CN110452142B - Preparation method of S- (carboxymethyl) -cysteine - Google Patents
Preparation method of S- (carboxymethyl) -cysteine Download PDFInfo
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- CN110452142B CN110452142B CN201910853513.XA CN201910853513A CN110452142B CN 110452142 B CN110452142 B CN 110452142B CN 201910853513 A CN201910853513 A CN 201910853513A CN 110452142 B CN110452142 B CN 110452142B
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- GBFLZEXEOZUWRN-UHFFFAOYSA-N carbocisteine Chemical compound OC(=O)C(N)CSCC(O)=O GBFLZEXEOZUWRN-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000000047 product Substances 0.000 claims abstract description 40
- 239000012065 filter cake Substances 0.000 claims abstract description 35
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 15
- VLSOAXRVHARBEQ-UHFFFAOYSA-N [4-fluoro-2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(F)C=C1CO VLSOAXRVHARBEQ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003513 alkali Substances 0.000 claims abstract description 11
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 11
- 239000012043 crude product Substances 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 11
- 238000010438 heat treatment Methods 0.000 claims abstract description 10
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229940106681 chloroacetic acid Drugs 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 8
- 239000007864 aqueous solution Substances 0.000 claims abstract description 7
- 150000007524 organic acids Chemical class 0.000 claims abstract description 4
- 229910000831 Steel Inorganic materials 0.000 claims description 27
- 239000010959 steel Substances 0.000 claims description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 238000001035 drying Methods 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 15
- 238000001914 filtration Methods 0.000 claims description 14
- 229920006332 epoxy adhesive Polymers 0.000 claims description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 claims description 8
- 229960003067 cystine Drugs 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 235000019393 L-cystine Nutrition 0.000 claims description 7
- 239000004158 L-cystine Substances 0.000 claims description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 3
- 229960000583 acetic acid Drugs 0.000 claims description 3
- 229960001305 cysteine hydrochloride Drugs 0.000 claims description 3
- 239000012362 glacial acetic acid Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 238000006722 reduction reaction Methods 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 238000002425 crystallisation Methods 0.000 abstract 1
- 230000008025 crystallization Effects 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 12
- 238000001816 cooling Methods 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 description 6
- 229960004399 carbocisteine Drugs 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- LJPYJRMMPVFEKR-UHFFFAOYSA-N prop-2-ynylurea Chemical compound NC(=O)NCC#C LJPYJRMMPVFEKR-UHFFFAOYSA-N 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- 238000002386 leaching Methods 0.000 description 4
- 210000003097 mucus Anatomy 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 238000007670 refining Methods 0.000 description 4
- 239000011343 solid material Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 241000521257 Hydrops Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 210000000959 ear middle Anatomy 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 229910052755 nonmetal Inorganic materials 0.000 description 2
- 210000003695 paranasal sinus Anatomy 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010009137 Chronic sinusitis Diseases 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 208000027157 chronic rhinosinusitis Diseases 0.000 description 1
- 210000000254 ciliated cell Anatomy 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000420 mucociliary effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002843 nonmetals Chemical class 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 208000005923 otitis media with effusion Diseases 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000012749 thinning agent Substances 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- WCTAGTRAWPDFQO-UHFFFAOYSA-K trisodium;hydrogen carbonate;carbonate Chemical compound [Na+].[Na+].[Na+].OC([O-])=O.[O-]C([O-])=O WCTAGTRAWPDFQO-UHFFFAOYSA-K 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of compound preparation, and particularly relates to a preparation method of S- (carboxymethyl) -cysteine; firstly, pretreating the L-cysteine hydrochloride by using a reducing agent before reaction, adding a chloroacetic acid aqueous solution into a system, continuously reacting in a positive reaction direction along with the dropwise addition of an alkali liquor until the pH value of the system is 6.0-12.0, finishing the reaction, dropwise adding acid to the vicinity of the isoelectric point of a product, and performing low-temperature crystallization to obtain a crude product; dissolving the mixture in alkali liquor at room temperature, dropwise adding organic acid until the pH value is about 2.8 to separate out a product, putting the separated product into a tray, putting the tray on the water surface, pretreating the product by heating, heating the water in a filter cake until small bubbles are generated in the pretreatment process, reacting the generated bubbles to the filter cake, further generating the separated product by the substances in the water in the filter cake through the vibration effect of the bubbles, and finally putting the pretreated separated product into an integrated machine to obtain the product.
