CN102219706B - Method for preparing acetyl tyrosine ethyl ester monohydrate and product of acetyl tyrosine ethyl ester monohydrate - Google Patents
Method for preparing acetyl tyrosine ethyl ester monohydrate and product of acetyl tyrosine ethyl ester monohydrate Download PDFInfo
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- -1 acetyl tyrosine ethyl ester monohydrate Chemical class 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- 239000000243 solution Substances 0.000 claims abstract description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 24
- CAHKINHBCWCHCF-UHFFFAOYSA-N N-acetyltyrosine Chemical compound CC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 CAHKINHBCWCHCF-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000001816 cooling Methods 0.000 claims abstract description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 12
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims abstract description 12
- 238000001035 drying Methods 0.000 claims abstract description 12
- 239000011259 mixed solution Substances 0.000 claims abstract description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 12
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000005917 acylation reaction Methods 0.000 claims abstract description 10
- 239000012736 aqueous medium Substances 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 24
- 238000002425 crystallisation Methods 0.000 claims description 17
- 238000009413 insulation Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 8
- 239000011707 mineral Substances 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 239000012141 concentrate Substances 0.000 claims description 6
- 238000010790 dilution Methods 0.000 claims description 6
- 239000012895 dilution Substances 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000013019 agitation Methods 0.000 claims description 5
- 238000005119 centrifugation Methods 0.000 claims description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- 230000006837 decompression Effects 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract 1
- 238000007865 diluting Methods 0.000 abstract 1
- 150000007522 mineralic acids Chemical class 0.000 abstract 1
- 229940024606 amino acid Drugs 0.000 description 17
- 235000001014 amino acid Nutrition 0.000 description 17
- 239000000543 intermediate Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 229960004756 ethanol Drugs 0.000 description 8
- 229960004441 tyrosine Drugs 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- CAHKINHBCWCHCF-JTQLQIEISA-N N-acetyl-L-tyrosine Chemical compound CC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CAHKINHBCWCHCF-JTQLQIEISA-N 0.000 description 4
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229960001682 n-acetyltyrosine Drugs 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108010064696 N,O-diacetylmuramidase Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000003064 anti-oxidating effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- GNTDGMZSJNCJKK-UHFFFAOYSA-N divanadium pentaoxide Chemical compound O=[V](=O)O[V](=O)=O GNTDGMZSJNCJKK-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 239000008396 flotation agent Substances 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229940056360 penicillin g Drugs 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- SKAWDTAMLOJQNK-UHFFFAOYSA-N 2-acetamido-3-(4-hydroxyphenyl)propanoic acid ethyl ester Chemical compound CCOC(=O)C(NC(C)=O)CC1=CC=C(O)C=C1 SKAWDTAMLOJQNK-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229940093740 amino acid and derivative Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- SKAWDTAMLOJQNK-LBPRGKRZSA-N ethyl N-acetyl-L-tyrosinate Chemical compound CCOC(=O)[C@@H](NC(C)=O)CC1=CC=C(O)C=C1 SKAWDTAMLOJQNK-LBPRGKRZSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 238000010094 polymer processing Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 229940001516 sodium nitrate Drugs 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- REZQBEBOWJAQKS-UHFFFAOYSA-N triacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO REZQBEBOWJAQKS-UHFFFAOYSA-N 0.000 description 1
- ZNRSXPDDVNZGEN-UHFFFAOYSA-K trisodium;chloride;sulfate Chemical compound [Na+].[Na+].[Na+].[Cl-].[O-]S([O-])(=O)=O ZNRSXPDDVNZGEN-UHFFFAOYSA-K 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
The invention discloses a method for preparing acetyl tyrosine ethyl ester monohydrate and a product of the acetyl tyrosine ethyl ester monohydrate, which aim to solve defects of the prior art. The method for preparing the acetyl tyrosine ethyl ester monohydrate, disclosed by the invention, has the advantages of low energy consumption, simplicity in operation, small environment pollution, high product yield, low production cost and suitability for mass production. The method disclosed by the invention comprises the following steps of: (1) carrying out acylation reaction on tyrosine and acetic anhydride in an alkaline aqueous medium; (2) adding inorganic acid to a solution treated in the step (1) so as to adjust pH value to be 0.5-3.5, and decompressing, concentrating, cooling and crystallizing to obtain an acetyltyrosine intermediate; (3) adding the acetyltyrosine intermediate obtained in the step (2) to the ethanol; and (4) adding thionyl chloride to a mixed solution obtained in the step (3) to react with the mixed solution, decompressing and concentrating in a vacuum way, diluting a concentrated reaction solution, and cooling, crystallizing, centrifugally separating and drying the reaction solution to obtain a finished product.
