CN106045904B - A kind of niacinamide production method - Google Patents
A kind of niacinamide production method Download PDFInfo
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- CN106045904B CN106045904B CN201610387716.0A CN201610387716A CN106045904B CN 106045904 B CN106045904 B CN 106045904B CN 201610387716 A CN201610387716 A CN 201610387716A CN 106045904 B CN106045904 B CN 106045904B
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- niacinamide
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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Abstract
The present invention relates to technical field of fine, especially a kind of niacinamide production method, by in hydrolytic process, using water as solvent, manganese dioxide is as catalyst, nicotinonitrile is subjected to heating hydrolysis, so that in hydrolysis reaction, without alcohol as solvent, reduce the production cost of niacinamide, and make the yield of niacinamide higher, 85% or more can be reached, the purity of product uses high effective liquid chromatography for measuring, it can reach 99.93% or more, effectively reduce the cost to solvent and catalyst manganese dioxide recycling, reduce the waste rate of raw material, reduce the emission index of waste liquid.
Description
Technical field
The present invention relates to technical field of fine, especially a kind of niacinamide production method.
Background technique
Niacinamide popular name VB3, the entitled Niacinamide of chemistry are white, needle-shaped crystals or powder, fusing point 129-131
DEG C, ethyl alcohol and glycerol can be dissolved in.Niacinamide is the component part of Coenzyme I and Coenzyme I I, and when shortage can influence normally exhaling for cell
It inhales and is metabolized and causes pellagra.Therefore niacinamide is widely used in food and feed additive, drug and bulk pharmaceutical chemicals, biochemistry
The fields such as agent, colour former, brightening agent.
The production of niacinamide is mainly hydrolyzed to nicotinonitrile by microbial hydrolytic or metal oxide oxidation catalyst
Primary synthetic methods.The niacinamide yield of domestic production at present is higher, can achieve 90% or more, in content, whiteness and other
Index of correlation can also reach the standard of European Pharmacopoeia.But the nicotinoyl that niacinamide production technology in the prior art obtains
Amine product is in acicular crystal or powdery mostly, so that easily generating after ingress of air and reuniting or agglomerate, influences the outer of product
It sees.
It in the prior art, is all to obtain solvent, then will after mixing using alcohol with water mostly for the production method of niacinamide
It is used to promote the hydrolysis of nicotinonitrile, so that the yield of nicotinoyl amine product and purity are higher；As number of patent application is
The preparation side of the niacinamide of the production method and Patent No. CN201010192136 of high-purity niacinamide of CN201410672124
In method, the alcohol of ethyl alcohol or C1-C4 are all made of to be handled, and are finally carrying out heating removing alcoholic solvent, and at this moment, it rises
During temperature removing solvent, causes the loss amount of alcohol to be unable to control, and alcohol and water is easy to happen azeotropic, cause to solvent
More difficulty is recycled, even if being recycled jointly to water and alcohol, and the produce load of equipment will be made to increase, so that cigarette
The higher cost of amide production.
Summary of the invention
In order to solve the above technical problems existing in the prior art, the present invention provides a kind of niacinamide production method.
It is achieved particular by following technical scheme:
Directly using water as solvent, and under conditions of manganese dioxide is as catalyst, heating, so that nicotinonitrile is sent out
Raw hydrolysis, and by heat filtering, decoloration, concentration, suction filtration, recrystallization, granulation, drying, detection and etc. after processing, obtain
Niacinamide final products.By directlying adopt water as solvent, the load of equipment is reduced, so that subsequent carrying out solvent recovery
When cost is relatively low, improve the purity and whiteness of product, reduce to the energy consumption and environmental pollution in solvent recovery process.
