CN110452142A - A kind of preparation method of high-purity S- (carboxymethyl)-cysteine - Google Patents
A kind of preparation method of high-purity S- (carboxymethyl)-cysteine Download PDFInfo
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- CN110452142A CN110452142A CN201910853513.XA CN201910853513A CN110452142A CN 110452142 A CN110452142 A CN 110452142A CN 201910853513 A CN201910853513 A CN 201910853513A CN 110452142 A CN110452142 A CN 110452142A
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Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- GBFLZEXEOZUWRN-UHFFFAOYSA-N carbocisteine Chemical compound OC(=O)C(N)CSCC(O)=O GBFLZEXEOZUWRN-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 239000012065 filter cake Substances 0.000 claims abstract description 40
- 239000000047 product Substances 0.000 claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 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 15
- 239000002253 acid Substances 0.000 claims abstract description 13
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 13
- 238000001556 precipitation Methods 0.000 claims abstract description 13
- 239000000126 substance Substances 0.000 claims abstract description 13
- 238000010438 heat treatment Methods 0.000 claims abstract description 11
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000012043 crude product Substances 0.000 claims abstract description 10
- 238000002425 crystallisation Methods 0.000 claims abstract description 10
- 230000008025 crystallization Effects 0.000 claims abstract description 10
- 239000007864 aqueous solution Substances 0.000 claims abstract description 7
- 230000000694 effects Effects 0.000 claims abstract description 7
- 230000035939 shock Effects 0.000 claims abstract description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 45
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 229920006332 epoxy adhesive Polymers 0.000 claims description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 9
- 239000000908 ammonium hydroxide Substances 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- -1 NaHCO3 Organic acid Chemical class 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 239000008213 purified water Substances 0.000 claims description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 7
- 235000017550 sodium carbonate Nutrition 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 235000019441 ethanol Nutrition 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 229910052742 iron Inorganic materials 0.000 claims description 6
- 229910052755 nonmetal Inorganic materials 0.000 claims description 6
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 6
- 229910052725 zinc Inorganic materials 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 5
- 238000006722 reduction reaction Methods 0.000 claims description 4
- 229910010084 LiAlH4 Inorganic materials 0.000 claims description 3
- 229960000583 acetic acid Drugs 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910052782 aluminium Inorganic materials 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 239000007810 chemical reaction solvent Substances 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- 239000012362 glacial acetic acid Substances 0.000 claims description 3
- 150000004678 hydrides Chemical class 0.000 claims description 3
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 3
- 229910052987 metal hydride Inorganic materials 0.000 claims description 3
- 150000004681 metal hydrides Chemical class 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 239000007789 gas Substances 0.000 description 13
- 238000001914 filtration Methods 0.000 description 12
- 238000004321 preservation Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 description 7
- 238000005352 clarification Methods 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-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
- 238000005119 centrifugation Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229910003460 diamond Inorganic materials 0.000 description 4
- 239000010432 diamond Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000003097 mucus Anatomy 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 238000007670 refining Methods 0.000 description 4
- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 4
- 239000011343 solid material Substances 0.000 description 4
- 206010036790 Productive cough Diseases 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- LJPYJRMMPVFEKR-UHFFFAOYSA-N prop-2-ynylurea Chemical compound NC(=O)NCC#C LJPYJRMMPVFEKR-UHFFFAOYSA-N 0.000 description 3
- 210000003802 sputum Anatomy 0.000 description 3
- 208000024794 sputum Diseases 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
- 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
- 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 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000000254 ciliated cell Anatomy 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000000959 ear middle Anatomy 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 210000003695 paranasal sinus Anatomy 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 239000011701 zinc Substances 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
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 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
- 238000004458 analytical method Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-M chloroacetate Chemical compound [O-]C(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-M 0.000 description 1
- 229940089960 chloroacetate Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000000420 mucociliary effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 208000025301 tympanitis Diseases 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
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
Abstract
The invention belongs to technical field of compound preparation, specifically a kind of preparation method of high-purity S- (carboxymethyl)-cysteine；First, it is pre-processed before reacting L-cysteine hydrochloride using reducing agent, chloroacetic aqueous solution is added into system, with the dropwise addition of lye, reaction is constantly carried out to positive reaction direction, it completes, is added dropwise near acid to the isoelectric point of product, low temperature crystallization obtains crude product to be reacted when 6.0-12.0 to system pH；It is dissolved in lye at room temperature, organic acid is added dropwise to pH2.8 or so precipitation product, the product of precipitation is put into pallet, pallet is placed on the water surface, passes through heating, it is pre-processed, during pretreated, the moisture heating in filter cake is until generate minute bubbles, the bubble reaction of generation is to filter cake, make the substance in the moisture in filter cake further generate precipitation product by the shock effect of bubble finally the product that pretreatment is precipitated is put into all-in-one machine, obtains product.
