CN105732466B - A kind of preparation method of 4- hydroxy phenyl bis (indolyl) methane - Google Patents
A kind of preparation method of 4- hydroxy phenyl bis (indolyl) methane Download PDFInfo
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- CN105732466B CN105732466B CN201610269690.XA CN201610269690A CN105732466B CN 105732466 B CN105732466 B CN 105732466B CN 201610269690 A CN201610269690 A CN 201610269690A CN 105732466 B CN105732466 B CN 105732466B
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Abstract
The invention discloses a kind of preparation methods of 4- hydroxy phenyl bis (indolyl) methane.Specific step is as follows by the present invention: 1) weighing parahydroxyben-zaldehyde and first indoles, using ethanol amine acetate ion liquid as catalyst, react 1-1.5h at a temperature of 30-40 DEG C；2) second batch indoles is added into reaction mass, at a temperature of 120-140 DEG C, the reaction was continued 1.5-2h；Wherein: the amount of the second batch indoles is equal with the amount of first indoles；3) material that reaction terminates in step 2) is cooled to room temperature, water is added, filtering, filter cake is crude product, and crude product object is carried out purification process, 4- hydroxy phenyl bis (indolyl) methane can be obtained.The beneficial effects of the present invention are: simple process, while catalyst preparation is simple, raw material is easy to get cheaply, and catalyst can recycle, and is not needed in reaction process using organic solvent, more environmentally protective.
Description
Technical field
The invention belongs to synthesize chemical technology field more particularly to a kind of preparation side of 4- hydroxy phenyl bis (indolyl) methane
Method.
Background technique
4- hydroxy phenyl bis (indolyl) methane, appearance are orange powder shape solid, and CAS registration number is [151358-47-3], knot
Structure formula are as follows:
Benzazole compounds are widespread in nature, and many indole derivatives all have certain physiological activity.Such as
4- hydroxy phenyl bis (indolyl) methane can promote the metabolism of female hormone in human body, be a kind of alkaloid intermediate.Traditional
Synthetic method is that electrophilic substitution reaction occurs for indoles and carbonyls under the catalysis of acid, and acid generally has lewis acid, matter
Sub- acid and heteropoly acid, but this kind of acid is big there is catalyst amount and is difficult to reuse, and the reaction time is long, and environmental pollution is big etc.
Problem, while most of reaction is required using volatile organic solvent.Researcher improved later, was urged with ionic liquid
Change.Ionic liquid has been subjected to the receiving on countries in the world catalysis circle and petroleum chemical enterprise circle as " cleaning " solvent and new catalyst system
And concern.Al is reported using [bmim] Br ionic liquid as solvent within 2009, Zare, Abdolkarim et, in 400W microwave
Under the conditions of 18 minutes temperature of intermittent reaction reach 150 DEG C under radiant power, gained 4- hydroxy phenyl bis (indolyl) methane yield is
83% (Canadian Journal of Chemistry, 87 (2), 416-421；2009)；Kundu in 2010, S.K.et al
It reports with Bu4NBr3For catalyst, ethyl alcohol is solvent, and the yield for reacting at room temperature obtained 4- hydroxy phenyl bis (indolyl) methane is only
65% (Russian Journal of Organic Chemistry, 46 (1), 126-128；2010, this two documents report
Ionic liquid has the halogen anion to severe environmental pollution.Shafeek A.R. is reported using EAN as solvent within 2012
And catalyst, 4- hydroxy phenyl bis (indolyl) methane yield obtained are 92%.Although products collection efficiency is higher, ionic liquid
EAN is needed when preparing using environmental pollution and to the nitric acid of instrument seriously corroded, and EAN dosage is that raw material feeds intake in reaction process
2 times of amount, dosage is larger.There are no find others to prepare 4- hydroxy phenyl bis (indolyl) methane with ionic liquid so far
Document.Therefore, it excavates simple and the synthetic method of the ionic liquid-catalyzed bisindole methane derivative of high-efficiency environment friendly seems outstanding
It is important.
The ethanol amine acetate ion liquid of the present invention is to be in a liquid state at normal temperature, by ethanol amine quaternary ammonium cation and second
Acid radical anion composition, ionic liquid is forced down with steam, and the small post-reaction treatment of environmental pollution is simple, environmentally friendly advantage.
Summary of the invention
Defect present in view of the above technology, technical problem to be solved by the invention is to provide a kind of simple processes
The preparation method of 4- hydroxy phenyl bis (indolyl) methane, the solvent-free participation of this method preparation process is environmentally protective, low in cost；Together
When stepwise reaction of the present invention, catalyst materials are few, can solve catalyst amount in the prior art is big, catalyst is difficult to prepare,
Recycling and the technical problem that catalyst is expensive, environmental pollution is big.
