CN1242982C - Method for preparing nitrate ethoxide in ammonium nitrate group - Google Patents
Method for preparing nitrate ethoxide in ammonium nitrate group Download PDFInfo
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- CN1242982C CN1242982C CN 200310117371 CN200310117371A CN1242982C CN 1242982 C CN1242982 C CN 1242982C CN 200310117371 CN200310117371 CN 200310117371 CN 200310117371 A CN200310117371 A CN 200310117371A CN 1242982 C CN1242982 C CN 1242982C
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Abstract
The present invention relates to a method for preparing ammonium nitrate group ethanol nitric ether. The method comprises the steps: (1) fuming nitric acid is added to acetic anhydride to form a mixed system (I) of nitric acid and acetic anhydride; (2) glacial acetic acid drops in ethanolamine to form an ammonium salt mixed system (II) of acetic acid and ethyl acetate; (3) the mixed liquid II drops in the mixed liquid I, solids are filtered out after reaction, and the solids are treated by the steps of washing, drying, recrystallization and active carbon decolorization to obtain ammonium nitrate group ethanol nitric ether(III) . The method has the advantages of moderate reaction, controllable reaction, easy treatment of products, high yield and high purity of products.
Description
Technical Field
The invention relates to the field of organic chemistry, in particular to a method for preparing ammonium nitrate-based ethanol nitrate.
Background
Nitrate esters represented by nitroglycerin play an important role in clinical treatment of cardiovascular diseases, and are the first choice for treating angina pectoris. However, nitrate esters, particularly nitroglycerin, have short biological half-life and many adverse reactions after long-term application, so that the application of the medicaments is limited. The N- (2-hydroxyethyl) ferulamide nitrate has mild action, long half life and obviously prolonged action maintenance time, and is a good medicament for treating angina. We found that the preparation method of the intermediate is very key in the process of synthesizing N- (2-hydroxyethyl) ferulamide nitrate, and the preparation method has obvious influence on the effect of the final product. In the past, people adopt a conventional method to directly react fuming nitric acid with aminoethanol, the temperature is not easy to control, explosion is easy to occur, the product yield is low, impurities are more, and the post-treatment is complicated. Through years of research and experiments, the invention is completed by finding that ammonium nitrate ethanol nitrate which is a synthetic intermediate for synthesizing N- (2-hydroxyethyl) ferulamide nitrate by taking acetic acid as a medium has mild reaction, easy control and high yield.
Object of the Invention
The invention aims to solve the defects and find a way for synthesizing the intermediate ammonium nitrate ethanol nitrate with mild reaction conditions, high yield and high product purity.
It is therefore an object of the present invention to provide a process for the preparation of ammonioethanolic nitrate.
Disclosure of Invention
The purpose of the invention is realized by the following technical scheme:
the method of the invention comprises the following steps:
① fuming nitric acid is added into acetic anhydride, and a nitric acid-acetic anhydride mixed system (I) is formed under the controlled temperature;
② controlling the temperature, dripping glacial acetic acid into ethanolamine, and stirring to form acetic acid-ethyl acetate ammonium salt mixed system (II);
③ and adding the mixed solution II into the mixed solution I, fully reacting, filtering and collecting solid, washing, drying, recrystallizing and decoloring by active carbon to obtain the ammonium nitrate ethanol nitrate (III).
In step ①, the ratio (molar ratio) of acetic anhydride to fuming nitric acid is 1: 0.5-5, preferably 1: 1-2, the temperature is lower than 10 ℃, preferably-20-10 ℃;
in step ②, the ratio (molar ratio) of ethanolamine to glacial acetic acid is 1: 0.5-5, preferably 1: 1-2, the temperature is lower than 20 ℃, preferably-10-20 ℃;
in step ③, the temperature range of the nitric acid acetic anhydride mixed system (I) and the acetic acid-ethyl acetate ammonium salt mixed system is lower than 20 ℃, preferably-10-20 ℃.
Preferred embodiments
In step ①, fuming nitric acid 1-5 mol is added into acetic anhydride 150-250 ml, and the dropping speed is controlled to make the system at-10 ℃ to form nitric acid-acetic anhydride mixed system (I).
In step ②, 0.5-2 mol of glacial acetic acid is added dropwise into 0.25-4 mol of ethanolamine, the temperature is-10-15 ℃, the mixture is fully stirred to form an acetic acid-ethyl acetate ammonium salt mixed system (II), in step ③, the temperature is controlled to be-5-15 ℃, the (I) and the (II) are mixed, and the mixture is fully stirred until the reaction is completed.
