Mizoroki-Heck cross-coupling - Palladium based catalysts and operation modes

Nemanja Vučetić*

*Korresponderande författare för detta arbete

Forskningsoutput: Typer av avhandlingarDoktorsavhandlingSamling av artiklar


Present market trends in the sector of fine chemicals along with the need for rapid commercialization and less expensive production technologies boosts extensive research in this area. Mass-production of fine chemicals imposes a requirement to implify and shift the production from traditional batch and semi-batch processes to continuous operation mode. It is important to maintain the purity of the produced compounds since the biggest share of synthesized chemicals are used in pharmaceutical industry. Impurities of any kind are not tolerated in the final products implying that the production processes have to be truly efficient and selective.

Different cross-coupling reactions are an integral part of the production of fine chemicals. Among them, palladium catalyzed Mizoroki-Heck reaction is one of the most utilized one due to its flexibility towards various functional groups. The evident shortcomings of this reaction such as inefficient reactant conversion, catalyst instability and metal eaching are often the
bottlenecks of the whole process. The current study tackles these issues through the development of sufficiently active and stable catalysts for Mizoroki-Heck reaction in batch and
continuous flow reactors.

Various amorphous silica supported ionic liquid catalysts (SILCAs) with a double ionic liquid layer loaded with palladium were designed and compared with other catalysts, such as grafted ordered mesoporous silica and metal-organic frameworks (MOFs) deposited with palladium. Throughout the work, the dynamic nature of the metal catalysis of this reaction via a release-and-catch mechanism was observed. This required a special attention on both operation modes, however, naturally it was more detrimental under continuous operation. High catalyst activity and stability that guarantee complete reactant conversion in a single flow pass is a prerequisite for implementing continuous operation policy. To reach this goal, all the synthesized materials were first tested in Mizoroki-Heck reaction of methyl or butyl acrylate with iodobenzene in batch mode under optimized conditions.

During the optimization of the reaction conditions, it was confirmed that the catalysts were mostly active in polar aprotic solvents and at increased reaction temperatures. Use of tertiary
amines as a base is the most favorable option and they should be used in excess because the lack of it can lead to rapid catalyst deactivation. An excess of acrylate is also necessary due to its volatility.

The study of potential catalysts that are suitable for the reaction with methyl acrylate showed that the bis-layered supported ionic liquid catalysts composed of covalently anchored imidazolium bromide and pyridine-carboxylate balanced with tetramethylguanidinium displays extremely high activity and stability in five to six cycles. The existence of N-heterocyclic carbenes, carbon monoxide and nitrogen rich tetramethylguanidine (TMG) in the structure of the ionic liquid layer was mostly important for palladium stabilization. The activity of SILCA
was higher by order of magnitude compared to the palladium deposited ordered mesoporous silica which was grafted with melamine ligands SBA-15/Pr-NH-CH2-melamin-Pd(0), amino-functionalized metal-organic framework IRMOF-3 and magnetized MOF catalysts Fe3O4-NH2@MIL-101-NH2-Pd(OAc)2 tested in the batch reactor under the optimized conditions. A high catalytic activity that enables good conversion at a relatively short residence time is crucial for the application of continuous processes.

In order to upgrade designed bis-layered SILCA, different grafting molecules i.e. carboxylic acids, bases and metal sources were used to modify the surface of SiO2 and the catalytic effect of obtained SILCAs were studied in the reaction with the less reactive butyl acrylate. The impact of the ionic liquid layer structure on the catalyst activity and stability was observed. The rigidity of the ionic liquid layer was attributed to the existence of imidazole ring, while the carboxylic group in the layer coordinated the TMG cations that are most efficient in stabilizing palladium nanoparticles. Fine-tuning of the layer structure resulted in a SILCA with propyl imidazolium bromide-tetramethylguanidinium pentanoate modified SiO2 and loaded with PdCl2 as an optimal choice for the use in the continuous reactor.

Low SILCA loadings were used in simple and long-lasting process in a continuous packed bed reactor for the reaction with butyl acrylate. In contrary to what was observed in the batch
reactor, excessive amounts of the catalyst did not result in deactivation caused by metal agglomeration. Catalyst leaching was verified with on-line UV-VIS spectrometry, and the
catalytic behavior was rationalized to certain extent elucidating the catalytic cycle within the ionic liquid layer. Poisoning was adopted as the main reason for the catalyst deactivation and leaching, which was resolved by the catalyst washing sequences. The new packed bed reactor concept was competitive and even outperforming the commercially available concepts showing the real potential of the designed SILCA and its use for production of fine chemicals in continuous operation mode.
  • Mikkola, Jyri-Pekka, Handledare
  • Salmi, Tapio, Handledare
  • Virtanen, Pasi, Handledare
Tryckta ISBN978-952-12-4120-8
Elektroniska ISBN978-952-12-4121-5
StatusPublicerad - 2021
MoE-publikationstypG5 Doktorsavhandling (artikel)


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