The present invention provides a kind of preparation method of 4- hydroxy phenyl bis (indolyl) methane, the specific steps are as follows:
1) parahydroxyben-zaldehyde and first indoles are weighed, using ethanol amine acetate ion liquid as catalyst, 30-40 DEG C
At a temperature of react 1-1.5h；Wherein: the molar ratio of parahydroxyben-zaldehyde and first indoles is 1:1-1.5:1, ethanol amine acetic acid
The inventory of ionic liquid is the 5%-10% of first indoles molal quantity；
2) second batch indoles is added into reaction mass, at a temperature of 120-140 DEG C, the reaction was continued 1.5-2h；Wherein: described
Second batch indoles amount it is equal with the amount of first indoles；
3) material that reaction terminates in step 2) is cooled to room temperature, water is added, filtering, filter cake is crude product, will slightly be produced
Object is purified, and 4- hydroxy phenyl bis (indolyl) methane can be obtained.
Above-mentioned steps 3) in, purification process uses means re-crystallization.Preferably, the solvent of recrystallization is 95vol% ethyl alcohol.
After step 3), further include the steps that catalyst recycles.The step of catalyst recycles is as follows: being added in the filtrate of step 3) organic
Solvent extraction, water phase extracted obtain catalyst ethanol amine acetate ion liquid through vacuum dehydration.Preferably, described to have
Solvent is methylene chloride.Preferably, when vacuum dehydration, vacuum degree 5-10mmHg, temperature is 60 DEG C.
In the present invention, ethanol amine acetate ion liquid is directly mixed to prepare by ethanol amine and acetic acid.
Compared to the prior art, the beneficial effects of the present invention are:
(1) it is double to prepare 4- hydroxy phenyl by two-step reaction using ethanol amine acetate ion liquid as catalyst by the present invention
Indole methyl hydride, preparation process is simple, and last handling process is simple, high income；
(2) organic solvent-free participates in preparation process, environmentally protective；
(3) catalyst preparation is simple, and raw material is easy to get cheaply, and catalyst can recycle, and recovery method is simple.
Detailed description of the invention
Fig. 1 is the 4- hydroxy phenyl bis (indolyl) methane that embodiment 1 obtains1HNMR spectrogram.
Fig. 2 is the partial enlargement for the 4- hydroxy phenyl bis (indolyl) methane that embodiment 1 obtains1HNMR spectrogram.
Specific embodiment
The present invention is described in further detail below by specific embodiment.
The chemical equation of the preparation method of 4- hydroxy phenyl bis (indolyl) methane of the present invention is as follows:
Embodiment 1
Parahydroxyben-zaldehyde 0.183g (1.5mmol), indoles 0.117g are put into the round-bottomed flask of a 50mL
(1.0mmol), shakes up, and is added catalyst ion liquid ethanol amine acetate ionic liquid 0.121g (0.1mmol), is warming up to 35
DEG C, 1.5h is stirred, is then added in the reaction system indoles 0.117g (1.0mmol), reaction temperature is 130 DEG C, when reaction
Between be 1.5h；After reaction, it is cooled to room temperature, 10mL water, filtering is added, filtrate rotary evaporation obtains ethanol amine acetate ion
Liquid can be recycled.Filter cake obtains 4- hydroxy phenyl bis (indolyl) methane after being obtained with 95% ethyl alcohol recrystallization, product is orange
Pulverulent solids, yield 83%, fusing point are 150.2-150.3 DEG C.
Using Buker AM-500 (500M) Nuclear Magnetic Resonance, using TMS as internal standard, CDCl3For solvent, Fig. 1 is embodiment 1
Nucleus magnetic hydrogen spectrum figure, Fig. 2 is partial enlarged view, and surveyed nuclear-magnetism modal data is as follows:1H NMR(CDCl3): δ=5.85 (s, 1H),
6.69 (s, 2H), 6.76-6.78 (d, 2H), 7.01-7.04 (t, J=7.75Hz, 2H), 7.18-7.24 (m, 4H), 7.38-
7.42 (m, 4H), 7.95 (s, 2H), 9.90 (s, 1H), wherein δ stronger absorption peak at 7.285 is CDCl3Dissolvent residual
Peak.Proof product is 4- hydroxy phenyl bis (indolyl) methane.
