CN103588648A - Amantadine formate compound and preparation method thereof - Google Patents
Amantadine formate compound and preparation method thereof Download PDFInfo
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- CN103588648A CN103588648A CN201310542065.4A CN201310542065A CN103588648A CN 103588648 A CN103588648 A CN 103588648A CN 201310542065 A CN201310542065 A CN 201310542065A CN 103588648 A CN103588648 A CN 103588648A
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Abstract
The invention discloses an amantadine formate compound applied to the field of drug synthesis. A preparation method for the amantadine formate compound comprises the following steps: reacting amantadine with formic acid in water or ethanol, cooling, crystallizing, and filtering to obtain amantadine formate; carrying out reaction between amantadine and formic acid in water, and cooling and crystallizing in acetone to obtain amantadine formate. The amantadine formate compound is used for manufacturing light-sensing materials, electronic materials and lubricating oil; the reaction temperature of amantadine and formic acid is 40-55 DEG C; the molar ratio of amantadine to formic acid is 1 to (1-3); the weight ratio of amantadine to acetone is 1 to (2-4). The preparation method has the following characteristics: the water or ethanol is adopted as a reaction solvent, the operation is simple, the crystallizing process is conducted in acetone, the amantadine formate compound is high in yield and good in purity, the used raw materials are easy to obtain and can be all recycled, the cost is low, and the environment is greatly protected.
Description
Technical field
The present invention relates to a kind of amantadine formate compounds in the synthetic field of medicine and preparation method thereof.
Background technology
Diamantane (Adamantane is called for short ADH) is a kind of cage shape hydrocarbon of height symmetry, chemical name three ring [3.3.1.1
3,7] decane, molecular formula C
10h
16, colourless crystalline solid, has camphor smell.Its structure is by 10 carbon atoms and 16 ring-type tetrahedrons that hydrogen atom forms.
ADH is the new fine chemicals growing up over nearly 30 years, and it has unique structure and character.ADH essentially consist unit has chair form configuration, undistorted, and whole ring system has symmetry and rigidity, and three-dimensional ring-type system is without tension force.Therefore there is following characteristics: fusing point high (268 ℃), Heat stability is good; Intermolecular forces a little less than, there is good oilness, and easily distillation; Fat-soluble good, be slightly soluble in benzene, water insoluble; Nontoxic, tasteless.ADH has extensive use in the various fields such as medicine, functional polymer, lubricating oil, catalyzer, tensio-active agent, sensitive materials, agricultural chemicals, thereby is described as fine chemical material of new generation.
Adamantanamine hydrochloride (Amantadine) is the earliest for suppressing the antiviral drug of influenza virus, and what the U.S. caught a cold popular in Asia ratifies it as prophylactic agent in 1966.And on the basis at prophylactic agent, confirmed as curative in 1976.In Japan, adamantanamine hydrochloride is always as Parkinsonian curative, until within 1998, be just approved for the treatment of influenza virus A type infectious diseases.
Amantadine formate (1-adamantanamine formic acid salt) is the salt that amantadine and formic acid reaction generate, stability and the solubleness of amantadine have been increased, it is soluble in water, ethanol, methyl alcohol, is insoluble to the organic solvents such as ethyl acetate, acetone, ether.Because it has all features such as good of fast light, moisture-proof, thermotolerance, drug-resistant corrodibility, solvent resistance, therefore it is for the manufacture of sensitive materials, electronic material, lubricated wet goods, to improve product thermotolerance, oxidation-resistance and directional stability, increase polymer strength.Therefore, researching and developing a kind of amantadine formate compounds and preparation method thereof is current new problem anxious to be resolved.
Summary of the invention
The object of the present invention is to provide a kind of amantadine formate compounds and preparation method thereof, that this compound has is fast light, the equal feature such as good of moisture-proof, thermotolerance, drug-resistant corrodibility, solvent resistance, therefore it is for the manufacture of sensitive materials, electronic material, lubricated wet goods, to improve product thermotolerance, oxidation-resistance and directional stability, increase polymer strength; This preparation method's raw material is cheaply easy to get, and cost is low, and reactions steps is short, simple to operate, and product quality is good.
