Two-chamber reactors and flow chemistry as valuable tools in organic synthesis

In this thesis, an attempt was made to develop organic synthesis methodology involving dangerous gases. The idea was to provide tools to the academic and industrial research society to work in a safe manner with these products. In general, in an academic lab setting, organic reactions involving gaseous reagents are avoided because of both practical and safety concerns. Therefore, alternatives for these reactions are needed. A convenient and safe method was developed to generate carbon monoxide, a synthetically useful but highly dangerous gas. The gas is formed in a closed system where it is consumed as well. This new method uses formic acid, mesyl chloride and triethylamine to generate carbon monoxide, 3 commodity chemicals available in every organic synthesis lab and is one of the cheapest ways known to generate carbon monoxide on laboratory scale. This methodology was applied by means of a two-chamber reactor to the development of minimalist α-helix peptidomimetics, scaffolds that can display amino acid side chains in a geometrically similar way as a protein α-helix. Palladium catalyzed aminocarbonylation reactions were used to assemble the helix mimetics. Previously unreported pyrazine based oligoamide α-helix mimetics were generated in this fashion. Next, the use of sulfur dioxide as reactant in organic synthesis was examined. Facing similar problems as with carbon monoxide, we developed a method for the large scale laboratory synthesis of DABSO, a common gas surrogate for sulfur dioxide, again making use of two-chamber reactors. Finally, flow chemistry was used to expand classic batch synthetic tools. In a first example, the use of a carbon monoxide precursors was explored in flow using at tube in tube reactor setup. Another example involves the application of flow chemistry to the synthesis of glycerol carbonate from glycerol. Glycerol is an industrial waste product of the production of biodiesel while glycerol carbonate is considered a green chemical.status: publishe