CN102093228A - Method for synthesizing 1, 3-adamantane diamine - Google Patents
Method for synthesizing 1, 3-adamantane diamine Download PDFInfo
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- CN102093228A CN102093228A CN2011100203214A CN201110020321A CN102093228A CN 102093228 A CN102093228 A CN 102093228A CN 2011100203214 A CN2011100203214 A CN 2011100203214A CN 201110020321 A CN201110020321 A CN 201110020321A CN 102093228 A CN102093228 A CN 102093228A
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Abstract
The invention discloses a method for synthesizing 1, 3-adamantane diamine. The 1, 3-adamantane diamine synthesized by the method is prepared by the following steps of: performing amination on 1, 3-dibromoadamantane and urea in a high boiling point solvent; and performing separated purification through acidification, neutralization and extraction. The method particularly comprises the following steps of: mixing the 1,3-dibromoadamantane and the urea uniformly according to the molar ratio of the 1,3-dibromoadamantane to the urea of 1:2-10; adding the high boiling point solvent; heating the mixture to a preset temperature in an oil bath and reacting under stirring; after the reaction is finished, cooling to 50 DEG C; adding hydrochloric acid and stirring to dissolve the product; filtering to remove insoluble impurities; adding sodium hydroxide solution into filtrate to neutralize; adding an excessive organic solvent to perform extraction; distilling the obtained extract liquid under reduced pressure to remove the solvent; and performing vacuum drying to obtain the product 1,3-adamantane diamine. The method has the advantages of short reaction route, simpleness and convenience in operation, mild condition, clean and environmentally-friendly process, high product yield and the like.
Description
Technical field
The present invention relates to a kind of 1, the synthetic method of 3-diamantane diamines.The diamantane diamines is used for polymer monomer at present more, contains 1, and the polymkeric substance of 3-diamantane diamines can be used for aspects such as microelectronics, gas delivery.Has the potential medical value.
Background technology
1,3-diamantane diamines is owing to contain inflexible diamantane cage structure simultaneously and active very strong amido, thereby has important use at macromolecular material, fine chemistry industry, electronic applications and field of medicaments.In the synthesized polymer material field, 1,3-diamantane diamines can be used for the polyimide gas separation membrane material of synthetic excellent performance, can be used for the synthetic higher luminous organic material of thermostability, also can be used as polymerization single polymerization monomer or the modification group is incorporated in other macromolecular material, change performances such as its thermally-stabilised and hydrothermally stable; In fine chemistry industry, 1,3-diamantane diamines is a kind of important chemical intermediate, can be used to prepare the adamantyl tertiary amine, fine chemicals such as quaternary ammonium salt also can be used for preparing photo-resist.At field of medicaments, 1,3-diamantane diamines is the synthetic antiviral intermediate that waits specific medicament.
Disclosed at present 1,3-diamantane diamines has following four kinds of synthetic methods:
Patent US3053907 disclosed 1; 3-diamantane diamines synthetic method; be to be solvent with the Glacial acetic acid, under nitrogen protection, diamantane and concentrated nitric acid are converted into 1 under High Temperature High Pressure; 3-dinitrobenzene diamantane (yield 18%); in alcohol solvent, adopt Raney nickel catalysis 1, the hydrogenation reaction of 3-dinitrobenzene diamantane and hydrogen then; be reduced into 1,3-diamantane diamines.This method needs higher temperature of reaction and pressure, the operational condition harshness, and the product overall yield is lower.
