CN103864663A - Simple synthesis method of important pharmaceutical and chemical intermediate 5-cyano indole - Google Patents
Simple synthesis method of important pharmaceutical and chemical intermediate 5-cyano indole Download PDFInfo
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- CN103864663A CN103864663A CN201410071148.4A CN201410071148A CN103864663A CN 103864663 A CN103864663 A CN 103864663A CN 201410071148 A CN201410071148 A CN 201410071148A CN 103864663 A CN103864663 A CN 103864663A
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- Prior art keywords
- synthesis method
- reagent
- cyano indole
- indole
- cyanoindole
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
Abstract
The invention belongs to the technical field of organic synthesis, and in particular relates to a synthesis method of 5-cyano indole. The synthesis method comprises the key steps of adding N-methylpyrrolidine as a reaction solvent by using 5-bromoindole as a raw material, performing a reflux reaction in the existence of a cyaniding reagent, then quenching cyanide by using an inorganic alkali, and extracting and concentrating to obtain a product, namely 5-cyano indole; 5-cyano indole prepared by the synthesis method disclosed by the invention has a yield of 98% and a purity of more than 98%.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to a kind of synthetic method of 5-cyanoindole.
Background technology
5-cyanoindole (5-Nitroindole), No. CAS: 15861-24-2, molecular formula C
9h
6n
2, molecular weight: 142.15.Proterties: off-white color crystallization, be dissolved in the organic solvents such as ethanol, methyl alcohol, methylene dichloride, trichloromethane, ethyl acetate, water-soluble hardly, fusing point (℃): 106 ~ 108.Be usually used in the synthetic Wella oxazolone with antidepressant effect, the mechanism of Wella oxazolone antidepressant effect is understood not yet completely, think at present its by selectivity suppress serotonin (5-HT) re-uptake increase serotonin can activity relevant, Wella oxazolone is also the partial agonist of 5-HT1A acceptor, but the result that 5-HT is transmitted is still unknown at present in the antidepressant effect of Wella oxazolone with it.。Synthetic method bibliographical information about 5-cyanoindole is less, most take phenylhydrazine compounds as raw material, one is that cyano group phenylhydrazine and acetaldehyde reaction are gone to preparation, because phenylhydrazine compounds is larger to the harm of environment, and toxicity is larger, and this reaction yield is lower, is not suitable for industry amplificationization and produces.How solving the feasibility of industrialized production, reduce environmental pollution, reduce the harm to 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 take 5-bromo indole as 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, the simple method for synthesizing of the 5-cyanoindole of environment amenable applicable suitability for industrialized production.
The present invention adopts following technical scheme:
Take 5-bromo indole as raw material, adding DMF is reaction soln, carries out back flow reaction under the existence of cyanating reagent, then through mineral alkali quencher prussiate, extraction, concentrated products therefrom is 5-cyanoindole.
Described DMF can replace with N-crassitude, and this reagent using is through the reagent after treatment that dewaters, and cyanating reagent is cuprous cyanide, and 5-bromo indole and cuprous cyanide mol ratio are 1:1 ~ 1.1.
The time of described cyanogenation is 18 ~ 25h, and temperature is 80 ~ 85 ℃, uses apparatus,Soxhlet's to carry out back flow reaction.
Described use mineral alkali is ammoniacal liquor, and what extraction was used is the one in ether or normal hexane.
Advantage of the present invention is:
1, abandoning using to environment and the larger phenylhydrazine compounds of operator's harm is raw material.
2, technological process is easy, easy handling.
3, reactions steps is simple, and yield is high, and total recovery can reach more than 95%, and purity is more than 98%.
Embodiment
Embodiment 1:
In the round-bottomed flask of apparatus,Soxhlet's, add 19.6g5-bromo indole (0.1mol), add 200ml N-crassitude, add 9.5g cuprous cyanide, 85 ℃ of back flow reaction are spent the night, and after reaction finishes, are cooled to room temperature, add 20ml ammoniacal liquor, stir, use twice of 30ml n-hexane extraction, merge normal hexane, concentrating part solvent, puts refrigerator crystallization 2h, suction filtration, obtain 5-cyanoindole 14g, productive rate 98.6%.
Embodiment 2:
In the round-bottomed flask of apparatus,Soxhlet's, add 39.8g5-bromo indole (0.2mol), add 400ml N-crassitude, add 18.8g cuprous cyanide, 85 ℃ of back flow reaction are spent the night, and after reaction finishes, are cooled to room temperature, add 40ml ammoniacal liquor, stir, use twice of 50ml extracted with diethyl ether, merge normal hexane, concentrating part solvent, puts refrigerator crystallization 2h, suction filtration, obtain 5-cyanoindole 27.9g, productive rate 98.2%.
