CN105272863B - The preparation method of paraphenetidine - Google Patents
The preparation method of paraphenetidine Download PDFInfo
- Publication number
- CN105272863B CN105272863B CN201510314205.1A CN201510314205A CN105272863B CN 105272863 B CN105272863 B CN 105272863B CN 201510314205 A CN201510314205 A CN 201510314205A CN 105272863 B CN105272863 B CN 105272863B
- Authority
- CN
- China
- Prior art keywords
- paraphenetidine
- mixed liquor
- reactor
- catalyst
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of preparation method of paraphenetidine.This method is hydrogenated in the presence of Ternary Amorphous Alloy alloy catalyst is Ni Mo B or Ni Co P with batch (-type) hydrogenation to paranitroanisole liquid phase, so as to obtain the paraphenetidine of selectivity up to more than 99.7%.The preparation method reaction condition of the paraphenetidine of the present invention is gentle, and solvent, catalyst can be recycled, and be easy to industrialized production.
Description
Technical field
The present invention relates to a kind of preparation method of paraphenetidine.
Background technology
Paraphenetidine, alternatively referred to as P-nethoxyaniline, it is the intermediate of important dyestuff, medicine and spices.With
O-aminoanisole is compared, and application of the paraphenetidine in dye industry is more extensive.For example, in dye industry, it is right
Aminoanisole be used to synthesize blue salt VB, purplish red base GP, azoic coupling component AS-SG, AS-RL, vat scarlet.In addition, using to ammonia
Base methyl phenyl ethers anisole can synthesize 2- amino -4- acetyl-anisidines, and the latter is the important source material of disperse dyes, can be used for into one
Step synthesizes a series of disperse dyes, such as the scattered orchids 79,139,226,265,301 of C.I., disperse violet 58, Disperse Navy Blue S-2GL etc..
In medical industry, paraphenetidine is mainly used in synthesizing atabrine, primary quinoline, indocin etc., and wherein indocin is to amino
The bigger kind of methyl phenyl ethers anisole consumption figure.
At the beginning of phase late 1980s, some main paraphenetidine production enterprises of West Europe and Japan and other countries
Industry sequentially switches off its process units.And in contrast, with the emergence of China's dye industry, paraphenetidine production capacity and
Yield rapid growth, China have become global paraphenetidine major producing country and supply country, have thousands of tons of every year to ammonia
Base methyl phenyl ethers anisole products export, China's paraphenetidine yield account for 80% or so of global total output.
In traditional industrial process, domestic manufacturer is mostly to use " chemical reduction method ", i.e., with iron powder or
Paranitroanisole is reduced as reducing agent and prepares paraphenetidine by vulcanized sodium.But this technique there is
Consumption is big, cost is high, shortcomings, especially waste water, the waste sludge discharge amount such as of poor quality are big, causes serious environmental pollution,
The developing direction for the green chemical industry advocated with China is runed counter to.If handling waste water, waste residue, can not only increase considerably into
This, it is also possible to because deal with improperly and caused by secondary pollution.
In order to reduce pollution, improve yield and product quality, preparation of each seminar to paraphenetidine are carried out
The research and discovery of each side, paraphenetidine is prepared with " catalytic hydrogenation method ", accessory substance is water, environmentally friendly, yield
Height, good product quality, be substituted chemistry reducing process ideal technology.
A kind of method that paranitroanisole is prepared with catalytic hydrogenation method is disclosed in Chinese patent CN1861570.Should
Method is using methanol as solvent, using nitrobenzoyl ether mixture as raw material, is catalyst using Raney-Ni or Pd-C, is passed through hydrogen
Catalytic hydrogenating reduction reaction is carried out, terminates catalytic hydrogenation reaction when hydrogen is no longer consumed；Catalysis is reclaimed from reaction mixture
After agent, oil phase is separated through Liquid liquid Separation, and is recrystallized, to obtain required paraphenetidine.This method is a kind of cleaning
Production technology, it is small to equipment corrosion, pollution can be reduced.But this method is that standard terminates to urge with " no longer consuming hydrogen "
Change hydrogenation reduction, therefore the terminal point control to reaction is not very accurate, so as to be difficult to make in high yield and with high selectivity
For paraphenetidine is gone out, catalytic hydrogenation conversion per pass is only 85%, and the purity of target product is only 98%.
X.Xi et al. is in document 1：Palladium complex of poly(4-vinylpyridine-co-acrylic
acid)for homogeneous hydrogenation of aromatic nitro compounds,J Mol Catal,
2003,192:1-7；S.Xu et al. is in document 2：A homogeneous catalyst made of poly(4-
vinylpyridine-co-N-vinylpyrrolidone)-Pd(0)complex for hydrogenation of
aromatic nitro compounds.J Mol Catal,2000,160:In 287-292, report and homogeneously urged with palladium base
Agent is in 0.1MPa, and reaction temperature prepares paraphenetidine under conditions of being less than 50 DEG C, but the separation of this catalyst is difficult,
Cost is high, is not easy to industrialize.
F.Zhao is in document 3：Hydrogenation of nitro compounds with supported
platinum catalyst in supercritical carbon dioxide.Catal Today,2004,98:523-528
In report and hydrogen is catalyzed in supercritical carbon dioxide with w (Pt)=5% Pt/C prepares paraphenetidine, reaction pressure surpasses
8MPa is crossed, equipment investment is high, is not easy to promote.
Zhao Lin is in document 4：" Synthesis of P-Aminophenol Methyl Ether by Catalytic Hydrogenation ", Henan science, in June, 2006, volume 24 the 3rd
Phase, in 345-346 pages, disclose and a kind of replace pure hydrogen with the ammonia synthesis gas of synthesis ammonia plant to be catalyzed reduction paranitroanisole
To prepare the method for paraphenetidine.This technique compared with vulcanized sodium reducing process, product cost can reduce by 1500 yuan/
T or so, while the nearly 3.5t/t of few waste discharge.In the process, when catalyst amount 1%, 140 DEG C of reaction temperature, reaction pressure
Power 4MPa, reaction time 3h, yield can reach more than 96%.But not only severe reaction conditions, and to amino in the technique
The highest yield of methyl phenyl ethers anisole is also only 96.4%, product purity 99.38%, still can not reach industry requirement.
