A Simple and Versatile Reactor for Photochemistry - Organic Process

Article pubs.acs.org/OPRD

A Simple and Versatile Reactor for Photochemistry Charlotte A. Clark,† Darren S. Lee,† Stephen J. Pickering,‡ Martyn Poliakoff,*,† and Michael W. George*,†,§ †

School of Chemistry, ‡Department of Mechanical, Materials and Manufacturing Engineering, The University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom § Department of Chemical and Environmental Engineering, The University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China S Supporting Information *

ABSTRACT: A photoreactor that generates a thin film upon rotation for efficient irradiation of solutions is described. The reactor is based around a standard piece of equipment found in most synthetic laboratories, namely, a rotary evaporator. Three different photo-oxidation reactions have been used to examine the effects of several parameters such as irradiated volume, flask size, rotation speed, and light intensity. The reactor can be operated in a semicontinuous manner, and two possible configurations are described. The thickness of the generated film and the rate of mixing under different conditions have been examined using in situ electronic absorption spectroscopy.

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INTRODUCTION There is an increasing drive for new synthetic approaches, processing methods, and techniques in the fine chemicals and pharmaceutical industries,1−4 and the area has recently been extensively reviewed.5−8 This drive has contributed to the increased interest in photochemical reactions since they have the potential to be more selective and more atom efficient than many thermal reactions even though the industrial potential was outlined more than 100 years ago.9,10 There has been increased research activity utilizing photochemistry by exploiting highly innovative work on promoting photoredox reactions using visible light with the promise of new reactions that can be performed considerably more cleanly than by alternative routes.11−17 It has previously been shown that it is also possible to use solar irradiation for many reactions, removing the need for an additional irradiation source but at the cost of improved heat removal.18,19 However, one issue still remains amidst this new research, namely, how to scale-up the photochemical reactions in a generic way beyond the small scale that is normally used in laboratories. This article presents one possible solution, which is a rotary evaporator simply modified for automated sequential batch photochemistry. [We have coined the name “PhotoVap” for the reactor to reflect the simplicity of modifying a well-known piece of laboratory equipment (rotary evaporator), colloquially termed a “RotaVap”.] Irradiation is provided by external light emitting diodes (LEDs) onto a thin film of the reaction mixture, created by the rotation of the evaporator flask. The reactor is a straightforward concept that, as far as we are aware, has not previously been applied in this context and should be relatively simple to implement in most synthetic laboratories, adding to the list of simple photoreactors available for use in teaching laboratories.20−22 The problem of scale-up of photochemical processes arises from the very obvious fact that such reactions require the absorption of light and, if a solution absorbs light strongly, © 2016 American Chemical Society

Beer−Lambert’s law dictates that the light cannot penetrate very deep into that solution. This means that one requires a thin film (or equivalent) of solution in the reactor. Alternatively, one can use large volume reactors with sufficient agitation to bring successive layers of the solution closer to the light source. Another quite significant problem is that most light sources are not directional; therefore, the source usually needs to be placed at the center of the reactor to avoid wasting any light. This requirement leads to further engineering complications as nearly all light sources generate heat as well as light, and this heat has to be removed from a relatively confined location in the center of the solution. The problem of heat management increases rapidly as the light source is made bigger, and heat problems can sometimes be further exacerbated by the need to run the photochemical reaction at a controlled temperature either well above or well below room temperature. Numerous different reactor designs have been published, and the area has been reviewed.23−27 Traditionally, photochemical reactions have been carried out in an immersion-well reactor.28 This consists of a lamp, usually an Hg arc, within a water-cooled jacket placed at the center of a cylindrical reaction vessel, which may itself be cooled or heated by a jacket or water bath. The reaction vessel is usually stirred, and the reactor is almost invariably run as a batch process. A major drawback of this design is that stirring is usually inefficient, with the result that different molecules experience different irradiation times within the reactor. Nevertheless, several photochemical reactions have successfully been run at industrial scales over the past 100 years, several of which are still in use today.29,30 An example of which is the irradiation of cyclohexane with NOCl and HCl to produce caprolactam, which is used in the manufacture of nylon.31 The production of 1α-hydroxy-vitamin D332,33 and several other related comReceived: August 3, 2016 Published: September 21, 2016 1792

