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

Abstract

Nucleating agent intermediate 2,2′-methylene-bis­(4,6-di-tert-butylphenol) phosphate chloride was synthesized successfully in a continuous flow by the phosphorylation reaction for the first time. After evaluating several different continuous flow reactors, the continuous Coflore agitated cell reactor (ACR) designed based on the continuous stirred-tank reactor (CSTR) principle was proved capable of overcoming the severe channel clogging caused by the precipitation product triethylamine hydrochloride. This can be attributed to the violent agitation and particle size control by the moving agitators. The yield in continuous flow after optimization reached nearly 98% at 100 °C within the residence time of only 4 min and the optimal equivalents of triethylamine and POCl3 are 2.8 and 1.1, respectively. In contrast to the batch operation, the yield has been increased through continuous operation. This is an effective method for the synthesis of the desired product and exhibits the merits of short residence time, easy operation, and straightforward scale-up.

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

“…34 Moreover, on the basis of our previous research, the reaction was almost impossible to proceed in the absence of triethylamine because of the weak activity of phenol (1). 35 Therefore, triethylamine was also regarded as one of the reactants in the reaction kinetics study. When the reaction was operated in batch mode, a molar ratio of 3.0 for triethylamine with respect to phenol (1) was required to ensure the complete conversion, though as described in the reaction mechanism only two equivalent triethylamine worked.…”

“…According to the condensation reaction mechanism shown in Scheme , instead of simply serving as a base to neutralize generated HCl, triethylamine also participated in the reaction by deprotonating the phenol ( 1 ) . Moreover, on the basis of our previous research, the reaction was almost impossible to proceed in the absence of triethylamine because of the weak activity of phenol ( 1 ) . Therefore, triethylamine was also regarded as one of the reactants in the reaction kinetics study.…”

“…To verify the fitted kinetic model, the calculation results were compared with those obtained from several isothermal experiments. All the operational details were identical to those described in Section , and the product was characterized after a complicated hydrolysis–purification procedure described in our previous publication . As illustrated in Figure , the simulated conversions agreed well with the experimental ones, showing the validity of the kinetic model as well as the superiority of the in-line calorimetric method.…”

Continuous stirred tank reactors in fine chemical synthesis for efficient mixing, solids-handling, and rapid scale-up

“…In contrast to the previous systems, the agitation is performed by moving the whole reactor rather than only the agitator parts. Figure 12 shows one such system [31][32][33].…”

“…AMTech Coflore ACR system used for phosphorylation reaction. Adapted with permission from [33]. Copyright 2021 American Chemical Society.…”