803949B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060089509A1 (en) * | 2003-09-16 | 2006-04-27 | Carroll Glenn T | Preparation of substituted alkanesulfonates from 2-hydroxyalkanesulfonates |
Non-Patent Citations (1)
| Title |
|---|
| 卞克建 等: "磺酸型生物缓冲剂的合成", 《化学试剂》 * |
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| CN110683995A (en) * | 2019-09-17 | 2020-01-14 | 苏州亚科科技股份有限公司 | Piperazine ethanesulfonic acid derivative preparation method |
| CN114591266A (en) * | 2022-01-28 | 2022-06-07 | 苏州亚科科技股份有限公司 | Preparation process of compound containing sulfonic group |
| WO2023142797A1 (en) * | 2022-01-28 | 2023-08-03 | 苏州亚科科技股份有限公司 | Preparation process for sulfonic acid-containing compound |
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