CN104628575A - Preparation method of 2-aminoindan - Google Patents
Preparation method of 2-aminoindan Download PDFInfo
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- CN104628575A CN104628575A CN201510066012.9A CN201510066012A CN104628575A CN 104628575 A CN104628575 A CN 104628575A CN 201510066012 A CN201510066012 A CN 201510066012A CN 104628575 A CN104628575 A CN 104628575A
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Abstract
The invention provides a preparation method of 2-aminoindan. Under the catalytic effect of lewis acid such as lithium chloride, aluminium chloride and magnesium chloride, 2-indene oxime is reduced by using potassium borohydride to prepare 2-aminoindan. The synthesis method disclosed by the invention can be completed in one step and has the advantages of less reaction steps, convenient operation, simple separation and purification method and operation, high yield and low cost; the product has good appearance, good color and luster and high purity (99.5%); in addition, the reducing agent used in the method is low in price and easily available; therefore, the preparation method is suitable for industrial production.
Description
Technical field
The invention belongs to organic chemical synthesis field, be specifically related to the preparation method of medicine intermediate, particularly relate to a kind of preparation method of 2-aminoidan.
Background technology
2-aminoidan is a kind of important medicine intermediate, can be used for synthesizing multi-medicament.2-aminoidan has all been used in the such as preparation of depressor delapril, arrhythmia medicine Aprindine etc.
At present, the synthetic method of 2-aminoidan mainly contains: be 1. raw material with indenes, after itself and the addition of chloro t-butyl carbamate, is obtaining product 2-aminoidan through reduction dechlorination; 2. with 2-indenes oxime for raw material, reduce to obtain product 2-aminoidan by high-pressure hydrogenation.
But first method is because yield is too low and poor reproducibility and do not have industrial utility value; And second method uses the transition-metal catalysts such as expensive palladium due to needs and makes high cost on the one hand, pressure hydration reduction reaction belongs to special reaction on the other hand, require quite high to reaction vessel, and need special operational, there is larger potential safety hazard, be very unfavorable for suitability for industrialized production.
Summary of the invention
The object of the invention is to the defect overcoming prior art, provide that a kind of reactions steps is few, easy and simple to handle, separating and purifying method and simple to operate, yield superelevation, cost are low, be applicable to the preparation method of the 2-aminoidan of suitability for industrialized production.
For achieving the above object, the present invention utilizes potassium borohydride reduction 2-indenes oxime to be achieved under having catalyzer to exist, and specifically comprises the steps:
In reaction flask, 2-indenes oxime, POTASSIUM BOROHYDRIDE, catalyzer and organic solvent is added successively, 60 ~ 120 DEG C of condition return stirring stoichiometric numbers hour after reinforced under room temperature; Reaction terminates rear cooling, filtration or suction filtration, adds in aqueous sodium hydroxide solution and rear chloroform extraction in filter cake; Or reaction terminates rear cooling, add in mixed solution after a small amount of hydrochloric acid stirs and filter or suction filtration, then add in aqueous sodium hydroxide solution in filter cake and rear chloroform extraction; Organic phase is merged rear desiccant dryness, filters, then filtrate decompression is steamed and desolventize, after resistates rectification under vacuum, obtain product liquid 2-aminoidan;
Wherein, the reaction equation of described reaction is shown in formula 1:
formula 1.
The catalyzer of above-mentioned reaction is Lewis acid, and described Lewis acid is any one in lithium chloride, magnesium chloride, aluminum chloride, zinc chloride, boron trifluoride ethyl ether complex and sulfuric acid, preferred aluminum chloride and boron trifluoride ethyl ether complex.
The organic solvent of above-mentioned reaction is any one in tetrahydrofuran (THF), 2-methyltetrahydrofuran, dioxane, glycol dimethyl ether, is preferably tetrahydrofuran (THF).
The temperature of reaction of above-mentioned reaction preferably 60 ~ 80 DEG C.
Above-mentioned reaction reaction times be 2-8 hour, be preferably 6 hours.
Above-mentioned post-reaction treatment hydrochloric acid used is commercially available concentrated hydrochloric acid, and the concentration of aqueous sodium hydroxide solution used is massfraction 10%.
2-indenes oxime, POTASSIUM BOROHYDRIDE and the lewis acidic mol ratio of feeding intake in above-mentioned reaction is 1:1 ~ 4:1 ~ 4, is preferably 1:2:1.
In above-mentioned reaction, the quality proportioning of 2-indenes oxime and organic solvent is 1:4-20, is preferably 1:10.
Above-mentioned siccative comprises anhydrous magnesium sulfate, anhydrous sodium sulphate, anhydrous sodium carbonate, anhydrous calciumsulphate, Anhydrous potassium carbonate.
