CN106699633A - Preparation method for benzo [e] indole compound - Google Patents
Preparation method for benzo [e] indole compound Download PDFInfo
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- CN106699633A CN106699633A CN201611233252.4A CN201611233252A CN106699633A CN 106699633 A CN106699633 A CN 106699633A CN 201611233252 A CN201611233252 A CN 201611233252A CN 106699633 A CN106699633 A CN 106699633A
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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
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a preparation method for a benzo [e] indole compound, and belongs to the technical field of chemical synthesis. According to the preparation method, the benzo [e] indole compound is synthesized at a high yield by taking aromatic aldehyde, 2-naphthylamine and nitro-paraffin as raw materials, taking lewis acid as a catalyst, and taking ethyl alcohol as a solvent under the catalysis of the lewis acid. The preparation method has the advantages that used raw materials are conventional organic reagents which are low in cost, reaction conditions in a catalytic system are mild and easy to control, the catalyst is low in cost and easy to obtain, an experimental operation is simple, green and pollution-free, and product structures are diversified and the like. Moreover, the ethyl alcohol is taken as the solvent; post-treatment is relatively simple; the pollution to the environment is low; the preparation method is beneficial to realization of green synthesis; industrial production is easy to realize.
Description
Technical field：
It is to be related to one kind to use three groups more specifically the present invention relates to a kind of preparation method of benzindole compound
The method for dividing one kettle way to prepare benzindole compound, belongs to chemosynthesis technical field.
Technical background：
During compound containing indoles parent nucleus is universally present in natural products, expand with such as antianxiety, step-down, blood vessel
, resistance amine, anti-inflammatory, the pharmaceutical activity such as antitumor, be organic compound that a class has important biomolecule activity.Therefore, synthesize
Compound with indoles parent nucleus and being oriented to it is constructed and its functionalization is for development methodology of organic synthesis and medicine
Chemistry is significant.
The construction method of classical indole ring is famous Fischer indole synthesis, i.e., experience 3 with reactive ketone with phenylhydrazine,
3- σ are migrated and are obtained Benzazole compounds.Up to the present, the synthetic method of benzazolyl compounds is concentrated mainly on three below side
Face：(1) required substituted radical is first incorporated into substrate, then synthesizes substituted indole, realize indoles parent nucleus diverse location (1,2,3
Position) functionalization.(2) using indoles as raw material, reacted by the Michael of indoles, acylation, bis-indolyl alkyl etc., realize Yin
The functionalization that diindyl is 1 or 3.(3) study on the synthesis of indoles alkaloid.These research and developments indoles functionizing method, be
The synthesis of difference in functionality indoles provides some new synthetic methods, with learning value very high.But current document report
Indoles functionalization be mainly in indoles parent nucleus 1, two or three-digit, the research to other positions functionalization is seldom reported.Yin
The diversity in diindyl substitution region and the diversity of substitution form need further exploration.Research shows, indoles skeleton construct and
Its functionalization is subject to huge limitation, it is impossible to provide the benzazolyl compounds with various structures and bioactivity.Therefore, indoles is developed
The construction method of skeleton, realizes the diversity of the diversity, the diversity in substitution region and substitution form of indole structure, realizes Yin
The functionalization of the diverse location of diindyl ring, with important learning value.
Often there is problems with the synthetic method of existing document report：Multistep reaction accessory substance is more, and post processing is cumbersome,
Gross production rate is relatively low；It is related to some violent experiment conditions, is unfavorable for scale and industrialized production；Catalyst is expensive, and
Many catalyst can not be recycled.We have invented a kind of by the use of lewis acid cheap and easy to get as catalyst, gentle
Experiment condition under three component one kettle ways, high yield obtain benzo [e] benzazolyl compounds synthetic method.
The content of the invention：
First aspect present invention purpose is to provide a kind of preparation method of benzo [e] benzazolyl compounds with high yield,
Benzo [e] benzazolyl compounds being related to, its structural formula is as shown in Equation 1：
In formula 1：Ar is aryl and heterocyclic base；R is alkyl.
The technical scheme that the present invention takes is as follows：
A kind of preparation method of benzo [e] benzazolyl compounds, it is characterised in that comprise the following steps：With aldehyde and its derivative
Thing, 2- naphthylamines and nitroparaffins are raw material, and lewis acid carries out reaction and prepare benzo [e] as catalyst, in ethanol backflow
Benzazolyl compounds.
The principle that the present invention takes is as follows：
The present invention, by lewis acid acid catalysis, synthesizes benzo with aldehyde and its derivative, 2- naphthylamines and nitroparaffins raw material
[e] benzazolyl compounds.The raw material of present invention selection is cheap and easy to get, catalyst efficiency high, simple to operate effective, by molten
Agent, reaction temperature, reaction time control, can make product yield improve a lot, and this method post processing is simple, and reaction condition is gentle
It is easily-controllable, with fine practicality and economic worth.
