CN102675079A - Recovery method of aliphatic calcium alpha-keto acid - Google Patents
Recovery method of aliphatic calcium alpha-keto acid Download PDFInfo
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- CN102675079A CN102675079A CN2012100811248A CN201210081124A CN102675079A CN 102675079 A CN102675079 A CN 102675079A CN 2012100811248 A CN2012100811248 A CN 2012100811248A CN 201210081124 A CN201210081124 A CN 201210081124A CN 102675079 A CN102675079 A CN 102675079A
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- calcium
- picrolonate
- recovery method
- keto acid
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Abstract
The invention relates to a recovery method of aliphatic calcium alpha-keto acid. The recovery method of aliphatic calcium alpha-keto acid includes acidifying productive mother liquid of low-level aliphatic calcium alpha-keto acid, and converting the calcium alpha-keto acid into corresponding alpha-keto acid; performing extraction and concentration by organic solvents such as methyl tertiary butyl ether, ethyl acetate or diethyl ether to obtain alpha-keto acid; and finally allowing the alpha-keto acid to react with calcium chloride under partially neutral condition to generate salt to obtain calcium alpha-keto acid. Therefore, the calcium alpha-keto acid in the mother liquor is recovered, product yield is increased, emission of COD (chemical oxygen demand) is reduced effectively, and economic benefit and social benefit are increased.
Description
Technical field
The present invention relates to bulk drug synthetic technical field, be specifically related to the recovery method of alpha-calcium picrolonate.
Technical background
Alpha-ketoacid is one type of organic acid that has vital role in vivo, in amino acid metabolism and the process of keeping redox state, plays a central role.Medically alpha-ketoacid the disease that is reused in the treatment chronic renal failure; It utilizes for the patient through the transamination synth essential amino acid of enzyme in vivo; When not increasing the kidney burden, improve the patient nutritional status, mitigation symptoms, delay PD, also can reduce the number of times that the renal insufficiency patient uses dialysis treatment.
At present, as a kind of important product, alpha-ketoacid mainly exists with the form of its calcium salt on the market.The synthesis technique of commercially producing the aliphatics alpha-calcium picrolonate mainly is to be starting raw material with the glycolylurea, obtains midbody with corresponding alkanoic or alkanone condensation, obtains alpha-calcium picrolonate through steps such as hydrolysis, extraction, salifies.Wherein in the aqueous solution, carry out as the salify step 1.For example glycolylurea respectively with isobutyric aldehyde, butanone and acetone generation condensation reaction, just can obtain alpha-keto-leucine-calcium, α-ketone Isoleucine calcium and α-keto-valine calcium respectively through hydrolysis, salify etc. again.
The applicant finds that the aliphatics alpha-calcium picrolonate has certain dissolving in water.At 20 ℃, solubilized alpha-keto-leucine-calcium 2-3g, dissolving α-ketone Isoleucine calcium 3-4g, dissolving α-keto-valine calcium 5-6g in the 100ml water.Though low temperature crystallization can improve yield, have too much impurity and separate out, it is qualified to make that the product related substance is difficult for.So general alpha-calcium picrolonate Tc still has considerable product to exist in the mother liquor at 10-30 ℃ under this temperature condition,, not only caused waste but also increased environmental protection pressure if the mother liquor discharging then causes sewage effluent COD value higher.
Summary of the invention
The objective of the invention is in order to reclaim the aliphatics alpha-calcium picrolonate, especially the lower aliphatic alpha-calcium picrolonate is produced the alpha-calcium picrolonate product that contains in the mother liquor, thereby effectively reduces the discharging of COD, improves product yield, increases benefit.Compare and not extra increase raw material or varieties of reagent with the production technique of alpha-calcium picrolonate simultaneously, can form a systems engineering with it.The carbonatoms of said lower aliphatic alpha-calcium picrolonate is 4-6.
The invention is characterized in and may further comprise the steps:
A. under 0 ℃-60 ℃, will contain the mother liquor acidifying of alpha-calcium picrolonate with diluted acid.Activated carbon decolorizing, filtration.