DOI: 10.1021/acs.oprd.6b00257 Org. Process Res. Dev. 2016, 20, 1792−1798

Organic Process Research & Development

Article

could not be carried out continuously.66 Our reactor, described here, overcomes this residence time problem by operating in a semicontinuous mode. Like Raston’s device, our reactor works on the principle of creating a thin film by rotation of the reaction flask but at much slower rotation speeds.

pounds involves a photochemical isomerization step. Singlet oxygen has also been used at scale, as shown in the manufacture of rose oxide, a compound important in the fragrance industry,34 and in the semisynthetic production of artemisinin developed by Sanofi and recently described in this journal.35 A highly successful family of photochemical reactor designs involves coiling a long length of UV transparent polymer fluorinated ethylene propylene (FEP) tubing generally around a cylindrical lamp. The reaction mixture is then flowed through the tube, which is of sufficiently narrow bore that the light can penetrate through it.27 Indeed, in some designs, there are multiple layers of tube much like the thread wrapped onto a cotton reel.27,36 In this type of reactor, the residence time, the time over which the reactants are irradiated, is determined by the volume of the tubing and the speed of the pump. Such a design overcomes problems of modest scale-up as larger quantities of product can be obtained by running the reactor for a longer period of time. With this type of reactor, it is possible to separate the liquid into segments and obtain higher gas− liquid mass transfer by manipulating the flow rates of the reactants and gas such that a slug flow pattern is achieved.37,38 In the FEP reactor, changing the pumping speed also changes the residence time and increasing the size of the lamp may lead to problems of heat management. Nevertheless, such approaches have been used successfully in a wide range of applications. Recent examples include cycloadditions,27,36,37,39 redox,38,40−42 and halogenations.43−45 The continued improvements in LED technology now make LEDs an effective light source for visible photochemistry, particularly as they are almost point sources and their light beams are highly directional. This means that LEDs can be used effectively by placing them outside a reaction vessel without the need for focusing optics. Furthermore, the necessary cooling can be applied to the back of the LED, away from the light beam. FEP reactors have been used with LED irradiation with a relatively high production rate for the synthesis of artemisinin.40 LEDs have also been used in variety of other visible light photochemical reactor designs.25,46−53 A simple scale-up strategy that involves a “numbering-up” approach of a photomicroreactor has also been reported.23 UV-LEDs are also being applied in a range of technologies and photochemical reactions.22,54,55 Our research group has previously devised continuous reactors based on short-path length high-pressure optical cells.56 Alternative reactor designs include irradiation of falling-films.57,58 In such designs, the thin film is generated by gravity as a stream of liquid “falls” from the top of the reactor to the bottom. This reactor has proved successful for photochemistry as a flow of gas can be applied and by having a window the film can then be efficiently irradiated by a light source in close proximity.26,59 We have created similar thin films for photochemical reactions using a high-pressure tubular reactor that is filled with relatively large diameter glass balls, allowing the reaction mixture to also be efficiently mixed.47,53,60 Other photochemical reactor designs that utilize thin films for efficient irradiation and mass-transfer include bubble column61 and spinning disc photoreactors.62−64 Raston and colleagues recently described a photochemical modification of their innovative continuous vortex microfluidic device, based on a very rapidly rotating 10 mm NMR tube that creates high shear forces and unusual mixing regimes within a thin fluid film.65,66 However, the fact that flow rate and residence time are inherently linked in their design meant that some reactions

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PRINCIPLE OF THE REACTOR The reactor is shown schematically in Figure 1 and is described in more detail in the Supporting Information. It is based on a

Figure 1. Reactor is based on a slightly modified lab rotary evaporator. It works in a semicontinuous mode: a measured volume of reaction mixture, R, is pumped from a reservoir into the flask, F; the LEDs are switched on, F starts spinning, and the mixture forms a thin film around the inside of the flask. After the desired reaction time, the reactor stops, the product solution, P, is pumped out, F is refilled, and the procedure is repeated. All operations are carried out under computer control.

