CN101817758B - Preparation method of L-valine nitrate - Google Patents
Preparation method of L-valine nitrate Download PDFInfo
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- CN101817758B CN101817758B CN 201010170380 CN201010170380A CN101817758B CN 101817758 B CN101817758 B CN 101817758B CN 201010170380 CN201010170380 CN 201010170380 CN 201010170380 A CN201010170380 A CN 201010170380A CN 101817758 B CN101817758 B CN 101817758B
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- nitric acid
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- xie ansuan
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Abstract
The invention discloses a preparation method of L-valine nitrate, comprising the following steps of: adding L-valine into purified water under the normal temperature, evenly stirring and then adding nitric acid, wherein the mol ratio of the L-valine to the nitric acid is 1:1-1.1, and the weight ratio of the L-valine to the water of 1:0.4; gradually clarifying the solution at the reaction temperature of 40 to 70 DEG C and regulating the pH value of the solution to be 1 to 2 by using the nitric acid; cooling the clarified solution to 10 to 25 DEG C; carrying out solid-liquid separation on precipitated crystals; flushing the crystals and then drying at 60 to 85 DEG C to obtain an L-valine nitrate finished product; taking liquid subjected to the solid-liquid separation as a mother solution, and continuously recycling. In the preparation method of the L-valine nitrate, the food-grade L-valine and chemical reagent-grade-nitric acid are adopted to react, therefore, the reaction conditions are mild, the process is reasonable, simple and convenient, and the product has good quality and high purity up to more than 99 percent; in addition, the crystallized mother solution can be continuously recycled in the production, therefore, the invention has the yield coefficient up to more than 98 percent and is suitable for industrial large production.
Description
Technical field
The invention belongs to the preparation method of a seed amino acid nitrate, specifically is a kind of good product quality, yield height, the preparation method of L-valine nitrate that cost is low.
Background technology
Amino acid is the base substance that constitutes the Animal nutrition desired protein.General people self generate or can obtain to satisfy by food each seed amino acid of somagenic need.But under the special situation as under sick, the injured or large amount of exercise situation of taking exercise, in order to recover the balance of various metabolism in the body, strengthening immunity and the sportsmen increase muscle strength that regains one's strength as early as possible just needs extra each seed amino acid that replenishes.
L-Xie Ansuan (Valine) is wherein a kind of in 20 kinds of Argine Monohydrochlorides.Chemical name is: L-2-amino-3 Methylbutanoic acid.From the viewpoint of trophology, the L-Xie Ansuan is one of eight kinds of necessary amino acid of needed by human body nutrition.
The L-Xie Ansuan acts on corpus luteum, mammary gland and ovary.Experiment confirm is when Xie Ansuan is not enough, and the central nervous system in rat function can get muddled, ataxia and trembling of limbs occurs.By the anatomical slice cerebral tissue, discovery has rubrum cytopathy phenomenon, the liver cirrhosis end-stage patients are because of hepatic disorder, easily form hyperinsulinemia, cause branched-chain amino acid minimizing in the blood, the ratio of branched-chain amino acid and die aromatischen Aminosaeuren is down to 1.0～1.5 by normal people's 3.0～3.5, so the diseases such as injection for treating liver failure of branched-chain amino acids such as L-Xie Ansuan commonly used.In addition, it also can be used as the therapeutical agent of accelerating wound healing.Be mainly used in amino acid transfusion at present, make immune antibiotic, in the treatment of hemato encephalic barrier, hepatic coma, chronic liver cirrhosis, renal failure.Septicemia, diabetes, surgical wound healing, tumour patient nutritional support there is application.
Because amidates is transformed into amino acid at last through conversions such as oxydase in vivo, is absorbed by health easily.So present a lot of amino acid is all made amidates and taken, as L-Xie Ansuan salts such as L-valine methyl ester hydrochloride, L-Xie Ansuan carbethoxy hydrochloride are domestic manufacturer production arranged.The U.S. parties concerned discover that amino acid whose nitrate more is conducive to the amino acid absorption in vivo recently, therefore the L-Xie Ansuan are made into the L-valine nitrate, with the easier L-Xie Ansuan that changes into, are absorbed by health.Dosage was littler when therefore it used, and oral absorption efficient is higher.But the producer that does not also have suitability for industrialized production L-valine nitrate product at present in the world.
Summary of the invention
The present invention for the problem that solves the large-scale production of L-valine nitrate provide a kind of can suitability for industrialized production and yield height, product purity height, the preparation method of the L-valine nitrate that cost is low.