The reaction equation in hydrolytic process specifically is occurring are as follows:
The specific process flow of the invention is:
Water, nicotinonitrile, manganese dioxide are put into reaction kettle according to weight ratio for 50-60: 40-50: 2-5, it will be warm
Degree is set in the range of 95-110 DEG C, is stirred to react 8-10h；Mixing speed herein is so that manganese dioxide hangs in the solution
It floats, avoids the deposition of manganese dioxide, prevent that hot-spot occurs in the solution, it is ensured that the harmony of reaction process avoids
Solution generates boiling explosion phenomenon；In the proportion to above-mentioned raw materials ingredient, nicotinonitrile is reacted completely, so that ensuring cigarette
Under the premise of the yield of amide is not affected, reduce the usage amount of water, reduce the subsequent cost for carrying out recycling circular treatment,
Reduce energy consumption, avoid a large amount of discharge of wastewater in the environment so that raw material obtain sufficiently dissolve reaction when, be unlikely to so that
When the excessive concentration of product, occur the defect that crystal is quickly precipitated after the cessation of the heating, reduce the difficulty of filtration step, reduces
Energy consumption.
It is transferred to above-mentioned in filtration step after reaction again, carries out suction filtration twice and handle, and will be filtered
After reusing or using 95 DEG C or more of hot water injection in catalyst return hydrolysing step, then return it into hydrolysing step
It reuses；By filtering twice, so that when using industrial filter paper, it can be ensured that the product of the nicotinoyl amine product of production
Matter, so that the rate of recovery of catalyst is higher, avoiding the filter paper industrially used will lead to manganese dioxide particle through remaining in
The defects of filtrate when improving filtrate purity, improves the rate of recovery of catalyst.
Above-mentioned filtered filtrate is sent into active carbon decolorizer again, and by the liquid after active carbon decolorizer
It is concentrated, so that the moisture that concentration process steams precipitates crystal after 20-30 parts by weight, to be carried out cooling；And by being somebody's turn to do
Step makes the whiteness of nicotinoyl amine product be significantly improved.
The mixed liquor that above-mentioned cooling is precipitated crystal again carries out suction filtration processing, and the solid for filtering out belongs to head product,
And be placed on environment and dry processing, filtered liquid returns in hydrolysing step and carries out recycling processing, so that obtaining
Moisture content of the head product in subsequent recrystallization process it is lower, the solvent that can be effectively reduced in recrystallization process uses
Amount, reduces cost, while can also avoid a large amount of discharging of waste liquid, avoids environmental pollution.
According to mass ratio it is 1: 1-3: 1 hybrid reaction by above-mentioned head product and ethyl alcohol, ethyl acetate, and heats extremely
Head product is completely dissolved, then is stood decrease temperature crystalline, then by it, suction filtration is handled while stirring, is obtained and is filtered solid and smoke filtrate
Body, suction filtration solid are niacinamide crude product, filter liquid and return to re-crystallization step；Again by niacinamide crude product, according to 3- cyano
15-25 parts of water are added in the parts by weight of pyridine parts by weight timing, and are heated to and are completely dissolved so that the purity of product obtain into
The raising of one step, whiteness are further improved, and reduce impurity content.And the material after being completely dissolved is placed in mist projection granulating
Machine carries out mist projection granulating processing, so that the specific surface area of the product obtained is reduced, reduces the probability of reunion and agglomeration；Again
By it in thermostatic drying chamber, using 80-110 DEG C of drying and processing 2-5h, niacinamide finished product is obtained.
Compared with prior art, technical effect of the invention is embodied in:
By nicotinonitrile being added as catalyst as solvent, manganese dioxide using water in hydrolytic process
Pyrohydrolysis reaction, so that, without alcohol as solvent, the production cost of niacinamide is reduced in hydrolysis reaction, and
And make the yield of niacinamide higher, 85% or more can be reached, the purity of product uses high effective liquid chromatography for measuring, energy
Enough reach 99.93% or more, effectively reduces the cost to solvent and catalyst manganese dioxide recycling, reduce raw material
Waste rate, reduce the emission index of waste liquid.
And in the invention, in conjunction with subsequent treatment process, so that the purity of nicotinoyl amine product, whiteness, yield etc.
Apparent improvement has been obtained, by heat filtering effective component has all been filtered in heat filtering filtrate, reduces impurity
Content；In conjunction with decoloration so that whiteness is significantly improved；And again pass by concentration, suction filtration, recrystallization using ethyl alcohol with
Ethyl acetate processing is granulated, drying steps, so that the purity of the niacinamide of preparation is higher, whiteness is more excellent, and it can also have
The reduction of effect is reunited or the probability of agglomeration, reduces the difficulty of niacinamide storage, improves the quality of niacinamide；And upper
In the processing step stated, enables to each material composition and waste liquid to obtain multiple recycling, reduce waste liquid discharging amount, subtract
Energy consumption and environmental pollution are lacked.
