microchemical engineering in practice (dietrich/microchemical) || photoreactions

CHAPTER 17

PHOTOREACTIONS

TElJlRO ICHIMURA, YOSHlHlSA MATSUSHITA, KOSAKU SAKEDA, and TADASHI SUZUKI

17.1 THEORY

17.1 .I

“Photochemistry” is a science concerned with the description of the physical and chemical processes triggered by the absorption of photons [l]. It serves as a useful basis for future technologies and industries with a microreactor. Photochemical reactions differ considerably from conventional thermal reactions in the following important respects. Because the reaction is initiated with the irradiation of light and absorption of the photon by an organic molecule, the electronic structure and nuclear configuration of the excited molecule will be different from those in the ground state. The excited molecule possesses high internal energy and will give rise to the formation of a photoproduct, which is unobtainable through a thermal reaction in the ground state.

Absorption of a photon results in the excitation from a lower to a higher electronic state. The excited molecule relaxes into the stable state through photophysical or photochemical processes (Fig. 17.1): radiative and/or nonradiative processes. The fluorescence spectrum is usually independent of the excitation wavelength in the condensed phase (Kasha-Vavilov’s law). Generally, the lifetime of the T I state (pswms), T ~ , is longer than that of the S1 state (ns), T ~ .

A unimolecular or bimolecular chemical reaction will take place in the excited state (the S1 or T I state) or higher excited state (the S,, or T, state) such as bond fission (dissociation and decomposition), isomerization, inter- and intra-molecular hydrogen atom abstraction, charge and proton transfer, and cyclo-addition [2]. When an intense laser is used as the excitation light source, multiphoton absorption easily occurs,

Photochemical and Photophysical Processes

Microchemical Engineering in Practice. Edited by Thomas R. Dietrich Copyright 0 2009 John Wiley & Sons, Inc.

386 PHOTOREACTIONS

FIGURE 17.1 A schematic energy diagram of a molecule in the excited and ground states, and relaxation processes. The solid and wavy lines indicate radiative and nonradiative processes. The k value denotes a rate constant of the corresponding process. VR, vibrational relaxation; Fluo., fluorescence; IC, internal conversion; ISC, intersystem crossing; and Phos., phosphorescence.

followed by excitation to the higher excited state or ionization to form cation. The reaction quantum yield in the S1 or T I state is defined as the ratio of the number of reaction products to the number of absorbed photons, equal to the rate constants k of the reaction and relaxation processes as

c#f = (number of reaction products)/(number of absorbed photons)

= @/ks = @TS (17.1)

ks = 1/Ts = kf +kit +kIsc +$ 4; = (number of reaction products)/(number of absorbed photons)

= kT/kT = k,'T,y (1 7.2)

kT = 1 / T T = k,, +kist + k,'

Hence, the estimation of the reaction quantum yield and lifetime of the excited state can lead to the reaction rate constant.

17.1.2 Excitation Light Source

As conventional light sources [3] for photochemistry in the UV-visible wavelength region, you can use a mercury lamp, xenon arc lamp, and lasers. The laser has become widespread in photochemistry and spectroscopy since its discovery in 1960. The laser beam, in principle, can be focused to the size of the wavelength.

17.2 PHOTOREACTIONS IN MICROREACTORS 387

17.1.3 Analysis and Detection Methods

In a photochemical reaction, product analysis is quite important to determine the quantum yield of a reaction and to investigate the reaction mechanism. Chromatography is a powerful technique for the separation of the reaction mixture and can identify each component. The electronic absorption and emission spectra measurements also provide information on the photoproducts. Direct investigation of the photochemical reaction mechanism in a microreactor is especially important because photochemistry in a bulk system may be different from that in a microreactor. Nanosecond laser flash photolysis will provide temporal information such as data on the lifetime and concentration of reaction intermediates. However, it is not applicable to a microreactor because the detection sensitivity is quite low due to the ultra-short light path length. Therefore, fluorescence, Raman, or thermal lensing spectroscopy coupled with laser irradiation and/or a microscope [4-71 can be applied to a photochemical study in a microreactor.

17.2 PHOTOREACTIONS IN MICROREACTORS

In the last decade, a microreaction system has developed using the features unique to microspace such as short molecular diffusion distance, excellent heat-transfer characteristics, laminar flow, and large surface-to-volume ratio [8-121. Although microreaction systems have been examined successfully in a wide range of applications of analytical and organic chemistry, there are only several reports on photoreactions in microreactors, as described in the following section [13-181. We can expect microreactors to exhibit higher spatial illumination homogeneity and better light penetration throughout the entire reactor depth in comparison to large-scale reactors. Thus, we continue to investigate the applications of microreactors in organic photoreactions. In this section, we will describe our results on asymmetric photoreactions and photocatalytic reactions in microreactors.

17.2.1 Experimental Section

Figure 17.2 shows our typical experimental set-up. Sample solution and/or gas were fed into a microreactor with a syringe pump. We used lasers and also lamps and even

FIGURE 17.2 Typical experimental set-up.

388 PHOTOREACTIONS

UV-LEDs, and irradiated the sample solution fmm the top of the microchannel. Reaction products were analyzed by gas and high-pressure liquid chromatography (HPLC).

