CN1706829A - Double indolyl derivative synthesizing process - Google Patents
Double indolyl derivative synthesizing process Download PDFInfo
- Publication number
- CN1706829A CN1706829A CN 200510040053 CN200510040053A CN1706829A CN 1706829 A CN1706829 A CN 1706829A CN 200510040053 CN200510040053 CN 200510040053 CN 200510040053 A CN200510040053 A CN 200510040053A CN 1706829 A CN1706829 A CN 1706829A
- Authority
- CN
- China
- Prior art keywords
- aldehyde
- bis
- double
- indolyl
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Indole Compounds (AREA)
Abstract
The present invention discloses the synthesis process of double indolylalkyl derivative. Aldehyde and indole are made to produce synthesis reaction, and the aldehyde is selected from C1-C10 aliphatic aldehyde and aromatic aldehyde. The present invention features that super solid acid SO42-/TiO2 is used as catalyst in the amount of 30-80 mg for each millimole of aldehyde, and that double indolylalkyl compound is prepared through grinding reaction for 0.5-5 hr and subsequent washing with solvent, filtering and filtrate concentration. The present invention adopts super solid acid to replace traditional protonic acid or Lewis acid, and no solvent in preparing double indolylalkyl compound, and has no environmental pollution caused by organic solvent, high reaction yield, short production period and simple operation.
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 synthetic of bis-indolyl alkyl compounds just has report as far back as 19th century, and over more than 100 year, bis-indolyl alkyl compounds synthetic obtained significant progress.Main synthetic method be by indoles and aldehydes or ketones protonic acid or Lewis acid as: polynite K-10, LiClO
4, In (OTf)
3, InCl
3, I
2, CAN, FeCl
3Deng catalysis under obtain with productive rate preferably.But these methods all exist certain deficiency, have all limited the popularization of these methods to a certain extent as the poisonous and hazardous volatile organic solvent of a large amount of uses, use that expensive catalysts, harsh reaction conditions, complicated operations program and catalyzer can not be recycled etc.This just needs people to go to seek a kind of reaction system that more meets the Green Chemistry developing direction, for later suitability for industrialized production is laid a solid foundation.
In recent years, along with the enhancing of people's environmental consciousness and environmental legislation are strict day by day, the pollution problem in the chemical industry is Cheng Wei Yi Han problem to be solved.People wish that each molecule in the raw material can both be converted into product, realize the zero release of pollution, adopt nontoxic raw material, the friendly product of production environment.And catalyzer is stated in the purpose in realization and is played a crucial role.Acid catalyst is as H
2SO
4, HF, H
3PO
4Be widely used Deng in catalytic field, but use this class catalyzer to exist some row such as producing a large amount of waste liquids, equipment corrosion seriously reaches catalyzer and the isolating difficulty of product, be difficult to realize shortcomings such as continuous production on the chemical technology, and solid acid catalyst can address the above problem to a great extent.Thereby replacing liquid acid catalyst with solid acid is a most important approach that realizes the environmental friendliness Catalytic processes.Along with the development of catalytic science and the enhancing day by day of environmental protection consciousness, the technology of employing solid acid catalyst becomes the focus of present research.This type of technology is in not homophase because of catalyzer and reactant, and is recyclable and reuse, and do not have equipment corrosion and problem of environmental pollution, thereby be called as cleaning procedure.This technology is at first succeeded in developing in refining of petroleum and petrochemical industry, after be introduced into the Minute Organic Synthesis field.Super acids is the acid also stronger than 100% sulfuric acid, in catalyzed reaction, and to olefines double bond isomerizing, hydrolysis, olefin alkylation, acidylate, aspects such as esterification all show higher activity, such catalyst reaction mild condition has wide practical use.Yet, but do not see the pertinent literature report with this synthetic reaction as the catalyst bis-indolyl alkyl compounds.