Relative to prior art, the beneficial effect that the present invention has is as follows: synthetic method of the present invention only has a step to complete, reactions steps is few, easy and simple to handle, safety, the method for separating-purifying and simple to operate, to reaction vessel without particular requirement, yield superelevation, cost are low, and product appearance is good, color and luster is good, high purity 99.5%, the recyclable recycling of solvent, and the present invention's reductive agent used is also cheap and easy to get, be applicable to suitability for industrialized production.
Embodiment
Below in conjunction with several preferred embodiment, the present invention is described in further details, but protection scope of the present invention is not limited thereto.
Embodiment 1
In 3000mL three-necked bottle, add 147 grams of 2-indenes oximes, 54 grams of POTASSIUM BOROHYDRIDE, 150 grams of aluminum chlorides and 1000mL tetrahydrofuran (THF)s under room temperature successively, the 70 degrees Celsius of return stirrings that heat up after reinforced react 6 hours.Reaction terminates rear cooling, suction filtration recycling design, 30mL10% aqueous sodium hydroxide solution heating reflux reaction is added 1 hour in filter cake, be cooled to after room temperature with 6 × 100mL chloroform extraction, with after anhydrous sodium sulfate drying after organic phase is merged, remove solvent under reduced pressure, after resistates rectification under vacuum, obtain 87 grams of amber transparent product liquid 2-aminoidans.Gas Chromatographic Determination normalization method purity: 99.5%.
Nucleus magnetic resonance: [1H-NMR (CDCl
3, 400MHz) and δ: 2.94-2.98(m, 2H), 3.24-3.30 (m, 3H), 5.20-5.28 (ws, 2H), 7.20-7.24 (m, 4H).
Low Resolution Mass Spectra: LRMS (ESI) m/z:126.1 (M+H)].
Embodiment 2.
In 3000mL three-necked bottle, add 147 grams of 2-indenes oximes, 54 grams of POTASSIUM BOROHYDRIDE, 1000mL tetrahydrofuran (THF) and 100 grams of sulfuric acid under ice bath successively, the 70 degrees Celsius of return stirrings that heat up after reinforced react 2 hours.Then add 30mL hydrochloric acid after cooling, stir suction filtration recycling design after half an hour.Add in 100mL 10% aqueous sodium hydroxide solution in filter cake and rear use 6 × 100mL chloroform extraction, with after anhydrous sodium sulfate drying after organic phase is merged, remove solvent under reduced pressure, after resistates rectification under vacuum, obtain 82 grams of amber transparent product liquid 2-aminoidans.Gas Chromatographic Determination normalization method purity: 99.6%.
Nucleus magnetic resonance and Low Resolution Mass Spectra information consistent with embodiment 1.
Embodiment 3.
In 3000mL three-necked bottle, add 147 grams of 2-indenes oximes, 54 grams of POTASSIUM BOROHYDRIDE, 1000mL tetrahydrofuran (THF) and 130mL boron trifluoride ethyl ether complexs under ice bath successively, the 75 degrees Celsius of return stirrings that heat up after reinforced react 2 hours.Then add 30mL hydrochloric acid after cooling, stir filtered and recycled solvent after half an hour.Add in 100mL 10% aqueous sodium hydroxide solution in solid much filtrate and rear use 6 × 100mL chloroform extraction, with after dried over anhydrous sodium carbonate after organic phase is merged, remove solvent under reduced pressure, after resistates rectification under vacuum, obtain 94 grams of amber transparent product liquid 2-aminoidans.Gas Chromatographic Determination normalization method purity: 99.5%.
Nucleus magnetic resonance and Low Resolution Mass Spectra information consistent with embodiment 1.
Embodiment 4
In 3000mL three-necked bottle, add 147 grams of 2-indenes oximes, 54 grams of POTASSIUM BOROHYDRIDE, 134 grams of magnesium chlorides and 1500mL tetrahydrofuran (THF)s under room temperature successively, the 80 DEG C of return stirrings that heat up after reinforced react 6 hours.Reaction terminates rear cooling, suction filtration recycling design.30mL10% aqueous sodium hydroxide solution heating reflux reaction is added 1 hour in filter cake, be cooled to after room temperature with 6 × 100mL chloroform extraction, with after anhydrous magnesium sulfate drying after organic phase is merged, remove solvent under reduced pressure, after resistates rectification under vacuum, obtain 80 grams of amber transparent product liquid 2-aminoidans.Gas Chromatographic Determination normalization method purity: 99.5%.
Nucleus magnetic resonance and Low Resolution Mass Spectra information consistent with embodiment 1.