Microreactor Chips We employed microreactor chips made of quartz, which is transparent to UV light. The microreactor chips have a straight microchannel 200 to 500 p m in width, 10 to 500 p m in depth, and 40 mm in length. A TiOz layer was immobilized in microchannels of 5 0 0 - ~ m width for photocatalytic reactions. It has been widely recognized that the illuminated specific surface area of the photocatalyst within a reactor is the most important design parameter of photocatalytic reactors. The illuminated specific surface areas per unit of liquid of the microreactor with a microchannel depth of 100, 300, and 500 p m were calculated to be 1.4 x lo4, 7.3 x lo3, and 6.0 x 103m2/m3, respectively, without taking into account the roughness of the photocatalyst surface. Thus, the microreactors with an immobilized photocatalyst have much larger values of illuminated specific surface area of photocatalyst than typical conventional batch reactors [ 191.

Excitation Light Source The reactants in the microreactor were irradiated by a KrF excimer laser (248 nm, with a pulse duration of 20 ns and repetition rate of 20 Hz), a tunable OPO laser excited with a Nd+ : YAG Laser, or a Xe or Hg lamp. To make the most of the advantages of a miniaturized reaction vessel, a light source of minimal space and lower photon cost is suitable for microreaction systems. Therefore, in addition to lamps and lasers, we employed UV-light-emitting diodes (UV-LEDs; 365, 375, and 385 nm) for the excitation light source of photocatalytic reactions.

17.2.2 Asymmetric Photosensitized Reactions in Microreactors

The chirality of molecules is known to play a crucial role in biological systems. Numerous efforts have been made to develop various methodologies for asymmetric chemical synthesis. Recently, the effective control and enhancement of the stereoselectivity of asymmetric photoreactions in a batch system have been reported [20-231, which is likely a new field of vital importance in synthetic chemistry. We reexamined the two asymmetric photosensitized reactions in a microreactor [24].

Photosensitized lsomerization of (Z)-cyclo-octene The Z-E photoisomeri- zation [21, 221 of (Z)-cyclo-octene sensitized by chiral aromatic ester gives (R)-(-)- and (S)-( +)-(E)-cyclo-octene (Scheme 17.1). The product’s enantiomeric excess (ee) value is defined as follows:

A solution of (Z)-cyclo-octene (25 mM) and the optically active saccharide esters of benzenetetracarboxylic acid (5 mM) as a sensitizer in ethyl ether was introduced into a microreactor. By varying the residence time under 248-nm laser irradiation, the E/Z ratio and product’s ee value were examined and shown in Fig. 17.3. The


SCHEME 17.1 Photosensitized isomerization of (Z)-cyclo-octene,

0.0 -I/ I I I I 1

0 2 4 6 8 10 Residence time (s)

I I I I I I

0 2 4 6 8 10 Residence time (s)

FIGURE 17.3 The plots of (a) E/Z ratio and (b) ee value against residence time in the microreactor (with a width of 200 pm and depth of 20 pm).

390 PHOTOREACTIONS

higher the laser power becomes, the more quickly the E/Z ratio reaches its highest value. The E/Z ratio increased to 0.45 at the residence time of 10 s in the microreactor, while it was 0.28 at the residence time of 30 min in a batch system [25]. A very high ee value (- 63% ee) was successfully obtained with an irradiation period less than 200 laser shots of -20-ns pulse duration, as shown in Fig. 17.3(b).

Photosensitized Addition of (R)-(+)-Limonene to Methanol The photoreaction (Scheme 17.2) gives three major products [23], that is, cis- and trans-4-iso- propenyl- 1 -methoxy- 1 -methylcyclohexane (cis and trans) and exocyclic isomer (em). The diastereomeric excess (de) value is defined as follows:

de = ([trans] - [cisl)/([trunsl + [cis]) (17.4)

A solution of (R)-(+)-limonene (25 mM) and toluene (10 mh4) as a sensitizer in methanol was fed into a microreactor. For comparison, batch reactions were per- formed in a quartz cell (with an optical length of 3 mm) containing a 1-mL sample solution. Figure 17.4 indicates the yields of photoproducts and conversion of (R)-(+)-limonene with a Hg lamp. In the batch system, the yield of the cis and trans isomers linearly increased in 20 min and reached its plateau value, whereas the yield in the microreactor more quickly increased in linear relation to the obser- vation time (1 35 s).

In order to compare the formation rate of the photoproducts in the batch and those in the microreactor systems, the observed values of quantum yield were evaluated by Eq. (17.1) and are summarized in Table 17.1. The steady-state approximation of the concentration of triplet toluene led to the formation rate constants of the cis (k,.L,T) and trans (k,,,,) isomers, with information on the quenching rate constant of triplet toluene by (R)-( +)-limonene determined by the transient absorption measurement. The apparent formation rate constants in microreactors were successfully evaluated and are listed in Table 17.2. As the size of the microchannel became smaller, the quantum yield significantly increased. In this case, the krrans/kcis ratio in the microreactors became slightly higher (-5%) than that in the batch system. The de values in the batch and microreactor systems were examined against irradiation time. The de value was up to 28.5% de (15 min) in the batch system, whereas the value in the microreactor reached 30.6% de (36 s), because the microfluidic system could suppress the side reactions.

