Continuous Ozonolysis as a Key Step of the Darunavir Synthesis Using the IceCube™ Flow Reactor

AIDS is one of the most threatening diseases spread across the planet, affecting about 35 million people worldwide. To improve the quality of life of those affected by HIV, a number of antivirals were developed, such as Darunavir. This molecule has a complex bicyclic core, the synthesis of which is well documented in the literature.

State of the art: An approach described by Ghosh and his co-workers includes an ozonolysis step, which is performed under batch conditions resulting in the desired ketone with 98% yield after 3 hours.[6,7] However, handling the gaseous ozone and working at a very low temperature (78°C) is inconvenient. Adapting the synthesis to a continuous flow system
provides a safe and rapid alternative solution by using in-situ generated ozone, a closed system, and higher temperatures. In this application note, we demonstrate that continuous flow ozonolysis can easily be carried out utilizing the IceCube™ Flow Reactor, developed by ThalesNano, in a safe and efficient way.

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.

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.

Chemistry at high temperature and pressure – using the X-Cube Flash™ continuous flow reactor

The X-Cube Flash™ is a continuous-flow system that can heat and pressurize solutions up to 350°C and 200 bar respectively. The high temperature and pressure significantly decrease reaction times and allows solvents to be reacted under supercritical
conditions. This application note demonstrates the results of important chemical reactions carried out in the X-Cube Flash™ reactor with comparison to literature results based on conventional batch or microwave-assisted reactions.

Efficient Curtius-rearrangement using X-Cube Flash™ continuous flow reactor

ThalesNano has developed a high pressure/high temperature continuous flow reactor, called X-Cube Flash™, to allow chemists to reach chemistry reaction extremities easier and safer compared to batch. In this application note we will focus on the study of the Curtius-reaction from an acyl azide as well ans from acids through in situ formation of the acyl azide using the X-Cube Flash™ reactor.

Aromatic nucleophilic substitutions using X-Cube Flash™ continuous flow reactor

ThalesNano has developed a high pressure/high temperature continuous flow reactor, called X-Cube Flash™, as a viable alternative to MW-chemistry. Several reactions previously reported under MW conditions were realized in the X-Cube Flash™ with improved yield and radically shortened reaction time under safe operation. Our objective was to study the nucleophilic aromatic substitution reaction (F-amine exchange) in metapositions, since the substituted mono- and diaminobenzonitriles are important biological active molecules.

Reductive amination of ketones: novel one-step transfer hydrogenations

Amines are indispensable building blocks in numerous drugs, pesticides and colour pigments. Development of general and efficient methods to prepare amino-compounds is still of high interest to the chemical industry. One of the most convenient methods to synthesize amines is the reductive amination of carbonyl compounds.

Ruthenium-catalyzed metathesis reaction using fixed-bed continuous flow reactor

Olefin metathesis is an excellent method for the preparation of new rings and valuable intermediates in organic synthesis and polymer chemistry. The development of metathesis catalysts that combine high activity with a tolerance towards different functional groups has been important for the widespread utilization of this application. Out of all the various catalysts that have been reported, the ruthenium type catalysts have the widest application due to their easy handling and substrate variability.

Lipase-catalyzed kinetic resolution using X-Cube™ continuous flow reactor

Enzyme catalyzed biotransformation reactions are now widely used in the chemical industry, most commonly in the synthesis of fine chemicals, but also in the production of drugs, agrochemicals and plastics. One of these enzymes is the lipase which can catalyze hydrolysis and also the esterification of ester chemical bonds in lipid substrates. The main reason for using these enzymes is that they provide enantiomerically pure products during a reaction, often with higher purity than what can be achieved by non-enzyme enantiomer catalysts. Enzymes can be utilized in kinetic resolution, based on the different activity of enantiomers in certain reactions.