CN104693091A - Synthetic method of 4-hydroxy-indole - Google Patents
Synthetic method of 4-hydroxy-indole Download PDFInfo
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- CN104693091A CN104693091A CN201310670561.8A CN201310670561A CN104693091A CN 104693091 A CN104693091 A CN 104693091A CN 201310670561 A CN201310670561 A CN 201310670561A CN 104693091 A CN104693091 A CN 104693091A
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- synthetic method
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- 0 *c1cc(O)ccc1 Chemical compound *c1cc(O)ccc1 0.000 description 1
- HJSLFCCWAKVHIW-UHFFFAOYSA-N O=C(CCC1)CC1=O Chemical compound O=C(CCC1)CC1=O HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 description 1
- RGZJJSULCNPOOQ-UHFFFAOYSA-N O=C1C2C=CNC2CCC1 Chemical compound O=C1C2C=CNC2CCC1 RGZJJSULCNPOOQ-UHFFFAOYSA-N 0.000 description 1
- AVLLVOJKDJJUTK-UHFFFAOYSA-N OC(C1=COC(CCC2)C1C2=O)=O Chemical compound OC(C1=COC(CCC2)C1C2=O)=O AVLLVOJKDJJUTK-UHFFFAOYSA-N 0.000 description 1
- GHMLBKRAJCXXBS-UHFFFAOYSA-N Oc1cccc(O)c1 Chemical compound Oc1cccc(O)c1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
Abstract
The invention discloses a synthetic method of 4-hydroxy-indole. The synthetic method comprises the following steps: performing dehydroisomerization reaction on indole-4-one and a Pd/C catalyst in a solvent under the protection of an inert gas atmosphere, and performing silica gel column separation on the reaction product to obtain a high-purity 4-hydroxy-indole product. The synthetic method has the characteristics of high yield, easy product separation and few byproducts and can be directly used for industrial production.
Description
Technical field
The present invention relates to a kind of synthetic method of 4-oxyindole, belong to technical field of fine; Specifically relate to adopt in indoles-4-ketone and the solvent of Pd/C catalyzer under atmosphere of inert gases is protected and carry out dehydroisomerization reaction, reaction product is separated through silicagel column and obtains 4-oxyindole, is a kind of new reaction route and product separation mode.
Background technology
4-oxyindole (4-Hydroxyindole) is a kind of fine chemical product of high added value, and its outward appearance is faint yellow or off-white color crystalline powder, is slightly soluble in water, is dissolved in acetone, is mainly used to be used as intermediate in synthesis medicine intermediate and organic synthesis.
The industrial production producer of current domestic 4-oxyindole is less, be small serial production, the synthesis technique adopted is that raw material obtains 1 through catalytic hydrogenation, isomerization with Resorcinol, hydroresorcinol, be that raw material obtains Pyruvic Acid Ethyl ester through bromination again with ethyl lactate, then the two cyclization is obtained 4-oxo tetrahydrochysene left Malong carboxylic acid, added in the saturated methanol solution of ammonia, reacting by heating in autoclave, generate 4-oxo tetrahydro indole, obtain 4-oxyindole finally by dehydrogenation-isomerization, synthetic route is such as formula 1.
Formula 1.4-oxyindole synthetic route
Chinese patent CN101195600A
[2]disclose a kind of method preparing 4-oxyindole, the method is by 4-oxo-1,5,6,7-tetrahydro indole is in catalyzer and diethylene glycol dimethyl ether or diethylene glycol monomethyl ether solvent, 3 ~ 10%Pd/ catalyzer carries out catalytic dehydrogenating reaction, obtains 4-oxyindole 53% ~ 55% mass yield through distillation process.
More than synthesize the shortcoming that existing for the method for 4-oxyindole, yield is low, product separation is difficult, by-product is many.
Summary of the invention
In order to overcome in current 4-oxyindole synthetic method, yield is low, product separation is difficult, by product indoles is separated the deficiencies such as difficult, the invention provides a kind of high yield, product is easily separated, by-product is few and segregative 4-oxyindole synthetic method, can be directly used in suitability for industrialized production.
Technical scheme of the present invention is: a kind of synthetic method of 4-oxyindole; it is characterized in that: adopt in a kettle. in indoles-4-ketone and the solvent of Pd/C catalyzer under atmosphere of inert gases is protected and carry out dehydroisomerization reaction, reaction product is separated through silicagel column and obtains 4-oxyindole.
Temperature of reaction is 50 ~ 370 DEG C, and reaction pressure is 0.01 ~ 10.5MPa, and the reaction times is 2 ~ 100h.
Catalyzer is Pd content is 0.5% ~ 10%Pd/C catalyzer.
The mass ratio of indoles-4-ketone and solvent is 1: 2 ~ 25.
The mass ratio of indoles-4-ketone and catalyzer is 1: 0.001 ~ 2.
Solvent is one or more mixing in dimethylbenzene, trimethylbenzene, phenylate class, 2,6-dimethyl-4 heptanone.
Reaction process needs to protect with rare gas element.
Product separation adopts silicagel column to be separated, flash liberation developping agent selects sherwood oil to isolate reaction solvent, and secondary separation developping agent selects sherwood oil and methylene dichloride (sherwood oil and methylene chloride volume proportional range 8 ~ 1: 1) to isolate product 4-oxyindole.
Production cost of the present invention is low, and catalyzer is recyclable, and yield is high, and product is easily separated, has the stronger market competitiveness, easy industrial production.
Accompanying drawing explanation
Fig. 1 4-oxyindole H NMR spectrogram;
Fig. 2 4-oxyindole H NMR spectrogram;
Fig. 3 4-oxyindole H NMR spectrogram.