Specific embodiment
It is limited below with reference to specific embodiment technical solution of the present invention is further, but claimed
Range is not only limited to made description.
Embodiment 1
A kind of production method of niacinamide is to use water, nicotinonitrile, manganese dioxide according to weight ratio for 50: 40:
It after 2, is dropped in reactive tank, controlled at 95 DEG C, stirring hydrolysis 8h is made, and mixing speed is that control solution does not occur
Bumping is advisable.
Embodiment 2
A kind of niacinamide production method is to use water, nicotinonitrile, manganese dioxide according to weight part ratio for 60: 50:
It after 5, is dropped in reactive tank, controlled at 95~110 DEG C, stirs hydrolysis 10h, using heat filtering, decoloration, dense
Contract, filter, recrystallizing, refiltering, dissolving, being granulated, drying steps be made, be to control solution and bumping does not occur in whipping process
It is advisable.
Embodiment 3
A kind of niacinamide production method is to use water, nicotinonitrile, manganese dioxide according to weight ratio for 55: 45: 3
Afterwards, be dropped in reactive tank, controlled at 95~110 DEG C, stir hydrolysis 9h, using heat filtering, decoloration, concentration,
Filter, recrystallize, refiltering, dissolving, being granulated, drying steps are made, be bumping not to occur to control solution to be in whipping process
Preferably.The heat filtering is after the completion of hydrolysis, and immediately by its filtration treatment, and the suction filtration twice used is handled, solid
Return to hydrolysing step；The decoloration is by the filtrate after heat filtering by decolorization in active carbon decolorizer；Described is dense
Contracting is the material after decolorization to be distilled out to 20 parts by weight, then its decrease temperature crystalline is handled, until crystal amount no longer increases
It adds as stopping；The filtering is that the mixed liquor for precipitating crystal cooling carries out suction filtration processing, obtains head product and filtered fluid, mistake
Filtrate returns to hydrolysing step；The recrystallization is to mix head product instead for 1: 1: 1 according to mass ratio with ethyl alcohol, ethyl acetate
It answers, and heats to head product and be completely dissolved, then stood decrease temperature crystalline, until crystal amount is not further added by；It is described
Refilter be will recrystallization processing mixed material carry out suction filtration processing, obtain niacinamide crude product and filter liquid, filter
Liquid returns to re-crystallization step；The dissolution is the water that 15 parts by weight are added to niacinamide crude product, heat treatment to nicotinoyl
Amine crude product is completely dissolved；The granulation is that material is placed in sponging granulator makes by spraying by treated in dissolving step
Grain；The drying is the particle by mist projection granulating completion in thermostatic drying chamber, using 80 DEG C of drying and processing 2h, obtains nicotinoyl
Amine finished product.
Embodiment 4
A kind of niacinamide production method:
Deionized water 60kg, nicotinonitrile 40kg and catalyst manganese dioxide 3.2kg are put into reaction kettle, setting adds
Hot temperature is 100 DEG C, and stirs hydrolysis, and bumping, which does not occur, for mixing speed control solution is advisable, and reacts 8h, reaction was completed；
While hot, material after reaction is carried out suction filtration twice to handle, filters solid and return in hydrolysis step, takes out
Filtrate body is sent into decolorization in active carbon decolorizer, and after the liquid concentration after decolorization to be distilled out to the moisture of 25kg,
By its decrease temperature crystalline, and suction filtration processing is carried out, obtain the head product of solid, and carries out appropriate drying processing；
Head product is put into reaction kettle, 120kg ethyl alcohol and ethyl acetate is added, wherein the quality of ethyl alcohol and ethyl acetate
It than being 1: 2, after heat treatment is completely dissolved to head product, is stood and is precipitated crystal, then carried out suction filtration processing, obtained thick
Product；And crude product is placed in reaction kettle again, 20kg deionized water is added, is heated to after being completely dissolved, is sent into mist projection granulating
Granulation is handled in machine, and the material being granulated after completing is placed in thermostatic drying chamber, using 80 DEG C of drying and processing 5h, obtain at
Product niacinamide.
