CN103554002B - 1-Phenylindole and preparation method thereof - Google Patents

1-Phenylindole and preparation method thereof Download PDF

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Publication number
CN103554002B
CN103554002B CN201310463193.XA CN201310463193A CN103554002B CN 103554002 B CN103554002 B CN 103554002B CN 201310463193 A CN201310463193 A CN 201310463193A CN 103554002 B CN103554002 B CN 103554002B
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Prior art keywords
phenylindole
bromobenzene
reaction
indoles
cuprous chloride
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CN103554002A (en
Inventor
宋国强
唐龙
曹引梅
冯筱晴
陈鹏
魏涛
沈梦笔
郭文驿
孟凯成
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Changzhou University
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Changzhou University
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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
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)

Abstract

1-Phenylindole of the present invention and preparation method thereof, belongs to organic synthesis field.The present invention is with indoles and bromobenzene for starting raw material, and bromobenzene is from as reaction solvent, and cuprous chloride is catalyzer, and potassium hydroxide is acid binding agent, L-PROLINE is additive synthesis 1-Phenylindole.Instant invention overcomes many deficiencies of prior art, reaction solvent DMSO, DMF etc. in original process are replaced to make solvent with reaction raw materials bromobenzene, copper class catalyzer is recyclable to be reused, productive rate reaches more than 90%, the synthesis cost of 1-Phenylindole can be made generally greatly to reduce, there is good industrial prospect.