The object of the present invention is achieved like this: a kind of amantadine formate compounds, and this structural formula of compound is as follows:
Described preparation method comprises the steps, amantadine and formic acid react in water or ethanol, cooling, and crystallization, filters and obtains amantadine formate; Amantadine and formic acid react in water, and the crystallization of lowering the temperature in acetone obtains amantadine formate; Amantadine formate compounds is for the manufacture of sensitive materials, electronic material, lubricating oil; The temperature of reaction of amantadine and formic acid is 40-55 ℃; The mol ratio of amantadine and formic acid is 1:1-3; The weight ratio of amantadine and acetone is 1:2-4.
Main points of the present invention are a kind of amantadine formate compounds and preparation method thereof.Its principle is: amantadine reacts with formic acid and generates amantadine formate in water or ethanol, because amantadine is insoluble in water, amantadine formate is soluble in water, be insoluble to acetone, therefore can whether complete according to dissolving situation judgement reaction, the soluble in water and ethanol of amantadine formate, therefore in water and ethanol, crystallization yield is low, add acetone, reduce solubleness, yield is high.
A kind of amantadine formate compounds and preparation method thereof compared with prior art; have the method for preparing amantadine formate adopt water or ethanol as reaction solvent, simple to operate, in acetone crystallization, yield is high, purity good, raw materials used be easy to get and all recyclablely apply mechanically, not only cost is low but also the unusual advantage such as environmental protection, will be widely used in the synthetic field of medicine.
Accompanying drawing explanation
Below in conjunction with drawings and Examples, the present invention is described in detail.
Fig. 1 amantadine formate compounds structural formula figure.
Fig. 2 is adamantane compound structural formula figure.
Fig. 3 adamantanamine hydrochloride structural formula of compound figure.
Fig. 4 amantadine formate compounds synthetic route chart.
Embodiment
Concrete preparation method of the present invention, have following implementation example explanation, but protection scope of the present invention is not limited to this.
Embodiment mono-(water is reaction solvent)
By 30 grams of amantadines (moisture 54%), 15 ml waters add 250 milliliters of reaction flasks, stir, be added dropwise to 8.2 milliliters of formic acid, be heated to 45-50 ℃, stir molten clear, cool to 20 ℃, stirring and crystallizing 30 minutes, cools to 0 ℃ and stirs 3 hours, filters, with a small amount of cold wash reaction flask and filter cake, 11.5 grams, dry amantadine formic acid, yield 63.9%, content: 99.5% fusing point: 238 ℃.
Embodiment bis-(water is reaction solvent)
By 30 grams of amantadines (moisture 54%), 20 ml waters add 250 milliliters of reaction flasks, stir, be added dropwise to 12.3 milliliters of formic acid, be heated to 45-50 ℃, stir molten clear, cool to 20 ℃, stirring and crystallizing 30 minutes, cools to-5 ℃ and stirs 3 hours, filters, with a small amount of cold wash reaction flask and filter cake, 11.0 grams, dry amantadine formic acid, yield 61.1%, content: 99.5% fusing point: 238 ℃.
Embodiment tri-(ethanol is reaction solvent)
By 30 grams of amantadines (moisture 54%), 20 milliliters of ethanol add 250 milliliters of reaction flasks, stir, be added dropwise to 8.2 milliliters of formic acid, be heated to 45-50 ℃, stir molten clear, cool to 25 ℃, stirring and crystallizing 30 minutes, cools to 10 ℃, stir 1 hour, then cool to-5 ℃ of stirrings 2 hours, filter, with cold ethanol, wash reaction flask and filter cake, 12 grams, dry amantadine formic acid, yield 66.7%, content: 99.6% fusing point: 238 ℃.