Summary of the invention
The present invention seeks to solid super acid catalyst was introduced in synthesizing of bis-indolyl alkyl compounds,, need not the bis-indolyl alkyl compounds synthetic method that organic solvent participates in so that a kind of productive rate height to be provided.
For achieving the above object, the technical solution used in the present invention is: a kind of synthetic method of double indolyl derivative, carry out building-up reactions by aldehyde and indoles, and described aldehyde is selected from C
1To C
10Alkanoic or aromatic aldehyde, adopt solid super-strong acid SO
4 2-/ TiO
2As catalyzer, the aldehyde of corresponding every mmole, the add-on of catalyzer is the 30-80 milligram, and griding reaction 0.5 hour to 5 hours is used solvent wash then, filters, and filtrate concentrating promptly obtains bis-indolyl alkyl compounds.
In the technique scheme, the temperature during described griding reaction is between 25 ℃ to 60 ℃.Temperature can influence the speed of reaction, and usually, when temperature was higher, speed of response was very fast, for example, 50 ℃ of following reaction times between 0.5 hour to 1.5 hours, but the too high meeting of temperature causes the decomposition of aldehyde, therefore, is advisable to be controlled at below 60 ℃.When carrying out suitability for industrialized production, grinding can adopt ball mill to carry out.
Carry out for reacting fully, to improve degree of purity of production, optimized technical scheme is that the mol ratio of described aldehyde and indoles is 1: 2.
In the technique scheme, described solvent is an ethyl acetate.
In the technique scheme, the solid of gained is exactly a solid super acid catalyst during filtration, and the catalyzer process is simple dry, and in the catalyzed reaction that activation promptly can be used for next time in two minutes in microwave oven.
The solid super-strong acid SO of this programme
4 2-/ TiO
2Preparation of catalysts has bibliographical information, can adopt following method: add TiCl in the round-bottomed flask that magnetic stirring apparatus, dropping funnel are housed
4Liquid slowly splashes into strong aqua then under violent stirring, equal 8 until the pH value of reaction mixture.The precipitate with deionized water washing of gained is to can not detecting Cl
-Existence till, then 100 ℃ dry 24 hours down.Gained blocks of solid grind into powder joins the H of an amount of 0.5mol/L then
2SO
4In, going out to anhydrate under the decompression, the gained sample promptly got solid super acid catalyst in 4 hours in 600 ℃ of following calcinations afterwards in 100 ℃ times dry 12 hours.
Because the technique scheme utilization, the present invention compared with prior art has following advantage:
1. because adopting, the present invention is easy to realize that the solid super acid catalyst of recycle replaces traditional protonic acid or Lewis acid catalyst to prepare bis-indolyl alkyl compounds under condition of no solvent, the pollution of having avoided organic solvent that environment is produced;
2. productive rate height of the present invention, the time is short, and is simple to operate, and catalyzer can recycle several times easily, and activity can not reduce.
Embodiment
Below in conjunction with embodiment the present invention is further described:
Embodiment one: bis (indolyl) methane synthetic
Get the formaldehyde of 1 mmole and the indoles of 2 mmoles and place grinding, add solid super-strong acid SO
4 2-/ TiO
2Catalyzer, 50 milligrams of consumptions at 50 ℃ of following griding reaction 0.5-1.5 hours, with the ethyl acetate washing, filter then, and filtrate concentrating obtains thick product, further purifies to obtain the bis (indolyl) methane of higher degree.
Embodiment two: 3,3'-(Phenylmethylene)bis[1H-indole] synthetic
Get the phenyl aldehyde of 1 mmole and the indoles of 2 mmoles and place reaction flask, add the solid super-strong acid SO of 60mg
4 2-/ TiO
2, place grinding, grind evenly, in being warming up under the infrared lamp about 50 ℃, through 0.5 hour, the TLC detection reaction was complete, with the ethyl acetate washing, filtered, and the filtrate vacuum concentration obtains thick product, and further purification promptly obtains the 3,3'-(Phenylmethylene)bis[1H-indole] of higher degree.