Yuan Zhongyi etc. is in document 5：" backbone ruthenium nickel carbon selectivity catalytic hydrogenation prepares paraphenetidine ", fine chemistry industry,
The 5th phase of volume 23, in 5 months 2006, disclose using skeletal isomerzation as catalyst, paranitroanisole liquid phase selective hydrogenation
To prepare paraphenetidine, but target product selectivity only reaches 99.4%, and further need to separate and purify can still obtain mesh
Mark the sterling of product.The research group also in Chinese patent CN1775353, disclose it is a kind of include main catalyst ruthenium and
By the skeleton ruthenium catalyst of Al, Ni, M (Fe, Mn, Mo or Cr) and the C co-catalyst formed, using adding for the skeleton ruthenium catalyst
Hydrogen reacts, and may be such that 4g paranitroanisoles 100% are converted into paraphenetidine, and the yield of the product is 99%.
Applicant in this case discloses a kind of synthetic method of alkoxyl aniline, the party in Chinese patent CN101492379
Method is to pass through alkoxyl nitrobenzene for raw material to add hydrogen reaction generation alkoxyl aniline under catalysts conditions.In the patent
In embodiment 2 disclosed in application, by 100g paranitroanisoles, 1g Raney Ni, 100mL methanol is added in reactor,
And be passed through hydrogen in 80 DEG C and reacted, stop until hydrogen half an hour after is no longer inhaled in reaction.This method is other compared to before
Prior art, larger lifting is obtained in terms of selectivity and yield.But this method only in the lab can be real
Apply, when being scaled up to industrial production, high selectivity (high-purity), p-aminophenyl in high yield can not be obtained at all
Methyl ether.Especially, even in laboratory scale, the species and dosage of catalyst, the species of solvent and dosage, temperature and pressure
The difference of the factors such as power, the fluctuation of selectivity and yield can be caused, it is difficult to reach in high yield and high selectivity simultaneously.It is special by this
Embodiment 1,2,3,7 disclosed in profit, it can be seen that this influence.For example, embodiment 1 is compared with Example 2, only it is Ni contents
Reduce, methanol is reduced, and pressure and temp reduces, then the conversion ratio in embodiment 1 is then reduced to 82% by 100%, and selective
But 100% is risen to by 99.5%.Only be that pressure and temp rises for another example embodiment 7 is compared with embodiment 2, then embodiment 7
In conversion ratio remain to holding 100%, and selectivity drops to 90% by 99.5%.At least, from the point of view of the disclosure of the patent,
This method is also unstable in laboratory scale, and can not expect and how can be only achieved while obtain high selectivity, height
The paraphenetidine of yield.
In summary, prior art fails to realize in industrial scale so far, high selectivity, prepares in high yield
The method of paraphenetidine.
The content of the invention
It is an object of the invention to provide it is a kind of take into account high selectivity, in high yield and cleaning can be produced on an industrial scale
The preparation method of paraphenetidine, this method can substantially solve many disadvantages present in prior art.
The preparation method of paraphenetidine provided by the invention, be in the presence of Ternary Amorphous Alloy alloy catalyst, with
Batch (-type) hydrogenation paranitroanisole liquid phase is hydrogenated, so as to obtain selectivity up to more than 99.7% to amino
Methyl phenyl ethers anisole, the reaction condition of the preparation method is gentle, and solvent, catalyst can be recycled, and be easy to industrialized production.
The preparation method of paraphenetidine provided by the invention, including the steps：
1) feed intake：By paranitroanisole, catalyst and methanol using mass ratio as 100：0.2~2：80~100 ratio
Add in reactor, form mixed liquor；
Wherein, the catalyst be Ni-Mo-B (wherein Ni, Mo, B percentage by weight be respectively 95.0wt%,
3.0wt% and 2.0wt%) or Ni-Co-P (wherein Ni, Co, P percentage by weight be respectively 95.0wt%, 3.0wt% and
2.0wt%)；
2) deoxygenation：Nitrogen is passed through with the air in replacement reaction kettle；Then, hydrogen is passed through with the nitrogen in replacement reaction kettle
Gas；
3) batch (-type) is hydrogenated with：It is replaced, hydrogen is passed through into reactor to 0.8~1.8MPa, mixed liquor is stirred
Mix, carry out hydrogenation reaction；In course of reaction, controlling reaction temperature is 80~120 DEG C, and keeps the Hydrogen Vapor Pressure in reactor to be
0.8~1.8MPa；
Detect mixed liquor once per hour；When the content (removal solvent) for measuring the paranitroanisole in mixed liquor
When dropping to 20%, every 0.5 hour detection mixed liquor is changed to once；When the content for measuring the paranitroanisole in mixed liquor
When (removal solvent) drops to 5%, every 10 minutes detection mixed liquors are changed to once；Until (removing solvent to contain in mixed liquor
Amount) the content to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene when being below 0.1%, close hydrogen valve, stop
Hydrogenation；
4) cooling discharge：Reduce mixing speed and cooled with cooling water, when temperature is down to 30~50 DEG C, stop stirring
Mix, the material on upper strata is extruded after standing, the material of lower floor is mainly catalyst；
5) purified product：The material on the upper strata that step 4) is extruded isolates methanol into method separation tower, isolates
Methanol recycled as solvent when preparing paraphenetidine next time, this is eliminated into the material after methanol through film
Evaporator boils off moisture, obtains required paraphenetidine.
In an embodiment of the invention, the deoxygenation in step 2) empties again to be passed through nitrogen to 0.5MPa, repeats 3
~5 times to remove the air in reactor；Then, it is passed through hydrogen to empty again to 0.5MPa, repeats 3~5 times to remove reactor
In nitrogen.
