Daniel Kopetzki

Surface Area Control and Photocatalytic Activity of Conjugated Microporous Poly(benzothiadiazole) Networks

P-conjugated microporous polymers, such as organic semiconductors with additional porosity in the nanorange, are versatile materials. In addition to typical applications for high-surface-area materials, such as gas separation and storage, 3] conjugated polymer networks are also potential heterogeneous catalysts and can be used in optoelectronics and for energy applications. Given the importance of surface area and porosity, a simple methodology to influence these parameters is needed. In order to use conjugated polymer networks as catalysts and catalyst supports their chemical stability needs to be improved. Therefore we designed a stable, fully conjugated network by linking benzothiadiazole as a strong electron-withdrawing moiety through three Csp Csp bonds to benzene as a weak electrondonating component. The surface area of these novel conjugated microporous polymer networks could be adjusted by a simple synthetic protocol. Benzothiadiazole monomers have proven great stability towards oxidation in photovoltaic applications. The lowband-gap character, high absorption coefficient, and suitable energy levels of benzothiadiazole result in a very strong acceptor to be used in optoelectronic materials, such as lowband-gap polymers, 8] non-fullerene acceptors, or n-type field effect transistors. The combination of weak electron donors, such as a phenyl group with benzothiadiazole, may prevent a fast recombination of excitons and increase the yield of intersystem crossing to the triplet state of the polymer, thereby rendering it suitable for photosensitizing. Conjugated linear polymers with backbones based on the poly(phenylene ethynylene) structure or the polythiophene–porphyrin dyad repeat unit can generate singlet oxygen in water upon irradiation. Singlet oxygen is used for a number of applications, such as for treatment of waste water or in the synthesis of fine chemicals. An industrial process carried out on a scale of several tons a year is the photochemical oxidation of citronellol to rose oxide. Different dyes and transition metal complexes can generate singlet oxygen upon irradiation, and these sensitizers can be used in homogeneous solution or immobilized on a solid support. Working under heterogeneous conditions allows for easy separation of the sensitizer after reaction and reusability. Traditional systems suffer however from quenching of the produced singlet oxygen by the solid support, which reduces the quantum yield. Incorporation of a photosensitizing structure into a polymer backbone is particularly attractive, because no support to immobilize the sensitizer is needed when an insoluble photoactive polymer network is used. Therefore the ability of the conjugated microporous polymer (CMP) network to act as a singlet oxygen photosensitizer was evaluated by employing the oxidation of a-terpinene to ascaridole. The pore size and structure as well as specific surface area are beneficial in providing a high accessibility of exited solid polymer for solubilized oxygen, thus resulting in high efficiency for singlet oxygen generation in dependence of the pore architecture. A series of polymer networks based on benzothiadiazole as building block was synthesized through palladium-catalyzed Sonogashira–Hagihara cross-coupling polycondensation of 4,7-dibromobenzo[c][1,2,5]thiadiazole with 1,3,5-triethynylbenzen (Scheme 1).

A Continuous‐Flow Process for the Synthesis of Artemisinin

Isolation of the most effective antimalarial drug, artemisinin, from the plant sweet wormwood, does not yield sufficient quantities to provide the more than 300 million treatments needed each year. The high prices for the drug are a consequence of the unreliable and often insufficient supply of artemisinin. Large quantities of ineffective fake drugs find a market in Africa. Semisynthesis of artemisinin from inactive biological precursors, either dihydroartemisinic acid (DHAA) or artemisinic acid, offers a potentially attractive route to increase artemisinin production. Conversion of the plant waste product, DHAA, into artemisinin requires use of photochemically generated singlet oxygen at large scale. We met this challenge by developing a one-pot photochemical continuous-flow process for the semisynthesis of artemisinin from DHAA that yields 65 % product. Careful optimization resulted in a process characterized by short residence times. A method to extract DHAA from the mother liquor accumulated during commercial artemisinin extractions, a material that is currently discarded as waste, is also reported. The synthetic continuous-flow process described here is an effective means to supplement the limited availability of artemisinin and ensure increased supplies of the drug for those in need.

Continuous‐Flow Oxidative Cyanation of Primary and Secondary Amines Using Singlet Oxygen

Primary and secondary amines can be rapidly and quantitatively oxidized to the corresponding imines by singlet oxygen. This reactive form of oxygen was produced using a variable-temperature continuous-flow LED-photoreactor with a catalytic amount of tetraphenylporphyrin as the sensitizer. α-Aminonitriles were obtained in good to excellent yields when trimethylsilyl cyanide served as an in situ imine trap. At 25°C, primary amines were found to undergo oxidative coupling prior to cyanide addition and yielded secondary α-aminonitriles. Primary α-aminonitriles were synthesized from the corresponding primary amines for the first time, by an oxidative Strecker reaction at -50 °C. This atom-economic and protecting-group-free pathway provides a route to racemic amino acids, which was exemplified by the synthesis of tert-leucine hydrochloride from neopentylamine.