Description
Technical field
The invention belongs to technical field of compound preparation, specifically a kind of high-purity S- (carboxymethyl)-cysteine
Preparation method.
Background technique
S- (carboxymethyl)-cysteine, alias carbocisteine, white crystalline powder；It is odorless slightly molten in the hot water, in second
It is insoluble in alcohol or acetone；It is readily soluble in acid or aqueous slkali.Carbocisteine is a kind of mucus desaturation agent, is mainly influenced in cellular level
The secretion of bronchus body of gland can be such that the cystine linkage of mucin in mucus is broken, and secrete the saliva mucin of low-viscosity and increase, and high
The rock algae mucin of viscosity generates reduction, so that making the viscosity of sputum reduces, is conducive to sputum discharge.
The site of action of carbocisteine is air flue, nasal cavity, nasal sinus and epithelial, the muccus gland of middle ear etc..Respiratory tract, nose
The epithelial of chamber, nasal sinus and middle ear is covered with ciliated cell, and ciliated cell plays an important role in eliminating foreign matter and mucus.It is logical
It crosses the balance for improving mucus ingredient and makes impaired mucous epithelium normalization, Lai Gaishan Mucociliary transport function, promotion sputum,
The excretion of chronic nasosinusitis nasal cavity hydrops, tympanitis hydrops.In addition, carbocisteine is that the first is drained with exudative otitis media
Indication oral preparation.
Patent CN106083673A and CN106565565A disclose S- (carboxymethyl)-cysteine synthetic method,
This route is the regular course for synthesizing carbocisteine, prepares carbocisteine with L-cysteine hydrochloride and chloroacetate reaction, is received
Rate is 96% or so, purity 99.2%.PH is adjusted using liquefied ammonia and ammonium hydrogen carbonate, liquefied ammonia is stored using pressurized tank, has safety to ask
Topic, additional amount is not easy to control, while ammonium salt, chloride are easily exceeded in finished product.
In addition, raw material L-cysteine hydrochloride is oxidizable at cystine under neutral or strong alkaline condition, whole production is caused
The purity of product reduces, while is needed in the preparation by handling in centrifugation, filtering and dry three machines it, efficiency compared with
It is low.Therefore to solve the above-mentioned problems, the present invention provides a kind of preparation methods of high-purity S- (carboxymethyl)-cysteine.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of preparation sides of high-purity S- (carboxymethyl)-cysteine
Method, to solve the problems mentioned in the above background technology.
To achieve the above object, the invention provides the following technical scheme: a kind of high-purity S- (carboxymethyl)-cysteine
Preparation method comprises the following steps that
It is pre-processed before the reaction of a.L- cysteine hydrochloride using reducing agent；
B. chloroacetic aqueous solution is added into system, with the dropwise addition of lye, reaction is constantly carried out to positive reaction direction,
It is completed to system pH to be reacted when 6.0-12.0；
C. it is added dropwise near acid to the isoelectric point of product, the acid of dropwise addition is inorganic acids or the glacial acetic acid such as dilute hydrochloric acid, dilute sulfuric acid
Equal inorganic acids；Crystallization temperature is -10 to 30 DEG C, and the crystallization time is 10 hours or more, and low temperature crystallization obtains crude product；
D. be dissolved in lye at room temperature, preferred alkali be the inorganic bases such as NaOH, KOH, Na2CO3, NaHCO3 and ammonium hydroxide,
Organic acid is added dropwise to pH2.8 or so precipitation product in the organic bases such as triethylamine；
E. the product of precipitation is put into pallet, pallet is placed on the water surface, by heating, it pre-processed, In
During pretreated, until generating minute bubbles, the bubble reaction of generation makes in filter cake the moisture heating in filter cake to filter cake
Moisture in substance precipitation product is further generated by the shock effect of bubble；
F. the product that pretreatment is precipitated is put into all-in-one machine, is filtered, is centrifuged, it is dry, obtain product.
