CN1699341A - Process for synthesizing bis-indolyl alkyl compounds - Google Patents
Process for synthesizing bis-indolyl alkyl compounds Download PDFInfo
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- CN1699341A CN1699341A CN 200510040054 CN200510040054A CN1699341A CN 1699341 A CN1699341 A CN 1699341A CN 200510040054 CN200510040054 CN 200510040054 CN 200510040054 A CN200510040054 A CN 200510040054A CN 1699341 A CN1699341 A CN 1699341A
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- indolyl alkyl
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Abstract
The invention discloses a process for synthesizing bis-indolyl alkyl compounds characterized in that, using Michler's acid as catalyst, under aqueous phase, carrying out synthesizing reaction between aldehydes and indoles, thus obtaining bis-indolyl alkyl compound, wherein the content of the Michler's acid is 1-5% of aldehyde measured by molar weight, the aldehyde is selected from C1-C10 fat aldehydes or aromatic aldehydes. The synthesis requires no toxic and unwanted organic solvents.
Description
Technical field
The present invention relates to a kind of pentatomic ring that contains, condense with other ring, heteroatoms is the preparation of the heterogeneous ring compound of nitrogen-atoms, is specifically related to a kind of synthetic method of bis-indolyl alkyl compounds.
Background technology
Benzazole compounds is widespread in nature, and the derivative of many indoles all has certain physiologically active.Bis-indolyl alkyl compounds and derivative thereof are present in the continent and the ocean protista has in the bioactive metabolite, these compounds have certain activity, as: therefore multiple physiologically actives such as antitumor, antiviral, antibiotic and anti-inflammatory have caused organic chemist and medicine scholar keen interest.Wherein bis (indolyl) methane has formed the commodity of suitability for industrialized production.
The basic skills of synthetic bis-indolyl alkyl compounds is that aldehydes or ketones and indoles are reacted in the presence of catalyzer, and reaction is carried out in organic solvent usually, reports that at present more catalyzer comprises, covers and takes off K-10, LiClO
4, In (OTf)
3, InCl
3, I
2Deng, use these catalyzer can be with the synthetic bis-indolyl alkyl compounds derivative of productive rate preferably.Yet, in this process, needing to use a large amount of poisonous and hazardous organic solvents, the catalyzer of Shi Yonging is also relatively more expensive simultaneously.This needs people to remove to seek the synthetic environment that meets the Green Chemistry developing direction, for further suitability for industrialized production provides possibility.Over past ten years, the scientific research personnel always for seek efficiently, friendly, economic reaction system effort.
Since A.N.Meldrum in 1908 reported synthesizing of Michaelis acid (Meldrum ' s acid), it had been subjected to increasing attention as a kind of high reactivity reagent, but did not but see the pertinent literature report with this reaction as catalyzer.
Summary of the invention
The purpose of this invention is to provide a kind of method for preparing bis-indolyl alkyl compounds that is easy to realize, reaction does not need with an organic solvent, to reduce environmental pollution, reduces cost.
For achieving the above object, the technical solution used in the present invention is: a kind of synthetic method of bis-indolyl alkyl compounds, with Michaelis acid as catalyzer, under water, make aldehyde and indoles carry out building-up reactions, obtain bis-indolyl alkyl compounds, the amount of described Michaelis acid is counted the 1-5% of aldehyde with molar equivalent, and described aldehyde is selected from C
1To C
10Alkanoic or aromatic aldehyde.
In the technique scheme, adopt water as solvent, entire reaction is carried out under water, usually, for 1 mole aldehyde, the consumption of water is raised between 6 liters, in fact 2, the consumption of water is relevant with the aldehyde of employing in the reaction, when aldehyde was solid, the consumption of water should be more, and the aldehyde of liquid state is when participating in reaction, the consumption of water can suitably reduce, and those skilled in the art can select the addition of suitable water according to the kind of aldehyde.The general formula of above-mentioned reaction is,
In the formula, R can be hydrogen, C
1To C
9Alkyl, aromatic base, substituted aromatic base, heterocyclic aromatic base.
Wherein, when R be hydrogen, C
1To C
9Alkyl the time, described aldehyde is alkanoic, at this moment, the RCHO in the following formula can be expressed as,
In the formula, n=0,1 ..., 9
In the technique scheme, described aldehyde can be aromatic aldehyde, and for example phenyl aldehyde, heteroaromatic aldehyde comprise furfural, thiophenecarboxaldehyde, etc.
