Scale-up of the Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization Using Continuous Flow Processing

ABSTRACTCopper(0)‐mediated controlled radical polymerization (CRP), or single‐electron transfer‐living radical polymerization (SET‐LRP) is a robust and dynamic technique that has attracted considerable academic and industrial interest as a synthetic tool for novel value‐added materials. Although SET‐LRP possesses many advantages over other forms of CRP, this novel chemistry still requires concurrent engineering solutions for successful commercial application. In this highlight, the evolution of atom‐transfer radical polymerization chemistry and development in continuous processes is presented, leading to recent research on the use of SET‐LRP in continuous flow tubular reactors. The proofs of concept are reviewed, and remaining challenges and unexplored potential on the use of continuous flow processes with SET‐LRP as a powerful platform for the synthesis of novel polymeric materials are discussed. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3081–3096

An automated continuous flow system capable of producing protected deoxy‐sugar donors from commercial material is described. Four 2,6‐dideoxy and two 3‐amino‐2,3,6‐trideoxy sugars with orthogonal protecting groups were synthesized in 11–32 % overall yields in 74–131.5 minutes of total reaction time. Several of the reactions were able to be concatenated into a continuous process, avoiding the need for chromatographic purification of intermediates. The modular nature of the experimental setup allowed for reaction streams to be split into different lines for the parallel synthesis of multiple donors. Further, the continuous flow processes were fully automated and described through the design of an open‐source Python‐controlled automation platform.

Visible light-driven complete photocatalytic oxidation of organic dye by plasmonic Au-TiO2 nanocatalyst under batch and continuous flow condition

Upgrading from batch to continuous flow process for the pyrolysis of sugarcane bagasse: Structural characterization of the biochars produced

Synthesis of layered double hydroxides through continuous flow processes: A review

Dynamic evolution of PSD in continuous flow processes: A comparative study of fixed and moving grid numerical techniques

This comprehensive review provides a detailed examination of controlled polymerization in the development of nanogels‐based microfluidic devices. Here, we have explored the integration of atom transfer radical polymerization (ATRP) and reversible addition‐fragmentation chain transfer (RAFT) techniques within microfluidic platforms for the synthesis of nanogels. The synergistic combination of ATRP and RAFT with microfluidics has emerged as a powerful tool for precise control over polymerization reactions, enabling the fabrication of well‐defined, multifunctional nanogels with tailored properties. The review begins with a thorough introduction to the principles of ATRP and RAFT, highlighting their respective advantages in controlled radical polymerization. Subsequently, it elucidates the principles of microfluidics and its profound impact on polymerization processes. The merging of these techniques enables precise control over reaction kinetics, monomer conversions, and molecular weight distributions, facilitating the synthesis of nanogels with unprecedented precision and reproducibility. Furthermore, this review delves into the chemical mechanisms underlying ATRP and RAFT reactions in microfluidic environments, emphasizing the role of various initiators, catalysts, and chain transfer agents. Special attention is given to the impact of microscale flow conditions on reaction kinetics and polymer structure. In addition, the review discusses emerging trends in the field, such as the incorporation of novel monomers and the exploration of environmentally benign reaction conditions.Highlights The controlled polymerization is the mechanism by which we can obtain tailormade material. The nanogel synthesis must ensure the gelation to be in confined dimensions here microfluidics plays key role.

The influence of irradiation conditions on the livingness in xanthate supported photo-iniferter RAFT polymerization is investigated. Multiblock and diblock systems are used to assess chain extension in batch and flow.

Microwave-assisted rapid one-step synthesis of poly(2-oxazoline)-based block copolymers using a dual initiator for CROP and RAFT polymerization

Summary: The ambient temperature (20 °C) reversible addition fragmentation chain transfer (RAFT) polymerization of N‐isopropylacrylamide (NIPAAm) and acrylic acid (AA) conducted directly in aqueous media under γ‐initiation (at dose rates of 30 Gy · h−1) proceeds in a controlled fashion (typically, $\overline M _{\rm w} /\overline M _{\rm n}$ < 1.2) to near quantitative conversions and up to number‐average molecular weights of 2.5 × 105 g · mol−1 for PNIPAAm and 1.1 × 105 g · mol−1 for PAA via two water‐soluble trithiocarbonate chain transfer agents, i.e., S,S‐bis(α,α′‐dimethyl‐α″‐acetic acid)trithiocarbonate (TRITT) and 3‐benzylsulfanylthiocarbonylsulfanyl propionic acid (BPATT). The generated polymers are successfully chain extended, which suggests that the RAFT agents are stable throughout the polymerization process so that complex and well‐defined architectures can be obtained.An increase of the monomer/CTA ratio leads to an increase of the molecular weight for the RAFT polymerization of NIPAAm under γ‐radiation in water using TRITT at ambient temperature.imageAn increase of the monomer/CTA ratio leads to an increase of the molecular weight for the RAFT polymerization of NIPAAm under γ‐radiation in water using TRITT at ambient temperature.