Description
Technical Field
The invention belongs to the technical field of compound preparation, and particularly relates to a preparation method of S- (carboxymethyl) -cysteine.
Background
S- (carboxymethyl) -cysteine, alias carbocisteine, white crystalline powder; odorless, slightly soluble in hot water, and insoluble in ethanol or acetone; is easily soluble in acid or alkali solution. Carbocisteine is a mucus thinning agent, mainly affects the secretion of bronchial glands at the cellular level, and can break the disulfide bond of mucin in mucus, increase the secretion of low-viscosity sialogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogog.
The carbocisteine has effects in airway, nasal cavity, nasal sinuses and epithelial mucosa of middle ear, mucous gland, etc. The epithelial mucosa of the respiratory tract, nasal cavity, sinuses and middle ear is covered with ciliated cells, which play an important role in the elimination of foreign bodies and mucus. Improving mucociliary transport function and promoting excretion of phlegm, chronic sinusitis nasal hydrops and otitis media hydrops by improving balance of mucus component and normalizing damaged mucosal epithelium. In addition, carbocisteine is the first oral formulation to have indications for the drainage of otitis media with effusion.
Patents CN106083673A and CN106565565A both disclose a synthesis method of S- (carboxymethyl) -cysteine, which is a conventional route for synthesizing carbocisteine, wherein carbocisteine is prepared by reacting L-cysteine hydrochloride with chloroacetic acid, the yield is about 96%, and the purity is 99.2%. Liquid ammonia and ammonium bicarbonate are adopted to adjust the pH value, the liquid ammonia is stored in a pressure tank, the safety problem exists, the adding amount is not easy to control, and simultaneously ammonium salt and chloride in the final product are easy to exceed the standard.
In addition, the raw material L-cysteine hydrochloride is easily oxidized into cystine under neutral or strong alkaline conditions, so that the purity of a final product is reduced, and the L-cysteine hydrochloride needs to be treated in three machines of centrifugation, filtration and drying during preparation, so that the efficiency is low. Therefore, in order to solve the above problems, the present invention provides a method for preparing S- (carboxymethyl) -cysteine.
Disclosure of Invention
In view of the deficiencies of the prior art, the present invention provides a method for preparing S- (carboxymethyl) -cysteine, which solves the problems mentioned in the background art.
In order to achieve the purpose, the invention provides the following technical scheme: a method for preparing S- (carboxymethyl) -cysteine, comprising the steps of:
a.L-pretreatment is carried out by adopting a reducing agent before the reaction of cysteine hydrochloride, wherein the reducing agent is iron powder;
b. adding chloroacetic acid aqueous solution into the system, and continuously reacting in the positive reaction direction along with the dropwise addition of the alkali liquor until the pH value of the system is 6.0-12.0;
c. dripping acid to the vicinity of the isoelectric point of the product, wherein the dripped acid is dilute hydrochloric acid, dilute sulfuric acid or glacial acetic acid; crystallizing at-10 to 30 ℃ for more than 10 hours to obtain a crude product;
d. dissolving in alkali solution at room temperature, wherein the alkali is NaOH, KOH or Na2CO3NaHCO3, ammonia water or triethylamine, and dripping organic acid until the pH value is about 2.8 to separate out a product;
e. putting the precipitated product into a tray, putting the tray on the water surface, and pretreating the product by heating, wherein in the pretreatment process, the water in the filter cake is heated until small bubbles are generated, and the generated bubbles react with the filter cake to further generate the precipitated product by the vibration action of the bubbles;
f. and putting the product separated out by the pretreatment into an all-in-one machine, filtering, centrifuging and drying to obtain the product.
Preferably, the L-cysteine hydrochloride is a mixture of L-cystine and L-cysteine hydrochloride, and the amount of the reducing agent added is calculated according to the content of the L-cystine; the solvent of the reduction reaction is aqueous solution or anhydrous organic solvent, and the reaction temperature is 35-80 ℃.