conventional rotary evaporator that has been modified in three ways: (i) there is no vacuum pump, (ii) two thin PTFE tubes are threaded through the rotating neck of the flask to allow a solution to be pumped in and out of the reactor, and (iii) LEDs are placed around the flask. The operation of the reactor is very simple and is summarized in the figure caption. It can be used in two different modes: either as a batch reactor or run semicontinuously using a series of sequential batches. In the semicontinuous mode, a computer controls the filling and emptying of the reactor, as well as switches the rotation of the rotary evaporator on and off. Many modern rotary evaporators permit such computer control, and older designs can often be modified quite simply to permit such operation. Our reactor has several potential advantages when employed as a photoreactor: (i) The size of the flask can easily be changed, and we have already achieved ca. ×6.5 scale-up in productivity (μmol min−1) for one reaction by changing the flask size from 50 to 3000 mL, enabling a larger volume to be processed. Such scale-up could be quite important in process development because only small amounts of valuable starting material may be available in the early stages and/ or the amounts of solvent may be prohibitive for major discovery programmes. (ii) The water bath of the evaporator can easily be used to heat and cool (with appropriate apparatus) the reaction vessel as appropriate. The rotation of the flask aids in maintaining a consistent reactor temperature under irradiation as demonstrated by thermal imaging (see the Supporting Information). 1793



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(iii) The semicontinuous operation decouples the residence time from the flow rate of the reaction mixture through the equipment. By contrast, residence time and flow rate are directly linked in almost all other designs of continuous flow photoreactors. The reactor works efficiently, and we now give three examples of reactions carried out to illustrate the effect of some of the operational parameters and to demonstrate possibilities for scale-up. All of these examples involve oxidation with air or pure O2. The first example we chose to investigate was exploring the effect of residence time in the reactor on the photochemical dihydroxylation of benzene-1,4-diboronic acid (1). Safety Warning. Any experiment involving flammable organic solvents and air or pure oxygen is potentially hazardous, especially when partially contained, as is the case of the flask of our reactor. We took the following precautions and encountered no problems, but we stress the need for readers to make safety assessments for their own experiments as peripheral circumstances may be different from ours. All experiments were carried out in a fume hood or ventilated enclosure with adequate ventilation and the front lowered. Any obvious sources of ignition were removed. Oxygen was fed from a cylinder fitted with a compliant regulator and was delivered at a maintained pressure of 1 bar using a mass flow controller compatible with oxygen. The equipment was maintained and cleaned free of grease at all times to prevent any incompatibilities with oxygen. Temperatures were kept at ambient. When working above the solvent flash point and LOC, care must be taken to ensure that all possible risks have been considered. Appropriate safeguards and suitable safety measures must be implemented. Photodesymmetrization of Benzene-1,4-diboronic Acid (1). We recently described studies of this reaction photocatalyzed by [Ru(bpy)3]2+ or rose bengal (Scheme 1) in a

Figure 2. Effect of residence time vs conversion and selectivity to 2 as determined by 1H NMR. A selected NMR spectrum is given in the Supporting Information. Experimental conditions: a 5 mL volume of solution in a 1 L flask rotated at 175 rpm.

Photo-oxidation of α-Terpinene (4). The reaction of αterpinine (4) by photogenerated singlet O2 (1O2) to form ascaridole (5) (Scheme 2) was first reported67 in the 1940s, Scheme 2. Photo-oxidation of α-Terpinene (4) To Form Ascaridole (5)

and the reaction has subsequently been studied in both conventional solvents and in supercritical CO2.38,50,53,68−70 Here, we have used EtOH as an alternative, greener solvent compared to the chlorinated solvents traditionally used for such reactions even though the lifetime of 1O2 is shorter in this solvent.71,72 Initially, air was bubbled through the solution (achieved by passing an additional PTFE tube into the flask), and by varying the photolysis residence time, we were able to obtain conversion (>95%) with a yield of 79% of 5 after only 90 s of photolysis (entry 1, Table 1). Replacing air with oxygen results in a significant reduction in the residence time, with only 30 s required to obtain very high conversion (>99%) of 4 and a 75% yield of 5 (entry 2). Higher productivities are observed compared with the stationary flask (i.e., not rotating, entry 3), indicating that the photolysis of the thin film leads to more efficient irradiation. Light intensity was found to be important as demonstrated by the increased productivity when replacing the LEDs with ones of higher intensity (entry 6). In all of our experiments, we observe only small amounts of the known sideproduct, p-cymene (see the Supporting Information). The lifetime of 1O2 is significantly longer in chlorinated solvents compared to that in many organic solvents.71,72 We examined productivity using similar operating conditions but with CH2Cl2 and CCl4 solvents and using 1 mol % TPP as the photosensitizer (entries 7 and 8, Table 1). However, under these conditions, no significant improvements were observed relative to those performed in EtOH, possibly indicating that any change in fluid dynamics as a result of the different densities and surface tensions of these solvents under these

