CN104592088A - Method for preparing 3-amino alkyl indole through catalyzing by lauric acid - Google Patents
Method for preparing 3-amino alkyl indole through catalyzing by lauric acid Download PDFInfo
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- CN104592088A CN104592088A CN201510011864.8A CN201510011864A CN104592088A CN 104592088 A CN104592088 A CN 104592088A CN 201510011864 A CN201510011864 A CN 201510011864A CN 104592088 A CN104592088 A CN 104592088A
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- China
- Prior art keywords
- aromatic aldehyde
- indoles
- preparation
- lauric acid
- amine alkyl
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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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Abstract
The invention relates to a preparation method of organically synthesized midbody 3-amino alkyl indole. According to the preparation method, lauric acid is directly used as a catalyst, and the 3-amino alkyl indole is prepared by aromatic aldehyde, indole and secondary amine through a single-step method. The preparation method has the characteristics of being free of catalyst preparation, safe, low in cost, mild in reaction condition, simple to operate, free of organic solvent in the reaction process and relatively high in productivity.
Description
Technical field
The present invention relates to a kind of preparation method of indole derivatives, particularly relating to a kind of employing linear saturated fatty acids lauric acid is catalyzer, is prepared the method for 3-amine alkyl-indol by aromatic aldehyde, indoles and secondary amine.
Background technology
Indoles is important pharmaceutical intermediate, and its structural unit is present in many important natural product.In the known natural indole derivatives of kind more than 3000, kind more than 40 is had to be therapeutic type medicine.Many medicines all contain indole structure unit in the market, and wherein 3-substituted indole derivative occupies certain ratio, and such as tryptophane is necessary amino acid, is also the biosynthesizing precursor of various tryptamines, indoles; Psilocybin is that some toadstool causes unreal composition; N-dimethylserotonin has anesthetic action; Brazil's alkali is the phytoalexin of opposing microbial challenge; 5-hydroxyl look ammonia is important transmitter substance, and its derivative can treat migraine; INDOMETHACIN is used for the treatment of rheumatic arthritis etc.The synthesis of current most of 3-amine alkyl-indol compound is carried out in organic solvent, produces VOCs and pollutes, do not meet the Economic Development Mode of green low-carbon to environment.
Summary of the invention
The object of this invention is to provide a kind of without the need to preparation, the inexpensive saturated fatty acid lauric acid of safety as catalyzer, with aromatic aldehyde, indoles and secondary amine for raw material, in water, single stage method gentleness prepares the method for 3-amine alkyl-indol.
Technical solution of the present invention is as follows:
The present invention directly adopts aromatic aldehyde, indoles and secondary amine to react in water, and by saturated fatty acid lauric acid as catalyzer, stirring reaction prepares 3-amine alkyl-indol.Wherein said aromatic aldehyde, its R is hydrogen, halogen, alkoxyl group or nitro.Reaction formula of the present invention is as follows:
The present invention prepares the method for 3-amine alkyl-indol, and step is as follows:
1) in reaction flask, aromatic aldehyde, methylphenylamine, catalyzer lauric acid and a certain amount of aqueous solvent is added, wherein aromatic aldehyde and methylphenylamine mol ratio are 1: 1.0 ~ 1.5, aromatic aldehyde and lauric mol ratio are 1: 0.2, stirring reaction 5-10min under 80 DEG C of conditions, obtain white opacity thing imine intermediate, add the indoles equal with aromatic aldehyde mole number afterwards and continue stirring reaction certain hour, TLC follows the tracks of reaction.
2) reaction adds extraction into ethyl acetate after terminating and uses anhydrous sodium sulfate drying organic phase, steams after desolventizing and obtains crude product.Crude product sherwood oil and ethyl acetate are done after eluent carries out column chromatography for separation and are obtained red-purple solid 3-amine alkyl-indol.
Described step 1) preferably aromatic aldehyde, methylphenylamine and indoles mol ratio are 1: 1.2: 1;
Preferably, described step 1) catalyzer lauric acid is 20% relative to the molecular fraction of aromatic aldehyde.
The present invention has catalyzer without the need to preparation, and safety is inexpensive, reaction times short, mild condition, environmental friendliness, simple to operate, productive rate comparatively advantages of higher.
Embodiment
Below in conjunction with embodiment, the present invention is described further, but be not limited thereto.