And recrystallizing the ammonium nitrate-ethyl alcohol nitrate (III) crude product by using an organic solvent, and decoloring by using activated carbon to obtain a product, wherein the yield is 70-95%.
More preferred embodiment
In step ①, 138.6g of fuming nitric acid is added into 200ml of acetic anhydride, the mixture is cooled by a ice salt bath, and the dropping speed is controlled to enable the system to be at the temperature of-10-5 ℃ to form a nitric acid-acetic anhydride mixed system (I).
In step ②, 67ml of glacial acetic acid is added dropwise into 61g of ethanolamine, the ambient temperature is-5 ℃, the system temperature is 5-15 ℃, the mixture is fully stirred, and then 50ml of glacial acetic acid is added, so as to form an acetic acid-ethyl acetate ammonium salt mixed system (II).
In step ③, controlling the temperature of the system to be lower than 5 ℃, dropwise adding the mixed solution (II) into the mixed solution (I), standing at 5 ℃ for 15 minutes after the addition is finished, then naturally recovering to 18-20 ℃, stirring for 4-5 hours, standing for precipitation, filtering, washing with diethyl ether, drying, recrystallizing with isopropanol (the ratio of solid to solvent W/V is 1: 10 (g/ml)), and decolorizing with activated carbon to obtain 147g of white flaky crystals with the yield of 87%.
The invention is further illustrated by the following examples. It should be understood that the preparation methods described in the examples are only for illustrating the present invention and are not to be construed as limiting the present invention, and that the simple modifications of the preparation methods of the present invention based on the concept of the present invention are within the scope of the present invention as claimed. Percentages in the present invention are by weight unless otherwise indicated.
Example 1: preparation of ammonium nitrate EtOH nitrate Using the method of the invention
Adding 200ml of acetic anhydride into a 1000ml three-neck flask provided with a mechanical stirrer, a low-temperature thermometer, a 250ml constant-pressure funnel and an anhydrous calcium chloride drying tube, cooling a salt-freezing bath to about-10 ℃, dropwise adding 138.6g (2.2mol) of fuming nitric acid into the mixture at a speed of preferably not more than-5 ℃ of the system temperature, and stirring the mixture for 30 minutes at-5-0 ℃ after the addition is finished to form a nitric acid-acetic anhydride mixed system (I).
Adding 61g (1.0mol) of ethanolamine into a 250ml three-necked bottle provided with a mechanical stirring device, a thermometer, a 100ml constant pressure funnel and an anhydrous calcium chloride drying tube, cooling the system to about 10 ℃, dropwise adding 67ml (1.16mol) of glacial acetic acid into the system, reducing the ambient temperature to about 0 ℃ while dropwise adding (reacting in an ice water bath), maintaining the system temperature to about 10 ℃ through acid-base reaction heat release, not overheating and not solidifying, stirring for 15 minutes after the feeding is finished, supplementing 50ml of glacial acetic acid into the system, stirring and mixing uniformlyto completely dissolve solids, transferring the system into the 250ml constant pressure funnel, washing the three-necked bottle twice with 30ml of glacial acetic acid, and shaking uniformly to form an acetic acid-ethyl acetate ammonium salt mixed system (II).
Controlling the temperature within the range of 0-5 ℃, dropwise adding the mixed solution (II) into the mixed solution (I), clarifying the nitric acid-acetic anhydride mixed system (I) when feeding is started, enabling the mixed solution (I) to be turbid when feeding is carried out to one third, properly ensuring the temperature of the system not to exceed 5 ℃, stirring for 15 minutes at the temperature of 5 ℃ after feeding is finished, naturally recovering the system to 18-20 ℃, stirring for 4-5 hours within the temperature range, stopping stirring to ensure that the system can form obvious solid-liquid separation, enabling the precipitate to be loose, ensuring that the reaction is basically finished if the supernatant is yellowish green, and continuing stirring until the reaction is complete if the supernatant is brownish red.