Continuous synthesis of artemisinin-derived medicines

Described is a continuous, divergent synthesis system which is coupled to continuous purification and is capable of producing four anti-malarial APIs. The system is comprised of three linked reaction modules for photooxidation/cyclization, reduction, and derivatization. A fourth module couples the crude reaction stream with continuous purification to yield pure API.

Hydrothermal formose reaction

The self-condensation of formaldehyde is a one pot reaction resulting in a complex mixture of carbohydrates. Based on a simple chemical, the reaction was previously considered as a prebiotic source for sugar generation. Usually, a high pH and the presence of catalytically active species are required. Here, the formose reaction was performed under hydrothermal temperatures up to 200 °C, and carbohydrates were obtained under even simpler conditions. We found no pronounced catalytic influence of active cations, and a slightly alkaline pH was sufficient to induce the reaction. Maximum yield was reached in very short times, partly less than 1 minute. No selectivity for a particular carbohydrate, although searched for, was found. Contrary to reactions performed at lower temperatures, hexoses were only formed in negligible yields, whereas the shorter carbohydrates accounted for the major fraction. Among the pentoses, ribose and the ketoses with corresponding stereochemistry were formed in higher yields compared to the reaction at lower temperature. Furthermore, we identified 2-deoxyribose in the product mix and found strong indications for the presence of other deoxy compounds. Hence, the hydrothermal formose reaction shows some remarkable differences compared to the conventional reaction at moderate temperatures.

Continuous Photochemical Cleavage of Linkers for Solid-Phase Synthesis

Photolabile linkers are an attractive alternative for solid-phase synthesis because they can be cleaved using light. However, irradiation in a classical batch photoreactor results in incomplete cleavage of the photolabile linkers. It is demonstrated that a continuous flow photoreactor is superior to a batch photoreactor for the cleavage of a linker from polystyrene resin.

Mechanistic study of hydrothermal synthesis of aromatic polyimides

A mechanistic study regarding the synthesis of aromatic polyimides (PIs) under hydrothermal conditions is presented. We demonstrate evidence that the first step of the reaction is the formation of a nylon type salt, which can be isolated. Upon heating the salt in the presence of water at 180 °C, polyimides are formed from the salts. Additionally performed DFT calculations substantiate the experimental findings and give evidence that the formation of imides is energetically favorable in hot water. The intermediate salts as well as the resulting PIs are characterized by diverse analytical techniques (SEC, FT-IR, WAXS, SEM). By selective fractionation, it is possible to obtain polyimides of moderate to high molecular weights that form tough films. The polymerization mechanism is discussed, and it is shown that different loci of reaction are possible, namely interfacial polycondensation, heterophase polymerization and topochemical transformations, which seem to occur in parallel. Finally, poloxamers can be used as additives for the fine-tuning of the polymer morphology.

Photochemistry in Fight against Malaria

entdeckten Artemisinin bei der Suche nach einem wirksamen Pflanzenextrakt gegen Malaria. Über 2000 Kräuterzubereitungen wurden dazu untersucht und ein Extrakt des Einjährigen Beifuß (Artemisia annua) als höchst effektiv identifiziert. Es gelang schließlich, die wirksame Komponente abzutrennen und deren Struktur aufzuklären. Wegen der Bedeutsamkeit dieser Entdeckung erhielt die chinesische Wissenschaftlerin Tu Youyou im Jahr 2011 den Lasker DeBakey Clinical Medical Research Award. Die Komplexität der Struktur von Artemisinin (Abbildung 2) ist ziell für die Wirksamkeit ist, scheint die gesamte Anordnung der weiteren funktionellen Gruppen nötig zu sein, um den Parasiten zu töten. Einfachere Peroxide sind nämlich nicht gegen Malaria wirksam. Neben reinem Artemisinin wirken auch Derivate (Abbildung 2). Durch Reduktion ist beispielsweise Dihydroartemisinin zugänglich, das über die Alkoholgruppe weiter zu Ethern wie Artemether oder Estern umgewandelt werden kann. Aufgrund der komplexen Struktur ist die Totalsynthese von Artemisinin zu aufwendig und nicht wirtschaftlich. Daher wird der Wirkstoff ausschließlich durch ExDaniel Kopetzki, Peter H. Seeberger