B. under 0 ℃-50 ℃, filtrating extracts with extraction agent.Concentrating under reduced pressure extraction agent phase obtains alpha-ketoacid.Dilute with water obtains alpha-ketoacid solution again.
C. under 0 ℃-80 ℃, regulate alpha-ketoacid pH value of solution value 6-8, obtain alpha-calcium picrolonate with the calcium chloride solution reaction then with alkaline solution.
Preferred processing condition are following:
A. get the mother liquor that unit volume contains alpha-keto-leucine-calcium or α-ketone Isoleucine calcium or α-keto-valine calcium, the content of corresponding alpha-calcium picrolonate is at 1%-10% in the mother liquor.Sulfuric acid, hydrochloric acid or glacial acetic acid solution with 5%-50% are regulated pH value, the preferred 20%-50% of the concentration of diluted acid.The pH value is adjusted to 1-5, preferred 2-4.Controlled temperature is at 0 ℃-60 ℃, preferred 20 ℃-40 ℃.Add proper amount of active carbon decolouring 0.5-1 hour, filter.
B. under 0 ℃-50 ℃, preferred 20 ℃-40 ℃, filtrating is with 0.2-2 times of methyl tertbutyl
Ether, ETHYLE ACETATE or ether equal solvent extracted 0.5-1 hour.Phase-splitting keeps organic pressure of subtracting each other and concentrates, and obtains the oily alpha-ketoacid.Obtain alpha-ketoacid solution with being equivalent to alpha-ketoacid weight 1-10 water dilution doubly again, preferred 4-8 doubly.
C. under 0 ℃-80 ℃, preferred 30 ℃-60 ℃, regulate alpha-ketoacid pH value of solution value 6-8 with sodium hydroxide or the potassium hydroxide solution of 10%-30%.Within 1-3 hour, add the aqueous solution of calcium chloride then or contain the pure aqueous solution, wherein the mol ratio of contained alpha-calcium picrolonate is 1-1.05 in calcium chloride and the mother liquor: 1.Reduce to again below 20 ℃ and stirred 1-2 hour, filter or centrifugal, an amount of washing, get alpha-calcium picrolonate.Wherein, the concentration of preparation calcium chloride solution is 10%-30%, preferred 20%.
Adopt the present invention, corresponding alpha-calcium picrolonate productive rate can increase 10%-20%, and the total emission volumn of COD can reduce more than 50% in its mother liquor waste water, and on producing, can combine closely with the flow process of alpha-calcium picrolonate again, is convenient to management.So the present invention can reduce discharging protection environment, can improve yield again and increase output, has tangible economic and social benefit.
Unless otherwise indicated, per-cent of the present invention is mass percent.
Below in conjunction with specific examples the present invention is done further elaboration.
Embodiment
The recovery experiment one of embodiment 1 α-keto-valine calcium
A. get the mother liquor of 10L α-keto-valine calcium, wherein contain 6% of α-keto-valine calcium.About 40 ℃ of controlled temperature, stir, the dilute sulphuric acid with 30% is regulated the pH value to 3-4.Add the 30g gac, decoloured 30 minutes, filter.
B. filtrating is cooled to about 30 ℃, adds the 3L MTBE, fully stirs 30 minutes, leaves standstill phase-splitting.Keep organic phase, the control vacuum is concentrating under reduced pressure under-0.09MPa condition, till not having cut and coming out.Stir adding 1.2L water, get α-keto-valine solution.
C. above-mentioned solution is regulated pH value 7-8 with 20% sodium hydroxide solution, about 60 ℃ of controlled temperature, and the calcium chloride water of agitation and dropping 1250kg 20% added in 2 hours.There are a large amount of white solids to separate out, are cooled to 20 ℃ then and continue reaction 1 hour.Filter, with washing in right amount, vacuum-drying gets α-about 440g of keto-valine calcium.