Reaction equation of the present invention is as follows：
Further it is provided in：
Described reaction raw materials configuration, when aldehyde and its derivative, 2- naphthylamines and nitroparaffins mol ratio are 1:1:When 3, tool
There is optimal yield；
Described reaction temperature is alcohol reflux temperature, and conversion ratio is relatively low when temperature is relatively low, and temperature is higher, there is more pair
Product is generated, therefore, Comprehensive Control reaction temperature and time exist：Reaction temperature is 80 DEG C, and the reaction time is 6-10 hours, is had
Optimum response effect, can effectively improve product yield.
The present invention is preferably with lewis acid Yb (OTf)3It is catalyst, other catalyst bronsted acid (such as hydrochloric acid, sulphur
Acid, glacial acetic acid etc.) and lewis acid (such as alchlor, titanium tetrachloride, ferric trichloride, trifluoromethane sulfonic acid yttrium) catalytic effect
Poor, experiment is confirmed, when lewis acid catalyst consumption is 10mol%, catalytic effect is best.
The present invention can obtain certain product with protic such as water, methyl alcohol, ethanol etc., but be sent out by testing
Existing, the bad yield of substrate contact is relatively low when with water as solvent, and methyl alcohol boiling point is too low, can not obtain preferable yield.It is elected
Other solvents such as tetrahydrofuran, dichloromethane or ethyl acetate etc. are selected, not only reaction effect is not good, and has larger to environment
Side effect.With ethanol as solvent, reaction yield is preferable, and ethanol is green and environment-friendly solvent, does not result in environmental problem.
Prioritizing selection of the present invention is heated to reflux being reacted in ethanol, when being reacted in ethanol, substrate and Louis
This acid catalyst is respectively provided with good dissolubility, and experiment effect is relatively preferable.This reaction subsequent operation is relatively easy, only leads to
Cross pillar layer separation and can obtain purer target compound, with good operability.
Catalyst of the present invention is lewis acid Yb (OTf)3, raw material is cheap and easy to get, prepares simple, and storage is convenient, will not produce
Raw catalyst spoilage problems.We detect that experiment is tied with the substrate of embodiment 1 as model substrates to catalyst catalytic performance
Really show, catalyst Yb (OTf)3With good catalytic effect, other catalyst such as Y (OTf)3、Sc(OTf)3Deng having respectively
The respective weak point such as catalytic effect is good or expensive.
The invention provides a kind of preparation method of benzindole derivative, compared with prior art, with advantages below：
1st, using the response strategy of three components " one kettle way ", the reaction time is shortened, simplifies experimental procedures.
2nd, this reaction with aromatic aldehyde cheap and easy to get, nitroparaffins and 2- naphthylamines be Material synthesis polysubstituted benzo [e] Yin
Indole compound.
3rd, catalyst Yb (OTf)3Excellent catalytic effect, prepare it is simple, preserve convenient, and be unlikely to deteriorate with practicality very high
Property.
4th, reaction condition is gently easily-controllable, is conducive to industrially scalable metaplasia to produce.
Following examples will be helpful to understand the present invention, but be not limited to present disclosure：
Specific embodiment：
Embodiment 1：
1.0mmol benzaldehydes, 1.0mmol 2- naphthylamines and 3.0mmol nitromethanes is weighed successively to be separately added into and fill 3mL
In the reaction tube of ethanol, lewis acid Yb (OTf) is added3Catalyst, shakes up, and is heated to reflux in oil bath, and temperature is 80 DEG C,
TLC tracking test processes, are reacted about 6 hours, and room temperature is cooled to after the completion of question response, and solvent is spin-dried for, and are separated through post layer chromatography
Purification (ethyl acetate：Petroleum ether=1:10-1:4) water white oil, is obtained, yield is 80%.
Product confirms：
Oil,1H NMR(CDCl3,400MHz,ppm):δ 8.48 (br, s, 1H), 8.18 (d, J=8.0Hz, 1H), 7.96
(d, J=8.8Hz, 1H), 7.66-7.69 (m, 3H), 7.52-7.58 (m, 3H), 7.46-7.50 (m, 1H), 7.34-7.45 (m,
2H), 7.19 (d, J=2.0Hz, 1H)；13C NMR(CDCl3,100MHz,ppm):δ137.1,132.9,130.2,129.9,
128.8,128.7,128.3,126.7,125.4,123.8,123.3,123.2,121.5,121.3,119.5,112.9。
Embodiment 2：
1.0mmol p-tolyl aldehydes, 1.0mmol 2- naphthylamines and 3.0mmol nitromethanes are weighed successively is separately added into Sheng
Have in the reaction tube of 3mL ethanol, add lewis acid Yb (OTf)3Catalyst, shakes up, and is heated to reflux in oil bath, and temperature is 80
DEG C, TLC tracking test processes are reacted about 6 hours, and room temperature is cooled to after the completion of question response, and solvent is spin-dried for, through post layer chromatography point
From purification (ethyl acetate：Petroleum ether=1:10-1:4) brown solid, is obtained, yield is 75%.