Scheme 1. Mono- (2) and Dihydroxylated (3) Products of the Photochemical Desymmetrisation of Benzene-1,4diboronic Acid (1)

high-pressure tubular reactor.60 This reaction is a useful test for the reactor since the two products are formed sequentially; this means that selectivity is a function of irradiation time. Typical results obtained are summarized in Figure 2, which shows that as conversion increases there is a corresponding decrease in selectivity for the monohydroxylated product. As the products are produced in a stepwise manner, it would be possible, if one desired, to stop the reaction after a particular period of time to isolate the maximum amount of mono product. Next, we investigated another reaction in the reactor. This time, we explored the effects of irradiated volume, gas−liquid mass transfer, flask size, and solvent by monitoring the photooxidation of α-terpinene. We have also operated this reaction as a semicontinuous process in two ways, and these are compared in detail below. 1794



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Table 1. Photo-oxidation of 4 to 5 Using Various Parameters in the Photoreactora entry b

1 2 3c 4d 5 6e 7f 8f 9 10 11 12

solvent

flask size

irradiated volume (mL)

photolysis time (s)

yieldg (%)

productivityh (μmol min−1)

EtOH EtOH EtOH EtOH EtOH EtOH CH2Cl2 CCl4 EtOH EtOH EtOH EtOH

1L 1L 1L 1L 1L 1L 1L 1L 50 mL 1L 3L 3L

5 5 5 5 5 5 5 5 1.5 10 20 50

90 30 15 15 15 10 60 30 45 60 120 210

79 75 5 36 41 72 71 86 80 87 76 71

260 750 100 720 820 2200 360 860 160 870 760 1010

Unless specified otherwise, photolysis was undertaken in a 1 L round-bottom flask rotating at 175 rpm with O2 bubbling through the solution (see Safety Warning), using rose bengal (1 mol %) as the photosensitizer, and irradiating with 1000 lm LEDs. bAir was used instead of O2. cPhotolysis conducted on a stationary 1 L flask. dFlask rotated at 150 rpm. eUsing higher intensity LEDs of 8000 lm. fTetraphenylporphyrin (1 mol %) used as a photosensitizer. gDetermined from 1H NMR using an internal standard. hProductivity determined by [substrate concentration × irradiated volume × NMR yield]/photolysis time (min). a

conditions compared to EtOH has no apparent effect. Further work is underway to explore this and examine the interplay between these different parameters. Experiments were carried out using a range of solution and flask volumes (entries 9−12, Table 1); for testing on a smaller scale, we performed the same photo-oxidation reaction in a 50 mL flask with only 1.5 mL of solution, giving an 80% yield of 5 following 45 s of photolysis. This demonstrates that the reactor can be used even if only small volumes of solvent and quantities of starting material are available with minimal changes required. For scale-up, two approaches have been explored by increasing both the volume of reaction mixture and the size of the flask. These approaches, not surprisingly, resulted in a lengthening of the required photolysis time. Overall, these results at both smaller and larger relative scales demonstrate the potential scalability of the reactor. We have investigated continuous operation for the processing of a 50 mL solution volume in a 1 L flask with differing productivities and used two different methods. First, in Method 1, we operated the reactor in a manner similar to the fill and empty cycle of a stirred batch reactor: the 1 L flask was filled with 50 mL while being rotated at 175 rpm and irradiated at the same time. Once the 50 mL had been dispensed into the reactor and the irradiation period was complete, the flask was emptied and the process was repeated. Method 2 involved gradual filling of the rotating and irradiated flask in 5 mL portions with a short time delay between each addition. The addition process was repeated until the flask contained 50 mL; then, at regular intervals, 5 mL was removed and a further 5 mL aliquot was added. This pattern was repeated until all of the liquid had been processed. Comparing the two methods, Method 1 was found to be superior, with a productivity of 600 μmol min−1. A slightly longer time required for Method 2 to process the same volume resulted in a slightly lower productivity of 370 μmol min−1. Further work is underway to optimize methods of continuous operation further. Photo-oxidation of Citronellol (6). The photo-oxidation reaction of citronellol, 6, using 1O2 is one of the few photochemical reactions used at scale industrially (Scheme 3), in this case to manufacture rose oxide.73,74 It is a wellstudied reaction; therefore, it is convenient for benchmarking the operation of photochemical reactors. We have studied a

