CN103435528A - Simple synthesis process of important pharmaceutical chemical intermediate 5-nitroindole - Google Patents
Simple synthesis process of important pharmaceutical chemical intermediate 5-nitroindole Download PDFInfo
- Publication number
- CN103435528A CN103435528A CN2013102989875A CN201310298987A CN103435528A CN 103435528 A CN103435528 A CN 103435528A CN 2013102989875 A CN2013102989875 A CN 2013102989875A CN 201310298987 A CN201310298987 A CN 201310298987A CN 103435528 A CN103435528 A CN 103435528A
- Authority
- CN
- China
- Prior art keywords
- reaction
- acid
- hydrolysis
- nitroindole
- optimum
- 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.)
- Pending
Links
Landscapes
- Indole Compounds (AREA)
Abstract
The invention provides a simple synthesis process of an important pharmaceutical chemical intermediate 5-nitroindole. The synthesis process particularly comprises the steps: 2-sodium sulfonate-1-acetyl indole is used as raw material, an organic acid as a reaction solvent is added, a nitration reaction is carried out in the presence of a nitration reagent, then inorganic alkaline hydrolysis is carried out, the obtained product is namely 5-nitroindole, wherein the yield coefficient is up to 90%, and the purity is up to 98% or more.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to a kind of synthetic method of 5-nitroindoline.
Background technology
5-nitroindoline (5-Nitroindole), No. CAS: 6146-52-7, molecular formula C
8h
6n
2o
2, molecular weight: 162.15.The golden yellow crystallization of proterties, be dissolved in ethanol, ether, propylene glycol, sherwood oil and most of nonvolatile oil, be insoluble to glycerine and mineral oil fusing point (℃): 140-143.Be usually used in the synthetic pharmaceutical activity that has, 2-oxa--1-Pyrrolizidine analogue; The propylhomoserin dioxygenase inhibitor, pyridyl-vinyl-indoles is as potential antitumor immune modulating agent; The glutamate receptor 4 allosteric setters of definite metabotropic; Antifungal agents; Hemp chemical composition receptor type 1 (CB1) antagonistic drug; Potential carcinostatic agent; Potential anti-angiogenicization auxiliary agent; Selectivity leukemia auxiliary agent; A series of medicines such as inferior 1 type (HIV-1) auxiliary agent of anti-human immunodeficiency virus.Synthetic method bibliographical information about the 5-nitroindoline is less, majority be take the phenylhydrazine compounds as raw material, a kind of is that preparation is gone in paranitrophenylhydrazine and acetaldehyde reaction, another kind is to make by open loop after 4-bromophenyl-hydrazine hydrochloride and pimelinketone reaction, because the phenylhydrazine compounds is larger to the harm of environment, and toxicity is larger, be not suitable for the production of industry amplificationization.How improving the feasibility of industrialized production, reduce environmental pollution, reduce the harm to the production operation personnel, reduce production costs, is current main research direction.
Summary of the invention
The object of the present invention is to provide a kind of 2-of take sodium sulfonate-1-ethanoyl indoles is starting raw material; the environmental pollution that overcomes prior art is large; strong toxicity; the loaded down with trivial details shortcomings that waits of technique; provide a kind of simple to operation; environmentally friendly, the simple method for synthesizing of the 5-nitroindoline of the applicable suitability for industrialized production that toxicity is little.
The present invention adopts following technical scheme:
2-sodium sulfonate-1-ethanoyl the indoles of take is raw material, and adding organic acid is reaction solvent, carries out nitration reaction under the existence of nitrating agent, then, through the mineral alkali hydrolysis, products therefrom is the 5-nitroindoline.
Described raw material and nitrosonitric acid mol ratio are 1: 1～3.
Described organic acid is acetic acid, and nitrating agent is the nitrating agents such as nitric acid, nitrosonitric acid.The described nitration reaction time is 0.5～1.5h, and the nitration reaction temperature is 12～15 ℃.
The time of described hydrolysis reaction is 18～25h, and hydrolysis temperature is 60～75 ℃.
Advantage of the present invention is:
1, abandon using to environment and the larger phenylhydrazine compounds of operator's harm.
2, technological process is easy, easy handling.
3, whole reaction raw materials is easy to get, and yield is good, and total recovery can reach more than 90%, and purity is more than 98%.
