CN104370798A - Synthesis method of 2-fluorobenzopyrrole - Google Patents
Synthesis method of 2-fluorobenzopyrrole Download PDFInfo
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- CN104370798A CN104370798A CN201410632509.8A CN201410632509A CN104370798A CN 104370798 A CN104370798 A CN 104370798A CN 201410632509 A CN201410632509 A CN 201410632509A CN 104370798 A CN104370798 A CN 104370798A
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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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin
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Abstract
The invention discloses a synthesis method of 2-fluorobenzopyrrole. According to the synthesis method, phenylhydrazine and aldehyde or ketone are taken as raw materials, the intermediate phenylhydrazone is generated firstly, next, catalytic heating is performed to cause rearrangement of the intermediate phenylhydrazone and polyphosphoric acid so that one molecule of ammonia can be removed and benzopyrrole can be obtained, then the benzopyrrole reacts with hydrofluoric acid or a catalyst HCl/ethanol, and finally, the final product can be obtained by virtue of reduced pressure distillation, filtering, washing and drying; the 2-fluorobenzopyrrole yield is above 89%.
Description
Technical field
The present invention is a kind of synthetic method of compound, a kind of synthetic method of 2-fluorine benzopyrrole.
Background technology
Benzopyrrole distributes when occurring in nature one of the widest heterogeneous ring compound, is also that the very important heterocycle medicine of a class and organic chemical industry obtain intermediate.It is widely used in the field such as medicine, agricultural chemicals, so for a long time, benzopyrrole and derivative thereof in every respect potential application cause the extensive concern of people.In many diseases, cancer becomes threat people life already and obtains serious disease, various countries have the attention of height already to it, and benzopyrrole derivative not only has extensive and important activity, and extend antitumor field, know in the natural pyrrole derivative of kind more than 3000, kind more than 40 is had to belong to direct current medicine, this makes a lot of scientific research personnel that center is devoted in the research of benzopyrrole in medical, moreover, if be incorporated into by different modifying gene in benzopyrrole structure, a series of compound with antitumour activity can be produced.
Summary of the invention
The invention provides the synthetic method of the 2-fluorine benzopyrrole that a kind of reaction conditions is simple, productive rate is high, cost is low.
For achieving the above object, the synthetic route of 2-fluorine benzopyrrole of the present invention is:
The building-up process of the 2-fluorine benzopyrrole that the present invention relates to comprises the following steps:
1, the synthesis of benzopyrrole
(1) phenylhydrazine of 0.08mol ketone and 0.089mol is placed in the triangular flask of 50mL, slowly stirs under room temperature and heat until react completely;
(2) in above-mentioned solution, add 20g polyphosphoric acid, continue heat and make temperature remain on 175-190 DEG C, after having reacted cooling, then add 50mL cold water and dilute;
(3) be cooled to 20-25 DEG C, phase-splitting, the upper organic phase ether 15mL*4 separated extracts, and 7.5g potassium hydroxide is dry, after placing for some time, steams ether with water-bath, to not having cut, in underpressure distillation, collects 74-75 DEG C/13mmHg cut;
(4) resistates is carried out decompression precipitation to steam to absence of liquid, add 15g ethyl acetate and 20g water carries out washing and extracting, obtain obtaining organic phase 15g anhydrous sodium sulfate drying, filter, filtrate revolves steaming under vacuo, weighs.
2, the synthesis of 2-fluorine benzopyrrole
(1) in above-mentioned solution, 25mL hydrofluoric acid aqueous solution and 15gHCl/ ethanol is added, through stirring and dissolving 1-2h;
(2), after making it fully react, stratification, with 60g pure water 2 times, obtains lower floor's organic phase anhydrous sodium sulphate process, filter, obtain crude product through underpressure distillation, add the complete molten rear slow cooling crystallization of 20g ethyl acetate heating, filter, washing, dry, calculated yield.
