CN106279030B - Using the method for the MAA crystallization production COS analgins that the molten method of wine obtains - Google Patents
Using the method for the MAA crystallization production COS analgins that the molten method of wine obtains Download PDFInfo
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- CN106279030B CN106279030B CN201610642131.9A CN201610642131A CN106279030B CN 106279030 B CN106279030 B CN 106279030B CN 201610642131 A CN201610642131 A CN 201610642131A CN 106279030 B CN106279030 B CN 106279030B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
- C07D231/46—Oxygen atom in position 3 or 5 and nitrogen atom in position 4
- C07D231/48—Oxygen atom in position 3 or 5 and nitrogen atom in position 4 with hydrocarbon radicals attached to said nitrogen atom
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Abstract
The invention discloses a kind of methods of the MAA crystallization production COS analgins obtained using the molten method of wine.This approach includes the following steps：The preparation process of MAA crystallizations：Alcohol is added into MAA oil, MAA crystallizations and mother liquor are respectively obtained through standing, crystallization, centrifugation successively after mixing；Step of condensation：Condensation reaction is carried out by MAA crystallizations, with formaldehyde, sodium pyrosulfite, generates analgin feed liquid；Post-processing step：The analgin feed liquid is subjected to decrease temperature crystalline, centrifugation and drying successively, to obtain meeting the analgin of COS standards.The method of the present invention production COS standard analgin one-time success rates can reach 85% or more, and yield can monthly reach 20 25 tons, and cost saves about 3000 yuan/ton than existing method.
Description
Technical field
The invention belongs to field of medicine and chemical technology, more particularly to a kind of MAA crystallization production COS peaces obtained using the molten method of wine are
Close method.
Background technology
Analgin, common prescription medical insurance drug, entitled [(1, the 5- dimethyl -2- phenyl -3- oxos -2,3- bis- of chemistry
Hydrogen -1H- pyrazoles -4- bases) methylamino] Loprazolam sodium salt, structural formula is as shown in formula I, molecular formula：C13H16N3NaO4S, molecule
Amount：333.34, it is soluble easily in water, it is antipyretic, analgesic activity is fast and strong compared with aminopyrine.It is mainly used for bringing down a fever, is also used to treat acute
The diseases such as arthritis, headache, rheumatic pain, toothache and courbature.
The method of industrial production analgin is that antipyrine, antipyrine is made using pyrazolone as starting material at present
By nitrosation, reduction, hydrolysis, obtained 4-AA is neutralized, 4-AA is through acylated obtained 4- formyl ammonia
Base antipyrine, 4- formyl amino antipyrines are through methylating, hydrolyzing, neutralize and obtaining 4- novalgins (i.e. MAA oil), 4-
Analgin is made with formaldehyde, sodium sulfite condensation in novalgin.
In recent ten years, no matter China is presented swift and violent fast-developing trend in terms of the production of analgin or outlet,
Lasting for years export volume crosses ten thousand tons, annual export volume be more than annual total growth more than half.As analgin export volume is held
Continuous to increase, the trend steadily risen is presented in selling price, and benefit has also driven domestic associated production enterprise while raising
Enthusiasm.With the development of market competition, the demand of high standard especially COS standards analgin gradually increases.European Union's COS standards
Tightened up in terms of content and impurity requirement, this requires us to change existing production method, produces purity higher and (rolls over
Dry product content is 99.0%~101.0%), impurity is less (i.e. other any unknown impuritie≤0.05% detected), color
The analgin bulk drug of whiter (i.e. character is white or almost white crystalline powder), to meet COS standards.Existing method
The production of COS analgins is that the above MAA oil of content 92wt% obtained using production directly carries out condensation reaction, thick after reaction
Product weighs molten and is dried to obtain finished product through refining crystallization, wet product, and the molten method of analgin wet product weight packs previous process from product drying
Refining step is started with, and analgin refinement is got rid of the wet fine work of analgin that finishes of material put into be condensed in tank again and use
Alcohol carries out second and dissolves, and activated carbon decolorizing is added, to reduce the impurity wrapped up in analgin wet product, although the method also can
Satisfactory COS products are produced, but the method is cumbersome, working hour, product qualification rate was about compared with long, labor intensity is big
40% or so, it is relatively low, and the one-time success rate of finished product is relatively low, production cost is higher, therefore be badly in need of improving COS analgin finished products
One-time success rate, the yield for reducing production cost and expanding COS analgins.
Invention content
In order to solve the defect of prior art, the object of the present invention is to provide a kind of MAA obtained using the molten method of wine
The method of crystallization production COS analgins.The one-time success rate that this method produces COS finished products is high, and COS analgins yield is high, reduces
Production cost.
