CN101948448A - Preparation method of pyrrolidine - Google Patents
Preparation method of pyrrolidine Download PDFInfo
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- CN101948448A CN101948448A CN 201010504622 CN201010504622A CN101948448A CN 101948448 A CN101948448 A CN 101948448A CN 201010504622 CN201010504622 CN 201010504622 CN 201010504622 A CN201010504622 A CN 201010504622A CN 101948448 A CN101948448 A CN 101948448A
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- China
- Prior art keywords
- pyrrolidine
- zsm
- molecular sieve
- tetrahydrofuran
- thf
- 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.)
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title claims abstract description 99
- 238000002360 preparation method Methods 0.000 title claims description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 66
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 33
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000002808 molecular sieve Substances 0.000 claims abstract description 15
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000012043 crude product Substances 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 claims description 21
- 229910021529 ammonia Inorganic materials 0.000 claims description 12
- 230000004913 activation Effects 0.000 claims description 8
- 230000018044 dehydration Effects 0.000 claims description 5
- 238000006297 dehydration reaction Methods 0.000 claims description 5
- 238000006555 catalytic reaction Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 6
- 239000003054 catalyst Substances 0.000 abstract description 4
- 238000001035 drying Methods 0.000 abstract description 4
- 238000011112 process operation Methods 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000003213 activating effect Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000001172 regenerating effect Effects 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- PWACSDKDOHSSQD-IUTFFREVSA-N acrivastine Chemical compound C1=CC(C)=CC=C1C(\C=1N=C(\C=C\C(O)=O)C=CC=1)=C/CN1CCCC1 PWACSDKDOHSSQD-IUTFFREVSA-N 0.000 description 2
- 229960003792 acrivastine Drugs 0.000 description 2
- 229960004156 bepridil hydrochloride Drugs 0.000 description 2
- JXBBWYGMTNAYNM-UHFFFAOYSA-N bepridil hydrochloride Chemical compound [H+].[Cl-].C1CCCN1C(COCC(C)C)CN(C=1C=CC=CC=1)CC1=CC=CC=C1 JXBBWYGMTNAYNM-UHFFFAOYSA-N 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- ZDPACSAHMZADFZ-UHFFFAOYSA-N 1-[3-(2,4,6-Trimethoxybenzoyl)propyl]pyrrolidinium chloride Chemical compound [Cl-].COC1=CC(OC)=CC(OC)=C1C(=O)CCC[NH+]1CCCC1 ZDPACSAHMZADFZ-UHFFFAOYSA-N 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 238000004176 ammonification Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960002113 buflomedil hydrochloride Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a synthesis method of pyrrolidine. The method comprises the following steps: 1) preparing a catalyst Cu-ZSM-5; 2) placing the catalyst Cu-ZSM-5 in a fixed bed reactor, introducing tetrahydrofuran and ammonia gas to catalyze and obtain crude pyrrolidine; and 3) rectifying the crude product, and drying with the molecular sieve to obtain pyrrolidine. The invention has simple process operation and low cost; the catalyst is easy to prepare and can be activated many times to use; and the yield of pyrrolidine is high, the quality is good and the water content is low.
Description
Technical field
The present invention relates to the preparation method of Pyrrolidine.
Background technology
Pyrrolidine is the intermediate of production Buflomedil Hydrochloride (Bulglomedil Hydrochloride), Bepridil hydrochloride (Bepridil Hydrochloride), acrivastine a series of pharmaceutical prods such as (Acrivastine).The synthetic method of bibliographical information mainly contains: pyrroles or pyrrolin are catalytic material hydride process (Journal of theAmerican Chemical Society, 131 (16), 5816-5822; 2009).Succimide or pyrrolidone are that catalytic material becomes around-France [Chemistry ﹠amp; Industry (London, United Kingdom), (17), 547-8; 1990]; 1, the ammonification of 4-butyleneglycol High Temperature High Pressure becomes around-France [J.org.chem, 1994,59 (14), 3998] and tetrahydrofuran (THF) catalytic ammoniation method.Former three is all interrupter method, has all required high-temperature high-pressure apparatus.The cost of investment height is difficult to expand the scale of production.The back is a kind of for the operation of fixed bed continuous processing, though help in principle reducing cost, expands the scale of production.But the often yield that sees bibliographical information is on the low side, to catalyzer require special, be difficult to the preparation.