Scheme 3. Photo-oxidation of Citronellol (6) To Form Hydroperoxides (7 and 8) Then Reduction To Form Diols (9 and 10), of Which 9 Can Undergo Dehydrative Cyclisation To Yield Rose Oxide

number of variables including residence time and substrate/ photosensitizer concentration as well as increased the intensity of the LEDs used for photolysis. We have also monitored the hydroperoxide intermediates using in-line ATR-FTIR spectroscopy, and as in earlier experiments, the final products were quantified by 1H NMR. In the reactor, our initial results showed that as the concentration of citronellol was increased from 0.1 to 1 M the irradiation time required for conversion to 9 and 10 increased from 120 to 420 s (entries 1 and 10, Table 2). The viscosity of the reaction solution was noticeably greater at concentrations >0.75 M, and this may account for the nonlinear trend in photolysis times. However, decreasing the photosensitizer concentration caused no change in conversion of 6. Typically, 9 and 10 were produced in a 1.15:1 ratio, as determined from 1H NMR. In terms of productivity, the photoreactor demonstrates increased productivity compared to that of other reactors38,75,76 such as microreactors and flow reactors at ambient pressure and is comparable to those that conduct reactions under higher pressures of O2. Further increases in productivity were observed on replacing the LEDs with ones of increased lumen output (entries 3 and 8, Table 2). As above, comparison with the stationary flask (entry 4) shows that the thin film generated on rotation results in higher 1795



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Table 2. Photo-oxidation of 6 to 9 and 10 in the Photoreactora entry 1 2b 3c 4d 5e 6 7f 8c 9 10

citronellol (M)

photolysis time (s)

conversiong (%)

productivityh (μmol min−1)

0.1 0.1 0.1 0.5 0.5 0.5 0.5 0.5 0.75 1

120 120 40 90 90 180 180 100 240 420

90 91 96 6 51 86 93 77 81 99

230 230 720 100 850 720 780 1150 760 710

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OPERATING PARAMETERS

Even though the reactor is a relatively simple piece of equipment, there are a surprising number of different parameters that can be varied for a reaction. These include the size of flask, the speed of rotation, the amount of liquid in the flask, and the irradiation time, which has been discussed in some detail above. A full understanding of these parameters will require eventual modeling of the fluid inside the photoreactor, which is complicated by the fact that the axis of rotation is not perpendicular to the action of gravity. Such modeling is underway, but in the interim, we have conducted some semiquantitative experiments; a miniature incandescent bulb was placed in the center of the flask, and a fiber optic spectroscopic probe was positioned at various points above the outside surface of the rotating flask. As explained in the Supporting Information, a colored dye could be used together with appropriate calibration to obtain reasonable estimates of film thickness, and with a second dye solution, one can obtain an indication of the speed of mixing within the fluid film. The results are given in the Supporting Information, but, in summary, it was found that (i) Not unexpectedly, the thickness of the film increased with the speed of rotation of the flask (e.g., with a 3 L flask and containing 10 mL liquid, the film increased from 0.11 to 0.66 mm as the speed changed from 50 to 175 rpm). At higher spin speeds (from 250 rpm upward), a thicker band is formed around the flask rather than observing a uniform thin film (see the Supporting Information). (ii) The efficiency of mixing in the rotating flasks is strongly dependent on the presence of a pool of liquid in the flask. That is, mixing was relatively poor when the flask contained only a small amount of liquid as all of it was spread across the surface as a thin film. Mixing was much more rapid with larger volumes of liquid, such that even during rotation there was a pool of liquid in the bottom of the flask. Mixing may not be important for the photochemistry itself, but it is likely to be crucial for minimizing the buildup of solid byproducts on the inner surface of the flask because the shear forces on a film are very small. By contrast, the interaction of the film with the liquid pool is likely to have a beneficial cleaning effect on the glass.