The purpose of the present invention is what is be achieved through the following technical solutions：
A method of the MAA crystallization production COS analgins obtained using the molten method of wine are included the following steps：
The preparation process of MAA crystallizations：Alcohol is added into MAA oil, successively through standing, crystallization, centrifugation after mixing, respectively
To MAA crystallizations and mother liquor；
Step of condensation：Condensation reaction is carried out by MAA crystallizations, with formaldehyde, sodium pyrosulfite, generates analgin material
Liquid；
Post-processing step：The analgin feed liquid is subjected to decrease temperature crystalline, centrifugation and drying successively, to be met
The analgin of COS standards.
The preparation process of the MAA crystallizations of the method for the present invention is substantially to carry out removal of impurities processing to MAA oil using alcohol, is come
Purify MAA oil.Using the different solubility of MAA and other impurities in alcohol, MAA oil is dissolved by alcohol, is cooled down,
Crystallization, centrifugation, to realize the separating effect of MAA and partial impurities.
In the preparation process of the MAA crystallizations of the method for the present invention, the MAA crystalline contents >=95wt% (ratios being prepared
Such as 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%), most of content between 97-98wt%,
For percent crystallization in massecuite 75% or so, crystalline particle is big, and color is yellowish-white, and crystal form is good, and the one-time success rate of COS standard analgin finished products is
85% or more, for product yield up to 80% or more, finished product content is qualified.
In the preparation process of the MAA crystallizations of the method for the present invention, the MAA oil, that is, 4- novalgin oil, is that peace is
An intermediate in nearly production process, has following property：Brownish red oily liquids, is insoluble in water, is soluble in alcohol, organic
Solvent has alkalescent, and easily crystallizes, and this field conventional method may be used and prepare, for example, 4- formamido groups peace for than
Woods FAA is neutralized through methylating, hydrolyzing, once, is decolourized, secondary neutralization, being dehydrated obtained 4- novalgins (i.e. MAA oil),
The content (i.e. purity) of MAA oil is generally at 92wt% or more (such as 92.5wt%, 93wt%, 93.5wt%, 94wt%).
In the above-mentioned methods, as a preferred implementation manner, in the preparation process of MAA crystallizations, the alcohol
The content of middle ethyl alcohol 95wt% or more (such as 95wt%, 95.5wt%, 96wt%, 96.5wt%, 97wt%,
97.5wt%).
In the above-mentioned methods, as a preferred implementation manner, in the preparation process of MAA crystallizations, every kilogram of institute
State in MAA oil be added 0.3-0.4L alcohol (such as：0.31L alcohol/kg MAA oil, 0.33L alcohol/kg MAA oil, 0.35L
Alcohol/kg MAA oil, 0.36L alcohol/kg MAA oil, 0.37L alcohol/kg MAA oil, 0.38L alcohol/kg MAA oil, 0.39L
Alcohol/kg MAA oil).
In the preparation process of above-mentioned MAA crystallizations, when alcohol dosage is very few, the content of MAA crystallizations is low, and impurity content is high,
The analgin finished product obtained simultaneously is unqualified；When alcohol dosage is excessive, cost improves, and the yield of MAA crystallizations decreases.
In the above-mentioned methods, as a preferred implementation manner, in the preparation process of MAA crystallizations, the crystallization
It is specific as follows：The mixture of MAA oil and alcohol after standing is pumped into crystallizing tank, then heating crystalline tank, then crystallizing tank is dropped
Temperature, so that MAA is crystallized.
It is highly preferred that described stand is stood under the conditions of 60-70 DEG C (such as 61 DEG C, 63 DEG C, 65 DEG C, 68 DEG C, 69 DEG C)
30-60min (such as 31min, 35min, 40min, 48min, 52min, 55min, 58min).Completing standing at this temperature can
It is crystallized to avoid MAA.Standing can complete in the external stainless steel sink with chuck, in order to the control of dwell temperature, when
So other material and mode of heating can also be selected to be stood.Standing herein can allow in MAA oil the impurity wrapped up more preferable
Ground and the separation of MAA oil.
It is highly preferred that the suction crystallizing tank is by the MAA oil pick-up tubes after preheating by the MAA oil and alcohol after standing
Mixture is evacuated in crystallizing tank.Further, the MAA oil pick-up tubes after the preheating have 60-70 DEG C (such as 61 DEG C, 63 DEG C, 65
℃、68℃、70℃)。
The purpose of preheating oil pick-up tube is exactly to block pipeline after preventing material in pipeline from crystallizing, and extracts MAA oil and alcohol
Negative-pressure ward may be used in mixture.