In an embodiment of the invention, hydrogen is passed through in step 3) to 0.8~1.8MPa, preferably 1.0~
1.6MPa。
In an embodiment of the invention, the mixing speed of step 3) is 60~300rpm, preferably 80~160rpm.
In an embodiment of the invention, the reaction temperature of step 3) is 80~120 DEG C, preferably 90~100 DEG C.
In an embodiment of the invention, mixing speed is reduced in step 4) to 30~60rpm.
In an embodiment of the invention, the Matter Transfer of the lower floor in step 4) uses, into next time to ammonia
In the preparation flow of base methyl phenyl ethers anisole.In an embodiment of the invention, the material of the lower floor of step 4) is added to nitro
Methyl phenyl ethers anisole, methanol, and input catalyst is supplemented, to meet the matter of paranitroanisole, total catalyst and inert organic solvents
Amount is than being 100：0.2~2：80~100, then repeat step 2)-step 5), it is possible to achieve the recycling of catalyst.
In an embodiment of the invention, it is in the condition of method separation tower separation methanol in step 5)：Knockout tower
Column bottom temperature is 80~130 DEG C, and tower top temperature is 50~100 DEG C；Preferably, column bottom temperature is 90~120 DEG C, and tower top temperature is
60~80 DEG C.
In an embodiment of the invention, the condition for boiling off moisture in step 5) in thin film evaporator is：0.09
~-0.1MPa, preferably 90~130 DEG C, 100~120 DEG C.
The method of the present invention be by the use of specific ternary alloy three-partalloy Ni-Mo-B or Ni-Co-P as catalyst, with batch (-type) plus
Hydrogen method carries out hydro-reduction to paranitroanisole liquid phase, so as to obtain paraphenetidine.Compared with prior art, it is of the invention
Method the advantages of be：
(1) catalyst is used as using commercially available ternary alloy three-partalloy, you can with obtain than in the prior art using Raney-Ni,
Pd-C or higher selectivity during skeletal isomerzation catalyst and conversion ratio；
(2) it with " no longer consuming hydrogen " is that to terminate catalytic hydrogenating reduction anti-for standard that the catalytic hydrogenation method of prior art, which is,
Should, therefore the terminal point control to reaction is not very accurate, so as to be difficult to prepare p-aminophenyl in high yield and/or with high selectivity
Methyl ether.And the present invention is by monitoring in reaction mixture to the content of nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene,
Reaction end is precisely controlled so as to realize, therefore the hydrogenation reduction of the present invention can be caused while there is high conversion
The characteristics of rate, high selectivity (up to more than 99.7%)；
(3) hydrogen reduction of the invention uses cheap hydrogen as raw material, by step catalytic hydrogenation synthesis pair
Aminoanisole；And solvent, catalyst can be recycled, it is easy to industrialize, therefore reduce production cost；
(4) in hydrogen reduction of the invention, accessory substance is water, other waste water and dregs or waste gas is had no, hence in so that whole
The generation of the three wastes is avoided in individual building-up process, is environment amenable green reaction；
(5) present invention is after batch (-type) hydrogenation step, you can the paraphenetidine that purity is more than 99.7% is obtained, because
This causes follow-up purification step (post processing) to become simple, only by simple rectifying can obtain higher purity to amino
Methyl phenyl ethers anisole product.
Therefore, method of the invention not only avoid sodium sulfide reducing and cause pollution of the sulfur-containing waste water to environment, while again
Possesses the advantages that high yield, high selectivity and low accessory substance, it is easy to accomplish technical scale metaplasia is produced.
Embodiment
Embodiment 1
By 6000kg paranitroanisoles, 120kg catalyst ns i-Mo-B, (wherein Ni, Mo, B percentage by weight is respectively
95.0wt%, 3.0wt% and 2.0wt%) and 7500L methanol add 16000L reactors in, formed mixed liquor.
Nitrogen is passed through to reactor to empty again to 0.5MPa, is repeated 5 times to remove the air in reactor；Then, it is passed through
Hydrogen empties again to 0.5MPa, is repeated 5 times to remove the nitrogen in reactor.
It is replaced, hydrogen is passed through into reactor to 1.2MPa, steam valve is opened and reactor is heated up, work as temperature
When degree rises to 80 DEG C, steam off valve.Reactor agitator (slowly being raised speed by frequency converter) is opened with 80rpm stirring speed
Degree is stirred to mixed liquor, carries out hydrogenation reaction；In course of reaction, controlling reaction temperature is 80 ± 1 DEG C, and keeps reactor
In Hydrogen Vapor Pressure be 1.2MPa.
In course of reaction, mixed liquor is detected once per hour；When measure in mixed liquor (removal methanol content) to nitro
When the content of methyl phenyl ethers anisole drops to 20%, every 0.5 hour detection mixed liquor is changed to once；(methanol is removed when measuring in mixed liquor
Content) the content of paranitroanisole when dropping to 5%, be changed to every 10 minutes detection mixed liquors once；Until in mixed liquor
When the content to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene of (removal methanol content) is below 0.1%, Guan Qing
Air valve, stop hydrogenation.
Mixing speed is reduced to 30rpm, is cooled with cooling water；When temperature is down to 30 DEG C, stop stirring, stand half
The material on upper strata is extruded after hour, lower floor is mainly catalyst, is stayed in reactor, for hydrogenation next time.
The upper materials of extrusion are entered into method separation tower, are 120 DEG C in column bottom temperature, tower top temperature is 50 DEG C of condition
Under isolate methanol, then boil off moisture under the conditions of 0.06MPa, 90 DEG C through thin film evaporator again, obtain paraphenetidine
4756kg, its conversion ratio 100%, yield 98.6%, selectivity 99.8%, the purity 99.8% of paraphenetidine.
Embodiment 2
By 3000kg paranitroanisoles, 6kg catalyst ns i-Mo-B, (wherein Ni, Mo, B percentage by weight is respectively
95.0wt%, 3.0wt% and 2.0wt%) and 3030L methanol add embodiment 1 leave in the 16000L reactors of catalyst, shape
Into mixed liquor.