Standing for precipitation, G3The solids were collected by filtration through a sand core funnel, washed with 2X 80ml of anhydrous ether, P2O5Vacuum drying to obtain white powder weighing 123 g. Recrystallization from isopropanol (solid and solvent W/V1: 10 (g/ml, same below), decolorized with a small amount of activated carbon) gave white flaky crystals weighing 110g, m.p. 101-105 ℃. Adding 110ml of anhydrous ether into the filtrate, shaking up thoroughly, collecting the solid by filtration, washing with 2X 50ml of anhydrous ether, and washing with water2O5Vacuum drying to obtain white powder weighing 24 g. Recrystallization from isopropanol (solid and solvent W/V1: 10, decolorized with a small amount of activated carbon) gave white flaky crystals weighing 22g, m.p. 101-105 ℃. 147g of aminoethanol nitrate crude product is obtained(123g +24g), crude yield 87%.
Comparative examples
Adding 61g (1mol) of aminoethanol into a 100ml three-necked bottle, placing the bottle in an ice salt bath to be cooled to below 0 ℃, dropwise adding 138g (2.2mol) of fuming nitric acid under stirring, continuing stirring for 0.5 hour at minus 5-0 ℃ after dropwise adding, then pouring the reaction liquid into a 1000ml conical bottle, adding 500ml of absolute ethyl alcohol and 300ml of diethyl ether, freezing and crystallizing after stirring, and performing suction filtration to obtain white powder 2-aminoethanol nitrate (to obtain 22g of a product, wherein the yield is 20.7%).
In the experimental process of the comparative example in the prior art, fuming nitric acid is directly added into ethanolamine in a dropwise manner, the temperature is not easy to control, the reaction condition is severe and careless, and the temperature rises rapidly to cause explosion; the obtained product has high impurity content, is not easy to purify, is easy to yellow and has low yield.
Adding fuming nitric acid into acetic anhydride to form a nitric acid-acetic anhydride mixed system (I); dripping glacial acetic acid into ethanolamine, and fully stirring to form an acetic acid-ethyl acetate ammonium salt mixed system (II); the mixed system (I) and the mixed system (II) are mixed to react mildly, the reaction is controllable, the product is easy to process, the yield is high, and the product purity is high.
Claims (9)
1. A method for preparing ammonium nitrate radical ethanol nitrate ester, comprising the following steps:
① fuming nitric acid is added into acetic anhydride at the temperature lower than 10 ℃, the molarratio of acetic anhydride to fuming nitric acid is 1: 0.5-5, and a nitric acid-acetic anhydride mixed system (I) is formed;
②, controlling the temperature to be lower than 20 ℃, dropwise adding glacial acetic acid into ethanolamine, wherein the molar ratio of ethanolamine to glacial acetic acid is 1: 0.5-5, and forming an acetic acid-ethyl acetate ammonium salt mixed system (II);
③ and controlling the temperature to be lower than 20 ℃, dropwise adding the mixed solution II into the mixed solution I for reaction, filtering and collecting solid to obtain the ammonium nitrate ethanol nitrate (III).
2. A process according to claim 1 wherein in step ① the molar ratio of acetic anhydride to fuming nitric acid is 1: 1 to 2.
3. The method according to claim 2, wherein in step ②, the molar ratio of ethanolamine to glacial acetic acid is 1: 1-2.
4. The method according to claim 3, wherein the temperature is in the range of-10 to 20 ℃ in step ③.
5. The process according to any one of claims 1 to 4, wherein the temperature in step ① is in the range of-20 to 10 ℃.
6. The process according to any one of claims 1 to 4, wherein the temperature in step ② is in the range of-10 to 20 ℃.
7. The process according to any one of claims 1 to 4, wherein the product obtained in step ③ is subjected to recrystallization.
8. The process according to claim 7, wherein isopropanol is used as the recrystallization solvent in step ③.
9. The process of claim 8 wherein the recrystallization in step ③ is decolorized using activated carbon.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310117371 CN1242982C (en) | 2003-12-12 | 2003-12-12 | Method for preparing nitrate ethoxide in ammonium nitrate group |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200310117371 CN1242982C (en) | 2003-12-12 | 2003-12-12 | Method for preparing nitrate ethoxide in ammonium nitrate group |
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| CN1626500A CN1626500A (en) | 2005-06-15 |
| CN1242982C true CN1242982C (en) | 2006-02-22 |
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| CN101928226B (en) * | 2009-07-30 | 2013-08-21 | 许景峰 | N-(2-ethoxy) feriilamidoethyl nitrate compound and preparation method thereof |
| CN102816032B (en) * | 2012-09-11 | 2015-02-25 | 北京理工大学 | Xylitol nitrate ray-level simulation explosive mimics |
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