CN107827804A - A kind of preparation method of diindolylmethane derivative - Google Patents
A kind of preparation method of diindolylmethane derivative Download PDFInfo
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- CN107827804A CN107827804A CN201711204548.8A CN201711204548A CN107827804A CN 107827804 A CN107827804 A CN 107827804A CN 201711204548 A CN201711204548 A CN 201711204548A CN 107827804 A CN107827804 A CN 107827804A
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- preparation
- ethanol
- sulfonic acid
- catalyst
- diindolylmethane derivative
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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
-
- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses a kind of preparation method of diindolylmethane derivative, belong to organic synthesis field.This is using indoles and aromatic aldehyde as reaction substrate, using sulfonic acid ion exchange resin as catalyst, using water and/or ethanol as solvent, reacts di-indole methyl hydride class compound is made at normal temperatures and pressures.The present invention is using sulfonic acid ion exchange resin as catalyst, and yield is high, the reaction time is short, post processing is easy；Catalyst is cheap and easily-available, and cost is low.
Description
Technical field
The present invention relates to organic synthesis field, more particularly to a kind of preparation method of diindolylmethane derivative.
Background technology
For diindolylmethane derivative as very important one kind in numerous indole derivativeses, it is widely present in natural production
In thing, and there is many pharmacology and physiologically active.For example it can promote the metabolism of human body female hormone, certain can be adjusted
The hormone metabolism thing of a little cancer cells secretes, is a kind of effective cancer therapy drug, therefore the synthesis of diindolylmethane derivative is
Attract wide attention.
The most preparation of such compound at present is mainly carried out in traditional organic solvent, generally to use costliness
Or the larger lewis acid of toxicity is as catalyst, and the shortcomings of reaction time length, low yield, complex operation and environmental pollution.
Therefore new catalysis preparation method is developed to become as study hotspot.
Authorization Notice No. for " B of CN 103342675 " Chinese invention patent " a kind of catalysis prepare di-indole methyl hydride derivative
The method of thing ", its used catalyst are baroque ionic liquid, although using water as solvent and reaction rate it is fast, valency
Lattice are expensive, and catalyst synthesis is complicated, is unfavorable for commercial Application.
The content of the invention
In order to make up the deficiencies in the prior art, the invention provides a kind of preparation method of diindolylmethane derivative.
The technical scheme is that：
A kind of preparation method of diindolylmethane derivative, using indoles and aromatic aldehyde as reaction substrate, handed over sulfonic acid type ion
Resin is changed as catalyst, reacts di-indole methyl hydride class compound is made at normal temperatures and pressures.
Reaction equation is as follows：
Preferably, using water and/or ethanol as solvent.
Preferably, the mol ratio of indoles and aromatic aldehyde is 2-2.05:1.
Preferably, the mol ratio of sulfonic acid ion exchange resin catalyst and aromatic aldehyde is 0.01-0.2：1.
Preferably, the reaction time is 2-10 min.
Preferably, after completion of the reaction, water is added into reaction solution, treats that product separates out, filters, recrystallization.
Further, solvent for use is recrystallized as methanol and the mixed solvent of ethanol, and the volume ratio of methanol and ethanol is 1:
2-3。
Beneficial effects of the present invention are：
The present invention is using sulfonic acid ion exchange resin as catalyst, and yield is high, the reaction time is short, post processing is easy；Catalyst
Cheap and easily-available, cost is low.
Embodiment
Embodiment 1
Indoles 0.5mol, benzaldehyde 0.25mol, sulfonic acid ion exchange resin 0.0035mol, ethanol 50mL are sequentially added into list
Mouth reaction bulb, is stirred at room temperature 10 minutes, and TLC detections, raw material disappears.
A large amount of water are added, product separates out, and filtering, the sulfonic acid ion exchange resin in filter cake is removed, using methanol/ethanol
（Volume ratio 1:2）Solution recrystallizes to product, obtains pure product.Yield is 93%, purity 99%.3,3’-
（phenylmethylene）bis(1H-indole):1H NMR(400MHz,CDCl3) (ppm):7.92(s,2H),7.43-
7.35(m,6H),7.32(t,J=4.3Hz,2H),7.25-7.15(m,3H),7.06-6.98(m,2H),6.75-6.58(m,
2H),5.92(s,1H);13C NMR(100MHz, CDCl3) (ppm):144.00, 136.70, 128.73, 128.22,
127.09, 126.14, 123.60, 121.93, 119.95, 119.75, 119.24,111.01, 40.21。
Embodiment 2
By indoles 0.5mol, 4-methoxybenzaldehyde 0.25mol, sulfonic acid ion exchange resin 0.0035mol, ethanol 50mL according to
Secondary addition stand up reaction bottle, it is stirred at room temperature 5 minutes, TLC detections, raw material disappears.
A large amount of water are added, product separates out, and filtering, the sulfonic acid ion exchange resin in filter cake is removed, using methanol/ethanol
（Volume ratio 1:2）Solution recrystallizes to product, obtains pure product.Yield is 98%, purity 99%.