The recovery experiment two of embodiment 2 α-keto-valine calcium
Be to adopt among the step a 20% Hydrogen chloride with embodiment 1 difference; Extracted 2 times with the equivalent MTBE among the step b, remerged organic phase and concentrate.Get α-about 460g of keto-valine calcium at last.
The recovery experiment one of embodiment 3 alpha-keto-leucine-calciums
A. get the mother liquor of 10L alpha-keto-leucine-calcium, wherein contain 3% of alpha-keto-leucine-calcium.About 40 ℃ of controlled temperature, stir, the dilute sulphuric acid with 30% is regulated the pH value to 3-4.Add the 30g gac, decoloured 30 minutes, filter.
B. filtrating is cooled to about 30 ℃, adds the 5L MTBE, fully stirs 30 minutes, leaves standstill phase-splitting.Keep organic phase, the control vacuum is concentrating under reduced pressure under-0.09MPa condition, till not having cut and coming out.Stir adding 1.5L water, get alpha-keto-leucine solution.
C. above-mentioned solution is regulated pH value 7-8 with 20% sodium hydroxide solution.The calcium chloride water of preparation 560g20% is sneaked into 40g methyl alcohol therein.About 60 ℃ of controlled temperature, in 2 hours, drip calcium chloride solution, have a large amount of white solids to separate out.Be cooled to 20 ℃ then and continue reaction 1 hour.Filter, with washing in right amount, vacuum-drying gets the about 220g of alpha-keto-leucine-calcium.
The recovery experiment two of embodiment 4 alpha-keto-leucine-calciums
Be that with embodiment 3 differences the pH value transfers to 2-3 among the step a; Extraction agent is selected ETHYLE ACETATE for use among the step b; Adopt 20% potassium hydroxide solution among the step c.Get the about 240g of alpha-keto-leucine-calcium at last.
The recovery experiment one of embodiment 5 α-ketone Isoleucine calcium
A. get the mother liquor of 10L α-ketone Isoleucine calcium, wherein contain 4% of α-ketone Isoleucine calcium.About 40 ℃ of controlled temperature, stir, the dilute sulphuric acid with 30% is regulated the pH value to 2-3.Add the 30g gac, decoloured 30 minutes, filter.
B. filtrating is cooled to about 30 ℃, adds the 5L MTBE, fully stirs 30 minutes, leaves standstill phase-splitting.Keep organic phase, the control vacuum is concentrating under reduced pressure under-0.09MPa condition, till not having cut and coming out.Stir adding 1.5L water, get α-ketone Isoleucine solution.
C. above-mentioned solution is regulated pH value 7-8 with 20% sodium hydroxide solution.About 60 ℃ of controlled temperature, the calcium chloride water of agitation and dropping 750g 20% added in 2 hours, had a large amount of white solids to separate out.Be cooled to 20 ℃ then and continue reaction 1 hour.Filter, with washing in right amount, vacuum-drying gets α-about 310g of ketone Isoleucine calcium.
The recovery experiment two of embodiment 6 α-ketone Isoleucine calcium
Compare difference with embodiment 5 and be to adopt among the step a 20% Glacial acetic acid min. 99.5; Adopt ether to make extraction agent among the step b, temperature of reaction is 20 ℃; The pH value transfers to 6-7 among the step c.Get α-about 285g of ketone Isoleucine calcium at last.
Claims (8)
1. the recovery method of an aliphatics alpha-calcium picrolonate is characterized in that may further comprise the steps:
A. under 0 ℃-60 ℃, will contain the mother liquor acidifying of alpha-calcium picrolonate, activated carbon decolorizing, filtration with diluted acid.
B. under 0 ℃-50 ℃, filtrating is with the extraction agent extraction, and concentrating under reduced pressure extraction agent phase obtains alpha-ketoacid.Dilute with water obtains alpha-ketoacid solution again.
C. under 0 ℃-80 ℃, regulate alpha-ketoacid pH value of solution value 6-8, obtain alpha-calcium picrolonate with the calcium chloride solution reaction then with alkaline solution.