(R)-(+)-limonene cis trans ex0

Photosensitized addition of (R)-(+)-limonene to methanol. SCHEME 17.2


80 - h

8

F i

$ 40-

Y

60-

0

> c 0

20 -

0 - I I I

0 20 40 60 Irradiation time (min)

(b) 12

/ = / 21v, 0 , I 0.0 0.5 1 .o 1.5 2.0

Irradiation time (min)

FIGURE 17.4 The plots of yield of cis and trans isomer (square), and conversion of (R)- (+)-limonene(triang1e) in the batch (a) and in the microreactor (b) (with a width of 500 pm and depth of 300 pm) with a 40-W low-pressure Hg lamp.

TABLE 17.1 trans (khns) Isomers in the Batch and Microreactors Systems

Quantum Yield and Formation Rate Constant for the cis (kcis) and

Quantum Yield" k,,,, (10' M-' s-') kcis (108M-' s ')

Batch 0.008 0.37 0.21 Microreactors 500 pm x 300 pm 0.045 2.3 1.2 200 pm x 20 p m 0.087 4.4 2.4

"Summation of the yield for the cis and trans isomers.

392 PHOTOREACTIONS

TABLE 17.2 Phocatalytic N-ethlylation of Benzylamine (1.0 X M) in Microreactors Excited with 365-nm UV-LEDs and in a Batch Reactor

Yield (%)