The technical solution used in the present invention is: a kind of preparation method of L-valine nitrate: 1. under the normal temperature L-Xie Ansuan is joined in the purified water, stir, add nitric acid again, the mol ratio of L-Xie Ansuan and nitric acid is 1: 1～1.1, and the weight ratio of L-Xie Ansuan and purified water is 1: 0.4; Temperature of reaction is at 40 ℃～70 ℃, and solution is clarified gradually, is 1～2 with nitric acid regulator solution pH; Be cooled to 10 ℃～25 ℃ after the solution clarification, solid-liquid separation is carried out in the crystallization of separating out; Crystallisate flushing back is in 60 ℃～85 ℃ dry L-valine nitrate finished products that get, and the liquid after the solid-liquid separation is that mother liquor continues to recycle; 2. in the mother liquor that under the normal temperature 1. L-Xie Ansuan adding step is produced, stir, add nitric acid again, the mol ratio of L-Xie Ansuan and nitric acid is 1: 1, and the weight ratio of L-Xie Ansuan and mother liquor is 1: 0.4; Temperature of reaction is at 40 ℃～70 ℃, and solution is clarified gradually, is 1～2 with nitric acid regulator solution pH, is cooled to 10 ℃～25 ℃ after the solution clarification, and solid-liquid separation is carried out in the crystallization of separating out; Crystallisate flushing back is in 60 ℃～85 ℃ dry L-valine nitrate finished products that get, and the liquid after the separation is that mother liquor continues to recycle repeatedly.
Preparation method of the present invention is: 1. under the normal temperature L-Xie Ansuan is added in the purified water, stir, add nitric acid again; The mol ratio of L-Xie Ansuan and nitric acid is 1: 1, and the weight ratio of L-Xie Ansuan and purified water is 1: 0.4; Temperature of reaction is at 55 ℃ ± 5 ℃, and solution is clarified gradually, is 1～2 with nitric acid regulator solution pH, is cooled to 20 ℃ ± 2 ℃ after the solution clarification, and solid-liquid separation is carried out in the crystallization of separating out; Crystallisate flushing back is in 80 ℃ of dry L-valine nitrate finished products that get; Liquid after the solid-liquid separation is that mother liquor continues to recycle; 2. under the normal temperature L-Xie Ansuan is added in the mother liquor, stir, add nitric acid again, the mol ratio of L-Xie Ansuan and nitric acid is 1: 1, and the weight ratio of L-Xie Ansuan and mother liquor is 1: 0.4; Temperature of reaction is at 55 ℃ ± 5 ℃, and solution is clarified gradually, is 2 with nitric acid regulator solution pH, is cooled to 20 ℃ ± 2 ℃ after the solution clarification, and solid-liquid separation is carried out in the crystallization of separating out; Crystallisate flushing back is in 80 ℃ of dry L-valine nitrate finished products that get, and the liquid after the separation is that mother liquor continues to recycle repeatedly.
Advantage and positively effect that the present invention has are: the present invention adopts L-Xie Ansuan and nitric acid to react the reaction conditions gentleness under normal pressure.The starting material that the present invention adopts are the L-Xie Ansuan of food grade and the nitric acid of chemical reagent-grade, so the good product quality of producing just reaches more than 99% without recrystallization purity, have both guaranteed quality, have saved operation again, have improved production efficiency.The Recycling Mother Solution that produces when utilization of the present invention is produced is first used, and has improved yield, and product yield is reached more than 98%, has reduced cost.Preparation method of the present invention rationally, simply is fit to industrialized production.
Embodiment
The present invention is in order to guarantee the quality of L-valine nitrate, the L-Xie Ansuan of high-quality food grade and the nitric acid of chemical reagent-grade have been adopted, impurities is few in the raw material, and the L-valine nitrate good product quality that assurance is produced just reaches more than 99% without recrystallization purity.
Reaction of the present invention need add a certain amount of water, and water is deionized purified water, to guarantee the quality of product.The weight ratio of L-Xie Ansuan and water is 1: 0.4.
The mol ratio of L-Xie Ansuan and nitric acid should be 1: 1 among the present invention, but for the L-Xie Ansuan is reacted completely, nitric acid dosage should be more bigger than L-Xie Ansuan.Scope is between 1～1.1 mole.The concentration of nitric acid that the present invention adopts is 65～68%, for guarantee and the ratio of 1 mole of L-Xie Ansuan between 1 to 1.1 mole, the add-on of nitric acid can have certain variation with the concentration of nitric acid difference.