Embodiment 3:
In the round-bottomed flask of apparatus,Soxhlet's, add 9.8g5-bromo indole (0.05mol), add 100ml N-crassitude, add 4.7g cuprous cyanide, 85 ℃ of back flow reaction are spent the night, and after reaction finishes, are cooled to room temperature, add 10ml ammoniacal liquor, stir, use twice of 20ml n-hexane extraction, merge normal hexane, concentrating part solvent, puts refrigerator crystallization 2h, suction filtration, obtain 5-cyanoindole 7g, productive rate 98.5%.
Claims (4)
1. take 5-bromo indole as raw material, adding DMF is reaction soln, carries out back flow reaction under the existence of cyanating reagent, then through mineral alkali quencher prussiate, extraction, concentrated products therefrom is 5-cyanoindole.
2. DMF as claimed in claim 1 can replace with N-crassitude, and this reagent using is through the reagent after treatment that dewaters, and cyanating reagent is cuprous cyanide, and 5-bromo indole and cuprous cyanide mol ratio are 1:1 ~ 1.1.
3. the time of cyanogenation as claimed in claim 1 is 18 ~ 25h, and temperature is 80 ~ 85 ℃, uses apparatus,Soxhlet's to carry out back flow reaction.
4. use mineral alkali as claimed in claim 1 is ammoniacal liquor, and what extraction was used is the one in ether or normal hexane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410071148.4A CN103864663A (en) | 2014-03-01 | 2014-03-01 | Simple synthesis method of important pharmaceutical and chemical intermediate 5-cyano indole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410071148.4A CN103864663A (en) | 2014-03-01 | 2014-03-01 | Simple synthesis method of important pharmaceutical and chemical intermediate 5-cyano indole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103864663A true CN103864663A (en) | 2014-06-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410071148.4A Pending CN103864663A (en) | 2014-03-01 | 2014-03-01 | Simple synthesis method of important pharmaceutical and chemical intermediate 5-cyano indole |
Country Status (1)
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1684944A (en) * | 2002-08-02 | 2005-10-19 | 麻省理工学院 | Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds |
| CN1789262A (en) * | 2004-12-16 | 2006-06-21 | 上海美通生物科技有限公司 | Improvement of preparation of Naratriptan |
| WO2007098418A1 (en) * | 2006-02-17 | 2007-08-30 | Memory Pharmaceuticals Corporation | Compounds having 5-ht6 receptor affinity |
| CN102875276A (en) * | 2012-10-24 | 2013-01-16 | 大连理工大学 | Method for preparing cyan aromatic hydrocarbon by using aryl bromide |
-
2014
- 2014-03-01 CN CN201410071148.4A patent/CN103864663A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1684944A (en) * | 2002-08-02 | 2005-10-19 | 麻省理工学院 | Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds |
| CN1789262A (en) * | 2004-12-16 | 2006-06-21 | 上海美通生物科技有限公司 | Improvement of preparation of Naratriptan |
| WO2007098418A1 (en) * | 2006-02-17 | 2007-08-30 | Memory Pharmaceuticals Corporation | Compounds having 5-ht6 receptor affinity |
| CN102875276A (en) * | 2012-10-24 | 2013-01-16 | 大连理工大学 | Method for preparing cyan aromatic hydrocarbon by using aryl bromide |
Non-Patent Citations (4)
| Title |
|---|
| ATUL AGARWAL,等: "A new synthesis of the potent 5-HT1 receptor ligand,5-carboxyamidotryptamine (5-CT)", 《SYNTHETIC COMMUNICATIONS》, vol. 23, no. 8, 31 December 1993 (1993-12-31), XP000881512, DOI: 10.1080/00397919308018587 * |
| JACOPO ZANON,等: "Copper-Catalyzed Domino Halide Exchange-Cyanation of Aryl Bromides", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》, vol. 125, no. 10, 15 February 2003 (2003-02-15), pages 2891 - 2 * |
| TIAN CAI WANG,等: "Design, synthesis and anti-proliferative studies of a novel series of indirubin derivatives", 《CHINESE CHEMICAL LETTERS》, vol. 21, no. 12, 31 December 2010 (2010-12-31), pages 1408 - 1 * |
| 陈重,等: "3-取代-5-氟-1,2-二氢-3H-2-酮类化合物的合成及抗肿瘤活性", 《中国医药工业杂志》, vol. 40, no. 10, 31 October 2009 (2009-10-31) * |
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Application publication date: 20140618 |