It is highly preferred that the heating crystalline tank be by crystallizing tank be heated to 60 DEG C or more (such as 61 DEG C, 63 DEG C, 65 DEG C, 68
DEG C, 70 DEG C, 72 DEG C, 73 DEG C), further, crystallizing tank is heated to 60-70 DEG C (since MAA is molten in alcohol by steam
Solubility of the Xie Du ratios MAA in water is high, and temperature here refers to ensureing that MAA all dissolves in alcohol).When MAA oil and
After the mixture of alcohol enters crystallizing tank, temperature can decrease, and has sub-fraction and is crystallized on tank skin, at this moment just needs handle
After material, which reheats, makes the crystallization on tank skin dissolve, and the material in tank body is all in the state of dissolving, then carry out
The work of decrease temperature crystalline is conducive to the stabilization of material Crystal type and the homogeneity of material in this way.
It is highly preferred that crystallizing tank cooling is the crystallizing tank to be cooled to 10 DEG C or less (cooling to 10 DEG C or less is
In order to ensure the percent crystallization in massecuite of MAA crystallizations, 10 DEG C or more whens, also have small part MAA not crystallize to finish either MAA knots
Brilliant crystal form is also unstable) (such as 10 DEG C, 9 DEG C, 8 DEG C, 7 DEG C, 6 DEG C, 5 DEG C, 4 DEG C), the preferably described crystallizing tank is cooled to 5-10
DEG C, further, the crystallizing tank includes：Tank body is crystallized, top is equipped with material inlet valve, and bottom is equipped with material outlet valve, interior
Portion is equipped with agitating device；Chuck is close to the outer wall of the crystallization tank body, by being passed through steam, brine into the chuck or following
Ring water controls the temperature in the crystallizing tank body；Steam enters valve, is set on the pipeline that the chuck supplies steam, uses
Enter the speed of chuck in control steam；Steam exhaust dump valve is set to and is discharged on the pipeline of steam exhaust from the chuck, for controlling
The speed of the chuck is discharged in steam exhaust processed；Into brine valve, it is set on the pipeline that the chuck supplies brine, for controlling salt
Water enters the speed of chuck；Brine valve is returned, is set to and is discharged on the pipeline of brine from the chuck, for controlling brine discharge
The speed of the chuck；The crystallizing tank cooling in turn includes the following steps：
Step 1, open agitating device, rotating speed be 15-20 revs/min (such as 16 revs/min, 17 revs/min, 18 revs/min, 19
Rev/min, 20 revs/min), the working condition of the agitating device is continued until in the crystallizing tank that material discharging finishes；
Step 2, by after heating crystallizing tank Temperature fall 80min-100min (such as 82min, 85min, 90min,
95min, 98min), during the Temperature fall, material inlet valve, material outlet valve, steam enter valve, steam exhaust discharge
Valve is in closed state into brine valve, time brine valve；
Step 3, open after Temperature fall it is described return brine valve, while it will be (i.e. small described into brine valve will to open 20-40 degree
Drive brine valve into), it, will when the crystallizing tank is cooled to 45-55 DEG C (such as 46 DEG C, 48 DEG C, 50 DEG C, 52 DEG C, 53 DEG C, 54 DEG C)
It is described into brine valve open 50-70 degree (driving brine valve in i.e. into), when the crystallizing tank be cooled to 35-45 DEG C (such as 36 DEG C, 38
DEG C, 40 DEG C, 42 DEG C, 43 DEG C, 44 DEG C) when, described 80-90 degree (driving brine valve into greatly) will be opened into brine valve, until crystallizing
Tank is cooled to 10 DEG C or less (such as 10 DEG C, 9 DEG C, 8 DEG C, 7 DEG C, 6 DEG C, 5 DEG C, 4 DEG C).
The MAA Crystal types that are cooled down using the above method are stable, uniformly, the percent crystallization in massecuite of MAA crystallizations it is stable and
It is efficient, it is suitble to production；The method that the crystallizing tank cooling of the present invention can also use natural cooling cools down, and can also obtain
To preferable crystallization, but the time is too long, and efficiency is low, is not suitable for production；And if cooling whole process is quickly cooled down, it obtains
Crystal form appearance is irregular, crystal form is not of uniform size, uneven, and the percent crystallization in massecuite of MAA crystallizations is also unstable.
Valve used above can be ball valve.