The synthesis of embodiment 1, N-(3-indyl-phenyl) methyl-N-methyl aniline, structural formula is as follows:
1.0mmol phenyl aldehyde, 1.2mmol methylphenylamine, 0.2mmol lauric acid and 2.0ml aqueous solvent is added in 25ml round-bottomed flask, stirring reaction 5 minutes when 80 DEG C, add 1.0mmol indoles afterwards, continue stirring reaction 3.5 hours, the completely rear stopped reaction of TLC detection reaction.After being cooled to room temperature, adding extraction into ethyl acetate and use anhydrous sodium sulfate drying organic phase, adopting Rotary Evaporators removing solvent ethyl acetate to obtain crude product.Crude product ethyl acetate and sherwood oil do eluent (ethyl acetate: sherwood oil=1: 4), adopt gradient elution, after carrying out column chromatography for separation (200-300 order silica gel), obtain red brown solid N-(3-indyl-phenyl) the methyl-N-methyl aniline 244.0mg that purity is 99%, isolated yield is 78.1%, and fusing point is 128-130 DEG C.
The qualification of N-(3-indyl-phenyl) methyl-N-methyl aniline:
Infrared spectrogram IR (KBr) v:735,1453,1509,1612,2927,3363,3409cm
-1.
Nuclear magnetic resonance data:
1h NMR (500MHz, CDCl
3): δ 2.77 (s, 3H), 5.54 (s, 1H), 6.52 (d, J=8.0Hz, 3H), 6.69-6.83 (m, 3H), 7.04 (d, J=10.0Hz, 2H), 7.13-7.35 (m, 6H), 7.57 (s, 1H), 7.88 (s, 1H) ppm.
13c NMR (125MHz, CDCl
3): δ 30.6,47.8,111.0,112.4,119.3,119.8,122.1,124.0,126.8,128.1,128.9,129.5,130.2,133.1,136.6,144.9,147.9.
Product is consistent with bibliographical information through qualification.
The synthesis of embodiment 2, N-(3-indyl-(4-nitrophenyl)) methyl-N-methyl aniline, structural formula is as follows:
1.0mmol paranitrobenzaldehyde, 1.2mmol methylphenylamine, 0.2mmol lauric acid and 2.0ml aqueous solvent is added in 25ml round-bottomed flask, stirring reaction 5 minutes when 80 DEG C, add 1.0mmol indoles afterwards, continue stirring reaction 2.5 hours, the completely rear stopped reaction of TLC detection reaction.After being cooled to room temperature, adding extraction into ethyl acetate and use anhydrous sodium sulfate drying organic phase, adopting Rotary Evaporators removing solvent ethyl acetate to obtain crude product.Crude product ethyl acetate and sherwood oil do eluent (ethyl acetate: sherwood oil=1: 4), adopt gradient elution, after carrying out column chromatography for separation (200-300 order silica gel), obtain red brown solid N-(3-indyl-(4-nitrophenyl)) the methyl-N-methyl aniline 286.6mg that purity is 99%, isolated yield is 80.2%, and fusing point is 60-62 DEG C.
The qualification of N-(3-indyl-(4-nitrophenyl)) methyl-N-methyl aniline:
Infrared spectrogram IR (KBr) v:739,1347,1456,1521,1608,2935,3411cm
-1.
Nuclear magnetic resonance data:
1h NMR (500MHz, CDCl
3): δ 2.85 (s, 3H), 5.57 (s, 1H), 6.49-6.54 (m, 3H), 6.89-7.00 (m, 3H), 7.12-7.19 (m, 2H), 7.28-7.53 (m, 4H), 8.01 (s, 1H), 8.13 (d, J=10.0Hz, 2H);
13c NMR (125MHz, CDCl
3): δ 31.1,47.6,111.0,112.3,119.6,120.2,122.3,123.5,124.0,126.7,129.3,130.8,136.7,146.2,147.9,152.2.
Product is consistent with bibliographical information through qualification.