Preferably, the L-cysteine hydrochloride is L-cysteine hydrochloride, l-cysteine and its mixture, is passed through
The content of l-cysteine calculates the amount that reducing agent is added；The type of reducing agent is common alkali metal (such as Na, Al, Zn, Fe etc.),
Active metal hydride (such as LiAlH4), non-metal simple-substance (such as H2, S), Nonmetal hydride, when being in low chemical valence
Salt it is one or more, preferred reducing agent be Na, Zn, Fe and H2；Reduction reaction solvent is aqueous solution, anhydrous organic molten
Agent (methanol, ethyl alcohol) and its mixture, reaction temperature are 35-80 DEG C.
Preferably, the chloroacetic adding manner is to be directly added into be added dropwise with after purified water dissolution；It is chloroacetic to add
Entering amount is 1:1.0~1:1.2 (mol ratio)；Acid binding agent is lye, the inorganic bases such as preferred alkali NaOH, KOH, Na2CO3, NaHCO3
And the organic bases such as ammonium hydroxide, triethylamine；Middle prosecutor formula is pH control, range 7.0-14.0.
Preferably, the all-in-one machine includes body, and the internal body is provided with primary filter, by-pass filtration sieve bottom
It is provided with secondary filter, multiple mandrils are provided between primary filter and secondary filter, multiple mandril bottoms are set
Multiple bottom bars are equipped with, mandril and bottom bar are spaced apart in the x direction and the y direction respectively, and pass through rotation axis between mandril and bottom bar
Rotation connection；Reel is provided at the top of body；It is provided with wirerope at the position at the same diagonal line both ends of body, two
Wirerope is connect with close mandril and bottom bar end respectively, and two wirerope are connected on reel through the wall thickness of body,
The body side is fixed with feeding inlet, and feeding inlet is blocked by articulated slab；The primary filter and secondary filter pass through
Elastic plate connection, the primary filter and body inner wall are connected；When work, product, that is, filter cake of precipitation is put by feeding inlet
Enter at the top of the primary filter of internal body, when initial, mandril and bottom bar are mutually perpendicular to, the shape for surrounding mandril and bottom bar
An exactly square can not see mandril and bottom bar, primary filter can at this time when overlooking primary filter from top
, by rotating reel, twisting wirerope-winding when the size for the filter cake for needing to select is smaller through the filter cake of larger particles
On wheel, wirerope pulls mandril and bottom bar, the multiple diamond shapes of the shape for surrounding mandril and bottom bar, internal body to be initially equipped with
Heater, while organism bottom is equipped with motor, is able to drive body rotation, during body rotation, carries out to filter cake
Centrifugation, throws away the moisture in filter cake completely, enters body inside bottom by primary filter and secondary filter, heats
After the completion of centrifugation, the lesser filter cake of desiccation is fallen at the top of secondary filter from primary filter, such by-pass filtration
The substance of net, secondary filter and body inside bottom is respectively bulky grain filter cake, little particle filter cake and the water being centrifuged out.