In the technique scheme, carry out for making to react completely, the mol ratio of described aldehyde and indoles is 1: 2.
In the technique scheme, described reaction is at room temperature carried out, and stirs in the reaction process, and the reaction times is 6-10 hour.
Perhaps, described being reflected under the ultrasonic wave radiation carried out, and temperature of reaction is between 30-40 ℃, and the reaction times is being 6-10 hour.Under the ultrasonic wave radiation, react, can not stir, and the productive rate of reaction is higher.
In the technique scheme, reaction product is the solid of separating out in reaction, through the thick product of suction filtration acquisition bis-indolyl alkyl compounds, described thick product is further purified, and can obtain the bis-indolyl alkyl compounds of higher degree.
Because the technique scheme utilization, the present invention compared with prior art has following advantage:
1. because the present invention will be usually introduced in the building-up reactions as catalyzer as the Michaelis acid of reagent, make the synthetic of bis-indolyl alkyl compounds under water, to carry out, thereby do not need to use poisonous and hazardous organic solvent to have the advantage of environmental protection;
2. the catalyzer Michaelis acid cost of the present invention's use is low, obtains easily, adds and adopts water as reaction solvent, makes the cost of whole building-up reactions lower.
Embodiment
Below in conjunction with embodiment the present invention is further described:
Embodiment one: bis (indolyl) methane synthetic
Get 1 mole formaldehyde and 2 moles indoles and place reaction flask, the Michaelis acid that adds 0.02 mole, add 5 premium on currency as solvent, make and mix, under the ultrasonic wave radiation, keep 30-40 ℃ temperature of reaction, process was separated out a large amount of solids in about 6 hours, obtained thick product through suction filtration, and further purification promptly obtains the bis (indolyl) methane of higher degree.
Its reaction formula is,
Embodiment two: two indoles nonanes synthetic
Get 0.5 mole aldehyde C-9 and 1 mole indoles and place reaction flask, the Michaelis acid that adds 0.005 mole, add 2 premium on currency as solvent, make and mix, at room temperature stir, finish substantially, separate out a large amount of solids through reaction in about 8 hours, obtain thick product through suction filtration, further purification promptly obtains two indoles nonanes of higher degree.
Its reaction formula is,
Embodiment three: 3,3'-(Phenylmethylene)bis[1H-indole] synthetic
Get 1 mole phenyl aldehyde and 2 moles indoles and place reaction flask, the Michaelis acid that adds 0.04 mole, add 5 premium on currency as solvent, make to mix, under the ultrasonic wave radiation, keep 30-40 ℃ temperature of reaction, through about 10 hours, reaction is finished, separate out a large amount of solids, obtain thick product through suction filtration, further purification promptly obtains the 3,3'-(Phenylmethylene)bis[1H-indole] of higher degree.
Its reaction formula is,
Embodiment four: two indoles furyl methane synthetic
Get 0.1 mole furfural and 0.2 mole indoles and place reaction flask, the Michaelis acid that adds 0.003 mole, add 0.6 premium on currency as solvent, make to mix, under the ultrasonic wave radiation, keep 30-40 ℃ temperature of reaction, through about 8 hours, reaction is finished, separate out a large amount of solids, obtain thick product through suction filtration, further purification promptly obtains two indoles furyl methane of higher degree.
Its reaction formula is,
Claims (5)
1. the synthetic method of a bis-indolyl alkyl compounds is characterized in that: with Michaelis acid as catalyzer, under water, make aldehyde and indoles carry out building-up reactions, obtain bis-indolyl alkyl compounds, the amount of described Michaelis acid is counted the 1-5% of aldehyde with molar equivalent, and described aldehyde is selected from C
1To C
10Alkanoic or aromatic aldehyde.
2. the synthetic method of bis-indolyl alkyl compounds according to claim 1, it is characterized in that: the mol ratio of described aldehyde and indoles is 1: 2.
3. the synthetic method of bis-indolyl alkyl compounds according to claim 1, it is characterized in that: described reaction is at room temperature carried out, and stirs in the reaction process, and the reaction times is 6-10 hour.