Embodiment
Embodiment 1:
Add 27.2g2-sodium sulfonate-1-ethanoyl indoles (0.1mo1) in the 500ml round-bottomed flask, add 100ml acetic acid, be cooled to 12 ℃; drip the 19ml nitrosonitric acid in 1h, after completion of the reaction, carefully pour in the broken water of 250ml; add 160gNaOH, slowly be warming up to 70 ° of C, keep 20h; suction filtration; with the washing of 2*100ml frozen water, dry, obtain golden yellow crystallization 14.6g; productive rate 90.1%, purity 98.5%.
Embodiment 2:
Add 54.4g2-sodium sulfonate-1-ethanoyl indoles (0.2mo1) in the 1000ml round-bottomed flask, add 200ml acetic acid, be cooled to 13 ℃; drip the 38ml nitrosonitric acid in 1h, after completion of the reaction, carefully pour in the broken water of 500ml; add 320gNaOH, slowly be warming up to 70 ° of C, keep 20h; suction filtration; with the washing of 2*200ml frozen water, dry, obtain golden yellow crystallization 29.3g; productive rate 90.4%, purity 98.7%.
Embodiment 3:
Add 27.2g2-sodium sulfonate-1-ethanoyl indoles (0.1mo1) in the 500ml round-bottomed flask, add 100ml acetic acid, be cooled to 13 ℃; drip the 19ml nitrosonitric acid in 1h, after completion of the reaction, carefully pour in the broken water of 250ml; add 160gNaOH, slowly be warming up to 70 ° of C, keep 20h; suction filtration; with the washing of 2*100ml frozen water, dry, obtain golden yellow crystallization 14.4g; productive rate 88.9%, purity 98.1%.
Embodiment 4:
Add 54.4g2-sodium sulfonate-1-ethanoyl indoles (0.2mo1) in the 1000ml round-bottomed flask, add 200ml acetic acid, be cooled to 12 ℃; drip the 38ml nitrosonitric acid in 1h, after completion of the reaction, carefully pour in the broken water of 500ml; add 320gNaOH, slowly be warming up to 70 ° of C, keep 20h; suction filtration; with the washing of 2*200ml frozen water, dry, obtain golden yellow crystallization 29.7g; productive rate 91.7%, purity 99%.
Embodiment 5:
Add 27.2g2-sodium sulfonate-1-ethanoyl indoles (0.1mo1) in the 500ml round-bottomed flask, add 100ml acetic acid, be cooled to 12 ℃; drip the 19ml nitrosonitric acid in 1h, after completion of the reaction, carefully pour in the broken water of 250ml; add 160gNaOH, slowly be warming up to 70 ℃, keep 20h; suction filtration; with the washing of 2*100ml frozen water, dry, obtain golden yellow crystallization 15.2g; productive rate 93.8%, purity 98.7%.
Claims (6)
1. the 2-sodium sulfonate-1-ethanoyl indoles of take is raw material, and adding organic acid is reaction solvent, carries out nitration reaction under the existence of nitrating agent, then through the mineral alkali hydrolysis, purified processing, products therefrom is qualified 5-nitroindoline.
2. raw material as claimed in claim 1 and nitrosonitric acid mol ratio are 1: 1～3, and the optimum mol ratio is 1: 2.5.
3. organic acid as claimed in claim 1 is acetic acid, and nitrating agent is nitric acid, nitrosonitric acid, and optimum nitrating agent is nitrosonitric acid.
4. the nitration reaction time as claimed in claim 1 is 0.5～1.5h, and the nitration reaction temperature is 12～15 ℃, and the optimum reaction times is 1h, and temperature of reaction is 13 ℃.
5. the mineral alkali for hydrolysis as claimed in claim 1 is the mineral alkalis such as sodium hydroxide, potassium hydroxide.
