Continuous-Flow Technology-A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients

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Abstract

In the past few years, continuous-flow reactors with channel dimensions in the micro- or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of this type, virtually instantaneous mixing can be achieved for all but the fastest reactions. Similarly, the accumulation of heat, formation of hot spots, and dangers of thermal runaways can be prevented. As a result of the small reactor volumes, the overall safety of the process is significantly improved, even when harsh reaction conditions are used. Thus, microreactor technology offers a unique way to perform ultrafast, exothermic reactions, and allows the execution of reactions which proceed via highly unstable or even explosive intermediates. This Review discusses recent literature examples of continuous-flow organic synthesis where hazardous reactions or extreme process windows have been employed, with a focus on applications of relevance to the preparation of pharmaceuticals.

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Singlet oxygen: there is indeed something new under the sun.

Peter Ogilby (2010)

Singlet oxygen, O(2)(a(1)Delta(g)), the lowest excited electronic state of molecular oxygen, has been known to the scientific community for approximately 80 years. It has a characteristic chemistry that sets it apart from the triplet ground state of molecular oxygen, O(2)(X(3)Sigma), and is important in fields that range from atmospheric chemistry and materials science to biology and medicine. For such a "mature citizen", singlet oxygen nevertheless remains at the cutting-edge of modern science. In this critical review, recent work on singlet oxygen is summarized, focusing primarily on systems that involve light. It is clear that there is indeed still something new under the sun (243 references).

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Deciding whether to go with the flow: evaluating the merits of flow reactors for synthesis.

Ryan L Hartman, Jonathan P McMullen, Klavs F. Jensen (2011)

The fine chemicals and pharmaceutical industries are transforming how their products are manufactured, where economically favorable, from traditional batchwise processes to continuous flow. This evolution is impacting synthetic chemistry on all scales-from the laboratory to full production. This Review discusses the relative merits of batch and micro flow reactors for performing synthetic chemistry in the laboratory.