Preparation of 1,4-bis(diphenylphosphine)butane_Kain Industrial Additive

Overview^[1]

Organophosphine ligands are one of the most widely used and versatile ligands in contemporary homogeneous catalysis, and are widely used in many fields such as basic theoretical research and large-scale industrial production. Compared with other ligands, organophosphine ligands have superior electronic effects and three-dimensional spatial effects, and can form complexes with many metal salts with novel spatial structures and excellent catalytic properties. Therefore, the synthesis and properties of such ligands are researched. It has always been a hot research topic. 1,4-Bis(diphenylphosphine)butane is an alkane organic compound that can be used as a pharmaceutical synthesis intermediate.

Related research

In recent years, with the continuous deepening of theoretical research on homogeneous catalysis, the study of bidentate phosphine ligands has attracted increasing attention. The results of modification studies on organic phosphine ligands show that bis-diphenylphosphine alkane Ph2P(CH2)nPPh2 is an ideal bidentate phosphine ligand. By increasing the number of methylene groups between two P atoms, the rigidity within the molecule can be weakened, making the distance between P-P more adjustable, and improving the flexibility of the coordination between the P atom and the central atom. Although some literature has reported the synthesis of this type of ligands, the reaction conditions are generally harsh, and the reaction yields are mostly below 90%. Ultrasound-assisted reaction is used to synthesize such ligands, with a yield of more than 90%. However, this method requires the removal of unreacted metallic lithium, by-product phenyllithium, etc., and the operation is complicated. At the same time, the ultrasonic reaction is currently in the laboratory stage. Even if it can be used in the future Industrialization also has unfavorable factors such as large investment and complex equipment, so this method is difficult to apply on a large scale. The well-known bisdiphenylphosphine alkanes include: 1,2-bis(diphenylphosphine)ethane, bisdiphenylphosphinemethane, 1,3-bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)ethane, Bis(diphenylphosphine)butane, 1,3-bis(diphenylphosphine)hexane, etc. 1,4-Bis(diphenylphosphine)butane can be used as a pharmaceutical synthesis intermediate.

Preparation^[1]

The preparation of 1,4-bis(diphenylphosphine)butane is as follows: add 700L tetrahydrofuran and 15kg metallic lithium into a 1000L reaction kettle, and add 220kg diphenylphosphine chloride and diphenyl chloride dropwise at 40°C. After the phosphine reaction is completed, add 62.5kg of 1,4-dichlorobutane dropwise at 50°C. After the reaction is completed, add 2kg of antioxidant 264, remove tetrahydrofuran under reduced pressure, add 500L2M dilute hydrochloric acid, stir, cool, and centrifuge. Use 400L for the filter cake. Methanol was recrystallized to obtain 207kg of white solid 1,4-bis(diphenylphosphine)butane with a purity of 96% and a yield of 97%.

Main reference materials

[1] CN201510026765.7 Preparation method of bisdiphenylphosphine alkane