Summary of the invention
It is higher to the purpose of this invention is to provide yield, and cost is lower, has the method for preparing Pyrrolidine of industrialization meaning.
Pyrrolidine preparation method of the present invention may further comprise the steps:
The first step: cupric nitrate is dissolved in the water, adds the ZSM-5 molecular sieve, soak after 6～10 hours,, get the Cu-ZSM-5 catalyzer 400～450 ℃ of activation 4～10 hours.The weight ratio of cupric nitrate and ZSM-5 molecular sieve is 1～5: 10.
Second step: the Cu-ZSM-5 catalyzer is put into fixed-bed reactor, feed tetrahydrofuran (THF) and ammonia continuously to fixed-bed reactor, the mol ratio of ammonia and tetrahydrofuran (THF) is 4-10: 1, the speed that tetrahydrofuran (THF) enters fixed bed is 10ml/hr, in 300～350 ℃ of continuous catalytic reactions, obtain the Pyrrolidine crude product;
The 3rd step: the Pyrrolidine crude product is used the ZSM-5 molecular sieve dehydration through rectifying, and the weight ratio of ZSM-5 molecular sieve and Pyrrolidine is 0.5～1: 1.
The present invention can carry out activating and regenerating to the Cu-ZSM-5 catalyzer that uses, process rises to 350～400 ℃ for the fixed bed temperature, bubbling air 4～5 hours, the speed 100ml of air～200ml/min, stop blowing air, change logical nitrogen 2～3 hours then, the speed 100ml of nitrogen～200ml/min stops logical nitrogen, feed ammonia 400ml～500ml/min then, at least 0.5 hour, cool to 300～350 ℃ then, obtain the Cu-ZSM-5 catalyzer of activating and regenerating.
Beneficial effect of the present invention is:
Technological operation of the present invention is simple, and cost is low; The simple easily system of catalyzer, and activation utilization repeatedly; Pyrrolidine yield height, quality is good, and water content is low.
Embodiment
Embodiment 1
The cupric nitrate of the first step: 0.95g is dissolved in the water of 100ml, adds the ZSM-5 of 4g, soaks after 6 hours, boils off water, 420 ℃ of activation 4 hours, gets the Cu-ZSM-5 catalyzer.
Second step: the Cu-ZSM-5 catalyzer is put into fixed-bed reactor, temperature rises to 330 ℃, feed ammonia with 420ml/min earlier, open sampling pump then, feed tetrahydrofuran (THF), tetrahydrofuran (THF) enters fixed bed with 10ml/hr speed, and ammonia and tetrahydrofuran (THF) raw materials components mole ratio were controlled at 10: 1, obtained the Pyrrolidine crude product;
The 3rd step: the Pyrrolidine crude product is carried out rectifying, receive 86-87 ℃ fraction, its moisture content is 1～3%.With the dehydration of ZSM-5 molecular sieve drying, the weight ratio of ZSM-5 molecular sieve and Pyrrolidine is 0.8: 1 then.Moisture drops to below 0.3%.The Pyrrolidine molar yield is 78.5%.
When Pyrrolidine content obviously descends, can carry out activating and regenerating to the Cu-ZSM-5 catalyzer: the fixed bed temperature rises to 380 ℃, bubbling air 5 hours, the speed 200ml/min of air, stop blowing air, change logical nitrogen 3 hours then, the speed 200ml/min of nitrogen stops logical nitrogen, feed ammonia 450ml/min then, 0.5 hour, cool to 300 ℃ then, repeat above-mentioned second step preparation Pyrrolidine crude product.Quite, can repeatedly activate before catalyst activated effect and the activation, repeatedly after the activation, when Pyrrolidine content obviously descends, the catalyzer that must more renew.
