CN1413991A - Method of fixed bed continuous synthetising piperazine series compound - Google Patents
Method of fixed bed continuous synthetising piperazine series compound Download PDFInfo
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- CN1413991A CN1413991A CN 02131097 CN02131097A CN1413991A CN 1413991 A CN1413991 A CN 1413991A CN 02131097 CN02131097 CN 02131097 CN 02131097 A CN02131097 A CN 02131097A CN 1413991 A CN1413991 A CN 1413991A
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- piperazine
- fixed bed
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- series compound
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Abstract
A process for continuously synthesizing piperazine-series compounds from N-beta-hydroxyethyl ethanediamine or its derivative in hydrogen gas by fixed bed features that its catalyst is composed of the carrier (gamma-Al2O3) and the active component, which may be Ni, Cu, Cr, Zn, or Fe, or their composite oxide, or the simple substance plus composite oxide. The reaction takes place at 120-380 deg.c, 100-2300/hr, and 0-10 MPa. The water, benzene and triethane can be used as the solvent or diluent of raw material. Its advantages are high stability of activity and long service life for catalyst, and high output rate of product.
Description
Technical field
The invention belongs to the synthesis technique of medicine intermediate piperazine series compound, exactly is by N-beta-hydroxyethyl quadrol or derivatives thereof (compound shown in the formula I)
The method of the piperazine compounds of synthesizing piperazine or replacement (compound shown in the formula II).
Wherein R is H or C
1～C
6Low carbon number alkyl or have C
1～C
4The aryl of alkyl substituent.R
1, R
2, R
3, R
4Be H or C
1～C
4Alkyl substituent.
Background technology
Piperazine compounds is the important organic chemical industry's intermediate of a class, is widely used in industries such as medicine, agricultural chemicals, dyestuff, tensio-active agent.For example: piperazine can be used for medicines such as synthetic Norxin, pipemidic acid and Rifampin; The 2-methylpiperazine can be used for the synthetic hydrochloric acid lomefloxacin; Cis 2,6-lupetazin are used for synthetic fluorine quinlone class medicine sparfloxacin; And the N-ethyl piperazidine is the important intermediate of synthetic veterinary drug anthracene Flucloxacillin.External very extensive to the research of this compounds, be example with the piperazine, relative patent report just reaches a hundreds of piece of writing.Press the raw material difference that is adopted, the synthetic method of piperazine mainly contains following several: EP163,253,04 grade has reported that with monoethanolamine be raw material, synthesizing piperazine under High Temperature High Pressure and catalyst action, the technology of coproduction quadrol, but this route piperazine yield is low, generally between 15～25%; US3,682,919 patent reports such as grade be the technology that raw material deamination under the effect of High Temperature High Pressure and catalyzer prepares piperazine with the diethylenetriamine, this method yield is higher relatively, can reach about 80%, but the prices of raw and semifnished materials is higher, has restricted its industrialization; JP49,11,712 and JP74,125, it is the operational path of raw material hydrogenation cyclization system piperazine that 375 grades have been reported with N-beta-hydroxyethyl quadrol, and these class methods are catalyzer with the oxide compound of metals such as copper, chromium, manganese, and it is less to have a by product, the yield advantage of higher, yield reaches as high as more than 90%, but reaction pressure is too high, generally at 8～26MPa, and be batch production, production efficiency is low; People such as Weitkamp have reported with the quadrol to be that raw material is a catalyzer with the KZSM-5 zeolite, produce the technology of piperazine by-product triethylene diamine, and this technology total recovery is higher, but catalyst life does not reach industrialization demands.In addition, abroad some produce the major company of aminated compounds, also extract piperazine from the by product of producing quadrol, diethylenetriamine as BASF, Nobel etc., but because the piperazine content in this series products is generally very low, extract phase is to difficulty.Synthesizing of other piperazine compounds, what have is raw material with the piperazine, it is carried out the piperazine compounds that the N-alkylated reaction prepares corresponding N-replacement, the piperazine compounds to replace with the synthetic C-of substituent raw material accordingly that has, they all exist problems such as the higher or catalyst life of cost is short.Therefore, the synthetic research to piperazine compounds is necessary.
