CN103342675B - Preparation method of diindolylmethane derivative through catalysis - Google Patents
Preparation method of diindolylmethane derivative through catalysis Download PDFInfo
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- 0 C*=[N+](CCCC*1(C*(CCCC*)(C2)C3)C*3(CCCCN=O)C*2(CCCCN=O)C1)[O-] Chemical compound C*=[N+](CCCC*1(C*(CCCC*)(C2)C3)C*3(CCCCN=O)C*2(CCCCN=O)C1)[O-] 0.000 description 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N O=Cc1ccccc1 Chemical compound O=Cc1ccccc1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N c1c[nH]c2ccccc12 Chemical compound c1c[nH]c2ccccc12 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P20/584—Recycling of catalysts
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Abstract
The invention provides a preparation method of diindolylmethane derivative through catalysis, belonging to the technical field of organic chemistry synthesis. During a reaction of preparing the diindolylmethane derivative, a mole ratio of indole and aromatic aldehyde is 2-5 : 1, a molar amount of a catalyst is 1-3 % of the amount of aromatic aldehyde, a volume amount (mL) of a reaction solvent water is 2-10 times of a molar amount (mmol) of the aromatic aldehyde, a reaction temperature is 25-30 DEG C, a reaction time is 2-30 minutes, and a reaction pressure is an atmospheric pressure. After the reaction, the product is filtered through pumping, and filter residues are recrystallized by 98 % aqueous ethanol and then dried to obtain the pure diindolylmethane derivative. The catalyst contained in the filtrate can be recycled without any treatment. Compared with preparation methods using traditional proton acid and Lewis acid as catalysts, the method provided by the invention is little in reaction time, mild in reaction conditions and few in catalyst amount, and the catalyst can be recycled.
Description
Technical field
The invention belongs to organic chemical synthesis technical field, be specifically related to a kind of method that diindolylmethane derivative is prepared in catalysis.
Background technology
Diindolylmethane derivative is as one very important in numerous indole derivatives, and it is extensively present in natural product, and has many pharmacology and physiologically active.Such as it can promote the metabolism of female hormone in human body, can regulate the hormone metabolism thing of some cancer cells secrete, is a kind of effective cancer therapy drug.Therefore, the synthesis of diindolylmethane derivative has caused the extensive concern of people.The at present most preparation of this compounds is mainly carried out in traditional organic solvent, usually will use costliness or the larger Lewis acid of toxicity as catalyzer, there is the shortcomings such as long reaction time, productive rate is low, environmental pollution is serious simultaneously.Therefore, the catalysis preparation method of development of new just becomes the study hotspot of synthesis men.
With the acidic ion liquid of acidic functionality, because it has good thermostability, non-easy volatile, organic and mineral compound is had to the advantages such as good solubility and the acidic site that is evenly distributed and be employed in the catalysis preparation of diindolylmethane derivative.If Hojat Veisi etc. is with lewis acidity ionic liquid [BTBAC] Cl-FeCl
3as catalyzer, high productivity catalysis aldehydes or ketones and indole reaction di-indole methyl hydride and derivative (Highly efficient method for synthesis of bis (indolyl) methanes catalyzed by FeCl3-based ionic liquid thereof can be prepared under condition of no solvent, Journal of the Chinese Chemical Society, 2009,56:240-245).Meet water and occur to decompose to solve above-mentioned lewis acidity ionic liquid thus cause the shortcoming that can not recycle, A.Rajendran etc. use relatively large containing HSO
4 -acidic ion liquid [Et
3nH] [HSO
4] to hold concurrently catalyzer as the green solvent preparing diindolylmethane derivative, (A domino green synthesis of bis (indolyl) methanes catalyzed by ionic liquid [Et can be recycled in a mild condition
3nH] [HSO
4], International Journal of ChemTech Research, 2011,3:298-302).In order to improve the acidity of acidic ion liquid and then reduce the consumption of acidic ion liquid in preparation process, what the utilization such as Seyed Mohammad Vahdat synthesized contains four-SO
3the acidic ion liquid of H makes catalyzer, successfully " one kettle way " condensation reaction can be occurred for various alkanoic, fragrant aldehydes or ketones and indoles and generate corresponding diindolylmethane derivative, this preparation process has reaction conditions gentleness, used time short, productive rate high.But comparatively complicated and costly (An efficient one-pot synthesis of bis (indolyl) the methanes catalyzed by ionic liquid with multi-SO of the preparation of this acidic ion liquid
3h groups under ambient temperature in water, World Applied Science Journal, 2011,15 (6): 877-884).