4. the synthetic method of bis-indolyl alkyl compounds according to claim 1, it is characterized in that: described being reflected under the ultrasonic wave radiation carried out, and temperature of reaction is between 30-40 ℃, and the reaction times is being 6-10 hour.
5. according to the synthetic method of claim 3 or 4 described bis-indolyl alkyl compounds, it is characterized in that: separate out solid in the reaction, through the thick product of suction filtration acquisition bis-indolyl alkyl compounds, described thick product is purified, obtain required bis-indolyl alkyl compounds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100400541A CN100412058C (en) | 2005-05-12 | 2005-05-12 | Process for synthesizing bis-indolyl alkyl compounds |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100400541A CN100412058C (en) | 2005-05-12 | 2005-05-12 | Process for synthesizing bis-indolyl alkyl compounds |
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|---|---|
| CN1699341A true CN1699341A (en) | 2005-11-23 |
| CN100412058C CN100412058C (en) | 2008-08-20 |
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| CNB2005100400541A Expired - Fee Related CN100412058C (en) | 2005-05-12 | 2005-05-12 | Process for synthesizing bis-indolyl alkyl compounds |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102617442A (en) * | 2011-01-27 | 2012-08-01 | 桂林商源植物制品有限公司 | Preparation method and use of 3,3'-methylenebis(1H-Indole) |
| CN104016900A (en) * | 2014-06-19 | 2014-09-03 | 罗田县新普生药业有限公司 | Preparation method of 3, 3'-diindolylmethane |
| CN105272900A (en) * | 2015-01-21 | 2016-01-27 | 南通大学 | Bis(indolyl) derivatives, preparation method and applications |
| CN110256325A (en) * | 2019-07-16 | 2019-09-20 | 杭州志源生物科技有限公司 | A kind of process synthesizing 3,3 '-di-indole methyl hydrides |
| CN110408660A (en) * | 2019-07-09 | 2019-11-05 | 南京工业大学 | Method for synthesizing bisindole compound under catalysis of lipase |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0887348A1 (en) * | 1997-06-25 | 1998-12-30 | Boehringer Mannheim Italia S.p.A. | Bis-Indole derivatives having antimetastatic activity, a process for their preparation and pharmaceutical compositions containing them |
| CA2260711C (en) * | 1998-02-05 | 2005-03-15 | Kagome Kabushiki Kaisha | Antibacterial compounds for ralstonia solanacearum |
| US20030191320A1 (en) * | 2000-10-18 | 2003-10-09 | Eliu Victor Paul | Process for the preparation of bis-benzazolyl compounds |
-
2005
- 2005-05-12 CN CNB2005100400541A patent/CN100412058C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102617442A (en) * | 2011-01-27 | 2012-08-01 | 桂林商源植物制品有限公司 | Preparation method and use of 3,3'-methylenebis(1H-Indole) |
| CN104016900A (en) * | 2014-06-19 | 2014-09-03 | 罗田县新普生药业有限公司 | Preparation method of 3, 3'-diindolylmethane |
| CN105272900A (en) * | 2015-01-21 | 2016-01-27 | 南通大学 | Bis(indolyl) derivatives, preparation method and applications |
| CN105272900B (en) * | 2015-01-21 | 2018-06-19 | 南通大学 | Bisindole derivative and preparation method and application |
| CN110408660A (en) * | 2019-07-09 | 2019-11-05 | 南京工业大学 | Method for synthesizing bisindole compound under catalysis of lipase |
| CN110408660B (en) * | 2019-07-09 | 2022-09-16 | 南京工业大学 | Method for synthesizing bisindole compound under catalysis of lipase |
| CN110256325A (en) * | 2019-07-16 | 2019-09-20 | 杭州志源生物科技有限公司 | A kind of process synthesizing 3,3 '-di-indole methyl hydrides |
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| Publication number | Publication date |
|---|---|
| CN100412058C (en) | 2008-08-20 |
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Application publication date: 20051123 Assignee: Suzhou Tianma Fine Chemical Product Co., Ltd. Assignor: Soochow University Contract record no.: 2010320000317 Denomination of invention: Process for synthesizing bis-indolyl alkyl compounds Granted publication date: 20080820 License type: Exclusive License Record date: 20100329 |
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