Continuous-Flow High Pressure Hydrogenation Reactor for Optimization and High-Throughput Synthesis

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The atom economy concept is one of the earliest recognition for green and sustainable aspects of organic synthesis. Over the years, novel technologies emerged that made this important feature of reactions into practice. Continuousflow devices increased the efficiency of the chemical transformations with novel process windows (high T, high p and heterogeneous packed catalysts etc.) and increased safety which turned the attention to reexamine old, industrial processes. Oxidation can be performed under flow catalytic conditions with molecular oxygen; alcohols can be oxidized to carbonyl compounds with high atom economy (AE=87 %). Using O 2 and 1 % Au/TiO 2 , alcohol oxidation in flow was achieved with complete conversion and >90 % yield. N-alkylation is another good example for achieving high atom economy. Under flow catalytic conditions (Raney Ni), amines were successfully reacted with alcohols directly (AE=91 %) with >90 % conversion and selectivity. In both examples, the effective residence time was less than 1 min. These two examples demonstrate the significant contribution of flow technology to the realization of key principles in green and sustainable chemistry.

Section: Case Study 1: Oxidation With Elemental Oxygen Inmentioning

confidence: 99%

Important Industrial Procedures Revisited in Flow: Very Efficient Oxidation and N-Alkylation Reactions with High Atom-Economy

Sipos¹,

Gyóllai²,

Sipőcz³

et al. 2013

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“…The hydrogenation of compounds 5a-c and 9a-c and the indoles 10a,b (purchased from Apollo Scientific) to the corresponding amines was performed directly under continuous-flow conditions with an H-Cube® reactor [18], using 10% Pd/C cartridges as catalyst ( Figure 7).…”

Section: Resultsmentioning

confidence: 99%

Multistep Continuous-Flow Synthesis of Condensed Benzothiazoles

Lövei

Greiner²,

Éles³

et al. 2015

In medicinal chemistry, the development of synthetic procedures for the access of new heterocyclic systems as potential scaffolds is elementary. Herein, we report our results on the formation of small drug-like heterocycles, utilizing flow chemistry. This approach enables the extension of the reaction parameter window, including high-pressure/high-temperature or hazardous chemistry. In our work, various novel condensed tricyclic benzothiazoles fused with furo-and thieno-rings were synthesized applying a multistep continuous-flow protocol. The process includes two ring closure steps and a nitro group reduction step. Batch and telescoped continuous-flow syntheses were also designed and performed.

“…Albeit further work is clearly required to building a robust and practical tool, it will also simplify the choice of reactor technologies. Testing this methodology with other intensified technologies such as, e.g., Corning Advanced Reactor Technology for hydrogenations [42] or the H-cube from ThalesNano are in progress [43].…”

Section: Resultsmentioning

confidence: 99%

A Method to Identify Best Available Technologies (BAT) for Hydrogenation Reactors in the Pharmaceutical Industry

Doan¹,

Stavárek²,

Bellefon³

2012

A methodology that may be applied to help in the choice of a continuous reactor is proposed. In this methodology, the chemistry is first described through the use of eight simple criteria (rate, thermicity, deactivation, solubility, conversion, selectivity, viscosity, and catalyst). Then, each reactor type is also analyzed from their capability to answer each of these criteria. A final score is presented using "spider diagrams." Lower surfaces indicate the best reactor choice. The methodology is exemplified with a model substrate nitrobenzene and a target pharmaceutical intermediate, N-methyl-4-nitrobenzenemethanesulphonamide, and for three different continuous reactors, i.e., stirred tank, fixed bed, and an advanced microstructured reactor. Comparison with the traditional batch reactor is also provided.