Embodiment 2
The cupric nitrate of the first step: 0.4g is dissolved in the water of 100ml, adds the ZSM-5 of 4g, soaks after 6 hours, boils off water, 420 ℃ of activation 4 hours, gets the Cu-ZSM-5 catalyzer.
Second step: the Cu-ZSM-5 catalyzer is put into fixed-bed reactor, temperature rises to 300 ℃, feed ammonia with 400ml/min earlier, open sampling pump then, feed tetrahydrofuran (THF), tetrahydrofuran (THF) enters fixed bed with 10ml/hr speed, and ammonia and tetrahydrofuran (THF) raw materials components mole ratio were controlled at 10: 1, obtained the Pyrrolidine crude product;
The 3rd step: the Pyrrolidine crude product is carried out rectifying, receive 86-87 ℃ fraction, its moisture content is 1～3%.With the dehydration of ZSM-5 molecular sieve drying, the weight ratio of ZSM-5 molecular sieve and Pyrrolidine is 0.5: 1 then.Moisture drops to below 0.4%.The Pyrrolidine molar yield is 76.7%.
Embodiment 3
The cupric nitrate of the first step: 2g is dissolved in the water of 100ml, adds the ZSM-5 of 4g, soaks after 6 hours, boils off water, 420 ℃ of activation 4 hours, gets the Cu-ZSM-5 catalyzer.
Second step: the Cu-ZSM-5 catalyzer is put into fixed-bed reactor, temperature rises to 350 ℃, feed ammonia with 450ml/min earlier, open sampling pump then, feed tetrahydrofuran (THF), tetrahydrofuran (THF) enters fixed bed with 10ml/hr speed, and ammonia and tetrahydrofuran (THF) raw materials components mole ratio were controlled at 10: 1, obtained the Pyrrolidine crude product;
The 3rd step: the Pyrrolidine crude product is carried out rectifying, receive 86-87 ℃ fraction, its moisture content is 1～3%.With the dehydration of ZSM-5 molecular sieve drying, the weight ratio of ZSM-5 molecular sieve and Pyrrolidine is 1: 1 then.Moisture drops to below 0.25%.The Pyrrolidine molar yield is 78.9%.
Claims (1)
1. the preparation method of Pyrrolidine may further comprise the steps:
The first step: cupric nitrate is dissolved in the water, adds the ZSM-5 molecular sieve, soak after 6～10 hours,, get the Cu-ZSM-5 catalyzer 400～450 ℃ of activation 4～10 hours.The weight ratio of cupric nitrate and ZSM-5 molecular sieve is 1～5: 10.
Second step: the Cu-ZSM-5 catalyzer is put into fixed-bed reactor, feed tetrahydrofuran (THF) and ammonia continuously to fixed-bed reactor, the mol ratio of ammonia and tetrahydrofuran (THF) is 4-10: 1, the speed that tetrahydrofuran (THF) enters fixed bed is 10ml/hr, in 300～350 ℃ of continuous catalytic reactions, obtain the Pyrrolidine crude product;
The 3rd step: Pyrrolidine crude product ZSM-5 molecular sieve dehydration, the weight ratio of ZSM-5 molecular sieve and Pyrrolidine are 0.5～1: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010504622 CN101948448A (en) | 2010-10-12 | 2010-10-12 | Preparation method of pyrrolidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010504622 CN101948448A (en) | 2010-10-12 | 2010-10-12 | Preparation method of pyrrolidine |
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|---|---|
| CN101948448A true CN101948448A (en) | 2011-01-19 |
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| CN 201010504622 Pending CN101948448A (en) | 2010-10-12 | 2010-10-12 | Preparation method of pyrrolidine |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105820182A (en) * | 2016-05-10 | 2016-08-03 | 常州大学 | Thermal stable copper metal organic framework material and preparation method and application thereof |