Description

1-Phenylindole and preparation method thereof
Technical field
The present invention relates to a kind of 1-Phenylindole and preparation method thereof, belong to organic synthesis field.
Background technology
Benzazole compounds is an important branch in heterogeneous ring compound, because it has various physiologically active, so be widely used as the intermediate into medicine, agricultural chemicals, spices, dyestuff and other fine chemical products.The compounds of this invention 1-Phenylindole is not only the important source material of other indole derivatives of preparation, or (iminostilbene not only itself can be used for prevention and therapy hepatitis C to the important source material of synthesis medicine intermediate iminostilbene, or the important intermediate of synthesis antiepileptic drug Carbamzepine, oxcarbazepine and thymoleptic imipramine), therefore, the synthesis of 1-Phenylindole is very important.
Synthesis report (the MonatshChem of 1-Phenylindole (1), 2011,142:801-806, SynthCommun, 2012,42:114-121, ChemCatChem, 2010,2:1312-1317, ChinChemLett, 2006,17 (3): 313-316, CN, 101463010A.2009-06-24. and relevant quoted passage) more be that mineral alkali or organic bases are acid binding agent with iodobenzene and indoles for starting raw material, copper and copper compounds are catalyzer, and DMSO, DMF, ethylene glycol etc. are made solvent reaction 24-48h and obtained 1-Phenylindole.This reaction shortcoming or deficiency have: (1) raw material iodobenzene and catalyzer cuprous iodide expensive, not easily obtain; (2) in reaction, by product is more, and indoles cannot not react completely all the time, affects output; (3) reaction in use DMSO, DMF, ethylene glycol equal solvent difficulty reclaim reuse, cost is high, pollution is heavy; (4) reaction time is long, does not meet industrialized production condition.
Structural formula 11-Phenylindole
Summary of the invention
For solving the problem, the problems such as namely supplementary material is expensive, pollution is heavy, raw material reaction is not complete, reaction time is long, the invention provides a kind of method of low cost, low stain, the synthesis 1-Phenylindole in short reaction cycle.
The present invention is with indoles and bromobenzene for starting raw material, and bromobenzene is from as reaction solvent, and cuprous chloride is catalyzer, and potassium hydroxide is acid binding agent, L-PROLINE is additive synthesis 1-Phenylindole.Process provides a kind of low cost, pollute less, the method for high yield synthesis 1-Phenylindole.
The reaction formula of synthesis is as follows:
The synthetic method of 1-Phenylindole of the present invention, carry out according to following step:
(1) in four-hole boiling flask, add bromobenzene and indoles, stir, be heated to 150-160 DEG C of backflow;
(2) add the reaction of cuprous chloride, L-PROLINE and potassium hydroxide 8-12 hour, TLC respectively and follow the tracks of reaction; Treat that indole reaction is complete, slightly cold, filtration, brown solid washes with water, and insolubles is cuprous chloride, and dry, recovery is reused, and organic layer filtrate water washs three times, and bromobenzene is reclaimed in first underpressure distillation, and last underpressure distillation obtains 1-Phenylindole.
Wherein in step (1), namely bromobenzene is reaction raw materials, and be also reaction solvent, the weightmeasurement ratio of indoles and bromobenzene is: 1/ (10-30) (g/mL).
Wherein in step (2), the mol ratio of cuprous chloride and indoles is 1:4-1:20.
Wherein in step (2), the mol ratio of L-PROLINE and indoles is 1:2-1:10.
Wherein in step (2), the mol ratio of potassium hydroxide and indoles is: 2:1-10:1.
Instant invention overcomes many deficiencies of prior art; reaction solvent DMSO, DMF etc. in original process are replaced to make solvent with reaction raw materials bromobenzene; raw material indole reaction not only can be made complete; but also recyclablely to reuse, protection of the environment, cost-saving; copper class catalyzer is recyclable to be reused; productive rate reaches more than 90%, the synthesis cost of 1-Phenylindole can be made generally greatly to reduce, have good industrial prospect.
Embodiment
Describe the present invention with specific embodiment.Protection scope of the present invention is not limited with embodiment, but is limited by claim.
Embodiment 1
(1) in four-hole boiling flask, add indoles 11.7g (0.1mol), bromobenzene 117mL, stir, be heated to 150-160 DEG C of backflow.(2) add cuprous chloride 2.47g (0.025mol), L-PROLINE 5.75g (0.05mol) and potassium hydroxide 11.22g (0.2mol) respectively and react 8-12 hour, TLC follows the tracks of reaction, treats that indole reaction is complete, slightly cold, filtration, brown solid washes with water, insolubles is cuprous chloride, and dry, recovery is reused, organic layer filtrate water washs, bromobenzene is reclaimed in underpressure distillation, and last underpressure distillation obtains 1-Phenylindole 17.76g, productive rate 92.02%.
Embodiment 2
(1) in four-hole boiling flask, add indoles 11.7g (0.1mol), bromobenzene 351mL, stir, be heated to 150-160 DEG C of backflow.(2) add cuprous chloride 0.49g (0.005mol), L-PROLINE 1.15g (0.01mol) and potassium hydroxide 56.11g (1mol) respectively and react 8-12 hour, TLC follows the tracks of reaction, treats that indole reaction is complete, slightly cold, filtration, brown solid washes with water, insolubles is cuprous chloride, and dry, recovery is reused, organic layer filtrate water washs, bromobenzene is reclaimed in underpressure distillation, and last underpressure distillation obtains 1-Phenylindole 17.17g, productive rate 88.96%.
Embodiment 3
(1) in four-hole boiling flask, add indoles 11.7g (0.1mol), bromobenzene 175.5mL, stir, be heated to 150-160 DEG C of backflow.(2) add cuprous chloride 0.99g (0.01mol), L-PROLINE 2.30g (0.02mol) and potassium hydroxide 28.05g (0.5mol) respectively and react 8-12 hour, TLC follows the tracks of reaction, treats that indole reaction is complete, slightly cold, filtration, brown solid washes with water, insolubles is cuprous chloride, and dry, recovery is reused, organic layer filtrate water washs, bromobenzene is reclaimed in underpressure distillation, and last underpressure distillation obtains 1-Phenylindole 17.19g, productive rate 89.06%.
Embodiment 4
(1) in four-hole boiling flask, add indoles 11.7g (0.1mol), bromobenzene 234mL, stir, be heated to 150-160 DEG C of backflow.(2) add cuprous chloride 0.66g (0.0066mol), L-PROLINE 1.44g (0.012mol) and potassium hydroxide 44.88g (0.8mol) respectively and react 8-12 hour, TLC follows the tracks of reaction, treats that indole reaction is complete, slightly cold, filtration, brown solid washes with water, insolubles is cuprous chloride, and dry, recovery is reused, organic layer filtrate water washs, bromobenzene is reclaimed in underpressure distillation, and last underpressure distillation obtains 1-Phenylindole 17.04g, productive rate 88.29%.
Embodiment 5
(1) in four-hole boiling flask, add indoles 11.7g (0.1mol), bromobenzene 175.5mL, stir, be heated to 150-160 DEG C of backflow.(2) add cuprous chloride 0.49g (0.005mol), L-PROLINE 1.15g (0.01mol) and potassium hydroxide 11.22g (0.2mol) respectively and react 8-12 hour, TLC follows the tracks of reaction, treats that indole reaction is complete, slightly cold, filtration, brown solid washes with water, insolubles is cuprous chloride, and dry, recovery is reused, organic layer filtrate water washs, bromobenzene is reclaimed in underpressure distillation, and last underpressure distillation obtains 1-Phenylindole 17.37g, productive rate 90%.