Product confirms：
Mp:46-48℃；1H NMR(CDCl3,400MHz,ppm):δ 8.48 (br, s, 1H), 8.20 (d, J=8.4Hz,
1H), 7.95 (d, J=7.6Hz, 1H), 7.67 (d, J=8.0Hz, 3H), 7.32-7.42 (m, 5H), 7.17 (d, J=2.4Hz,
1H),2.52(s,3H)；13C NMR(CDCl3,100MHz,ppm):δ136.5,134.1,132.8,130.0,129.7,129.1,
128.9,128.7,127.3,125.2,123.8,123.7,123.3,123.2,121.6,121.2,119.6,112.9。
Embodiment 3：
1.0mmol 2 thiophene carboxaldehydes, 1.0mmol 2- naphthylamines and 3.0mmol nitromethanes are weighed successively is separately added into Sheng
Have in the reaction tube of 3mL ethanol, add lewis acid Yb (OTf)3Catalyst, shakes up, and is heated to reflux in oil bath, and temperature is 80
DEG C, TLC tracking test processes are reacted about 6 hours, and room temperature is cooled to after the completion of question response, and solvent is spin-dried for, through post layer chromatography point
From purification (ethyl acetate：Petroleum ether=1:10-1:4) brown oil, is obtained, yield is 68%.
Product confirms：
Oil；1H NMR(CDCl3,400MHz,ppm):δ8.49(br,s,1H),8.17-8.21(m,1H),7.93-7.95
(m, 1H), 7.67 (d, J=8.8Hz, 1H), 7.52-7.58 (m, 2H), 7.38-7.44 (m, 4H), 7.24 (d, J=2.4Hz,
1H)；13C NMR(CDCl3,100MHz,ppm):δ137.0,132.9,130.1,129.8,128.8,125.6,125.3,
123.8,123.3,122.6,121.7,120.0,117.8,115.5,112.8。
Embodiment 4：
1.0mmol benzaldehydes, 1.0mmol 2- naphthylamines and 3.0mmol nitroethanes is weighed successively to be separately added into and fill 3mL
In the reaction tube of ethanol, lewis acid Yb (OTf) is added3Catalyst, shakes up, and is heated to reflux in oil bath, and temperature is 80 DEG C,
TLC tracking test processes, are reacted about 8 hours, and room temperature is cooled to after the completion of question response, and solvent is spin-dried for, and are separated through post layer chromatography
Purification (ethyl acetate：Petroleum ether=1:10-1:4) brown solid, is obtained, yield is 73%.
Product confirms：
Mp:52-54℃；1H NMR(CDCl3,410MHz,ppm):δ8.17(br,s,1H),7.94(t,J1=6.8Hz, J2
=7.2Hz, 2H), 7.63 (d, J=8.4Hz, 1H), 7.56-7.57 (m, 4H), 7.45-7.50 (m, 2H), 7.38-7.42 (m,
1H),7.29-7.32(m,1H),2.35(s,3H)；13C NMR(CDCl3,100MHz,ppm):δ137.2,131.3,131.2,
130.4,129.8,128.7,128.5,128.3,126.8,125.1,123.3,122.9,122.5,120.9,117.2,
112.4,11.9。
Embodiment 5：
1.0mmol 4-chloro-benzaldehydes, 1.0mmol 2- naphthylamines and 3.0mmol nitroethanes is weighed successively to be separately added into and fill
In the reaction tube of 3mL ethanol, lewis acid Yb (OTf) is added3Catalyst, shakes up, and is heated to reflux in oil bath, and temperature is 80
DEG C, TLC tracking test processes are reacted about 8 hours, and room temperature is cooled to after the completion of question response, and solvent is spin-dried for, through post layer chromatography point
From purification (ethyl acetate：Petroleum ether=1:10-1:4) brown solid, is obtained, yield is 78%.