Nitrogen is passed through to reactor to empty again to 0.5MPa, is repeated 3 times to remove the air in reactor；Then, it is passed through
Hydrogen empties again to 0.5MPa, is repeated 3 times to remove the nitrogen in reactor.
It is replaced, hydrogen is passed through into reactor to 1.0MPa, steam valve is opened and reactor is heated up, work as temperature
When degree rises to 90 DEG C, steam off valve.Reactor agitator (slowly being raised speed by frequency converter) is opened with 120rpm stirring
Speed is stirred to mixed liquor, carries out hydrogenation reaction；In course of reaction, controlling reaction temperature is 90 ± 1 DEG C, and keeps reacting
Hydrogen Vapor Pressure in kettle is 1.0MPa.
In course of reaction, mixed liquor is detected once per hour；When measure in mixed liquor (removal methanol content) to nitro
When the content of methyl phenyl ethers anisole drops to 20%, every 0.5 hour detection mixed liquor is changed to once；(methanol is removed when measuring in mixed liquor
Content) the content of paranitroanisole when dropping to 5%, be changed to every 10 minutes detection mixed liquors once；Until in mixed liquor
When the content to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene of (removal methanol content) is below 0.1%, Guan Qing
Air valve, stop hydrogenation.
Mixing speed is reduced to 40rpm, is cooled with cooling water；When temperature is down to 45 DEG C, stop stirring, stand half
The material on upper strata is extruded after hour, lower floor is mainly catalyst, is stayed in reactor, for hydrogenation next time.
The upper materials of extrusion are entered into method separation tower, are 130 DEG C in column bottom temperature, tower top temperature is 80 DEG C of condition
Under isolate methanol, then boil off moisture under the conditions of 0.08MPa, 130 DEG C through thin film evaporator again, obtain paraphenetidine
2385kg, its conversion ratio 100%, yield 98.9%, selectivity 99.7%, the purity 99.7% of paraphenetidine.
Embodiment 3
By 6000kg paranitroanisoles, 12kg catalyst ns i-Mo-B, (wherein Ni, Mo, B percentage by weight is respectively
95.0wt%, 3.0wt% and 2.0wt%) and 7000L methanol add embodiment 2 leave in the 16000L reactors of catalyst, shape
Into mixed liquor.
Nitrogen is passed through to reactor to empty again to 0.5MPa, is repeated 4 times to remove the air in reactor；Then, it is passed through
Hydrogen empties again to 0.5MPa, is repeated 4 times to remove the nitrogen in reactor.
It is replaced, hydrogen is passed through into reactor to 1.6MPa, steam valve is opened and reactor is heated up, work as temperature
When degree rises to 100 DEG C, steam off valve.Reactor agitator (slowly being raised speed by frequency converter) is opened with 160rpm stirring
Speed is stirred to mixed liquor, carries out hydrogenation reaction；In course of reaction, controlling reaction temperature is 90 ± 1 DEG C, and keeps reacting
Hydrogen Vapor Pressure in kettle is 1.6MPa.
In course of reaction, mixed liquor is detected once per hour；When measure in mixed liquor (removal methanol content) to nitro
When the content of methyl phenyl ethers anisole drops to 20%, every 0.5 hour detection mixed liquor is changed to once；(methanol is removed when measuring in mixed liquor
Content) the content of paranitroanisole when dropping to 5%, be changed to every 10 minutes detection mixed liquors once；Until in mixed liquor
When the content to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene of (removal methanol content) is below 0.1%, Guan Qing
Air valve, stop hydrogenation.
Mixing speed is reduced to 60rpm, is cooled with cooling water；When temperature is down to 50 DEG C, stop stirring, stand half
The material on upper strata is extruded after hour, lower floor is mainly catalyst, is stayed in reactor, for hydrogenation next time.
The upper materials of extrusion are entered into method separation tower, are 90 DEG C in column bottom temperature, tower top temperature is 50 DEG C of condition
Under isolate methanol, then boil off moisture under the conditions of 0.06MPa, 90 DEG C through thin film evaporator again, obtain paraphenetidine
4776kg, its conversion ratio 100%, yield 99.0%, selectivity 99.9%, the purity 99.9% of paraphenetidine.
Embodiment 4
By 3000kg paranitroanisoles, 6kg catalyst ns i-Mo-B, (wherein Ni, Mo, B percentage by weight is respectively
95.0wt%, 3.0wt% and 2.0wt%) and 3600L methanol add embodiment 3 leave in the 16000L reactors of catalyst, shape
Into mixed liquor.
Nitrogen is passed through to reactor to empty again to 0.5MPa, is repeated 4 times to remove the air in reactor；Then, it is passed through
Hydrogen empties again to 0.5MPa, is repeated 4 times to remove the nitrogen in reactor.
It is replaced, hydrogen is passed through into reactor to 0.8MPa, steam valve is opened and reactor is heated up, work as temperature
When degree rises to 120 DEG C, steam off valve.Reactor agitator (slowly being raised speed by frequency converter) is opened with 100rpm stirring
Speed is stirred to mixed liquor, carries out hydrogenation reaction；In course of reaction, controlling reaction temperature is 90 ± 1 DEG C, and keeps reacting
Hydrogen Vapor Pressure in kettle is 0.8MPa.
In course of reaction, mixed liquor is detected once per hour；When measure in mixed liquor (removal methanol content) to nitro
When the content of methyl phenyl ethers anisole drops to 20%, every 0.5 hour detection mixed liquor is changed to once；(methanol is removed when measuring in mixed liquor
Content) the content of paranitroanisole when dropping to 5%, be changed to every 10 minutes detection mixed liquors once；Until in mixed liquor
When the content to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene of (removal methanol content) is below 0.1%, Guan Qing
Air valve, stop hydrogenation.