Preferably, the body inner wall is provided with gas cell, and gas cell is connect with mandril, mandril and elastic plate；Due to logical
When crossing wirerope multiple mandrils and bottom bar being pulled mutually to rotate, the shape surrounded becomes diamond shape by square, at this point, whole
Body length is elongated, and width shortens, and shortens and locates mandril and the distance between bottom bar and body are increasing, due to there is the work of air-impulse bag
With the mandril and bottom bar at elongated place squeeze gas cell, make the gas in air-impulse bag to movement at the mandril and bottom bar at the place that shortens, will
Air-impulse bag swell herein is filled gap between the place's of shortening mandril and bottom bar and body, prevents mandril and bottom bar in quilt
When wirerope pulling becomes more flat, the leak hole of some primary filter can not be stopped by mandril and bottom bar.
Preferably, the gas cell is Nian Jie by epoxy adhesive with mandril, mandril and elastic plate；Epoxy adhesive tool
There are the excellent properties of high temperature resistant, thermally conductive and low linear expansion, therefore the hot environment of internal body will not influence epoxy adhesive
Adhesive strength, while mandril and bottom bar and the heat of air-impulse bag can be enable sufficiently to be passed by epoxy adhesive thermal conductivity
Lead, and when mandril and bottom bar pull deformation by wirerope, the low linear expansion of epoxy adhesive, it can be made with mandril and
The stability of bottom bar connection is guaranteed.
Technical effect and advantage of the invention:
1, the preparation method of a kind of high-purity S- (carboxymethyl)-cysteine provided by the invention, by the way that filter cake to be put into
Into all-in-one machine, realizes centrifugation, filtering and dry three steps and all completed in a container, while can be according to need
It wants, right, the deformation extent for adjusting mandril and bottom bar obtains desired product size to be filtered to various sizes of filter cake.
2, the preparation method of a kind of high-purity S- (carboxymethyl)-cysteine provided by the invention, by centrifugation, filtering
And drying, the product of precipitation is put into pallet, pallet is placed on the water surface, by heating, it is pre-processed, is being located in advance
During reason, for the moisture heating in filter cake until generating minute bubbles, the bubble reaction of generation makes the water in filter cake to filter cake
Substance in point is further generated by the shock effect of bubble is precipitated product, not only reduces the duration of subsequent drying, also realizes
The raising of product yield.
Detailed description of the invention
The present invention will be further explained below with reference to the attached drawings.
Fig. 1 is method flow diagram of the invention；
Fig. 2 is the stereoscopic schematic diagram of all-in-one machine used in the present invention；
Fig. 3 is the interarea cross-sectional view of all-in-one machine used in the present invention；
Fig. 4 is mandril and bottom bar structural schematic diagram of the invention；
Fig. 5 is the HPLC spectrogram of product made of the embodiment of the present invention 3；
Fig. 6 is the HPLC spectrogram of product made of the embodiment of the present invention 4；
In figure: body 1, primary filter 2, secondary filter 3, mandril 4, bottom bar 5, reel 6, wirerope 7, feeding inlet 8,
Articulated slab 9, elastic plate 10, gas cell 11.
Specific embodiment
In order to be easy to understand the technical means, the creative features, the aims and the efficiencies achieved by the present invention, tie below
Specific embodiment is closed, the present invention is further explained.
As shown in figures 1 to 6, the preparation method of a kind of high-purity S- (carboxymethyl)-cysteine of the present invention, including
Following step:
It is pre-processed before the reaction of a.L- cysteine hydrochloride using reducing agent；
B. chloroacetic aqueous solution is added into system, with the dropwise addition of lye, reaction is constantly carried out to positive reaction direction,
It is completed to system pH to be reacted when 6.0-12.0；
C. it is added dropwise near acid to the isoelectric point of product, the acid of dropwise addition is inorganic acids or the glacial acetic acid such as dilute hydrochloric acid, dilute sulfuric acid
Equal inorganic acids；Crystallization temperature is -10 to 30 DEG C, and the crystallization time is 10 hours or more, and low temperature crystallization obtains crude product；
D. be dissolved in lye at room temperature, preferred alkali be the inorganic bases such as NaOH, KOH, Na2CO3, NaHCO3 and ammonium hydroxide,
Organic acid is added dropwise to pH2.8 or so precipitation product in the organic bases such as triethylamine；
E. the product of precipitation is put into pallet, pallet is placed on the water surface, by heating, it pre-processed, In
During pretreated, until generating minute bubbles, the bubble reaction of generation makes in filter cake the moisture heating in filter cake to filter cake
Moisture in substance precipitation product is further generated by the shock effect of bubble；
F. the product that pretreatment is precipitated is put into all-in-one machine, is filtered, is centrifuged, it is dry, obtain product.
