CN102850255A - Preparation method of 5-alkyl-2,3-diphenylindole - Google Patents
Preparation method of 5-alkyl-2,3-diphenylindole Download PDFInfo
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- CN102850255A CN102850255A CN2012103565071A CN201210356507A CN102850255A CN 102850255 A CN102850255 A CN 102850255A CN 2012103565071 A CN2012103565071 A CN 2012103565071A CN 201210356507 A CN201210356507 A CN 201210356507A CN 102850255 A CN102850255 A CN 102850255A
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Abstract
The invention relates to a preparation method of 5-alkyl-2,3-diphenylindole. The technical scheme is as follows: 4-alkylphenylhydrazine derivatives and aryl ketones used as raw materials react in a solvent in the presence of Lewis acid, wherein the solvent is acetic acid, methanol or ethanol, and the catalyst acid is solvent acetic acid, p-toluenesulfonic acid or anhydrous zinc chloride, or uses chlorine hydride in hydrochloride as the Lewis acid without adding any catalyst; and the raw materials, solvent and the like react in a sealed space in a high-pressure autoclave, sealed tank or any other facility to prepare the 5-alkyl-2,3-diphenylindole. The preparation method provided by the invention has the advantages of accessible raw materials, low facility request, low production cost and short preparation route, can easily industrial production, and is mild, non-toxic and efficient. The invention solves the technical problems of severe facility conditions, high toxicity, great purification difficulty, environment pollution and the like.
Description
Technical field
The present invention relates to a kind of 5-alkyl-2,3-diphenyl indole preparation method.
Background technology
5-alkyl-2,3-diphenyl indole are a kind of fine-chemical intermediates that has wide application prospects in fields such as luminescent materials.But the domestic and foreign literature report is relatively less, be fit to industrialization and amplify, and the low technological method of production cost rarely has report especially.Like the reference class roughly there be such compounds process for production thereof, method one, by the phenylbenzene ethyl ketone with to alkyl hydrazinobenzene hydrochloride salt reaction, obtain 4-alkylbenzene hydrazone derivative, and then resulting product catalyzed and synthesized target product at the Eorontrifluoride etherate solution with phosphorus trichloride or severe toxicity, such as document Tetrahedron, 1985, vol.41, #20p.4615 – 4620 and Journal oft he Chemical Society, 1953, p.612,61619573175,3179.The shortcoming of the method is, two-step reaction, and use the solvent benzol of carcinogens hypertoxicity in the synthetic 4-alkylbenzene hydrazone derivative process, and also the second step reaction requires anhydrous and oxygen-free, is unfavorable for operation.Method two, tolane and 2'-bromo-4'-exalgine react Tetrahedron Letters, 2008, vol.49, #21p.3458 – 3462 under palladium catalysis.The shortcoming of the method is, temperature is high, and the time is long, and catalyzer is expensive, and the raw materials cost height.Method three is utilized tolane and para-nitrotoluene, and CO (carbon monoxide converter) gas is at boron trifluoride-1, and synthetic product under the catalysis of 10-phenanthroline palladium is such as document Journal of Organic Chemistry, 2006, vol.71, #10p.3748-3753.The shortcoming of the method is to be unfavorable for using catalyzer costliness, the high-temperature high-voltage reaction that employing is dangerous as the poisonous gas carbon monoxide.Method four, with comparing class of the present invention seemingly, all adopt phenylbenzyl ketone with the alkyl hydrazinobenzene hydrochloride salt is reacted, such as document Journal of Heterocyclic Chemistry, 2011, vol.48, #5p.1095 – 1102.But this report method shortcoming is obvious equally, needs the synthetic means of employing microwave, is unfavorable for a large amount of production operations of this product, and the limitation of equipment seriously restricts the further industrial applications of the method.