Embodiment 5
A kind of niacinamide production method:
Deionized water 50kg, nicotinonitrile 50kg and catalyst manganese dioxide 4kg are put into reaction kettle, setting heating
Temperature is 100 DEG C, and stirs hydrolysis, and bumping, which does not occur, for mixing speed control solution is advisable, and reacts 10h, reaction was completed；
While hot, material after reaction is carried out suction filtration twice to handle, filters solid and return in hydrolysis step, takes out
Filtrate body is sent into decolorization in active carbon decolorizer, and after the liquid concentration after decolorization to be distilled out to the moisture of 25kg,
By its decrease temperature crystalline, and suction filtration processing is carried out, obtain the head product of solid, and carries out appropriate drying processing；
Head product is put into reaction kettle, 150kg ethyl alcohol and ethyl acetate is added, wherein the quality of ethyl alcohol and ethyl acetate
It than being 1: 3, after heat treatment is completely dissolved to head product, is stood and is precipitated crystal, then carried out suction filtration processing, obtained thick
Product；And crude product is placed in reaction kettle again, 25kg deionized water is added, is heated to after being completely dissolved, is sent into mist projection granulating
Granulation is handled in machine, and the material being granulated after completing is placed in thermostatic drying chamber, using 90 DEG C of drying and processing 3h, obtain at
Product niacinamide.
Embodiment 6
A kind of niacinamide production method:
Deionized water 10kg, nicotinonitrile 50kg and catalyst manganese dioxide 4kg are put into reaction kettle, setting heating
Temperature is 110 DEG C, and stirs hydrolysis, and bumping, which does not occur, for mixing speed control solution is advisable, and reacts 9h, reaction was completed；
While hot, material after reaction is carried out suction filtration twice to handle, filters solid and return in hydrolysis step, takes out
Filtrate body is sent into decolorization in active carbon decolorizer, and after the liquid concentration after decolorization to be distilled out to the moisture of 30kg,
By its decrease temperature crystalline, and suction filtration processing is carried out, obtain the head product of solid, and carries out appropriate drying processing；
Head product is put into reaction kettle, 150kg ethyl alcohol and ethyl acetate is added, wherein the quality of ethyl alcohol and ethyl acetate
It than being 1: 2, after heat treatment is completely dissolved to head product, is stood and is precipitated crystal, then carried out suction filtration processing, obtained thick
Product；And crude product is placed in reaction kettle again, 25kg deionized water is added, is heated to after being completely dissolved, is sent into mist projection granulating
Granulation is handled in machine, and the material being granulated after completing is placed in thermostatic drying chamber, using 100 DEG C of drying and processing 3h, is obtained
Finished product niacinamide.
For the composition detection experiment of product prepared by embodiment 4,5,6, surveyed according to European Pharmacopoeia niacinamide standard
It is fixed, laboratory testing: whiteness, fusing point, solution clarity, granularity, pH value；So-and-so inspection center is detected: liquid phase, heavy metal are residual
It stays, concrete outcome is as shown in table 1 below:
Table 1
By the data of upper table, it can be concluded that, the invention enables to the yield of product and purity higher, and keeps away
Exempted from alcohol as solvent so that cost significantly reduces, but also after reducing subsequent recovery solvent difficulty, reduce energy
Consumption；And the whiteness and particle diameter distribution of the product prepared can reach the requirement of corresponding product standard.
Above embodiments are only limitted to and explanation further elucidated above to technical solution of the present invention, not to skill of the invention
Art scheme further limits, non-protruding essential characteristics that those skilled in the art make on this basis and it is non-significant into
The improvement of step belongs to protection category of the invention.