The L-cysteine hydrochloride is L-cysteine hydrochloride, l-cysteine and its mixture, passes through L- Guang ammonia
The content of acid calculates the amount that reducing agent is added；The type of reducing agent is common alkali metal (such as Na, Al, Zn, Fe etc.), active
Metal hydride (such as LiAlH4), non-metal simple-substance (such as H2, S), Nonmetal hydride, salt when in low chemical valence
One or more, preferred reducing agent is Na, Zn, Fe and H2；Reduction reaction solvent is aqueous solution, anhydrous organic solvent (first
Alcohol, ethyl alcohol) and its mixture, reaction temperature is 35-80 DEG C.
The chloroacetic adding manner is to be directly added into be added dropwise with after purified water dissolution；Chloroacetic additional amount is 1:
1.0~1:1.2 (mol ratio)；Acid binding agent is lye, the inorganic bases such as preferred alkali NaOH, KOH, Na2CO3, NaHCO3 and ammonium hydroxide,
The organic bases such as triethylamine；Middle prosecutor formula is pH control, range 7.0-14.0.
The all-in-one machine includes body 1, and the body 1 is internally provided with primary filter 2, and 2 bottom of primary filter is set
It is equipped with secondary filter 3, multiple mandrils 4, multiple 4 bottoms of mandril are provided between primary filter 2 and secondary filter 3
Multiple bottom bars 5 are provided with, mandril 4 and bottom bar 5 are spaced apart in the x direction and the y direction respectively, and are passed through between mandril 4 and bottom bar 5
Rotation axis rotation connection；Reel 6 is provided at the top of body 1；Steel is provided at the position at the same diagonal line both ends of body 1
Cord 7, two wirerope 7 are connect with close mandril 4 and 5 end of bottom bar respectively, and two wirerope 7 run through the wall of body 1
Thickness is connected on reel 6, and 1 side of body is fixed with feeding inlet 8, and feeding inlet 8 is blocked by articulated slab 9；The level-one mistake
Strainer 2 and secondary filter 3 are connected by elastic plate 10, and the primary filter 2 is connected with 1 inner wall of body；When work, it will analyse
Product, that is, filter cake out is put into 2 top of primary filter inside body 1, when initial, mandril 4 and bottom bar 5 by feeding inlet 8
It being mutually perpendicular to, the shape for surrounding mandril 4 and bottom bar 5 is exactly a square, when overlooking primary filter 2 from top, nothing
Method sees mandril 4 and bottom bar 5, and primary filter 2 can penetrate the filter cake of larger particles at this time, when the ruler for the filter cake for needing to select
When very little smaller, by rotating reel 6, it is wrapped in wirerope 7 on reel 6, wirerope 7 pulls mandril 4 and bottom bar 5, makes mandril 4
It is multiple diamond shapes with the shape that bottom bar 5 surrounds, 1 inside of body is initial to install having heaters, while 1 bottom of body is equipped with electricity
Machine is able to drive the rotation of body 1, during body 1 rotates, is centrifuged to filter cake, gets rid of the moisture in filter cake completely
Out, 1 inside bottom of body is entered by primary filter 2 and secondary filter 3, after the completion of heating and centrifugation, desiccation
Lesser filter cake falls to 3 top of secondary filter, such primary filter 2, secondary filter 3 and machine from primary filter 2
The substance of 1 inside bottom of body is respectively bulky grain filter cake, little particle filter cake and the water being centrifuged out.