Claims (10)
1. a preparation method for 2-aminoidan, is characterized in that: it utilizes potassium borohydride reduction 2-indenes oxime to be achieved under having catalyzer to exist, and specifically comprises the steps:
In reaction flask, 2-indenes oxime, POTASSIUM BOROHYDRIDE, catalyzer and organic solvent is added successively, 60 ~ 120 DEG C of condition return stirring stoichiometric numbers hour after reinforced under room temperature or ice bath; Reaction terminates rear cooling, filtration or suction filtration, adds in aqueous sodium hydroxide solution and rear chloroform extraction in filter cake; Or reaction terminates rear cooling, add in mixed solution after a small amount of hydrochloric acid stirs and filter or suction filtration, then add in aqueous sodium hydroxide solution in filter cake and rear chloroform extraction; Organic phase is merged rear desiccant dryness, filters, then filtrate decompression is steamed and desolventize, after resistates rectification under vacuum, obtain product liquid 2-aminoidan;
Wherein, the reaction equation of described reaction is shown in formula 1:
formula 1.
2. the preparation method of a kind of 2-aminoidan as claimed in claim 1, is characterized in that: described catalyzer is Lewis acid.
3. the preparation method of a kind of 2-aminoidan as claimed in claim 2, it is characterized in that: described Lewis acid is any one in lithium chloride, magnesium chloride, aluminum chloride, zinc chloride, boron trifluoride ethyl ether complex and sulfuric acid, preferred aluminum chloride and boron trifluoride ethyl ether complex.
4. the preparation method of a kind of 2-aminoidan as claimed in claim 1, is characterized in that: described organic solvent is any one in tetrahydrofuran (THF), 2-methyltetrahydrofuran, dioxane, glycol dimethyl ether, is preferably tetrahydrofuran (THF).
5. the preparation method of a kind of 2-aminoidan as claimed in claim 1, is characterized in that: described temperature of reaction preferably 60 ~ 80 DEG C.
6. the preparation method of a kind of 2-aminoidan as claimed in claim 1, is characterized in that: the described reaction times is 2-8 hour, is preferably 6 hours.
7. the preparation method of a kind of 2-aminoidan as claimed in claim 1, is characterized in that: described 2-indenes oxime, POTASSIUM BOROHYDRIDE and lewis acidic mol ratio are 1:1 ~ 4:1 ~ 4, is preferably 1:2:1.
8. the preparation method of a kind of 2-aminoidan as claimed in claim 1, is characterized in that: described 2-indenes oxime and the quality proportioning of organic solvent are 1:4-20, is preferably 1:10.
9. the preparation method of a kind of 2-aminoidan as claimed in claim 1, is characterized in that: described hydrochloric acid is commercially available concentrated hydrochloric acid, the concentration of described aqueous sodium hydroxide solution is massfraction 10%.
10. the preparation method of a kind of 2-aminoidan as claimed in claim 1, is characterized in that: described siccative comprises anhydrous magnesium sulfate, anhydrous sodium sulphate, anhydrous sodium carbonate, anhydrous calciumsulphate, Anhydrous potassium carbonate.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945265A (en) * | 2015-06-09 | 2015-09-30 | 成都大学 | Synthetic method for indan-2-amine |
| CN109369417A (en) * | 2018-10-19 | 2019-02-22 | 诚达药业股份有限公司 | A kind of preparation method of 2- aminoidan derivatives |
| CN110229067A (en) * | 2019-06-05 | 2019-09-13 | 南京焕然生物科技有限公司 | A kind of 2- amino indenes preparation method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3196181A (en) * | 1963-03-01 | 1965-07-20 | Ciba Geigy Corp | Catalytic reduction of 2-oximinoindane to 2-amino-indane |
| WO2014089324A1 (en) * | 2012-12-07 | 2014-06-12 | Calitor Sciences, Llc | Substituted cyclic compounds and methods of use |
-
2015
- 2015-02-09 CN CN201510066012.9A patent/CN104628575A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3196181A (en) * | 1963-03-01 | 1965-07-20 | Ciba Geigy Corp | Catalytic reduction of 2-oximinoindane to 2-amino-indane |
| WO2014089324A1 (en) * | 2012-12-07 | 2014-06-12 | Calitor Sciences, Llc | Substituted cyclic compounds and methods of use |
Non-Patent Citations (2)
| Title |
|---|
| 冯光熙 等: "《无机化学丛书（第一卷）》", 31 May 1984, article "稀有气体、氢、碱金属", pages: 201 * |
| 张胜建主编: "《有机中间体工艺开发实用指南——从选题到试生产》", 30 September 2010, article "有机中间体工艺开发实用指南——从选题到试生产", pages: 91-92 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945265A (en) * | 2015-06-09 | 2015-09-30 | 成都大学 | Synthetic method for indan-2-amine |
| CN104945265B (en) * | 2015-06-09 | 2017-04-12 | 成都大学 | Synthetic method for indan-2-amine |
| CN109369417A (en) * | 2018-10-19 | 2019-02-22 | 诚达药业股份有限公司 | A kind of preparation method of 2- aminoidan derivatives |
| CN110229067A (en) * | 2019-06-05 | 2019-09-13 | 南京焕然生物科技有限公司 | A kind of 2- amino indenes preparation method |
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Application publication date: 20150520 |