Claims (1)
1. a kind of niacinamide production method, which is characterized in that it is using water, nicotinonitrile, manganese dioxide according to parts by weight
It after being 50-60: 40-50: 2-5, is dropped in reactive tank, controlled at 95-110 DEG C, stirs hydrolysis 8-10h, then
By heat filtering, decoloration, concentration, filtering, recrystallize, refilter, dissolve, be granulated, drying steps are made；
The heat filtering is after the completion of hydrolysis, and immediately by its filtration treatment, and the suction filtration twice used is handled, solid
Return to hydrolysing step；The decoloration is by the filtrate after heat filtering by decolorization in active carbon decolorizer；Described is dense
Contracting is the material after decolorization to be distilled out to 20-30 parts by weight, then its decrease temperature crystalline is handled, until crystal amount is no longer
Until increase；The filtering is that the mixed liquor for precipitating crystal cooling carries out suction filtration processing, obtains head product and filtered fluid,
Filtered fluid returns to hydrolysing step；It according to mass ratio is 1 that the recrystallization, which is by head product and ethyl alcohol, ethyl acetate: (1-3): 1
Hybrid reaction, and heat to head product and be completely dissolved, then is stood decrease temperature crystalline, up to crystal amount be not further added by for
Only；Described refiltering is that the mixed material of recrystallization processing is carried out suction filtration processing, obtains niacinamide crude product and smoke filtrate
Body filters liquid and returns to re-crystallization step；The dissolution is the water that 15-25 parts by weight are added to niacinamide crude product, heating
Processing to niacinamide crude product is completely dissolved；The granulation is that material is placed in sponging granulator by treated in dissolving step
Middle mist projection granulating；The drying is the particle by mist projection granulating completion in thermostatic drying chamber, at 80-110 DEG C of drying
2-5h is managed, niacinamide finished product is obtained.
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| CN201610387716.0A CN106045904B (en) | 2016-06-03 | 2016-06-03 | A kind of niacinamide production method |
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| CN106045904B true CN106045904B (en) | 2019-04-09 |
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| CN113321614B (en) * | 2021-08-02 | 2021-11-26 | 北京四环制药有限公司 | Recycling method of nicotinamide crystallization mother liquor |
| CN115925620A (en) * | 2022-12-23 | 2023-04-07 | 态创生物科技(广州)有限公司 | Purification method of biobased nicotinamide |
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| CN1741997A (en) * | 2002-12-23 | 2006-03-01 | 科学与工业研究委员会 | Process for conversion of cyanopyridines tonicotinamides and catalyst therefor, process for preparing said catalyst |
| CN101239311A (en) * | 2002-12-23 | 2008-08-13 | 科学与工业研究委员会 | Method for converting cyanopyridine compounds into niacinamide compounds, its catalyst and the catalyst preparation |
| CN101602718A (en) * | 2009-07-21 | 2009-12-16 | 南京第一农药集团有限公司 | A kind of method for preparing high-purity nicotinamide compound |
| CN101851194A (en) * | 2010-06-03 | 2010-10-06 | 浙江新赛科药业有限公司 | Method for preparing nicotinamide |
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2016
- 2016-06-03 CN CN201610387716.0A patent/CN106045904B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1741997A (en) * | 2002-12-23 | 2006-03-01 | 科学与工业研究委员会 | Process for conversion of cyanopyridines tonicotinamides and catalyst therefor, process for preparing said catalyst |
| CN101239311A (en) * | 2002-12-23 | 2008-08-13 | 科学与工业研究委员会 | Method for converting cyanopyridine compounds into niacinamide compounds, its catalyst and the catalyst preparation |
| CN101602718A (en) * | 2009-07-21 | 2009-12-16 | 南京第一农药集团有限公司 | A kind of method for preparing high-purity nicotinamide compound |
| CN101851194A (en) * | 2010-06-03 | 2010-10-06 | 浙江新赛科药业有限公司 | Method for preparing nicotinamide |
Non-Patent Citations (2)
| Title |
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| Hydration of 3-cyanopyridine to nicotinamide;Subhash Chandra Roy et al.,;《Applied Catalysis A: General》;20050706;第290卷;175-180 |
| 二氧化锰催化水解3-氰基吡啶生成烟酰胺;肖志斌等;《南昌大学学报(理科版)》;20010831;第35卷(第4期);第366页左栏1.3 |
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