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Effective Phosphorylation in the Coflore® ACR continuous flow reactor

AM Technology are pleased to share a recent publication in OPR&D by the team led by Professor Zhong Xin at the Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology (ECUST), titled “Effective Phosphorylation of 2,2′-Methylene-bis(4,6-di-tert-butyl) Phenol in Continuous Flow Reactors” features the Coflore® ACR.

Reaction schematic showing an overview of the phosphorylation reaction in a Coflore ACR
An overview of the phosphorylation, taken from the publication abstract: Org. Process Res. Dev. 2021, 25, 9, 2060–2070

The article reports that the Zhong Xin lab were able to successfully synthesize nucleating agent intermediate 2,2′-methylene-bis(4,6-di-tert-butylphenol) phosphate chloride in a continuous flow by phosphorylation for the first time.

The paper states “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.

A render of the Coflore ACR system
The Coflore ACR by AM Technology - A highly configurable and versatile continuous flow reactor.

The high-shear agitators within the Coflore® ACR cell block enabled the heterogenous mixture to achieve excellent mixing and disturbance and was particularly able to avoid sedimentation of solids during the phosphorylation reaction process.

A cutaway render of the ACR cell block
A cutaway render of the ACR cell block

We extend our sincere gratitude to the team at ECUST for highlighting the Coflore® ACR in this publication and we can’t wait to read their future papers on flow chemistry! If you would like to access the paper, it can be found here: and if you would like to find out more about the Coflore® range of flow chemistry reactors please email


“One of today's most important tools for modernizing the pharmaceutical industry is a process known as continuous manufacturing”

Director of the FDA’s Centre for Drug Evaluation and Research,

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