Description
Technical field
The present invention relates to amino acid derived products production technical field, particularly preparation method of a kind of acetyl tyrosine ethyl ester monohydrate and products thereof.
Background technology
The esterification of amino acid and derivative thereof is synthetic to be a recent studies on field that develops rapidly in recent years, they have application more and more widely at aspects such as medicine, chemical industry, food, agriculturals, useful as drug intermediate, foodstuff additive, cosmetics additive, mineral flotation agent and sterilization and disinfestation mixture etc., application prospect is very wide.
In medicine industry, amino acid ester useful as drug or pharmaceutical intermediate; The multiple amino acids ester can be used for the treatment of different illnesss directly or indirectly, can be antitumor as phenylalanine ester, halfcystine lauryl tool antibechic, reduce phlegm, anti-inflammatory, bring down a fever, curative effect such as pain relieving, can be used for treating respiratory system disease; Amino acid benzyl ester is easy to be penetrated into red corpuscle, can anti-anaemia during lower concentration; The multiple amino acids ester can reduce narcotic side effect as the composition of local anesthetic; Amino acid ester also has strong anti-oxidation, and body is delayed senility; Amino acid ester adds in penicillin G and the N,O-Diacetylmuramidase can make penicillin G and N,O-Diacetylmuramidase show strong antimicrbial power and bacteriolyze power.
In foodstuffs industry, amino acid ester replaces amino acid to be used for foodstuff additive, can change mouthfeel and the local flavor of food, increases the freshness date of food; Amino acid ester is used for food, has also increased its amino acid whose solvability and enzymatic specificity, is conducive to digestion and the absorption of body, plays the nutrition and health care dual function.
In cosmetic industry, amino acid whose multi-hydroxy ester, N-monoacylphosphine ester etc. all are used in hair care and the skin care product, outstanding emulsifying property, whipability and lyotropy have been shown, can make hair soft, bulk, gloss and pliable and tough, make skin smooth tender, amino acid can infiltrate body, integrates health and beauty; And for example cysteine ester can be used as the composition of cold hair-waving solution.
In chemical engineering industry, amino acid ester can be made into mineral flotation agent, for separating of NaCl and KCl; The hydrochloride of the high triacontanol ester of multiple amino acids and vitriol not only have good surfactivity effect, but also have characteristics such as suppressing ethylene content in the plant materials, antimicrobial, oxidation-resistance and softening fibre.
In pesticide industry, be that main component can be made various sterilization deinsectization mixture with the amino acid ester, they are very easy by daylight or by natural microbiological deterioration, do not stay residual hazard in soil, plant materials and in the fruit, its degradation material can also improve quality and the output of farm crop as the nutritive substance of farm crop.
The disclosure of the Invention of publication number CN1594283A the preparation method of a kind of N-acetyl-L-tyrosine; it be with tyrosine in water medium; utilize the acylating agent diacetyl oxide; in acetylize under 50～80 ℃ the temperature condition after 45～75 minutes; concentrating catches up with acid crystal to get the Acetyl tyrosine crude product; the crude product of drying is dissolved in 75～80 ℃ of hot water, decolouring, filters, concentrate post crystallization, dry.How to prepare N-acetyl-L-tyrosine though this method is mentioned, do not provide method then how to prepare acetyl tyrosine ethyl ester monohydrate.And the N-acetyl-L-tyrosine raw material consumption of this method preparation is big, and temperature requirement is higher, and the reaction times is longer, like this integral production cost height.