Embodiment 3, N-(synthesis of 3-indyl-(4-p-methoxy-phenyl) methyl-N-methyl aniline, structural formula is as follows:
1.0mmol aubepine, 1.2mmol methylphenylamine, 0.2mmol lauric acid and 2.0ml aqueous solvent is added in 25ml round-bottomed flask, stirring reaction 5 minutes when 80 DEG C, add 1.0mmol indoles afterwards, continue stirring reaction 4.5 hours, the completely rear stopped reaction of TLC detection reaction.After being cooled to room temperature, adding extraction into ethyl acetate and use anhydrous sodium sulfate drying organic phase, adopting Rotary Evaporators removing solvent ethyl acetate to obtain crude product.Crude product ethyl acetate and sherwood oil do eluent (ethyl acetate: sherwood oil=1: 4), adopt gradient elution, after carrying out column chromatography for separation (200-300 order silica gel), obtain red brown solid N-(3-indyl-(4-p-methoxy-phenyl) methyl-N-methyl aniline 234.5mg that purity is 98.5%, isolated yield is 68.5%, and fusing point is 142-143 DEG C.
N-(qualification of 3-indyl-(4-p-methoxy-phenyl) methyl-N-methyl aniline:
Infrared spectrogram IR (KBr) v:IR (KBr): 745,1026,1181,1451,1510,1616,2925,3041,3403cm
-1.
Nuclear magnetic resonance data:
1h NMR (500MHz, CDCl
3): δ 2.79 (s, 3H), 3.77 (s, 3H), 5.53 (s, 1H), 6.50-6.57 (m, 2H), 6.82-6.89 (m, 3H), 6.98-7.07 (m, 3H), 7.13 (d, J=10.0,3H), 7.23-7.39 (m, 3H), 7.87 (s, 1H);
13c NMR (125MHz, CDCl
3): δ 30.8,47.7,55.1,111.2,112.5,113.6,119.7,119.8,121.8,123.5,123.7,127.0,129.6,129.7,133.1,136.8,147.5,157.6.
Product is consistent with bibliographical information through qualification.
Content disclosed according to the present invention, those skilled in the art can apply the present invention to greatest extent.Therefore, above-mentioned preferred specific embodiment only illustrates, but not limits the scope of the invention by any way.
Claims (3)
1. one kind with aromatic aldehyde, indoles and secondary amine for the method for 3-amine alkyl-indol prepared by raw material, when it is characterized in that 80 DEG C, aromatic aldehyde and methylphenylamine are added to the water, add lipid acid simultaneously and make catalyst reaction 5 minutes, add indoles afterwards and continue stirring reaction 2.5-6 hour, obtain thick product, wherein aromatic aldehyde, methylphenylamine and indoles mol ratio are 1: 1.2: 1, and described aromatic aldehyde is the aromatic aldehyde of various replacement, and its R is hydrogen, halogen, alkoxyl group or nitro.Crude by column chromatography obtains 3-amine alkyl-indol sterling after being separated
2. the preparation method of 3-amine alkyl as claimed in claim 1, is characterized in that described water is distilled water.
3. the preparation method of 3-amine alkyl as claimed in claim 1, it is characterized in that described catalyzer lipid acid is lauric acid, its optimum amount is 20% of aromatic aldehyde molecular fraction.
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| CN201510011864.8A CN104592088B (en) | 2015-01-05 | 2015-01-05 | The method that laurel acid catalysis prepares 3- amine alkyl-indol |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020198252A1 (en) * | 2001-05-24 | 2002-12-26 | Joseph Payack | Process for the preparation of alkylamine substituted indoles |
| CN102015642A (en) * | 2008-02-19 | 2011-04-13 | 赛诺菲-安万特 | Novel 3-aminoalkyl-1,3-dihydro-2H-indol-2-one derivatives, preparation thereof and therapeutic use thereof |
| CN103342675A (en) * | 2013-05-17 | 2013-10-09 | 安徽工业大学 | Preparation method of diindolylmethane derivative through catalysis |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020198252A1 (en) * | 2001-05-24 | 2002-12-26 | Joseph Payack | Process for the preparation of alkylamine substituted indoles |
| CN102015642A (en) * | 2008-02-19 | 2011-04-13 | 赛诺菲-安万特 | Novel 3-aminoalkyl-1,3-dihydro-2H-indol-2-one derivatives, preparation thereof and therapeutic use thereof |
| CN103342675A (en) * | 2013-05-17 | 2013-10-09 | 安徽工业大学 | Preparation method of diindolylmethane derivative through catalysis |
Non-Patent Citations (5)
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Granted publication date: 20190101 Termination date: 20200105 |