a

Unless indicated otherwise, photolysis was undertaken on a 5 mL volume of a EtOH solution containing 6 using 3 mM rose bengal as the photosensitizer in a 1 L round-bottom flask rotating at 175 rpm with O2 bubbling through the solution (see Safety Warning) and irradiating with 1000 lm LEDs. bUsing a lower concentration of rose bengal (1 mM). cUsing higher intensity LEDs of 8000 lm. dPhotolysis conducted on a stationary 1 L flask. eFlask rotated at 150 rpm. f Reaction ran in CH2Cl2 with 2 mol % TPP as photosensitizer. g Determined from 1H NMR. hProductivity determined using photolysis residence time only and determined by [substrate concentration × irradiated volume × conversion (from NMR)]/ photolysis time (min).

productivities. Finally, as with the α-terpinene photo-oxidation described above, changing the solvent from EtOH to CH2Cl2 resulted in only a minimal increase in conversion, indicating that the difference in lifetime of 1O2 between the two solvents does not seem to affect the productivity under these conditions. We have followed the progress of the formation of 9 and 10 using 1H NMR and the formation of hydroperoxides 7 and 8 using ATR-FTIR. Selected ATR-FTIR difference spectra from an experiment containing 0.5 M of 6 are shown in Figure 3. The spectra demonstrate that it is possible to follow the reaction in real-time. The spectrum recorded after 180 s of photolysis shows a depletion at 1051 cm−1 assigned to ν(C−O) modes of 6 by reference to previous studies77,78 and bands at 1149, 1039, 972, and 900 cm−1 that continue to increase with increasing photolysis time. The positions of the bands are consistent with the presence of hydroperoxides.79,80 The rate of growth of these IR bands matches the rate of formation of 9 and 10, as observed by 1H NMR.

Figure 3. ATR-FTIR difference spectra recorded after photolysis at specific timed intervals (15−180 s) of a 0.5 M EtOH solution of 6 containing 3 mM rose bengal as the photosensitizer. 1796



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The rotation of the flask is important for maintaining a constant reactor temperature. During irradiation, this is especially significant as localized heating would be expected to occur. Using an internal thermocouple, we have determined that the rate of temperature equilibration during irradiation is directly related to flask rotation speed, with the fastest rate observed at the highest speed. This observation is confirmed by thermal imaging photographs that also indicate upon rotation and irradiation that the temperature of the film is uniform (see the Supporting Information). The overall time taken for the reaction clearly depends on the intensity of the light. Initially, experiments were conducted with two banks of 1000 lm visible white-light LEDs. However, upon replacing these LEDs with ones that are significantly brighter (ca. 8000 lm), the reaction time was correspondingly reduced. Although, experiments described here have used only two banks of LEDs, even on this scale there is room to use additional banks if desired.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank EPSRC (EP/L021889/1) and The University of Nottingham EPSRC Impact Acceleration fund (EP/K503800/ 1). We are grateful to C. Welsh, J. Hunter, R. Howie, Dr. Z. Amara, and Dr. R. Horvath for helpful discussions and W. Golding and K. Patel for help with some of the experimental work. We are grateful to EnLumo for advice on the most appropriate types of LED for this work. We also thank D. Litchfield, M. Dellar, R. Wilson, P. Fields, M. McAdam, and M. Guyler for technical support at the University of Nottingham. C.A.C. is grateful to Nottingham Hackspace for use of their workshop facilities for the construction of a prototype pumping system used in the initial photoreactor.

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POTENTIAL FOR SCALE-UP The rotary evaporator used in these experiments had a maximum flask size of 3 L, but, in principle, there is no reason why the same approach cannot be used with much larger flasks because even the largest rotary evaporators still produce thin films on the surface of the glass. Commercial rotary evaporators are available with volumes of at least 200 L. Furthermore, evaporators of that size normally include automatic fill and empty facilities that should, in principle, make conversion to a photoreactor even simpler. It is reasonable to suppose that relatively large amounts of material could be produced in a 200 L reactor operating around the clock in a semicontinuous mode.