Patent CA813899A is disclosed 1, and 3-diamantane diamines synthetic method is to adopt 1,3-dihydroxyl diamantane and prussic acid are under the oleum effect, and reaction generates 1,3-diformamide diamantane, with after the reaction system dilution, obtain 1,3-diamantane diamines (94%) through hydrolysis, neutralization more then.This method products therefrom yield is higher, but because raw material 1,3-dihydroxyl diamantane costs an arm and a leg, and causes product cost higher.In addition, hazardous substance such as oleum and prussic acid are used in operating process, and environmental issue and operational safety hidden danger are arranged.(J Polym Sci Part A:Polym Chem 2004 such as Seino, 42,144) above method is improved, adopt 1,3-dibromodiamantane and acetonitrile 90 ℃ of following backflow 24h under vitriol oil effect generate 1,3-diethylamide diamantane (61%), 100 ℃ of following backflow 60h hydrolysis obtains 1 under the hydrochloric acid effect of 2M again, the hydrochloride (96%) of 3-diamantane diamines.But the reaction times is longer, and step is many.
(Ber. 1941 for Prelog etc., 74,1769) disclosed 1,3-diamantane diamines synthetic method: by adamantane acid and thionyl chloride reflux, make the diamantane dimethyl chloride, make acid amides with the reaction of cold ammoniacal liquor again, with the gained acid amides in the presence of bromine, sodium hydroxide through Hofmann degradation, make 1,3-diamantane diamines.This early stage synthetic method complicated operation, raw material sources are restricted, use poisonous in the reaction process and the strong reagent of corrodibility, and environmental issue is obvious, and product cost is also higher.
(Synth Commun. 2006 such as Matthew C. Davis; 36 (15): 2113-2119) also announced a kind of 1; the synthetic method of 3-diamantane diamines: with 1; 3-dibromodiamantane and excessive repeatedly nitrogen trimethyl silane are in the presence of tin tetrachloride; under the nitrogen protection, the repeatedly nitrogen diamantane (74%) of generation two that refluxes is then under palladium-carbon catalyst in the methylene dichloride; become 1 with hydrogen reducing, 3-diamantane diamines (93%).This method yield is higher relatively, but agents useful for same has higher risk, raw material and catalyzer shortcoming such as cost an arm and a leg.
Therefore, research and develop a kind of operational safety, environmental protection, reaction scheme is short, and cost of material is lower, is suitable for 1 of suitability for industrialized production, and 3-diamantane diamines synthetic method is significant.
Summary of the invention
The objective of the invention is to overcome the prior art shortcoming, provide a kind of raw material sources extensive, easy and simple to handle, mild condition, the products therefrom yield and than purity high 1,3-diamantane diamines synthetic method.
The present invention realizes by following technological line:
A kind of 1, the synthetic method of 3-diamantane diamines, described 1,3-diamantane diamines is in high boiling solvent, by 1, the amination reaction of 3-dibromodiamantane and urea, and then acidified, neutralization, extraction means separate and purify and get; Reaction formula is as follows:
?。
The concrete steps of above-mentioned synthetic method are as follows:
With mol ratio is 1 of 1:2～10, and 3-dibromodiamantane and urea mix, and adds high boiling solvent, and oil bath is heated to the design temperature stirring reaction; Reaction is cooled to 50 ℃ after finishing, and adds the hydrochloric acid stirring and makes the product dissolving; Remove by filter insoluble impurity, filtrate adds the sodium hydroxide solution neutralization, adds excessive organic solvent extraction then; The extraction liquid underpressure distillation that obtains removed desolvate, vacuum-drying obtains 1,3-diamantane two amine products.
Above-mentioned high boiling solvent is a kind of in dibutyl phthalate, ethylene glycol dibutyl ether, isophorone, the phenyl ether; 1, the mass ratio of 3-dibromodiamantane and above-mentioned high boiling solvent is 1:0.5～10.
Above-mentioned temperature of reaction is 100～200 ℃.
The above-mentioned reaction times is 1～15h.
Above-mentioned concentration of hydrochloric acid is 1～6M.
Above-mentioned used organic extraction solvent is a kind of in tetracol phenixin, ethylene dichloride, chlorobenzene, ethylene dibromide, the chloroform.
Compared with the prior art, the invention has the beneficial effects as follows:
(1) provide a kind of novelty, green 1,3-diamantane diamines synthetic method.
