reduces the number of steps required to get to the desired product and gives cleaner reaction mixtures that are easier to purify . Photochemistry also allows access to chemistries that cannot easily be achieved using round-bottom flasks and traditional methods . For example , photocatalysed C – H activation methods have reduced the number of reagents required and expanded the scope of available chemistry .
Flow reactors to the rescue
Chemists ask a lot of questions and follow trends , from planning experiments – using new techniques , transformations and catalysts – to the analysis and purification of the target product . This is exactly what has happened in continuous flow photochemistry , whose uptake is reflected in the dramatic increase of publications and conferences in recent years . 1 Parallel to the increasing awareness of new photochemistry methods is the growing use of modern flow chemistry techniques to enhance reaction control . The benefits of flow chemistry over traditional batch techniques are widely known , and all of these translate equally to flow photochemistry reactors . In a flow photochemistry reactor , control of the reaction parameters can be further increased by improved irradiation of the reaction for better selectivity , reaction scalability and reproducibility . Controlling exposure times also prevents overirradiation of the reaction , minimising product degradation and unwanted side reactions . Most photochemistry reactors now use single-wavelength LED light sources that are energy efficient and have a low heat load , enabling them to be used at high intensities with relatively low cooling . Their small irradiation window also allows light to be directed towards the channels in flow reactors . However , photons still lose energy quickly over very short distances from these LEDs . The limited scale- up potential of photochemistry is the main reason why its uptake has suffered in industry . This is attributed to the light attenuation effect , described by the Bouguer-Lambert-Beer law equation . Attenuation of photon transfer is a problem when increasing reactor volumes and flow rates , which is more apparent with the round-bottom flasks used in batch processes as only the outer region of the reactor is exposed . By contrast , the microcapillaries used in flow reactors ensure that there is homogeneous irradiation . The improved illumination offers better selectivity , reaction scalability and reproducibility . Increasing the photon flux and the number of photons can allow for efficient scale-up . Throughput can be improved by running the reactions for longer – a well-known benefit of traditional flow chemistry – or by increasing the number of reactors , either by linearly expanding the number of reactors in series , or by external or internal numbering , although this can be more costly . Further key advantages include the increased safety window of reactors of this type and the ability to perform multi-phase chemistry .
Applications
Photochemistry has already been successfully used across a wide range of chemistry applications , including organic synthesis in drug discovery , fine chemicals and agrochemicals .
From the point of view of a synthetic organic chemist , it is only in more recent years that key transformations have been developed in flow photochemistry . These include photocycloadditions , photoisomerisations , photooxygenations , cyanation and halogenation reactions , light-induced cross-coupling reactions and latestage C – H activation . Halogenations are of great value to the pharmaceutical and agrochemical industries . Brominated compounds are common building blocks for organic synthesis . Unlike batch procedures , flow photo-bromination can be achieved using light activation of N-bromosuccinimide and it does not need a toxic radical initiator , such as azobisisobutyronitrile . This presents a much higher yield and selectivity for mono- over di-brominated products on both small and large scales , in a shorter time . 6 The importance of fluorine atoms in molecules – for improved chemical stability , modulation of lipophilicity and binding selectivity due to acid and base characteristics – is of particular interest in pharmaceutical and agrochemical development . Photocatalytic trifluoromethylation and perfluoroalkylation of a range of heteroarenes , using inexpensive gases and reagents , has been applied successfully in flow to achieve high conversion and isolated yields ‣
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