| CN106693972A (en) * | 2016-12-16 | 2017-05-24 | 常州大学 | Preparation method of catalyst for synthesizing pyrrolidine from tetrahydrofuran by catalytic amination |
| CN107793340A (en) * | 2017-11-15 | 2018-03-13 | 昌邑市瑞海生物科技有限公司 | A kind of method for using 1,4 butanediols and ammonia to prepare nafoxidine for raw material |
| CN107876086A (en) * | 2017-11-15 | 2018-04-06 | 昌邑市瑞海生物科技有限公司 | A kind of nafoxidine catalyst for preparing |
| CN107973735A (en) * | 2017-11-13 | 2018-05-01 | 江苏康恒化工有限公司 | A kind of preparation method of N- ethyl-2-aminomethylpentazaneands |
| WO2019101568A1 (en) | 2017-11-23 | 2019-05-31 | Basf Se | Method for producing bispyrrolidine compounds |
| CN112521346A (en) * | 2020-12-22 | 2021-03-19 | 中国石化长城能源化工（宁夏）有限公司 | Method for synthesizing pyrrolidine by continuously catalyzing amine with tetrahydrofuran |
| CN115108962A (en) * | 2022-08-01 | 2022-09-27 | 上海巽田科技股份有限公司 | Method for continuously synthesizing azabicyclo compound |
| CN115232059A (en) * | 2022-08-01 | 2022-10-25 | 上海巽田科技股份有限公司 | Synthetic method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
-
2010
- 2010-10-12 CN CN 201010504622 patent/CN101948448A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| 《JOURNAL OF CATALYSIS》 19761231 YOSHIO ONO et al. Type L Zeolites as Selective Catalysts for the Ring Transformation of Cyclic Ethers into Cyclic Imines 322-328 1 第41卷, 2 * |
| 《中国优秀博硕士学位论文全文数据库 (硕士) 工程科技Ⅰ辑》 20040915 于煦 四氢呋喃和氨气气相催化合成四氢吡咯的研究 B014-45 1 , 第3期 2 * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105820182A (en) * | 2016-05-10 | 2016-08-03 | 常州大学 | Thermal stable copper metal organic framework material and preparation method and application thereof |
| CN106693972A (en) * | 2016-12-16 | 2017-05-24 | 常州大学 | Preparation method of catalyst for synthesizing pyrrolidine from tetrahydrofuran by catalytic amination |
| CN107973735A (en) * | 2017-11-13 | 2018-05-01 | 江苏康恒化工有限公司 | A kind of preparation method of N- ethyl-2-aminomethylpentazaneands |
| CN107793340A (en) * | 2017-11-15 | 2018-03-13 | 昌邑市瑞海生物科技有限公司 | A kind of method for using 1,4 butanediols and ammonia to prepare nafoxidine for raw material |
| CN107876086A (en) * | 2017-11-15 | 2018-04-06 | 昌邑市瑞海生物科技有限公司 | A kind of nafoxidine catalyst for preparing |
| WO2019101568A1 (en) | 2017-11-23 | 2019-05-31 | Basf Se | Method for producing bispyrrolidine compounds |
| US11345680B2 (en) | 2017-11-23 | 2022-05-31 | Basf Se | Method for producing bispyrrolidine compounds |
| CN112521346A (en) * | 2020-12-22 | 2021-03-19 | 中国石化长城能源化工（宁夏）有限公司 | Method for synthesizing pyrrolidine by continuously catalyzing amine with tetrahydrofuran |
| CN115108962A (en) * | 2022-08-01 | 2022-09-27 | 上海巽田科技股份有限公司 | Method for continuously synthesizing azabicyclo compound |
| CN115232059A (en) * | 2022-08-01 | 2022-10-25 | 上海巽田科技股份有限公司 | Synthetic method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
| CN115232059B (en) * | 2022-08-01 | 2023-11-21 | 上海巽田科技股份有限公司 | Synthesis method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
| CN115108962B (en) * | 2022-08-01 | 2024-03-19 | 上海巽田科技股份有限公司 | Method for continuously synthesizing azabicyclo compound |
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Open date: 20110119 |