阅读说明：本技术 一种3-氨基-1-金刚烷醇的制备方法 (Preparation method of 3-amino-1-adamantanol ) 是由 李彬 刘万里 李春贵 许晓勇 于 2020-12-14 设计创作，主要内容包括：本发明公开了一种3-氨基-1-金刚烷醇的制备方法,包括以下步骤：A、将盐酸金刚烷胺加入温度为5～10℃的硝酸溶液中,搅拌1h；B、在硝酸溶液中加入硫酸和硝酸钠的混合水溶液,搅拌2～5h,搅拌过程保持温度为10～15℃；C、在步骤B制得的溶液中缓慢加入过量固体氢氧化钠,持续搅拌,温度控制在低于50℃；D、使用过滤器对含有固体氢氧化钠的悬浮液进行抽滤,过滤液经过萃取、干燥后得到3-氨基-1-金刚烷醇成品。本发明能够改进现有技术的不足,提高了通过硝化反应制备3-氨基-1-金刚烷醇的收率。(The invention discloses a preparation method of 3-amino-1-adamantanol, which comprises the following steps: A. adding amantadine hydrochloride into a nitric acid solution at the temperature of 5-10 ℃, and stirring for 1 h; B. adding a mixed aqueous solution of sulfuric acid and sodium nitrate into a nitric acid solution, stirring for 2-5 hours, and keeping the temperature at 10-15 ℃ in the stirring process; C. slowly adding excessive solid sodium hydroxide into the solution prepared in the step B, and continuously stirring, wherein the temperature is controlled to be lower than 50 ℃; D. and (3) carrying out suction filtration on the suspension containing the solid sodium hydroxide by using a filter, and extracting and drying the filtrate to obtain a finished product of the 3-amino-1-adamantanol. The invention can improve the defects of the prior art and improve the yield of the 3-amino-1-adamantanol prepared by nitration reaction.)

1. A preparation method of 3-amino-1-adamantanol is characterized by comprising the following steps:

A. adding amantadine hydrochloride into a nitric acid solution at the temperature of 5-10 ℃, and stirring for 1 h;

B. adding a mixed aqueous solution of sulfuric acid and sodium nitrate into a nitric acid solution, stirring for 2-5 hours, and keeping the temperature at 10-15 ℃ in the stirring process;

C. slowly adding excessive solid sodium hydroxide into the solution prepared in the step B, and continuously stirring, wherein the temperature is controlled to be lower than 50 ℃;

D. and (3) carrying out suction filtration on the suspension containing the solid sodium hydroxide by using a filter, and extracting and drying the filtrate to obtain a finished product of the 3-amino-1-adamantanol.

2. The method for producing 3-amino-1-adamantanol according to claim 1, characterized in that: in the step A, the concentration of the nitric acid solution is 65 wt%, and the mixing volume ratio of the nitric acid solution to the amantadine hydrochloride is 25: 1.

3. The method for producing 3-amino-1-adamantanol according to claim 2, characterized in that: in the step B, the molar ratio of the sulfuric acid to the sodium nitrate in the mixed aqueous solution is 5:1, and the volume ratio of the nitric acid solution to the mixed aqueous solution is 1: 1.

4. The method for producing 3-amino-1-adamantanol according to claim 1, characterized in that: the filter comprises a filter cylinder (1), a top cover (2) is fixed at the top of the filter cylinder (1), the side wall of the filter cylinder (1) is connected with a vacuum pump (4) through a vacuum tube (3), a plurality of layers of filter screens (5) are arranged in the top cover (2), a layer of filter paper (6) is laid on each layer of filter screen (5), and the side wall of the top cover (2) is provided with feed openings (7) which correspond to the filter screens one by one.

5. The method for producing 3-amino-1-adamantanol according to claim 4, characterized in that: an adsorber (8) is arranged at the joint of the vacuum tube (3) and the filter cartridge (1).