Claims (1)

  1. The synthetic method of 1.1-Phenylindole, is characterized in that carrying out according to following step:
    (1) in four-hole boiling flask, add bromobenzene and indoles, stir, be heated to 150-160 DEG C of backflow;
    (2) add the reaction of cuprous chloride, L-PROLINE and potassium hydroxide 8-12 hour, TLC respectively and follow the tracks of reaction; Treat that indole reaction is complete, slightly cold, filtration, brown solid washes with water, and insolubles is cuprous chloride, and dry, recovery is reused, and organic layer filtrate water washs, and bromobenzene is reclaimed in underpressure distillation, and last underpressure distillation obtains 1-Phenylindole;
    Wherein in step (1), the weightmeasurement ratio of indoles and bromobenzene is: 1g/ (10-30) mL;
    In step (2), the mol ratio of cuprous chloride and indoles is 1:4-1:20;
    Wherein in step (2), the mol ratio of L-PROLINE and indoles is 1:2-1:10;
    Wherein in step (2), the mol ratio of potassium hydroxide and indoles is: 2:1-10:1.
CN201310463193.XA 2013-10-08 2013-10-08 1-Phenylindole and preparation method thereof Expired - Fee Related CN103554002B (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998008842A1 (en) * 1996-08-29 1998-03-05 Takeda Chemical Industries, Ltd. Cyclic ether compounds as sodium channel modulators
CN1518534A (en) * 2001-04-24 2004-08-04 麻省理工学院 Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds
CN101091923A (en) * 2007-07-13 2007-12-26 浙江大学 Carbon nitrogen coupling reaction catalyst composed of heterocycle functional group 1,3 diketone and halogenated univalence copper, and preparation method
WO2008004088A2 (en) * 2006-07-05 2008-01-10 Centre National De La Recherche Scientifique (C.N.R.S.) Iron-copper co-catalyzed process for carbon-carbon or carbon-heteroatom bonding
CN102382058A (en) * 2011-08-26 2012-03-21 浙江工业大学 Preparation method of N-aryl-heterocyclic nitrogen compound

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998008842A1 (en) * 1996-08-29 1998-03-05 Takeda Chemical Industries, Ltd. Cyclic ether compounds as sodium channel modulators
CN1518534A (en) * 2001-04-24 2004-08-04 麻省理工学院 Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds
WO2008004088A2 (en) * 2006-07-05 2008-01-10 Centre National De La Recherche Scientifique (C.N.R.S.) Iron-copper co-catalyzed process for carbon-carbon or carbon-heteroatom bonding
CN101091923A (en) * 2007-07-13 2007-12-26 浙江大学 Carbon nitrogen coupling reaction catalyst composed of heterocycle functional group 1,3 diketone and halogenated univalence copper, and preparation method
CN102382058A (en) * 2011-08-26 2012-03-21 浙江工业大学 Preparation method of N-aryl-heterocyclic nitrogen compound

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CuI/Proline-catalyzed N-Arylation of Nitrogen Heterocycles;Wei DENG等;《Chinese Chemical Letters》;20061231;第17卷(第3期);313-316 *

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