Patent, paper that the preparation method's of present research amino acid ester technology is at home and abroad delivered are still considerably less, in the majority as the above research that substantially all is limited on it is used of stating, by the understanding of industry and some external achievements in research are found, the main production technology that adopts all needs to carry out building-up reactions under extremely low temperature environment abroad, power consumption of polymer processing is big, environment and equipment requirements are higher, are unfavorable for large-scale industrialization preparation.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of acetyl tyrosine ethyl ester monohydrate, its energy consumption is low, simple to operate and environmental pollution is little, the product yield height, and production cost is low, is fit to large-scale production.
The acetyl tyrosine ethyl ester monohydrate that provides a kind of method for preparing to obtain is provided.
The technical solution adopted for the present invention to solve the technical problems is: a kind of preparation method of acetyl tyrosine ethyl ester monohydrate
,Described preparation method may further comprise the steps:
Step is 1. :-0.01MPa～-vacuum condition of 0.06MPa under, be that tyrosine and the diacetyl oxide of 1:1.1～2.3 carries out acylation reaction in alkaline aqueous medium with weight ratio, temperature of reaction is controlled at 20～80 ℃, reaction times 30～60min; Acetyl tyrosine ethyl ester monohydrate full name: N-ethanoyl-L-tyrosine ethyl ester monohydrate, or claim N-acetyl-L-tyrosine ethyl ester monohydrate.Acylation reaction of the present invention is specially and earlier tyrosine is dissolved in the pure water of 1 ~ 7 times of weight, adds alkali (as sodium hydroxide, calcium hydroxide, potassium hydroxide) and reconciles pH to alkalescence, adds diacetyl oxide then and carries out acylation reaction; The acylation reaction of this step is all carried out under vacuum condition, control vacuum tightness-0.01MPa～-0.06MPa, can improve reaction efficiency like this, reduce the delay of diacetyl oxide under water surrounding, thus effectively avoid diacetyl oxide in water decomposition and consume with alkali generation neutralization reaction; Anaerobic under the vacuum condition can play the effect of anti-oxidation;-0.01MPa～-acetic acid that produces in can the evaporation reaction process under the 0.06MPa vacuum condition, make reaction environment, condition be easier to the carrying out that reacts, guarantee quality and the purity of product; Be reflected in the alkaline aqueous medium and carry out, be easier to the carrying out of acylation reaction like this, the standard of alkaline aqueous medium alkalescence is that pH is greater than 7; This step is by the control of reaction conditions, and reagent consumption obviously reduces, reacts quickening, quality lifting, yield rising;
Step is 2.: adds mineral acid in the solution after 1. handling to step and regulates PH to 0.5～3.5, and concentrating under reduced pressure under the vacuum condition of-0.085MPa～-0.1 MPa, crystallisation by cooling obtains the Acetyl tyrosine intermediate; The Acetyl tyrosine full name: N-acetyl-L-tyrosine, regulate PH to 0.5～3.5, purpose is acidizing crystal, transfers to the iso-electric point of Acetyl tyrosine, is beneficial to crystallization; Concentrating under reduced pressure is in order to reclaim solvent (acidic aqueous solution) and by product (salt: as sodium-chlor, sodium sulfate, SODIUMNITRATE) under the vacuum condition;
Step is 3.: under agitation condition, in ethanol, add the Acetyl tyrosine intermediate that 2. step obtains, consumption of ethanol is 1. 3 ~ 5.9 times of used tyrosine weight of step, and the control temperature is below 60 ℃, add continue to stir 0.5 ~ 2 hour behind the Acetyl tyrosine intermediate mixed solution;
Step is 4.: 3. obtain to add in the mixed solution sulfur oxychloride to step and carry out building-up reactions; the sulfur oxychloride consumption is 1. 0.6～1.7 times of used tyrosine weight of step; the control temperature of reaction is being carried out below 60 ℃; stirring reaction got reaction solution in 2 ~ 12 hours; the vacuum decompression concentration of reaction solution is to concentrating 25 ~ 50% of front volume, reaction solution to the 3.0～6.0 times volume after dilution concentrates then, crystallisation by cooling; centrifugation gets acetyl tyrosine ethyl ester monohydrate after the drying.Begin to react the synthesis of acetyl tyrosine ethyl ester after adding the chlorination sulfoxide, the purpose of vacuum decompression concentration of reaction solution is to reclaim solvent; The concentration of the purpose control reaction solution of dilution makes crystallization more complete, improves degree of purity of production and yield.