Preferably, the all-in-one machine comprises a machine body, a primary filter screen is arranged in the machine body, a secondary filter screen is arranged at the bottom of the primary filter screen, a plurality of ejector rods are arranged between the primary filter screen and the secondary filter screen, a plurality of bottom rods are arranged at the bottoms of the ejector rods, the ejector rods and the bottom rods are respectively distributed at intervals in the X direction and the Y direction, and the ejector rods and the bottom rods are rotatably connected through rotating shafts; a reel is arranged at the top of the machine body; the two steel wire ropes are arranged at the positions of two ends of the same diagonal line of the machine body, one end of one steel wire rope is connected with the end part of the top rod close to the steel wire rope, one end of the other steel wire rope is connected with the end part of the bottom rod close to the steel wire rope, the other ends of the two steel wire ropes penetrate through the side wall of the machine body respectively and are connected to the reel, a feeding port is fixedly connected to one side of the machine body, and the feeding; the first-stage filter screen and the second-stage filter screen are connected through an elastic plate, and the first-stage filter screen is fixedly connected with the inner wall of the machine body; when the machine works, a separated product, namely a filter cake, is placed at the top of a first-stage filter screen in the machine body through a feeding port, initially, the ejector rod and the bottom rod are mutually vertical, so that the shape formed by the ejector rod and the bottom rod is just a square, when the first-stage filter screen is overlooked from the upper side, the ejector rod and the bottom rod cannot be seen, the first-stage filter screen can permeate filter cakes with larger particles, when the size of the filter cake to be selected is smaller, a steel wire rope is wound on a reel by rotating the reel, the ejector rod and the bottom rod are pulled by the steel wire rope, so that the shape formed by the ejector rod and the bottom rod is a plurality of rhombuses, a heater is initially arranged in the machine body, a motor is arranged at the bottom of the machine body and can drive the machine body to rotate, the filter cake is centrifuged in the rotating process of the machine body, after heating and centrifugation are completed, the smaller filter cake which becomes dry drops to the top of the secondary filter screen from the primary filter screen, and the substances at the bottom of the inner side of the primary filter screen, the secondary filter screen and the machine body are large-particle filter cake, small-particle filter cake and water which is centrifuged out.
Preferably, the inner wall of the machine body is provided with an inflatable bag, and the inflatable bag is connected with the ejector rod, the bottom rod and the elastic plate; because when taking place to rotate each other through a plurality of ejector pins of wire rope pulling and sill bar, the shape that it encloses becomes the rhombus by the square, at this moment, whole length becomes long, the width shortens, shorten the distance between department ejector pin and sill bar and the organism and bigger, owing to there is the effect of gas cell, the ejector pin and the sill bar extrusion gas cell of length changing department, make the gas in the gas cell to the ejector pin and the sill bar department removal of shortening department, rise the gas cell here, fill the space between department ejector pin and sill bar and the organism of shortening, prevent that ejector pin and sill bar are when becoming more flat by the wire rope pulling, the small opening that has partly one-level filter screen can't be blockked by ejector pin and sill bar.
Preferably, the inflatable bag is bonded with the top rod, the bottom rod and the elastic plate through epoxy adhesive; the epoxy adhesive has excellent performances of high temperature resistance, heat conduction and low linear expansion, so that the bonding strength of the epoxy adhesive cannot be influenced by the high-temperature environment in the machine body, meanwhile, the heat of the ejector rod, the bottom rod and the inflatable bag can be fully conducted through the heat conductivity of the epoxy adhesive, and when the ejector rod and the bottom rod are pulled and deformed by the steel wire rope, the low linear expansion of the epoxy adhesive can ensure the stability of the epoxy adhesive in connection with the ejector rod and the bottom rod.
The invention has the technical effects and advantages that:
1. according to the preparation method of S- (carboxymethyl) -cysteine, provided by the invention, the filter cake is placed in the integrated machine, so that the three steps of centrifugation, filtration and drying are all completed in one container, and simultaneously, the deformation degree of the top rod and the bottom rod can be adjusted according to requirements to filter the filter cakes with different sizes, so as to obtain the required product size.
2. The S- (carboxymethyl) -cysteine preparation method provided by the invention comprises the steps of centrifuging, filtering and drying, putting a precipitated product into a tray, putting the tray on a water surface, and pre-treating the tray by heating, wherein in the pre-treatment process, water in a filter cake is heated until small bubbles are generated, and the generated bubbles react with the filter cake to further precipitate the product from substances in the water in the filter cake under the vibration action of the bubbles, so that the subsequent drying time is reduced, and the product yield is improved.
Drawings
The invention will be further explained with reference to the drawings.