Summary of the invention
The object of the present invention is to provide a kind of method of fixed bed continuous synthetising piperazine series compound.This method has operational condition easily to be controlled, catalyzer long service life, the characteristics that product yield is high.
The present invention is realized by following technical proposals.To synthesize the piperazine compounds suc as formula piperazine shown in the II or replacement suc as formula the N-beta-hydroxyethyl quadrol or derivatives thereof shown in the I, R is H or C in the formula
1～C
6Low carbon number alkyl or have C
1～C
4The aryl of alkyl substituent.R
1, R
2, R
3, R
4Be H or C
1～C
4Alkyl substituent.This method adopts fixed bed, compound shown in the formula I of feeding gas phase or liquid phase under atmosphere of hydrogen.It is characterized in that catalyzer is with γ-Al
2O
3Be carrier, active ingredient is Ni, Cu, Cr, Zn, Fe simple substance composite catalyst; Or the catalyzer of their composite oxides; Or the composite catalyst of simple substance and oxide compound, each components contents≤10%, gross activity composition are 10～45%, air speed is 100～23000h
-1, temperature of reaction is 120～380 ℃, and reaction pressure is 0～10MPa, and solvent or thinner are water, benzene, dimethylbenzene, DMF, DMSO, CH
2Cl
2, CHCl
3, ether, propyl alcohol, butanols, dioxane, triethylamine, its consumption is 20～90%.
The above-mentioned preferred Ni/Cu/Cr/Zn of catalyst activity component, Ni/Cu/Cr/Fe, Ni/Cr/FeCu/Cr
2O
3/ ZnO, Cu/Cr
2O
3/ Fe
2O
3, NiO/Cr
2O
3/ Fe
2O
3, CuO/Cr
2O
3/ Fe
2O
3, NiO/Cr
2O
3/ Fe
2O
3/ ZnO.
The excellent control of above-mentioned temperature of reaction is at 150～320 ℃.
The excellent control of above-mentioned reaction pressure is at 0.5～5MPa.
Above-mentioned thinner preferably water, DMF, CHCl
3, ether and butanols.
Its consumption preferred 40～80%.
The Preparation of Catalyst that the invention has the advantages that use is easy, and is activity stabilized, and the life-span is long, catalysis synthetic product yield height.
Embodiment example 1
Reactor is a fixed-bed tube reactor, and internal diameter is 25mm, and pipe range 480mm, apparatus with catalyst inside 58g, catalyzer are the γ-Al of nickeliferous 5%, copper 4%, chromium 2%, zinc 1%
2O
340% the aqueous solution of N-beta-hydroxyethyl quadrol through preheating with 300h
-1Speed to enter temperature be 250 ℃ beds, hydrogen pressure is 1MPa.Reaction result: the transformation efficiency of N-beta-hydroxyethyl quadrol is 98.2%, and the selectivity of piperazine is 94.3%.Example 2
Filling 50g catalyzer in above-mentioned fixed-bed tube reactor, consisting of of catalyzer is nickeliferous 10%, the γ-Al of copper 5%, chromium 2%, iron 2%
2O
3The toluene solution process preheating of N-beta-hydroxyethyl quadrol is with 200h
-1Speed to enter temperature be 220 ℃ beds, hydrogen pressure is 2MPa.Reaction result: the transformation efficiency of N-beta-hydroxyethyl quadrol is 93.5%, and the selectivity of piperazine is 94.2%.Example 3
Filling 55g catalyzer in above-mentioned fixed-bed tube reactor, catalyzer consist of the γ-Al that contains nickel oxide 5.5%, chromic oxide 3%, ferric oxide 5%
2O
3The dioxane solution process preheating of N-beta-hydroxyethyl quadrol is with 2000h