Embodiment three: two indoles thiophene phenyl methane synthetic
Get the thiophene phenol-2-formaldehyde of 1 mmole and the indoles of 2 mmoles and place reaction flask, add the solid super-strong acid SO of 45mg
4 2-/ TiO
2, place grinding, grind evenly, in being warming up under the infrared lamp about 50 ℃, through 1.5 hours, the TLC detection reaction was complete, with the ethyl acetate washing, filtered, and the filtrate vacuum concentration obtains thick product, and further purification promptly obtains the 3,3'-(Phenylmethylene)bis[1H-indole] of higher degree.
Embodiment four: two indoles nonyl methane synthetic
Get the aldehyde C-9 of 1 mmole and the indoles of 2 mmoles and place reaction flask, add the solid super-strong acid SO of 50mg
4 2-/ TiO
2, place grinding, grind evenly, in being warming up under the infrared lamp about 50 ℃, through 1.5 hours, the TLC detection reaction was complete, with the ethyl acetate washing, filtered, and the filtrate vacuum concentration obtains thick product, and further purification promptly obtains the 3,3'-(Phenylmethylene)bis[1H-indole] of higher degree.
Embodiment five: two 5-skatole p-nitrophenyl methylmethanes synthetic
Get the paranitrobenzaldehyde of 1 mmole and the 5-skatole of 2 mmoles and place reaction flask, add the solid super-strong acid SO of 50mg
4 2-/ TiO
2, place grinding, grind evenly, in being warming up under the infrared lamp about 50 ℃, through 0.5 hour, the TLC detection reaction was complete, with the ethyl acetate washing, filtered, and the filtrate vacuum concentration obtains thick product, and further purification promptly obtains the 3,3'-(Phenylmethylene)bis[1H-indole] of higher degree.
Claims (4)
1. the synthetic method of a double indolyl derivative is carried out building-up reactions by aldehyde and indoles, and described aldehyde is selected from C
1To C
10Alkanoic or aromatic aldehyde, it is characterized in that: adopt solid super-strong acid SO
4 2-/ TiO
2As catalyzer, the aldehyde of corresponding every mmole, the add-on of catalyzer is the 30-80 milligram, and griding reaction 0.5 hour to 5 hours is used solvent wash then, filters, and filtrate concentrating promptly obtains bis-indolyl alkyl compounds.
2. the synthetic method of bis-indolyl alkyl compounds according to claim 1 is characterized in that: the temperature during described griding reaction is between 25 ℃ to 60 ℃.
3. 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.
4. the synthetic method of bis-indolyl alkyl compounds according to claim 1, it is characterized in that: described solvent is an ethyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100400537A CN1332948C (en) | 2005-05-12 | 2005-05-12 | Double indolyl derivative synthesizing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100400537A CN1332948C (en) | 2005-05-12 | 2005-05-12 | Double indolyl derivative synthesizing process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1706829A true CN1706829A (en) | 2005-12-14 |
| CN1332948C CN1332948C (en) | 2007-08-22 |
Family
ID=35580960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100400537A Expired - Fee Related CN1332948C (en) | 2005-05-12 | 2005-05-12 | Double indolyl derivative synthesizing process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1332948C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103467354A (en) * | 2013-09-16 | 2013-12-25 | 陕西师范大学 | Method for preparing diindolyl methane derivatives |
| CN111606838A (en) * | 2020-06-19 | 2020-09-01 | 宁夏大学 | Preparation method of bis-indolyl methane compound |
Family Cites Families (2)
| 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 |
| US20030191320A1 (en) * | 2000-10-18 | 2003-10-09 | Eliu Victor Paul | Process for the preparation of bis-benzazolyl compounds |
-
2005
- 2005-05-12 CN CNB2005100400537A patent/CN1332948C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103467354A (en) * | 2013-09-16 | 2013-12-25 | 陕西师范大学 | Method for preparing diindolyl methane derivatives |