In the above-mentioned methods, as a preferred implementation manner, in the preparation process of MAA crystallizations, the centrifugation
It is to centrifuge the material in the crystallizing tank after cooling, stops centrifugation when the mother liquor being discharged in centrifuge is zero.It is more excellent
Selection of land, centrifugation time are 20-25min (such as 21min, 22min, 23min, 24min, 25min).
Under normal circumstances, MAA is counted after centrifugation and crystallize weight, packed by 30kg/ parts, MAA crystalline content >=95%
(MAA crystallization content be to be obtained by chemical titration commonly used in the art, MAA crystalline contents such as be 95%, 95.5%,
96%, 96.5%, 97%, 97.5%, 98%, 98.5%).
In the above-mentioned methods, as a preferred implementation manner, in the preparation process of MAA crystallizations, the mother liquor
It is back to after activated carbon decolorizing adsorbs and produces the condensation process of common analgin (analgin of i.e. non-COS standards) and apply mechanically.
The mother liquor of MAA crystallizations cannot be applied mechanically since impurity is more in the batch of production COS material, can only be common in production
It is used through decolorization rear enclosure when analgin material, in order to ensure that common analgin (meets Chinese Pharmacopoeia version first in 2010 to augment
This standard requirement) quality, for every batch of produce 1500kg analgins for, the mother liquor amount that every batch of can apply mechanically is about 200 liters.
In the above-mentioned methods, as a preferred implementation manner, in the step of condensation, first the MAA is tied
Crystalline substance input condensation tank, is then added the ratio of 2.2-2.3L (such as 2.21L, 2.25L, 2.29L) alcohol according to every kilogram of MAA crystallization
Example is added alcohol into the condensation tank, then by the condensation tank be warming up to 70-80 DEG C (such as 71 DEG C, 72 DEG C, 75 DEG C, 77 DEG C,
79 DEG C), sodium pyrosulfite is added after MAA crystallizations dissolving in the condensation tank and formaldehyde carries out condensation reaction, wherein is described
MAA crystallization scale (be added MAA crystallization gross mass × MAA crystalline contents), formaldehyde, sodium pyrosulfite mass ratio be
1:(0.13-0.15):(0.44-0.46), it is preferable that the alcohol is commercially available edible alcohol, and ethanol content requires
95wt% or more (such as 95wt%, 95.5wt%, 96wt%, 96.5wt%, 97wt%).
In the above-mentioned methods, as a preferred implementation manner, in the rear in processing step, the decrease temperature crystalline refers to
The design parameter of the decrease temperature crystalline of the analgin feed liquid obtained after to condensation reaction, the drying is as follows：Inlet temperature is
148-165 DEG C (such as 149 DEG C, 150 DEG C, 155 DEG C, 160 DEG C, 164 DEG C), outlet temperature be 60-80 DEG C (such as 61 DEG C, 65 DEG C,
70 DEG C, 75 DEG C, 79 DEG C), the time is 5.5-6h (such as 5.6h, 5.7h, 5.8h, 5.9h).It is highly preferred that processing walks in the rear
In rapid, the decrease temperature crystalline is specific as follows：First be naturally cooling to 65-75 DEG C (such as 66 DEG C, 67 DEG C, 68 DEG C, 70 DEG C, 72 DEG C, 73
DEG C, 74 DEG C), then use circulating water cooling to 25-35 DEG C (such as 26 DEG C, 27 DEG C, 28 DEG C, 29 DEG C, 31 DEG C, 32 DEG C, 34 DEG C).
The present invention has the advantages that compared with prior art：
The analgin that the method for the present invention obtains meets COS standards, the one-time success rate for increasing COS finished products, expands COS
The yield of analgin reduces production cost.In the existing method, directly the MAA oil that MAA processes obtain is used to be condensed anti-
It answers, then obtains the analgin finished product for meeting COS standards, existing method production by carrying out repeatedly purifying to analgin feed liquid
The one-time success rate of the analgin of COS standards is 40% hereinafter, product yield is low, and yield is monthly 10 tons, and the method for the present invention
The one-time success rate of production COS analgins can reach 85% or more, and yield can monthly reach 20-25 tons, and cost compares existing method
Save about 3000 yuan/ton.In addition the method for the present invention product yield can reach 80% or more, and finished product content is qualified, defects inspecting item
Unknown impuritie is low, and generally 0.035%~0.05%, colorimetric is good.
Description of the drawings
Fig. 1 is the schematic diagram of crystallizing tank of the present invention, wherein 1, crystallization tank body；11, material inlet valve；12, material outlet
Valve；13, agitating device；2, chuck；21, steam enters valve；22, steam exhaust dump valve；23, into brine valve；24, brine valve is returned；25、
Compression valve；26, pressure gauge.
