Development and Scale-up of the Rapid Synthesis of Triphenyl Phosphites in Continuous Flow

Abstract

A novel method for the synthesis of triphenyl phosphite and its derivatives has been developed in continuous flow. With a total residence time of 20 s, the target product was prepared in a microreactor, and the reaction time was significantly shortened compared with standard single batch reaction conditions. In addition, the reaction of various substrates gave the corresponding products in good to excellent yields under optimized conditions. The reactants could be employed in a stoichiometric ratio, making the reaction more efficient, economical, and environmentally friendly. In addition, scale-up apparatus was designed and assembled, and the kilogram-scale production (up to 18.4 kg/h) of tris­(2,4-di-tert-butylphenyl) phosphite was achieved in 88% yield.

Thermal and Kinetic Research on a Highly Exothermic Condensation Reaction by Powerful Calorimeters

“…In addition, many plastic additive products, such as nucleating agents NA-10 and NA-40 and antioxidants TPP and 168, also contain phosphorus−oxygen bonds formed by exothermic condensation reactions with a similar mechanism. 28 In recent decades, relevant researches have always focused on the synthetic process, but the kinetic and calorimetric data are deficient. The methodology is envisioned to be broadly applied to these similar preparation reactions.…”

Effective Phosphorylation of 2,2′-Methylene-bis(4,6-di-tert-butyl) Phenol in Continuous Flow Reactors

“…20 flow reactors, such as acoustic power, 24,25 oil drop coating, 26 mechanical energy input (continuous stirring tank and oscillating flow), 27,28 and solvent dissolvable for the precipitation. 29 Noel et al have overcome the clogging challenges of palladium-catalyzed amination reactions in flow via acoustic irradiation and achieved stable operation of the process. 25 Pomberger et al developed a small continuous stirred-tank reactor (CSTR) cascade to handle solid-containing photoreactions and realized gram-scale synthesis in 13 h of stable operation, offering a strategy for solid-containing heterogeneous photoflow chemistry.…”

“…30 Mao et al achieved the continuous flow synthesis of antioxidant 168 with chloroform as the solvent rather than toluene (also the most common solvent in this reaction) due to the excellent solubility of the same product 3 in chloroform. 29 In this work, we successfully overcame the clogging problem caused by precipitation product 3 and optimized the reaction process conditions in the continuous Coflore agitated cell reactor (ACR). The performances of different continuous flow reactors were also compared.…”

“…However, product 3 is almost insoluble in toluene (the most common solvent in this reaction) and appeared as precipitates. In fact, the manipulation of precipitation reactions in continuous flow reactors is still a huge challenge that persistently hinders the application of continuous flow in fields ranging from fine chemical synthesis to advanced materials manufacturing. , Accumulation of precipitation products (like halide salts) often results in the sharp increase of system pressure, and then leads to clogging and compelled process shutdown. − A few methods have been proposed to handle solids in continuous flow reactors, such as acoustic power, , oil drop coating, mechanical energy input (continuous stirring tank and oscillating flow), , and solvent dissolvable for the precipitation . Noël et al have overcome the clogging challenges of palladium-catalyzed amination reactions in flow via acoustic irradiation and achieved stable operation of the process .…”

“…Pomberger et al developed a small continuous stirred-tank reactor (CSTR) cascade to handle solid-containing photoreactions and realized gram-scale synthesis in 13 h of stable operation, offering a strategy for solid-containing heterogeneous photoflow chemistry . Mao et al achieved the continuous flow synthesis of antioxidant 168 with chloroform as the solvent rather than toluene (also the most common solvent in this reaction) due to the excellent solubility of the same product 3 in chloroform …”