Product confirms：
Mp:85-86℃；1H NMR(CDCl3,400MHz,ppm):δ 8.28 (br, s, 1H), 7.91 (d, J=8.0Hz,
1H), 7.84 (d, J=8.4Hz, 1H), 7.60 (d, J=8.8Hz, 2H), 7.45-7.52 (m, 5H), 7.32-7.39 (m, 1H),
7.28-7.31(m,1H),2.36(s,3H)；13C NMR(CDCl3,100MHz,ppm):δ135.7,132.7,132.3,131.3,
130.4,129.8,128.8,128.5,128.1,125.2,123.0,122.9,122.7,120.8,116.0,112.2,11.9。
Embodiment 6：
1.0mmol p-tolyl aldehydes, 1.0mmol 2- naphthylamines and 3.0mmol nitroethanes are weighed successively is separately added into Sheng
Have in the reaction tube of 3mL ethanol, add lewis acid Yb (OTf)3Catalyst, shakes up, and is heated to reflux in oil bath, and temperature is 80
DEG C, TLC tracking test processes are reacted about 8 hours, and room temperature is cooled to after the completion of question response, and solvent is spin-dried for, through post layer chromatography point
From purification (ethyl acetate：Petroleum ether=1:10-1:4) brown solid, is obtained, yield is 75%.
Product confirms：
Mp:76-78℃；1HNMR(CDCl3,400MHz,ppm):δ8.26(br,s,1H),7.90(t,J1=6.8Hz, J2
=7.2Hz, 2H), 7.58 (d, J=8.8Hz, 1H), 7.50 (d, J=8.8Hz, 1H), 7.42 (d, J=8.0Hz, 2H), 7.34
(d, J=8.0Hz, 3H), 7.24-7.27 (m, 1H), 2.52 (s, 3H), 2.38 (s, 3H)；13C NMR(CDCl3,100MHz,
ppm):δ136.2,134.0,131.1,130.9,130.3,129.8,129.1,128.6,128.3,125.1,123.2,
122.8,122.4,121.0,117.2,112.2。
Claims (8)
1. a kind of preparation method of benzo [e] benzazolyl compounds, it is characterised in that comprise the following steps：With aldehyde and its derivative,
2- naphthylamines and nitroparaffins are raw material, and lewis acid carries out reaction and prepare benzo [e] indoles as catalyst, in ethanol backflow
Compound.
2. the preparation method of a kind of benzo [e] benzazolyl compounds according to claim 1, it is characterised in that：Described is anti-
Raw material is answered to configure, the mol ratio of aldehyde and its derivative, 2- naphthylamines and nitroparaffins is 1:1:3.
3. the preparation method of a kind of benzo [e] benzazolyl compounds according to claim 1, it is characterised in that：Described is anti-
It is 80 DEG C to answer temperature.
4. the preparation method of a kind of benzo [e] benzazolyl compounds according to claim 1, it is characterised in that：The reaction
Time be 6-8 hours.
5. the preparation method of a kind of benzo [e] benzazolyl compounds according to claim 1, it is characterised in that：The catalysis
Agent
It is lewis acid Yb (OTf)3。
6. a kind of preparation method of benzo [e] benzazolyl compounds according to claim 1 or 5, it is characterised in that：It is described to urge
Agent consumption is 10 mol%.
7. the preparation method of a kind of benzo [e] benzazolyl compounds according to claim 1, it is characterised in that：The reaction
Carried out under conditions of solvent, the solvent is ethanol, the reaction temperature is alcohol reflux temperature.
8. the preparation method of a kind of benzo [e] benzazolyl compounds according to claim 1, it is characterised in that：Including following
Step：1.0 mmol aromatic aldehydes, 1.0 mmol 2- naphthylamines and 3.0 mmol nitroparaffins are weighed successively to be separately added into and fill 3mL
In the reaction tube of ethanol, shake up, be heated to reflux in oil bath, alcohol reflux temperature is 80 DEG C, TLC tracking test processes, reaction
About 6-8 hours, room temperature is cooled to after the completion of question response, solvent is spin-dried for, post layer chromatography separating-purifying（Ethyl acetate：Petroleum ether
= 1:10-1:4）, obtain target product.
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| CN201611233252.4A CN106699633A (en) | 2016-12-28 | 2016-12-28 | Preparation method for benzo [e] indole compound |
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| CN201611233252.4A CN106699633A (en) | 2016-12-28 | 2016-12-28 | Preparation method for benzo [e] indole compound |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116532109A (en) * | 2023-05-04 | 2023-08-04 | 济南大学 | Preparation method of supported catalyst, obtained product and application |
-
2016
- 2016-12-28 CN CN201611233252.4A patent/CN106699633A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| FUREN ZHANG,等: "Facile synthesis of benzoindoles and naphthofurans through carbonaceous material-catalyzed cyclization of naphthylamines/naphthols with nitroolefins in water", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 * |
| 小野嘉夫: "《固体碱催化》", 31 May 2013, 复旦大学出版社 * |
| 张富仁,等: "手性三氟磺酸盐催化合成氢化吡咯衍生物", 《第十八届全国金属有机化学学术讨论会》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116532109A (en) * | 2023-05-04 | 2023-08-04 | 济南大学 | Preparation method of supported catalyst, obtained product and application |
| CN116532109B (en) * | 2023-05-04 | 2024-05-28 | 济南大学 | Preparation method of supported catalyst, obtained product and application |
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