CN101239957B - Method for synthesizing N-methylpiperazine - Google Patents
Method for synthesizing N-methylpiperazine Download PDFInfo
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- CN101239957B CN101239957B CN2008100197368A CN200810019736A CN101239957B CN 101239957 B CN101239957 B CN 101239957B CN 2008100197368 A CN2008100197368 A CN 2008100197368A CN 200810019736 A CN200810019736 A CN 200810019736A CN 101239957 B CN101239957 B CN 101239957B
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- piperazine
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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
- 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
Abstract
The invention relates to a synthesis method of N-methylpiperazine and chemical synthesis methods of chemical products, particularly to a synthesis process of N-methylpiperazine using vermex, formaldehyde and hydrogen as materials. Vermex is reacted with formaldehyde under atmosphere pressure to generate a condensate, and then the condensate is reacted with hydrogen in a same reaction container and under catalysis of Raney nickel catalyst to obtain N-methylpiperazine, wherein, the hydrogenation pressure is 1.0-6.0 MPa, the hydrogenation temperature is 70-100 DEG C, the catalyst dosage is 4%-12% of vermex dosage, the reaction solvent is methanol. The method has advantages of short process, low investment, high efficiency, etc.
Description
Technical field
The present invention relates to a kind of chemical synthesis process of Chemicals, is the synthesis technique of the N methyl piperazine of raw material with piperazine and formaldehyde, hydrogen particularly.
Background technology
N methyl piperazine is one of derived product of piperazine, is a kind of important fine chemical product, pharmaceutically can be used for spiritual class medicines such as anti-microbial type medicine such as synthetic Ofloxacine USP 23, Levofloxacin, fleroxacin and leoponex, olanzapine; Industry also is widely used in high molecular industrial and commercial banks such as rubber, plastics.
This product also is in the exploitation developmental stage at home at present, and the synthetic method of the domestic-developed of document record mainly contains two kinds:
Method one: reaction earlier in dehydrated alcohol generates piperazine hydrochloride with piperazine and hydrochloric acid, boil off ethanol isolate behind the piperazine hydrochloride again with formaldehyde, formic acid react the N methyl piperazine hydrochloride, with the sodium hydroxide neutralization, behind the separation sodium-chlor, get product through rectifying more then.This method technological process is long, will use very strong hydrochloric acid of corrodibility and formic acid in the production, and seriously polluted, operating environment is poor, yield only 49%.
Method two: make methylating reagent and solvent with methyl alcohol, piperazine and methyl alcohol vaporization back are reacted by the fixed bed catalyst layer, part material generates N methyl piperazine, and the high-temperature gas reaction mixture is collected through condensation, obtains product again after rectifying.This method temperature of reaction is up to 300 ℃, and energy consumption is big, and per pass conversion also can only reach 50%, and by product is many, and product purity is low; The immovable bed catalyzer that this production method is used is difficult for changing, and along with catalyst activity reduction, transformation efficiency is more and more lower, and energy consumption is more and more higher, can only thoroughly change to certain the time, and replacement charge is very high, and production cost is difficult to decline.
Summary of the invention
The objective of the invention is in order to overcome above deficiency, provide a kind of environmentally friendly, feed stock conversion is high, product selectivity good, flow process is simple, is fit to the synthetic method of industrialized N methyl piperazine.
The present invention includes following steps:
1) condensation reaction: with methyl alcohol is solvent, and piperazine and formaldehyde feed intake with mol ratio 1: 0.8～1.6, carries out condensation reaction in reactor;
2) after condensation is finished, add catalyzer in same reactor, and after replacing with nitrogen and hydrogen, hydrogen boosts to 1～6Mpa, control material in reactor temperature is 70～100 ℃, keeps stirring and finishes until hydrogenation; Wherein, the add-on of catalyzer is 4～12% of a piperazine quality;
3) the cooling material is to normal temperature, and after stopping to stir, discharging is filtered, and reclaims catalyzer;
4) with filtrate rectifying, behind recovery methyl alcohol and the unreacted piperazine, collect 137 ℃ of cuts, get N methyl piperazine.
Once through yield of the present invention can be up to 73～83%, and existing two kinds of method energy consumptions descend significantly, so production cost also descends significantly; Need in the current methods technology through several lock out operation, many, the long flow path of number of devices, total overall reaction of the present invention is finished in a reactor, and facility investment, maintenance are little, have fairly obvious technology advance; In addition, produce a large amount of waste water in the existing method one, environment is had certain influence, production process of the present invention does not have the three wastes substantially and produces; The purity that current methods is made N methyl piperazine can only reach 99.0%, and the present invention can make product purity reach 99.95%.
Catalyzer of the present invention can be selected from Raney's nickel or contain the palladium/charcoal of palladium 5%.
Formaldehyde of the present invention adopts the method that in batches adds to add in the reactor.Its advantage is to make the condensation exothermic process be easy to control.
In addition, the present invention is reflected in the autoclave of being with high speed agitator and carries out, and mixing speed is 80～800 rev/mins, helps gas-liquid and distributes.
Embodiment
Embodiment 1:
To capacity is to add 86 gram piperazines (1mol), 800 gram methyl alcohol in 2 liters the autoclave, starts agitator, adds the formaldehyde (1mol) of 81 gram concentration 37% from charge cavity in batches, adds 4 Cray Buddhist nun nickel catalyzators then, the sealing autoclave.
