CN1562968A - Method for synthesizing N-substitution pyrrole in ion liquid - Google Patents
Method for synthesizing N-substitution pyrrole in ion liquid Download PDFInfo
- Publication number
- CN1562968A CN1562968A CN 200410026556 CN200410026556A CN1562968A CN 1562968 A CN1562968 A CN 1562968A CN 200410026556 CN200410026556 CN 200410026556 CN 200410026556 A CN200410026556 A CN 200410026556A CN 1562968 A CN1562968 A CN 1562968A
- Authority
- CN
- China
- Prior art keywords
- ionic liquid
- synthesizing
- pyrrole
- reaction
- substituted
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 16
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 10
- 239000007788 liquid Substances 0.000 title 1
- 238000006467 substitution reaction Methods 0.000 title 1
- 239000002608 ionic liquid Substances 0.000 claims abstract description 20
- 150000001422 N-substituted pyrroles Chemical class 0.000 claims abstract description 16
- 239000012039 electrophile Substances 0.000 claims abstract description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 14
- IQQRAVYLUAZUGX-UHFFFAOYSA-N 1-butyl-3-methylimidazolium Chemical compound CCCCN1C=C[N+](C)=C1 IQQRAVYLUAZUGX-UHFFFAOYSA-N 0.000 claims description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- 230000002152 alkylating effect Effects 0.000 claims description 3
- RKSOPLXZQNSWAS-UHFFFAOYSA-N tert-butyl bromide Chemical group CC(C)(C)Br RKSOPLXZQNSWAS-UHFFFAOYSA-N 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 12
- 230000010933 acylation Effects 0.000 abstract description 4
- 238000005917 acylation reaction Methods 0.000 abstract description 4
- 230000006103 sulfonylation Effects 0.000 abstract description 4
- 238000005694 sulfonylation reaction Methods 0.000 abstract description 4
- 230000036632 reaction speed Effects 0.000 abstract description 3
- 230000029936 alkylation Effects 0.000 abstract description 2
- 238000005804 alkylation reaction Methods 0.000 abstract description 2
- 239000012141 concentrate Substances 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- IIYSNNBEZBAQCQ-UHFFFAOYSA-N 1-butylpyrrole Chemical compound CCCCN1C=CC=C1 IIYSNNBEZBAQCQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- -1 pyrrole cation Chemical class 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
Abstract
本发明公开了一种在离子液体中合成N－取代吡咯的方法。该方法包括如下步骤：(1)、将1～3mmol吡咯、2～6mmol亲电试剂与2～4mmol碱加入1～4mL离子液体中，在40℃～80℃下反应1～2h；(2)、将步骤(1)得到的产物萃取，浓缩后减压蒸馏或重结晶，即得到N－取代吡咯。本发明具有反应温和、反应速度快、产率高等特点，特别是反应适用范围广；不仅有效发生烷基化、酰基化，还可以磺酰化及micheal反应，选择高；并可以高选择性甚至专一性地得到N－取代产物。The invention discloses a method for synthesizing N-substituted pyrrole in ionic liquid. The method comprises the following steps: (1), adding 1 to 3 mmol of pyrrole, 2 to 6 mmol of electrophile and 2 to 4 mmol of base into 1 to 4 mL of ionic liquid, and reacting at 40°C to 80°C for 1 to 2 hours; (2) 1. Extract the product obtained in step (1), concentrate it, and then distill it under reduced pressure or recrystallize to obtain N-substituted pyrrole. The present invention has the characteristics of mild reaction, fast reaction speed, high yield, etc., especially the wide application range of reaction; not only effective alkylation and acylation, but also sulfonylation and micheal reaction, high selection; and high selectivity or even Specificity to N-substituted products.
Description
技术领域technical field
本发明涉及一种合成N-取代吡咯的方法。The invention relates to a method for synthesizing N-substituted pyrrole.
