Deprotection reactions using the H-Cube® continuous flow reactor

Protecting groups play a central role in modern organic synthesis. The benzyl groups and benzyl carbamate or Cbz groups are some of the most commonly used protecting groups and play a central role in the protection of alcohols, carboxylic acids and amines. The benzyl and benzyl carbamate groups are removed using catalytic hydrogenation using elevated temperature. The H-Cube® is able to remove benzyl groups from amines, acids or alcohols very efficiently in one pass through a 10% Pd/C CatCart®. This application note gives examples of deprotection reactions performed on the H-Cube®.

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Asymmetric hydrogenation using H-Cube® continuous flow reactor

Catalytic asymmetric hydrogenation is one of the most efficient and convenient methods for synthesizing optically active compounds, e.g. amino acids, chiral amines and itaconic acids, which are widely used in the pharmaceutical and fine chemical industries.
At ThalesNano we have performed asymmetric hydrogenation on the H-Cube® flow hydrogenation system using solid-supported Rh catalysts bearing chiral phophorus ligands. The catalyst PTA/Al2O3/[Rh(COD)(chiral ligand)] was tested in the chiral hydrogenation of (Z)-α-acetamidocinnamic acid methyl ester.

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Fast and continuous transfer hydrogenation of aromatic nitriles to amines

The reduction of nitriles is one of the most common route to synthesize primary amines, which are key intermediates in fine-chemical, pharmaceutical, and agricultural industries. Both direct (employing H2 gas) and transfer hydrogenation can be used for this purpose. The latter is a rapidly growing field taking into account green chemistry and economic considerations, avoiding the handle of hazardous hydrogen gas. By considering the last restriction, smart systems with in situ H2 gas production could be also an alternative solution.

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Fast hydrogenation reaction examples using the H-Cube® flow reactor

The hydrogenation of a series of functional groups has been performed using H-Cube®, a novel continuous-flow microfluidic hydrogenation reactor. These experiments demonstrate that the H-Cube® can perform a diverse range of heterogeneous hydrogenation reactions with high yields and conversion rates, and with reaction times of minutes.

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Difficult hydrogenations – saturation of functionalized pyridines

The saturation of aromatic ring systems is one of the hardest reactions in hydrogenation. Reactions are typically performed at high temperature and pressure (above 80 bar, 80 °C). Typical laboratory batch reactors are not capable of reaching these conditions and so, either the reaction does not work or the reactions take days. The H-Cube® flow hydrogenation reactor is capable of performing reactions at 100 °C and 100 bar safely. The H-Cube®’s improved mixing efficiency coupled with high temperature and pressure abilities means difficult reactions can be performed in minutes. Here are a few examples.

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