1 inner wall of body is provided with gas cell 11, and gas cell 11 is connect with mandril 4, mandril 4 and elastic plate 10；Due to
When pulling multiple mandrils 4 and bottom bar 5 mutually to rotate by wirerope 7, the shape surrounded becomes diamond shape by square, this
When, entire length is elongated, and width shortens, and shortens and locates mandril 4 and the distance between bottom bar 5 and body 1 are increasing, due to there is punching
The effect of air bag, the mandril 4 and bottom bar 5 at elongated place squeeze gas cell 11, make mandril 4 He of the gas in air-impulse bag to the place that shortens
It is mobile at bottom bar 5, air-impulse bag swell herein is filled gap between the place's of shortening mandril 4 and bottom bar 5 and body 1, prevents
Only when becoming more flat by the pulling of wirerope 7, the leak hole of some primary filter 2 can not be by mandril 4 for mandril 4 and bottom bar 5
Stop with bottom bar 5.
The gas cell 11 is Nian Jie by epoxy adhesive with mandril 4, mandril 4 and elastic plate 10；Epoxy adhesive has
High temperature resistant, thermally conductive and low linear expansion excellent properties, therefore to will not influence epoxy adhesive viscous for the hot environment inside body 1
Intensity is connect, while mandril 4 and bottom bar 5 and the heat of air-impulse bag can be enable sufficiently to be passed by epoxy adhesive thermal conductivity
It leads, and when mandril 4 and bottom bar 5 pull deformation by wirerope 7, the low linear expansion of epoxy adhesive can make itself and top
The stability that bar 4 and bottom bar 5 connect is guaranteed.
Embodiment 1
By 100.0g L-cysteine hydrochloride mixture, (L-cysteine hydrochloride content 50.2%, l-cysteine contains
49.0%) amount is added in 1L reaction kettle with 500mL purified water, open stirring at room temperature, and iron powder 30.0g is added, is warming up to 60 DEG C,
30min is reacted after reaching temperature, is cooled down, when temperature of reaction kettle reaches 30-40 DEG C, monoxone 66.4g is added into reaction kettle
Start that sodium hydroxide solution is added dropwise, control reaction temperature is no more than 60 DEG C.When monitoring pH is 7.0-8.0, stop that hydroxide is added dropwise
Sodium solution, 60 DEG C of heat preservation 30min.It is cooled to room temperature, starts that dilute sulfuric acid is added dropwise, control reacting liquid temperature is lower than 30 DEG C.It is added dropwise to
When system pH2.5-3.0 or so, reach terminal, be cooled to -5 to 10 DEG C of heat preservation 16h, filter cake is eluted with 30g water, is filtered, dry
Obtain crude product 95.2g, yield 93.3%, purity 99.5%.
Crude product is put into refining kettle, at room temperature addition ammonium hydroxide to solid material whole dissolved clarification, stirs lower dropwise addition dilute sulfuric acid,
When to system pH being 2.5-3.0, reaches terminal, be cooled to -5 to 0 DEG C of heat preservation 16h, filter cake 30g water elution is added to one
In machine, filtering is dried to obtain product 93.5g, total recovery 91.7%, purity 99.90%.
Embodiment 2
By 100.0g L-cysteine hydrochloride monohydrate (L-cysteine hydrochloride content 99.5%) and 300mL
Purified water is added in 1L reaction kettle, opens stirring, and at room temperature after dissolved clarification, iron powder 5.0g is added, is warming up to 60 DEG C, after reaching temperature
30min is reacted, monoxone 56.5g is added into reaction kettle and starts that carbon is added dropwise when temperature of reaction kettle reaches 30-40 DEG C for cooling
Sour hydrogen sodium solution, control reaction temperature are no more than 60 DEG C.When monitoring pH is 7.0-8.0, stopping dropwise addition sodium bicarbonate solution, 60 DEG C
Keep the temperature 30min.When being cooled to 15-30 DEG C, start that dilute sulfuric acid is added dropwise, control reacting liquid temperature is lower than 30 DEG C.It is added dropwise to system
When pH2.5-3.0 or so, reach terminal, be cooled to -5 to 0 DEG C of heat preservation 12h, filter cake is eluted with 30g water, filtering, is dried to obtain thick
Product 98.5g, yield 96.6%, purity 99.2%.