背景技术Background technique
以从价廉试剂为原料，发展温和、高效、高选择性的合成方法是有机合成的重要挑战之一。吡咯及其衍生物的合成和有关反应已有一百多年的历史，是因为它具有广泛的生物活性，是生物碱的主要组成部分，广泛存在于天然产物中。N-取代吡咯主要是通过吡咯正离子与不同的烷基化试剂、酰基化试剂、磺酰基化试剂发生亲核取代反应来获得。然而，由于发生亲核取代反应的位置可以在氮和碳原子上，通常N-取代吡咯产物混有C-取代吡咯产物。而且这些方法经常需要比较苛刻的条件、较长的反应时间、有时较低的产率、和用到环境不友好的试剂和催化剂。因此发展温和、高效、高选择性和环境友好的合成N-取代吡咯方法是十分必要的。One of the important challenges in organic synthesis is to develop mild, efficient, and highly selective synthetic methods using cheap reagents as raw materials. The synthesis and related reactions of pyrrole and its derivatives have a history of more than 100 years, because it has a wide range of biological activities, is the main component of alkaloids, and widely exists in natural products. N-substituted pyrrole is mainly obtained by nucleophilic substitution reaction between pyrrole cation and different alkylating reagents, acylation reagents and sulfonylation reagents. However, N-substituted pyrrole products are usually mixed with C-substituted pyrrole products because the sites for nucleophilic substitution reactions can be on nitrogen and carbon atoms. Moreover, these methods often require harsher conditions, longer reaction times, sometimes lower yields, and the use of environmentally unfriendly reagents and catalysts. Therefore, it is necessary to develop a mild, efficient, highly selective and environmentally friendly method for the synthesis of N-substituted pyrroles.
发明内容Contents of the invention
本发明的目的在于针对已有技术存在的缺点，提供一种反应温和、反应速度快、产率高、高选择性和环境友好的N-取代吡咯的合成方法。The purpose of the present invention is to provide a mild reaction, fast reaction speed, high yield, high selectivity and environment-friendly synthesis method of N-substituted pyrrole aiming at the shortcomings of the prior art.
为达到上述目的，本发明采取了如下技术方案：To achieve the above object, the present invention has taken the following technical solutions:
一种在离子液体中合成N-取代吡咯的方法，具体如下：A method for synthesizing N-substituted pyrrole in ionic liquid, specifically as follows:
(1)、将1～3mmol吡咯、2～6mmol亲电试剂与2～4mmol碱加入到1～4mL离子液体中，在40～80℃下反应1～2h；(1) Add 1-3mmol of pyrrole, 2-6mmol of electrophile and 2-4mmol of base into 1-4mL of ionic liquid, and react at 40-80°C for 1-2h;
(2)、将步骤(1)得到的产物萃取，浓缩后减压蒸馏或重结晶，即得到N-取代吡咯。(2) The product obtained in step (1) is extracted, concentrated and then distilled under reduced pressure or recrystallized to obtain N-substituted pyrrole.
所述的亲电试剂为烷基化试剂、酰基化试剂或磺酰基化试剂；The electrophilic reagent is an alkylating reagent, an acylation reagent or a sulfonylation reagent;
所述的烷基化试剂可以为叔丁基溴；The alkylating agent can be tert-butyl bromide;
所述的碱为氢氧化钾；Described alkali is potassium hydroxide;
所述的离子液体为[Bmim][PF6]或[Bmim][BF4]，是按文献制备的(G.S.Owensand M.M.Abu-Omer，J.Mol.Cata.A：Chem.，2002，187，211)。The ionic liquid is [Bmim][PF 6 ] or [Bmim][BF 4 ], which is prepared according to the literature (GSOwensand MMAbu-Omer, J.Mol.Cata.A: Chem., 2002, 187, 211) .
同已有技术相比，本发明具有如下有益效果：Compared with the prior art, the present invention has the following beneficial effects:
本发明具有反应温和、反应速度快、产率高等特点，特别是反应适用范围广：不仅有效发生烷基化、酰基化、还可以磺酰化及micheal反应，选择高：可以高选择性甚至专一性地得到N-取代产物。The invention has the characteristics of mild reaction, fast reaction speed, high yield, etc., especially the reaction has a wide range of application: not only effective alkylation, acylation, but also sulfonylation and micheal reaction, high selection: high selectivity and even specialization The N-substituted product was obtained uniformly.
具体实施方式Detailed ways
以下结合具体的实施例来对本发明做进一步的说明。The present invention will be further described below in conjunction with specific examples.
实施例1～14Examples 1-14
亲电试剂、反应条件及产率如表1所示。The electrophiles, reaction conditions and yields are shown in Table 1.
实施例3、10、12同时用离子液体[Bmim][BF4]，其余为[Bmim][PF6]，离子液体的用量为2ml。Examples 3, 10, and 12 used ionic liquid [Bmim][BF 4 ] at the same time, and the rest were [Bmim][PF 6 ], and the amount of ionic liquid used was 2ml.