6. the time of hydrolysis reaction as claimed in claim 1 is 18～25h, and hydrolysis temperature is 60～75 ℃, and optimum is 20h, 70 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102989875A CN103435528A (en) | 2013-07-17 | 2013-07-17 | Simple synthesis process of important pharmaceutical chemical intermediate 5-nitroindole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102989875A CN103435528A (en) | 2013-07-17 | 2013-07-17 | Simple synthesis process of important pharmaceutical chemical intermediate 5-nitroindole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103435528A true CN103435528A (en) | 2013-12-11 |
Family
ID=49689275
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2013102989875A Pending CN103435528A (en) | 2013-07-17 | 2013-07-17 | Simple synthesis process of important pharmaceutical chemical intermediate 5-nitroindole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103435528A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09316052A (en) * | 1996-05-24 | 1997-12-09 | Nippon Steel Chem Co Ltd | Production of 5-nitroindole compound |
| CN102558017A (en) * | 2011-12-27 | 2012-07-11 | 郑州凯美克化学有限公司 | Method for preparing 5-bromoindole |
-
2013
- 2013-07-17 CN CN2013102989875A patent/CN103435528A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09316052A (en) * | 1996-05-24 | 1997-12-09 | Nippon Steel Chem Co Ltd | Production of 5-nitroindole compound |
| CN102558017A (en) * | 2011-12-27 | 2012-07-11 | 郑州凯美克化学有限公司 | Method for preparing 5-bromoindole |
Non-Patent Citations (3)
| Title |
|---|
| HENRY F. RUSSELL ET AL: "5-substituted indoles via sodium indole-2-sulfonate. A reexamination", 《ORGNIC PREPARETIONS AND PROCEDURES》 * |
| 林峰 等: "《精细有机合成技术》", 31 August 2009, 科学出版社 * |
| 申川生: "某些吲哚衍生物的合成与应用研究", 《吉林大学硕士学位论文》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10730838B2 (en) | Green preparation method for quinoline compounds | |
| JP2014522413A5 (en) | ||
| CN104327008A (en) | Synthesis method of benzoxazole compound | |
| CN102731373A (en) | Preparation method of intermediate of antitumor drug GDC-0449 (vismodegib) | |
| CN104447686A (en) | Polysubstituted 2-pyrrolopyridine derivative and preparation method thereof | |
| CN102775344B (en) | Method for preparing 2,3,6-trichloro-trichloromethylpyridine from DCTC (dichlorobenzotrichloride) flash bottoms | |
| CN107417478B (en) | Method for synthesizing asymmetric disubstituted urea by catalytic oxidation carbonylation | |
| CN103694153B (en) | The method of styracin and arylsulfinate Reactive Synthesis alkenyl sulfone compound | |
| Wang et al. | Synthesis of a novel diol-functionalized poly (ethylene glycol)-bridged dicationic ionic liquid and its application in copper-catalyzed amination of aryl halides | |
| CN102351621B (en) | Method for preparing N-sulfonyl amidine | |
| CN103435528A (en) | Simple synthesis process of important pharmaceutical chemical intermediate 5-nitroindole | |
| CN104592104A (en) | Method for preparing 2-chloronicotinic acid | |
| CN103351376B (en) | Synthetic method of 2-thiophene ethylamine | |
| CN109956871B (en) | Preparation method of 3,4, 5-trifluoro-2' -nitrobiphenyl | |
| CN105294415A (en) | Preparation method of 3-halogenated fluorenone compound | |
| CN104557661A (en) | Preparation method for synthesizing indoline through idodine catalysis of amide compound | |
| CN113816925A (en) | A trematopsin 3 "-tert-butyl-4 '- (2-hydroxyethoxy) -4" -pyrrolidin-1-yl [1, 1'; process for preparing 3 ', 1' ] -terphenyl-4-carboxylic acid | |
| CN105254611A (en) | Preparation method for benzothiophene-2-carboxylic acid | |
| PE20131097A1 (en) | NEW PROCEDURE FOR THE SYNTHESIS OF IVABRADINE AND ITS SALTS BY ADDITION TO A PHARMACEUTICALLY ACCEPTABLE ACID | |
| HRP20170394T1 (en) | Method for synthesising 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile and use for synthesising ivabradine and the added salts thereof with a pharmaceutically acceptable acid | |
| CN102295614B (en) | Synthetic method of 2-methyl-4-dimethylamino-6-methoxy-1,3,5-triazine | |
| Wang et al. | 2, 2′-Diamino-6, 6′-dimethylbiphenyl as an efficient ligand in the CuI-catalyzed Sonogashira reaction of aryl iodides and bromides with terminal alkynes | |
| CN103450070B (en) | Synthesis process of xylylenimine | |
| MA35806B1 (en) | Novel process for the synthesis of 3- (2-bromo-4,5-dimethoxyphenyl) propanenitrile, and application to the synthesis of ivabradine and its addition salts with a pharmaceutically acceptable acid | |
| CN103288780A (en) | Preparation method of 1-phenyl-1-cyclopentyl epoxy ethane |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C05 | Deemed withdrawal (patent law before 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20131211 |