Crude product is put into refining kettle, at room temperature addition ammonium hydroxide to solid material whole dissolved clarification, stirs lower dropwise addition dilute hydrochloric acid,
When to system pH being 2.5-3.0, reaches terminal, be cooled to -5 to 0 DEG C of heat preservation 12h, filter cake 30g water elution is added to one
In machine, filtering is dried to obtain product 95.5g, total recovery 93.6%, purity 99.97%.
Embodiment 3
It weighs 375kg purified water and puts into 1000L reaction kettle, starting stirring weighs L-cysteine hydrochloride monohydrate
150.0kg at room temperature after dissolved clarification, stirs 10 minutes, 4.5Kg iron powder is added, and has bulk gas generation, and 35-45 DEG C is stirred 60 points
Clock.It weighs monoxone 89.2kg to be added in reaction kettle, insulated and stirred 30-40 minutes.Start that sodium carbonate liquor is added dropwise, adjusts
PH7.0-8.0,60 DEG C of heat preservation 30min.When being cooled to 15-30 DEG C, start that dilute sulfuric acid is added dropwise, control reacting liquid temperature is lower than 30
℃.When being added dropwise to system pH2.5-3.0 or so, reach terminal, be cooled to -5 to 0 DEG C of heat preservation 12h, filter cake centrifugal filtration is dry
Obtain crude product 146.9kg, yield 96.0%, purity 99.5%.
Crude product is put into refining kettle, NaOH solution is added at room temperature to solid material whole dissolved clarification, ethyl alcohol is added
320kg stirs lower dropwise addition 1mol/L dilute hydrochloric acid, until reaching terminal when system pH is 2.5-3.0, being cooled to -5 to 0 DEG C of heat preservations
12h is added in all-in-one machine, centrifugal filtration, is dried to obtain product 140.5kg, total recovery 91.8%, purity 99.91%.
Embodiment 4
It weighs 375kg purified water and puts into 1000L reaction kettle, starting stirring weighs L-cysteine hydrochloride monohydrate
150.1kg at room temperature after dissolved clarification, stirs 10 minutes, 4.5Kg iron powder is added, and has bulk gas generation, and 35-45 DEG C is stirred 60 points
Clock.It weighs monoxone 89.2kg to be added in reaction kettle, insulated and stirred 30-40 minutes.Start that ammonium hydroxide is added dropwise, adjust pH7.0-8.0,
60 DEG C of heat preservation 30min.When being cooled to 15-30 DEG C, start that dilute hydrochloric acid is added dropwise, control reacting liquid temperature is lower than 30 DEG C.It is added dropwise to body
When being pH2.5-3.0 or so, reach terminal, be cooled to -5 to 10 DEG C of heat preservation 18h, filter cake centrifugal filtration obtains filter cake 280.3kg
(weight in wet base).Crude product is put into refining kettle, at room temperature addition NaOH solution to solid material whole dissolved clarification, ethyl alcohol 320kg is added,
Stirring is lower to be added dropwise 1mol/L dilute hydrochloric acid, until reaching terminal when system pH is 2.5-3.0, being cooled to -5 to 10 DEG C of heat preservation 18h, add
Enter into all-in-one machine, centrifugal filtration, is dried to obtain product 144.6kg, total recovery 94.4%, purity 99.94%.
Embodiment 3,4 sample detection results
。
The basic principles, main features and advantages of the invention have been shown and described above.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes and improvements
It all fall within the protetion scope of the claimed invention.The claimed scope of the invention is by appended claims and its equivalent circle
It is fixed.