Specific implementation mode
The production method of the COS standard analgins of the present invention is illustrated with reference to the accompanying drawings and examples.It should be understood that
These embodiments are only used for explaining the present invention rather than limit the scope of the invention.Externally it should be understood that reading the present invention
Content after, those skilled in the art make various changes or modifications the present invention, and such equivalent forms equally fall within the application
The appended claims limited range.
The crystallizing tank and be condensed two kinds of equipment that tank is commonly used in the art that the present invention uses, are equipped with folder outside tank body
Set, with the work that the substance to tank interior is heated up, kept the temperature or cooled down, the temperature control principle phase of two kinds of tanks of chuck pair
Together, the crystallization jar structure that the present invention uses simply is introduced below, and referring to Fig. 1, the crystallizing tank includes：Tank body 1 is crystallized,
Top is equipped with material inlet valve 11, is used for the entrance of control material, and bottom is equipped with material outlet valve 12, is used for the row of control material
Go out, is internally provided with agitating device 13, the material for being stirred in crystallizing tank；Chuck 2 is close to crystallize the outer wall of tank body 1, be led to
It crosses and is passed through steam, brine or recirculated water into chuck 2 to control the temperature in crystallization tank body 1；Steam enters valve 21, be set to
Chuck 2 supplies on the pipeline of steam, and the speed of chuck 2 is entered for controlling steam；Steam exhaust dump valve 22 is set to from chuck 2
On the pipeline of middle discharge steam exhaust, the speed of chuck 2 is discharged for controlling steam exhaust；Into brine valve 23, it is set to chuck 2 and supplies salt
On the pipeline of water, the speed of chuck 2 is entered for controlling brine；Brine valve 24 is returned, the pipe that brine is discharged from chuck 2 is set to
On the road, the speed of chuck 2 is discharged for controlling brine；Compression valve 25 and pressure gauge 26, are set to the pipeline being connected to chuck 2
On, by the pressure in the display observation chuck 2 of pressure gauge 26 and the pressure in chuck 2 is adjusted by compression valve 25.
The preparation method of the MAA oil used in following embodiment is as follows：
4- formyl amino antipyrines FAA methylates：900L water is added in the tank that methylates, puts into 750kgFAA, opens
Stirring is added 600kg dimethyl suflfates, while constantly cooling, liquid caustic soda is added when temperature reaches 10 DEG C in tank, surveys pH value 9
When left and right, methylate qualification.
Hydrolysis：The qualified feed liquid that will methylate is squeezed into hydrolytic decomposition pot, and stirring is opened, and 890kg sulfuric acid is added, and opens steam heating
Hydrolytic decomposition pot, temperature control keep the temperature 4 hours at 135-145 DEG C, after survey percent hydrolysis, percent hydrolysis reaches 98% or more and is considered as conjunction
Lattice are put into a neutralizing tank after qualified.
It is primary to neutralize：It opens a neutralizing tank air draft and stirs, water of 700L is added, opens steam and is warming up to 80 DEG C, so
Ammonium hydroxide is added afterwards to neutralize, it is that 2.0-2.5 stops adding ammonium hydroxide to be neutralized to pH value, and MAA oil proportions are measured in 1.19-1.22 with densimeter
Between (pycnometric purpose be in order to enable MAA oil smoothly separated from mother liquor provide reference frame).
Decoloration：After primary neutralization, 30kg activated carbons are added in a neutralizing tank, keep 80-90 DEG C of temperature, heat preservation
1 hour.
Secondary neutralization：Feed liquid is pressed by filter in secondary neutralizing tank after decoloration, proportion is adjusted with a water,
When proportion is 1.23 or so, it is passed through liquefied ammonia and adjusts acidity, maintain the temperature at 70-90 DEG C, pH value stops neutralizing when reaching 7.2-7.5,
Stratification later.
Dehydration：Mother liquor after layering is separated, then MAA oil is evacuated in drain sump through suction filtration tank, steam is opened and adds
Heat carries out dehydrating operations under vacuum, and dehydration temperaturre is 95 DEG C, about 1 hour time.4- novalgins are made
The content of (i.e. MAA oil), MAA oil is 92wt%.
The alcohol used in following embodiment is commercially available alcohol, ethanol content 95wt%.