实施例1和12所用的碱为氢氧化钙，实施例4、5和10所用的碱为氢氧化钠，其余为氢氧化钾。The used alkali of embodiment 1 and 12 is calcium hydroxide, and the used alkali of embodiment 4,5 and 10 is sodium hydroxide, and all the other are potassium hydroxide.
化合物的熔点仪用数字显示熔点仪，温度计没有校正。红外光谱仪是Bruker的VECTOR22。核磁共振仪是Bruker的AVANCED M X 400。试剂为国产分析纯。The melting point apparatus of the compound is displayed digitally, and the thermometer is not calibrated. The infrared spectrometer is Bruker's VECTOR22. The nuclear magnetic resonance instrument is Bruker's AVANCED MX 400. Reagents were domestic analytically pure.
表1 Table 1
实施例 亲电试剂2 反应条件 吡咯∶亲电试剂∶碱(mmol∶mmol∶mmol) 产率Example Electrophile 2 Reaction Conditions Pyrrole: Electrophile: Base (mmol: mmol: mmol) Yield
1 CH3I 2h，40℃ 1∶2∶2 821 CH 3 I 2h, 40°C 1:2:2 82
2 i-C3H7Br 2h，60℃ 2∶4∶4 702 iC 3 H 7 Br 2h, 60°C 2:4:4 70
3 n-C4H9Br 1h，80℃ 2∶4∶4 98(95a)3 nC 4 H 9 Br 1h, 80°C 2:4:4 98(95 a )
4 n-C4H9Cl 2h，80℃ 2∶4∶4 764 nC 4 H 9 Cl 2h, 80°C 2:4:4 76
5 t-C4H9Br 2h，70℃ 2∶4∶4 575 tC 4 H 9 Br 2h, 70°C 2:4:4 57
6 CH2＝CHCH2Br 1h，70℃ 2∶5∶4 1006 CH 2 =CHCH 2 Br 1h, 70°C 2:5:4 100
7 C6H5CH2Br 1h，80℃ 2∶4∶4 1007 C 6 H 5 CH 2 Br 1h, 80°C 2:4:4 100
8 C6H5CH2Cl 1h，80℃ 3∶3∶4 998 C 6 H 5 CH 2 Cl 1h, 80°C 3:3:4 99
9 CH2＝CHCN 1h，80℃ 3∶6∶4 829 CH 2 =CHCN 1h, 80°C 3:6:4 82
10 CH2＝CHCOOCH3 1h，80℃ 1∶2∶4 78(70a)10 CH 2 =CHCOOCH 3 1h, 80°C 1:2:4 78(70 a )
11 CH2＝CHCOOCH3 1h，80℃ 2∶4∶4 8011 CH 2 =CHCOOCH 3 1h, 80°C 2:4:4 80
12 C6H5SO2Cl 1h，80℃ 3∶6∶2 10012 C 6 H 5 SO 2 Cl 1h, 80°C 3:6:2 100
(100a)( 100a )
13 p-CH3C6H5SO2Cl 1h，80℃ 2∶4∶4 10013 p-CH 3 C 6 H 5 SO 2 Cl 1h, 80°C 2:4:4 100
14 C6H5COCl 1h，80℃ 2∶4∶4 10014 C 6 H 5 COCl 1h, 80°C 2:4:4 100
a为在离子液体[Bmim][BF4]中反应得到的产率，其余为在离子液体[Bmim][PF6]中反应得到的产率。 a is the yield obtained from the reaction in ionic liquid [Bmim][BF 4 ], and the rest are the yields obtained from the reaction in ionic liquid [Bmim][PF 6 ].
从表1可以看出本方法比传统的方法具有较多的优点：包括选择性好、产率高、操作简单、环境友好等。而且离子液体可以重复使用，重复三次的实验结果基本一致，表2为实施例1～3中离子液体[Bmim][PF6]的循环使用结果。It can be seen from Table 1 that this method has more advantages than the traditional method: including good selectivity, high yield, simple operation, and environmental friendliness. Moreover, the ionic liquid can be reused, and the experimental results repeated three times are basically the same. Table 2 shows the recycling results of the ionic liquid [Bmim][PF 6 ] in Examples 1-3.