Successively with nitrogen, hydrogen exchange qualified after, then, hydrogen pressure in the still is risen to 2.0Mpa, close the hydrogenation valve, keep to stir, and will expect that slowly temperature rise to 70-80 ℃, keeps this temperature, keep still to press 2.0Mpa, carry out hydrogenation, finish (not inhaling hydrogen) until hydrogenation.To reactor cooling, release, take out reactant.
Filter, elimination catalyzer Raney's nickel is used for batch reaction down.Get filtrate, behind distillating recovering solvent methyl alcohol and the unreacted piperazine, collect 137 ℃ of cuts, get the N methyl piperazine of purity 〉=99.95%.
Embodiment 2:
Add 97.3 gram 37% formaldehyde (1.2mol), all the other conditions are with example 1 in batches.
Embodiment 3:
Add 113.5 gram 37% formaldehyde (1.6mol), all the other conditions are with example 1 in batches.
Embodiment 4:
Add 64.9 gram 37% formaldehyde (0.8mol), all the other conditions are with example 1 in batches.
Embodiment 5
Hydrogenation pressure 3.0Mpa, all the other conditions are with example 1.
Embodiment 6:
Hydrogenation pressure 6.0Mpa, all the other conditions are with example 1.
Embodiment 7:
Hydrogenation temperature 90-100 ℃, all the other conditions are with example 1.
Embodiment 8:
Hydrogenation temperature 60-70 ℃, all the other conditions are with example 1.
Embodiment 9:
Catalyst levels 8 grams, all the other conditions are with example 1.
Embodiment 10:
Catalyst levels 12 grams, all the other conditions are with example 1.
More than each routine relevant data see the following form:
Annotate: piperazine is a Piperazine anhydrous among all embodiment, feeds intake after also can using the moisture piperazine of all size to be converted to Piperazine anhydrous.Formaldehyde is 37% industrial formol, and solvent methanol quantity is 800 grams.
Catalyzer of the present invention can be Raney's nickel (the vesicular metallic nickel that obtains after al-ni alloy powder is activated), also can use 5% Pd/carbon catalyst (palladium/charcoal that contains palladium 5%) of same quantity.
According to last table data analysis:
When one timing of piperazine quantity, along with the increase of formaldehyde proportioning, by product N, N-lupetazin quantity rises; Hydrogen pressure rises, and the reaction times shortens; Control higher hydrogenation temperature, the reaction times shortens, but the by product increase, otherwise the lower hydrogenation temperature of control, the reaction times prolongs, and the principal product yield improves; Increase catalyst levels, the reaction times obviously shortens, and by product is also had certain restraining effect.
Claims (1)
1. the synthetic method of a N methyl piperazine may further comprise the steps:
To capacity is to add 86 gram piperazines, 800 gram methyl alcohol in 2 liters the autoclave, starts agitator, adds the formaldehyde of 81 gram concentration 37% from charge cavity in batches, adds 4 Cray Buddhist nun nickel catalyzators then, the sealing autoclave; Successively with nitrogen, hydrogen exchange qualified after, then, hydrogen pressure in the still is risen to 2.0Mpa, close the hydrogenation valve, keep stirring, and will expect that slowly temperature rise to 70-80 ℃, keeps this temperature, keep still pressure 2.0Mpa, carry out hydrogenation, finish until hydrogenation; To reactor cooling, release, take out reactant; Filter, elimination catalyzer Raney's nickel is used for batch reaction down; Get filtrate, behind distillating recovering solvent methyl alcohol and the unreacted piperazine, collect 137 ℃ of cuts, get the N methyl piperazine of purity 〉=99.95%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2008100197368A CN101239957B (en) | 2008-03-13 | 2008-03-13 | Method for synthesizing N-methylpiperazine |
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| CN2008100197368A CN101239957B (en) | 2008-03-13 | 2008-03-13 | Method for synthesizing N-methylpiperazine |
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| CN101239957A CN101239957A (en) | 2008-08-13 |
| CN101239957B true CN101239957B (en) | 2010-11-17 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102304102B (en) * | 2011-09-16 | 2013-08-21 | 浙江中欣化工股份有限公司 | Preparation method of 1-methyl piperazine |
| CN102627608B (en) * | 2012-03-31 | 2014-03-26 | 武汉武药制药有限公司 | Preparation method for analgesic and antipyretic drug-analgin |
| CN108499614B (en) * | 2018-04-28 | 2021-06-04 | 西南医科大学附属医院 | Method for preparing drug intermediate for central nervous system from modified nickel catalytic material |
| CN111233788A (en) * | 2020-03-20 | 2020-06-05 | 山东国邦药业有限公司 | Synthesis method of N-hydroxyethyl piperazine |
| CN111675677B (en) * | 2020-07-13 | 2022-07-19 | 江苏富比亚化学品有限公司 | Synthesis process of N-methylmorpholine |
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Address after: 225200 Shuanggou Caozhuang village, Xiannv Town, Jiangdu District, Yangzhou City, Jiangsu Province Patentee after: Yangzhou Xinhua Chemical Co.,Ltd. Address before: 225200 No. 55 Renmin Road, Jiangdu, Jiangsu Patentee before: JIANGDU XINHUA CHEMICAL Co.,Ltd. |
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Effective date of registration: 20220321 Address after: No. 66, xiahong Road, high tech Industrial Development Zone, Anqing City, Anhui Province Patentee after: Anhui Changhua Chemical Co.,Ltd. Address before: 225200 Shuanggou Caozhuang village, Xiannv Town, Jiangdu District, Yangzhou City, Jiangsu Province Patentee before: Yangzhou Xinhua Chemical Co.,Ltd. |
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