Specific embodiments
The building-up process of a kind of 2-fluorine benzopyrrole that the present invention relates to comprises the following steps:
The phenylhydrazine of 0.08mol ketone and 0.089mol is placed in the triangular flask of 50mL, slowly stirs under room temperature and heat until react completely; In above-mentioned solution, add 20g polyphosphoric acid, continue heat and make temperature remain on 175-190 DEG C, after having reacted cooling, then add 50mL cold water and dilute; Be cooled to 20-25 DEG C, phase-splitting, the upper organic phase ether 15mL*4 separated extracts, and 7.5g potassium hydroxide is dry, after placing for some time, steams ether with water-bath, to not having cut, in underpressure distillation, collects 74-75 DEG C/13mmHg cut; Resistates is carried out decompression precipitation steam to absence of liquid, add 15g ethyl acetate and 20g water carries out washing and extracting, obtain obtaining organic phase 15g anhydrous sodium sulfate drying, filter, filtrate revolves steaming under vacuo, weighs.25mL hydrofluoric acid aqueous solution and 15gHCl/ ethanol is added, through stirring and dissolving 1-2h in above-mentioned solution; After making it fully react, stratification, with 60g pure water 2 times, obtains lower floor's organic phase anhydrous sodium sulphate process, filters, obtains crude product through underpressure distillation, adds the complete molten rear slow cooling crystallization of 20g ethyl acetate heating, filters, washing, dry, calculated yield.
Example 1
The phenylhydrazine of 0.08mol ketone and 0.089mol is placed in the triangular flask of 50mL, slowly stirs under room temperature and heat until react completely; In above-mentioned solution, add 20g polyphosphoric acid, continue heat and make temperature remain on 175 DEG C, after having reacted cooling, then add 50mL cold water and dilute; Be cooled to 20 DEG C, phase-splitting, the upper organic phase ether 15mL*4 separated extracts, and 7.5g potassium hydroxide is dry, after placing for some time, steams ether with water-bath, to not having cut, in underpressure distillation, collects 74 DEG C/13mmHg cut; Resistates is carried out decompression precipitation steam to absence of liquid, add 15g ethyl acetate and 20g water carries out washing and extracting, obtain obtaining organic phase 15g anhydrous sodium sulfate drying, filter, filtrate revolves steaming under vacuo, weighs.25mL hydrofluoric acid aqueous solution and 15gHCl/ ethanol is added, through stirring and dissolving 1h in above-mentioned solution; After making it fully react, stratification, with 60g pure water 2 times, obtains lower floor's organic phase anhydrous sodium sulphate process, filter, obtain crude product through underpressure distillation, add the complete molten rear slow cooling crystallization of 20g ethyl acetate heating, filter, washing, dry, yield reaches more than 89%.
Example 2
The phenylhydrazine of 0.08mol ketone and 0.089mol is placed in the triangular flask of 50mL, slowly stirs under room temperature and heat until react completely; In above-mentioned solution, add 20g polyphosphoric acid, continue heat and make temperature remain on 180 DEG C, after having reacted cooling, then add 50mL cold water and dilute; Be cooled to 23 DEG C, phase-splitting, the upper organic phase ether 15mL*4 separated extracts, and 7.5g potassium hydroxide is dry, after placing for some time, steams ether with water-bath, to not having cut, in underpressure distillation, collects 74 DEG C/13mmHg cut; Resistates is carried out decompression precipitation steam to absence of liquid, add 15g ethyl acetate and 20g water carries out washing and extracting, obtain obtaining organic phase 15g anhydrous sodium sulfate drying, filter, filtrate revolves steaming under vacuo, weighs.25mL hydrofluoric acid aqueous solution and 15gHCl/ ethanol is added, through stirring and dissolving 1.5h in above-mentioned solution; After making it fully react, stratification, with 60g pure water 2 times, obtains lower floor's organic phase anhydrous sodium sulphate process, filter, obtain crude product through underpressure distillation, add the complete molten rear slow cooling crystallization of 20g ethyl acetate heating, filter, washing, dry, yield reaches more than 89%.