FIG. 1 is a flow chart of a method of the present invention;
FIG. 2 is a perspective view of the kiosk used in the present invention;
FIG. 3 is a main sectional view of the all-in-one machine used in the present invention;
FIG. 4 is a schematic view of the top and bottom bar construction of the present invention;
FIG. 5 is an HPLC chromatogram of the product made in example 3 of the present invention;
FIG. 6 is an HPLC chromatogram of the product made in example 4 of the present invention;
in the figure: the machine body 1, a primary filter screen 2, a secondary filter screen 3, a top rod 4, a bottom rod 5, a reel 6, a steel wire rope 7, a feeding port 8, a hinged plate 9, an elastic plate 10 and an inflatable bag 11.
Detailed Description
In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the invention is further described with the specific embodiments.
As shown in fig. 1 to 6, the preparation method of S- (carboxymethyl) -cysteine according to the present invention comprises the following steps:
a.L-pretreatment is carried out by adopting a reducing agent before the reaction of cysteine hydrochloride, wherein the reducing agent is iron powder;
b. adding chloroacetic acid aqueous solution into the system, and continuously reacting in the positive reaction direction along with the dropwise addition of the alkali liquor until the pH value of the system is 6.0-12.0;
c. dripping acid to the vicinity of the isoelectric point of the product, wherein the dripped acid is dilute hydrochloric acid, dilute sulfuric acid or glacial acetic acid; crystallizing at-10 to 30 ℃ for more than 10 hours to obtain a crude product;
d. dissolving in alkali solution at room temperature, wherein the alkali is NaOH, KOH or Na2CO3、NaHCO3, ammonia water or triethylamine, and organic acid is dripped until the pH value is about 2.8 to separate out a product;
e. putting the precipitated product into a tray, putting the tray on the water surface, and pretreating the product by heating, wherein in the pretreatment process, the water in the filter cake is heated until small bubbles are generated, and the generated bubbles react with the filter cake to further generate the precipitated product by the vibration action of the bubbles;
f. and putting the product separated out by the pretreatment into an all-in-one machine, filtering, centrifuging and drying to obtain the product.
The L-cysteine hydrochloride is a mixture of L-cystine and L-cysteine hydrochloride, and the amount of the reducing agent added is calculated according to the content of the L-cystine; the kind of the reducing agent is alkali metal such as Na, Al, Zn, Fe; reactive metal hydrides, e.g. LiAlH4(ii) a Elemental non-metals, e.g. H2S; a non-metal hydride; the solvent of the reduction reaction is aqueous solution or anhydrous organic solvent, and the reaction temperature is 35-80 ℃.
The all-in-one machine comprises a machine body 1, wherein a primary filter screen 2 is arranged in the machine body 1, a secondary filter screen 3 is arranged at the bottom of the primary filter screen 2, a plurality of ejector rods 4 are arranged between the primary filter screen 2 and the secondary filter screen 3, a plurality of bottom rods 5 are arranged at the bottoms of the ejector rods 4, the ejector rods 4 and the bottom rods 5 are respectively distributed at intervals in the X direction and the Y direction, and the ejector rods 4 and the bottom rods 5 are rotatably connected through rotating shafts; a reel 6 is arranged at the top of the machine body 1; the two steel wire ropes 7 are arranged at the positions of two ends of the same diagonal of the machine body 1, one end of one steel wire rope 7 is connected with the end part of the top rod 4 close to the steel wire rope, one end of the other steel wire rope 7 is connected with the end part of the bottom rod 5 close to the steel wire rope, the other ends of the two steel wire ropes 7 penetrate through the side wall of the machine body 1 respectively and are connected onto the reel 6, a feeding port 8 is fixedly connected to one side of the machine body 1, and the feeding port 8 is; the primary filter screen 2 and the secondary filter screen 3 are connected through an elastic plate 10, and the primary filter screen 2 is fixedly connected with the inner wall of the machine body 1; when the filter cake processing machine works, a separated product, namely a filter cake, is placed at the top of a first-stage filter screen 2 in a machine body 1 through a feeding port 8, initially, a top rod 4 and a bottom rod 5 are perpendicular to each other, so that the shape enclosed by the top rod 4 and the bottom rod 5 is exactly a square, when the first-stage filter screen 2 is overlooked from the top, the top rod 4 and the bottom rod 5 cannot be seen, at the moment, the first-stage filter screen 2 can penetrate through filter cakes with larger particles, when the size of the filter cake to be selected is smaller, a steel wire rope 7 is wound on a reel 6 by rotating the reel 6, the top rod 4 and the bottom rod 5 are pulled by the steel wire rope 7, so that the shape enclosed by the top rod 4 and the bottom rod 5 is a plurality of diamonds, a heater is initially installed in the machine body 1, a motor is installed at the bottom of the machine body 1 to drive the machine body 1, get into 1 inboard bottom of organism through one-level filter screen 2 and second grade filter screen 3, after heating and centrifugation are accomplished, become the less filter cake of drying and drop to 3 tops of second grade filter screen from one-level filter screen 2, the material of one-level filter screen 2 like this, second grade filter screen 3 and 1 inboard bottoms of organism is, large granule filter cake, tiny particle filter cake and the water of centrifugation play respectively.