Summary of the invention:
The present invention is intended to develop a kind of 5-alkyl-2, the preparation method of 3-diphenyl indole, and the method raw material is easy to get, and equipment requirements is not high, and production cost is low, syntheti c route is short, be easy to the technological method of suitability for industrialized production.A gentleness, nontoxic, efficient preparation method are provided.Solved that appointed condition is harsh, toxicity is large, purification difficult, be unfavorable for the technical problem such as environmental protection,
Technical scheme of the present invention:
The present invention is to react in solvent in the situation that Lewis acid exists alkyl hydrazinobenzene hydrochloride salt and phenylbenzyl ketone, and corresponding reaction formula is as follows:
In the above-mentioned reaction formula, the alkylation groups such as R represent methylidene, ethyl, solvent are a kind of in acetic acid, anhydrous methanol, the dehydrated alcohol.Catalyst acid is solvent acetic acid, tosic acid, Zinc Chloride Anhydrous, a kind of in the hydrochloric acid in the raw material salt hydrochlorate.Material rate is roughly: to alkyl hydrazinobenzene hydrochloride salt 5mol, phenylbenzyl ketone 6～7mol, solvent be: 1.0L/mol～1.6L/mol, tosic acid or Zinc Chloride Anhydrous consumption are 0.15mol.
The reaction systems such as raw material, solvent, catalyzer adopt autoclave or vexed tank equipment to be prepared at the enclosed space internal reaction.Temperature of reaction is at T=70 ℃～125 ℃, and the reaction times is 7～17h, and reaction pressure is normal pressure.Suction filtration is adopted in aftertreatment, is spin-dried for, and the methods such as making beating obtain overall yield of reaction at the target product more than 80%.Reaction conditions is gentle, and is simple and quick.
The beneficial effect that the present invention has:
A kind of 5-alkyl-2 of the present invention, 3-diphenyl indole preparation method raw material is easy to get, and equipment requirements is not high, and production cost is low, syntheti c route is short, be easy to suitability for industrialized production, is a gentleness, nontoxic, efficient preparation method.Solved that appointed condition is harsh, toxicity is large, purification difficult, be unfavorable for the technical problem such as environmental protection.
Embodiment:
Following implementing helps understand the present invention, but is not limited only to content of the present invention.
Agents useful for same of the present invention is the commercially available prod, does not do further processing.
Embodiment 1
5-alkyl-2, the preparation of 3-diphenyl indole
In the autoclave reaction unit, add 5mol to the anhydrous methanol of alkyl hydrazinobenzene hydrochloride salt, 5L volume, add the 0.15mol tosic acid, add again the phenylbenzyl ketone of 6.5mol, open and stir.Be warming up to T=70 ℃～80 ℃, reaction 10h.TLC judgement reaction is finished substantially, is cooled to room temperature.After reaction was finished, with the system suction filtration, filter cake washed with anhydrous methanol.Filtrate merges, and vacuum rotary steam obtains the yellowish brown solid.With the mixed solvent making beating washing of this solid with ethyl acetate and sherwood oil, suction filtration obtains solid pure product.Oven dry obtains target compound.
Wherein:
5-methyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.27mol.About yield 85.4%.
1HNMR((δ,CDCl
3):8.279(s,1H,NH),7.356~7.352(d,1H,ArH),7.142~7.124(m,11H,ArH),7.006~6.902(q,1H,ArH),2.42(s,3H,CH
3)HPLC:≥98%
5-ethyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.28mol.About yield 85.6%.
1HNMR((δ,CDCl
3):8.280(s,1H,NH),7.355~7.351(d,1H,ArH),7.146~7.126(m,11H,ArH),7.012~6.913(q,1H,ArH),2.42(q,2H,CH
2),1.26(t,3H,CH
3)HPLC:≥98%
Embodiment 2
5-alkyl-2, the preparation of 3-diphenyl indole
In the autoclave reaction unit, add 5mol to the dehydrated alcohol of alkyl hydrazinobenzene hydrochloride salt, 6L volume, add again the phenylbenzyl ketone of 7mol, open and stir, add the tosic acid of 0.15mol.Be warming up to T=80 ℃～90 ℃, reaction 9h.TLC judgement reaction is finished substantially, is cooled to room temperature.Aftertreatment: with the system suction filtration, the filter cake absolute ethanol washing.Filtrate merges, and vacuum rotary steam obtains the yellowish brown solid.With the mixed solvent making beating washing of this solid with ethyl acetate and sherwood oil, suction filtration obtains the solid pure product oven dry, obtains target compound.