-1Speed to enter temperature be 200 ℃ beds, hydrogen pressure is 1.5MPa.Reaction result: the transformation efficiency of N-beta-hydroxyethyl quadrol is 90.8%, and the selectivity of piperazine is 94.6%.Example 4
Filling 50g catalyzer in above-mentioned fixed-bed tube reactor, the γ-Al that consists of cupric 6%, chromic oxide 3%, zinc oxide 4% of catalyzer
2O
3The aqueous solution process preheating of N-β-hydroxypropyl quadrol is with 800h
-1Speed to enter temperature be 240 ℃ beds, hydrogen pressure is 1.8MPa.Reaction result: the transformation efficiency of N-β-hydroxypropyl quadrol is 94.8%, and the selectivity of 2-methylpiperazine is 93.7%.Example 5
Filling 55g catalyzer in above-mentioned fixed-bed tube reactor, the γ-Al that consists of cupric 10%, chromic oxide 10%, ferric oxide 3% of catalyzer
2O
3N-β-hydroxypropyl 1, the diethyl ether solution process preheating of 2-propylene diamine is with 1000h
-1Speed to enter temperature be 260 ℃ beds, hydrogen pressure is 2MPa.Reaction result: N-β-hydroxypropyl 1, the transformation efficiency of 2-propylene diamine are 91.5%, 2, and the selectivity of 6-lupetazin is 95.3%.Example 6
Filling 50g catalyzer in above-mentioned fixed-bed tube reactor, catalyzer consist of the γ-Al that contains nickel oxide 6%, chromic oxide 4%, ferric oxide 2%, zinc oxide 1.5%
2O
3The butanol solution process preheating of N-ethyl-beta-hydroxyethyl quadrol is with 500h
-1Speed to enter temperature be 180 ℃ beds, hydrogen pressure is 1MPa.Reaction result: the transformation efficiency of N-ethyl-beta-hydroxyethyl quadrol is 94.1%, and the selectivity of N-ethyl piperazidine is 93.2%.
Claims (4)
1. the method for a fixed bed continuous synthetising piperazine series compound, this method is a main raw material with the N-beta-hydroxyethyl quadrol or derivatives thereof shown in the I formula, in the piperazine shown in the synthetic II formula of the atmosphere of hydrogen of fixed bed or the piperazine compounds of replacement,
Wherein R is H or C
1～C
6Low carbon number alkyl or have C
1～C
4The aryl of alkyl substituent; R
1, R
2, R
3, R
4Be H or C
1～C
4Alkyl substituent;
It is characterized in that: the carrier that catalyzer adopts is γ-Al
2O
3, active ingredient is Ni, Cu, Cr, Zn, Fe simple substance composite catalyst; Or the catalyzer of their composite oxides; Or the composite catalyst of simple substance and oxide compound, each components contents≤10%, gross activity composition are 10～45%, the air speed of reactor is 100～23000h
-1, temperature of reaction is 120～380 ℃, and reaction pressure is 0～10MPa, and the solvent of raw material or thinner are water, benzene, dimethylbenzene, DMF, DMSO, CH
2Cl
2, CHCl
3, ether, propyl alcohol, butanols, dioxane, triethylamine, its consumption is 20～90%.
2. the method for fixed bed continuous synthetising piperazine series compound as claimed in claim 1 is characterized in that: the preferred Ni/Cu/Cr/Zn of catalyst activity component, Ni/Cu/Cr/Fe, Ni/Cr/Fe, Cu/Cr
2O
3/ ZnO, Cu/Cr
2O
3/ Fe
2O
3, NiO/Cr
2O
3/ Fe
2O
3, CuO/Cr
2O
3/ Fe
2O
3, NiO/Cr
2O
3/ Fe
2O
3/ ZnO.
3. the method for fixed bed continuous synthetising piperazine series compound as claimed in claim 1, it is characterized in that: the excellent control of temperature is at 150～320 ℃, and the excellent control of reaction pressure is at 0.5～5MPa.
