An overview is given on the state-of-the-art in synthesis of sequence-controlled and sequence-defined oligomers and polymers.

A technique for the continuous on-line monitoring of polymerization processes by electrospray ionization mass spectrometry (ESI-MS) is presented via coupling with a commercial microreactor system. The potential is demonstrated by monitoring polymerizations in real time under synthesis conditions. Furthermore, a single acrylate monomer insertion into a oligo-RAFT agent, as used in the synthesis of monodisperse sequence controlled materials, was optimized by on-line screening of reaction conditions.

Polymerizations are challenging to monitor online. Next to spectrometric information, which indicates the composition, progress, and identity of polymers, other characterization methods also need to be employed for paramount monitoring. Information on molecular weight distributions and end group patterns are often indispensable for accurate process (and product) control. An overview of existing characterization methods, which can be used for online monitoring, and eventually for automating, multistep polymerizations, is given.

The utility of automated high-throughput methods for the one pot synthesis of functional polymers of increased complexity is reported.

The reaction efficiency of single unit monomer insertion (SUMI) reactions via the reversible addition fragmentation chain transfer (RAFT) method is investigated in detail by the determination of obtained product yields of optimized batch and microflow synthesis procedures in combination with kinetic simulations of the radical insertion process. A method is developed to obtain exact concentration information on different SUMI products from calibration of the corresponding electrospray ionization mass spectra that are recorded on-line during synthesis. Experimental data show that isolated yields decrease for each subsequent SUMI reaction. This effect is investigated via kinetic modelling to understand which parameters have a beneficial or negative influence on the reaction outcome. Although most reaction conditions (such as monomer concentration or radical flux) do not play a considerable role in the obtainable yield of the insertion reaction, the model clearly shows that the propagation rate coefficient must display a strong chain-length dependency in order to explain the experimental observations. When taken into account, the simulations very well fit the experimental data obtained from optimized microreactor flow synthesis and recommendations for SUMI reactions are formulated. Finally, the optimized SUMI conditions obtained from microreactor experiments and kinetic modelling insights have been applied to upscale the SUMI synthesis reactions in a mesoflow reactor. This demonstrates the simple upscalability of continuous flow reactions and opens the pathway towards future synthesis of longer sequence controlled oligomers.

Well-defined multiblock copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization in a fully continuous multireactor cascade. The reactor is designed to accommodate a broad variety of monomers to be polymerized to various chain lengths close to full monomer conversion under identical conditions. Based on theoretical considerations, reactor volumes and reactant concentrations were optimized, and reactions were carried out with residence times of 40 min and at 100 °C in most cases. A broad variety of homo-, diblock-, triblock and tetrablock copolymers was obtained. The reactor can be used for high-throughput experimentation and can in principle be operated by non-specialists due to its automated character. Further, the setup allows for upscaling of reactions. The tetrablock copolymer PnBuA-b-PMA-b-PEA-b-PtBuA was obtained in quantities of 150 g in one day reactor runtime, illustrating the high potential and applicability of continuous flow processes for polymerizations.