Embodiment 2
Parahydroxyben-zaldehyde 0.183g (1.5mmol), indoles 0.117g are put into the round-bottomed flask of a 50mL
(1.0mmol), shakes up, and ionic liquid ethanol amine acetate ion liquid 0.121g is added, and [wherein 0.110g is followed in embodiment 1
Catalyst+the 0.011g that loopback is received is new], 35 DEG C are warming up to, 2h is stirred, then adds indoles in the reaction system
(1.0mmol), reaction temperature are 130 DEG C, reaction time 2h；After reaction, it is cooled to room temperature, 10mL water is added, filter,
Filtrate rotary evaporation obtains ethanol amine acetate ion liquid, can be recycled.Filter cake obtains after being obtained with 95% ethyl alcohol recrystallization
4- hydroxy phenyl bis (indolyl) methane, product are orange powder shape solid, yield 82%.
Embodiment 3
It is 140 DEG C by reaction temperature control after second of addition indoles in embodiment 1, other conditions and embodiment 1
Identical, obtained product yield is 80%.
Embodiment 4
Catalyst amount in embodiment 1 is changed to 0.05mol, other conditions are identical as embodiment 1, obtained product
Yield is 80%.
Above said content is only the basic explanation under present inventive concept, and is appointed made by technical solution according to the present invention
What equivalent transformation, is within the scope of protection of the invention.
Claims (7)
1. a kind of preparation method of 4- hydroxy phenyl bis (indolyl) methane, which is characterized in that specific step is as follows:
1) parahydroxyben-zaldehyde and first indoles are weighed, using ethanol amine acetate ion liquid as catalyst, 30-40 DEG C of temperature
Lower reaction 1-1.5h；Wherein: the molar ratio of parahydroxyben-zaldehyde and first indoles is 1:1-1.5:1, ethyl alcohol amine acetate from
The inventory of sub- liquid is the 5%-10% of first indoles molal quantity；
2) second batch indoles is added into reaction mass, at a temperature of 120-140 DEG C, the reaction was continued 1.5-2h；Wherein: described
The amount of two batches of indoles and the amount of first indoles are equal；
3) material that reaction terminates in step 2) is cooled to room temperature, water is added, filtering, filter cake is crude product, by crude product into
4- hydroxy phenyl bis (indolyl) methane can be obtained in row purification process.
2. preparation method as described in claim 1, which is characterized in that in step 3), purification process uses means re-crystallization.
3. preparation method as claimed in claim 2, which is characterized in that the solvent of recrystallization is 95vol% ethyl alcohol.
4. preparation method as described in claim 1, which is characterized in that after step 3), further include the steps that catalyst recycles.
5. preparation method as claimed in claim 4, which is characterized in that the step of catalyst recycles is as follows: in the filter of step 3)
Organic solvent extraction is added in liquid, water phase extracted obtains catalyst ethanol amine acetate ion liquid through vacuum dehydration.
6. preparation method as claimed in claim 5, which is characterized in that the organic solvent is methylene chloride.
7. preparation method as claimed in claim 5, which is characterized in that when vacuum dehydration, vacuum degree 5-10mmHg, temperature is
60℃。
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| CN107827764A (en) * | 2017-11-27 | 2018-03-23 | 上海应用技术大学 | A kind of preparation method of double β amino ketones or double β amino esters |
| CN111606838B (en) * | 2020-06-19 | 2023-06-30 | 宁夏大学 | Preparation method of bisindolyl methane compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102766081A (en) * | 2012-07-30 | 2012-11-07 | 李佰林 | Method for synchronizing diindolylmethane derivatives |
| CN103880728A (en) * | 2014-03-21 | 2014-06-25 | 台州学院 | Method for preparing diindolylmethane compound |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102766081A (en) * | 2012-07-30 | 2012-11-07 | 李佰林 | Method for synchronizing diindolylmethane derivatives |
| CN103880728A (en) * | 2014-03-21 | 2014-06-25 | 台州学院 | Method for preparing diindolylmethane compound |
Non-Patent Citations (3)
| Title |
|---|
| Efficient, rapid synthesis of bis(indolyl)methane using ethyl ammonium nitrate as an ionic liquid;Shafeek A. R. Mulla et al.，;《RSC Advances》;20121231;第2卷;第3525-3529页 |
| Friedel–Crafts Alkylation of Indoles Exclusively in Water Catalyzed by Ionic Liquid Supported on a Polyacrylonitrile Fiber: A Simple "Release and Catch" Catalyst;Xian-Lei Shi et al.,;《ChemCatChem》;20140829;第6卷;第2947-2953页 |
| Synthesis of aryl/alkyl(2,20-bis-3-methylindolyl)methanes and aryl(3,30-bis indolyl)methanes promoted by secondary amine based ionic liquids and microwave irradiation;Pranab J. Das et al.,;《Tetrahedron Letters》;20120628;第53卷;第4718页右栏倒数第1-11行，第4719页Scheme 2和Table2 |
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