Embodiment 1
The preparation of MAA crystallizations：MAA oil is added in the external MAA oil storage tanks equipped with chuck, then according to every kilogram of MAA
Alcohol is added to MAA oil storage tanks in the amount that alcohol 0.3L is added in oil, and crack steam controls the temperature of MAA oil storage tanks at 65 DEG C or so
(preventing MAA from crystallizing) stands 30 minutes；Vacuum is opened, is pumped by the way of negative-pressure ward by being preheated to 65 DEG C or so of MAA
The upper solution that pipe extracts MAA oil storage tanks enters in crystallizing tank；The steam being then turned on crystallizing tank enters valve 21, by crystallizing tank
Interior material is risen again to 65 DEG C, checks whether each valve switch is correct (other each valves should be at closed state) on crystallizing tank, weary
Vapour dump valve 22 should be at closed state at this time；It opens agitating device later to start to stir, rotating speed is 18 revs/min, until crystallizing tank
All discharge just stops stirring to interior material；By crystallizing tank Temperature fall 1.5 hours；Brine valve 24 is opened back later, it is small to drive into
Brine valve 23 (i.e. will into brine valve 23 open 30 degree) cool down to crystallizing tank, when being cooled to 50 DEG C, in open brine valve 23 (i.e.
60 degree will be opened into brine valve 23) cool down, when being cooled to 40 DEG C, open brine valve 23 greatly (will open 90 into brine valve 23
Spend) crystallizing tank is cooled to 10 DEG C, prepare centrifugally operated；Material in crystallizing tank is put into centrifuge and is centrifuged, observation is set to
When the mother liquor amount flowed out in mother liquor pipeline on centrifuge is almost nil, stop centrifuge by MAA crystallize take out, according to 30 ㎏/
Part is packed for being condensed process, sample examination, and obtained MAA crystalline contents are 97.90wt%.
It is condensed purification step：MAA is crystallized in input condensation tank, 2.25L alcohol amounts are added to contracting according to 1kg MAA crystallizations
It closes in tank and alcohol is added, condensation tank, which is then warming up to 75 DEG C, makes MAA crystallization dissolvings, and (MAA is tied the scale crystallized according still further to MAA
Brilliant total amount * 97.90wt%), formaldehyde, sodium pyrosulfite mass ratio be 1:0.14:0.45 amount is condensed into condensation tank
Analgin feed liquid is pressed into crystallizing tank by reaction after completion of the reaction, is naturally cooling to 65 DEG C, is opened recirculated water valve and is dropped
Temperature when being cooled to 25-35 DEG C, closes recirculated water valve, prepares centrifugation.By analgin wet product input air flow drying machine after centrifugation
In, 150 DEG C of inlet temperature, 60 DEG C of outlet temperature is 5.5 hours dry, obtains analgin finished product.Determination of Analgin 99.9%, it is miscellaneous
Matter E (≤0.15%) is 0.13%, and unknown impuritie (≤0.05%) is 0.038%, meets COS standards.Product yield is 82%.
It is multiple batches of to produce obtained statistical result showed, produce COS standard analgins according to 1 process of embodiment, one
Secondary success rate is 86%, that is, COS standards analgin can successfully be prepared 86 times by carrying out the production of 100 batches.
Embodiment 2
The preparation of MAA crystallizations：MAA oil is added in the external MAA oil storage tanks equipped with chuck, then according to every kilogram of MAA
Oil is added the amount of commercially available 95wt% alcohol 0.35L and is added alcohol to MAA oil storage tanks, and crack steam is by the temperature of MAA oil storage tanks
Control stands 45 minutes 65 DEG C or so (preventing MAA from crystallizing)；Vacuum is opened, by being preheated to 65 DEG C by the way of negative-pressure ward
The upper solution that the MAA oil pick-up tubes of left and right extract MAA oil storage tanks enters in crystallizing tank；The steam being then turned on crystallizing tank enters
Valve 21 rises again material in crystallizing tank to 70 DEG C, checks whether correctly (other each valves should be at each valve switch on crystallizing tank
Closed state), steam exhaust dump valve 22 should be at closed state at this time；Agitating device is opened later to start to stir, rotating speed be 18 turns/
Point, until all discharge just stops stirring to the material in crystallizing tank；By crystallizing tank Temperature fall 20 minutes 1 hour；It opens later
Brine valve 24 is returned, the small brine valve 23 (will open 30 degree into brine valve 23) that drives into cools down to crystallizing tank, is cooled to 50 DEG C
When, in open brine valve 23 (i.e. will into brine valve 23 open 60 degree) cool down, when being cooled to 40 DEG C, open brine valve 23 greatly (i.e.
90 degree will be opened into brine valve 23) crystallizing tank is cooled to 8 DEG C, prepare centrifugally operated；Material in crystallizing tank is put into centrifuge
Interior centrifugation, observe the mother liquor amount flowed out in the mother liquor pipeline that is set on centrifuge it is almost nil when, stop centrifuge and tie MAA
Crystalline substance takes out, and is packed according to 30 ㎏/part for being condensed process, sample examination, obtained MAA crystalline contents are 98.2wt%.