(2) be raw material with dibromodiamantane, urea etc., raw material is easy to get, product is higher than rate.
(3) synthetic 1 by single step reaction, 3-diamantane diamines, method is easy, mild condition, can realize suitability for industrialized production.
Embodiment
The following examples will be further explained the present invention, but the present invention is not limited only to these embodiment, the scope that these embodiment do not limit the present invention in any way.Some change that those skilled in the art is made within the scope of the claims and adjust also should be thought and belongs to scope of the present invention.
Embodiment 1
With 2.94g (10mmol) 1, the 3-dibromodiamantane, 1.2g (20mmol) urea, 1.5g isophorone add in the 100ml there-necked flask, and the oil bath heating is warming up to 180 ℃, stirring reaction 1.5h.Reaction mixture is cooled to 50 ℃, the hydrochloric acid soln that adds 120ml 1M stirs 30min, suction filtration is removed insoluble impurity then, adding massfraction and be 40% sodium hydroxide solution in filtrate is neutralized to solution and is alkalescence, use the 100ml carbon tetrachloride extraction, underpressure distillation removes desolvates, with the gained solid in 60 ℃ of following vacuum-dryings, the products obtained therefrom quality is 1.07g, productive rate 66.00%.
Embodiment 2
With 2.94g (10mmol) 1, the 3-dibromodiamantane, 3.0g (50mmol) urea, the 12g phenyl ether adds the 100ml there-necked flask, the oil bath heating, be warming up to 100 ℃, stirring reaction 15h is cooled to 50 ℃ with reaction mixture, the hydrochloric acid soln that adds 40ml 3M stirs 30min, suction filtration is removed insoluble impurity then, adds massfraction and is 40% sodium hydroxide solution in filtrate and be neutralized to solution and be alkalescence, with the extraction of 120ml ethylene dichloride, underpressure distillation removes and desolvates, in 60 ℃ of following vacuum-dryings, the products obtained therefrom quality is 1.17g, productive rate 70.48% with the gained solid.
Embodiment 3,
With 2.94g (10mmol) 1, the 3-dibromodiamantane, 1.80g (30mmol) urea, the 18g dibutyl phthalate adds in the 100ml there-necked flask, the oil bath heating is warming up to 145 ℃, stirring reaction 8h, reaction mixture is cooled to 50 ℃, the hydrochloric acid soln that adds 20ml 6M stirs 30min, and suction filtration is removed insoluble impurity then, adds massfraction and is 40% sodium hydroxide solution in filtrate and be neutralized to solution and be alkalescence, extract with the 80ml chlorobenzene, underpressure distillation removes desolvates, and obtains white solid, with the gained solid in 60 ℃ of following vacuum-dryings, the products obtained therefrom quality is 1.11g, productive rate 68.87%
Embodiment 4
With 2.94g (10mmol) 1, the 3-dibromodiamantane, 3.0g (50mmol) urea, the 29g ethylene glycol dibutyl ether adds the 100ml there-necked flask, and the oil bath heating is warming up to 165 ℃, stirring reaction 4h.Reaction mixture is cooled to 50 ℃, the hydrochloric acid soln that adds 60ml 2M stirs 30min, suction filtration is removed insoluble impurity then, add massfraction and be 40% sodium hydroxide solution in filtrate and be neutralized to solution and be alkalescence, with the extraction of 200ml ethylene dibromide, underpressure distillation removes and desolvates, obtain white solid, in 60 ℃ of following vacuum-dryings, the products obtained therefrom quality is 0.20g, productive rate 12.05% with the gained solid.
Embodiment 5
With 2.94g (10mmol) 1, the 3-dibromodiamantane, 6.0g (100mmol) urea, the 10g phenyl ether adds the 100ml there-necked flask, and the oil bath heating is warming up to 200 ℃, stirring reaction 1h.Reaction mixture is cooled to 50 ℃, the hydrochloric acid soln that adds 30ml 4M stirs 30min, suction filtration is removed insoluble impurity then, adding massfraction and be 40% sodium hydroxide solution in filtrate is neutralized to solution and is alkalescence, use the 150ml chloroform extraction, underpressure distillation removes desolvates, with the gained solid in 60 ℃ of following vacuum-dryings, the products obtained therefrom quality is 0.20g, productive rate 12.05%.