As preferably, the drying conditions of step described in 4. is: under the vacuum condition of-0.085MPa～-0.1 MPa, the control drying temperature is at 30 ~ 60 ℃, dry 3 ~ 12 hours.
As preferably, the mineral acid of step described in 2. is selected from a kind of in hydrochloric acid, sulfuric acid, the nitric acid.
As preferably, the mass concentration of described mineral acid is 15～33%.
As preferably, the condition of the crystallisation by cooling of step described in 2. for the control temperature in insulation below 8 ℃ more than 12 hours.
As preferably, the condition of the crystallisation by cooling of step described in 4. for the control temperature in insulation below 20 ℃ more than 12 hours.
The acetyl tyrosine ethyl ester monohydrate that a kind of preparation method of acetyl tyrosine ethyl ester monohydrate makes.
The invention has the beneficial effects as follows: energy consumption is low, simple to operate and environmental pollution is little, and production cost is low, and the product yield height is fit to large-scale production.
Embodiment
Below by specific embodiment, technical scheme of the present invention is described in further detail.
Embodiment 1:
A kind of preparation method of acetyl tyrosine ethyl ester monohydrate
,Described preparation method may further comprise the steps:
Step is 1.: under the vacuum condition of-0.01MPa, 100g tyrosine is dissolved in the 100g pure water, hydro-oxidation sodium is regulated pH to 7.5, adds the 110g diacetyl oxide then and carries out acylation reaction, and temperature of reaction is controlled at 20 ℃, reaction times 60min;
Step is 2.: the hydrochloric acid that adds mass concentration 15% in the solution after 1. handling to step is regulated PH to 0.5, concentrating under reduced pressure under the vacuum condition of-0.1 MPa, and the control temperature obtains the Acetyl tyrosine intermediate at 20 hours crystallisation by cooling of 8 ℃ of insulations;
Step is 3.: under agitation condition, add the Acetyl tyrosine intermediate that 2. step obtains in ethanol, consumption of ethanol is 300g, and the control temperature is at 60 ℃, add continue to stir 0.5 hour behind the Acetyl tyrosine intermediate mixed solution;
Step is 4.: 3. obtain to add in the mixed solution sulfur oxychloride to step and carry out building-up reactions; the sulfur oxychloride consumption is 60g; the control temperature of reaction is carried out at 60 ℃; stirring reaction got reaction solution in 2 hours; the concentrating under reduced pressure reaction solution is to concentrating 50% of front volume under the vacuum condition of-0.1 MPa; reaction solution to 3.0 times volume after dilution concentrates then; 12 hours crystallisation by cooling of 20 ℃ of insulations; centrifugation; under the vacuum condition of-0.085MPa; 30 ℃ of temperature, drying got acetyl tyrosine ethyl ester monohydrate in 12 hours.