Example 3
The phenylhydrazine of 0.08mol ketone and 0.089mol is placed in the triangular flask of 50mL, slowly stirs under room temperature and heat until react completely; In above-mentioned solution, add 20g polyphosphoric acid, continue heat and make temperature remain on 190 DEG C, after having reacted cooling, then add 50mL cold water and dilute; Be cooled to 25 DEG C, phase-splitting, the upper organic phase ether 15mL*4 separated extracts, and 7.5g potassium hydroxide is dry, after placing for some time, steams ether with water-bath, to not having cut, in underpressure distillation, collects 75 DEG C/13mmHg cut; Resistates is carried out decompression precipitation steam to absence of liquid, add 15g ethyl acetate and 20g water carries out washing and extracting, obtain obtaining organic phase 15g anhydrous sodium sulfate drying, filter, filtrate revolves steaming under vacuo, weighs.25mL hydrofluoric acid aqueous solution and 15gHCl/ ethanol is added, through stirring and dissolving 2h in above-mentioned solution; After making it fully react, stratification, with 60g pure water 2 times, obtains lower floor's organic phase anhydrous sodium sulphate process, filter, obtain crude product through underpressure distillation, add the complete molten rear slow cooling crystallization of 20g ethyl acetate heating, filter, washing, dry, yield reaches more than 89%.
Claims (2)
1. a synthetic method for 2-fluorine benzopyrrole, is characterized in that the synthesis of benzopyrrole:
(1) phenylhydrazine of 0.08mol ketone and 0.089mol is placed in the triangular flask of 50mL, slowly stirs under room temperature and heat until react completely;
(2) in above-mentioned solution, add 20g polyphosphoric acid, continue heat and make temperature remain on 175-190 DEG C, after having reacted cooling, then add 50mL cold water and dilute;
(3) be cooled to 20-25 DEG C, phase-splitting, the upper organic phase ether 15mL*4 separated extracts, and 7.5g potassium hydroxide is dry, after placing for some time, steams ether with water-bath, to not having cut, in underpressure distillation, collects 74-75 DEG C/13mmHg cut;
(4) resistates is carried out decompression precipitation to steam to absence of liquid, add 15g ethyl acetate and 20g water carries out washing and extracting, obtain obtaining organic phase 15g anhydrous sodium sulfate drying, filter, filtrate revolves steaming under vacuo, weighs.
2. the synthetic method of a kind of 2-fluorine benzopyrrole according to claim 1, is characterized in that:
(1) in above-mentioned solution, 25mL hydrofluoric acid aqueous solution and 15gHCl/ ethanol is added, through stirring and dissolving 1-2h;
(2), after making it fully react, stratification, with 60g pure water 2 times, obtains lower floor's organic phase anhydrous sodium sulphate process, filter, obtain crude product through underpressure distillation, add the complete molten rear slow cooling crystallization of 20g ethyl acetate heating, filter, washing, dry, calculated yield.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410632509.8A CN104370798A (en) | 2014-11-11 | 2014-11-11 | Synthesis method of 2-fluorobenzopyrrole |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002022576A2 (en) * | 2000-09-15 | 2002-03-21 | Abbott Laboratories | 3-substituted indole carbohydrazides useful as cell proliferation and angiogenesis inhibitors |
| CN1626515A (en) * | 2003-12-10 | 2005-06-15 | 上海化学试剂研究所 | Method for preparing nitro indole-2-carboxylic acid |
| CN1721405A (en) * | 2004-07-15 | 2006-01-18 | 上海化学试剂研究所 | Process for preparing 4-bromo-7-methyl indole-2-carboxylic acid |
| CN1962635A (en) * | 2006-11-17 | 2007-05-16 | 浙江工业大学 | Indoles compound preparation method |
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- 2014-11-11 CN CN201410632509.8A patent/CN104370798A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002022576A2 (en) * | 2000-09-15 | 2002-03-21 | Abbott Laboratories | 3-substituted indole carbohydrazides useful as cell proliferation and angiogenesis inhibitors |
| CN1626515A (en) * | 2003-12-10 | 2005-06-15 | 上海化学试剂研究所 | Method for preparing nitro indole-2-carboxylic acid |
| CN1721405A (en) * | 2004-07-15 | 2006-01-18 | 上海化学试剂研究所 | Process for preparing 4-bromo-7-methyl indole-2-carboxylic acid |
| CN1962635A (en) * | 2006-11-17 | 2007-05-16 | 浙江工业大学 | Indoles compound preparation method |
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Application publication date: 20150225 |