2. the recovery method of aliphatics alpha-calcium picrolonate according to claim 1; The mother liquor that it is characterized in that the alpha-calcium picrolonate of indication among the step a is the aqueous solution of the different bright sour calcium of alpha-keto-leucine-calcium, α-ketone or α-keto-valine calcium, and the content of corresponding alpha-calcium picrolonate is between 1%-10% in the solution.
3. the recovery method of aliphatics alpha-calcium picrolonate according to claim 1 is characterized in that diluted acid used among the step a is the aqueous solution of sulfuric acid, hydrochloric acid or Glacial acetic acid min. 99.5.
4. the recovery method of aliphatics alpha-calcium picrolonate according to claim 1 is characterized in that the alpha-calcium picrolonate mother liquor need be acidified to pH value 1-5 among the step a.
5. the recovery method of aliphatics alpha-calcium picrolonate according to claim 1 is characterized in that extraction agent used among the step b is MTBE, ETHYLE ACETATE or ether.The amount of used extraction agent is 0.2-2 a times of mother liquor volume.
6. the recovery method of aliphatics alpha-calcium picrolonate according to claim 1 is characterized in that among the step b, and the water yield of dilution alpha-ketoacid is 1-10 a times of alpha-ketoacid weight.
7. the recovery method of aliphatics alpha-calcium picrolonate according to claim 1 is characterized in that among the step c that used alkaline solution is the aqueous solution of sodium hydroxide or Pottasium Hydroxide.
8. the recovery method of aliphatics alpha-calcium picrolonate according to claim 1 is characterized in that among the step c, and used calcium chloride solution is the aqueous solution of calcium chloride or the aqueous solution that contains alcohol.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019108809A3 (en) * | 2017-11-29 | 2020-03-26 | Hull Edgar L Jr | Alpha keto acid compositions for treating hypo-albuminemia |
| US11484579B2 (en) | 2017-11-29 | 2022-11-01 | Edgar L Hull | Vitamins and alpha keto acid compositions for use in a treatment program for chronic kidney disease patients |
Citations (3)
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|---|---|---|---|---|
| US4076745A (en) * | 1976-07-08 | 1978-02-28 | Syntex (U.S.A.) Inc. | Process for calcium salts α-ketocarboxylic acids |
| CN101607888A (en) * | 2009-07-23 | 2009-12-23 | 河北九派制药有限公司 | The preparation method of alpha-keto-leucine-calcium |
| CN101759553A (en) * | 2008-11-21 | 2010-06-30 | 扬子江药业集团北京海燕药业有限公司 | Method for preparing alpha-calcium picrolonate |
-
2012
- 2012-03-26 CN CN201210081124.8A patent/CN102675079B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4076745A (en) * | 1976-07-08 | 1978-02-28 | Syntex (U.S.A.) Inc. | Process for calcium salts α-ketocarboxylic acids |
| CN101759553A (en) * | 2008-11-21 | 2010-06-30 | 扬子江药业集团北京海燕药业有限公司 | Method for preparing alpha-calcium picrolonate |
| CN101607888A (en) * | 2009-07-23 | 2009-12-23 | 河北九派制药有限公司 | The preparation method of alpha-keto-leucine-calcium |
Non-Patent Citations (2)
| Title |
|---|
| 《中国硕士学位论文全文数据库》 20070415 丁威 海因法合成几种alpha-酮酸及alpha-酮酸盐 , * |
| 丁威: "海因法合成几种α-酮酸及α-酮酸盐", 《中国硕士学位论文全文数据库》, 15 April 2007 (2007-04-15) * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019108809A3 (en) * | 2017-11-29 | 2020-03-26 | Hull Edgar L Jr | Alpha keto acid compositions for treating hypo-albuminemia |
| US11253496B2 (en) | 2017-11-29 | 2022-02-22 | Edgar L. Hull | Alpha keto acid compositions for treating hypo-albuminemia |
| US11484579B2 (en) | 2017-11-29 | 2022-11-01 | Edgar L Hull | Vitamins and alpha keto acid compositions for use in a treatment program for chronic kidney disease patients |
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| CN102675079B (en) | 2014-07-02 |
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