Mixing speed is reduced to 50rpm, is cooled with cooling water；When temperature is down to 40 DEG C, stop stirring, stand half
The material on upper strata is extruded after hour, lower floor is mainly catalyst, is stayed in reactor, for hydrogenation next time.
The upper materials of extrusion are entered into method separation tower, are 130 DEG C in column bottom temperature, tower top temperature is 80 DEG C of condition
Under isolate methanol, then boil off moisture under the conditions of 0.08MPa, 130 DEG C through thin film evaporator again, obtain paraphenetidine
2383kg, its conversion ratio 100%, yield 98.8%, selectivity 99.7%, the purity 99.7% of paraphenetidine.
Embodiment 5
By 6000kg paranitroanisoles, 100kg catalyst ns i-Co-P, (wherein Ni, Co, P percentage by weight is respectively
95.0wt%, 3.0wt% and 2.0wt%) and 7500L methanol add 16000L reactors in, formed mixed liquor.
Nitrogen is passed through to reactor to empty again to 0.5MPa, is repeated 5 times to remove the air in reactor；Then, it is passed through
Hydrogen empties again to 0.5MPa, is repeated 5 times to remove the nitrogen in reactor.
It is replaced, hydrogen is passed through into reactor to 1.0MPa, steam valve is opened and reactor is heated up, work as temperature
When degree rises to 95 DEG C, steam off valve.Reactor agitator (slowly being raised speed by frequency converter) is opened with 120rpm stirring
Speed is stirred to mixed liquor, carries out hydrogenation reaction；In course of reaction, controlling reaction temperature is 95 ± 1 DEG C, and keeps reacting
Hydrogen Vapor Pressure in kettle is 1.0MPa.
In course of reaction, mixed liquor is detected once per hour；When measure in mixed liquor (removal methanol content) to nitro
When the content of methyl phenyl ethers anisole drops to 20%, every 0.5 hour detection mixed liquor is changed to once；(methanol is removed when measuring in mixed liquor
Content) the content of paranitroanisole when dropping to 5%, be changed to every 10 minutes detection mixed liquors once；Until in mixed liquor
When the content to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene of (removal methanol content) is below 0.1%, Guan Qing
Air valve, stop hydrogenation.
Mixing speed is reduced to 30rpm, is cooled with cooling water；When temperature is down to 30 DEG C, stop stirring, stand half
The material on upper strata is extruded after hour, lower floor is mainly catalyst, is stayed in reactor, for hydrogenation next time.
The upper materials of extrusion are entered into method separation tower, are 80 DEG C in column bottom temperature, tower top temperature is 70 DEG C of condition
Under isolate methanol, then boil off moisture under the conditions of 0.01MPa, 100 DEG C through thin film evaporator again, obtain paraphenetidine
4771kg, its conversion ratio 100%, yield 98.9%, selectivity 99.9%, the purity 99.9% of paraphenetidine.
Embodiment 6
By 3000kg paranitroanisoles, 6kg catalyst ns i-Co-P, (wherein Ni, Co, P percentage by weight is respectively
95.0wt%, 3.0wt% and 2.0wt%) and 3300L methanol add embodiment 5 leave in the 16000L reactors of catalyst, shape
Into mixed liquor.
Nitrogen is passed through to reactor to empty again to 0.5MPa, is repeated 3 times to remove the air in reactor；Then, it is passed through
Hydrogen empties again to 0.5MPa, is repeated 3 times to remove the nitrogen in reactor.
It is replaced, hydrogen is passed through into reactor to 1.5MPa, steam valve is opened and reactor is heated up, work as temperature
When degree rises to 80 DEG C, steam off valve.Reactor agitator (slowly being raised speed by frequency converter) is opened with 140rpm stirring
Speed is stirred to mixed liquor, carries out hydrogenation reaction；In course of reaction, controlling reaction temperature is 80 ± 1 DEG C, and keeps reacting
Hydrogen Vapor Pressure in kettle is 1.5MPa.
In course of reaction, mixed liquor is detected once per hour；When measure in mixed liquor (removal methanol content) to nitro
When the content of methyl phenyl ethers anisole drops to 20%, every 0.5 hour detection mixed liquor is changed to once；(methanol is removed when measuring in mixed liquor
Content) the content of paranitroanisole when dropping to 5%, be changed to every 10 minutes detection mixed liquors once；Until in mixed liquor
When the content to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene of (removal methanol content) is below 0.1%, Guan Qing
Air valve, stop hydrogenation.
Mixing speed is reduced to 50rpm, is cooled with cooling water；When temperature is down to 50 DEG C, stop stirring, stand half
The material on upper strata is extruded after hour, lower floor is mainly catalyst, is stayed in reactor, for hydrogenation next time.
The upper materials of extrusion are entered into method separation tower, are 130 DEG C in column bottom temperature, tower top temperature is 100 DEG C of bar
Methanol is isolated under part, then moisture is boiled off under the conditions of 0.01MPa, 120 DEG C through thin film evaporator again, obtains p-aminophenyl first
Ether 2390kg, its conversion ratio 100%, yield 99.1%, selectivity 99.7%, the purity 99.7% of paraphenetidine.
Embodiment 7
By 6000kg paranitroanisoles, 12kg catalyst ns i-Co-P, (wherein Ni, Co, P percentage by weight is respectively
95.0wt%, 3.0wt% and 2.0wt%) and 6060L methanol add embodiment 6 leave in the 16000L reactors of catalyst, shape
Into mixed liquor.
Nitrogen is passed through to reactor to empty again to 0.5MPa, is repeated 4 times to remove the air in reactor；Then, it is passed through
Hydrogen empties again to 0.5MPa, is repeated 4 times to remove the nitrogen in reactor.
It is replaced, hydrogen is passed through into reactor to 1.6MPa, steam valve is opened and reactor is heated up, work as temperature
When degree rises to 100 DEG C, steam off valve.Reactor agitator (slowly being raised speed by frequency converter) is opened with 80rpm stirring
Speed is stirred to mixed liquor, carries out hydrogenation reaction；In course of reaction, controlling reaction temperature is 100 ± 1 DEG C, and keeps anti-
It is 1.6MPa to answer the Hydrogen Vapor Pressure in kettle.