4. the method for fixed bed continuous synthetising piperazine series compound as claimed in claim 1 is characterized in that: the solvent of raw material or thinner preferably water, DMF, CHCl
3, ether and butanols, its consumption is 40～80%.
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|---|---|---|---|
| CN 02131097 CN1413991A (en) | 2002-10-09 | 2002-10-09 | Method of fixed bed continuous synthetising piperazine series compound |
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|---|---|---|---|
| CN 02131097 CN1413991A (en) | 2002-10-09 | 2002-10-09 | Method of fixed bed continuous synthetising piperazine series compound |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100334078C (en) * | 2005-03-22 | 2007-08-29 | 建德市新化化工有限责任公司 | Method for synthesizing piperazine |
| CN102952096A (en) * | 2011-08-17 | 2013-03-06 | 烟台万华聚氨酯股份有限公司 | Anhydrous piperazine preparation method |
| WO2014184039A1 (en) | 2013-05-16 | 2014-11-20 | Basf Se | Method for preparing n-alkyl-piperazines |
| CN106984343A (en) * | 2017-03-20 | 2017-07-28 | 钦州学院 | A kind of catalyst for being used for N β AEEAs synthesizing piperazines and N methyl piperazines and preparation method thereof |
| CN110343077A (en) * | 2019-07-12 | 2019-10-18 | 四川久凌制药科技有限公司 | A kind of 1- benzyl homopiperazine alkane separation method |
| CN112724105A (en) * | 2021-04-02 | 2021-04-30 | 苏州丰倍生物科技有限公司 | Piperazine derivatives, their preparation and use |
| CN114247449A (en) * | 2021-11-23 | 2022-03-29 | 中海油天津化工研究设计院有限公司 | Catalyst for synthesizing piperazine from hydroxyethyl ethylenediamine, and preparation method and application thereof |
| CN114436993A (en) * | 2020-11-05 | 2022-05-06 | 中国石油化工股份有限公司 | Process for preparing piperazine |
-
2002
- 2002-10-09 CN CN 02131097 patent/CN1413991A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100334078C (en) * | 2005-03-22 | 2007-08-29 | 建德市新化化工有限责任公司 | Method for synthesizing piperazine |
| CN102952096A (en) * | 2011-08-17 | 2013-03-06 | 烟台万华聚氨酯股份有限公司 | Anhydrous piperazine preparation method |
| WO2014184039A1 (en) | 2013-05-16 | 2014-11-20 | Basf Se | Method for preparing n-alkyl-piperazines |
| CN106984343A (en) * | 2017-03-20 | 2017-07-28 | 钦州学院 | A kind of catalyst for being used for N β AEEAs synthesizing piperazines and N methyl piperazines and preparation method thereof |
| CN106984343B (en) * | 2017-03-20 | 2019-08-13 | 钦州学院 | It is a kind of for N- beta-hydroxyethyl ethylenediamine synthesizing piperazine and catalyst of N methyl piperazine and preparation method thereof |
| CN110343077A (en) * | 2019-07-12 | 2019-10-18 | 四川久凌制药科技有限公司 | A kind of 1- benzyl homopiperazine alkane separation method |
| CN114436993A (en) * | 2020-11-05 | 2022-05-06 | 中国石油化工股份有限公司 | Process for preparing piperazine |
| CN112724105A (en) * | 2021-04-02 | 2021-04-30 | 苏州丰倍生物科技有限公司 | Piperazine derivatives, their preparation and use |
| CN114247449A (en) * | 2021-11-23 | 2022-03-29 | 中海油天津化工研究设计院有限公司 | Catalyst for synthesizing piperazine from hydroxyethyl ethylenediamine, and preparation method and application thereof |
| CN114247449B (en) * | 2021-11-23 | 2023-08-22 | 中海油天津化工研究设计院有限公司 | Catalyst for synthesizing piperazine by hydroxyethyl ethylenediamine, and preparation method and application thereof |
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