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, provide that a kind of cost is low, productive rate is high, technique is simple and the method for diindolylmethane derivative is prepared in eco-friendly catalysis.
Catalyst structure formula used in the present invention is:
The method of diindolylmethane derivative is prepared in a kind of catalysis provided by the present invention, and its reaction formula is:
Wherein in reaction, indoles (I) and aromatic aldehyde (II) mol ratio are 2 ~ 5:1, the molar weight of catalyzer is 1 ~ 3% of aromatic aldehyde used, 2 ~ 10 times that the volume (mL) of reaction solvent water is aromatic aldehyde molar weight (mmol), temperature of reaction is 25 ~ 30 DEG C, reaction times is 2 ~ 30min, and reaction pressure is a normal atmosphere.After reaction terminates, suction filtration, obtains pure diindolylmethane derivative (III) after gained filter residue 98% aqueous ethanolic solution recrystallization, drying.
The present invention's aromatic aldehyde used be phenyl aldehyde, 4-chloro-benzaldehyde, Ortho Nitro Benzaldehyde, paranitrobenzaldehyde, p-tolyl aldehyde, p-Hydroxybenzaldehyde, aubepine, to cyanobenzaldehyde, p-Fluorobenzenecarboxaldehyde, p-bromobenzaldehyde, 2, any one in 4-dichlorobenzaldehyde, 2,4-dimethylbenzaldehydes.
In above-mentioned preparation feedback, the catalyzer contained in filtrate after suction filtration is directly used in without the need to any process and reacts next time, can reuse repeatedly, and the catalytic efficiency of catalyzer does not have obvious decline.
The preparation method of used catalyst of the present invention, is shown in pertinent literature (Synthesis of a novel multi – SO
3h functionalized ionic liquid and its catalytic activities for biodiesel synthesis, Green Chemistry, 12 (2010), 201-204; A preparation method for multi-sulfonic functional ion liquid, CN101348487A).
The present invention, compared with the synthetic method of traditional protonic acid, Louis's acid as catalyst, has following characteristics:
1, the acidity of catalyzer is high, and catalytic activity is good, and the reaction used time is few, and productive rate is high;
2, catalyzer can recycle, and catalytic activity almost remains unchanged in recycling;
3, using water as reaction solvent, the problem of environmental pollution brought because using volatile organic solvent can being alleviated;
4, the preparation process of catalyzer is comparatively simple and preparation expense is lower.
Embodiment
Below in conjunction with specific embodiment, technical solution of the present invention is described further, but protection scope of the present invention is not limited thereto.
Embodiment 1: 2mmol indoles, 1mmol phenyl aldehyde, 0.01mmol catalyzer and 2mL water are joined 25mL with in the single port bottle of stirrer.Vigorous stirring reaction at 25 DEG C, thin-layer chromatography (TLC) (developping agent is normal hexane: ethyl acetate=4:1) follows the tracks of extent of reaction.Reaction used time 6min, reaction pressure is a normal atmosphere.Reaction terminates rear suction filtration, and obtain pure two indoles phenylmethanes after gained filter residue 98% aqueous ethanolic solution recrystallization, drying, productive rate is 93%.Filtrate (comprising catalyzer and the complete raw material of unreacted) is directly used in without the need to any process and reacts next time.
Embodiment 2: 2mmol indoles, 1mmol 4-chloro-benzaldehyde, 0.01mmol catalyzer and 2mL water are joined 25mL with in the single port bottle of stirrer.Vigorous stirring reaction at 25 DEG C, thin-layer chromatography (TLC) (developping agent is normal hexane: ethyl acetate=4:1) follows the tracks of extent of reaction.Reaction used time 8min, reaction pressure is a normal atmosphere.Reaction terminates rear suction filtration, and obtain pure rubigan di-indole methyl hydride after gained filter residue 98% aqueous ethanolic solution recrystallization, drying, productive rate is 94%.Filtrate (comprising catalyzer and the complete raw material of unreacted) is directly used in without the need to any process and reacts next time.
