Kilogram scale synthesis of a Linezolid analogue intermediate via tandem N-arylation and nitro group reduction in a Phoenix™ II. professional continuous flow reactor system

The morpholine ring bears utmost importance in synthetic chemistry and drug design1, since it can be found in numerous bioactive compounds. Analgesics Phenadoxone and Dextromoramide, antihypertensive Timolol, antidepressants Moclobemide and Reboxetine, antibiotics Linezolid and Finafloxacin, as well as the anticancer drug Gefitinib are all FDA approved drugs that contain a morpholine moiety. Using morpholine itself as a nucleophile is one of the most important techniques in the synthesis of such compounds. In this work, we present a large scale, two-step tandem technique for the synthesis of a Linezolid analogue key intermediate via the N-arylation of morpholine followed by a nitro group reduction2, in a flow reactor system that conveniently fits inside a single fume hood.

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High Pressure CO2 activation in gas phase with the Phoenix Flow Reactor™

The emission of carbon dioxide into the atmosphere, the main cause of global warming, is still increasing every year since carbon-rich fossil fuels are still the primary source of energy.

Catalytic hydrogenation of CO2 using sustainable hydrogen sources not only reduces the emission of carbon dioxide, but also produces valuable fuels and chemicals.

High-pressure methanol synthesis is a well-documented commercial process, its industrial implementation started already in the late 1990s. Nowadays, the largest plant is the GO (György Oláh) Methanol Plant located in Iceland, which can convert 5500 tons/year of CO2 (4000 tons/year of methanol). Conventional thermo-catalytic reactors operating at atmospheric pressure are excellent solutions for methane production, however, obtaining higher molecular weight products with good selectivity can be problematic.1,2

This application note evaluates the performance of the Phoenix Flow Reactor™ in the production of value-added chemicals (other than methane) from a low-cost renewable carbon dioxide source.

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Simple flow deuterodehalogenation using polymer-based activated carbon (PBSAC) supported palladium catalysts in CatCart®

Deuterium-labelling is a widely used method in the fields of biomedical, chemical and pharmaceutical industry.

The FDA recently approved the first deuterated API, and nowadays several molecules with deuterated moieties are under clinical testing in order to treat Alzheimer’s, cystic fibrosis, Freidreich’s ataxia, and psoriasis. The kinetic isotope effect enhances pharmacokinetic properties of deuterium-labelled molecules, which might lead to high therapeutic values.

Continuous-flow deuteration has been demonstrated in the H-Cube® before, however the possibility to use it in a green chemical solvent is practically unexplored.

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Ethanol oxidation with heterogeneous catalysis in flow: a batch to flow conversion

Acetic acid is considered to be an important chemical commodity as both a solvent and Bronsted acid. Being one of the first organic molecules that was synthesized in history (Kolbe, 1845), there are a wide range of procedures for its manufacturing. Despite this fact, industrial scale production now requires more environmentally friendly solutions for its sustainable production.

Heterogeneous catalysis has been found to be a useful alternative method to the current Monsanto process industry currently utilizes. With the combination of ThalesNano’s Phoenix Flow Reactor™ and Gas Module™ a reactor system has been built, which is capable to control high temperature–high pressure triphasic gas-liquid-solid reactions providing a safe and efficient environment for organic chemists.

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Polymerization and grafting onto particle surfaces via continuous flow chemistry

Polymer grafted inorganic particles are attractive building blocks for numerous chemical and material applications. Surface initiated controlled radical polymerization (SI-RAFT) is one of the most feasible methods to fabricate these materials. However, conventional in-batch approaches still suffer from several disadvantages, such as time-consuming purification processes, inefficient grafting, and possible gelation problems. A facile method was demonstrated to synthesize homopolymers and block copolymer grafted inorganic particles using continuous flow chemistry in an environmentally friendly aqueous media using the Phoenix Flow Reactor.

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Sonogashira and Suzuki reactions using H-Cube® continuous flow reactor

ThalesNano’s H-Cube® is mainly used to perform hydrogenation reactions, however it can also perform reactions in the absence of hydrogen. When utilizing the “No H2” mode, the H-Cube® acts like a general flow reactor capable of performing other heterogeneous reactions at temperatures and pressures up to 100°C and 100 bar respectively.

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Application note for ScavCarts™ – using H-Cube®

Metal contamination is a major problem for the pharmaceutical and fine chemical industries. A large amount of time and
resource is spent purifying compounds after catalytic steps, so that the metal concentration is within the acceptable limit. Generally, the acceptable limit is 0.05-10 ppm, for those metals that are utilized in hydrogenation. Scavenger resins are often used for metal contamination purification. In this application note, we will demonstrate how the H-Cube® and a scavenger cartridge (ScavCart™) may be combined to perform a reaction and purification in 1 step.

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