Cover: The Reversible Addition-Fragmentation chain Transfer (RAFT) method is a convenient and versatile process to control free radical polymerization. A key feature of this process is that the so-called RAFT end groups are retained in the polymer product, which may be unfavorable in certain applications. One of the methods for removing the RAFT end group is based on the radical-induced reduction of the end group in the presence of an H-atom source. Herein we describe a novel continuous flow process for this radical-induced reduction. Further details can be found in the article by C. H. Hornung,* A. Postma, S. Saubern, J. Chiefari* on page 246.

Controlled radical polymerization using the reversible addition−fragmentation chain transfer approach (RAFT) was successfully conducted under continuous flow processing conditions, provided that steel tubing was used to prevent quenching of the radical process by oxygen. A series of different monomers, including acrylamides, acrylates, and vinyl acetate, were polymerized to high conversions (between 80 and 100%) at temperatures between 70 and 100 °C using various initiators, solvents, and RAFT agents. Low dispersities, typically between 1.15−1.20, and average molecular weights similar to those of batch RAFT polymerizations were obtained. The methodology provides a facile, alternative scale-up route to conventional batch polymerization, which can be challenging because of the oxygen-sensitive nature of the RAFT process.

In still another procedure, supercritical fluids can be uniquely used to encapsulate very hydrophobic molecules such as potent anticancer drugs, for example, paclitaxel, camptothecin, (a very effective topoisomerase-I inhibitor), and other anti-infective (antiHIV) agents [49]. In this case, the hydrophobic drug and the phospholipids are directly solubilized in the supercritical fluids prior to their injection into a phosphate buffered saline (PBS) or some other biocompatible solvents. After decompression through a nozzle, the supercritical fluids evaporate leaving an aqueous dispersion of liposomes containing hydrophobic molecules entrapped within their lipid bilayer.

The well-defined photoresponsive polymethacrylate containing azo chromophore, poly{1‘-octyloxy-4‘-(6-methacryloxy)hexyloxy-5‘-phenylmethaneone-(2-phenyl)azobenzene (AHMA)} (PAHMA), was prepared via reversible addition−fragmentation chain transfer (RAFT) polymerization in anisole solution using 2-cyanoprop-2-yl 1-dithionaphthalate (CPDN) as the RAFT agent and 2,2‘-azobis(isobutyronitrile) (AIBN) as an initiator. The kinetic plots of polymerization were first-order and the molecular weights (Mn(GPC)s) of the homopolymer (PAHMA) with relatively low polydispersity index values (PDIs ≤ 1.37) increased with monomer conversions throughout the polymerization processes. Furthermore, the kinetic plots of chain extension with both methyl methacrylate (MMA) and styrene (St) using the obtained PAHMA as a macro-RAFT agent were also first-order. The Mn(GPC)s of the diblock copolymers, PAHMA-b-PMMA and PAHMA-b-PS, increased with the respective monomer conversions. These results indicated that most of the PAHMA chains were still “living”. The structure and properties of the polymers were characterized by 1H NMR, GPC, and UV−vis spectra. The photoisomerization of the polymer was examined. On irradiation with a linearly polarized Kr+ laser beam, the birefringence was induced in the polymer films to the level of 0.075. With illumination of linearly polarized Kr+ laser beam at modest intensities (120 mW/cm2), significant surface relief gratings (SRGs) formed on the polymer films were observed.

In this paper, we present the development of a safe water-based synthesis of 1,2,3-triazole using cheap raw materials. Starting from glyoxal and hydrazine, a safe and efficient three-step end-to-end continuous process was developed. This protocol transforms heterogeneous batch reactions into a homogeneous streamlined continuous flow system. This advancement not only obviated the separation of hazardous intermediates, thereby mitigating potential risks, but also significantly diminished the reaction time of each step. This has ensured a rapid and stable supply of 1,2,3-triazole for downstream product development such as tazobactam. Additionally, the study delves into the insights gained from transitioning from batch reactions to continuous flow processes, highlighting the practical and safety benefits of continuous flow synthesis.