It is condensed purification step：MAA is crystallized in input condensation tank, 2.3L alcohol amounts are added to contracting according to 1kg MAA crystallizations
It closes in tank and commercially available 95wt% alcohol is added, condensation tank, which is then warming up to 70 DEG C, makes MAA crystallization dissolvings, is crystallized according still further to MAA
The scale total amount * 96wt% of crystallization (MAA), formaldehyde, sodium pyrosulfite mass ratio be 1:0.14:0.44 amount is into condensation tank
Condensation reaction is carried out, analgin feed liquid is pressed into crystallizing tank after completion of the reaction, is naturally cooling to 75 DEG C, opens recirculated water valve
Cool down, when being cooled to 25-35 DEG C, closes recirculated water valve, prepare centrifugation.Analgin wet product input air flow is done after centrifugation
In dry machine, 160 DEG C of inlet temperature, 75 DEG C of outlet temperature obtains analgin finished product in dry 6 hours.Determination of Analgin 99.8%, it is miscellaneous
Matter E (≤0.15%) is 0.13%, and unknown impuritie (≤0.05%) is 0.040%, meets COS standards.Product yield is 81%.
It is multiple batches of to produce obtained statistical result showed, produce COS standard analgins according to 2 process of embodiment, one
Secondary success rate is 85%, that is, COS standards analgin can successfully be prepared 85 times by carrying out the production of 100 batches.
Comparative example
MAA oil is put into condensation tank, alcohol is added into condensation tank according to 1kg MAA oil addition 2.6L alcohol amounts, then
Mass ratio according to MAA oil scale (MAA oil total amount * 92wt%), formaldehyde, sodium pyrosulfite is 1:0.14:0.45 amount is to contracting
It closes in tank and carries out condensation reaction, material is pressed into refining crystallization tank after completion of the reaction, be naturally cooling to 75 DEG C, open circulating-water valve
Door cools down, and when being cooled to 30 DEG C, closes recirculated water valve, prepares centrifugation.The analgin wet product that centrifugation obtains is thrown again
Enter to be condensed in tank, 2.6L alcohol amounts, which are added, according to 1kgMAA oil is added alcohol dissolving, and activated carbon is added.It opens steam and is warming up to 85
DEG C, 30 minutes are kept the temperature, binder is filtered after decoloration and enters refining crystallization tank, repeats the work of crystallization cooling centrifugation, obtaining peace is
Nearly wet product, by analgin wet product input air flow drying machine, 155 DEG C of inlet temperature, 70 DEG C of outlet temperature is 6 hours dry, obtains
Analgin finished product.Determination of Analgin 99.5%, impurity E (≤0.15%) are 0.13%, and unknown impuritie (≤0.05%) is
0.032%, meet COS standards.Product yield is 65%.
It is multiple batches of to produce obtained statistical result showed, produce COS standard analgins according to 1 process of comparative example, one
Secondary success rate is 40%, that is, COS standards analgin can successfully be prepared 40 times by carrying out the production of 100 batches.
From the foregoing, it will be observed that the effect and haveing an advantage that of the present invention provides a kind of MAA crystallization productions obtained using the molten method of wine
The method of COS analgins, the method increase the one-time success rate of COS finished products, expand the yield of COS analgins, reduce
Production cost.
Claims (14)
1. a kind of method of the MAA crystallization production COS analgins obtained using the molten method of wine, which is characterized in that include the following steps：
The preparation process of MAA crystallizations：Alcohol is added into MAA oil, is respectively obtained successively through standing, crystallization, centrifugation after mixing
MAA is crystallized and mother liquor；
Step of condensation：Condensation reaction is carried out by MAA crystallizations, with formaldehyde, sodium pyrosulfite, generates analgin feed liquid；
Post-processing step：The analgin feed liquid is subjected to decrease temperature crystalline, centrifugation and drying successively, to obtain meeting COS marks
Accurate analgin；Wherein,
In the preparation process of MAA crystallizations, the alcohol of 0.3-0.4L is added in every kilogram of MAA oil；
The standing is to stand 30-60min under the conditions of 60-70 DEG C.
2. according to the method described in claim 1, it is characterized in that, the MAA crystallization preparation process in, in the alcohol
The content of ethyl alcohol is in 95wt% or more.