Reactor Irradiation N-ethyl- N,N-diethy 1- (Depth, w) Photocatalyst Time benzylamine benzylamine

~~~ ~

Batch" Ti02/Pt 5 h 84.4 2.4 Batch" Ti02/Pt 10h 6.8 74.1 Batch" Ti02 - 0 0 Microreac tor Ti02/Pt 150 s 85 0

Microreactor Ti02 90 s 98 0



(500)

(300)

(500)

( 1,000) "In suspended solution excited with a 400-W Hg lamp [31]

In conclusion, the experimental results clearly proved that a microreactor should enhance reaction efficiency due to high spatial illumination homogeneity and excellent light penetration throughout the reactor. The stereoselectivity of the photoreactions in a microreactor can be superior to that in a batch system.

17.2.3 Photocatalytic Reactions in Microreactors

The study of light-induced electron-transfer reactions in a semiconductor catalyst has become one of the most attractive research areas in photochemistry. Wide varieties of organic reactions have been successfully examined by using a semiconductor photocatalyst. A photocatalytic reaction can take place on an irradiated surface. Therefore, most research on the reaction is camed out using dispersed powders with conventional batch reactors. A separation step using powders is required after the reaction takes place. Although systems with an immobilized catalyst can avoid this step, they tend to have low interfacial surface areas.

A microreactor with an immobilized photocatalyst that has a large surface-to- volume ratio may prove advantageous in a photocatalytic reaction. Thus, we investigated the photocatalytic oxidation and reduction of organic compounds [26], and a process involving the N-alkylation of amines [27] in microreactors.

Photocatalytic Oxidation and Reduction Photoexcited Ti02 oxidizes a reactant that donates an electron to Ti02 while it reduces a reactant that receives an electron. Photoxidations of organic compounds using TiOz as a photocatalyst have been fruitfully investigated, and there are some reports on the photoreduction process as it relates to the TiOz surface [28, 291. First, we examined the photodegradation


TiO,, hv 2 CIC,H,OH + 13 0, + 12 CO, + 4 H,O + 2 HC1

SCHEME 17.3 Photocatalytic degradation of chlorophenol.

TiO,, hv EtOH 4 + 6CH,CH,OH -

CH3 CH3

SCHEME 17.4 Photocatalytic reduction of p-nitrotoluene.

(photooxidation, Scheme 17.3) and photoreduction (Scheme 17.4) of organic compounds in a microreactor with an immobilized photocatalytic Ti02 layer. As illustrated in Fig. 17.5, the reactions take place quite quickly in comparison to conventional batch reactors.

Figure 17.6 shows an action spectrum of degradation of dimethylformamide in the photocatalytic microreactor obtained by using a tunable OPO laser. It indicates that the reaction efficiency should be very sensitive to the excitation wavelength. Considering the band gap energy and action spectrum, we can expect higher reaction efficiencies with a light source of higher photon energy. Therefore, an array of 365-nm UV-LEDs (Nichia NSHU590B, with an optical power output of 10 mW) were employed for the photocatalytic reactions described in the following sections.

Mulfiphase Photocatalytic Oxidation We further investigated the oxidation process of p-chlorophenol by using a gas-liquid-solid multiphase microreaction system. Although numerous attempts have been made to study multiphase catalytic reactions, there are still difficulties in evaluating the conduction of the reactions as a result of the low reaction yield arising from the very low efficiency of interaction and mass transfer between different phases [30]. To produce high interfacial area between the phases, we introduced an aqueous solution of p-chlorophenol and oxygen gas into a microchannel. The yield of phtodegradation is shown in Fig. 17.7. The horizontal axis indicates the gas injection rate, while the injection rate of the sample solution is kept at a constant value of 10 pL/min. At a lower gas injection rate, microbabbles were formed and so-called slug flow was observed. At a gas injection rate higher than 500pL/min, a pipe flow, gas flowed through the center of the microchannel, while liquid flowing close to the photocatalyst surface was formed as schematically illustrated in Fig. 17.8. The reaction yield increased to 43% at the residence time of 14 s in the pipe flow, whereas it was 10% at the residence time of 75 s without the injection of oxygen gas. Under the pipe-flow condition, the liquid phase is always saturated with oxygen even in the final part of the microchannel.

394 PHOTOREACTIONS

(b) 1 .o

0.8 - 0 .- I

9 5 0.6 - c

0 c 8 9 0.4 - .- c m 0, - [r 0.2 -

0.0

0 1 2 3 4 5 Irradiation time (s)

A Intermediate

-0

0

0 I3

0 A A A

I3 I3

-P I I I

0 20 40 60 Irradiation time (s)

FIGURE 17.5 Photocatalytic degradation of rn-chlorophenol (1.1 x M) (a) and reduction of p-nitrotoluene ( 1 . 0 ~ 10-4M) (b) in a microreactor of 100-pm depth and 500- wrn width excited with 385-nm UV-LEDs.

In addition, as the gas injection rate increases, the thickness of the liquid phase decreases. At the gas injection rate of 750 pL/min, the thickness of the liquid phase is estimated to be 25 pm. These facts may increase the reaction yield.

Phofcafalyfic Alkylafion It has been recognized that depositing Pt on Ti02 enhances photocatalytic activity by serving as an electron sink and consequently slow- ing charge recombination. Ohtani et al. [3 13 studied the photocatalytic preparation of asymmetrical secondary and tertiary amines by Pt-loaded Ti02 (TiO,/Pt) particles suspended in a variety of alcohols as solvents by using conventional batch reactors.


8 -

- 8 6- v

C 0 m n m 0

.- c F 4 -

n

El El

0" 0.8 -

3 0.7 -

0.6 -

0.5 -

El

A

Air A A

El

El j I I , , , , : 0

300 320 340 360 380 400 Wavelength (nrn)

FIGURE 17.6 in a photocatalytic microreactor excited with an OPO laser.

Action spectrum of photodegradation of dimethylformamide (1.0 x lop4 M)

They reported that the N-alkylation of benzylamine occurred with a yield up to 84.4% after 4 h of irradiation under a 400-W high-pressure mercury lamp, while the N- alkylation of amines could not be observed by the irradiation of Pt-free Ti02 (Scheme 17.5).

The photoirradiation of benzylamine in ethanol introduced into a microreactor with immobilized TiO,/Pt led to N-ethylation. The reaction proceeded within only 150-s UV irradiation to yield 85% of N-ethylbenzylamine. The reaction mechanism can be interpreted as follows. The dehydrogenation of ethanol occurs on the surface of TiOz/Pt to form acetoaldehyde and HZ. Substrate benzylamine is N-ethylated by

0.9 "OI rn 0 El

0

El 0

iI

FIGURE 17.7 Phocatalytic degradation of/j-chlorophenol (1.1 x 10 M) in a gas-liquid -solid multiphase microreactor of 500-nm depth and width.

396 PHOTOREACTIONS

, Photocatalyst Layer

Gas \

Substrate, Solvent

FIGURE 17.8 Schematic view of a multiphase microreactor

the condensation of photoproduct carbonyl with benzylamine. The reduction of the resulting intermediate by Hz occurs, yielding N-ethylbenzylamine.

In contrast to the result in a batch reactor, we successfully observed the N- alkylation reaction of benzylamine by using the microreactor with immobilized Pt-free TiOZ as well as TiOz/Pt. The ethylation of benzylamine proceeds very rapidly and reaction efficiency increased as the depth of the microchannel decreased (Table 17.2). The reaction proceeded within only 90 s to yield 98% of N-ethylbenzylamine with a microreactor of 300-p.m depth.

The reaction efficiencies are influenced by a series of processes, including electron transfer from the conduction band of TiOz to the substrate and oxidation of the solvent by an electron hole. Since the electron-hole recombination within the photocatalyst is in competition with the reaction process, the reaction efficiencies must be strongly affected by the surface-to-volume ratio of a photocatalytic reactor. Thus, the photoreaction can proceed rapidly in the microreactor, which has a remarkably large surface-to-volume ratio as compared with conventional batch reactors. For the above reason, the N-alkylation of benzylamine may be observed even in the microreactor without a Pt cocatalyst. Ohtani et al. [31] reported that the UV irradiation of Ti02/Pt suspended in ethanol led to N-alkylation and N, N-dialkylation. In contrast, the irradiation of benzylamine in the photocatalytic microreactor with Pt- free Ti02 as well as Ti02/Pt did not yield any detectable N , N-dialkylated products (Table 17.2). The absence of N, N-dialkylated products can be attributed to the nature of a continuous-flow microreaction system. In the microflow system, the residence time of the substrate is very short and the reaction vessel does not retain the reaction

H2 H2

SCHEME 17.5 Ethylation of benzylamine on photocatalyst surface.

17.3 TYPICAL EXAMPLES OF OTHER RESEARCH 397

intermediates. These facts may inhibit or prevent the consecutive N-alkylation process of N-ethylbenzylamine.

Summary and Future Pmspects We have investigated the application of microreactors to asymmetric photosensitized reactions concerned with the reaction efficiency and stereoselectivity. The reaction efficiency in a microreactor was significantly improved. The E/Z ratio obtained in the microreactor was about 1.6 times higher than that in the batch system. The quantum yield of the reaction of (R)-limonene in the microreactor was significantly larger than that in the batch system. Even in a very short irradiation time, high ee and de values were obtained in microreactors due to the efficient utilization of photon energy there.

We have developed a photocatalytic microreactor and examined the processes of reduction and oxidation of organic compounds, and amine N-alkylation reaction in microspace. These model reactions proceeded very rapidly, and the yield increased as the surface-to-volume ratio increased. In contrast to the result in a batch reactor, we successfully observed the N-alkylation reaction of benzylamine by using the microreactor with immobilized Pt-free TiOz as well as Ti02/Pt. The use of a continuous-flow micoreactor inhibited the formation of N, N-dialkylation products.

These results suggest the applicability of microreaction systems to organic photoreactions. We must further investigate other model photoreactions to prove the advantages, especially high efficiencies and reaction selectivity, that might be introduced by such systems. The optimization of excitation wavelength and photon density, design of the microreactor, flow rate, and irradiation time are under study for the establishment of a photochemical microreaction system.

17.3 TYPICAL EXAMPLES OF OTHER RESEARCH

F. Jensen’s group [ 131 at MIT in Cambridge, Massachusetta, carried out pioneering work in the research field of photochemical reactions in microfabricated reactors and detectors. Two different microfabricated reactors were designed for the integration of the reaction and detection modules. It also succeeded in bonding quartz substrates to micropatterned silicon devices at low temperature using a per- fluorinated polymer-CYTOPTM, where quartz substrates allowed reaction and detection with UV light of shorter wavelengths (higher energies) than ones made of Pyrex glass permit. The photoreaction of benzophenone in isopropanol to form benzopinacol and acetone was investigated as a model reaction. Crystallization of the product (benzopinacol) in the microreactors was avoided with a continuous-flow system by controlling the residence time and, consequently, the extent of the reaction. Off-chip analysis of the photoproduct using HPLC confirmed the results obtained from online UV spectroscopy to observe the absorbance of the reaction mixture at different flow rates. The estimated reaction quantum yield revealed that the reactor design should improve the overall reaction efficiency, which was defined by the ratio of moles of reaction (the conversion of the reactant benzophenone) and the amount of light from the miniaturized UV lamp.

398 PHOTOREACTIONS

A. J. de Mello’s group [12] at the Imperial College London, London, UK has studied a microfabricated nanoreactor for the safe, continuous generation and use of singlet oxygen. The term “nanoreactor” refers to reactors with an instantaneous reaction volume most conveniently measured in nanoliters. Because the efficiency of mixing and separation can be increased in nanoreactors in combination with high rates of thermal and mass transfer, nanoreactors may be ideal for processing valuable or hazardous reaction components and in many cases for improving reaction selectivities. In this study, singlet oxygen was effectively and safely generated in nanoscale reactor and used for the synthesis of ascaridole. The technique allowed for the generation of singlet oxygen without the inherent dangers of large quantities of oxygenated solvents. In addition, the low Reynolds number encountered within most nanofluidic devices could control processes taking place in continuous-flow systems. More impotant, the choice of a continuous-flow system instead of tradi- tional batch processes can facilitate the use of a multiparallel (or scale-out) approach. Thus, this group demonstrated the applicability of nanoreactor technology to the safe, efficient, and continuous-flow synthesis of ascaridole from a-terpinene.

N. Kitamura’s group [ 141 at Hokkaido University, Sapporo, Japan has investigated the photocyanation of pyrene(PyH) across an oil-water interface. It used two types of polymer microchannel chips in its study. The chips (with a depth of 20 k m and width of 100 km) were fabricated with photolithography and an imprinting method. An aqueous NaCN solution and propylene carbonate solution of PyH and 1,4-dicyanobenzene were injected separately into a Y-structured chip with the same flow velocity, and the irradiation of a high-pressure Hg lamp onto the chip resulted in the formation of I -cya- nopyrene (PyCN). The results proved that the interfacial photochemical reaction of PyH proceeded very efficiently. Under optimum conditions by using a three-layer channel chip, an absolute PyCN yield of 73% was obtained with a reaction time of 210 s.

T. Kitamori’s group [33] at the University of Tokyo published a review focusing on the integration of chemical and biochemical analysis systems into glass microchips for general use. By combining multiphase laminar flow driven by pressure and micro unit operations, such as mixing, reaction, extraction, and separation, continuous-flow chemical processing systems can be realized in the microchip format, whereas the application of electrophoresis-based chip technology is limited. The performance of several analysis systems was greatly improved by microchip integration because of some characteristics of microspace described elsewhere. This same group also demonstrated that several different analysis systems, such as wet analysis of cobalt ion, multi-ion, multi-ion sensor, immunoassay, and cellular analysis, could be successfully integrated on a microchip, and concluded that these microchip technologies should be promising for meeting the future demands of high-throughput chemical processing.

S. J. Haswell’s group [34] at the University of Hull, Hull, UK has studied the chemical reactions in microreactors using an inverted Raman microscopic spectrometer. Raman spectroscopy has the advantage of being applicable to monitoring nonradiative (nonfluorescent) species, which means that spectroscopy, in principle, may detect any kind of reaction species with reasonable sensitivity. In this study, an inverted Raman microscope spectrometer was used to obtain information on the

17.3 TYPICAL EXAMPLES OF OTHER RESEARCH 399

spatial evolution of reactant and product concentrations for a chemical reaction in a hydrodynamic flow-controlled microreactor. The Raman spectrometer was equipped with a laser (780-nm) source, confocal optics, holographic grating, and charge- coupled device (CCD) detector. The details of Raman microscopy are discussed in “Raman Analysis in Microreactor Channels,” HORIBA JOBIN YVON Raman Application Note. The microreactor consisted of a T-shaped channel network of a 0.5-mm-thick glass bottom plate with a 0.5-mm-thick glass top plate. The ends of the channel network were connected to reagent reservoirs that were linked to a syringe pump to inject the solutions by a hydrodynamic flow into the channels. The microchannels were 221 p m wide and 73 pm deep. The synthesis of ethyl acetate from ethanol and acetic acid in the microreactor was investigated as a model system as Raman scat- tering bands for each reactant and product species were clearly resolved. It was proven that the signal intensities of each band obtained by Raman spectroscopy are propotional to the concentration for each species. Accordingly, all concentrations could be quanti- tatively measured after calibration. By scanning specific Raman bands within a selected area in the microchannel network at given steps in the X-Y plane, spatially resolved concentration profiles were obtained under steady-state flow conditions. Under the flow conditions used, different positions within the concentration profile correspond to different times after contact and mixing of the reagents, thereby enabling one to observe the time dependence of the product formation. In conclusion, Raman microscopy could provide a useful complementary technique for UV/VIS absorbance and fluorescence methods for the in situ monitoring and analysis of chemical reactions within channel networks, and could be used to optimize reactions in microreactors.

E. Verpoorte [35] at the University of Groningen, Groningen, The Netherlands reviewed micro-optics for lab-on-a-chip devices in 2003, and in her article she wrote that “the examples of microfluidic devices incorporating microfabricated light sources are still few and far between. One notable exception is the work. . . . ” This statement seems to be still true at present. A small number of papers dealing with photoreactions has been published thus far, but that number is increasing remarkably.

R. Gorge’s group [15] at Friedrich Schiller University, Jena, Germany has studied photocatalysis in microreactors. This paperappears to be the first report concerned with photocatalitic reaction in microreactors. A photocatalytic microreactor with immobilized titanium dioxide(Ti02) as a photocatalyst and illuminated by UV-A LED light (385nm) was constructed and tested for the degradation of the model substance 4-chlorophenol. The microreactor consisted of 19 channels with a cross section of approximately 200 p m x 300 pm. The intrinsic kinetic parameters of the reaction could be determined and mass-transfer limitations for the operating conditions employed could be excluded by calculating appropriate Damkohler numbers. Photonic efficiencies for the degradation of 4-chlorophenol were given. The quantum yield of a photocatalic reaction is very difficult to determine because the amount of absorbed photons by the catalyst is hard to estimate. Therefore, photonic efficiency is practically defined by the ratio of rate of reaction to incident monochromatic light intensity. This group concluded that the illuminated specific surface of the microstructured reactor should surpass that of conventional photocatalytic reactors by a factor of 4 to 400.

400 PHOTOREACTIONS

T. Kitamori’s group [18] at the University of Tokyo has studied photocatalytic redox-combined synthesis in a microchannel chip. In this work, a titania-modified microchannel chip (TMC) was fabricated to implement an efficient photocatalytic synthesis of L-pipecolinic acid from L-lysine. The in-chip conversion rate was found to be 70 times larger than that in a batch system (cuvette) by using nm-sized titania particles with almost the same selectivity and enantiomeric excess. The experimental results have proven that TMC does have satisfactory potential to allow its application to photocatalytic synthesis as well as photodegradation.

H. Maeda’s group [16] at the National Institute of Advanced Industrial Science and Technology (AIST), Tosu, Japan applied a simple method using the self- assembly of colloidal particles to modify a microcapillary inner surface and investigated photocatalytic and enzyme reactions. It arranged nano-particles on the capillary inner wall and controlled particle layer thickness and layer patterning by choosing adequate combinations of the solvent and drying temperature. In addition, this group utilized SiOz composite particles coated by Ti02 (anatase type) for the purpose of the particle arrangement process in the microreactor to cany an anatase-type Ti02 catalyst. Such a process was likely to be a simple catalyst-carrying method onto the microreactor inner wall. A similar process was also applied to a few catalytic reaction systems, including enzyme reaction and photocatalytic reaction. The experimental results showed that an enzyme reaction could be enhanced, probably due to the increased reactor surface area, and reasonable enhancement of a photocatalytic reaction was also observed for a reaction in a microreactor.

I. Ryu’s group [36] at Osaka Prefecture University has investigated a photochemical [2 + 21 cyclo-addition reaction in a microflow system using glass-made microchannels (with a width of 100 pm and depth of 500 pm). The reaction of cyclohexenones with vinyl acetates in a microflow system under irradiation (300 W, a Hg lamp) gave [ 2 + 21 cyclo-addition products in good yield with a residence time of 2 h, which is a remarkable shortened reaction time compared with a batch system using the same light source.

K. Mizuno’s group [I71 at Osaka Prefecture University has studied the intramolecular ( 2 ~ + 2 4 photocyclo-addition of a 1 -cyanonaphthalene derivative in microreactors made of poly(dimethylsi1oxane) (PDMS). By using the microreactors and flow system, both the efficiency and regioselectivity increased compared with those obtained under batch conditions.

K. Jahnisch’s group [37] at the Institut fur Angewandte Chemie Berlin- Adlershof, Berlin, Germany applied a falling-film microreactor for a photochemical gas-liquid reaction and demonstrated the selective photochlorination of toluene-2, 4-diisocyanate (TDI). Photochlorination of TDI with chlorine gas forms 1- chloromethyl-2, 4-diisocyanate (1 Cl-TDI) by side-chain chlorination together with the ring-chain chlorinated product of XI-TDI. The selectivity to form 1CI-TDI was significantly higher in a microreactor than in a conventional batch reactor. The space-time yield in the microreaction also was orders of magnitude higher compared to a batch system. This same group also demonstrated that a falling-film microreactor should be applicable to the photooxygenation of cyclopentadiene by singlet oxygen [38]. The intermediate of explosive endoperoxide was successfully reduced to yield the final product of cyclopentendiol.

BIBLIOGRAPHY AND OTHER SOURCES 401

BIBLIOGRAPHY AND OTHER SOURCES

1. Wayne, C. E., and Wayne, R. P. (1996). Photochemistry. New York: Oxford University Press. 2. Turro, N. J. (1991). Modern Molecular Photochemistry. Sausalito, CA: University Science

3. Moor, J. H., Davis, C. C., and Coplan, M. A. (2003). Building Scient$c Apparatus, 3rd ed. A Practical Guide to Design and Construction. Boulder, CO: Westview Press.

4. Ichimura, T. (1999). Photodissociation dynamics of chlorinated benzene derivatives. In J. Laane, H. Takahashi, and D. A. Bandrauk (eds.), Structure and Dynamics ot Electronic Excited States, pp. 233-262. Berlin Heidelberg: Springer-Verlag.

5. Ichimura, T., and Suzuki, T. (2000). Photophysics and photochemical dynamics of methy- lanisole molecules in a supersonic jet. J. Photochem. Phorobiol. C: Photochem. Rev., l :

6. Suzuki, T., Omori, T., and Ichimura, T. (2000). Excited state reaction of short-lived 2-methylbenzophenone enols studied by two-color time-resolved thermal lensing technique. J. Phys. Chem., A104: 11671-11676.

7. Nagano, M., Suzuki, T., Ichimura, T., et al. (2005). Production and excited state dynamics of photo-rearranged isomer of benzyl chloride and its methyl derivatives studied by step- wise two-color laser excitation transient absorption and time-resolved thermal lensing techniques. J. Phys. Chem., A109: 5825-5831.

8. Ehrfeld, W., Hessel, V., and Lowe, H. (2000). In Microreactors. Weinheim: Wiley-VCH. 9. Hessel, V., Hardt, S., and Lowe, H. (2004). In Chemical Micro Process Engineering.

Weinheim: Wiley-VCH. 10. Haswell, S. J., O’Sullivana, B., and Styring, P. (2001). Kumada-Comu reactions in a

pressure-driven microflow reactor. Lab Chip, 1 : 164- 166. 11. Aoki, N., Hasebe, S., and Mae, K. (2004). Mixing in microreactors: Effectiveness of

lamination segments as a form of feed on product distribution for multiple reactions. Chem. Eng. J., 101: 323.

12. Suga, S., Nagaki, A,, and Yoshida, J. (2003). Highly selective friedel-crafts show mono- alkylation using micromixing. Chem. Commun., 3: 354-355.

13. Lu, H., Schmidt, M. A,, and Jensen, K. F. (2001). Photochemical reactions and on-line UV detection in microfabricated reactors. Lab Chip, 1: 22-28.

14. Ueno, K., Kitagawa, F., and Kitamura, N. (2002). Photocyanation of pyrene across an oil/water interface in a polymer microchannel chip. Lab Chip, 2: 23 1-234.

15. Gorges, R., Meyer, S., and Kreisel, G. (2004). Photocatalysis in microreactors. J. Photochem. Photobiol., A167: 95-99.

16. Nakamura, H., Li, X., Wang, H., Uehara, M., Miyazaki, M., Shimizu, H., et al. (2004). A simple method of self-assembled nano-particles deposition on the micro-capillary inner walls and the reactor application for photo-catalytic and enzyme reactions. Chem. Eng.

17. Maeda, H., Mukae, H., and Mizuno, K. (2005). Enhanced efficiency and regioselectivity of intramolecular (27r + 277) photocycloaddition of 1 -cyanonaphthalene derivative using microreactors. Chem. Lett., 34: 66-67.

18. Takei, G., Kitamori, T., and Kim, H.-B. (2005). Photocatalytic redox-combined synthesis of L-pipecolinic acid with a titania-modified microchannel chip. Cat. Commun., 6:

Books.

79- 107.

J., 101: 261-268.

357-360.

402 PHOTOREACTIONS

19. Ray, A. K., and Beenackers, A. A. C. M. (1998). Novel photocatalytic reactor for water

20. Rau, H. (1983). Asymmetric photochemistry in solution. Chem. Rev., 83: 535-547. 21. Everitt, S. R. L., and Inoue, Y. (1999). Asymmetric photochemical reactions in solution.

In: Organic Molecular Photochemistry, V. Ramamurthy, and K. Schanze (eds.), pp. 7 I - 130, New York: Marcel Dekker.

22. Inoue, Y., Wada, T., Asaoka, S., Sato, H., and Pete, J.-P. (2000). Photochirogenesis: Multidimensional control of asymmetric photochemistry. Chem. Commun., 25 1-259.

23. Shim, S. C., Kim, D. S., Yoo, D. J., Wada, T., and Inoue, Y. (2002). Diastereoselectivity control in photosensitized addition of methanol to (R)-(+)-limonene. J. Org. Chem., 67:

24. Sakeda, K., Wakabayashi, K., Matsushita, Y., Suzuki, T., Ichimura, T., Wada, T., and Inoue, Y. (2007). Asymmetric photosensitized addition of methanol to (R)-(+)-(Z)- limonene in a microreactor. J. Photochem. Photobiol. A: Chemistry, 192: 166- 171.

25. Wada, T., and Inoue, Y. (private communication). 26. Matsushita, Y., Kumada, S., Wakabayashi, K., Sakeda, K., Suzuki, T., and Ichimura, T.,

(2006). Photocatalytic reduction in microreactors. Chem. Lett., 4: 410-41 1. 27. Matsushita, Y., Ohba, N., Suzuki, T., and Ichimura, T. (2008). N-Alkylation of amines by

photocatalytic reaction in a microreaction system. Catalysis Today, 132: 153- 158. 28. Joyce-Pruden, C., Pross, S., Kreisel, J. K., and Li, Y. (1992). Photoinduced reduction on

titanium dioxide. J. Org. Chem., 57: 5087-5091. 29. Mahadavi, F., Bruton, T. C., and Li, Y. (1993). Photoinduced reduction of nitro com-

pounds on semiconductor particles, J. Org. Chem., 58: 744-746. 30. Kobayashi, J., Mori, Y., Okamoto, K., Akiyama, R., Ueno, M., Kitamori, T., et al. (2005).

A Microfluidic device for conducting gas-liquid-solid hydrogenation reactions. Science,

31. Ohtani, B., Osaki, H., Nishimoto, S., and Kagiya, T. (1986). A novel photocatalytic process of amine N-alkylation by platinized semiconductor particles suspended in alcohols. J. Am. Chern. SOC., 108: 308-310.

32. Wootton, R.C. R., Fortt, R., and de Mello, A. J. (2002). A microfabricated nanoreactor for safe, continuous generation and use of singlet oxygen. Org. Pro. Rex & Dev., 6: 187- 189.

33. Sato, K., Hibara, A., Tokeshi, M., Hisamoto, H., and Kitamori, T. (2003). Integration of chemical and biological analysis systems into a glass microchip. Analy. Sci., 19: 15-22.

34. Fletcher, P. D. I., Haswell, S. J., and Zhang, X. (2003). Monitoring of chemical reactions within microreactors using an inverted Raman microscopic spectrometer. Electrophoresis, 24: 3239-3245.

purification. AIChE J., 44: 477-483.

57 18-5726.

304: 1305-1308.

35. Verpoorte, E., (2003). Chip vision-optics for microchips. Lab Chip, 3: 42N-52N. 36. Fukuyama, T., Hino, Y., Kamata, N., and Ryu, I. (2004). Quick execution of [2 + 21 type

photochemical cycloaddition reaction by continuous flow system using a glass-made microreactor. Chem. Lett., 33: 1430- 1431.

37. Ehrich, H., Linde, D., Morgenschweis, B. M., and Jahnisch, K. (2002). Application of microstructured reactor technology for the photochemical chlorination of alkylaromatics. Chimia, 56: 647-653.

38. Jiihnisch, K., and Dingerdissen, U. (2005). Photochemical generation and [4 + 21-cyclo- addition of singlet oxygen in a falling-film microreactor. Chem. Eng. Technol., 28: 426-427.

microchemical engineering in practice (dietrich/microchemical) || photoreactions

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