The inner wall of the machine body 1 is provided with an inflatable bag 11, and the inflatable bag 11 is connected with the ejector rod 4, the bottom rod 5 and the elastic plate 10; because when a plurality of ejector pins 4 and the bottom rod 5 are pulled to rotate mutually through the steel wire rope 7, the shape enclosed by the ejector pins 4 and the bottom rod 5 is changed into a rhombus from a square, at the moment, the whole length is lengthened, the width is shortened, the distance between the ejector pins 4 and the bottom rod 5 at the shortened part and the machine body 1 is larger and larger, and due to the action of the inflatable bag 11, the ejector pins 4 and the bottom rod 5 at the shortened part extrude the inflatable bag 11, so that the gas in the inflatable bag 11 moves to the ejector pins 4 and the bottom rod 5 at the shortened part, the inflatable bag 11 at the position is expanded, gaps between the ejector pins 4 and the bottom rod 5 at the shortened part and the machine body 1 are filled, and when the ejector pins 4 and the bottom rod 5 are pulled to be flatter by the steel wire rope 7, part of leakage holes of the primary filter screen.
The inflatable bag 11 is bonded with the ejector rod 4, the bottom rod 5 and the elastic plate 10 through epoxy adhesive; the epoxy adhesive has excellent performances of high temperature resistance, heat conduction and low linear expansion, so that the bonding strength of the epoxy adhesive cannot be influenced by the high-temperature environment in the machine body 1, meanwhile, the heat of the ejector rod 4 and the bottom rod 5 and the inflatable bag 11 can be fully conducted through the heat conductivity of the epoxy adhesive, and when the ejector rod 4 and the bottom rod 5 are pulled and deformed by the steel wire rope 7, the low linear expansion of the epoxy adhesive can ensure the stability of the epoxy adhesive in connection with the ejector rod 4 and the bottom rod 5.
Example 1
Adding 100.0g L-cysteine hydrochloride mixture (the content of L-cysteine hydrochloride is 50.2 percent, and the content of L-cystine is 49.0 percent) and 500mL of purified water into a 1L reaction kettle, starting stirring at room temperature, adding 30.0g of iron powder, heating to 60 ℃, reacting for 30min after the temperature is reached, cooling, adding 66.4g of chloroacetic acid into the reaction kettle when the temperature of the reaction kettle reaches 30-40 ℃, starting to dropwise add sodium hydroxide solution, and controlling the reaction temperature not to exceed 60 ℃. When the pH value is monitored to be 7.0-8.0, the dropwise addition of the sodium hydroxide solution is stopped, and the temperature is kept at 60 ℃ for 30 min. After the temperature is reduced to room temperature, dilute sulfuric acid is added dropwise, and the temperature of the reaction solution is controlled to be lower than 30 ℃. And (3) dropwise adding the mixture until the pH value of the system is about 2.5-3.0, reaching the end point, cooling to-5-10 ℃, preserving the heat for 16h, leaching a filter cake with 30g of water, filtering, and drying to obtain 95.2g of a crude product, wherein the yield is 93.3%, and the purity is 99.5%.
And putting the crude product into a refining kettle, adding ammonia water at room temperature until the solid material is completely dissolved, dropwise adding dilute sulfuric acid while stirring until the pH value of the system is 2.5-3.0, reaching the end point, cooling to-5-0 ℃, preserving heat for 16h, leaching a filter cake with 30g of water, adding into an all-in-one machine, filtering, and drying to obtain 93.5g of a product, wherein the total yield is 91.7%, and the purity is 99.90%.