Claims (7)
1. one kind 1, the synthetic method of 3-diamantane diamines is characterized in that: described 1,3-diamantane diamines is in high boiling solvent, by 1, and the amination reaction of 3-dibromodiamantane and urea, and then acidified, neutralization, extraction means separate and purify and get; Reaction formula is as follows:
2. synthetic method as claimed in claim 1 is characterized in that the concrete steps of above-mentioned synthetic method are as follows:
With mol ratio is 1 of 1:2～10, and 3-dibromodiamantane and urea mix, and adds high boiling solvent, and oil bath is heated to the design temperature stirring reaction; Reaction is cooled to 50 ℃ after finishing, and adds the hydrochloric acid stirring and makes the product dissolving; Remove by filter insoluble impurity, filtrate adds the sodium hydroxide solution neutralization, adds excessive organic solvent extraction then; The extraction liquid underpressure distillation that obtains removed desolvate, vacuum-drying obtains 1,3-diamantane two amine products.
3. synthetic method as claimed in claim 1 or 2 is characterized in that: above-mentioned high boiling solvent is a kind of in dibutyl phthalate, ethylene glycol dibutyl ether, isophorone, the phenyl ether; 1, the mass ratio of 3-dibromodiamantane and above-mentioned high boiling solvent is 1:0.5～10.
4. synthetic method as claimed in claim 2 is characterized in that: above-mentioned temperature of reaction is 100～200 ℃.
5. synthetic method as claimed in claim 2 is characterized in that: the above-mentioned reaction times is 1～15h.
6. synthetic method as claimed in claim 2 is characterized in that: above-mentioned concentration of hydrochloric acid is 1～6M.
7. synthetic method as claimed in claim 2 is characterized in that: above-mentioned used organic extraction solvent is a kind of in tetracol phenixin, ethylene dichloride, chlorobenzene, ethylene dibromide, the chloroform.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103833555A (en) * | 2012-11-23 | 2014-06-04 | 上海京新生物医药有限公司 | Memantine hydrochloride preparation method |
| JP2017039656A (en) * | 2015-08-19 | 2017-02-23 | 大日本印刷株式会社 | Method for manufacturing highly-pure memantine hydrochloride |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1544415A (en) * | 2003-11-12 | 2004-11-10 | 中国人民解放军北京军医学院 | Namenda synthesis method |
| WO2008062472A2 (en) * | 2006-10-24 | 2008-05-29 | Cadila Healthcare Limited | Process for the preparation of memantine |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1544415A (en) * | 2003-11-12 | 2004-11-10 | 中国人民解放军北京军医学院 | Namenda synthesis method |
| WO2008062472A2 (en) * | 2006-10-24 | 2008-05-29 | Cadila Healthcare Limited | Process for the preparation of memantine |
Non-Patent Citations (3)
| Title |
|---|
| 丁方华: "金刚烷胺的合成", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》, no. 1, 15 January 2008 (2008-01-15), pages 15 * |
| 李娅琼: "金刚烷胺及其衍生物的合成", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》, no. 8, 15 August 2010 (2010-08-15) * |
| 邵桂真 等: "盐酸金刚烷胺的合成工艺", 《设备工艺》, no. 7, 31 December 2009 (2009-12-31) * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103833555A (en) * | 2012-11-23 | 2014-06-04 | 上海京新生物医药有限公司 | Memantine hydrochloride preparation method |
| JP2017039656A (en) * | 2015-08-19 | 2017-02-23 | 大日本印刷株式会社 | Method for manufacturing highly-pure memantine hydrochloride |
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