Embodiment 2:
A kind of preparation method of acetyl tyrosine ethyl ester monohydrate
,Described preparation method may further comprise the steps:
Step is 1.: under the vacuum condition of-0.06MPa, 100g tyrosine is dissolved in the 700g pure water, hydro-oxidation potassium is regulated pH to 8, adds the 230g diacetyl oxide then and carries out acylation reaction, and temperature of reaction is controlled at 80 ℃, reaction times 30min;
Step is 2.: the nitric acid that adds mass concentration 33% in the solution after 1. handling to step is regulated PH to 3.5, concentrating under reduced pressure under the vacuum condition of-0.085 MPa, and the control temperature obtains the Acetyl tyrosine intermediate at 15 hours crystallisation by cooling of 4 ℃ of insulations;
Step is 3.: under agitation condition, add the Acetyl tyrosine intermediate that 2. step obtains in ethanol, consumption of ethanol is 590g, and the control temperature is at 40 ℃, add continue to stir 2 hours behind the Acetyl tyrosine intermediate mixed solution;
Step is 4.: 3. obtain to add in the mixed solution sulfur oxychloride to step and carry out building-up reactions; the sulfur oxychloride consumption is 170g; the control temperature of reaction is carried out at 25 ℃; stirring reaction got reaction solution in 12 hours; the concentrating under reduced pressure reaction solution is to concentrating 25% of front volume under the vacuum condition of-0.085 MPa; reaction solution to 6.0 times volume after dilution concentrates then; 20 hours crystallisation by cooling of 10 ℃ of insulations; centrifugation; under the vacuum condition of-0.1MPa; 60 ℃ of temperature, drying got acetyl tyrosine ethyl ester monohydrate in 3 hours.
Embodiment 3:
A kind of preparation method of acetyl tyrosine ethyl ester monohydrate
,Described preparation method may further comprise the steps:
Step is 1.: under the vacuum condition of-0.04MPa, 100g tyrosine is dissolved in the 200g pure water, adding calcium hydroxide is regulated pH to 8.2, adds the 150g diacetyl oxide then and carries out acylation reaction, and temperature of reaction is controlled at 50 ℃, reaction times 40min;
Step is 2.: the sulfuric acid that adds mass concentration 20% in the solution after 1. handling to step is regulated PH to 2.0, concentrating under reduced pressure under the vacuum condition of-0.09 MPa, and the control temperature obtains the Acetyl tyrosine intermediate at 12 hours crystallisation by cooling of 2 ℃ of insulations;
Step is 3.: under agitation condition, add the Acetyl tyrosine intermediate that 2. step obtains in ethanol, consumption of ethanol is 400g, and the control temperature is at 30 ℃, add continue to stir 1 hour behind the Acetyl tyrosine intermediate mixed solution;
Step is 4.: 3. obtain to add in the mixed solution sulfur oxychloride to step and carry out building-up reactions; the sulfur oxychloride consumption is 100g; the control temperature of reaction is carried out at 30 ℃; stirring reaction got reaction solution in 8 hours; the concentrating under reduced pressure reaction solution is to concentrating 30% of front volume under the vacuum condition of-0.09 MPa; reaction solution to 4.0 times volume after dilution concentrates then; 16 hours crystallisation by cooling of 15 ℃ of insulations; centrifugation; under the vacuum condition of-0.09MPa; 40 ℃ of temperature, drying got acetyl tyrosine ethyl ester monohydrate in 10 hours.
The yield of product of the present invention is between 110% ~ 115% after testing, and compared with prior art preparation method of the present invention cost-saved about 20%.
The physics and chemistry detected result of product of the present invention (acetyl tyrosine ethyl ester monohydrate) is as follows:
1, outward appearance: white crystals or white powder;
2, specific rotation [α]
d 20+ 21.0 ~+26.0 °: claim 1.00 grams product of the present invention to dissolve in the 100ml dehydrated alcohol, in the impouring polarization tube, insert polarimeter, at 20 degrees centigrade, detect reading under the sodium lamp;
3, dissolving situation is more than or equal to 99.0%: claim 5.00 grams product of the present invention to dissolve in the 100ml dehydrated alcohol, in the impouring colorimetric cylinder, insert spectrophotometer, detect reading under 430nm;
4, weight loss on drying is smaller or equal to 8%: claim 1.0000 grams product of the present invention to go in the weighing bottle, insert in the vacuum drier that fills Vanadium Pentoxide in FLAKES, keep 50 degrees centigrade, dry 10 hours;
5, ignition residue is smaller or equal to 0.5%: with reference to the 92nd edition detection method＜13 of Japanese aginomoto〉or 25 editions limit test＜281 of American Pharmacopeia;
6, purity is more than or equal to 98.0 %:F254 silica gel G thin layer chromatographys: sample product 100 micrograms of the present invention, to Acetyl tyrosine 2 micrograms in the same old way, the assorted spot in the sample must not compare that spot is darker in the same old way.