Example 2
Adding 100.0g L-cysteine hydrochloride monohydrate (the content of L-cysteine hydrochloride is 99.5%) and 300mL of purified water into a 1L reaction kettle, starting stirring, dissolving at room temperature, adding 5.0g of iron powder, heating to 60 ℃, reacting for 30min after reaching the temperature, cooling, adding 56.5g of chloroacetic acid into the reaction kettle when the temperature of the reaction kettle reaches 30-40 ℃, starting to dropwise add a sodium bicarbonate solution, and controlling the reaction temperature to be not more than 60 ℃. When the pH value is monitored to be 7.0-8.0, the dropping of the sodium bicarbonate solution is stopped, and the temperature is kept at 60 ℃ for 30 min. When the temperature is reduced to 15-30 ℃, dilute sulphuric acid is dripped, and the temperature of the reaction solution is controlled to be lower than 30 ℃. And (3) dropwise adding the mixture until the pH value of the system is about 2.5-3.0, reaching the end point, cooling to-5 to 0 ℃, preserving the heat for 12 hours, leaching a filter cake with 30g of water, filtering, and drying to obtain 98.5g of a crude product, wherein the yield is 96.6%, and the purity is 99.2%.
And putting the crude product into a refining kettle, adding ammonia water at room temperature until the solid material is completely dissolved, dropwise adding dilute hydrochloric acid while stirring until the pH value of the system is 2.5-3.0, reaching the end point, cooling to-5-0 ℃, keeping the temperature for 12h, leaching a filter cake with 30g of water, adding into an all-in-one machine, filtering, and drying to obtain 95.5g of a product, wherein the total yield is 93.6% and the purity is 99.97%.
Example 3
375Kg of purified water is weighed into a 1000L reaction kettle, stirring is started, 150.0Kg of L-cysteine hydrochloride monohydrate is weighed, after the L-cysteine hydrochloride monohydrate is dissolved at room temperature, stirring is carried out for 10 minutes, 4.5Kg of iron powder is added, a large amount of gas is generated, and stirring is carried out for 60 minutes at 35-45 ℃. 89.2kg of chloroacetic acid is weighed and added into the reaction kettle, and the mixture is stirred for 30 to 40 minutes under the condition of heat preservation. Dropping sodium carbonate solution, regulating pH to 7.0-8.0, and maintaining at 60 deg.c for 30 min. When the temperature is reduced to 15-30 ℃, dilute sulphuric acid is dripped, and the temperature of the reaction solution is controlled to be lower than 30 ℃. Dropwise adding until the pH value of the system is about 2.5-3.0, reaching the end point, cooling to-5-0 ℃, preserving heat for 12h, centrifugally filtering a filter cake, and drying to obtain 146.9kg of crude product, wherein the yield is 96.0%, and the purity is 99.5%.
Putting the crude product into a refining kettle, adding NaOH solution at room temperature until the solid material is completely dissolved, adding 320kg of ethanol, dropwise adding 1mol/L of dilute hydrochloric acid while stirring until the pH value of the system is 2.5-3.0, reaching the end point, cooling to-5-0 ℃, keeping the temperature for 12h, adding into an all-in-one machine, centrifugally filtering, and drying to obtain 140.5kg of a product, wherein the total yield is 91.8%, and the purity is 99.91%.
Example 4
375Kg of purified water is weighed into a 1000L reaction kettle, stirring is started, 150.1Kg of L-cysteine hydrochloride monohydrate is weighed, after the L-cysteine hydrochloride monohydrate is dissolved at room temperature, stirring is carried out for 10 minutes, 4.5Kg of iron powder is added, a large amount of gas is generated, and stirring is carried out for 60 minutes at 35-45 ℃. 89.2kg of chloroacetic acid is weighed and added into the reaction kettle, and the mixture is stirred for 30 to 40 minutes under the condition of heat preservation. Ammonia water is added dropwise, the pH value is adjusted to 7.0-8.0, and the temperature is kept at 60 ℃ for 30 min. When the temperature is reduced to 15-30 ℃, dilute hydrochloric acid is dripped, and the temperature of the reaction solution is controlled to be lower than 30 ℃. And (3) dropwise adding the mixture until the pH value of the system is about 2.5-3.0, reaching the end point, cooling to-5-10 ℃, preserving the heat for 18 hours, and centrifugally filtering a filter cake to obtain 280.3kg of the filter cake (wet weight). And putting the crude product into a refining kettle, adding NaOH solution at room temperature until the solid material is completely dissolved, adding 320kg of ethanol, dropwise adding 1mol/L of dilute hydrochloric acid while stirring until the pH value of the system is 2.5-3.0, reaching the end point, cooling to-5-10 ℃, preserving heat for 18h, adding into an integrated machine, centrifugally filtering, and drying to obtain 144.6kg of a product, wherein the total yield is 94.4% and the purity is 99.94%.