3,3’-((4-methoxyphenyl)methylene)bis(1H-indole):1HNMR(400MHz,CDCl3)
(ppm): 7.92(s,2H), 7.40(m,4H), 7.28(d,J=2.0Hz,2H), 7.21-7.12(m,2H), 7.06-6.99
(m,2H), 6.88-6.81(m,2H), 6.67(d=J=1.5Hz,2H), 5.87(s,1H), 3.79(s,3H)。
Embodiment 3
By indoles 0.5mol, m-methoxybenzaldehyde 0.25mol, sulfonic acid ion exchange resin 0.0040mol, ethanol 50mL according to
Secondary addition stand up reaction bottle, it is stirred at room temperature 5 minutes, TLC detections, raw material disappears.
A large amount of water are added, product separates out, and filtering, the sulfonic acid ion exchange resin in filter cake is removed, using methanol/ethanol
（Volume ratio 1:2）Solution recrystallizes to product, obtains pure product.Yield is 97%, purity 99%.
Embodiment 4
Indoles 0.5mol, 4- chlorobenzaldehyde 0.25mol, sulfonic acid ion exchange resin 0.0045mol, ethanol 50mL are added successively
Enter stand up reaction bottle, be stirred at room temperature 10 minutes, TLC detections, raw material disappears.
A large amount of water are added, product separates out, and filtering, the sulfonic acid ion exchange resin in filter cake is removed, using methanol/ethanol
（Volume ratio 1:3）Solution recrystallizes to product, obtains pure product.Yield is 96%, purity 99%.
Embodiment 5
By indoles 0.5mol, 4- tolyl aldehyde 0.25mol, sulfonic acid ion exchange resin 0.0040mol, ethanol 50mL successively
Stand up reaction bottle is added, is stirred at room temperature 7 minutes, TLC detections, raw material disappears.
A large amount of water are added, product separates out, and filtering, the sulfonic acid ion exchange resin in filter cake is removed, using methanol/ethanol
（Volume ratio 1:2）Solution recrystallizes to product, obtains pure product.Yield is 95%, purity 99%.
Claims (7)
- A kind of 1. preparation method of diindolylmethane derivative, using indoles and aromatic aldehyde as reaction substrate, it is characterised in that：With Sulfonic acid ion exchange resin reacts di-indole methyl hydride class compound is made at normal temperatures and pressures as catalyst.
- 2. the preparation method of diindolylmethane derivative as claimed in claim 1, it is characterised in that：Using water and/or ethanol to be molten Agent.
- 3. the preparation method of diindolylmethane derivative as claimed in claim 1 or 2, it is characterised in that：Indoles and aromatic aldehyde Mol ratio is 2-2.05:1.
- 4. the preparation method of diindolylmethane derivative as claimed in claim 1 or 2, it is characterised in that：Sulfonic acid type ion exchanges The mol ratio of resin catalyst and aromatic aldehyde is 0.01-0.2：1.
- 5. the preparation method of diindolylmethane derivative as claimed in claim 1 or 2, it is characterised in that：Reaction time is 2-10 min。
- 6. the preparation method of diindolylmethane derivative as claimed in claim 1 or 2, it is characterised in that：After completion of the reaction, to anti- Answer and water is added in liquid, treat that product separates out, filter, recrystallization.
- 7. the preparation method of diindolylmethane derivative as claimed in claim 6, it is characterised in that：Recrystallization solvent for use is first The volume ratio of the mixed solvent of alcohol and ethanol, methanol and ethanol is 1:2-3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711204548.8A CN107827804A (en) | 2017-11-27 | 2017-11-27 | A kind of preparation method of diindolylmethane derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711204548.8A CN107827804A (en) | 2017-11-27 | 2017-11-27 | A kind of preparation method of diindolylmethane derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107827804A true CN107827804A (en) | 2018-03-23 |
Family
ID=61645555
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711204548.8A Pending CN107827804A (en) | 2017-11-27 | 2017-11-27 | A kind of preparation method of diindolylmethane derivative |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN113880748A (en) * | 2021-11-15 | 2022-01-04 | 西安久中生物科技有限公司 | Green preparation process of 3, 3-diindolylmethane |
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| CN1837193A (en) * | 2006-04-26 | 2006-09-27 | 浙江大学 | Process for preparing diindolylmethane derivatives |
| CN102153500A (en) * | 2011-03-02 | 2011-08-17 | 河北大学 | Method for synthesizing diindolylmethane derivative |
| CN102766081A (en) * | 2012-07-30 | 2012-11-07 | 李佰林 | Method for synchronizing diindolylmethane derivatives |
| CN103333097A (en) * | 2013-06-18 | 2013-10-02 | 重庆大学 | Synthesis method of diindolylmethane derivatives |
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2017
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN113880748A (en) * | 2021-11-15 | 2022-01-04 | 西安久中生物科技有限公司 | Green preparation process of 3, 3-diindolylmethane |
| CN113880748B (en) * | 2021-11-15 | 2023-06-23 | 西安久中生物科技有限公司 | Green preparation process of 3, 3-diindolylmethane |
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