| CN103467354B (en) * | 2013-09-16 | 2015-04-08 | 陕西师范大学 | Method for preparing diindolyl methane derivatives |
| CN111606838A (en) * | 2020-06-19 | 2020-09-01 | 宁夏大学 | Preparation method of bis-indolyl methane compound |
| CN111606838B (en) * | 2020-06-19 | 2023-06-30 | 宁夏大学 | Preparation method of bisindolyl methane compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1332948C (en) | 2007-08-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111995635B (en) | Method for preparing organosilicon compound by catalyzing chitosan loaded copper film material | |
| CN110590819B (en) | Process for producing organoboron compound and process for producing beta-hydroxyorganoboron compound | |
| CN112778218B (en) | Method for preparing quinazolinone and derivative thereof by using chitosan-supported copper catalyst | |
| Cheng et al. | Asymmetric Hydrogenation of α, β‐Unsaturated Carboxylic Acids Catalyzed by Ruthenium (II) Complexes of Spirobifluorene Diphosphine (SFDP) Ligands | |
| CN101492457B (en) | Method of preparing hydronol | |
| Wu et al. | A novel C3-symmetric prolinol-squaramide catalyst for the asymmetric reduction of ketones by borane | |
| Mhaldar et al. | Highly effective cellulose supported 2-aminopyridine palladium complex (Pd (II)-AMP-Cell@ Al2O3) for Suzuki-Miyaura and Mizoroki–Heck cross-coupling | |
| Shi et al. | Synthesis Cu (I)–CN-based MOF with in-situ generated cyanogroup by cleavage of acetonitrile: Highly efficient for catalytic cyclization of propargylic alcohols with CO2 | |
| CN109096318B (en) | Method for preparing organic boron compound and beta-hydroxy compound under catalysis of copper ion-loaded Y-type molecular sieve | |
| CN1332948C (en) | Double indolyl derivative synthesizing process | |
| CN112321628B (en) | Preparation method of beta-dimethylphenyl silicon substituted organic nitrile compound | |
| CN113333021A (en) | Porous polymer supported palladium catalyst with high catalytic activity and application thereof in catalyzing Suzuki-Miyaura reaction | |
| CN112076776A (en) | Protonated carbon nitrides for selective photocatalytic oxidation of alcohols to esters and uses thereof | |
| Du et al. | A new method for optical resolution of BINOL by molecular complexation with (S)-5-oxopyrrolidine-2-carboxanilide | |
| CN102250005B (en) | Preparation method of Eslicarbazepine | |
| CN105037589A (en) | Carboxymethyl hemicellulose supported palladium catalyst, preparation method therefor and application thereof | |
| CN106748844B (en) | A kind of synthetic method of L- homophenylalanins | |
| CN101012194A (en) | Method for preparing 2,3,5-trimethylpyridine | |
| CN112824423B (en) | Chiral ferrocenylphosphine-indolylaminophosphine ligand and preparation method and application thereof | |
| CN114570428B (en) | Cellulose-loaded heterojunction catalytic material and method for preparing chiral boride by using same | |
| CN108383755B (en) | Method for synthesizing alkene dinitrile compound | |
| CN115197143B (en) | Dinaphtholoazepine and derivatives thereof and nickel catalytic synthesis method thereof | |
| CN105772101B (en) | The Mn Anderson types heteropolyacid catalyst of 1 Phenethylthiourea modification, preparation method and applications | |
| CN113354552B (en) | Synthetic method of V-type organic ligand, synthetic V-type organic ligand and application thereof | |
| CN114768877A (en) | Cellulose-loaded Cu2O/TiO2Catalytic material and method for applying catalytic material to boron addition reaction of p-benzoquinone methide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20051214 Assignee: Suzhou Kaiyuan Minsheng Science and Technology Co., Ltd. Assignor: Soochow University Contract record no.: 2010320000323 Denomination of invention: Double indolyl derivative synthesizing process Granted publication date: 20070822 License type: Exclusive License Record date: 20100331 |
|
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070822 Termination date: 20130512 |