3. according to the method described in claim 1, it is characterized in that, in the preparation process of MAA crystallizations, the crystallization has
Body is as follows：
The mixture of MAA oil and alcohol after standing is pumped into crystallizing tank, then heating crystalline tank, then crystallizing tank is cooled down, with
MAA is set to crystallize.
4. according to the method described in claim 3, it is characterized in that, the crystallizing tank that is pumped into is by the MAA oil pumping after preheating
The mixture of MAA oil and alcohol after standing is evacuated in crystallizing tank by pipe；MAA oil pick-up tubes after the preheating have 60-70 DEG C
Temperature.
5. according to the method described in claim 3, it is characterized in that, the heating crystalline tank be by crystallizing tank be heated to 60 DEG C with
On；The crystallizing tank cooling is that the crystallizing tank is cooled to 10 DEG C or less.
6. according to the method described in claim 5, it is characterized in that, crystallizing tank is heated to 60-70 DEG C by steam；The knot
Brilliant tank cooling is that the crystallizing tank is cooled to 5-10 DEG C.
7. according to the method described in claim 3, it is characterized in that, the crystallizing tank includes：
Tank body is crystallized, top is equipped with material inlet valve, and bottom is equipped with material outlet valve, is internally provided with agitating device；
Chuck is close to the outer wall of the crystallization tank body, by being passed through steam, brine or recirculated water into the chuck to control
State the temperature in crystallizing tank body；
Steam enters valve, is set on the pipeline that the chuck supplies steam, the speed of chuck is entered for controlling steam；
Steam exhaust dump valve is set to and is discharged on the pipeline of steam exhaust from the chuck, the chuck is discharged for controlling steam exhaust
Speed；
Into brine valve, it is set on the pipeline that the chuck supplies brine, the speed of chuck is entered for controlling brine；
Brine valve is returned, is set to and is discharged on the pipeline of brine from the chuck, the speed of the chuck is discharged for controlling brine
Degree.
8. according to the method described in claim 3, it is characterized in that, crystallizing tank cooling in turn includes the following steps：
Step 1 opens the agitating device, and rotating speed is 15-20 revs/min, and the working condition of the agitating device is continued until
Material discharging finishes in the crystallizing tank；
Step 2, by the crystallizing tank Temperature fall 80min-100min after heating, during the Temperature fall, material into
Mouth valve, material outlet valve, steam enter valve, steam exhaust dump valve, are in closed state into brine valve, time brine valve；
Step 3, open after Temperature fall it is described return brine valve, while opening 20-40 degree, that is, small by described into brine valve and drive salt into
Water valve drives described opened during 50-70 degree is into brine valve into brine valve, works as institute when the crystallizing tank is cooled to 45-55 DEG C
When stating crystallizing tank and being cooled to 35-45 DEG C, opens 80-90 degree by described into brine valve and drive brine valve into greatly, until crystallizing tank drops
Temperature is to 10 DEG C or less.
9. according to the method described in claim 1, it is characterized in that, in the preparation process of MAA crystallizations, the centrifugation is
Material in crystallizing tank after cooling is centrifuged, stops centrifugation when the mother liquor being discharged in centrifuge is zero.
10. according to the method described in claim 9, it is characterized in that, the MAA crystallization preparation process in, centrifugation time
For 20-25min.
11. according to the method described in claim 1, it is characterized in that, the MAA crystallization preparation process in, the mother liquor
It is back to after activated carbon decolorizing adsorbs and produces the condensation process of common analgin and apply mechanically.
12. according to the method described in claim 1, it is characterized in that, in the step of condensation, first the MAA is tied
Wine is added into the condensation tank in crystalline substance input condensation tank, the ratio that 2.2-2.3L alcohol then is added according to every kilogram of MAA crystallization
Essence, then the condensation tank is warming up to 70-80 DEG C, sodium pyrosulfite and first is added after MAA crystallizations dissolving in the condensation tank
Aldehyde carries out condensation reaction, wherein the scale of MAA crystallization, formaldehyde, sodium pyrosulfite mass ratio be 1:0.13-0.15:
0.44-0.46。
13. according to the method for claim 12, which is characterized in that in the step of condensation, second in the alcohol
Alcohol content is in 95wt% or more.
14. according to the method described in claim 1, it is characterized in that, in the rear in processing step, the decrease temperature crystalline refers to
The decrease temperature crystalline of the analgin feed liquid obtained after condensation reaction, it is specific as follows：It is first naturally cooling to 65-75 DEG C, is then adopted
With circulating water cooling to 25-35 DEG C；The design parameter of the drying is as follows：Inlet temperature is 148-165 DEG C, and outlet temperature is
60-80 DEG C, time 5.5-6h.
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