Research on the preparation of tris(hydroxymethyl)nitromethane

Tris(hydroxymethyl)nitromethane, or abbreviated as Tris, also known as 2-Hydroxymethyl-2-nitro-1,3-propanediol,is an important biochemical and chemical buffer and pharmaceutical intermediate. Tris is the buffer component and titration standard for the most common biochemical and molecular biology experiments. It can effectively treat acidosis in patients with acute lung injury and induce a monolayer of corrugated structure by phospholipid bilayer membrane. It is also widely used as a solvent for nucleic acids and proteins, etc.

Preparation of tris(hydroxymethyl)nitromethane

1) Direct hydrogenation

The condensation reaction solution was placed in a 2.0 L autoclave, and 650 mol of methanol, 10 mol of dichloromethane and 12 g of Raney nickel were added. After the autoclave has passed the test and replace the air with nitrogen and hydrogen for 4~5 times, the stirrer is started to adjust the rotation speed. Slowly heat up, then inlet hydrogen gas, the reaction temperature rises to the specified temperature, and reacts at a specified temperature and pressure for 2.5 h. After the reaction is completed, the filtrate is poured into a beaker, cooled to −5°C with brine, and the white crystals are precipitated and then suction filtration, the filtrate was concentrated under reduced pressure, and then cooled and crystallized by suction filtration, and treated three times in the same manner. The product was dried under vacuum.

2) Two-step method

120 g of tris(hydroxymethyl)nitromethane (THNM), 500 g of methanol, 15 g of dichloromethane, and 12 g of Raney nickel (wet) were weighed and added to the autoclave. After the autoclave has passed the test, replace the air with nitrogen and hydrogen for 4~5 times, start the stirrer, and adjust the rotation speed. The temperature is slowly raised, then hydrogen is inletted, the reaction temperature is raised to 50~55°C, the pressure is 2.0~2.5 MPa, and the reaction is carried out at this temperature for 2.5 hours. After the reaction is completed, the catalyst is filtered off, the reaction liquid is cooled and crystallized, and the product is vacuum dried.

Comparison of research data on preparation methods

1) Direct hydrogenation

The direct hydrogenation process for the production of tris(hydroxymethyl)aminomethane was carried out under the different experimental conditions as described above, and the results are shown in Table 1.

2) Two-step production of tris(hydroxymethyl)aminomethane

Since the average yield of direct hydrogenation of tris(hydroxymethyl)aminomethane is low (50% or less) due to condensation of nitromethane with aqueous formaldehyde solution, it does not have the conditions for large-scale industrial production, so the formaldehyde aqueous solution condensation method is used in production. A two-step process for the production of tris(hydroxymethyl)nitromethane is used. The effects of different reaction conditions on the yield were tested. The results are shown in Table 2.

Conclusion

Direct and two-step process for the production of tris(hydroxymethyl)aminomethane, the process is stable, but the yield of tris(hydroxymethyl)aminomethane by direct hydrogenation is lower than two-step process. Most importantly, the cost produced by direct hydrogenation is higher than that of two-step process. It is recommended to produce tris(hydroxymethyl)aminomethane with a two-step process. .

Related links: TRIS

Edited by Suzhou Yacoo Science Co., Ltd.