(1) Modular, flexible, sustainable: the future of chemical manufacturing; Horizon 2020, European Commission. https://ec.europa.eu/ programmes/horizon2020/en/news/modular-flexible-sustainablefuture-chemical-manufacturing (accessed July 31, 2016). (2) Pharma 2020: From Vision to Decision; PricewaterhouseCoopers. http://www.pwc.com/gx/en/pharma-life-sciences/pharma2020/ assets/pwc-pharma-success-strategies.pdf (accessed July 31, 2016). (3) Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G. R.; Leazer, J. L.; Linderman, R. J.; Lorenz, K.; Manley, J.; Pearlman, B. A.; Wells, A.; Zaks, A.; Zhang, T. Y. Green Chem. 2007, 9, 411. (4) Giraud, R. J.; Williams, P. A.; Sehgal, A.; Ponnusamy, E.; Phillips, A. K.; Manley, J. B. ACS Sustainable Chem. Eng. 2014, 2, 2237. (5) Cambié, D.; Bottecchia, C.; Straathof, N. J. W.; Hessel, V.; Noël, T. Chem. Rev. 2016, DOI: 10.1021/acs.chemrev.5b00707. (6) Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, DOI: 10.1021/ acs.chemrev.6b00057. (7) Kärkäs, M. D.; Porco, J. A.; Stephenson, C. R. J. Chem. Rev. 2016, DOI: 10.1021/acs.chemrev.5b00760. (8) Ghogare, A. A.; Greer, A. Chem. Rev. 2016, DOI: 10.1021/ acs.chemrev.5b00726. (9) Ciamician, G. Science 1912, 36, 385. (10) Albini, A.; Fagnoni, M. Green Chem. 2004, 6, 1. (11) Chen, J.-R.; Hu, X.-Q.; Lu, L.-Q.; Xiao, W.-J. Chem. Soc. Rev. 2016, 45, 2044. (12) Angnes, R. A.; Li, Z.; Correia, C. R. D.; Hammond, G. B. Org. Biomol. Chem. 2015, 13, 9152. (13) Xi, Y.; Yi, H.; Lei, A. Org. Biomol. Chem. 2013, 11, 2387. (14) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322. (15) Xuan, J.; Xiao, W.-J. Angew. Chem., Int. Ed. 2012, 51, 6828. (16) Tucker, J. W.; Stephenson, C. R. J. J. Org. Chem. 2012, 77, 1617. (17) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102. (18) Esser, P.; Pohlmann, B.; Scharf, H.-D. Angew. Chem., Int. Ed. Engl. 1994, 33, 2009. (19) Oelgemöller, M. Chem. Rev. 2016, DOI: 10.1021/acs.chemrev.5b00720. (20) Aung, T.; Liberko, C. A. J. Chem. Educ. 2014, 91, 939. (21) Taber, D. F.; Paquette, C. M. J. Chem. Educ. 2013, 90, 1105. (22) Thompson, M. P.; Agger, J.; Wong, L. S. J. Chem. Educ. 2015, 92, 1716. (23) Su, Y.; Kuijpers, K.; Hessel, V.; Noël, T. React. Chem. Eng. 2016, 1, 73. (24) Baumann, M.; Baxendale, I. R. React. Chem. Eng. 2016, 1, 147. (25) Loponov, K. N.; Lopes, J.; Barlog, M.; Astrova, E. V.; Malkov, A. V.; Lapkin, A. A. Org. Process Res. Dev. 2014, 18, 1443. (26) Jähnisch, K.; Dingerdissen, U. Chem. Eng. Technol. 2005, 28, 426.

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CONCLUSIONS We have demonstrated a simple and versatile apparatus for conducting efficient photochemical reactions based upon a conventional rotary evaporator, a piece of equipment available in nearly every synthetic laboratory. The reactor can be automated to operate semicontinuously, and we have described its application to three reactions with O2 or air. An important feature despite the simplicity is that the concept is extremely flexible, allowing different modes of operation, sizes of flasks, and light sources. Our results indicate that the reactor is capable of efficient gas−liquid mass transfer as a consequence of the large surface area of the thin-film generated upon spinning. We envisage that the reactor may also be useful for separation of solid products. A possible limitation is that reactions may be conducted only at or below ambient pressure. All of the examples described here involve visible light, but experiments are currently underway with UV light in our laboratory to extend the capabilities and versatility of the reactor further.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.oprd.6b00257. Experimental details and selected NMR spectra (PDF)

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REFERENCES

AUTHOR INFORMATION

Corresponding Authors

*E-mail: martyn.poliakoff@nottingham.ac.uk (M.P.). *E-mail: [email protected] (M.W.G.). 1797



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