Embodiment 3: 2mmol indoles, 1mmol paranitrobenzaldehyde, 0.01mmol catalyzer and 4mL water are joined 25mL with in the single port bottle of stirrer.Vigorous stirring reaction at 27 DEG C, thin-layer chromatography (TLC) (developping agent is normal hexane: ethyl acetate=4:1) follows the tracks of extent of reaction.Reaction used time 3min, reaction pressure is a normal atmosphere.Reaction terminates rear suction filtration, and obtain pure p-nitrophenyl di-indole methyl hydride after gained filter residue 98% aqueous ethanolic solution recrystallization, drying, productive rate is 97%.Filtrate (comprising catalyzer and the complete raw material of unreacted) is directly used in without the need to any process and reacts next time.
Embodiment 4: 3mmol indoles, 1mmol2,4-dichlorobenzaldehyde, 0.02mmol catalyzer and 6mL water are joined 50mL with in the single port bottle of stirrer.Vigorous stirring reaction at 30 DEG C, thin-layer chromatography (TLC) (developping agent is normal hexane: ethyl acetate=4:1) follows the tracks of extent of reaction.Reaction used time 10min, reaction pressure is a normal atmosphere.Reaction terminates rear suction filtration, and obtain pure 2,4 dichloro benzene base di-indole methyl hydride after gained filter residue 98% aqueous ethanolic solution recrystallization, drying, productive rate is 94%.Filtrate (comprising catalyzer and the complete raw material of unreacted) is directly used in without the need to any process and reacts next time.
Embodiment 5: 4mmol indoles, 1mmol2,4-dimethylbenzaldehyde, 0.03mmol catalyzer and 8mL water are joined 50mL with in the single port bottle of stirrer.Vigorous stirring reaction at 30 DEG C, thin-layer chromatography (TLC) (developping agent is normal hexane: ethyl acetate=4:1) follows the tracks of extent of reaction.Reaction used time 18min, reaction pressure is a normal atmosphere.Reaction terminates rear suction filtration, and obtain pure 2,4-3,5-dimethylphenyl di-indole methyl hydrides after gained filter residue 98% aqueous ethanolic solution recrystallization, drying, productive rate is 95%.Filtrate (comprising catalyzer and the complete raw material of unreacted) is directly used in without the need to any process and reacts next time.
Embodiment 6: 3mmol indoles, 1mmol are joined 25mL with in the single port bottle of stirrer to cyanobenzaldehyde, 0.01mmol catalyzer and 2mL water.Vigorous stirring reaction at 25 DEG C, thin-layer chromatography (TLC) (developping agent is normal hexane: ethyl acetate=4:1) follows the tracks of extent of reaction.Reaction used time 5min, reaction pressure is a normal atmosphere.Reaction terminates rear suction filtration, and obtain pure to cyano-phenyl di-indole methyl hydride after gained filter residue 98% aqueous ethanolic solution recrystallization, drying, productive rate is 95%.Filtrate (comprising catalyzer and the complete raw material of unreacted) is directly used in without the need to any process and reacts next time.
Embodiment 7: 2mmol indoles, 1mmol Ortho Nitro Benzaldehyde, 0.01mmol catalyzer and 2mL water are joined 25mL with in the single port bottle of stirrer.Vigorous stirring reaction at 25 DEG C, thin-layer chromatography (TLC) (developping agent is normal hexane: ethyl acetate=4:1) follows the tracks of extent of reaction.Reaction used time 4min, reaction pressure is a normal atmosphere.Reaction terminates rear suction filtration, and obtain pure Chloro-O-Phenyl di-indole methyl hydride after gained filter residue 98% aqueous ethanolic solution recrystallization, drying, productive rate is 96%.Filtrate (comprising catalyzer and the complete raw material of unreacted) is directly used in without the need to any process and reacts next time.
Embodiment 8: with embodiment 1 for probe reaction, make the active replica test of catalysts, catalyzer reuses 6 times, and the change of its catalysis productive rate is in table 1.