Above-described embodiment is a kind of preferable scheme of the present invention, is not that the present invention is done any pro forma restriction, also has other variant and remodeling under the prerequisite that does not exceed the technical scheme that claim puts down in writing.
Claims (6)
1. the preparation method of an acetyl tyrosine ethyl ester monohydrate
,It is characterized in that: described preparation method may further comprise the steps:
Step is 1. :-0.01MPa～-vacuum condition of 0.06MPa under, be that tyrosine and the diacetyl oxide of 1:1.1～2.3 carries out acylation reaction in alkaline aqueous medium with weight ratio, temperature of reaction is controlled at 20～80 ℃, reaction times 30～60min;
Step is 2.: adds mineral acid in the solution after 1. handling to step and regulates PH to 0.5～3.5, and concentrating under reduced pressure under the vacuum condition of-0.085MPa～-0.1 MPa, crystallisation by cooling obtains the Acetyl tyrosine intermediate;
Step is 3.: under agitation condition, in ethanol, add the Acetyl tyrosine intermediate that 2. step obtains, consumption of ethanol is 1. 3 ~ 5.9 times of used tyrosine weight of step, and the control temperature is below 60 ℃, add continue to stir 0.5 ~ 2 hour behind the Acetyl tyrosine intermediate mixed solution;
Step is 4.: 3. obtain to add in the mixed solution sulfur oxychloride to step and carry out building-up reactions; the sulfur oxychloride consumption is 1. 0.6～1.7 times of used tyrosine weight of step; the control temperature of reaction is being carried out below 60 ℃; stirring reaction got reaction solution in 2 ~ 12 hours; the vacuum decompression concentration of reaction solution is to concentrating 25 ~ 50% of front volume, reaction solution to the 3.0～6.0 times volume after dilution concentrates then, crystallisation by cooling; centrifugation gets acetyl tyrosine ethyl ester monohydrate after the drying.
2. preparation method according to claim 1 is characterized in that: the drying conditions of step described in 4. is: under the vacuum condition of-0.085MPa～-0.1 MPa, the control drying temperature is at 30 ~ 60 ℃, dry 3 ~ 12 hours.
3. preparation method according to claim 1 and 2 is characterized in that: the mineral acid of step described in 2. is selected from a kind of in hydrochloric acid, sulfuric acid, the nitric acid.
4. preparation method according to claim 3, it is characterized in that: the mass concentration of described mineral acid is 15～33%.
5. preparation method according to claim 1 and 2 is characterized in that: the condition of the crystallisation by cooling of step described in 2. for the control temperature in insulation below 8 ℃ more than 12 hours.
6. preparation method according to claim 1 and 2 is characterized in that: the condition of the crystallisation by cooling of step described in 4. for the control temperature in insulation below 20 ℃ more than 12 hours.
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| CN109530094B (en) * | 2019-01-17 | 2021-05-28 | 湖南中医药大学 | Amidohydroxycarboxylic acid/hydroxamic acid compounds and their application in mineral flotation |
| CN111153829A (en) * | 2019-12-26 | 2020-05-15 | 烟台鲁银药业有限公司 | Preparation method of N-acetyl-L-tyrosine |
| CN111170883A (en) * | 2020-01-06 | 2020-05-19 | 岳阳科罗德联合化学工业有限公司 | Fatty acyl amino acid polyhydroxy ester compound and preparation method thereof |
| CN114716335A (en) * | 2020-12-22 | 2022-07-08 | 武汉远大弘元股份有限公司 | Process for preparing N-acetyl-L-tyrosine |
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Cited By (3)
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