Wherein: 5-methyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.31mol.About yield 86.2%.
1HNMR ((δ, CDCl
3) and the HPLC data as described in Example 1.
5-ethyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.32mol.About yield 86.4%.
1HNMR ((δ, CDCl
3) and the HPLC data as described in Example 1.
Embodiment 3
5-alkyl-2, the preparation of 3-diphenyl indole
In the autoclave reaction unit, add 5mol to the dehydrated alcohol of alkyl hydrazinobenzene hydrochloride salt, 6L volume, add again the phenylbenzyl ketone of 6.6mol, open and stir.Be warming up to about T=85 ℃～90 ℃ reaction 17h.TLC judgement reaction is finished substantially, is cooled to room temperature.Aftertreatment: with the system suction filtration, the filter cake absolute ethanol washing.Filtrate merges, and vacuum rotary steam obtains the yellowish brown solid.With the mixed solvent making beating washing of this solid with ethyl acetate and sherwood oil, suction filtration obtains the solid pure product oven dry, obtains target compound.
Wherein: 5-methyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.02mol.About yield 80.4%.
1HNMR ((δ, CDCl
3) and the HPLC data as described in Example 1.
5-ethyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.05mol.About yield 81.0%.
1HNMR ((δ, CDCl
3) and the HPLC data as described in Example 1.
Embodiment 4
5-alkyl-2, the preparation of 3-diphenyl indole
In the autoclave reaction unit, add 5mol to the Glacial acetic acid of alkyl hydrazinobenzene hydrochloride salt, 7L volume, add the Zinc Chloride Anhydrous of 0.15mol, add again the phenylbenzyl ketone of 6.5mol, open and stir.Be warming up to T=110 ℃～120 ℃, reaction 16h.TLC judgement reaction is finished substantially, is cooled to room temperature.After reaction was finished, with the system suction filtration, filter cake washed with Glacial acetic acid.Filtrate merges, and most of solvent is fallen in decompression, and with the mixed solvent making beating washing of ethyl acetate and sherwood oil, suction filtration obtains solid pure product.Oven dry obtains target product.
Wherein: 5-methyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.30mol.About yield 86.0%.
1HNMR ((δ, CDCl
3) and the HPLC data as described in Example 1.
5-ethyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.25mol.About yield 85.0%.
1HNMR ((δ, CDCl
3) and the HPLC data as described in Example 1.
Embodiment 5
5-alkyl-2, the preparation of 3-diphenyl indole
In the autoclave reaction unit, add 5mol to the acetic acid of alkyl hydrazinobenzene hydrochloride salt, 8L volume, add again the phenylbenzyl ketone of 6mol, open and stir, be warming up to T=120 ℃～125 ℃, reaction 7h.TLC judgement reaction is finished substantially, is cooled to room temperature.Aftertreatment: with the system suction filtration, filter cake washs with acetic acid.Filtrate merges, and vacuum rotary steam falls most of solvent, adds the mixed solvent making beating washing of ethyl acetate and sherwood oil, and suction filtration obtains solid pure product.Oven dry obtains target compound.
Wherein: 5-methyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.20mol.About yield 84.0%.
1HNMR ((δ, CDCl
3) and the HPLC data as described in Example 1.
5-ethyl-2, the 3-diphenyl indole obtains the off-white color solid about 4.13mol.About yield 82.6%.
1HNMR ((δ, CDCl
3) and the HPLC data as described in Example 1.
More than preferred embodiment of the present invention is had been described in detail, but described content only is the preferred embodiment of present technique, can not be considered to be used to limiting practical range of the present invention.All equalizations of doing according to the present patent application scope change and improve etc., all should still belong within the patent covering scope of the present invention.