The reaction of Xie Ansuan and nitric acid is thermopositive reaction, so temperature is normal temperature when beginning to react, does not heat, and controls the adding speed of nitric acid simultaneously, can not be too fast, if speed is too fast, reaction is violent, and the untimely easy generation of dispelling the heat is acutely decomposed.So when adding nitric acid, will control temperature all the time, avoid temperature too high.But therefore the low temperature effect speed of response begins to improve temperature of reaction after adding nitric acid, general temperature is preferably in below 60 ℃ below 70 ℃, can guarantee speed of response, can guarantee the quality of product again.But also can when just beginning to drip nitric acid, control low temperature, control rate of addition and temperature subsequently, utilize the temperature of the heat reacting by heating solution of reaction generation, fast reaction speed.Temperature of reaction can not surpass 70 ℃, otherwise the L-Xie Ansuan can be damaged, and influences the yield of final product.Along with temperature raises, speed of response is accelerated, and solution is more and more clarified, and stirs all the time in this process, makes reactant distribution even, and reaction is accelerated.Reaction finishes to begin cooling when solution is clarified fully.
It is acid that product L-valine nitrate of the present invention is, pH should be 2, generally finish before measurement pH in reaction, if acidity is little, drip nitric acid, with the pH of nitric acid control solution 2, because the mol ratio of nitric acid is slightly larger than the L-Xie Ansuan when producing, if so the pH value allows, can not influence quality product between 2～1.
The present invention makes L-valine nitrate solid separation method without limits after reaction is finished, and the method that every suitable L-valine nitrate is separated out can be used.Adopt method of cooling among the embodiment, cooling temperature is 10 ℃～25 ℃.General cooling temperature is advisable at 20 ℃ ± 2 ℃.
Solid-liquid separation, drying, process of washing all are prior aries in the industry in the inventive method, and the method that is fit to the preparation of L-valine nitrate can be used.
The solvent that the present invention washes usefulness is ethanol, and its concentration is more than 95%, and what adopt among the embodiment is dehydrated alcohol flushing crystallisate.
The present invention to the method for drying without limits, the method for every suitable L-valine nitrate drying can be used, as moisture eliminator, spray method drying.No matter the temperature of which kind of method drying is generally 60 ℃～85 ℃, and temperature is lower than below 60 ℃, and product easily lumps.Surpass 85 ℃, the L-valine nitrate can decompose, and quality is affected.The present invention adopts 80 ℃ of temperature dryings.
Liquid after crystallisate separates is mother liquor, wherein also is dissolved with many L-valine nitrates.Yield has only about 30% when using purified water to produce first, but yield can reach nearly 100% when utilizing mother liquor to produce later on.Owing to contain more water in the mother liquor, so when using mother liquor to produce, nitric acid adds speed can suitably be accelerated, and has shortened the production time, has improved production efficiency.
For further understanding summary of the invention of the present invention, characteristics and effect, exemplify following examples now and be described in detail as follows:
Embodiment 1
Under the room temperature double centner L-Xie Ansuan is joined in 40 kilograms of purified water, stir, add 81 kilogram 68% nitric acid more while stirring, progressively be heated to 55 ℃ ± 5 ℃ after adding nitric acid.Along with temperature rising solution is progressively clarified, detection pH before reaction finishes is 2 with the pH of nitric acid regulator solution.Be cooled to 20 ℃ after solution is clarified fully immediately and produce crystallization, with centrifugal method fractional crystallization thing and mother liquor, crystallisate dries, dehydrated alcohol flushing crystallisate with crystallisate weight 10～20%, dry, namely get L-valine nitrate finished product after 80 ℃ of dryings, yield 30%.Mother liquor continues to recycle repeatedly after the centrifugation.
Embodiment 2
Under the room temperature double centner L-Xie Ansuan joined in about 40 kilograms of mother liquors that embodiment 1 produces, stir, add 81 kilogram 68% nitric acid again, progressively be heated to 45 ℃ ± 5 ℃ after adding nitric acid.Along with temperature raises, solution is progressively clarified, and detection pH before reaction finishes is 2 with the pH of nitric acid regulator solution.Be cooled to 15 ℃ after solution is clarified fully immediately and produce crystallization, with centrifugal method fractional crystallization thing and mother liquor, crystallisate dries, dehydrated alcohol flushing crystallisate with crystallisate weight 10～20%, dry, namely get L-valine nitrate finished product after 80 ℃ of dryings, yield nearly 100%.Mother liquor continues to recycle repeatedly
Embodiment 3
Double centner L-Xie Ansuan is joined in about 40 kilograms of mother liquors of embodiment 2 generations under the room temperature, the back that stirs adds 81 kilogram 68% nitric acid, and the limit adds the nitric acid limit stirs, and makes it to mix.Control nitric acid adds speed, makes solution temperature reach 40 ℃ gradually, does not need the outside to heat.Along with stirred solution is progressively clarified, detection pH before reaction finishes is 2 with the pH of nitric acid regulator solution.Be cooled to 10 ℃ after solution is clarified fully immediately and produce crystallization, with centrifugal method fractional crystallization thing and mother liquor, crystallisate dries, with the dehydrated alcohol flushing crystallisate of crystallisate weight 10～20%, dry back 80 ℃ and be drying to obtain L-valine nitrate finished product, yield nearly 100%.Mother liquor continues to recycle repeatedly.