6. The method for producing 3-amino-1-adamantanol according to claim 5, characterized in that: the filter is characterized in that a rotating shaft (9) is movably connected to the center of the top cover (2), stirring blades (10) which correspond to the filter screens (5) one to one are fixed on the rotating shaft (9), a scraper blade (11) is fixed on one side, back to the rotating direction, of each stirring blade (10), the stirring blades (10) are in clearance fit with the filter paper (6), and the scraper blade (11) is in sliding contact with the filter paper (6).

7. The method for producing 3-amino-1-adamantanol according to claim 6, characterized in that: the novel scraper is characterized in that notches (12) are formed in two ends of the scraper (11), a plurality of diversion trenches (13) are formed in the liquid-facing surface of the scraper (11), and the diversion trenches (13) are communicated with the notches (12).

Technical Field

The invention relates to the technical field of chemical equipment, in particular to a preparation method of 3-amino-1-adamantanol.

Background

3-amino-1-adamantanol is an important pharmaceutical intermediate and is widely applied to the preparation of medicaments for resisting diabetes and viruses and synthesizing human hematopoietic components. In the process for producing 3-amino-1-adamantanol, nitration by using amantadine hydrochloride is an important mode. However, the yield of 3-amino-1-adamantanol in the preparation process is low, and how to further improve the yield of 3-amino-1-adamantanol becomes one of the hot spots of the research in the prior art.

Disclosure of Invention

The technical problem to be solved by the invention is to provide a preparation method of 3-amino-1-adamantanol, which can solve the defects of the prior art and improve the yield of 3-amino-1-adamantanol prepared by nitration reaction.

In order to solve the technical problems, the technical scheme adopted by the invention is as follows.

A preparation method of 3-amino-1-adamantanol comprises the following steps:

A. adding amantadine hydrochloride into a nitric acid solution at the temperature of 5-10 ℃, and stirring for 1 h;

B. adding a mixed aqueous solution of sulfuric acid and sodium nitrate into a nitric acid solution, stirring for 2-5 hours, and keeping the temperature at 10-15 ℃ in the stirring process;

C. slowly adding excessive solid sodium hydroxide into the solution prepared in the step B, and continuously stirring, wherein the temperature is controlled to be lower than 50 ℃;

D. and (3) carrying out suction filtration on the suspension containing the solid sodium hydroxide by using a filter, and extracting and drying the filtrate to obtain a finished product of the 3-amino-1-adamantanol.

Preferably, in the step A, the concentration of the nitric acid solution is 65 wt%, and the mixing volume ratio of the nitric acid solution and the amantadine hydrochloride is 25: 1.

Preferably, in step B, the molar ratio of the sulfuric acid to the sodium nitrate in the mixed aqueous solution is 5:1, and the volume ratio of the nitric acid solution to the mixed aqueous solution is 1: 1.

Preferably, the filter comprises a filter cylinder, a top cover is fixed at the top of the filter cylinder, the side wall of the filter cylinder is connected with a vacuum pump through a vacuum tube, a plurality of layers of filter screens are arranged in the top cover, a layer of filter paper is laid on each layer of filter screen, and the side wall of the top cover is provided with feed ports which correspond to the filter screens one to one.

Preferably, the joint of the vacuum tube and the filter cartridge is provided with an adsorber.

Preferably, the center of the top cover is movably connected with a rotating shaft, stirring blades which correspond to the filter screens one by one are fixed on the rotating shaft, a scraping plate is fixed on one side of each stirring blade, which faces away from the rotating direction, the stirring blades are in clearance fit with the filter paper, and the scraping plates are in sliding contact with the filter paper.

Preferably, the two ends of the scraper are provided with notches, the liquid level of the scraper is provided with a plurality of diversion trenches, and the diversion trenches are communicated with the notches.

Adopt the beneficial effect that above-mentioned technical scheme brought to lie in: the invention improves the utilization rate of the reactants by reasonably using the reactants and reaction conditions, thereby improving the yield of the 3-amino-1-adamantanol. In order to improve the treatment efficiency in the suction filtration operation, a large-volume suction filtration apparatus and a high-vacuum treatment environment are required, which increases the risk of breakage of the filter paper. The invention specially designs the filter for suction filtration, reduces the pressure difference born by a single filter layer by adopting a multi-layer filtration mode, and can avoid the damage of the filter paper by using the filter screen to support the filter paper. Through the rotary stirring of the stirring blades, the distribution uniformity of the solid sodium hydroxide and the mixed solution in each layer can be improved, and the utilization rate of the mixed solution is improved. The scraper is used for scraping and flattening the filter paper, so that the filter paper is prevented from being wrinkled. In the rotating scraping process of the scraper, the stirring blade positioned on the front side can effectively disperse nearby sodium hydroxide, and direct friction of sodium hydroxide particles on filter paper is reduced. The scraper blade is provided with the notch and the diversion trench, so that sodium hydroxide particles flowing to the position near the scraper blade can be further guided, and the cleanliness of the scraping part is ensured.

Drawings

FIG. 1 is a block diagram of one embodiment of the present invention.

In the figure: 1. a filter cartridge; 2. a top cover; 3. a vacuum tube; 4. a vacuum pump; 5. filtering with a screen; 6. filtering paper; 7. a feed inlet; 8. an adsorber; 9. a rotating shaft; 10. a stirring blade; 11. a squeegee; 12. a notch; 13. and a diversion trench.

Detailed Description

One embodiment of the present invention comprises the steps of:

A. adding amantadine hydrochloride into a nitric acid solution with the temperature of 5 ℃, and stirring for 1 h;

B. adding a mixed aqueous solution of sulfuric acid and sodium nitrate into a nitric acid solution, stirring for 2.5 hours, and keeping the temperature at 10 ℃ in the stirring process;

C. slowly adding excessive solid sodium hydroxide into the solution prepared in the step B, and continuously stirring, wherein the temperature is controlled to be lower than 50 ℃;

D. and (3) carrying out suction filtration on the suspension containing the solid sodium hydroxide by using a filter, and extracting and drying the filtrate to obtain a finished product of the 3-amino-1-adamantanol.

In the step A, the concentration of the nitric acid solution is 65 wt%, and the mixing volume ratio of the nitric acid solution to the amantadine hydrochloride is 25: 1.

In the step B, the molar ratio of the sulfuric acid to the sodium nitrate in the mixed aqueous solution is 5:1, and the volume ratio of the nitric acid solution to the mixed aqueous solution is 1: 1.

Referring to fig. 1, the filter comprises a filter cartridge 1, a top cover 2 is fixed on the top of the filter cartridge 1, the side wall of the filter cartridge 1 is connected with a vacuum pump 4 through a vacuum tube 3, a plurality of layers of filter screens 5 are arranged in the top cover 2, a layer of filter paper 6 is laid on each layer of filter screen 5, and the side wall of the top cover 2 is provided with feed ports 7 which are in one-to-one correspondence with the filter screens. The joint of the vacuum tube 3 and the filter cartridge 1 is provided with an adsorber 8. The center of the top cover 2 is movably connected with a rotating shaft 9, stirring blades 10 which are in one-to-one correspondence with the filter screens 5 are fixed on the rotating shaft 9, a scraping plate 11 is fixed on one side of each stirring blade 10, which faces away from the rotating direction, the stirring blades 10 are in clearance fit with the filter paper 6, and the scraping plates 11 are in sliding contact with the filter paper 6. The two ends of the scraper 11 are provided with notches 12, the liquid level of the scraper 11 is provided with a plurality of diversion trenches 13, and the diversion trenches 13 are communicated with the notches 12.

The suspension is poured onto the filter screen 5 at the top of the top cover 2, the vacuum pump 4 is started, and the suspension is filtered by each filter paper 6 in turn and collected in the filter cartridge 1. The rotation shaft 9 is rotated while suction-filtering, and the stirring vanes 10 and the scraper 11 are continuously rotated. The thickness of the sodium hydroxide particle layer on each layer of filter paper 6 is kept to be more than 0.1mm in the suction filtration process, and when the sodium hydroxide is too little, the sodium hydroxide is supplemented through the feed inlet 7.

The invention can improve the yield of the 3-amino-1-adamantanol to more than 95 percent.

The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.