In course of reaction, mixed liquor is detected once per hour；When measure in mixed liquor (removal methanol content) to nitro
When the content of methyl phenyl ethers anisole drops to 20%, every 0.5 hour detection mixed liquor is changed to once；(methanol is removed when measuring in mixed liquor
Content) the content of paranitroanisole when dropping to 5%, be changed to every 10 minutes detection mixed liquors once；Until in mixed liquor
When the content to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene of (removal methanol content) is below 0.1%, Guan Qing
Air valve, stop hydrogenation.
Mixing speed is reduced to 40rpm, is cooled with cooling water；When temperature is down to 40 DEG C, stop stirring, stand half
The material on upper strata is extruded after hour, lower floor is mainly catalyst, is stayed in reactor, for hydrogenation next time.
The upper materials of extrusion are entered into method separation tower, are 90 DEG C in column bottom temperature, tower top temperature is 60 DEG C of condition
Under isolate methanol, then boil off moisture under the conditions of 0.02MPa, 110 DEG C through thin film evaporator again, obtain paraphenetidine
4776kg, its conversion ratio 100%, yield 99.0%, selectivity 99.8%, the purity 99.8% of paraphenetidine.
Embodiment 8
By 3000kg paranitroanisoles, 6kg catalyst ns i-Co-P, (wherein Ni, Co, P percentage by weight is respectively
95.0wt%, 3.0wt% and 2.0wt%) and 3600L methanol add embodiment 7 leave in the 16000L reactors of catalyst, shape
Into mixed liquor.
Nitrogen is passed through to reactor to empty again to 0.5MPa, is repeated 4 times to remove the air in reactor；Then, it is passed through
Hydrogen empties again to 0.5MPa, is repeated 4 times to remove the nitrogen in reactor.
It is replaced, hydrogen is passed through into reactor to 1.2MPa, steam valve is opened and reactor is heated up, work as temperature
When degree rises to 110 DEG C, steam off valve.Reactor agitator (slowly being raised speed by frequency converter) is opened with 150rpm stirring
Speed is stirred to mixed liquor, carries out hydrogenation reaction；In course of reaction, controlling reaction temperature is 110 ± 1 DEG C, and keeps anti-
It is 1.2MPa to answer the Hydrogen Vapor Pressure in kettle.
In course of reaction, mixed liquor is detected once per hour；When measure in mixed liquor (removal methanol content) to nitro
When the content of methyl phenyl ethers anisole drops to 20%, every 0.5 hour detection mixed liquor is changed to once；(methanol is removed when measuring in mixed liquor
Content) the content of paranitroanisole when dropping to 5%, be changed to every 10 minutes detection mixed liquors once；Until in mixed liquor
When the content to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene of (removal methanol content) is below 0.1%, Guan Qing
Air valve, stop hydrogenation.
Mixing speed is reduced to 30rpm, is cooled with cooling water；When temperature is down to 60 DEG C, stop stirring, stand half
The material on upper strata is extruded after hour, lower floor is mainly catalyst, is stayed in reactor, for hydrogenation next time.
The upper materials of extrusion are entered into method separation tower, are 110 DEG C in column bottom temperature, tower top temperature is 80 DEG C of condition
Under isolate methanol, then boil off moisture under the conditions of 0.01MPa, 120 DEG C through thin film evaporator again, obtain paraphenetidine
2381kg, its conversion ratio 100%, yield 98.7%, selectivity 99.7%, the purity 99.7% of paraphenetidine.
Comparative example 1
The synthetic method of the alkoxyl aniline disclosed according to applicant in this case in Chinese patent CN101492379, does
Comparative experiments.
According to the reaction condition of the embodiment 2 in CN101492379, scaled up to the industry rule of the application
Mould, i.e.,：By 3000kg paranitroanisoles, 30kg Raney Ni, 3000L methanol is added in reactor, and is passed through in 80 DEG C
Hydrogen (setting pressure as 1.5Mpa) is reacted, and is stopped until hydrogen half an hour after is no longer inhaled in reaction.After reaction terminates, by high pressure
Kettle is quenched to room temperature, filters out catalyst, takes filtrate to carry out gas chromatographic analysis, is found much less than it in laboratory scale
Result when (100g para-nitrotoluene).At laboratory stage (as disclosed in patent CN101492379), can obtain to nitre
Base methyl phenyl ethers anisole conversion ratio 100%, paraphenetidine selectivity 99.5%；And in the work for being amplified to 3000kg paranitroanisoles
After industry scale, the analysis for reacting filtrate is shown, conversion ratio only has 99.0%, paraphenetidine selectivity 96.5%, to ammonia
The purity 96.5% of base methyl phenyl ethers anisole, therefore, such product purity are clearly far can not meet the needs of downstream raw materials for production,
Purifying technique must be further carried out.
By comparison, the material rate of the embodiment of the present application 6 is closer to the comparative example 1, but the embodiment is last
Acquisition paraphenetidine 2390kg, its conversion ratio 100%, yield 99.1%, selectivity 99.7%, paraphenetidine
Purity 99.7%, fully meet when downstream produces to the demand of raw material, can directly use.It is appreciated that this of the present invention
Excellent effect is due to employ commercially available ternary alloy three-partalloy Ni-Co-P (wherein Ni, Co, P percentage by weights through especially selecting
Respectively 95.0wt%, 3.0wt% and 2.0wt%) catalyst is used as, and with by monitoring in reaction mixture to nitrosobenzene
The content of methyl ether, hydrazobenzene and azoxybenzene is used as standard and terminates catalytic hydrogenation reaction, thus than in comparative example 1 with
" no longer consuming hydrogen " is that standard can more be accurately controlled reaction end, therefore can be obtained simultaneously in plant-scale reaction
High selectivity and conversion ratio.