Claims (2)
1. the preparation method of a L-valine nitrate, it is characterized in that: 1. under the normal temperature L-Xie Ansuan is joined in the purified water, stir, add nitric acid again, the mol ratio of L-Xie Ansuan and nitric acid is 1: 1～1.1, and the weight ratio of L-Xie Ansuan and water is 1: 0.4; Temperature of reaction is at 40 ℃～70 ℃, and solution is clarified gradually, and adjusting pH value of solution with nitric acid is 1～2; Be cooled to 10 ℃～25 ℃ after the solution clarification, solid-liquid separation is carried out in the crystallization of separating out; Crystallisate flushing back is in 60 ℃～85 ℃ dry L-valine nitrate finished products that get, and the liquid after the solid-liquid separation is that mother liquor continues to recycle; 2. in the mother liquor that under the normal temperature 1. L-Xie Ansuan adding step is produced, stir, add nitric acid again, the mol ratio of L-Xie Ansuan and nitric acid is 1: 1～1.1, and the weight ratio of L-Xie Ansuan and mother liquor is 1: 0.4; Temperature of reaction is at 40 ℃～70 ℃, and solution is clarified gradually, and adjusting pH value of solution with nitric acid is 1～2, is cooled to 10 ℃～25 ℃ after the solution clarification, and solid-liquid separation is carried out in the crystallization of separating out; Crystallisate flushing back is in 60 ℃～85 ℃ dry L-valine nitrate finished products that get, and the liquid after the separation is that mother liquor continues to recycle repeatedly.
2. the preparation method of L-valine nitrate according to claim 1 is characterized in that: 1. under the normal temperature L-Xie Ansuan is added in the purified water, stir, add nitric acid again; The mol ratio of L-Xie Ansuan and nitric acid is 1: 1, and the weight ratio of L-Xie Ansuan and water is 1: 0.4; Temperature of reaction is at 55 ℃ ± 5 ℃, and solution is clarified gradually, and adjusting pH value of solution with nitric acid is 2, is cooled to 20 ℃ ± 2 ℃ after the solution clarification, and solid-liquid separation is carried out in the crystallization of separating out; Crystallisate flushing back is in 80 ℃ of dry L-valine nitrate finished products that get; Liquid after the solid-liquid separation is that mother liquor continues to recycle; 2. in the mother liquor that under the normal temperature 1. L-Xie Ansuan adding step is produced, stir, add nitric acid again, the mol ratio of L-Xie Ansuan and nitric acid is 1: 1, and the weight ratio of L-Xie Ansuan and mother liquor is 1: 0.4; Temperature of reaction is at 55 ℃ ± 5 ℃, and solution is clarified gradually, and adjusting pH value of solution with nitric acid is 2, is cooled to 20 ℃ ± 2 ℃ after the solution clarification, and solid-liquid separation is carried out in the crystallization of separating out; Crystallisate flushing back is in 80 ℃ of dry L-valine nitrate finished products that get, and the liquid after the separation is that mother liquor continues to recycle repeatedly.
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| CN 201010170380 CN101817758B (en) | 2010-05-12 | 2010-05-12 | Preparation method of L-valine nitrate |
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| CN 201010170380 CN101817758B (en) | 2010-05-12 | 2010-05-12 | Preparation method of L-valine nitrate |
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| CN101817758B true CN101817758B (en) | 2013-07-10 |
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| CN103655532A (en) * | 2013-12-13 | 2014-03-26 | 天津天成制药有限公司 | Method for synthesizing branched chain amino acid nitrate |
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Non-Patent Citations (2)
| Title |
|---|
| Guo hong Tao,et al.New generation ionic liquids:cations derived from amino acids.《Chem.Commun》.2005,3562-3564. * |
| 陈来同等.氨基酸类生化产品制备技术.《生物化学产品制备技术1》.2003,146-147. * |
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