表2 Table 2
循环次数 N-丁基吡咯的产率(％) Number of cycles The yield of N-butylpyrrole (%)
1 1 981 1 1 98
2 2 962 2 96
3 3 973 3 97
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410026556 CN1252053C (en) | 2004-03-22 | 2004-03-22 | Method for synthesizing N-substitution pyrrole in ion liquid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410026556 CN1252053C (en) | 2004-03-22 | 2004-03-22 | Method for synthesizing N-substitution pyrrole in ion liquid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1562968A true CN1562968A (en) | 2005-01-12 |
| CN1252053C CN1252053C (en) | 2006-04-19 |
Family
ID=34480640
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410026556 Expired - Fee Related CN1252053C (en) | 2004-03-22 | 2004-03-22 | Method for synthesizing N-substitution pyrrole in ion liquid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1252053C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101511441B (en) * | 2006-09-12 | 2012-02-22 | 苏舍化学技术有限公司 | Method of purifying ionic liquids |
| CN107840966A (en) * | 2016-09-21 | 2018-03-27 | 天津大学 | Pentaerythritol triacrylate dopamine azole polymer and its application |
| CN113444030A (en) * | 2020-03-27 | 2021-09-28 | 石家庄圣泰化工有限公司 | Synthesis method of 1-pyrrole propionitrile |
-
2004
- 2004-03-22 CN CN 200410026556 patent/CN1252053C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101511441B (en) * | 2006-09-12 | 2012-02-22 | 苏舍化学技术有限公司 | Method of purifying ionic liquids |
| CN107840966A (en) * | 2016-09-21 | 2018-03-27 | 天津大学 | Pentaerythritol triacrylate dopamine azole polymer and its application |
| CN113444030A (en) * | 2020-03-27 | 2021-09-28 | 石家庄圣泰化工有限公司 | Synthesis method of 1-pyrrole propionitrile |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1252053C (en) | 2006-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ElMarrouni et al. | Silyl-mediated photoredox-catalyzed Giese reaction: addition of non-activated alkyl bromides | |
| EP2698393B1 (en) | Resin composition | |
| KR101178130B1 (en) | Sulfenamide, Vulcanization Accelerator Containing the Sulfenamide for Rubber, and Process for Producing the Same | |
| Lee et al. | Alkynylation of N-tosylimines with aryl acetylenes promoted by ZnBr2 and N, N-diisopropylethylamine in acetonitrile | |
| BRPI0409648A (en) | organic ammonium tungstate and molybdate compounds and process for preparing same | |
| Lovrić et al. | Scope and limitations of sodium and potassium trimethylsilanolate as reagents for conversion of esters to carboxylic acids | |
| RU2003136765A (en) | SYNTHESIS OF 4-Phenylbutyric Acid | |
| NO20032731L (en) | Process for the preparation of sulfonamide-substituted imidazotriazinones | |
| CN1562968A (en) | Method for synthesizing N-substitution pyrrole in ion liquid | |
| IE41482B1 (en) | The preparation of esters of aminocarboxylic acids | |
| Tan et al. | Photoinduced Arene C− H Amination with Ammonia: A Practical and Regioselective Strategy for Primary Amines | |
| Ding et al. | An efficient and highly regioselective fluorination of aziridines Using BF3· OEt2 as fluorine source | |
| Howarth et al. | A homochiral tripodal receptor with selectivity for sodium (R)-2-aminopropionate over sodium (S)-2-aminopropionate | |
| Chernykh et al. | Synthesis of tetrafluoroethyl-and tetrafluoroethylene-containing amines by the reaction of silanes with enamines under acidic conditions | |
| Moussa et al. | Mild deprotection of primary N-(p-toluenesulfonyl) amides with SmI2 following trifluoroacetylation | |
| CN1562964A (en) | Synthetic method of imine ramification | |
| WO2023098670A1 (en) | Polyphenol antioxidant and preparation method therefor and application thereof | |
| AU2018241298B2 (en) | Method for the synthesis of 9,10-bis(chloromethyl)anthracene | |
| CN108383747B (en) | Heavy oxygen-labeled amide compound synthesized with thioamide, preparation method and application | |
| DE60305003D1 (en) | PROCESS FOR THE PRODUCTION OF SYNERGISTIC STABILIZER MIXTURES | |
| Moura et al. | Synthesis of cyclic guanidine intermediates of anatoxin-a (s) in both racemic and enantiomerically pure forms | |
| Mokhov et al. | Colloid and nano-sized catalysts in organic synthesis: X. Synthesis of carboxamides by direct amidation of carboxylic acids and transamidation catalyzed by colloid copper | |
| CN102015629A (en) | Processes for synthesizing 1-(2-ethylbutyl) cyclohexane carbonitrile | |
| CN109020865A (en) | 3,3- bis- replaces Oxoindole and preparation method thereof | |
| CN104114530B (en) | The preparation method of hydroxy carboxylic acid amide compound and novel arylboronic acid compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |