Optimization of a Scalable Photochemical Reactor ... - ACS Publications

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Optimization of a Scalable Photochemical Reactor for Reactions with Singlet Oxygen Konstantin N. Loponov,† Joao Lopes,† Maciej Barlog,‡ Ekaterina V. Astrova,§ Andrei V. Malkov,∥ and Alexei A. Lapkin*,† †

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, United Kingdom School of Chemistry, Glasgow University, Glasgow G12 8QQ, United Kingdom § Ioffe Physico-Technical Institute, St. Petersburg 194021, Russian Federation ∥ Department of Chemistry, Loughborough University, Loughborough LE11 3TU, United Kingdom ‡

S Supporting Information *

ABSTRACT: Oxygenation of α-pinene using photochemically generated singlet oxygen (1O2) was studied in detail in several continuous flow photochemical reactors. Ferrioxalate actinometry and reaction kinetic data were used to compare light sources and reactor geometries, such as the immersed-well, an annular recirculating and microfluidic reactors. It is shown that reactor miniaturization, control of intensity and of spectral composition of light, and elevated oxygen pressure are the crucial factors for safe and efficient photo-oxygenation reactions. Higher quantum yields were generally obtained with the microreactor-LED assemblies due to better energy utilization, compared to all other systems studied. For the single-phase microreactor-LED system, an optimization model has been developed that revealed a broad optimal design window.

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INTRODUCTION Even though there are several large-scale industrial photochemical processes, their number is comparatively low due to the generally poor economics and complex scalability and safety issues of many photochemical transformations. Reactions with photochemical activation are not easily scalable mainly due to inefficient utilization of light and poor heat/mass transfer rates in large-volume reactors, as well as low power-to-photon efficiency of artificial light sources.1 At the same time, there are a number of reactions of high synthetic relevance that are frequently used in organic chemistry on the preparative scale, which would benefit from availability of readily scalable photochemical technology. A significant advance was made recently in scaling photochemical reactions through development of tubular flow reactors.2 An important contribution to this topic is a recent development of photochemical oxidation of artemisinic acid to artemisinin by Seeberger et al.3 Such examples show the potential of flow approaches to develop scalable and efficient photochemical processes. Another scalable reactor platform for photochemistry is the compact and microstructured flow reactor technology.4 Good heat management and radical quenching in small channels of microreactors allow safe exploitation of hazardous reactions, while also enabling optimal light absorption. Efficient, highpower LEDs with high photon fluxes, a wide range of available wavelengths, and long lifetime offer interesting new opportunities for optimization of the reactor design, especially in combination with microreactors. Although microstructured reactors were successfully examined in a wide range of applications of organic chemistry, including photochemistry,1b,5 no generalized design principles of photochemical microreactors were reported to date. © 2014 American Chemical Society

In this study, we focus on the application of microreactor technology in singlet oxygen ene reactions.6 We compare efficiencies of light utilization for several light sources, including conventional and LED lamps in several photoreactors, namely, an immersed well, annular recirculating reactor, and a silicon microreactor unit. These were tested in various lamp−reactor configurations and in different operation modes, summarized in Figure 1. As a case study we investigated oxygenation of αpinene to pinocarvone, as in Figure 2. Pinocarvone is used as a building block in many syntheses, including synthesis of antimalarial peroxides and chiral ligands for catalysis.7 Finally, we generalize the fundamental principles for design and optimization of scalable photochemical reactors. As far as we are aware, this is the first systematic study of operational parameters of continuous flow photochemistry, presenting a detailed optimization study.

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EXPERIMENTAL SECTION Annular Flow Reactor and Lamps. A description of the annular recirculating photoreactor rig can be found elsewhere.8 In this study we used an improved reactor design with an annular porous glass membrane introduced at the bottom of the reactor for better gas dispersion. A circular lamp (peak wavelength λ at 524 nm) was assembled from 10 strips of 24 LEDs each, providing a 15 cm long illumination zone. A fluorescent lamp (λ = 420 nm) consisting of two U-shaped actinic fluorescent bulbs (24 W, 23 cm illumination length, Catalina Aquarium) surrounded by aluminum cylindrical Special Issue: Continuous Processes 14 Received: June 5, 2014 Published: August 8, 2014 1443

dx.doi.org/10.1021/op500181z | Org. Process Res. Dev. 2014, 18, 1443−1454

Organic Process Research & Development

Article

Figure 1. A summary of photochemical reactors and lamps investigated in this study; schematic illustration of different operating regimes. (a) An immersed well (batch) reactor. (b) A recirculating annular reactor. (c) A microreactor in a continuous operation. (d) A microreactor operating with recirculation. (e) A microreactor with segmented gas−liquid flow.

depth 500 × 240 μm, length = 199.5 cm, V = 240 μL, illuminated area 9.98 cm2) was formed by anisotropic alkaline etching of a Si (110) wafer (n-type, 76 mm diameter). At the next step a Pyrex 7740 glass plate cover (77.5 × 40 × 2 mm) with two drilled holes (2 mm in diameter) for inlet and outlet ports was attached by anodic bonding. The reactor image and schematics are given in the Supporting Information. The reaction temperature was controlled by circulating thermostated water through the metal micro heat exchanger. The micro heat exchanger was a custom designed cross-flow exchanger, micromachined in stainless steel by Cawkwell Engineering, UK. A reaction mixture was pumped from a reservoir equipped with a pressure relief valve through the microreactor by a HPLC pump (Knauer). Different light sources (524 or 416 nm 5 × 9 LED arrays, 75 W Xe arc or 250 W metal halide (MH) lamp) were fixed above the microreactor at distances from the chip of 4.5 cm for the LEDs, 9.2 cm for the Xe lamp, and 11.3 cm for the halide lamp. LEDs were powered using a 60 V power supply via Supertex CL2 LED drivers and 1.2 kΩ resistors. The MH lamp (10000 K, UV cut glass bulb, iQuatix)

Figure 2. Oxygenation of α-pinene to pinocarvone.

reflector was assembled. A Xe 75 W short-arc lamp (Osram) was powered by an arc power supply (Photon Technology International) and provided a 3.5 cm illuminated reactor length. A conventional immersed well reactor (Photochemical Reactors) with a 125 W medium pressure Hg (Hg MP) lamp was used for comparison. A valveless rotary piston dispensing pump (Ismatec) was used for recirculation of the reaction mixture. Microreactor. The microreactor rig consisted of a silicon microfluidic chip pressed by two plastic flangeless fittings to a stainless steel heat exchanger. The microreactor chip was fabricated in two steps. First, a meandering channel (width × 1444



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Table 1. Efficiency of the annular recirculating photoreactor and reaction performance in annular recirculating and immersedwell (IW) photoreactors lamp 420 nm FL 524 nm LED Xe arc Hg MP (IW) a

IL (cm) 23 15 3.5 3c

Pin (W) 48 16 75 125

Ia × 104 (Einst L−1 s−1) 5.7 4.6 2.3 1.2

ηLR (%)

ηPL (%)

a

b

9.5−19 69.1

20−40 8.8

ηR (%)

rT0 × 105 (mol L−1 s−1)

rR0 × 104 (mol L−1 s−1)

ϕR

3.8 6.1

2.0 1.1 0.21 0.76

1.8 1.1 0.70 0.076

0.322 0.248 0.303 0.065

Value estimated using eq 1 and ηPL = 20−40%.12 bReference 12/ cDischarge length. IL = illuminated reactor length.

kept at 20 °C in all experiments. Conversions, C × C0−1, were calculated from 1H NMR spectra. Pinocarvone. 1H NMR (300 MHz, CDCl3) δ 0.74 (3H), 1.19 (d, J = 10.3 Hz, 1H) 1.29 (s, 2H), 2.13 (m, 1H), 2.46 (m, 1H), 2.60 (m, 2H) 2.7 (t, J = 6.1 Hz, 1H), 4.95 (s, 1H), 5.91 (s, 1H).11

was mounted in a rectangular metal box with cooling fans and IR glass filter window. The microreactor rig was operated in two different modes: continuous flow and batch recirculating mode; see Figure 1. Each mode of operation makes it possible to use two different approaches towards saturation of the reaction mixture by O2: bubbling the gas through reaction mixture in the reservoir to saturate the reactant/solvent mixture and allow a homogeneous oxygenation and segmented gas−liquid flow, which is a heterogeneous process. The single-phase reactions were performed at 1−6 barg O2 and the two-phase reactions at 1− 60 barg. Actinometry and Photochemical Reactions. The intensities of absorbed light for all of the light sources and reactors were measured under flow conditions following the Hatchard-Parker procedure;9 for details see the Supporting Information. Oxygenation of α-pinene (Figure 2) was carried out using a modification of the method reported in ref 10. The reaction mixture (100 mL), further referred to as “α-pinene mix”, was prepared as follows: 5.85 mL of α-pinene, 0.45 g of 4dimethylaminopyridine (DMAP), 4.23 mL of acetic anhydride, 5 mL of pyridine, and 5.5 × 10−2 g (8.1 × 10−5 mol) of tetraphenylporphine (TPP) were dissolved in CH2Cl2 inside a feed tank. The reaction mixture was recirculated/pumped through the reactor. Continuous saturation of the α-pinene mix was carried out by bubbling O2 through the feed tank at a flow rate of 30 mL min−1 (all of the O2 flow rates in this work are given at standard temperature and pressure conditions, STP) for 1 h before and during the experiments. The pressure of O2 was set at 1 barg in the cases of the annular recirculating and the immersed well reactors, while the microreactor in the continuous or the recirculating modes (homogeneous oxygenation) was operated at 1, 3.5, and 6 barg. The liquid flow rate was set at 40 mL min−1 in the case of the annular recirculating reactor. The microreactor was tested in the continuous mode at the liquid flow rates of 2.5, 2.0, 1.5, 1.0, 0.75, 0.5, 0.25, 0.1, and 0.05 mL min−1 or in the recirculating mode at 2 mL min−1. After 1 h saturation of the reaction mixture by O2, the lamp was switched on, and aliquots were collected from the reservoir at different times/residence times or directly from the outlet in the case of the microreactor operated in the continuous mode (Figure 1c). When the microreactor was operated in the segmented gas− liquid flow mode, O2 was supplied at various flow rates and pressures (1, 8, 18, 35, and 52 barg). The α-pinene feed was mixed with oxygen in a tee-mixer at the inlet to the microreactor and was fed at a constant flow rate of 0.1 mL min−1. The flow of O2 was controlled by a low-flow metering valve and measured volumetrically. Back-pressure regulators (2.8, 5.2, 7, 17, 34, 51 barg, Upchurch Scientific) were used in the experiments at elevated pressures. The temperature was

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RESULTS AND DISCUSSION Annular Recirculating and Immersed-Well Photoreactors. Oxygenation of α-pinene in the annular recirculating photoreactor was studied in three lamp-reactor geometries: (i) with circular LED lamp, (ii) with tubular actinic fluorescent light, and (iii) with the Xe arc lamp; experimental observations were compared in terms of different efficiencies defined below and summarized in Table 1. These results were compared with a standard immersed-well reactor illuminated by a Hg lamp. An overall photoreactor efficiency, ηR, taking into account efficiency of the light source and the specific lamp-reactor geometry, may be expressed as shown in eq 1: ηR = ηLR ηPL (1) where ηLR is the efficiency of a lamp-reactor geometry, ηPL is the efficiency of power-to-light conversion. ηLR = Phv/P0hv, ηPL = P0hv/Pin, where P0hv is the total emitted power output of the lamp, Phv is the power absorbed inside the photoreactor, and Pin is the supplied power. The efficiency of a lamp-reactor geometry may further be written as ηLR = (Ω/4π){1 − ∑ni αi exp(−εicSd)}. Here Ω is solid angle, Ω ≈ A/d2LR, A is the illuminated surface area of the reactor, dLR is the distance between a lamp and the reactor, αi is the fraction of power at the surface of the reactor for photons with the i-th wavelength to the total power of all of the emitted photons, αi = PSR(λi)/∑PSR(λi), εi is the molar extinction coefficient of a photosensitizer at the i-th wavelength, cS is the concentration of a photosensitizer, and d is the depth of the reactor. In the case of the 524 nm LED lamp, Figure 1b, it was possible to estimate P0hν and, therefore, efficiency of the lampreactor geometry, ηLR. Using the number of photons absorbed inside the photoreactor it was found that about 70% of light emitted by the lamp was used in the photoreaction; see Table 1. The observed high efficiency of light utilization stems from the circular geometry of the LED lamp and the narrow radiation pattern of a single LED bulb, with the off-axis angle where the intensity drops to 0.5 of the on-axis intensity being 7.5°. The origin of light losses in this system is most likely the reflection of light from different interfaces, such as air−glass, glass−liquid, and gas−liquid. Efficiency of the power-to-light conversion, ηPL, was found to be about 8.8%. This number is two to three times lower than that normally delivered by conventional light sources, such as fluorescent lamps, which routinely demonstrate about 20−40% power-to-light conversion efficiency.12 An overall efficiency of 1445



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the annular recirculating reactor, ηR, with the 524 nm LED lamp was found to be about 6.1% (see Table 1). Table 1 also summarizes actinometric intensity of absorbed photons, Ia, which was highest in the case of the 420 nm actinic fluorescent lamp, followed by the 524 nm LED lamp, while the Xe arc lamp demonstrated the lowest performance. Two other light sources, the 420 nm FL and Xe arc, showed even lower levels of light utilization when used with the annular photoreactor due to additional light losses. A value of ηR of only 3.8% was achieved with the fluorescent lamp illuminating the annular flow reactor. It was impossible to estimate efficiency of the Hg light from the available data. However, only ca. 5% of the total photon flux actually illuminated the reactor; thus the overall efficiency is likely to be very low. The initial rates of pinocarvone accumulation in the tank (rT0 ) and its generation inside the annular reactor (rR0 ) follow the expected trend with the amount of absorbed photons: the more photons are absorbed inside the reactor, the higher are the initial rates of generation and accumulation of the product. The highest rate was achieved with the 420 nm actinic fluorescent lamp followed by 524 nm LED lamp; see Figure 3 and Table 1. The lowest reaction rate was found with the Xe arc lamp. This trend is reflected in the quantum yields of pinocarvone generation.

than the optimum do not lead to any increase in the initial reaction rates. Moreover, a large excess of a photosensitizer may lead to concentration quenching of 1O2 and agglomeration of a photosensitizer, reducing the overall efficiency of oxygenation, as was shown in the literature.13 For comparison, we carried out oxygenation of α-pinene in a conventional immersed-well quartz photoreactor equipped with a 125 W Hg MP lamp. A 53% conversion was obtained after 7 h of illumination and continuous bubbling of O2 through the reaction mixture; see Figure 3 and Table 1. Complete conversion of α-pinene required several days of illumination. It is remarkable that quantum yields obtained in the annular photoreactor are higher compared to these found for the most frequently used immersed-well reactor. However, this can be explained by poor spectral overlap between the emission lines of the Hg MP lamp and absorption bands of TPP: nearly 23% of emission of Hg MP lamp is in the region of 546, 577, and 579 nm where the molar extinction coefficients of TPP are quite low (8033, 2814, and 3245 L mol−1 cm−1, respectively).14 According to Lambert−Beer equation, a 8.1 × 10−5 M solution of TPP absorbs (respectively) about 93, 62, and 66% of light at these wavelengths, in the optical path length of 1.8 cm, corresponding to the thickness of the reactor space in the immersed-well reactor. Overall, an estimate for this specific case gives approximately 93% absorption of all the photons emitted by a Hg MP lamp with about 68% being absorbed in a reaction layer of only 0.5 cm, corresponding to about 28% of the total volume of the immersed well reactor. The remaining (about 25% of the total flux of photons) is absorbed in the 72% volume of the reactor, thus forming a thick zone of low illumination. This, along with poor mixing between the layers with different illumination levels, results in a lower rate of 1O2 generation observed for the case of the immersed-well reactor. In the case of the annular recirculating reactor a better efficiency (more than 23 times difference) was achieved not only due to the higher intensity of the absorbed light (more than 5 times difference) but also owing to a more efficient mixing provided by the well-dispersed rising bubbles of O2, and good spectral overlap between the emission bands of the nearly monochromatic 420 nm fluorescent lamp and the most intensive absorption band of TPP (at 417 nm). At the same concentration of TPP (8.1 × 10−5 M), a complete absorption of all photons is already achieved in the well-mixed O2-rich narrow reactor space of 0.15 cm. Therefore, the thickness of the reaction layer and efficiency of the spectral overlap between emission bands of the light source and absorption bands of a photosensitizer, together with the intensity of the absorbed light, are the most important parameters responsible for high quantum yield of photochemical transformations.

Figure 3. Conversion of α-pinene in the annular recirculating photoreactor illuminated by 524 nm LED (○), 420 nm fluorescent (×), and Xe arc lamps (●) compared with that in the immersion well reactor illuminated by Hg MP lamp (△).

Data obtained in experiments with different concentrations of TPP show that the rate of reaction is proportional to the amount of absorbed photons and that for the fixed intensity of incident light there is an optimum in the photosensitizer concentration, which coincides with complete absorption of incident light by the reaction layer. The concentrations higher

Table 2. Light efficiency and homogeneous oxygenation rates in the microreactor operating in single pass through (continuous) or in the recirculation (batch) mode lamp

Pin (W)

Ia × 103 (Einst L−1 s−1)

ηLR (%)

ηPL (%)

ηR (%)

continuous ↓

Xe arc 524 nm LED 416 nm LED ↓

75 3.1 3.2 ↓

0.33 0.32 1.9 ↓

6.7 21.4 ↓

8.8 15.3 ↓

0.24 3.3 ↓

recirculating ↓

416 nm LED

3.2

1.9

21.4

15.3

3.3

mode of operation

1446

pO2 (barg) 1.0 1.0 1.0 3.5 6.0 1.0 6.0

rT0 × 106 (mol L−1 s−1)

rR0 × 103 (mol L−1 s−1)

ϕR

0.89 2.6

0.14 0.13 0.33 0.74 0.85 0.37 1.1

0.420 0.404 0.171 0.384 0.414 0.192 0.562



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Microreactor in a Single-Phase Continuous Operation. Using actinometry data for evaluation of absorbed photons flux in the silicon-glass microreactor with different illumination sources, it was found that the largest amount was absorbed in the case of the 416 nm LED array, followed by the Xe arc lamp and the 524 nm LED array; see Figure 1c, d, e for reactor configurations and Table 2 for results. This is due to efficient spectral overlap between the emission band of the 416 nm LED array and the absorption bands of sensitizer TPP, providing complete absorption of all photons in the 0.024 mm depth of a microchannel at TPP concentration of 8.1 × 10−4 M. This is in contrast to the case of the 524 nm array when only about 40% of all of the emitted photons are absorbed within the same depth of a microchannel. Based on the output power and the actinometry data, we estimated efficiency of the lamp-reactor geometry for both LED arrays, using the same definition of efficiency as above. It was found that about 7 and 21% of the light emitted by the 524 and 416 nm arrays was used in the photoreaction, Table 2. Low efficiencies of this lamp-reactor geometry are explained by the long distance between the microreactor and the light sources. In order to achieve better efficiency, the array should be situated at the shortest possible distance. This may then require additional cooling for the system. The overall efficiencies for the LED arrays were found to be 0.6% and 3.3% for the 524 and the 416 nm LED arrays correspondingly. Although the estimated efficiencies of the lamp-reactor geometry are quite low, the specific (per volume of the microreactor) intensities of light absorbed inside the microreactor are of the same order of magnitude, or even higher as in the case of the 416 nm LED array, as those found for the annular photoreactor; compare Tables 2 and 1. In the oxygenation of α-pinene it was found that conversion increased with a decrease in the flow rate until a stationary conversion was attained; see Figure 4a. This is associated with the increase in the residence time τ, defined as τ = VR/QL, where VR is the volume of the reactor and QL is the volumetric flow rate of the liquid phase. The steady state conversion at a given concentration of a sensitizer is limited either by the amount of α-pinene or by the amount of dissolved O2. Concentration of O2 in CH2Cl2 saturated at normal pressure is 8.8 × 10−3 M.15 Therefore, consumption of all the dissolved O2 in the reaction with 0.36 M solutions of α-pinene (about 40 times excess) corresponds to the maximum possible conversion of 2.4%. The saturation concentration of O2 in CH2Cl2 at 3.5 barg is about 3.1 × 10−2 M,15a which corresponds to the maximum conversion of 8.5%, while at 6 barg O2 solubility is increased up to 5.3 × 10−2 M,15a resulting in a maximum conversion of 14.7%. The obtained values are in good agreement with the experimental data; see Figure 4b. Slight discrepancies between experiments and the theory may be attributed to a lower Henry constant for dissolution of O2 in the α-pinene mixture compared to that of the pure solvent. The initial reaction rates and quantum yields estimated for different O2 pressures and sources of light are listed in Table 2. The obtained data suggest that higher conversions of α-pinene (inlet concentration of 0.36 M) may be obtained at higher O2 saturation pressures with suitable residence times. It was estimated that 40 bar is sufficient to attain a 0.36 M concentration of O2 in CH2Cl2. However, saturation of a reaction mixture by O2 at such a high pressure involves an increased risk of explosion and, therefore, should be avoided in

Figure 4. Conversion of α-pinene in the microreactor operated in a continuous mode with O2-saturated feed: (a) at 1 barg illuminated by △, Xe arc lamp; ▲, 524 nm LED array; □, 416 nm LED array; (b) at ▲, 6 barg; ○, 3.5 barg, and ●, 1 barg illuminated by the 416 nm LED array. Dotted lines represent maximum conversion corresponding to consumption of all of the dissolved O2.

all reactors that are not proven to be intrinsically safe in oxidation processes. Microreactor in a Single-Phase Operation with Recirculation (Batch Mode). The concentration of O2 dissolved in CH2Cl2 at atmospheric pressure is about 10−2 M. If the concentration of a reagent is higher than the amount of available O2, the compound will not be completely oxygenated in the continuous mode during one pass, as stoichiometry of the ene reaction is 1:1. For example, in the experiments carried out with 0.36 M solutions of α-pinene, about 97% of α-pinene remained unreacted. In order to obtain 100% conversion, the reaction mixture should be resaturated with O2 and passed through the reactor several times which can be done in a recirculation mode. We carried out recirculating experiments at a liquid flow rate of 2 mL min−1 using the 416 nm LED array for illumination of the microreactor and continuous saturation of the reaction mixture by bubbling O2 in the tank at 1 and 6 barg. These conditions correspond to conversions of about 1 and 2% obtained in a single pass in the continuous mode, while the 1447



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small volumes of gas bubbles, and excellent heat exchange; see for example Jahnisch et al.4a and references therein. Moreover, small dimensions and meandering geometry of a microchannel provide efficient internal mixing in segmented gas−liquid flows.16 Therefore, we studied the influence of O2 pressure and flow rate on conversion of α-pinene in segmented gas−liquid flow in more detail. The oxygenation was carried out at a fixed liquid flow rate (0.1 mL min−1) with O2 injected into the reaction mixture via a t-connector at different flow rates. The 416 nm LED array was used for illumination of the microreactor. Several different types of segmented flow were observed, depending on O2 flow rate. At low O2 flow rates (15 mL min−1 an annular flow was observed. There are many factors crucial for stability of segmented flow.17 Most important among them are the configuration of gas injector, geometric changes in the channel such as bends, and spatial variation of the surface roughness and the microchannel cross-section. In the current study a simple tconnector was used as gas-phase injector to form gas−liquid flow inside Teflon tubing. The obtained segmented flow was then introduced into rectangular meandering microchannel via a tight compression fitting connection. Such an arrangement is introducing significant changes to flow velocity profile and variations in pressure drop. Furthermore, the spring-loaded back-pressure regulators used are necessarily introducing fluctuation in the flow rate due to the difference in response of the BPR to compressible and incompressible fluid domains within segmented flow. As a consequence, variations in bubble lengths in the obtained flow were up to 30−40% of the bubble length. It was found that conversion of α-pinene increased with a decrease in the flow rate of O2 in the range of pressures studied (1−52 barg); see Figure 6a. This is explained by the shortening of total residence time, τT = VR/(uG + uL) and smaller liquid holdup, βL = uL/(uG + uL). The apparent O2 flow rate, uG, can be expressed as a function of O2 pressure from the mass balance

concentration of O2 is not depleted completely during the oxygenation. Kinetic curves obtained in both experiments are shown in Figure 5. One can see from these data that about 4−5

Figure 5. Conversion of α-pinene in the microreactor illuminated by a 416 nm LED array in the recirculating mode at continuous saturation of reaction mixture via O2 bubbling at 6 barg and at 1 barg.

days is required for complete oxygenation of all of the α-pinene (0.36 M) in 100 mL of the reaction mixture saturated by O2 at atmospheric pressure. The initial reaction rate and, therefore, the quantum yield as well are close to that estimated earlier in the continuous mode experiment; see Table 2. The initial rate of reaction increases approximately three times at 6 barg of O2 saturation pressure, similar to experiments carried out in the continuous mode. The obtained value is in satisfactory agreement with that obtained in the continuous mode. A period of about 2 days is required for complete conversion of 100 mL in the microreactor unit at elevated pressure. Microreactor in a Gas−Liquid Segmented Flow Operation. The major drawback of operating a microreactor in the recirculating or continuous modes with presaturation of the reaction mixtures by O2 in a reservoir at normal and elevated pressures is the hazard of explosion of the formed O2organic vapor mixtures in the feed reservoir. It was reported earlier that microreactors allow safe and efficient way of carrying outgas−liquid reactions in segmented flow including oxygenation of allylic substrates by photogenerated 1O2 at atmospheric pressures and gas-phase reactions at elevated O2 pressures due to short quenching distances in a microchannel,

Figure 6. Performance of the microreactor operated in the gas−liquid segmented flow mode. (a) Conversion of α-pinene vs O2 flow rate at 1, 8, 18, 35, and 52 barg. Vertical dotted lines are set at 1 and 30 mL min−1. Inset: an image of gas−liquid segmented flow in the microchannel. (b) Conversion (filled symbols) and liquid holdup (empty symbols) vs O2 pressure for gas flow rates of 1 mL min−1 (○, ●) and 30 mL min−1 (△, ▲). The liquid flow rate is 0.1 mL min−1; the 416 nm LED array was used for illumination. 1448



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Table 3. Oxygenation of α-pinene carried out in the microreactor in segmented flow mode illuminated by the 416 nm LED array at different O2 pressures at fixed flow rates of O2 and reaction mixture (uG = 1 mL min−1, uL = 0.1 mL−1 min−1) and illuminated by the 250 W HID lamp at 2 barg and various uLa

a

lamp

L (cm)

Pin (W)

PO2/ uL/uG (barg/mL−1 min−1)

Ia × 103 (Einst L−1 s−1)

rR0 × 104 (mol L−1 s−1)

ϕR

416 nm LED ↓

4.5 ↓

3.2 ↓

1.9 ↓

HID ↓

11.3 ↓

250 ↓

1.0/0.1/1 8.0/0.1/1 18.0/0.1/1 35.0/0.1/1 2.0/0.025/0.436 2.0/0.05/0.503 2.0/0.1/0.605 2.0/0.2/0.716

1.0 2.4 3.3 4.1 4.9 6.2 9.5 11

0.053 0.125 0.171 0.217 0.136 0.172 0.263 0.306

3.6 ↓

Values of uG are taken at maximum performance of the microreactor.

Figure 7. Dependence of α-pinene conversion (C0 = 3.6 × 10−1 M) to pinocarvone on the flow rate of O2 at different liquid flow rates of the reaction mixture (a). Correlations of the productivity with the amounts of available O2 and α-pinene vs total residence time (b).

reactor while most of the photons are wasted. An improvement in light utilization can be achieved only if the lamp is used for illumination of several microreactors situated in a circular geometry around the lamp. Consumption of O2 during oxygenation of α-pinene was monitored using visual disappearance of O2 bubbles inside the microchannel. It was found that for the fixed liquid flow rate at low gas flow rates conversion of α-pinene varies in a linear manner as a function of the O2 flow rate, i.e., the reaction is limited by supply of O2; see Figure 7a. For the higher rates of O2 flow, the α-pinene conversion reaches a maximum and then decreases due to the shortening of the total residence time. A similar behaviour was observed in a gas−liquid−solid catalytic oxidation of benzyl alcohol in a compact multichannel reactor and in the hydrogenation of methylstyrene in monolith reactors.18 The decrease in conversion at longer residence times is explained by the lower rate of gas−liquid mass-transfer at low flow rates. The maximum of α-pinene conversion for each particular liquid flow rate corresponds to complete disappearance of gas bubbles at the outlet of the microchannel due to consumption of O2 in the reaction. At these conditions the microreactor operates at its maximum performance. A decrease in the liquid flow rate results in higher conversions of α-pinene but, at the same time, reaction rate is decreased; see Table 3. The higher conversions are explained by the longer total residence times while a decrease in the rate of the gas−liquid mass transfer and smaller gas or liquid holdups (and therefore, smaller amounts of α-pinene and O2 available for oxygenation per unit time) lead to lower reaction rates.18,19 It is worth mentioning that the rates of reaction are close to or even higher than these obtained in the annular and

eq 2, taking into account the amount of dissolved O2 at a given gas pressure, PO2·H·uL. PO02 RT

uG =

PO2 RT

uG0 + PO2HuL

(2)

P0O2

where PO2 is O2 pressure, = 1 atm, R is the ideal gas constant, T is temperature, uG and uL are the actual volumetric flow rates of O2 and the liquid phase, and H is Henry’s constant (H = 8.8 × 10−3 M atm−1 for CH2Cl215a). Conversion and, therefore, quantum yield of reaction increase with O2 pressure at low gas flow rates of O2 (u0G ≤ 1 mL min−1) while at the high gas flow rates (u0G > 30 mL min−1) conversion becomes virtually independent of pressure and governed by the total residence time and the liquid holdup; see Figure 6b and Table 3. The region of O2 flow rates below 1 mL min−1 was studied in more detail at a fixed O2 pressure of 2 barg and different liquid flow rates in order to determine optimal conditions for oxygenation of α-pinene. A more powerful 250 W MH lamp was used. It was expected that the high power lamp would provide higher conversions. However, the intensity of the absorbed photons estimated using the actinometry data was found to be about 3.6 × 10−3 Einst L−1 s−1 (see Table 3), which is only twice higher than that obtained for the 416 nm LED array, 1.9 × 10−3 Einst L−1 s−1. Such a low value found in the case of the 250 W MH lamp is explained by the inefficient lamp-reactor geometry, low level of spectral overlap (not all the emitted wavelengths are absorbed completely in the reactor space), and about 1.6 times longer distance between the lamp and the microreactor. The lamp emits light in all directions, and only a small part of the total flux of photons illuminates the 1449



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⎛ ∂ 2c ∂ 2c ⎞ ∂c Di⎜ 2i + 2i ⎟ = u(x , y) i + εcS( −9 i)e−εcS(d /2 − x) ∂z ∂y ⎠ ⎝ ∂x

immersed-well reactors due to better light utilization in the microreactor; compare Tables 1 and 3. Figure 7b represents the observed correlations between productivity and the amounts of available α-pinene and O2 versus total residence time τT calculated for the conditions of complete consumption of O2. These data suggest that using 5 identical microreactor units connected in series, providing a 5times longer single reaction channel, with independent supply of each unit by O2 similar to staged injection of O2 along the length of the microchannel applied in ref 18a in the regime of low conversions is more efficient in terms of productivity than the same 5 microreactors connected in parallel with the flow rates adjusted to obtain 100% conversions in each microreactor unit. It is worth to compare different types of photoreactors and operation conditions in terms of space-time yield (STY), defined as the amount of product per unit time per unit volume of a reactor, mol L−1 s−1), which for the case of the flow reactor may be expressed as STY =

(4)

where x and y are the coordinates measured from the center of the channel and along its depth d and width w, respectively. The species diffuse with a coefficient Di and the liquid stream flows in the axial direction z, with a fully developed velocity profile u. Only the top surface of the microchannel is being irradiated (Sirr = wL) and a unidirectional beam of light penetrates through the channel depth. The quantities relevant for describing light absorption are the sensitizer concentration cS and extinction coefficient ε. The reaction rate for the consumption of α-pinene and oxygen (−9 i) can be derived from a detailed mechanism for photosensitized oxygenation of substrates with singlet oxygen (see Supporting Information). The kinetic expression includes −1 light intensity at the irradiated surface I0 (in einst m−2 irr s ) and −1 concentrations ci (in mol L ), yielding the reaction rate (−9 i) −1 in mol m−2 irr s :

CpinocarvoneuL VR

(3)

− 9R = − 9 O2

where Cpinocarvone is the concentration of pinocarvone at the outlet of the continuous flow reactor. In the case of the immersed well photoreactor the initial reaction rate can be used as a measure of performance. One can see from the data shown in Figure 8 that STYs of a single

=

7.95 × 109I0c R cO2 (1.2 + 1.8 × 103cS + 4.3 × 104c R )(50 + 2.1 × 105cO2) (5)

Numerical coefficients are consistent with the units indicated above and operation at 20 °C. Conversion of a reactant is calculated from averaging the concentration field over the microchannel cross-sectional area A, Xi =

ci ,in − ⟨ci⟩ ci ,in

=1−

∬ uci dA ∬ uci , in dA

(6)

The parameters required to solve the model are given in Table 4. The molecular diffusivities of α-pinene and oxygen in the “α-pinene mix” (taken as being essentially solvent, i.e., dichloromethane) are estimated as described in the Supporting Information. The system of differential eqs (eq 4) is solved numerically using the “pdepe” function in Matlab R2013a. Simulations with the 3D geometry were compared with calculations using 2D planar plates for several values of the ratio between the channel width and depth. The differences in the values of conversion calculated were found negligible. Consequently, eqs 4 and 6 are simplified (the diffusive term in the y- direction disappears, and the averaged fluxes are integrated over a single transverse direction, x). Parabolic velocity profile was considered, since the flow is in the fully developed laminar regime. The results from the model simulation are compared with experimental data shown in Figure 4b. One can see that the model provides a reasonable description of experimental observations, especially taking into account that no parameter was fitted to quantities measured experimentally, and that no independent kinetic experiment was performed (i.e., simulations rely solely on information available in the literature for photosensitized oxygenations, see the Supporting Information). Given the acceptable validity of the model, a parametric study can be conducted to optimize the reactor design. The optimum dimensioning of the microchannel can be guided by the minimization of the levelized cost of pinocarvone

Figure 8. Space-time yields of different types of photoreactors calculated for different conditions (various sources of light, O2 pressures, flow rates, and modes of operation). ARR is the annular recirculating reactor, IW is the immersing well reactor, and MR-CF, MR-RF, and MR-SF represent the microreactor operating in the continuous, recirculating, and segmented flow modes correspondingly. 420FL is a 420 nm actinic lamp, and MH is a metal halide lamp (numbers represent the liquid flow rates in μL min−1). Quantum yields of pinocarvone generation (●) correspond to the right axis.

microreactor unit are up to 10 times higher than these estimated for the annular recirculating and the immersed-well reactors, while the quantum yields of α-pinene oxygenation are mostly similar or higher in the case of the microreactor, due to better utilization of light in the reaction. Modeling and Optimization of Homogeneous Continuous Flow Oxidation. Oxygenation of α-pinene (R) can be better understood and optimized by modeling the reactiontransport processes that occur in a single-phase microchannel flow. The mass balance to component i (i = R, O2) in a long rectangular channel is given by 1450



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Table 4. Variables for microreactor modeling and optimization variable

units

̇ Ppump =

value

m cm2

QL τ cR,in pO2

mL min−1 s M bar

cS ηpump

M

Operation

ε λ I0 Ṗin μf DR DO2 PR Pelect dopt costmin Ḟ P

6

8.1 × 10−4 0.9 Light Utilizationa m−1 M−1 3.45 × 107 nm 416 1− mol m−2 4.56 × 10−4 irr S W 24.1b Physical Properties cP 0.44c 2 −1 m s 2.02 × 10−9d 2 −1 m s 9.21 × 10−9d Cost Coefficients $/mol 0.112 $/(kW hr) 0.068 Optimization μm 173 $/mol 8.450 $ 56.25 g pinocarv/h 0.072

2Cf Q L2μf L ηpumpdh2A

=

μf Q L2

2 ⎛ d⎞ L Cf ⎜1 + ⎟ 2ηpump ⎝ w ⎠ wd3

A constant value for the pump efficiency (ηpump) was assumed, and the (Fanning) friction factor coefficient (Cf = f Reh) is given as a function of d/w for rectangular ducts22 (0 ≤ d/w ≤ 1); • The area of the surface being irradiated (Sirr) is considered to be fixed for a given reactor−lamp arrangement, and its base case value corresponds to that of the experimental setup (≃10 cm2). Regarding the behavior of the cost model, the following observations can be made (Figure 9):

1.995 9.975 1 14.4 0.36 1

ηpump

=

(8)

Geometry L Sirr

Q LΔp ̂

244 7.763 51.68 0.078

a

Using the 416 nm LED array. bPower consumed by drivers included. c Value for solvent (dichloromethane). dCalculated using the Wilke− Chang correlation (see Supporting Information).

production ($ per kg of pinocarvone produced). This objective function includes the cost of reactant and electricity consumed by lamp(s) and pump required to promote fluid flow. It is given by ̇ ) Pelect(Piṅ + Ppump P cost(d , L) = R + XR FṘ XR (7) The parameters included in this cost model are given in Table 4. Namely, the levelized cost of pinocarvone production depends on: • cR,in and ḞR are the molar concentration and flow rate of reactant in the feed stream (ḞR = QLcR,in, where QL is the flow rate in the cases of homogeneous flow); • XR is the conversion of reactant, calculated according to eq 6, with the concentration profile calculated from solving the system of differential equations eq 4; • PR is the price of reactant (α-pinene), which may be considered to vary between the costs of turpentine and pine oil, both given per kg of chemical.20 An average between these two limits suggests the value of PR indicated in Table 4; • Pelect is the price of electricity for industrial purposes;21 • Ṗin is the power supplied to the lamp (array of LEDs 416 nm), where the value of the power consumed by drivers (for stabilization of LED feed current) was included; • The power required by the pump for laminar channel flow is given by

Figure 9. Operating cost ($/mol of pinocarvone produced) as a function of microchannel depth d. Fixed variables in the cost model are specified in Table 4. (a) Influence of microchannel length L at pO2 = 6 bar. (b) Influence of oxygen pressure (pO2) for L = 2 m.

(a) The operating cost can be considered to be independent of the microchannel length for a wide range of channel depths (d > 50 μm). This occurs since conversion is independent of L for fixed Sirr and QL (provided that d ≪ L) and the only influence is introduced through the term accounting for pumping costs (which only becomes dominant at low channel 1451



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segmented gas−liquid flow in a safe manner even at elevated O2 pressures. Within the window of maximum performance, productivity of the microreactor increases with a decrease in the total residence time (opposite to conversion) due to higher gas and liquid holdup volumes. Using a mass transfer-reaction model coupled with a cost objective function, it was found that the microchannel depth is the relevant dimension to be optimized, which for continuous oxygenation should take values around 200 μm for minimum cost per kg of pinocarvone produced. Moreover, increasing the pressure of oxygen leads to optimum designs, which are associated with lower cost and are more robust (in the sense that for a wider range of depth values around the optimum, cost does not change significantly).

depths). This means that a wide range of values for w can be chosen, keeping the same irradiated surface area. (b) At the highest pressure of oxygen considered, Figure 9a, the optimum value found from the cost model practically coincides with the design of the experimental setup (dopt = 244 μm vs dexp = 240 μm). (c) The calculation of conversion when a flatter velocity profile is considered (plug-flow assumption) does not result in significant changes in the values of the cost function. Therefore, the analysis is equally useful for the cases where a more uniform flow profile is promoted. (d) There is a reasonably wide range of channel depths for which the cost does not vary significantly around the optimum value. For example, in the conditions of Figure 9a (L = 2 m), the deviation relative to the minimum cost is less than 5%, when d is between 105 and 1870 μm. This wide range ensures that near-optimal designs (with respect to operating cost minimization) can be attained, if other constraints are present. (e) There are several effects of increasing the pressure at which oxygen is supplied (Figure 9b): (i) for the same channel length, costs per amount of pinocarvone produced decrease; (ii) the cost decreases more significantly for larger depths; (iii) the size of the slowly varying cost region near the optimum is greatly increased; (iv) the value for the optimum depth is dislocated towards higher values of channel depth (since dopt = 173 μm for pO2 = 1 bar). (f) The product flow rate Ḟ P from a single channel with residence time of 14.4 s does not vary significantly for the whole range of depths. Values at the optimal point are indicated in Table 4.

■

■

ASSOCIATED CONTENT

S Supporting Information *

Description of the actinometry procedure and respective data processing. Kinetic modeling. Estimation of diffusion coefficients. Schematic representations of annular recirculating reactor and microreactor. Photo of the microreactor used. This material is available free of charge via the Internet at http:// pubs.acs.org.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]; fax: +44 (0) 1223 334796. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS The authors would like to acknowledge Dr Mikhail A. Kabeshov for help with the experiments in the immersed well reactor. The research leading to these results has received funding from the European Community’s Seventh Framework Programme for FREECATS under grant agreement no. FP7NMP3-SL-2012-280658, and Engineering and Physical Sciences Research Council via grant EP/E012183/1.

CONCLUSIONS

A laboratory-scale annular recirculating photoreactor was designed and tested with a 524 nm LED, a 420 nm actinic fluorescent, and Xe arc lamps in different lamp−reactor geometries. Based on the actinometry data, it was shown that the overall efficiency of the lamp−reactor design in the case of the LED lamp is superior to that of the more power-consuming actinic fluorescent lamp due to the several times more efficient circular lamp−reactor geometry and the narrow radiation pattern of a single LED bulb. The reactor was tested in the oxygenation of α-pinene to pinocarvone. It was shown that the reaction rate is proportional to intensity of absorbed photons. A comparison of performance of the annular reactor with that of a conventional immersed-well photoreactor confirmed the importance of narrow reaction space for efficient oxygenation. Based on the actinometry and the kinetic data, it was shown that in the case of a microreactor the intensities of absorbed light, rates, and quantum yields of oxygenation are close or several times higher than those found for the annular and the immersed-well photoreactors due to a better light utilization. Space−time yields calculated for a single microreactor unit were found to be about 3−7 times higher due to significantly better utilization of light in the microchannel. This study also proved the viability of a novel concept of compact reactors illuminated by LEDs, which are already comparable with the more power-consuming sources of light in terms of intensity of the absorbed light. It was found that the productivity of the microreactor in oxygenation of allylic substrates by photogenerated singlet oxygen increases with oxygen pressure. It was shown that oxygenation reactions can efficiently be performed in a

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REFERENCES

(1) (a) Fischer, M. Industrial Applications of Photochemical Syntheses. Angew. Chem., Int. Ed. Engl. 1978, 17 (1), 16−26. (b) Lu, H.; Schmidt, M. A.; Jensen, K. F. Photochemical reactions and on-line UV detection in microfabricated reactors. Lab Chip 2001, 1 (1), 22− 28. (c) Pape, M. Industrial Applications of Photochemistry. Pure Appl. Chem. 1975, 41 (4), 535−558. (2) Hook, B. D. A.; Dohle, W.; Hirst, P. R.; Pickworth, M.; Berry, M. B.; Booker-Milburn, K. I. A practical flow reactor for continuous organic photochemistry. J. Org. Chem. 2005, 70 (19), 7558−7564. (3) Kopetzki, D.; Lévesque, F.; Seeberger, P. H. A continuous-flow process for the synthesis of artemisinin. Chem.Eur. J. 2013, 19 (17), 5450−5456. (4) (a) Jahnisch, K.; Hessel, V.; Lowe, H.; Baerns, M. Chemistry in microstructured reactors. Angew. Chem., Int. Ed. 2004, 43, 406−446. (b) Fukuyama, T.; Rahman, M. T.; Sato, M.; Ryu, I. Adventures in inner space: Microflow systems for practical organic synthesis. Synlett 2008, 2, 151−163. (5) (a) Wootton, R. C. R.; Fortt, R.; Mello, A. J. d. A Microfabricated Nanoreactor for Safe, Continuous Generation and Use of Singlet Oxygen. Org. Process Res. Dev. 2002, 6, 187−189. (b) Ehrich, H.; Linke, D.; Morgenschweis, K.; Baerns, M.; Jahnisch, K. Application of Microstructured Reactor Technology for the Photochlorination of Alkylaromatics. Chimia 2002, 56, 647−653. (c) Ueno, K.; Kitagawa, F.; Kitamura, N. Photocyanation of Pyrene Across an Oil/Water Interface in a Polymer Microchannel Chip. Lab Chip 2002, 2, 231− 234. (d) Fukuyama, T.; Hino, Y.; Kamata, N.; Ryu, I. Quick execution

1452



Article

of [2 + 2] type photochemical cycloaddition reaction by continuous flow system using a glass-made microreactor. Chem. Lett. 2004, 33, 1430−1431. (e) Gorges, R.; Meyer, S.; Kreisel, G. Photocatalysis in Microreactors. Photochem. Photobiol. A: Chemistry 2004, 167, 95−99. (f) Maeda, H.; Mukae, H.; Mizuno, K. Enhanced efficiency and regioselectivity of intramolecular (2π+2π) photocycloaddition of 1cyanonaphthalene derivative using microreactors. Chem. Lett. 2005, 34, 66−67. (g) Hook, B. D. A.; Dohle, W.; Hirst, P. R.; Pickworth, M.; Berry, M. B.; Booker-Milburn, K. I. A Practical Flow Reactor for Continuous Organic Photochemistry. J. Org. Chem. 2005, 70, 7558− 7564. (h) Jahnisch, K.; Dingerdissen, U. Photochemical Generation and [4 + 2]-Cycloaddition of Singlet Oxygen in a Falling Film Microreactor. Chem. Eng. Technol. 2005, 28, 4. (i) Takei, G.; Kitamori, T.; Kim, H.-B. Photocatalytic Redox-Combined Synthesis of LPipecolinic Acid with a Titania-Modified Microchannel Chip. Catal. Commun. 2005, 6, 357−360. (j) Matsushita, Y.; Kumada, S.; Wakabayashi, K.; Sakeda, K.; Ichimura, T. Photocatalytic reduction in microreactors. Chem. Lett. 2006, 35, 410−411. (k) Sugimoto, A.; Sumino, Y.; Takagi, M.; Fukuyama, T.; Ryub, I. The barton reaction using a microreactor and black light. Continuous-flow synthesis of a key steroid intermediate for an endothelin receptor antagonist. Tetrahedron Lett. 2006, 47, 6197−6200. (l) Kitamura, N.; Yamada, K.; Ueno, K.; Iwata, S. Photodecomposition of Phenol by SilicaSupported Porphyrin Derivative in Polymer Microchannel Chips. J. Photochem. Photobiol., A 2006, 184, 170−176. (m) Meyer, S.; Tietze, D.; Rau, S.; Schäfer, B.; Kreisel, G. Photosensitized Oxidation of Citronellol in Microreactors. J. Photochem. Photobiol., A: Chemistry 2007, 186, 248−253. (n) Matsushita, Y.; Ohba, N.; Kumada, S.; Sakeda, K.; Suzuki, T.; Ichimura, T. Photocatalytic Reactions in Microreactors. Chem. Eng. J. 2007, 135S, S303−S308. (o) Carofiglio, T.; Donnola, P.; Maggini, M.; Rossetto, M.; Rossi, E. FullerenePromoted Singlet-Oxygen Photochemical Oxygenations in GlassPolymer Microstructured Reactors. Adv. Synth. Catal. 2008, 350, 2815−2822. (p) Bourne, R. A.; Han, X.; Poliakoff, M.; George, M. W. Cleaner Continuous Photo-Oxidation Using Singlet Oxygen in Supercritical Carbon Dioxide. Angew. Chem., Int. Ed. 2009, 48, 5322−5325. (q) Sugimoto, A.; Fukuyama, T.; Sumino, Y.; Takagi, M.; Ryu, I. Microflow photo-radical reaction using a compact light source: application Barton reaction leading to a key intermediate for myriceric acid A. Tetrahedron 2009, 65, 1593−1598. (r) Bourne, R. A.; Han, X.; Poliakoff, M.; George, M. W. Cleaner Continuous Photo-Oxidation Using Singlet Oxygen in Supercritical Carbon Dioxide. Angew. Chem., Int. Ed. 2009, 48, 5322−5325. (s) Oelgemoeller, M. Highlights of Photochemical Reactions in Microflow Reactors. Chem. Eng. Technol. 2012, 35 (7), 1144−1152. (t) Oelgemöller, M.; Shvydkiv, O. Recent Advances in Microflow Photochemistry. Molecules 2011, 16 (9), 7522−7550. (u) Carney, J. M.; Hammer, R. J.; Hulce, M.; Lomas, C. M.; Miyashiro, D. High-efficiency microphotooxidation using milliwatt LED sources. Tetrahedron Lett. 2011, 52 (2), 352−355. (v) Carney, J. M.; Hammer, R. J.; Hulce, M.; Lomas, C. M.; Miyashiro, D. Microphotochemistry using 5-mm light-emitting diodes: Energyefficient photooxidations. Synthesis (Germany) 2012, 44 (16), 2560− 2566. (w) Maurya, R. A.; Park, C. P.; Kim, D. P. Triple-channel microreactor for biphasic gas-liquid reactions: Photosensitized oxygenations. Beilstein J. Org. Chem. 2011, 7, 1158−1163. (x) Park, C. P.; Maurya, R. A.; Lee, J. H.; Kim, D. P. Efficient photosensitized oxygenations in phase contact enhanced microreactors. Lab Chip 2011, 11 (11), 1941−1945. (y) Lévesque, F.; Seeberger, P. H. Highly efficient continuous flow reactions using singlet oxygen as a ″Green″ reagent. Org. Lett. 2011, 13 (19), 5008−5011. (z) Lévesque, F.; Seeberger, P. H. Continuous-flow synthesis of the anti-malaria drug artemisinin. Angew. Chem., Int. Ed. 2012, 51 (7), 1706−1709. (aa) Yavorskyy, A.; Shvydkiv, O.; Limburg, C.; Nolan, K.; Delauré, Y. M. C.; Oelgemöller, M. Photooxygenations in a bubble column reactor. Green Chem. 2012, 14 (4), 888−892. (ab) Cantillo, D.; De Frutos, O.; Rincón, J. A.; Mateos, C.; Kappe, C. O. Continuous flow αtrifluoromethylation of ketones by metal-free visible light photoredox catalysis. Org. Lett. 2014, 16 (3), 896−899. (ac) Wang, X.; Cuny, G. D.; Noël, T. A mild, one-pot Stadler-Ziegler synthesis of arylsulfides

facilitated by photoredox catalysis in batch and continuous-flow. Angew. Chem., Int. Ed. 2013, 52 (30), 7860−7864. (ad) HernandezPerez, A. C.; Collins, S. K. A visible-light-mediated synthesis of carbazoles. Angew. Chem., Int. Ed. 2013, 52 (48), 12696−12700. (ae) Neumann, M.; Zeitler, K. Application of microflow conditions to visible light photoredox catalysis. Org. Lett. 2012, 14 (11), 2658−2661. (af) Tucker, J. W.; Zhang, Y.; Jamison, T. F.; Stephenson, C. R. J. Visible-light photoredox catalysis in flow. Angew. Chem., Int. Ed. 2012, 51 (17), 4144−4147. (ag) Garlets, Z. J.; Nguyen, J. D.; Stephenson, C. R. J. The development of visible-light photoredox catalysis in flow. Isr. J. Chem. 2014, 54 (4), 351−360. (ah) Schuster, E. M.; Wipf, P. Photochemical flow reactions. Isr. J. Chem. 2014, 54 (4), 361−370. (ai) Noël, T.; Wang, W.; Hessel, V. Chim. Oggi. 2013, 31, 10−14. (aj) Knowles, J. P.; Elliott, L. D.; Booker-Milburn, K. I. Flow photochemistry: Old light through new windows. Beilstein J. Org. Chem. 2012, 8, 2025−2052. (6) Schenck, G. O.; Eggert, H.; Denk, W. Photochemische Reaktionen III. Ü ber die Bildung von Hydroperoxyden bei photosensibilisierten Reaktionen von O2 mit geeigneten Akzeptoren, insbesondere mit α- und β-Pinen. Liebigs Ann. Chem. 1953, 584, 177−198. (7) (a) Cointeaux, L.; Berrien, J.-F.; Mahuteau, J.; Huu-Dâu, M. E. T.; Cicéron, L.; Danis, M.; Mayrargue, J. A Short Synthesis of Antimalarial Peroxides. Bioorg. Med. Chem. 2003, 11, 3791−3794. (b) Malkov, A. V.; Bell, M.; Orsini, M.; Pernazza, D.; Massa, A.; Herrmann, P.; Kocovsky, P. New Lewis-Basic N-Oxides as Chiral Organocatalysts in Asymmetric Allylation of Aldehydes. J. Org. Chem. 2003, 68, 9659−9668. (c) Malkov, A. V.; Orsini, M.; Pernazza, D.; Muir, K. W.; Langer, V.; Meghani, P.; Kocovsky, P. Chiral 2,2′Bipyridine-Type N-Monoxides as Organocatalysts in the Enantioselective Allylation of Aldehydes with Allyltrichlorosilane. Org. Lett. 2002, 4, 1047−1049. (d) Malkov, A. V.; Bell, M.; Castelluzzo, F.; Kocovsky, P. METHOX: A new pyridine N-oxide organocatalyst for the asymmetric allylation of aldehydes with allyltrichlorosilanes. Org. Lett. 2005, 7, 3219−3222. (e) Malkov, A. V.; Mariani, A.; MacDougal, K. N.; Kocovsky, P. Role of noncovalent interactions in the enantioselective reduction of aromatic ketimines with trichlorosilane. Org. Lett. 2004, 6, 2253−2256. (f) Malkov, A. V.; Stoncius, S.; MacDougal, K. N.; Mariani, A.; McGeoch, G. D.; Kocovsky, P. Formamides derived from N-methyl amino acids serve as new chiral organocatalysts in the enantioselective reduction of aromatic ketimines with trichlorosilane. Tetrahedron, Symp. Organocatalysis 2006, 62, 264−284. (g) Malkov, A. V.; Pernazza, D.; Bell, M.; Bella, M.; Massa, A.; Teply, P.; Meghani, P.; Kocovsky, P. Synthesis of new chiral 2,2′bipyridine ligands and their application in the copper-catalyzed asymmetric allylic oxidation and cyclopropanation. J. Org. Chem. 2003, 68, 4727−4742. (8) Lapkin, A. A.; Boddu, V.; Aliev, G. N.; Goller, B.; Polisski, S.; Kovalev, D. Photooxidation by Singlet Oxygen Generated on Nanoporous Silicon in a LED-Powered Reactor. Chem. Eng. J. 2008, 136, 331−336. (9) Hatchard, C. G.; Parker, C. A. A New Sensitive Chemical Actinometer. II. Potassium Ferrioxalate as a Standard Chemical Actinometer. Proc. R. Soc. London A 1956, 235, 518−536. (10) Mihelich, E. D.; Eickhoff, D. J. One-pot Conversion of Olefins to α, β-unsaturated Carbonyl Compounds. An Easy Synthesis of 2cyclopentenone and related compounds. J. Org. Chem. 1983, 48, 4135−4137. (11) Abraham, R. J.; Cooper, M. A.; Indyk, H.; Siverns, T. M.; Whittaker, D. The NMR spectra and conformations of cyclic compounds-VII: The conformations of β-pinene, pinocarvone and the cis- and trans-pinocarveols. Org. Magn. Reson. 1973, 5, 373−377. (12) Johnson, D. A. Handbook of Optical Through the Air Communications; Imagineering E-Zine: Thornton, CO, 2008. (13) (a) Wrobel, D.; Hanyz, I.; Bartkowiak, R.; Ion, R. M. Fluorescence and Time-Resolved Delayed Luminescence of Porphyrins in Organic Solvents and Polymer Matrices. J. Fluoresc. 1998, 8, 191−198. (b) Korinek, M.; Dedic, R.; Svoboda, A.; Hala, J. 1453



Article

Luminescence Study of Singlet Oxygen Production by MesoTetraphenylporphine. J. Fluoresc. 2004, 14, 71−74. (14) Montalti, M.; A. C, Prodi, L.; Gandolfi, M. T. Handbook of Photochemistry, 3rd ed.; CRC Press: Boca Raton, FL, 2006. (15) (a) Shirono, K.; Morimatsu, T.; Takemura, F. Gas Solubilities (CO2, O2, Ar, N2, H2, and He) in Liquid Chlorinated Methanes. J. Chem. Eng. Data 2008, 53, 1867−1871. (b) Kretschmer, C. B.; Nowakowska, J.; Wiebe, R. Solubility of Oxygen and Nitrogen in Organic Solvents from −25° to 50° C. Ind. Eng. Chem. 1946, 38, 506− 509. (16) (a) Waelchli, S.; Rohr, P. R. v. Two-phase flow characteristics in gas-liquid microreactors. Int. J. Multiphase Flow 2006, 32, 791−806. (b) Fries, D. M.; Wälchli, S.; Rohr, P. R. v. Gas-liquid two-phase flow in meandering microchannels. Chem. Eng. J. 2008, 135, 37−45. (17) Kim, N. Multiphase Flows in Polymer Microfluidic Systems; Louisiana State University: Baton Rouge, 2009. (18) (a) Plucinski, P. K.; Bavykin, D. V.; Kolaczkowski, S. T.; Lapkin, A. A. Liquid-Phase Oxidation of Organic Feedstock in a Compact Multichannel Reactor. Ind. Eng. Chem. Res. 2005, 44, 9683−9690. (b) Mogalicherla, A. K.; Kunzru, D. Effect of Gas and Liquid Superficial Velocities on the Performance of Monolithic Reactors. Ind. Eng. Chem. Res. 2010, 49, 1631−1641. (19) Berčič, G.; Pintar, A. The role of gas bubbles and liquid slug lengths on mass transport in the taylor flow through capillaries. Chem. Eng. Sci. 1997, 52 (21−22), 3709−3719. (20) ICIS Indicative Chemical Prices, http://www.icis.com/ chemicals/channel-info-chemicals-a-z/ (accessed 2014). (21) U.S. Energy Information Administration. Electricity Monthly Update, http://www.eia.gov/electricity/monthly/update/end_use.cfm (May 2014). (22) Shah, R. K.; London, A. L. Laminar flow forced convection in ducts; Academic Press: New York, 1978; Vol. Supplement 1.

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