Preparation of 3-amino-1-propanol_Industrial additives

Background and overview^[1][2]

3-Amino-1-propanol is a commonly used drug intermediate, used in the synthesis of cyclophosphamide, cardiodin and other drugs, and can also be used in the synthesis of DL-panthenol. The conventional method is obtained by catalytic hydrogenation of β-hydroxypropionitrile, adding β-hydroxypropionitrile, Rainy nickel, ethanol, and ammonia into an autoclave for reaction. The purity of the obtained 3-amino-1-propanol exceeds 95%, and the product is collected. The rate is close to 60%; in 2004, Sylvie Picard et al. synthesized 3-amino-1-propanol using DMSO and dichloromethane. The purity of the product obtained was 98%, but the yield was only 12%; in 2007, Springgerta et al. People use 3-aminopropionic acid ethyl ester and 2-cyanoethanol to synthesize 3-amino-1-propanol, and also obtain a high-purity product, but the yield is still very low. The above methods all have shortcomings such as dangerous raw materials, low yield, and harsh reaction conditions.

3-amino-1-propanol

Preparation^[2]

The production of amino-1-propanol mainly uses hydrogenation reduction. Among them, industrial production mainly uses catalytic hydrogenation synthesis. Among them, hydroxypropionitrile is used as raw material, ammonia is used as solvent, and Raney nickel is used. As a catalyst, hydrogenation at high temperature and low pressure to prepare 3-amino-1-propanol is the main production process. In this process, the conversion rate of hydrogenation of hydroxypropionitrile is as high as 99%, and the conversion rate of 3-amino-1-propanol is The recovery rate is also above 90%. However, this process has the problem of troublesome separation of by-products. Generally, at least the process of removing water, ammonia, by-products and distillation is required to achieve a purity of 3-amino-1-propanol above 99%.

Specific method:

Mix hydroxypropionitrile and ammonia at a mass ratio of 1:2.6, and use Raney nickel as a catalyst at 103°C and 10Kpa to hydrogenate hydroxypropionitrile in a fixed-bed reactor. The hydrogenation reaction The time is 24 minutes, and then the prepared product is obtained. The prepared product and the Raney nickel catalyst are separated by a precipitation method using sodium hydroxide in the range of 54-56°C to obtain 3-amino-1-propanol.

Refining process^[2]

1) Fix the catalyst on the partition plate in the reaction kettle, fix the partition plate in the reaction kettle through the grid plate, and set up at least five layers of non-contact partition plates in the reaction kettle;

2) Add hydroxypropionitrile into the reaction kettle. The mass ratio of hydroxypropionitrile to catalyst is 5-7:0.3, so that hydroxypropionitrile floods the uppermost partition in the reaction kettle;

3) Pour in a mixed gas of ammonia and hydrogen through the aeration plate at the bottom of the reactor. The volume ratio of ammonia to hydrogen in the mixed gas is 10-20:1, and the volume ratio of the mixed gas to hydroxypropionitrile is 12 -15:1, the temperature of the mixed gas is 100-140℃, and the pressure in the reactor is maintained at 60-80Kpa;

4) After the mixed gas is introduced, continue to introduce hydrogen at a temperature of 100-140°C for 20-30 minutes to obtain the product liquid in the reaction kettle;

5) Pass the product liquid into a distillation tower to purify 3-amino-1-propanol, and the distillation tower outputs 3-amino-1-propanol at the top.

Main reference materials

[1] Yao Yueliang, Zhou Zuxin, Tao Jianwei, Meng Jianliang, & Lu Qingning. (2004). 3-Aminopropanol. Pharmaceutical and Chemical Engineering, 000(006), 40-40.

[2] Chen Peirong, Zhu Changren, & Chu Minghua. (1980). Synthesis of 3-aminopropanol. Pharmaceutical Industry (01), 5-6.

[3] Xiao Wangchuan, Wang Yemin, Wang Renzhang, Zhang Lihua, & Zheng Keli. (2014). Controlled synthesis of superparamagnetic ferroferric oxide microspheres by 3-aminopropanol. Journal of Inorganic Chemistry, 30(11), 2559- 2563.