Catalyst activity replica test result in table 1 the present invention
| Catalyst recirculation access times | Two indoles phenylmethane productive rates (%) |
| 1 | 93 |
| 2 | 93 |
| 3 | 91 |
| 4 | 90 |
| 5 | 91 |
| 6 | 91 |
| 7 | 89 |
Can draw such conclusion by table 1 data: the productive rate that catalyzer is recycling two indoles phenylmethanes in process is in a slight decrease, but the amplitude of reduction being less, proving that it recycles in can reacting preparing diindolylmethane derivative.
Claims (2)
1. the method for diindolylmethane derivative is prepared in a catalysis, it is characterized in that, it is described that to prepare indoles and aromatic aldehyde mol ratio in the reaction of diindolylmethane derivative be 2 ~ 5:1, the molar weight of catalyzer is 1 ~ 3% of aromatic aldehyde used, be in 2 ~ 10 times of the aromatic aldehyde molar weight of mmole in the volume of the reaction solvent water of milliliter, temperature of reaction is 25 ~ 30 DEG C, reaction times is 2 ~ 30min, reaction pressure is a normal atmosphere, after reaction terminates, suction filtration, gained filter residue 98% aqueous ethanolic solution recrystallization, pure diindolylmethane derivative is obtained after drying,
The reaction formula that diindolylmethane derivative is prepared in described catalysis is:
Wherein R group be hydrogen, to chloro, adjacent nitro, to nitro, to methyl, to hydroxyl, to methoxyl group, to cyano group, to fluorine-based, to any one in bromo, 2,4-dichloride bases and 2,4-dimethyl;
The structural formula of described catalyzer is:
Described aromatic aldehyde be phenyl aldehyde, 4-chloro-benzaldehyde, Ortho Nitro Benzaldehyde, paranitrobenzaldehyde, p-tolyl aldehyde, p-Hydroxybenzaldehyde, aubepine, to cyanobenzaldehyde, p-Fluorobenzenecarboxaldehyde, p-bromobenzaldehyde, 2, any one in 4-dichlorobenzaldehyde, 2,4-dimethylbenzaldehydes.
2. the method for diindolylmethane derivative is prepared in a kind of catalysis as claimed in claim 1, and it is characterized in that, the catalyzer contained in the filtrate after described suction filtration can directly be reused without the need to any process.
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| CN103880728B (en) * | 2014-03-21 | 2016-03-30 | 台州学院 | A kind of method preparing di-indole methyl hydride compounds |
| CN104193718B (en) * | 2014-08-14 | 2016-03-30 | 安徽工业大学 | The method of temparin analog derivative is prepared in a kind of catalysis |
| CN104592089B (en) * | 2015-01-05 | 2019-04-16 | 内蒙古工业大学 | [HMim] BF in water4Ionic liquid-catalyzed synthesis 3- amine alkyl-indol |
| CN104592088B (en) * | 2015-01-05 | 2019-01-01 | 内蒙古工业大学 | The method that laurel acid catalysis prepares 3- amine alkyl-indol |
| CN106567104B (en) * | 2016-10-31 | 2018-12-11 | 华南理工大学 | The electrochemical method for synthesizing of 1,1 '-di-indole methyl hydride analog derivatives |
| CN107827804A (en) * | 2017-11-27 | 2018-03-23 | 菏泽海诺知识产权服务有限公司 | A kind of preparation method of diindolylmethane derivative |
| CN110016042B (en) * | 2019-05-09 | 2020-09-04 | 马鞍山市泰博化工科技有限公司 | Method for preparing 1, 4-dihydropyrido [3, 2-c ] [5, 6-c ] dicoumarin derivative through catalysis |
| 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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| WO2006025889A2 (en) * | 2004-05-21 | 2006-03-09 | The Texas A & M University System | Inhibition of atherosclerosis by diindolylmethane analogs |
| CN100376555C (en) * | 2006-04-26 | 2008-03-26 | 浙江大学 | Process for preparing diindolylmethane derivatives |
| CN101348487A (en) * | 2008-09-04 | 2009-01-21 | 华东师范大学 | Preparation of multi-sulfonic functional ion liquid |
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