Embodiment tetra-(crystallization in acetone)
By 30 grams of amantadines (moisture 54%), 10 ml waters add 250 milliliters of reaction flasks, stir, be added dropwise to 8.2 milliliters of formic acid, be heated to 45-50 ℃, stir molten clear, cool to 30 ℃, add 30 milliliters of acetone, stir 1 hour, there is crystal to separate out, then stir 1 hour, cool to-5 ℃ and stir 2 hours, filter, with acetone, wash reaction flask and filter cake, 13.5 grams, dry amantadine formic acid, yield 75%, content: 99.8% fusing point: 238 ℃.
Embodiment five (crystallization in acetone)
By 30 grams of amantadines (moisture 54%), 10 ml waters add 100 milliliters of reaction flasks, stir, and are added dropwise to 8.2 milliliters of formic acid, are heated to 45-50 ℃, stir molten clear.
In another reaction flask, add 60 milliliters of acetone, under stirring, drip above-mentioned reaction solution, within approximately 10 minutes, add, stir again 1 hour, cool to-5 ℃ and stir 2 hours, filter, with acetone, wash reaction flask and filter cake, 14.5 grams, dry amantadine formic acid, yield 80.5%, content: 99.6%, fusing point: 238 ℃.
Claims (7)
1. an amantadine formate compounds, is characterized in that: this structural formula of compound is as follows:
2. the preparation method of a kind of amantadine formate compounds as claimed in claim 1, is characterized in that: described preparation method comprises the steps, amantadine and formic acid react in water or ethanol, cooling, and crystallization, filters and obtains amantadine formate.
3. the preparation method of a kind of amantadine formate compounds as claimed in claim 1 or 2, is characterized in that: amantadine and formic acid react in water, and the crystallization of lowering the temperature in acetone obtains amantadine formate.
4. a kind of amantadine formate compounds as claimed in claim 1, is characterized in that: amantadine formate compounds is for the manufacture of sensitive materials, electronic material, lubricating oil.
5. the preparation method of a kind of amantadine formate compounds as claimed in claim 1 or 2, is characterized in that: the temperature of reaction of amantadine and formic acid is 40-55 ℃.
6. the preparation method of a kind of amantadine formate compounds as claimed in claim 1 or 2, is characterized in that: the mol ratio of amantadine and formic acid is 1:1-3.
7. the preparation method of a kind of amantadine formate compounds as described in claim 1 or 3, is characterized in that: the weight ratio of amantadine and acetone is 1:2-4.
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| CN201310542065.4A CN103588648A (en) | 2013-11-05 | 2013-11-05 | Amantadine formate compound and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112661629A (en) * | 2020-12-24 | 2021-04-16 | 中国科学院物理研究所 | All-organic pyroelectric material and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1942420A (en) * | 2004-04-27 | 2007-04-04 | 株式会社德山 | Production of halogenated adamantane compound |
-
2013
- 2013-11-05 CN CN201310542065.4A patent/CN103588648A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1942420A (en) * | 2004-04-27 | 2007-04-04 | 株式会社德山 | Production of halogenated adamantane compound |
Non-Patent Citations (3)
| Title |
|---|
| MILTON E . HER ET AL.: "The Microbiological Oxygenation of Acylated 1-Adamantanamines.Stereochemistry and Structural Determinations", 《THE JOURNAL OF ORGANIC CHEMISTRY》, vol. 33, no. 8, 31 August 1968 (1968-08-31), pages 3201 - 3207, XP003018058, DOI: 10.1021/jo01272a037 * |
| 何建勋等: "盐酸金刚烷胺的合成", 《中国医药工业杂志》, vol. 44, no. 1, 10 January 2013 (2013-01-10), pages 1 - 3 * |
| 朱华等: "特种润滑材料金刚烷制备技术的改进研究", 《润滑与密封》, vol. 33, no. 9, 30 September 2008 (2008-09-30) * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112661629A (en) * | 2020-12-24 | 2021-04-16 | 中国科学院物理研究所 | All-organic pyroelectric material and preparation method and application thereof |
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