Claims (6)
1. a kind of preparation method of high-purity S- (carboxymethyl)-cysteine, it is characterised in that: comprise the following steps that
It is pre-processed before the reaction of a.L- cysteine hydrochloride using reducing agent；
B. chloroacetic aqueous solution is added into system, with the dropwise addition of lye, reaction is constantly carried out to positive reaction direction, until body
It is that pH completes to react when 6.0-12.0；
C. it is added dropwise near acid to the isoelectric point of product, the acid of dropwise addition is the nothings such as inorganic acids or glacial acetic acid such as dilute hydrochloric acid, dilute sulfuric acid
Machine acid；Crystallization temperature is -10 to 30 DEG C, and the crystallization time is 10 hours or more, and low temperature crystallization obtains crude product；
D. it is dissolved in lye at room temperature, preferred alkali is inorganic bases and the ammonium hydroxide, three second such as NaOH, KOH, Na2CO3, NaHCO3
Organic acid is added dropwise to pH2.8 or so precipitation product in the organic bases such as amine；
E. the product of precipitation is put into pallet, pallet is placed on the water surface, by heating, it pre-processed, is being located in advance
During reason, for the moisture heating in filter cake until generating minute bubbles, the bubble reaction of generation makes the water in filter cake to filter cake
Substance in point is further generated by the shock effect of bubble is precipitated product；
F. the product that pretreatment is precipitated is put into all-in-one machine, is filtered, is centrifuged, it is dry, obtain product.
2. a kind of method of high-purity S- (carboxymethyl)-cysteine according to claim 1, it is characterised in that: described
L-cysteine hydrochloride is L-cysteine hydrochloride, l-cysteine and its mixture, is calculated by the content of l-cysteine
The amount of reducing agent is added；The type of reducing agent is common alkali metal (such as Na, Al, Zn, Fe etc.), active metal hydride
(such as LiAlH4), non-metal simple-substance (such as H2, S), Nonmetal hydride, one kind of salt when in low chemical valence or more
Kind, preferred reducing agent is Na, Zn, Fe and H2；Reduction reaction solvent is aqueous solution, anhydrous organic solvent (methanol, ethyl alcohol)
And its mixture, reaction temperature are 35-80 DEG C.
3. a kind of preparation method of high-purity S- (carboxymethyl)-cysteine according to claim 1, it is characterised in that:
The chloroacetic adding manner is to be directly added into be added dropwise with after purified water dissolution；Chloroacetic additional amount is 1:1.0~1:
1.2 (mol ratios)；Acid binding agent is lye, the inorganic bases and ammonium hydroxide, triethylamine etc. such as preferred alkali NaOH, KOH, Na2CO3, NaHCO3
Organic base；Middle prosecutor formula is pH control, range 7.0-14.0.
4. a kind of preparation method of high-purity S- (carboxymethyl)-cysteine according to claim 1, it is characterised in that:
The all-in-one machine includes body (1), and the body (1) is internally provided with primary filter (2), and primary filter (2) bottom is set
It is equipped with secondary filter (3), is provided between primary filter (2) and secondary filter (3) multiple mandrils (4), it is multiple described
Mandril (4) bottom is provided with multiple bottom bars (5), and mandril (4) and bottom bar (5) are spaced apart in the x direction and the y direction respectively, and is pushed up
It is rotatablely connected between bar (4) and bottom bar (5) by rotation axis；Reel (6) are provided at the top of body (1)；It is same positioned at body (1)
Be provided at the position at diagonal line both ends wirerope (7), two wirerope (7) respectively with close mandril (4) and bottom bar (5)
End connection, and wall thickness of two wirerope (7) through body (1) is connected on reel (6), body (1) side is connected
Have feeding inlet (8), feeding inlet (8) is blocked by articulated slab (9)；The primary filter (2) and secondary filter (3) pass through bullet
Property plate (10) connect, the primary filter (2) and body (1) inner wall are connected.
5. a kind of preparation method of high-purity S- (carboxymethyl)-cysteine according to claim 4, it is characterised in that:
Body (1) inner wall is provided with gas cell (11), and gas cell (11) is connect with mandril (4), mandril (4) and elastic plate (10).
6. a kind of preparation method of high-purity S- (carboxymethyl)-cysteine according to claim 5, it is characterised in that:
The gas cell (11) is Nian Jie by epoxy adhesive with mandril (4), mandril (4) and elastic plate (10).
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