Examples 3 and 4 test results of samples
The foregoing illustrates and describes the principles, general features, and advantages of the present invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (4)
1. A method for preparing S- (carboxymethyl) -cysteine, which is characterized in that: the method comprises the following steps:
a.L-pretreatment is carried out by adopting a reducing agent before the reaction of cysteine hydrochloride, wherein the reducing agent is iron powder;
b. adding chloroacetic acid aqueous solution into the system, and continuously reacting in the positive reaction direction along with the dropwise addition of the alkali liquor until the pH value of the system is 6.0-12.0;
c. dripping acid to the vicinity of the isoelectric point of the product, wherein the dripped acid is dilute hydrochloric acid, dilute sulfuric acid or glacial acetic acid; crystallizing at-10 to 30 ℃ for more than 10 hours to obtain a crude product;
d. at room temperatureDissolving in alkali solution such as NaOH, KOH, or Na2CO3、NaHCO3Ammonia water or triethylamine, organic acid is dripped until the pH value is about 2.8, and a product is separated out;
e. putting the precipitated product into a tray, putting the tray on the water surface, and pretreating the product by heating, wherein in the pretreatment process, the water in the filter cake is heated until small bubbles are generated, and the generated bubbles react with the filter cake to further generate the precipitated product by the vibration action of the bubbles;
f. putting the product separated out by pretreatment into an all-in-one machine, filtering, centrifuging and drying to obtain a product;
the all-in-one machine comprises a machine body (1), a primary filter screen (2) is arranged in the machine body (1), a secondary filter screen (3) is arranged at the bottom of the primary filter screen (2), a plurality of ejector rods (4) are arranged between the primary filter screen (2) and the secondary filter screen (3), a plurality of bottom rods (5) are arranged at the bottoms of the ejector rods (4), the ejector rods (4) and the bottom rods (5) are respectively distributed at intervals in the X direction and the Y direction, and the ejector rods (4) are rotatably connected with the bottom rods (5) through rotating shafts; a reel (6) is arranged at the top of the machine body (1); the steel wire ropes (7) are arranged at the positions of two ends of the same diagonal of the machine body (1), one end of one steel wire rope (7) is connected with the end part of the top rod (4) close to the steel wire rope, one end of the other steel wire rope (7) is connected with the end part of the bottom rod (5) close to the steel wire rope, the other ends of the two steel wire ropes (7) penetrate through the side wall of the machine body (1) respectively and are connected onto the reel (6), one side of the machine body (1) is fixedly connected with a feeding port (8), and the feeding port (8) is blocked through a hinged; the primary filter screen (2) is connected with the secondary filter screen (3) through an elastic plate (10), and the primary filter screen (2) is fixedly connected with the inner wall of the machine body (1); a heater is initially arranged in the machine body (1), and a motor is arranged at the bottom of the machine body (1).
2. A process according to claim 1 for the preparation of S- (carboxymethyl) -cysteine, characterized in that: the L-cysteine hydrochloride is a mixture of L-cystine and L-cysteine hydrochloride, and the amount of the reducing agent added is calculated according to the content of the L-cystine; the solvent of the reduction reaction is aqueous solution or anhydrous organic solvent, and the reaction temperature is 35-80 ℃.
3. A process according to claim 1 for the preparation of S- (carboxymethyl) -cysteine, characterized in that: the inner wall of the machine body (1) is provided with an inflatable bag (11), and the inflatable bag (11) is connected with the ejector rod (4), the bottom rod (5) and the elastic plate (10).
4. A process according to claim 3, characterized in that: the inflatable bag (11) is bonded with the ejector rod (4), the bottom rod (5) and the elastic plate (10) through epoxy adhesive.
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