Photochemical synthesis in batch and micro flow reactors

Mumtaz, Saira (2017) Photochemical synthesis in batch and micro flow reactors. PhD thesis, James Cook University.

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Abstract

This thesis aimed to discover new photochemical transformations and to develop novel flow chemical processes for photochemical reactions.

Despite being isoelectronic to the highly photoactive phthalimides, isatin derivatives remained unreactive and did not yield any inter- or intramolecular photoaddition products. The photochemical studies involving benzoylbenzamides resulted in the discovery of new transformations based on Norrish type II or photoinduced electron transfer processes. Visible light mediated photoredox decarboxylation reactions of N-phenylglycines with enones were successfully carried out using ruthenium tris(bipyridyl) chloride as a photocatalyst. The developed procedure proceeded efficiently under batch as well as flow conditions and yielded both, open and ring addition products.

The previously established photodecarboxylative addition of carboxylates to N-alkylphthalimides was used as a key step in the synthesis of biologically active compounds such as AL12, AL5 and their analogues. The initially formed photoproducts were readily converted by acid catalyzed dehydration followed by amination. A library of compounds was successfully synthesized following this procedure. The photodecarboxylative addition also served as a key step for aristolactam synthesis. The synthesis route combined photodecarboxylative addition, dehydration and photodehydrohalogenation, with the option of further thermal amination. This 3-4 step methodology was successfully applied to the syntheses of parent aristolactams.

The multistep synthesis of bioactive AL12 and its analogues could be successfully realized in-series under flow conditions. Compared to the stepwise batch protocols, the in-series operation prevented time- and resource-demanding isolation steps and gave the final product in high purity and improved yield. Likewise, the cardiovascular active AKS186 has been synthesized using an advanced, commercially available flow reactor. Following a tandem photochemical-thermal process, the desired AKS186 product was obtained in in high purity and in good yield, far exceeding the batch process. Selected examples of photodecarboxylative additions of phenyl acetates to phthalimide derivatives were furthermore realized in a concentrated solar trough flow reactor. The simple reactor achieved a threefold concentration of sunlight. Comparison reactions in batch and in direct sunlight failed to initiate any photoreactions even after prolonged exposure.

The monobromination of acetophenone was investigated by request of Takeda pharmaceuticals. The poor solubility of N-bromosuccinimide was found to be challenging for flow operations. The best reaction conditions gave moderate conversions in reasonable residence times and in diethyether as a solvent.

The Mallory reaction was investigated in supercritical carbon dioxide during a research stay at NAIST in Japan. While supercritical carbon dioxide is generally not an efficient medium for oxidative reactions, the photoisomerization-oxidative electrocyclization cascade furnished higher yields under microflow scCO₂ than under batch conditions.

Item ID: 51976
Item Type: Thesis (PhD)
Keywords: continuous-flow chemistry, green chemistry, history of photochemistry, multistep synthesis, NAIST, photochemistry, photodecarboxylation, solar chemistry, solar technology, Takeda
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Additional Information:

Publications arising from this thesis are available from the Related URLs field. The publications are:

Josland, Sam, Mumtaz, Saira, and Oelgemöller, Michael (2016) Photodecarboxylations in an advanced meso-scale continuous-flow photoreactor. Chemical Engineering and Technology, 39 (1). pp. 81-87.

Mumtaz, Saira, Sattler, Christian, and Oelgemöller, Michael (2015) Solar photochemical manufacturing of fine chemicals: historical background, modern solar technologies, recent applications and future challenges. In: Letcher, Trevor M., Scott, Janet L., and Patterson, Darrell A., (eds.) Chemical Processes for a Sustainable Future. Royal Society of Chemistry, Cambridge, UK, pp. 158-191.

Date Deposited: 11 Jan 2018 00:26
FoR Codes: 03 CHEMICAL SCIENCES > 0305 Organic Chemistry > 030503 Organic Chemical Synthesis @ 40%
03 CHEMICAL SCIENCES > 0305 Organic Chemistry > 030504 Organic Green Chemistry @ 20%
03 CHEMICAL SCIENCES > 0305 Organic Chemistry > 030505 Physical Organic Chemistry @ 40%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 100%
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