Comparative example 2
According to, using skeletal isomerzation as catalyst, paranitroanisole liquid phase selects disclosed in Chinese patent CN1775353
Property hydrogenation to prepare the method for paraphenetidine, its process conditions is scaled up to the commercial scale of the application, i.e.,：Will
Skeleton ruthenium catalyst after 4000kg paranitroanisoles, 20000 liters of tetrahydrofurans, 100kg activation, then passes to hydrogen and delays
Slow heating response kettle is warming up to 70 degree, keeps system pressure, reaction solution is determined after 2 hours.
In lab scale stage (magnitude of 4g paranitroanisoles), Chinese patent CN1775353 can obtain conversion ratio 100%
And yield is 99%.But after the commercial scale of 4000kg paranitroanisoles is amplified to, the analysis for reacting filtrate is shown
Show, conversion ratio only has 99.0%, and the purity 97.0% of paraphenetidine, yield is only 96.0%.The purity of the product is obvious
It is far can not meet the needs of downstream raw materials for production, it is necessary to be further carried out purifying technique.
The result of above-mentioned each comparative example demonstrates, and fails to realize on a commercial scale so far compared to prior art
High selectivity, paraphenetidine is prepared in high yield, the preparation method of paraphenetidine of the invention really can be in work
High conversion, high selectivity are taken into account simultaneously in industry scale, therefore there is far-reaching meaning for the industrially prepared of paraphenetidine
Justice.
Claims (7)
1. a kind of preparation method of paraphenetidine, including the steps：
1) feed intake：By paranitroanisole, catalyst and methanol using mass ratio as 100：0.2~2：80~100 ratio adds
In reactor, mixed liquor is formed；
Wherein, the catalyst is Ni-Mo-B, wherein Ni, Mo, B percentage by weight be respectively 95.0wt%, 3.0wt% and
2.0wt%；Or the catalyst is Ni-Co-P, wherein Ni, Co, P percentage by weight be respectively 95.0wt%,
3.0wt% and 2.0wt%；
2) deoxygenation：It is passed through nitrogen to empty again to 0.5MPa, repeats 3~5 times, with the air in replacement reaction kettle；Then, it is passed through hydrogen
Gas empties again to 0.5MPa, repeats 3~5 times, with the nitrogen in replacement reaction kettle；
3) batch (-type) is hydrogenated with：It is replaced, hydrogen is passed through into reactor to 0.8~1.8MPa, mixed liquor is stirred, entered
Row hydrogenation reaction；In course of reaction, controlling reaction temperature is 80~120 DEG C, and keep Hydrogen Vapor Pressure in reactor for 0.8~
1.8MPa；
Detect mixed liquor once per hour；When the content for measuring the paranitroanisole in mixed liquor drops to 20%, it is changed to
Every 0.5 hour detection mixed liquor is once；When the content for measuring the paranitroanisole in mixed liquor drops to 5%, it is changed to every
10 minutes detection mixed liquors are once；Until containing in mixed liquor to nitrosobenzene methyl ether, hydrazobenzene and azoxybenzene
When amount is below 0.1%, hydrogen valve is closed, stops hydrogenation；
4) cooling discharge：Reduce mixing speed and cooled with cooling water, when temperature is down to 30~50 DEG C, stop stirring,
The material on upper strata is extruded after standing, the material of lower floor is mainly catalyst；
5) purified product：The material on the upper strata that step 4) is extruded isolates methanol into method separation tower, and separation condition is：
Knockout tower column bottom temperature is 80~130 DEG C, and tower top temperature is 50~100 DEG C；
The methanol isolated recycles as solvent when preparing paraphenetidine next time, after this is eliminated into methanol
Material boils off moisture through thin film evaporator, obtains required paraphenetidine.
2. the preparation method of paraphenetidine according to claim 1, wherein：Be passed through in step 3) hydrogen to 1.0~
1.6MPa。
3. the preparation method of paraphenetidine according to claim 1, wherein：The mixing speed of step 3) be 60~
300rpm。
4. the preparation method of paraphenetidine according to claim 1, wherein：The mixing speed of step 3) be 80~
160rpm。
5. the preparation method of paraphenetidine according to claim 1, wherein：The reaction temperature of step 3) is 90~100 DEG C.