Claims (7)
1. 5-alkyl-2,3-diphenyl indole preparation method is characterized in that may further comprise the steps: take to alkyl hydrazinobenzene hydrochloride salt and alkyl ketone as raw material, in the situation that Lewis acid exists, in solvent, react, obtain 5-alkyl-2, the 3-dimethyl indole, corresponding reaction formula is as follows:
In the above-mentioned reaction formula, R represents alkyl, and such as methyl, ethyl etc., solvent is a kind of in acetic acid, methyl alcohol, the ethanol.
2. a kind of 5-alkyl-2 according to claim 1,3-diphenyl indole preparation method, it is characterized in that: catalyst acid is a kind of of solvent acetic acid, tosic acid, Zinc Chloride Anhydrous, perhaps utilizes the hydrogenchloride in the hydrochloride to be Lewis acid, and does not add any catalyzer.
3. a kind of 5-alkyl-2 according to claim 1,3-diphenyl indole preparation method is characterized in that: material rate is: to alkyl hydrazinobenzene hydrochloride salt 5mol, phenylbenzyl ketone 6～7mol, solvent be: 1.0L/mol～1.6L/mol, tosic acid or Zinc Chloride Anhydrous consumption are 0.15mol.
4. a kind of 5-alkyl-2 according to claim 1,3-diphenyl indole preparation method is characterized in that: reaction system adopts autoclave or vexed tank equipment to be prepared at the enclosed space internal reaction.
5. a kind of 5-alkyl-2 according to claim 4,3-diphenyl indole preparation method is characterized in that: reaction system is prepared at autoclave or vexed tank equipment.
6. a kind of 5-alkyl-2 according to claim 1,3-diphenyl indole preparation method is characterized in that: temperature of reaction is at T=70 ℃～125 ℃.
7. a kind of 5-halogen-2 according to claim 1,3-diphenyl indole preparation method is characterized in that: reaction times=7～17h.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108440433A (en) * | 2018-03-01 | 2018-08-24 | 湖北佰智昂生物化工有限公司 | The method that copper lewis acid Surfactant-Catalyzed prepares chlorination -3- substitution -2,5- diphenyltetrazolium bromides |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102249983A (en) * | 2011-05-24 | 2011-11-23 | 南通海迪化工有限公司 | Method for synthesizing tetrahydrocarbazoles compound |
| US8080566B1 (en) * | 2008-06-11 | 2011-12-20 | Kalypsys, Inc | Carbazole inhibitors of histamine receptors for the treatment of disease |
| KR20120083241A (en) * | 2011-01-17 | 2012-07-25 | 주식회사 엘지화학 | New hetero-cyclic compound and organic light emitting device using the same |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8080566B1 (en) * | 2008-06-11 | 2011-12-20 | Kalypsys, Inc | Carbazole inhibitors of histamine receptors for the treatment of disease |
| KR20120083241A (en) * | 2011-01-17 | 2012-07-25 | 주식회사 엘지화학 | New hetero-cyclic compound and organic light emitting device using the same |
| CN102249983A (en) * | 2011-05-24 | 2011-11-23 | 南通海迪化工有限公司 | Method for synthesizing tetrahydrocarbazoles compound |
Non-Patent Citations (2)
| Title |
|---|
| 《Journal of Heterocyclic Chemistry》 20110519 Evelyn Cuevas Creencia，et al. "One-Pot-One-Step, Microwave-Assisted Fischer Indole Synthesis" 第1095-1102页 1-7 第48卷, 第5期 * |
| EVELYN CUEVAS CREENCIA，ET AL.: ""One-Pot-One-Step, Microwave-Assisted Fischer Indole Synthesis"", 《JOURNAL OF HETEROCYCLIC CHEMISTRY》, vol. 48, no. 5, 19 May 2011 (2011-05-19), pages 1095 - 1102 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108440433A (en) * | 2018-03-01 | 2018-08-24 | 湖北佰智昂生物化工有限公司 | The method that copper lewis acid Surfactant-Catalyzed prepares chlorination -3- substitution -2,5- diphenyltetrazolium bromides |
| CN108440433B (en) * | 2018-03-01 | 2021-02-23 | 湖北佰智昂生物化工有限公司 | Method for preparing chlorinated-3-substituted-2, 5-diphenyl tetrazole by catalysis of copper Lewis acid surfactant |
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