Embodiment
Embodiment 1:
10g indoles-4-ketone is added in 500ml magnetic agitation still, 0.1g5%Pd/C catalyzer, dimethylbenzene and 2, 6-dimethyl-4 heptanone equal-volume mixed solvent 200ml, at 120 DEG C, 6h is reacted under 0.1MPa nitrogen protection pressure condition, catalyzer is filtered out after reaction, filtrate carries out post separation, first sherwood oil is selected to isolate solvent xylene and 2, 6-dimethyl-4 heptanone, sherwood oil and ethylene dichloride (volume ratio is 4:1) is used to isolate product and then, product entered distillation drying and obtained 6.7g, mass yield is 67%, product is through H NMR analysis confirmation (Fig. 1), purity is greater than 99.0%.
Embodiment 2:
100g indoles-4-ketone is added in 3000ml magnetic agitation still, 0.5g10%Pd/C catalyzer, dimethylbenzene and phenyl ether equal-volume mixed solvent 2000ml, at 150 DEG C, 10h is reacted under 0.05MPa nitrogen protection pressure condition, catalyzer is filtered out after reaction, filtrate carries out post separation, first sherwood oil is selected to isolate solvent xylene and phenyl ether, sherwood oil and ethylene dichloride (volume ratio is 4:1) is used to isolate product and then, product entered distillation drying and obtained 65.5g, mass yield is 65.5%, product is through H NMR analysis confirmation (Fig. 2), purity is greater than 99.0%.
Embodiment 3:
100g indoles-4-ketone, 5g1%Pd/C catalyzer, sym-trimethylbenzene solvent 2000ml is added in 3000ml magnetic agitation still; 150 DEG C, react 10h under 0.05MPa nitrogen protection pressure condition; catalyzer is filtered out after reaction; filtrate carries out post separation; first sherwood oil is selected to isolate solvent xylene and phenyl ether; sherwood oil and ethylene dichloride (volume ratio is 4: 1) is used to isolate product and then; product entered distillation drying and obtained 63.2g; mass yield is 63.2%; product purity is through H NMR analysis confirmation (Fig. 3), and purity is greater than 99.0%.
Claims (9)
1. a synthetic method for 4-oxyindole, is characterized in that: adopt in a kettle. in indoles-4-ketone and the solvent of Pd/C catalyzer under atmosphere of inert gases is protected and carry out dehydroisomerization reaction, and reaction product is separated through silicagel column and obtains 4-oxyindole.
2. require described synthetic method according to right 1, it is characterized in that: temperature of reaction is 50 ~ 370 DEG C, reaction pressure is 0.01 ~ 10.5MPa, and the reaction times is 2 ~ 100h.
3. require described synthetic method according to right 1, it is characterized in that: catalyzer to be Pd mass content be 0.5% ~ 10% Pd/C catalyzer.
4. require described synthetic method according to right 1, it is characterized in that: the mass ratio of indoles-4-ketone and solvent is 1:2 ~ 25.
5. require described synthetic method according to right 1, it is characterized in that: the mass ratio of indoles-4-ketone and catalyzer is 1:0.001 ~ 2.
6. require described synthetic method according to right 1, it is characterized in that: solvent is one or two or more kinds mixing in dimethylbenzene, trimethylbenzene, phenylate class, 2,6-dimethyl-4 heptanone.
7. require described synthetic method according to right 1, it is characterized in that: reaction process needs to protect with rare gas element, described rare gas element is any one in nitrogen, argon gas, helium.
8. require described synthetic method according to right 1, it is characterized in that: product separation adopts silicagel column to be separated, one or both mixing in sherwood oil and methylene dichloride selected by developping agent.
9. require described separation method according to right 1, it is characterized in that: product separation adopts silicagel column to be separated, flash liberation developping agent selects sherwood oil to isolate reaction solvent, and secondary separation developping agent selects sherwood oil and methylene dichloride (sherwood oil and methylene chloride volume proportional range 8 ~ 1: 1) to isolate product 4-oxyindole.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201310670561.8A CN104693091A (en) | 2013-12-10 | 2013-12-10 | Synthetic method of 4-hydroxy-indole |
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| CN201310670561.8A CN104693091A (en) | 2013-12-10 | 2013-12-10 | Synthetic method of 4-hydroxy-indole |
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| CN104693091A true CN104693091A (en) | 2015-06-10 |
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| CN201310670561.8A Pending CN104693091A (en) | 2013-12-10 | 2013-12-10 | Synthetic method of 4-hydroxy-indole |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60146870A (en) * | 1984-01-06 | 1985-08-02 | Kanegafuchi Chem Ind Co Ltd | Production of 4-hydroxyindole |
| JPH04208262A (en) * | 1990-11-30 | 1992-07-29 | Nippon Zeon Co Ltd | Production of 4-hydroxyindoles |
| CN101195600A (en) * | 2007-12-14 | 2008-06-11 | 常州市阳光精细化工有限公司 | Method for producing 4-hydroxyindole |
-
2013
- 2013-12-10 CN CN201310670561.8A patent/CN104693091A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60146870A (en) * | 1984-01-06 | 1985-08-02 | Kanegafuchi Chem Ind Co Ltd | Production of 4-hydroxyindole |
| JPH04208262A (en) * | 1990-11-30 | 1992-07-29 | Nippon Zeon Co Ltd | Production of 4-hydroxyindoles |
| CN101195600A (en) * | 2007-12-14 | 2008-06-11 | 常州市阳光精细化工有限公司 | Method for producing 4-hydroxyindole |
Non-Patent Citations (2)
| Title |
|---|
| MATTHEW D. LEBAR等: "Synthesis and Structure Reassessment of Psammopemmin A", 《AUST.J.CHEM.》 * |
| 吴秋业等: "4-羟基吲哚和4-甲氧基吲哚的合成", 《中国药物化学杂志》 * |
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