6. the preparation method of paraphenetidine according to claim 1, wherein：Reduce in step 4) mixing speed to 30~
60rpm。
7. the preparation method of paraphenetidine according to claim 1, wherein：The Matter Transfer of lower floor in step 4) makes
With into the preparation flow of paraphenetidine next time.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510314205.1A CN105272863B (en) | 2014-06-11 | 2015-06-10 | The preparation method of paraphenetidine |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410256913X | 2014-06-11 | ||
| CN201410256913 | 2014-06-11 | ||
| CN201510314205.1A CN105272863B (en) | 2014-06-11 | 2015-06-10 | The preparation method of paraphenetidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105272863A CN105272863A (en) | 2016-01-27 |
| CN105272863B true CN105272863B (en) | 2017-12-19 |
Family
ID=55142765
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510314205.1A Active CN105272863B (en) | 2014-06-11 | 2015-06-10 | The preparation method of paraphenetidine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105272863B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106187786B (en) * | 2016-06-29 | 2019-01-22 | 浙江闰土研究院有限公司 | A kind of clean preparation method of paraphenetidine |
| CN106496046A (en) * | 2016-09-28 | 2017-03-15 | 连云港泰盛化工有限公司 | The method that solvent-free catalytic hydrogenation produces aminoanisole |
| CN107746380B (en) * | 2017-11-06 | 2020-04-07 | 宁夏中盛新科技有限公司 | Industrial production method of 2-amino-4-acetamino anisole |
| CN107903182B (en) * | 2017-11-06 | 2020-04-07 | 宁夏中盛新科技有限公司 | Synthesis method of 2-amino-4-acetamino anisole |
| CN108047064B (en) * | 2017-11-06 | 2020-06-30 | 中国科学院兰州化学物理研究所 | Method for preparing p-anisidine by catalytic hydrogenation of p-nitroanisole |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1408474A (en) * | 2002-08-31 | 2003-04-09 | 复旦大学 | Amorphous hydrogenating 4,4'-dinitrodiphynyl ether catalyst and its preparing method |
| CN1861570A (en) * | 2006-06-19 | 2006-11-15 | 常州市佳森化工有限公司 | Tech. of preparing amino benz methyl-phenoxide by nitro methyl-phenoxide mixture catalyzing hydrogenation |
| CN101492379A (en) * | 2008-01-25 | 2009-07-29 | 南京理工大学 | Synthesis of alkoxyl aniline |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009094210A1 (en) * | 2008-01-22 | 2009-07-30 | Concert Pharmaceuticals Inc. | Vandetanib derivatives |
| EP2242493B1 (en) * | 2008-01-22 | 2013-06-05 | Concert Pharmaceuticals Inc. | Derivatives of gefitinib |
| CN101284783B (en) * | 2008-05-19 | 2011-07-20 | 江苏中丹集团股份有限公司 | Synthetic method of nitrobenzene ether compounds |
| CN100591664C (en) * | 2008-10-15 | 2010-02-24 | 湖北楚源高新科技股份有限公司 | H acid continuous nitration and denitration, extraction, hydrogenation reduction production process |
| CN102553597B (en) * | 2010-12-22 | 2013-10-30 | 太原理工大学 | Preparation method of supported Ni-B amorphous catalyst for selective hydrogenation |
| CN102850229A (en) * | 2012-07-24 | 2013-01-02 | 万达集团股份有限公司 | Process for preparing 4,4'-diaminodiphenyl ether by hydrogenation reduction method |
-
2015
- 2015-06-10 CN CN201510314205.1A patent/CN105272863B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1408474A (en) * | 2002-08-31 | 2003-04-09 | 复旦大学 | Amorphous hydrogenating 4,4'-dinitrodiphynyl ether catalyst and its preparing method |
| CN1861570A (en) * | 2006-06-19 | 2006-11-15 | 常州市佳森化工有限公司 | Tech. of preparing amino benz methyl-phenoxide by nitro methyl-phenoxide mixture catalyzing hydrogenation |
| CN101492379A (en) * | 2008-01-25 | 2009-07-29 | 南京理工大学 | Synthesis of alkoxyl aniline |
Non-Patent Citations (3)
| Title |
|---|
| 三相催化法制备对氨基苯甲醚;张杏金，施英俭;《江苏化工》;19921231(第3期);第19-20页 * |
| 对氨基苯甲醚合成试验研究及可行性论证;陶建国;《华东理工大学工程硕士学位论文》;20120520;第9页，第27页2）操作过程 * |
| 非晶态合金催化剂用于卤代硝基苯液相催化加氢的研究;孙军庆;《中国优秀硕士学位论文全文数据库 工程科技I辑》;20120315(第3期);第49页3.2.3 结论，第75页4.4.3 结论 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105272863A (en) | 2016-01-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105272863B (en) | The preparation method of paraphenetidine | |
| CN101962309B (en) | Method and device for continuously producing p-menthane by utilizing bipentene | |
| CN113402395A (en) | Method for continuously and efficiently synthesizing m-phenylenediamine based on fixed bed microreactor | |
| CN104402774B (en) | Method for preparing CLT acid through continuous catalytic hydrogenation reduction | |
| CN113563201B (en) | Method for continuously and efficiently synthesizing 3, 4-dichloroaniline based on fixed bed microreactor | |
| CN107746380B (en) | Industrial production method of 2-amino-4-acetamino anisole | |
| CN102964278B (en) | Method for preparing CLT acid (2-amino-4-methyl-5-chlorobenzene sulfonic acid) by continuous catalytic hydrogenation reduction | |
| CN110551278B (en) | Supported catalyst and preparation method and application thereof | |
| CN113429295B (en) | Method for preparing m-phenylenediamine by continuous catalytic hydrogenation based on fixed bed microreactor | |
| CN106588758A (en) | Synthetic process for 2-hydrazinylpyridine derivative | |
| CN105294456B (en) | The method that paraphenetidine is prepared with the device catalytic hydrogenation of industrially scalable | |
| CN107473954A (en) | A kind of greenization production method of succinic acid | |
| CN110627650B (en) | Device for continuously synthesizing benzylamine substances through heterogeneous hydrogenation in microreactor | |
| CN103086895B (en) | Method for preparing aromatic amine from mixed nitrochlorobenzene | |
| CN101607919A (en) | A kind of nitro-chlorobenzene that mixes reacts the method for producing anisidine in water solvent | |
| CN110054582B (en) | Preparation method of 3-amino-N-ethyl carbazole | |
| CN110183370B (en) | Industrial production method of N-ethyl pyrrolidone | |
| CN101007773A (en) | Process for preparing ethyl p-dimethylaminobenzoate | |
| CN107619374A (en) | A kind of method for continuously synthesizing of p-phenylenediamine | |
| CN107353271A (en) | The method for purifying the method for phthalide and phthalide being prepared by phthalic anhydride | |
| CN104744382B (en) | A kind of preparation method of homopiperazine | |
| CN110172029B (en) | Method for continuously synthesizing 2-amino-2-methyl-1-propanol | |
| CN108285417A (en) | The method that liquid phase continuous catalytic hydrogenation reduction nitrotoleune prepares methylaniline | |
| CN106278904B (en) | The method that cyclohexylamine is prepared by benzene one kettle way | |
| CN108997356B (en) | Method for synthesizing 2-methyl triethylene diamine by catalyzing ethylene imine and 2-methyl piperazine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 755000 north side of A4 Road, industrial park, the Ningxia Hui Autonomous Region. Patentee after: Ningxia Zhongsheng New Technology Co. Ltd. Address before: 755000 north side of A4 Road, industrial park, the Ningxia Hui Autonomous Region. Patentee before: NINGXIA MINGSHENG DYEING AND CHEMICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |