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CRC Handbook of Organic Photochemistry and Photobiology

Axel Griesbeck, Michael Oelgemöller, Francesco Ghetti

Microphotochemistry: Photochemical Synthesis in Microstructured Flow Reactors

Publication details https://www.routledgehandbooks.com/doi/10.1201/b12252-4 Oksana Shvydkiv, Michael Oelgemöller Published online on: 21 Mar 2012

How to cite :- Oksana Shvydkiv, Michael Oelgemöller. 21 Mar 2012, Microphotochemistry: Photochemical Synthesis in Microstructured Flow Reactors from: CRC Handbook of Organic Photochemistry and Photobiology CRC Press Accessed on: 30 Sep 2021 https://www.routledgehandbooks.com/doi/10.1201/b12252-4

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The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The publisher shall not be liable for an loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 Depending on the spectroscopic properties of the chromophoric reagent, complete light absorption is is absorption light complete reagent, chromophoric the of properties spectroscopic the on Depending reactors. chamber for used is lamps of fluorescent array an while reactors, well immersion ited to 1 photochemistry. laboratory-scale ( reactors chamber or reactors well Immersion 3.2 ( concept new appealing and apromising represents thus realized. of number a and documented, well have yields been and quantum chemical high with transformations furthermore elegant chemo- and enantioselective is method synthesis powerful a as photochemistry method. synthetic green a as serve likewise can photochemistry organic chemistry. green for advantageous additionally them make microreactions of scales small The materials. hazardous transport and store to need the neglects industry. icals andfine chem of totheadvantages relevance pharmaceutical offersofreactors many practical chemical the 10last only within years. was observed forreactions devices chemical structured rapidly application Its attention. of grows in deal as The many for evident, areas, development and in engineering. example, electronics ofgreat micro a received has microtechnology decades, last the Over 3.1 University Cook James Oelgemöller Michael University City Dublin Shvydkiv Oksana The application of batch systems for photochemical reactions has a number of disadvantages. disadvantages. of number a has reactions photochemical for systems batch of application The Introduction From

L. As common light sources, single low-, medium-, or high-pressure mercury lamps are used in in used are lamps low-, mercury single or medium-, sources, high-pressure As common light L. 24–26 The combination of microtechnology and photochemistry, that is, microphotochemistry, microphotochemistry, is, that photochemistry, and microtechnology of combination The 13,14

Conventional Also, the possibility of preparing chemicals in the required volume at the point of use ofpoint use volume at the required the in chemicals of preparing possibility the Also, References Acknowledgments 3.4 3.3 3.2 3.1 30

The total volume of such laboratory batch systems is typically lim typically is systems batch laboratory such of volume total The Photochemical Synthesis

Concluding Remarks Concluding Microreactors in Reactions Photochemical (Flow) (Batch) toMicro From Photoreactors Conventional Introduction Reactions Reactions Homogeneous (Batch) ...... Microphotochemistry:

•

Figure 3.2 Figure

Microphotochemistry in Industry in Microphotochemistry to ...... in Microstructured

Micro 15–19 Figure 3.1 Figure Since light is regarded as a “clean reagent,” “clean a as regarded is light Since ) are most commonly used in conventional conventional in used commonly most are )

...... •

Heterogeneous Reactions Heterogeneous

(Flow) Flow Reactors ). 27–29

20–23 Photoreactors The potential of organic organic of potential The ......

1–12 •

Catalytic Catalytic Miniaturization Miniaturization 3 ...... 49 68 68 68 49 49 51 - - - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 FIGURE 3.1 FIGURE 50 several centimetres to over a meter. Longer channels can be used to increase residence times, thus thus times, residence increase to used be can channels Longer meter. a over to centimetres several instead. laries microcapil flexible use base solid without reactors solid a “Open” microchannels. of more or consist one with reactors support These reactors. falling-film and reactors serpentine namely microreactors, 1 under are which of parameters inner the tures, devices. own their build tocustom continue researchers many although available, cially commer now are reactor, KeyChem-Lumino the as systems complete including devices, microreactor ( microchips or microreactors widespread. adopted havebut been not effects these reduce is wells immersion on deposits falling-film iron forexample, types, and novelreactor Some common. also films polymeric of formation The observed. decompositions frequently or are reactions follow-up and automated easily be cannot volumes fixed with processes ( of lamps lifetime limited The operations. during cooling air usage of water the intensive or andrequire efficiency energy the lower further heat of generation the to due losses Electric lamps. the of efficiency energy the (±50 emission broad of of or volume wavelengths numerous irradiation of emission show total the typically lamps limits Common which reaction. the source, light the to closest effectively most occur cesses pro photochemical addition, In Beer–Lambert effect. this the reduce to in applied commonly expressed thus (asare solution dilutions law). High reaction the of layer narrow a within observed typically reactor (Rayonet) with Schlenk flask, and top-irradiation chamber reactor (Luzchem) with petri dishes. petri with (Luzchem) reactor chamber top-irradiation and flask, Schlenk with (Rayonet) reactor 3.2 FIGURE The main feature of “closed” serpentine reactors is the long channel length, which can range from from range can which length, channel long the is reactors serpentine “closed” of feature main The struc three-dimensional with reactors absolutely) not but (generally, are reactors Microstructured in transformations photochemical out carrying by overcome be can disadvantages these of Many nm) at the chosen wavelength. Therefore, optical filters must be frequently applied, which reduce reduce which applied, frequently be must filters optical Therefore, wavelength. chosen the at nm) ∼ 2000 (See color insert.) color (See Se oo insert.) color (See h) additionally causes significant installation, maintenance, and operation costs. Batch Batch costs. and operation maintenance, installation, significant causes h) additionally Microsystem eng chemistr ine Organic ering y The concept of microphotochemistry. of concept The Figure 3.3 Figure Immersion well reactor (with courtesy of UV-consulting Peschl), chamber chamber Peschl), UV-consulting of courtesy (with reactor well Immersion h CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC ν h ν ), on demand equipped with miniaturized light sources. Many Many sources. light miniaturized with equipped demand on ), h ν h ν mm in size. in mm h ν h ν h ν 1 There are two main types of “closed” “closed” of types main two are There 31,32 Microphot or spinning-disc reactors, spinning-disc or oc hemist ry 33,34 can can - - - - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 and falling-film reactor (IMM). reactor falling-film and 3.3 FIGURE Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry: heterogenic catalysis). heterogenic heterogeneous solution), in i.e., phase, (reactions involve that reactions reagents),liquid and (reactions gaseous between reactions and catalytic same the in all are reagents (the reactions homogeneous ries: literature. the in exist already microreactors in performances photochemical concerning examples of number A 3.3 at demand on volume use. of point product the studies. generate to route optimization efficient or an offer scale-up for microreactors of clusters networks parallel Parallel in or series in operated and be can temperature, Microreactors pressure, to respect with easily more time. much residence controlled be proceeding can reactions volume the small Likewise, a automated. in be can and operation in safer are itself microreactor (LEDs). diodes light-emitting as such sources light saving toring requires UV online only allows and also design waste microreactor The of chemicals. of and amount solvents amounts small total the reduces microreactions of scale experimental controlled. small The precisely be can to formation product proportional rate, flow the directly is changing By it as system. the of rate changed, flow the easily is microreactor a in for time necessity the irradiation removing The thus sequence, premixing. specific a in region reaction the to introduced be also can reagents The channel. reaction actual the preceding channel a mixing in online directly mixed be may reagents starting The circum reactions. mode follow-up by flow caused decompositions or continuous reactions side typically undesired vents The transfer. mass and heat fast provides that ratio surface-area-to- volume large a have also devices Microstructured solutions. concentrated relatively for even (100–1000 microchannels the of layers thin The processes. photochemical for beneficial them make which characteristics, tional systems. batch for although Volman, and Porter by cussed plates. channel larger or models reactor falling-film reagent cylindrical using with realized be can Scale-up mixture gas. reaction the of presaturation require devices channel closed contrast, to In up phase. of area interfacial large The force. gravity by 20,000 move that films falling liq thin the generates channels, phase these In uid arranged. are microchannels parallel which on plate reaction the is design used be can and scale-up. for developed been also have can microreactors reagents of Multilane inlets. mixing separate On-chip using achieved needed. be is irradiation prolonged when advantageous them making The advantages of photochemical synthesis in microdimensioned reaction vessels were first dis first were vessels reaction microdimensioned in synthesis photochemical of advantages The reactions. gas–liquid for designed specifically were reactors Falling-film 38 Photochemical Microreactors Reactions in m of the reaction. The small reactor size enables employing miniaturized or compact energy- compact or miniaturized employing enables size reactor small The reaction. the of 2 /m 27,28 3 Based on the conditions required, these reactions can be divided into three basic catego basic three into divided be can reactions these required, conditions the on Based guarantees efficient saturation of the film with reactant gas that is flowing over the liquid the over flowing is that gas reactant with film the of saturation efficient guarantees (See color insert.) color (See 41 Thus, the risk of highly exothermic or explosive reactions can be reduced drastically. drastically. reduced be can reactions explosive or exothermic highly of risk the Thus,

μ m) ensure extensive penetration of light throughout the reaction mixture, mixture, reaction the throughout light of penetration extensive m)ensure Dwell device (Microglas), KeyChem-Lumino system (with courtesy of YMC), of courtesy (with system KeyChem-Lumino (Microglas), device Dwell 39,40 36 Microstructured flow systems have addi have systems flow Microstructured The processes in microreactors and the the and microreactors in processes The 35 The central element of its its of element central The 37 or IR moni 51 ------Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 3.3.1.1 3.3.1 3.1 SCHEME 52 3.2 SCHEME (300 sources light two and Pyrex) and glass, lime soda (quartz, covers glass transparent types of different three the setup. ofTherefore, application experimental saving hold-up of volume 4 1000 channel a with 16 Typehad lanes B Microreactor zation. 1000 of 107 channel one-lane a had A Type Microreactor Mfg). Screen Dainippon by factured (manu B Type or A Type microreactor steel stainless glass-covered a in out carried were experiments 4 as a for testing. model selected reaction microreactor product steroidal the of preparation The 3.3.1.2 500 of mixture. reaction of the depth complete irradiation enabled channel shallow the as reactors, microstructured dem of advantage effectively general solutions the concentrated onstrated these of use The reactions. photochemical for high 0.5 relatively was benzophenone of concentration The HPLC spectroscopy. using UV off-chip using monitored online was and reaction analysis the of progress The device. the clogging thus channel, 3 than lower rates flow At 60%. to up of versions to be conversion the 4 flowadequate rates, improved. An established ratewas No product detectable formation was for obtained flowratesgreater than 10 source. light as a used was lamp UV fluorescent aminiaturized investigation, this In lower wavelengths. with irradiation allowed and wafers quartz two between wafer of a silicon structure had sandwich plate. aThesecond reactor to a wafer Pyrex silicon a bypatterned bonding fabricated was zophenone of ben transformation the Jensen coworkersand studied detection. UV online with reactors structured micro in investigated was that reactions photochemical earliest the of one is photopinacolization The is a key intermediate for the synthesis of myriceric acid A (an endothelin receptor antagonist). The The antagonist). receptor endothelin (an A acid myriceric of synthesis the for intermediate key a is The initial work was concentrated on increasing reaction output through an optimized and energy- and optimized an through output reaction increasing on concentrated was work initial The benzopinacol to conversions greater For μ 2.2 depth, m Homogeneous Reactions Photopinacolization Reaction Barton 1 using isopropanol as solvent in two house-made microreactors (Scheme solvent3.1).as microreactors house-made isopropanol two in using O Photopinacolization of benzophenone. Photopinacolization Barton reaction. Barton 0.2 ofhold-up volume a and length, m mL. This reactor type was used for multigram-scale production. for used multigram-scale was type reactor This mL. ONO 3 Ph O O 1 Ph CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC O 4 60% co hν from substrate substrate from 2 hν (365 Ac 2-propanol 60%–71% yield 5.3 gaf , longer residence times or lower flow rates were required. required. were rates flow lower or times residence longer , (365 or352 etone orDMF nv μ L min L ersion nm) ter 40 42,43 nm) This reaction is of importance because product product because is ofimportance reaction This h −1 mL. It was used for the initial process optimi process initial the for used Itwas mL. product product 3 via the Barton reaction (Scheme 3.2) was was 3.2) (Scheme reaction Barton the via μ Ph 500 wide, m O Ph

W high-pressure Hg lamp and 15 and lamp Hg high-pressure W OH 2 tended to crystallize in the micro the in crystallize to tended 2 OH Ph Ph μ μ L min 4 μ OH 0.5 deep, m L min O NOH −1 . With reduced flow −1 and showedand con O 37 m long, and a and long, m One reactor M, which is is which M, μ m width, width, m μ

W m ------Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 After constant operation for 20 for operation constant After 20 × 8 with coupled and series in Type connected B reactors microstructured two using compound target the of synthesis gram-scale a reported also authors The processes. photochemical ate initi to strength lamp),sufficient have mercury high-pressure (comparedto intensity low their despite product 12 desired of time the residence a After A. Type microreactor with combination in suitable source light a as 35× (48 pieces UV-LED panel a examined authors same study, the ofthis extension of71%. an In light the and microreactor source. Underthe conditions, a optimized residence between time of 12 distance the and dependence temperature the examined also product of instability thermal the to Due source. light 15 desired the to suited most was Pyrex that determined was It investigated. were light) black Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry: 3.3 SCHEME (FOTURAN device dwell acetate vinyl synthesis. [2 photochemical + the organic coworkers2] and of selected cyclohex-2-enone cycloaddition Fukuyama in applied extensively been has and rings four-membered methods of versatile formation and the for powerful most the of one is reaction cycloaddition 2] + [2 photochemical The 3.3.1.3.1 3.3.1.3 of chemicals. production scale larger forthe optimization process and reactors microstructured ofup fornumbering potential the onstrated 40 for operation (15 small six and microreactor B Type a of set one employed It functions. safety important had moreover and software PC via monitoring operation provided system This Mfg). Screen Dainippon by (manufactured DS-AMS-1 system, photomicroreactor automated an synthesis. on multigram-scale workautomated and forthcoming practical of their development the focused coworkers and Sugimoto synthesis, gram-scale successful the by 47%–70% as regioisomeric mixtures. 47%–70% regioisomeric as alkenes, cyclohexenones, additional two and verified further was conditions flow at yield time. same increase the and times irradiation shorten can reactors microstructured Thus, 85%. of yield lated 1 of rate flow a at series in microreactors two with repeated was (10 reactor batch the conditions, same the 0.5 of rate (flow irradiation 1000 depth, In all cases examined, the corresponding cycloaddition products products cycloaddition corresponding the examined, cases all In micro for cycloaddition 2] + [2 photochemical the of suitability the work, the of extension an In 300 regular A 6b Reactions Photocycloaddition Vinyl Acetate with [2 Cyclohex-2-Enone of +2]Photochemical Cycloaddition and and μ 6a m width, and 1.4 and m width, Photochemical [2 + 2] cycloaddition of cyclohex-2-enone with vinyl acetate. vinyl with of cyclohex-2-enone [2 + 2] cycloaddition Photochemical as a model reaction (Scheme 3.3) for testing in a commercially available microreactor microreactor available commercially a in testing for 3.3) (Scheme reaction model a as 6c h, product product h, W high-pressure mercury lamp was used as a light source in this study. After 2 After study. this in source light a as used was lamp mercury high-pressure W , were examined (Scheme 3.4). , were examined 4 5a O was isolated in a yield of 70%. This result clearly demonstrated that UV-LEDs, that demonstrated clearly result This 70%. of yield a in isolated was ® glass, manufactured by mikroglas). by manufactured glass, 4 mL h mL 5.3 of amount an in obtained was + m length. h, the amount of product product of amount the h, −1 ) a GC yield of 88% for the desired product product desired the for 88% of yield GC a ) 6a OA c mL Pyrex flask) furnished only 8% of 8% only furnished flask) Pyrex mL 88% GCyieldinµ-reac 8% GC yield in batc hν (365 h 2 4 at temperatures greater than 50°C, the authors authors the 50°C, than greater temperatures at nm) min furnished the desired min product furnished 4 isolated was 3.1 was isolated h g (61% isolated yield). This clearly dem clearly (61%g This yield). isolated 44 W) black light lamps. After continuous continuous After lamps. light black W) tor mL h mL 500 of channel a has reactor This −1 7b , which resulted in a similar iso similar a in resulted which , O 43 – 5b For this research, they used used they research, this For e 7a were obtained in yields of yields in obtained were and and g (60% yield). Encouraged Encouraged yield). (60% g 7a OA 5c 7a was obtained. Under obtained. was c , and two additional additional two and , . The same reaction reaction same The . W black lights. lights. black W 4 in a yield W black black W 5a mW) with with min, min, h of h 24–26 μ 53 m - - - -

Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 54 3.5 SCHEME reoisomers reached system microflow completion in 0.5 the in photoreaction The lamp. Hg high-pressure common a by taneously 13 of (ID) diameter hold-up volume of 0.2 cyclopentene with auxiliary, chiral derivative cyclohexenonecarboxylate the of with reactor. batch results volume the larger a compared using and obtained reactions those asymmetric photoinduced in system microflow a of utility compounds. structural unique and products natural active biologically potentially of formation the to due importance special of are photoreactions Asymmetric 3.3.1.3.2 3.4 SCHEME 1000 of channel single a with microreactor A Cyclopentene with Enone Cyclic [2 aChiral of +2] Photocycloaddition Diastereoselective 10 O and and Photochemical [2 + 2] cycloaddition of cyclohexenones with alkenes. with of cyclohexenones [2 +2] cycloaddition Photochemical Diastereoselective [2 + 2] cycloaddition of a chiral cyclic enone and cyclopentene. and enone cyclic of achiral [2 +2] cycloaddition Diastereoselective R* 8 h, which was two times faster than in the batch (1h, than system faster which was two times CO 11 = mm was used for the batch comparison test. Both systems were irradiated simul irradiated were systems Both test. comparison batch the for used was mm 2 were almost identical in both systems. Additionally, the authors investigated the the investigated authors the Additionally, systems. both in identical almost were mL (Dainippon mL Screen (Dainippon Mfg) was employed. A simple test Pyrex tube an with inner R* + 5b 5a 5a 5c O O O O 9 + + + + CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC 9 (Scheme 3.5). T 0.5 h in µ-reac in h 0.5 oluene orCH 6b 6a 6a 6c hν (365nm) 1 h in batch OBu OA OA OA 8 c c c , which incorporated a (−)-8-(phenyl)menthyl group as a (−)-8-(phenyl)menthylas a group incorporated which , μ 2 tor m × 100 × m Cl 47% yield 64% yield 62% yield 70% yield 2 47 3.2 h 3.2 h 3.2 h 2 h The model reaction examined was the reaction reaction the was examined reaction model The hν hν hν hν R*O R*O μ 45,46 cis-syn- 2.2 × m O O 2 2 10b 10a Hence Ryu and colleagues explored the the explored colleagues and Ryu Hence C C H H H H H H cis m (width × depth × length) and a and length) × depth × (width m O O O O 7b 7d 7e 7c h). However, the ofratios ste + + OA OA OBu OA c c c R*O R*O O O cis 2 2 C C nti- -a H H 11b 11a H H H H cis - - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 lectivity and efficiency for batch and microstructured reactor conditions. reactor microstructured and for batch efficiency and lectivity has by been reported et nitrile Maeda (Schemeal. 3.6). intramolecular The studies. regioselectivity in [2 used been also have microreactors flow Continuous 3.3.1.3.3 for used be can photoreactions. microreactor flow asymmetric a that shown has study this summary, In chamber. reaction the of ratio surface-area-to-volume large very a with associated system microflow the in control temperature and values of excess diastereoisomeric The highest theofondiastereoselectivity. effect temperature Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry: naphthalene. 3.6 SCHEME source. alight as used was xenon lamp plates and from had of Pyrex a width 2.5 channel 100 of channel a with glass Pyrex from made was Technology),and Microchemical of Institute (ICCDI05, dimensions. 8 microchannel the and rate, flow of time, ­residence diameter a with tube (Pyrex reaction naphthalene-1-carbonitriles of photocycloadditions and 2-(2-alkenyloxymethyl)- Mizuno coworkers other intramolecular examined 3.3.1.3.4 Eu(hfc) using investigated also was enantioselectivity The compound. this for place take not does material ing to tocycloreversion cycloadduct formed mode. flow initially the The by explained was microreactor the in regioselectivity improved The microreactor. the and of 180 a longer time residence with system batch the in investigated also tocycloadduct photocycloadduct of 5% only contrast, In respectively. microreactor, the in 55:7 ring naphthalene the of time of an irradiation 3.4 After as optimal. 202 of a UV-29with pathlength filter.The channel 0.05 and 0.03 of rates flow two at microchannel the 300 channels π Two microreactor types were utilized. The first (Type A) microreactor was commercially available available commercially was microreactor A) (Type first The utilized. were types microreactor Two with poly(dimethylsiloxane) from made reactors custom-built in performed was transformation The + 2 μ 11 14 40 width, m (54%) were observed in the microflow reaction at −40°C. This was explained by a more accurate accurate a by more explained was This −40°C. at reaction microflow (54%) the in were observed were detected in a ratio of 56:17, respectively, but the regioselectivity was still not as good as in in as good as not still was regioselectivity 56:17,the of but ratio respectively, a in detected were π 3 and a small but significant enantiomeric excess of 2% excess determined. (e.e.)was enantiomeric but significant asmall and ] photocycloaddition of 1-cyano-2-((3-methyl-2-butenyloxy) methyl) naphthalene 1-cyano-2-((3-methyl-2-butenyloxy)naphthalene of methyl) photocycloaddition ] of 2-(2-Alkenyloxymethyl)-Naphthalene-1-Carbonitriles [2 +2] Intramolecular [2 and +3] Photocycloadditions Derivative [2 a1-Cyanonaphthalene of +2]Intramolecular Photocycloaddition μ 14 50 m wide, nrmlclr [2 Intramolecular were noticed under batch conditions after the same reaction time. This reaction was reaction This time. reaction same the after conditions batch under noticed were μ 120 and depth, m 12 . Extended irradiation times gave higher yields of yields higher gave times irradiation Extended . O 13 12 μ and the photocycloadduct at the 3,4-position 3,4-position the at photocycloadduct the and m deep, and 45 or45 202 and m deep, CN 15a–c π 2 + 13 (Scheme 3.7).(Scheme h is continuously removed from the system, therefore reducing pho reducing therefore system, the from removed continuously is ν (>290 mm length. A second (Type B) microreactor was made in-house in-house made was microreactor B) (Type second A length. mm MeCN π pooyladto o 1-cyano-2-((3-methyl-2-butenyloxy)methyl) of photocycloaddition ] min, the intramolecular photocycloadduct at photocycloadduct the 1,2-position the min, intramolecular nm) m ad suy n h efcs f usiuns solvent, substituents, of effects the on study a and mm) 49 mm, mm, a of depth 50 mm long. The reaction mixture was pumped through through pumped was mixture long. The mm reaction This investigation included a comparison to a batch batch a to comparison a included investigation This mm afforded prolonged reaction time and was found time prolongedafforded mm reaction mL h mL 55:7 af 48 O The authors in particular compared thecompared regiose Thein authors particular 13 56:17 af −1 and was irradiated by a xenon lamp coupled xenonlamp a by irradiated was and CN ter 3.4mininµ-reac 13:14 ratio: ter 3 h in batc + μ m, m, and ofa length 60 min and photocycloadducts photocycloadducts and min 14 14 14 h since reversion to the start the to reversion since O were detected in a ratio of ratio a in detected were tor CN 13 and traces of pho of traces and mm. A mm. 500 12 in aceto in 10 (82%) 55 13 W - - - - -

Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 56 3.8 SCHEME product material conversion ofstarting Complete time. dence condenser.and bar stirring magnetic a with fitted tom flask was attempted in a batch the transformation same mode, that is, in purposes, the roundbot comparison derivative coumarin of cycloaddition 2] + [2 intramolecular plates. quartz uranium-doped of set by a be provided could filtering wavelength selective demand, On arc (450lamp mercury pressure medium A channel. the of cover transparent a created also membrane This nitrogen. using membrane flow serpentine the of 0.98 was volume channels cell total The side. back the on channels cooling integrated contained that 1000 of microchannels reaction The intervention. human without executed and programmed be to microreactor conditions of set a enabled photochemical flow-based convenient a LOPHTOR. named designed recently have Laboratories Abbott 3.3.1.3.5 depth. channel ashallow maintaining outputwhile increase significantly can channels wider that demonstrated also was It system. batch the to compared reactors micro the in medium reaction the through penetration light better the by explained was efficiency in just 1 conversions of higher 69%–75%after Additionally, were suppressed. microreactors the in were achieved photoproducts 3.7 SCHEME Initially, Vasudevan and coworkers investigated the dependency between product yields and resi and yields product between dependency the investigated coworkers and Vasudevan Initially, known the using the authors by evaluated was synthesis LOPHTOR of for photochemical The utility initial the and regioselectivity increased allowed for microreactors the in performed irradiations The min, while the batch while min, reactor showed a lower conversion of 74% 3 after 19 Derivative [2 aCoumarin of +2]Intramolecular Photocycloaddition was isolated in a yield of 98%. In contrast, a much lower product yield of 30% was obtained obtained was 30% of yield lowermuchproduct a contrast, In 98%. of yield a in isolated was R Intramolecular photocycloaddition of 2-(2-alkenyloxymethyl)-naphthalene-1-carbonitriles. photocycloaddition Intramolecular Intramolecular enone photocycloaddition. enone Intramolecular 2 16a–c 15a–c R O 1 50 The unique aspect of this new tool was its integration with an autosampler that that autosampler an with integration its was tool new this of aspect unique The were selectively formed, while undesirable photocycloreversions yielding yielding photocycloreversions undesirable while formed, selectively were CN R mL and it was sealed during operation by a fluorinated ethylene (FEP)propylene ethylene fluorinated bya operation during sealed itwas and mL 1 μ 250 width, m 18 Benz O O O a: R a: R b: R h ν 1 1 W) with concentrator and cold integral mirror was used for irradiation. forused was irradiation. mirror concentrator and cold W) integral with 1 (>280 ene orMeCN R = R = M = CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC 2 2 e, H = M = μ nm) R 98% yieldaf 2 m depth, and 3.93 and depth, m e 30% yieldaf H = h ν Benz (300nm) ter 2hinL ter 24 h in batc 16a– O ene 18 was achieved after 2 after achieved was c CN m length were fabricated from stainless steel steel stainless from fabricated were length m R OPHT R 2 R 1 1 c: 10:90af 73:27af b: 93:7af a: 96:4af 18 55:45 af 3:97 af OR h + (Scheme 3.8) as model reaction. For reaction. model as 3.8) (Scheme ter 1mininµ-reac ter 1.5 h in batch ter 1 min in µ-reac in min 1 ter R R ter 2.9 min in ter 4 h in batc ter 4 h in batc 1 16:17 ratio: R 2 1 O H 17a– 19 h of irradiation. h Theincrease of irradiation. O O h in the microreactor and and microreactor the in h c H H H µ-r h h CN eac tor tor tor 17a–c - - -

Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 3.3.1.3.6 applications. discovery drug early suit ideally will that of material milligrams of hundreds generate to process this of scale-up for manner convenient a provides This observed. was of concentrations of side products. tion forma extensive by characterized were and times, reaction longer despite setup, photochemical batch conventional the using lower significantly were yields product The established. was tendency similar a examined, cases all In derivatives. coumarin to applied other was procedure reaction the and expanded 24 for irradiation prolonged after even system batch the in Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry: 3.9 SCHEME pent-4-enylpyrrole-2,5-dione 21 construction. for this abase as a or 400 with a well equipped An immersion 600 filter. or Vycor Pyrex standard a around wrapped were tubing this of layers five to One optimal. as OD 2700 dimensions the with tubing wider output, considered coworkers multigram and in Booker-Milburn interested Being employed. was diameter aforementioned the with tubing FEP 280 to up 60 from volumes hold-up with constructed were reactors flow different Four microchannel. a as of 700 diameter an inner with tubing FEP optimization design reactor the However,during microreactor. a than rather reactor simple where photochemistry as aflow system this on described The authors studies vessel. reaction the as used was research tubing FEP UV-transparent first the of one is This functionality. nonstop 24 and quality, product the to respect with reactor batch a over system flow continuous a al. et Booker-Milburn by was investigated scale large on photochemistry organic perform to technology flow continuous of application The to the cyclobutene product product cyclobutene the to Theeffect of the concentration onreactant the conversion of These reactors were assessed using the [2 + 2] photocycloaddition of maleimide maleimide of photocycloaddition 2] + [2 the using assessed were reactors These mL, which were entirely determined by the tubing length and dimensions. In two of these designs, designs, these of two In dimensions. and length tubing the by determined entirely were which mL, 3,4-Dimethyl-1-Pent-4-Enylpyrrole-2,5-Dione of [5 +2] Photocycloaddition Intramolecular and 1-Hexyne with [2 Maleimide of +2]Photochemical Cycloaddition [2 + 2] and [5 + 2] cycloaddition reactions of maleimide and its derivatives. its and of maleimide reactions [2 [5 +2] and +2] cycloaddition 18 R R 0.425 to 0.085 from range the in 20 23a,b O O μ O O NH N m and (OD)an outer diameter of 1100 23a 22 + and the intramolecular [5 + 2] photocycloaddition of 3,4-dimethyl-1- of [52] + photocycloaddition intramolecular the and to the bicyclic azepine azepine bicyclic the to 51 Bu 21 The main focus of this research was to show the superiority of superiority the show to was research this of focus main The [2 +2]cy [5 +2]cy MeCN orCH 83% co 178 gper24h 685 gper24h W medium pressure Hg lamp as light sources was used W Hg used was pressure sources as medium lamp light 80% yield R MeCN M = h h cloaddition cloaddition nv M were tested and no decrease in conversion rate conversionrate in decrease no and tested were M ν ν e, Cl ersion 2 24a Cl h. The substrate portfolio was subsequently subsequently was portfolio substrate The h. 2 as model systems (Scheme 3.9). Using an an 3.9).(Scheme Using systems model as 18 μ to m was used, which defines the reactor m defines which was used, Bu 19 was also evaluated. Five was evaluated. different also R R 22 24a,b O O O O NH N μ 20 m ID × 3100 × ID m h isolated yield, yield, isolated h with 1-hexyne 1-hexyne with μ 57 m - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 of 3,4-dichloro-1-pent-4-enyl-pyrrole-2,5-dione of 3,4-dichloro-1-pent-4-enyl-pyrrole-2,5-dione reaction To[5 2]+ photocycloaddition formation. intramolecular the by-product selected authors the principle, this limiting demonstrate and product of yield possible performed be highest could the reactions achieving continuously, photochemical problematic strategy, this Following rate. flow the and of azepine bicyclic 22 went83% conversion at0.8 0.4 A reactors. batch common to compared results outstanding layers three system with of optimized FEP tubing and a Vycor filter,these were reactions with performed 58 SCHEME 3.10 SCHEME ( methoxy-1-methylcyclohexane products: addition three of formation the with occurs transformation ( to methanol of toaddition pho toluene-sensitized the was microreactors in performed synthesis asymmetric of example Another 3.3.1.5 clogging. without Thereduction waste. in maleic sluganhydride flow was microreactor operated continuously for over 16 and conversions improvement of an for allowed This operation. recycle and circulation 75 continuous for of ID an with vessel glass 300 of (cylindrical height a and system batch the from that to compared when purity OD and 0.8 anhydride 25 maleic of solution 10% a that showed results experimental The source. light a as 400 employed standard A investigated. also were time con residence anhydride and maleic centration of effects the Additionally, examined. was conversion product on dimensions tube the of impact the and vessel reaction the as used were sizes various of tubes FEP tube. reactor the of precipitate within sedimentation and adhesion the inhibited vibrations ultrasound time, Atsame the precipitated products in the liquid segments. as a the reactor and tube transported spacer swept through N Inert ultrasonication. and flow slug of combination a by come a for microreactor. flow slug novel liquid/gas reaction model a as coworkers and by Yoshida selected was reaction This displays. crystal liquid (CBTA) dianhydride ylic maleic of photodimerization the is anhydride reaction photochemical problematic a of example important An 3.3.1.4 step. akey [5 as of the (±)-neostenine +2] using photocycloadditions synthesis group-free (45 reactor azepine desired the As expected, batch setups. 685 over of underwent a satisfactory conversion of 70% after a residence time of 22 of time residence a conversion of70%after satisfactory a underwent 24a Using flow reactors, the residence time could be tuned by adjusting the volume of the reactor reactor the of volume the adjusting by tuned be could time residence the reactors, flow Using The microreactor approach demonstrated that the clogging problem within the reactor can be over be can reactor the within problem clogging the that demonstrated approach microreactor The . Anhydride Maleic of Photodimerization ( to Methanol of Addition Diastereodifferentiating 25 g) compared to the batch system (0.5–1 system batch the to compared g) mm the of mm product ID,desired Therespectively. quality (Scheme 3.10). It is known that this reaction yields the insoluble cyclobutane tetracarbox cyclobutane insoluble the yields (Scheme reaction 3.10). this that It known is g/day. At the same flow rate a 0.1 a rate flow same the At g/day. Photodimerization of maleic anhydride. of maleic Photodimerization 24a mm). Moreover, the unique design of the slug flow microreactor made it adaptable adaptable it made microreactor flow slug the of design unique Moreover,mm).the was isolated in a yield of 80%. This remarkable result arepresents 24 result remarkable a in ofThis isolated yield was 80%. 26 25 O mL min mL O O R , which is used as raw material for polyimide and for alignment films for films alignment for and polyimide for material raw as used is which , )-(+)-( 26% co cis 26% co CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC −1

Z 28 flow rate representing a projected yield of the desired desired the yield of a projected rate representing flow )-limonene )-limonene nv and and 53 ersion af nv h ersion af Ethyl acetate ν trans , ultrasoun 24b ter 10mininµ-reac 23b M solution of compound compound of solution M

27 29 ter 6 h in batc was obtained in significantly higher yield in theinyieldflow higher significantly in obtained was (Scheme 3.11) as reported by Sakeda et al. et Sakeda by reported 3.11) as (Scheme g). The reactor was also applied to the protecting- the to applied also was reactor The g). to the bicyclic azepine isomers) and exocyclic isomer isomer exocyclic and isomers) d h M solution of the maleimide maleimide the of solution M tor 2 gas introduced into the solution flow solution the into introduced gas O O O 26 R )-(+)-( in the microreactor was ofwas in microreactor the higher 26 W high-pressure Hg lamp was was lamp Hg high-pressure W cis - and and - min in a FEP tube of1.4 tube FEP a in min 24b Z 23a O O O )-Limonene and ittested in flowand was irradiated and the the and irradiated was trans 30 -4-isopropenyl-1- . Compared to to Compared . h yield h of yield 178 52 cyclobutene ­cyclobutene 20 under 54 This This mm mm mm mm h g - - - - - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 SCHEME 3.11 SCHEME Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry: SCHEME 3.12 SCHEME 200 was microchannelIts For the second step, a microreactor that enabled simultaneous photo- reactions and thermal was utilized. 200 channel amicroreactor with quartz D min et al. by Takahashi recently described was microreactor a in reaction thermal and photochemical combined a of example first The 3.3.1.6 side reactions. suppressed which area, irradiated the from removal product ous continu and a and fast times, homogeneity, exposure short illumination spatial higher the penetration, light better a by explained was microreactor the of performance superior The (0.06). system batch the greater the was microreactors(0.11–0.29) andfor size Photonthan channel decreasing performed. with increased was efficiency efficiency photon the on size channel the of effect the on study comparison a thanhigher for for the the Thesewereconstants microchannels batchchamber. significantly In addition, for constants reaction bytheversus the batch estimated was cell clarified (15 (36 30.6% was value 20 excess to up diastereomeric the only linearly increased cell batch the in yield the period of 135irradiation of the examined during yield linearly increased The pump. syringe the of rate injection the by controlled was channels (40 lamp mercury low-pressure a using conducted volume a of total 1 with cell 400 reactors. in microchanneled (d.e.)values excess diastereomeric higher and reactions faster found authors the cell, microbatch a HO The first step of this transformation is a photochemical one and was carried out in a custom-made a in out carried was and one a photochemical is transformation this of step first The Co.) of sizes 500 microreactors channel with (Shimadzu kinds ofThree quartz min of min in the batch The oftheforirradiation) valuetheobserved cell. difference d.e. in origin the MR μ m ×40 3

32 Me D Vitamin of Synthesis Continuous-Flow was selected as a model transformation in this study (Scheme 3.12). study this in transformation amodel as selected was Pro μ vitamin D m ×100 31 Me Diastereodifferentiating photosensitized addition of methanol to ( methanol of addition photosensitized Diastereodifferentiating H Two-step conversion of provitamin D of provitamin Two-step conversion 27 3 30.6% d. 28.7% d. 200 and mm, R

μ m deep,1 m 55 mL (light passlength of 3 passlength (light mL The two-step conversion of provitamin D conversion two-step ofThe provitamin e. af e. af h ν , sensitizer CH ter 36 s in µ-reac in s 36 ter ter 15 min in batc h ν 3 μ OH

mm wide, and 500 and wide, mm m ×20

μ HO m deep,1 m μ Pr m ×100 evitamin D s of irradiation) in the microreactor while it was 28.7% 28.7% was it while microreactor the in irradiation) of s tor h H Me 3 32 to vitamin D vitamin to 3

mm wide, 250 wide, mm W, 254 CO mm) were utilized for this study. Irradiations were study.for Irradiations this mm) were utilized 28 cis mm (width × depth × length) and a quartz batch batch aquartz and ×length) ×depth (width mm

mm long and had an internal volume100ofinternal an hadlong and mm Me 3 H 3 nm). The irradiation time within the micro the within time irradiation The nm). + R min and reached a plateau. Furthermore, Furthermore, plateau. a reached and min 3 . tr s within the microreactors. In contrast, In contrast, the microreactors. s within h

29 mm long, and with a volume50 aof with long,and mm ν Δ (100°C) ans (360nm) OCH 3 3

31 cis to vitamin D to vitamin + and R )-(+)-( 32% isolatedyieldinµ-reac 20% yieldinindustrialproces HO exo trans 30 μ m × 300 cis Z )-limonene. and and isomer formation. V itamin D 3

33 33 trans μ via previta via m × 60 3 Me H isomers isomers R mm, mm,

μ μ tor 59 L. L. L. s - - - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 producttachysterol (not shown)D towardprevitamin D vitamin the ofstep D vitamin yield: 60%), whichhigher was significantly compared industrial theto process, existing wheretheyield of After chromatographic purification, the D desired vitamin D provitamin of tion the solvent, in particular concentration, and flowrate, carried wasout. A fairly concentrated30 conditions,reaction the onstudy optimization (100°C).bath an setup,hotoil a Usingthis in placed was filters (360 UV glass and Vicor a combination of a through irradiated was reactor second The 400 microreactorstwo Those polyetheretherketonevia were connected and (PEEK)tubingemployed single a 60 SCHEME 3.13 SCHEME 8 × (5UVA-panel a under 3.3.1.7) Section in (described examined; device were setups dwell reactor the microstructured of types Three study. comparison microreactor a for isopropanol of addition Oelgemöller and coworkers have the investigated also 4,4 3.3.1.8 ation reactions phenylglyoxolates.involving andphthalimides alkyl solution.the The same authorstheir extended study to intra-andother intermolecular photodecarboxyl penetrationthrough light better a by explained microreactorthus wasthe improved in the performance afteran extendedirradiation period of 3 2 weretestedundermicro conditions improvedand ofyields97% ( Themicroreactor was placedunder aUV panel (Luzchem) fitted with five UVB lamps. Only two reactions tine reaction channel (0.5 25 fluorescent lamps (8 16UVB with equippedreactor Rayonetchamber a in irradiated phenylacetates corresponding the and microflowconditions. under batch of Recently, phthalimide benzylations Oelgemöller et haveal. photodecarboxylative studied 3.3.1.7 the amounts of waste. D vitamin product lumisterol (not shown) was suppressed to less than 10%. Consequently, the microflowsynthesis of

h. Despite its larger lamp power, the batch reactor gave somewhat lower yields of 92% (

Conventional batch transformations were performed in a Pyrex Schlenk tube (volume 100 nm). The dwell reactor (mikroglas) was madefrom Foturan

W high-pressure mercury lamp. The first reactor was irradiated through athrough irradiated filterVycor high-pressurewas firstreactor lamp. W The mercury (313–578 Phthalimide of Benzylations Photodecarboxylative Furanones to Isopropanol of Photoaddition 3 3 did not require any purification ofintermediates orhigh-dilution conditions,thereby reducing is below20%. is 34 Photodecarboxylative addition of phenylacetates to phthalimide. to of phenylacetates addition Photodecarboxylative O O NH 3 3 synthesis shifted the equilibrium of the competing the photoisomerization of equilibrium the the side of shifted synthesis in 1,4-dioxane was introduced at a flow rate of 5 of rate flow a at introduced was 1,4-dioxane in 38

30 mm mm depth, 2 + 56 The parallel application of photo- and thermal conditions within the secondthe within conditions thermal and applicationphoto- of parallel The to furanones furanones to The benzylated hydroxyphthalimidines The hydroxyphthalimidines benzylated KO 2 C 35a 35a,b CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC R or

mm mm width, and 1.15

h. The cosolvent acetone (50 35b 37a–c Ac and phthalimide phthalimide and etone/pH 7bu„ (Scheme 3.14).(Scheme b: R M = a: R hν (300 F = 3

e nm) 32 ′ -dimethoxybenzophenone (DMBP)-sensitized -dimethoxybenzophenone . Moreover. generationthe secondofundesired 3

m length) and a top heat-exchanging channel.

33 er ™ was obtained in a yield of 32% (HPLC-UV 59–61 glass and consisted of a (bottom) serpen 34 80%yieldaf b: 98%yieldaf 92%yieldaf a: 97%yieldaf 36a (Scheme 3.13), respectively. The reaction was chosen as a model model a as chosen was reaction The 57,58

Vol-%) functioned as a sensitizer and ) and 98%and( ) 36a

and μ HO L min L 36a,b W), a microchip (Micronit (Micronit microchip a W), O ter 2hinµ-reac ter 2hinµ-rea ter 3 h in batc ter 3 h in batc 36b NH 36b −1 were synthesized from were synthesized with a syringe pump. syringe a with ) were) achieved after 36a

W each, W ) and 80% ( h h ct R tor

mL) that was or

λ mM mM solu

nm) and and nm) = 300 ± 300 =

nm). 36b - - - ) Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 SCHEME 3.14 SCHEME Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry: SCHEME 3.15 SCHEME yields. consequently improvement and of conversion rates Below a flowrate of 0.2 respectively. system, water/oil/water 73%the for and system oil/water the for 28% of yields in obtained 1-cyanopyrene 40 (DCB, nobenzene (300 lamp mercury high-pressure a from light with irradiated were microchips The respectively. interfaces, water water/oil water/oil/stable or of formation ensuring thus rates, flow equal with phases, water and oil the allowed forof introduction This a separate channels. reaction to either two the serpentine or inlets three 100 of width channel with substrate, rol Ueno coworkers. and pyrene of photocyanation The 3.3.1.9 improvement potential. and of handling terms in setup best the as seen was reactor (558 microcapillary the of diameters chip (150 of channel reaction the micro the shallow very through by transmission light the highest was explained This results. overall best the gave microchip LED-driven the examined, designs microreactor three the Of the to compared batchsystems gave process. results superiorthe microreactor calculations efficiency 2.5 after already conversions high versions to 16 (Rayonet, ×8 reactor tube chamber abatch in test irradiated conventional a in those to compared were systems microflow the from results The troscopy. 8 UVA-lamp× (1 single containing a tube Pyrex a around wrapped capillaries PTFE parallel two of consisted that microreactor 365 of panel a incorporating Microfluidics) An aqueous solution of sodium cyanide (1 cyanide sodium of solution aqueous An complete con almost togave high reactor microcapillary theand thedevice, dwell Thesystem, batch Pyrene of Photocyanation μ W) through a copper sulfate solution filter filter solution (>330 sulfate acopper through W) m depth), compared with the wider channel of the dwell device (500 of device dwell the channel m wider the depth), with compared O 39a–c 37a– Sensitized isopropanol addition to furanones. to addition isopropanol Sensitized 41 Photocyanation of pyrene. Photocyanation O after just 5 just after , remained in the oil layer. After a residence time of 210 of time residence a After layer. oil the in remained , c 62 mM) in propylene carbonate were pumped through the reactors. The product, product, The reactors. the through pumped were carbonate propylene in mM) R This transformation was performed in microchips made in-house frompolysty in-house made microchips in performed was transformation This μ L min + W) in its center. Conversion rates of rates Conversion center. its in W) min of irradiation. Despite its weaker light sources, the microchip reached reached microchip the sources, light weaker its Despite of irradiation. min 40 −1 no could which stable be preventedinterface oil/water obtained, further 40 38 OH (Scheme 3.15) across an oil/water interface has been described by described been has interface oil/water an across 3.15) (Scheme min. Based on the conversion rates, reactor geometries and energy energy and geometries reactor rates, conversion the on Based min. μ m) and the test tube (9 tube test the m)and c: R=(–)- b: R=raEt c-O a: R=H hν (350or365nm) 73% yieldaf μ 20 of depth m, DCB nm high-power UV-LEDs (6 × 75 × (6 UV-LEDs high-power nm hν, NaCN DMBP M) and a solution of pyrene pyrene of solution a and M) OMen , water/oil ter 210 t 100% conv W). 87%–90% co s μ m, and length of 350 of length and m, nm). mm), respectively. However, the capillary capillary However, the mm),respectively. ersion af O 37a–c nv 39a– ersion af O 41 were determined by NMR spec NMR by determined were ter 2.5–5mininµ-reac c R OH CN s, the photoproduct the s, ter 5 min in batch 40 (20 μ mW), and an in-house in-house an and mW), m depth) and the inner m depth) inner and the mm. The reactors had had reactors The mm. mM) and 1,4-dicya and mM) tor 41 was was 61 - - - - - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 was reported byWootton al. et reported was explosive in endoperoxide microreactor a the of synthesis potentially safe the study concerning Thefirst 3.3.2.1.1 3.3.2.1 well. as utilized been have systems reactor other but purpose, the for designed especially was reactor film-type falling- The media. reaction the to gas reagents. reagent of supply a gaseous provide continuously and to liquid necessary thus is It between interactions by characterized are reactions heterogeneous The 3.3.2 62 SCHEME 3.17 SCHEME 3.16 SCHEME synthesis. conventional large-scale for the concern (Scheme 3.17). generatedendoperoxide Theinitially 2-cyclopenten-1,4-diol to reduction the by followed oxygen, oxygen in the presence of TheRose Bengal. dissolved ofphotooxygenation cyclopentadiene singlet of generation photochemical continuous the for suitable also is IMM) by (FFMR microstructured microreactor a in reaction explosive Dingerdissen. and potentially Jähnisch by a described been has of reactor conduction safe the for example further A 3.3.2.1.2 5 of only 85% time at was aresidence and GC avoided outlet the at mixture ascaridole conversion of The solvents. product oxygenated of the accumulation of degassing nitrogen with together system the in solvent (20 lamp tungsten unfiltered an using performed was Irradiation 15 of 1 of rate flow a with channel inlet gent solution of A methanol channel. outlet an and 50 length (total area irradiation serpentine conditions. conventional in formed often are nature explosive with liquids organic oxygenated of quantities large therefore and saturation oxygen sufficient requires tion to oxygen singlet The reactor was built in-house from a glass substrate and consisted of two inlets at the start of the of start the at inlets two of consisted and substrate glass a from in-house built was reactor The μ L min L Reactions Heterogeneous Reactions Photooxygenation to Oxygen Singlet of Addition and Generation Photochemical Cyclopentadiene to Oxygen Singlet of Addition and Generation Photochemical −1 ). This design made presaturation of the of presaturation made design This ). Photoaddition of singlet oxygen to cyclopentadiene and subsequent reduction. subsequent and cyclopentadiene to oxygen of singlet Photoaddition Photoaddition of singlet oxygen to to oxygen of singlet Photoaddition α 44 -terpinene -terpinene + 1 O 42 2 42 63 in the presence of an organic dye as sensitizer (Scheme 3.16). dye presence of the in as sensitizer organic an reac This The photochemical synthesis of ascaridole ascaridole of synthesis photochemical The Rose bengal,MeOH + CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC 85% co 67% isolatedyieldaf 1 O μ hν 2 L min L nv 50 of depth average mm, ersion af s. Rose bengal, MeOH α α −1 -terpinene and Rose Bengal was introduced via a diver via introduced was Bengal Rose and -terpinene -terpinene. and mixed with oxygen on-chip (flow rate of oxygen oxygen of rate (flow on-chip oxygen with mixed and ter 5 s in µ-reac in s 5 ter

45

ν h ter 4 h in batc is potentially explosive, which explosive, represents a is potentially safety α -terpinene solution with oxygen unnecessary. unnecessary. oxygen with solution -terpinene 64 45 These authors showed that the falling-film falling-film the that showed authors These O O 46 , has been chosen as a model reaction reaction model a as chosen been has , tor h W,6 20% yield Thiourea α 43 -Terpinene μ after workup was determined by determined was workup after m, and average width of 150 of width average and m, V). The small volume of aerated aerated of volume small The V). 43 O O 43 proceeds via addition of addition via proceeds 46 OH OH 44 by singlet μ m) - - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 falling-film reactor (IMM). reactor falling-film toluene-2,4-diisocyanate of tochlorination photooxygenations. to limited not is reactions heterogeneous of portfolio The 3.3.2.2 as efficient as the ruthenium complex. comparisontizer study 450 with a higher photostability and quantum yields of singlet oxygen formation compared to Rose Bengal, a sensi 2,2 reactor. Schlenk a in process,complex rutheniumacontrast than In industrial to the (tris(4,4 microreactor a in higher magnitude oforder one about was STY the reactor.Likewise, Schlenk the for than The photonichigher HPLC.by times efficiency the two for LTF-microreactor was which 0.048, was (−)- 6.5 7.46 of The batch experiments were performedthein Schlenk-tubemodified illuminatedreactor an with volume 60–70 continuouslywas and microreactorthe pumped through loop. a in illumination tookThe place for about microreactoroutside the containerstoragedouble-wall a in compressedair with saturated was mixture 1 of width a with channel serpentine half-round single HT-residence a consisted of made of and was that GmbH)glass Factory Things (Little photonic efficiencies. and (STY) yields on space–time based study comparison for areactor 48 (−)-rose oxide. natobenzene natobenzene SCHEME 3.18 SCHEME Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry: The photochemical oxidation of ( of oxidation photochemical The 3.3.2.1.3 is suitable for photooxygenation reactions on a preparative scale. penten-1,4-diol rently to the liquid with a flow rate of 15 a safe level. As light source, a xenon lamp (1000 shortholdup insured that thequantity of theendoperoxide and theoxygenated solution wasalways kept at peroxide very thin layer of liquid. The reactor was additionally cooled to 10°C–15°C.solution The of effluentcyclopentadiene containing wasthe pumped endo through the microreactor at a reactor,flow rate which of 1 had 32 parallel microchannels of 66 and and The microscale oxidation of oxidation microscale The The photooxygenation step ofthis transformation took placein the reaction plate ofthe falling-film micro ′ mW/cm -dipyridyl)-ruthenium(II)-dichloride)was used asphotosensitizer. rutheniumthe complex While has β -citronellol was purged with compressedfor-citronellol 20 purged with air was

h using an LED array (4 × 10 LEDs, LEDs, 10(4× array LED an using h 40 volume (total mL 49 45 Reaction Photochlorination Citronellol of Oxidation Photosensitized (Scheme 3.18). This transformation was selected by Meyer and coworkers as a model reaction andascoworkers a reaction by model Meyer (Schemeselected 3.18).was transformation This 2 was passed into a solution of thiourea in methanol at 10°C. Theaforementioned techniquesand was placed at the center ofreactor. for this Prior to 5–8 irradiation 51 65,66 47 46 Sensitized photooxygenation of ( photooxygenation Sensitized (1Cl-TDI), is used industrially as an intermediate in the synthesis of polyurethanes. synthesis the in intermediate an as (1Cl-TDI), industrially used is CH was obtained in a yield of 20% (0.95 The Schenck-ene reaction of Schenck-ene The reaction 2 OH + 68 mL). A LED-stick (2 × 15 LEDs, LEDs, 15 × (2 LED-stick A mL). The main product of this transformation, 1-chloromethyl-2,4-diisocya transformation, this of product main The 1 O 47

W xenon lamp ( 2 0.048 f was carried out in a commercially available microstructured reactor microstructured available commercially a in out carried was Photonic e
ciencies S 0.022 f )-(−)- Ru(

mm, depth of 0.5 of depth mm,

L h or theµ-reac t hν bpy) β or the batch −1 (468nm) -citronellol -citronellol . Under nonoptimized conditions, the desired product 2-cyclo λ 50 3 max Cl

S W) was used. The oxygen was fed tothe reactor counter cur (TDI, Scheme 3.19) was examined by Jähnisch et al. in a in al. et Jähnisch by 3.19)examined Scheme was (TDI, )-(−)- 2 = 468 = 47 , EtOH

λ mm length, 600 = 50–1600 with singlet oxygen yields a mixture of the peroxides peroxides of the a mixture yields oxygen singlet with tor β :

-citronellol. g). This study provedthat a falling-film microreactor

nm) with light intensities from 1 to 7.98to 1 fromintensities light with nm) 47

min. The progress of the reaction was monitoredthe The was reaction progress of min. mm, and a total volume of 270 ofvolume total a and mm, is used in the fragrance industry to produce to industry fragrance the in used is

nm) showed that Rose Bengal is about twice λ

μ OOH max 48 m width, and 300 CH 468 = 2 OH nm) with a light intensity of intensity light a with nm) + h, the ethanol solution h, of the ethanol 35,68,69

mL/min, thus creating a

μ m depth. A methanol The selective pho selective The OOH 49

μ L. The reaction The L. CH 2 67 OH ′ - tert

mW/cm -butyl- 30 63 2 ------. Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 SCHEME 3.19 SCHEME 64 exhaust air, exhaust (TiO dioxide titanium is of improve also the can One feature process. the ofselectivity this the most widely used heterogeneous photocatalyst and flow the by catalyst the from separated simply material is product The catalyst reagents. of and light interactions with maximizes subsequently and photocatalyst the of area surface nated illumi specific the increases consequently walls channel the on catalyst a of Immobilization reactions. catalytic in use for interesting especially are microreactors ratios, surface-to-volume large their to Due 3.3.3 a15 using selectivity monochlorination high with realized were successfully chloride sulfuryl with cycloalkanes various of reactions the Likewise, chlorine. molecular and light ral reactors. microflow core instead. aromatic at the place prefers totake and decreases derivatives chlorinated side-chain desired the of selectivity the result, low.a As very is it reactor the of center the at while high, is source light the near concentration radical the reactor, tional areIn avoided. a toconven leads which recombination, concentration, local andhigh volume film total arethe over located radicals thechlorine Also films. liquid and thinner the in rates photons mass-transfer of higher the penetration better the by explained was microreactor falling-film in reaction rination (1.3 reactor conventional to the compared higher reactor (401 in the microstructured the batch in reactor (54%)higher theFFMR tocompared (5%). yieldachieved nificantly The space–time (5Cl-TDI)by-product ring-chlorinated the to selectivity the addition, In conditions. batch 1Cl-TDI product target the for selectivity batch),the in toluene-2,4-diisocyanate of rates conversion similar At source. light a as lamp of formation FeCl by the explained was 67%iron, for this nickel) and and one ofthe iron. desired The product selectivity after 14 51 81% when the residence increasing from time 5 to 14 (5Cl-TDI)ene-5-chloro-2,4-diisocyanate kept at a temperature of 130°C to reduce the sideundesired reaction to product the ring chlorinated tolu (1000 0.12 (residence of 14 time 50 300 decreased somewhat from 80% to 67%. The yield of of yield 1Cl-TDI The 67%. to 80% from somewhat decreased (100 The experiments were carried out using a reaction plate with 32 parallel channels of 600 of channels parallel 32 with plate reaction a using out carried were experiments The Catalytic microphotoreactors have been particularly studied for the treatment of waste water and and water waste of treatment the for studied particularly been have microphotoreactors Catalytic various using cycloalkanes of photochlorination the studied have coworkers and Ryu Recently, mercury high-pressure a using flask glass the in out carried were reactions batch comparison, For

μ m depth, and 66 and depth, m

W, unfiltered) through the quartz window of the reactor. The backside of the reaction plate was plate reaction the of backside The reactor. the of window quartz the through W,unfiltered)

s. The effect of the reactor material was investigated by using different nickel plates, one reaction using by was investigated the reactor s. material The of effect mmol in 30 in mmol Reactions Catalytic TDI 50 NC CH 40,72–79 O 3 NC Photochlorination of toluene-2,4-diisocyanate. Photochlorination while synthetic applications are rather rare. rather are applications synthetic while O 70

mL of tetrachloroethane) was introduced to the reactor at flow rates ranging from ranging rates flow at reactor the to introduced was tetrachloroethane) of mL Monochlorination of cyclohexane to chlorocyclohexane was achieved using natu using achieved was to chlorocyclohexane of cyclohexane Monochlorination

mm length each. A relatively concentrated solution of toluene-2,4-diisocyanate toluene-2,4-diisocyanate of solution concentrated relatively A each. length mm + 2

). s) to 0.57 71 Cl 2 55% co 65% co

mL/min (residence of 5 mL/min time CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC T mol L etrachloroethane nve nve rsion in µ-reac in rsion 52 −1 rsion in batc hν h . Theconversion ofTDI −1 ) for the formation of product mol L 51

s, while the selectivity of productthe target s, 1Cl-TDIthe selectivity while h tor notablywas affected bythe plate material (50% for −1 51 h −1 was 80% under micro- and only 45% under under 45% only and micro- under 80% was ). The advanced performance of photochlo performance ). Theadvanced 1Cl- 51 NC CH

TDI s) and was irradiated by the xenon by the lamp s) irradiated was and 51 O 2 Cl improved from 24% after 5 after 24% from improved 50 NC 3 , which functions as a Lewis acid. a Lewis as functions , which drastically increased from increased 30% to drastically O + 51 W black light. W black was orders of magnitude Cl 50 (55% in FFMR, 65% FFMR, (55% in 5Cl- CH 52 NC TDI 3 O NC 52

μ m width, width, m O

was sig was s to 54% to s ------Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 The first application of a photocatalytic microsystem in organic synthesis has been reported by Takei Takei by reported been has synthesis organic in microsystem a photocatalytic of application first The 3.3.3.1 3.20 SCHEME Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry: 3.21 SCHEME 7.310of × volume of unit per areas face amine TiO the was example remarkable A arrays. UV-LED as such source and Matsushita al. by et Ichimura studied intensively been has reactors microstructured in photocatalysis Synthetic 3.3.3.2 eluted. is product the while microchannel the in remains photocatalyst immobilized the as step, separation the of exclusion the reactor is microstructured catalytic the of advantage significant A future. the in microreactors of up ing (4 cuvette batch volume of the larger the in the (2.8 microchip × 10 50% was e.e. and 22% 47%). and was (selectivity setup bulk and micro- the in similar were and time reaction of independent were parameters these that (e.e.)revealed excess enantiomeric and selectivity of Analysis 1 of compa (0.29 was setups both volume in rable solution the to area surface illuminated of ratio the that TiO notable is and It suspension. cuvette bulk a comprising system batch results The a HPLC. to by compared analyzed were was and outlet reactor the from collected was mixture product crude irradiations. at0.2 agent reducing as of a 100 diameter with and made was of particles as catalyst ing served wide and 3.5 of 700 channels branched One with substrate substrates. study was composed of glass this two Pyrex 53 al. et (0.86 min (Scheme 3.20) in a home-made microchip. The titania-modified microchannel chip (TMC) used in used (TMC) chip microchannel titania-modified The microchip. home-made a in 3.20) (Scheme This reaction was studied in three house-made quartz microreactors with specific illuminated sur illuminated specific with microreactors quartz house-made three in studied was reaction This for productivity the In contrast, 2 A l -lysine -lysine 80 The authors studied the photocatalytic synthesis of synthesis photocatalytic the studied authors The mM aqueous solution of solution aqueous mM 55 of Synthesis Photocatalytic Photocatalytic (Scheme 3.21). 53 min). In the batch experiment the same conversion rate of 86% was achieved only after 1 after only achieved was 86% of rate conversion same the experiment batch the In min). μ to m deep was fused to another substrate with m a to with deep 300 was substrate fused another 72,81 N Photocatalytic synthesis of synthesis Photocatalytic l -ethylation of benzylamine. -ethylation 55 -pipecolinic acid acid -pipecolinic In their work they used not only miniaturized reactors but also miniaturized light light miniaturized also but reactors miniaturized only not used they work their In H 2 wt%. A high-pressure mercury lamp with a UV transmitting filter was used for used was filter transmitting UV a with lamp mercury high-pressure A wt%. 85% yieldaf N NH −10 m 84.4% yieldaf n 2 2

mol/min) compared to the system (1.9bulk × 10 Amines of -Alkylation 0.25 and TMC for/mL the 53 l -lysine was pumped through the microchip at different flow rates. The rates. flow different at microchip the through pumped was -lysine hν l ter 150sinµ-reac P 54 (365nm) -PCA -PCA EtOH t/T 87% co C in the microchip reached 87% after a residence time of less than than less of time residence a after 87% reached microchip the in ter 4 h in batc OOH iO NH 3 mL), but this disadvantage may be overcome through number may overcomebe through mL),disadvantage but this l 86% co , 6.0 × 10× 6.0 , 2 l -pipecolinic acid. -pipecolinic 54 Acid -Pipecolinic 2 nv , that is, the amount produced much , amount was per the is, minute, that lower ersion af nv ersion af h 3 tor , and 4.0 × 10× 4.0 and , Pt Wa ter 0.86mininµ-reac /T hν m ter iO 56 ter 1 h in batc 2 2 /mL for suspended particles). The conversion The particles). for/mL suspended l -pipecolinic acid acid -pipecolinic N H nm thick coating of coating nm thick TiO 3 Et

m 2 2 /m -catalyzed N-ethylation of benzyl of N-ethylation -catalyzed h + N H nm. The film contained platinum platinum film contained Thenm. tor 3 2 , respectively. These large areas areas large These respectively. , 25 (diameter particles 54 −8 C OOH

54 mol/min). wasThis due to 57 (L-PCA) from from (L-PCA) N Et 2 Et . The TiO l nm) in in nm) -lysine -lysine 2 coat μ 65 m h. h. - - - - - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 of 11% and 36%, respectively, after a residence time of time 180 of 11% a residence after respectively, 36%, and yields in products N-ethylated weregave and corresponding tested the butylamine and Aniline amines. other of reactions alkylation for applied was ethanol Consequently, intermediate. radical ethoxy its of 85%150 after 55 9.8 of output power 2 40 and between 1 Pt-free).A and 1000 500 of width a with channels reactor in realized were 66 3.22 SCHEME 3.22) microreactors. in benzaldehyde of reduction photocatalytic the examined authors The al. et Matsushita by reported also been has transformation useful synthetically a of example Another 3.3.3.3 flowconditions. and irradiation of the control by precise the outcome that demonstrate be ofclearly can controlled (mono-results the reaction vs. bis-alkylation) (60 dence time product main of the formation time (5 residence At ashorter aniline. for noticed trendwas same The 3.8% yield. in detected also 6 62%of after yield a in obtained example, For model. described previously the to compared faster ceeded 490 10 × 25 wide, conditions. flow and tion conditions. batch under observed frequently is bis-alkylation contrast, In reaction. follow-up undesired the prevented which irradiation, monochromatic and mode continuous-flow the by achieved was This platinum. of absence or presence product N,N-dialkylated no and microreactors the in high was Selectivity num. to other studies, trast product N-alkylated of 98% to upof yields and platinum cocatalyst the to attributed was observation This ratio. surface-to-volume depth. illuminated increased channel decreasing with enhanced was N-alkylation could be converted in high selectivity to the N-alkylated product product N-alkylated to the selectivity high in be converted could Ethanol was found to be the most suitable solvent for this transformation due to the kinetic stability stability kinetic the to due transformation forthis solvent suitable most the be to found was Ethanol The authors further expanded their study on the N-alkylation of amines by optimizing the irradia the optimizing by amines of N-alkylation the on study their expanded further authors The without even photocatalyst, dioxide of titanium presence the in proceeded reaction this Remarkably, of efficiency the that showed and examined also was microchannel the of depth the of effect The mW). In this microsystem, the alkylation of amines (benzylamine, aniline, and piperidine) pro piperidine) and aniline, (benzylamine, amines of alkylation the microsystem, this In mW). 3 μ

m m, respectively. The sides and bottom of the channels were coated with TiO with coated were channels the of bottom and sides The respectively. m, 2 /m μ Microreactors in Reduction Photocatalytic 50 and deep, m 3 ahee ws raitd ih mr pwru LD ra (oa otcl oe output power optical (total array LED powerful more a with irradiated was achieved ) s, respectively. s, s), the formation of the tertiary amine amine s), of formation tertiary the the (a) Photocatalytic reduction of (a) benzaldehyde and (b) nitrotoluene. and of (a) reduction benzaldehyde Photocatalytic mM alcohol solution of benzylamine benzylamine of solution alcohol mM μ 58 11% yieldaf L/min and was irradiated with an UV-LED array ( UV-LED an array with irradiated was and L/min mW. The product solutions were analyzed by GC or HPLC methods. Benzylamine Benzylamine methods. HPLC or GC by analyzed were mW.solutions product The 82 O N-alkylation did presence the notunder batch of without conditions occur plati N-alkylation 83 mm long was developed. The high surface area of TiO of area surface high The developed. was long mm 500 microchannel a with system microreaction photocatalytic novel A hν TiO ter 1mininµ-reac (365nm) 2 56 , EtOH s, however, the bis-alkylated product product however, bis-alkylated s, the increased with increasing light intensity, whereas at a intensity, prolongedwhereas light resi increasing with increased CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC

tor 59 OH 57 ) (b μ 55 enhanced with increasing light intensity. These light increasing with enhanced 40 of length m, 60 NO 46% yieldaf was fed into the microreactors at a flow rate flow a at microreactors the into fed was s. 2 hν TiO ter 1 min in µ-reac in min 1 ter (365nm) 56 56 2 λ , EtOH 58 max were achieved after 90 after wereachieved in yields of 43% after just 90 of just 43% after yields in N mm, and depth of 300, 500, or 500, 300, of depth and mm, , and nitrotoluene nitrotoluene and N = 365 N -diethylbenzylamine -diethylbenzylamine

-ethylbenzylamine -ethylbenzylamine nm) with a total optical optical a total nm) with 57 2 /Pt photocatalyst (4.0 photocatalyst /Pt was obtained in the the in obtained was 2 tor catalyst (Pt-loaded catalyst 61 NH 2 60 s. In con In s. (Scheme 56 57 s), the was was was was s or μ m 84 - - - - -

Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 organic compounds. organic for of efficientreduction the be utilized can reactor microstructured that demonstrated they optimized, p alcohol benzyl yield of and solvent gave efficient a most the to be power outputof 1.4 cal ofwereside the a walls coated microchannel with TiO10 × 1.4 approximately of liquid of unit per area surface illuminated specific of500 amicrochannel contained These reactors Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry: 3.23 SCHEME ecin sides. on both coating and 250 of output power high-pressure 350from to range 400 wavelength emission a UV mercury Noblelight) (Heraeus with emitters source, light As solution. reaction the of film thin very a produces design The by aspacer, acreates from40separated gap which to glass 100 quartz two comprise ofparallel They ( sources light vidual topotecan. and irinotecan Compounds plant. this in formed 63b Heraeus. by ized real was plant microphotoreactor a using derivatives camptothecin of production industrial first The 3.3.4.1 for tool low-volume processes. synthesis ing devices. control and tion complex clusters requires using microreactor automa quantity in kilograms product synthesis contrast, and tend to generate In additionally a lifetime, systems. amount oflarge cooling heat and therefore additional require limited a have run, to costly are lamps conventional These industry. in used dominantly pre still are lamps mercury high-pressure and medium- reactions, photochemical for sources light as reactor of fabrication LEDs The of energy-efficient utilization glass. increased Despite the complicated. and costly is also quartz microchannels or steel stainless as such materials, expensive from made ally gener are Microreactors neglect. this for factors contributing several are There rare. still are scale trial achieved. have been synthesis gram-scale have earlier However,beenThe performed onscales. described laboratory reactions isolated examples of 3.3.4 -nitrotoluene Alcoholic Alcoholic solutions of benzaldehyde fabricated. were photocatalyst immobilized with microreactors quartz study,photocatalytic this For The productivity of the microreactor plant was evaluated using the amount amount of 10-hydroxycamptoth the using evaluated was plant microreactor the of The productivity indi by irradiated and parallel in operated microreactors twelve of consisted plant developed The it make in microreactors an interest the provensynthesis of photochemical advantages Nevertheless, rm camptothecin- from 63a Camptothecin- Industry in Microphotochemistry produced within 24 produced within 7-Alkyl-10-Hydroxycamptothecin and 10-Hydroxycamptothecin of Synthesis O N + O R – 62a,b 60 Synthesis of camptothecin derivatives. of camptothecin Synthesis 85 gave The synthesis of 10-hydroxycamptothecin of 10-hydroxycamptothecin synthesis The N N-o W were used. These lamps also comprised spectral filters with a specific band pass band specific a with filters spectral comprised also lamps These used. were W Figure 3.4 Figure xide p HO mW was employed as a light source. mW employedalight as was -toluidine -toluidine N -oxide -oxide O h. h. At conversion ofrate 95% of ). The microreactors themselves are characterized by their simple design. their simple design. by arecharacterized themselves ). microreactors The O 61 62a 63a in yields of in yields 46% 60 after DMF orDMF/1,4- r -ty camptothecin- 7-ethyl or 58 and and E = b: R H = a: R (0.1 hν 42,43,51 (350–400nm) 63b mM) mM) saturated with nitrogen were used. Ethanol was found t In contrast, photochemical processes realized on indus realized processes photochemical contrast, In are precursors in the synthesis of the anticancer drugs drugs anticancer the of synthesis the in precursors are μ m width, 100 m width, 2 kg/da dio 2 layer. An of array 365 xane y 62a s. Although the reactions were not further were the reactions not s. Although further 63a μ , the desired product desired , the m depth, m and 40 depth, 59 and 7-ethyl-10-hydroxycamptothecin 7-ethyl-10-hydroxycamptothecin and N HO -oxide -oxide of 11%60 after 62b 10-h nm nm UV-LEDs an opti with N O R Shm 32) a per was 3.23) (Scheme 4 ydro

m mm length with a total with mm length 2 /m xy s. Photoreduction of Photoreduction s. 63a,b camptothecin 63a 3 nm and an optical optical an and nm N . The bottom and bottom The . is produced in is produced in HO O O μ m. m. 67 ------Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 68 References also We support. and 2008-S-ET-2). discussions Werner (Heraeus) Dr. for useful and Silvia Peschl), (UV-Consulting Peschl (DEHLG, Günther (Quantapplic), Braun André Government Prof. chemtech), (mikroglas Local Dietrich Thomas Dr. and thank Heritage the Environment, and 2008-ET-MS-2-S2), of (EPA, Agency Department Protection Environmental the 07/RFP/CHEF817), (SFI, Ireland Foundation Science by provided was microphotochemistry on work our for support Financial Acknowledgments International Congress of Applied inNew York Chemistry in1912. future.” the of istry photochem new “the as emerge may microphotochemistry Consequently, potential. this demonstrates as a clearly The technology. production process Heraeus ern lead and ultimately development processes, mod in for example tool, R&D future important an as emerge will microphotochemistry that hoped is It applications. forphotocatalytic advantageous especially is microchannels the within ratio to-volume photonic largearea- The andwastes. efficiency, increased and reductionhazards of selectivity, enhanced reactions, side of elimination complete or reduction the in results This microtechnology. of condition andflow dimensions thesmall of advantage full takes technology The types. reaction of photochemical for a broad range used successfully have been reactors Microstructured tool. a synthesis as tochemistry micropho of potential and versatility the demonstrate clearly chapter this in presented examples The 3.4 array. (0.6 microsystem the in used solution 85% camptothecin- Moreover,a ofmuch the and oflower 50%. concentration yield product the an amount of 2 3.4 FIGURE This remarkable process represents the examplerepresentsThisprocess first remarkable of in production a photochemical microreactor a 2. 1.

technology, technology, Int. Ed B. Ahmed-Omer, J. C. Brandt, and T. Wirth, Advanced organic synthesis using microreactor microreactor using synthesis organic Advanced Wirth, T. and Brandt, C. J. Ahmed-Omer, B. K. Jähnisch, V. Hessel, H. Löwe, and M. Baerns, Chemistry in microstructured reactors, Concluding Remarks ., 2004,43,406–446. (See color insert.) color (See kg/day kg/day (yield 90%).conversion the batch reached of a system In contrast, maximum only Org. Biomol. Chem Biomol. Org. This statement Ciamician’s This Giacomo to refers lecture, beforepresentedthe visionary Photochemical production plant. (Courtesy of Heraeus.) (Courtesy plant. production Photochemical CRC Handbook of Organic Photochemistry and Photobiology and Photochemistry of Organic Handbook CRC ., 2007, 5, 733–740. 5, 2007, ., wt%) was six times higher than in the batch system (0.1 system batch the in than higher times six was wt%) 86 Ang. Chem., wt%). N -oxide -oxide - - - Downloaded By: 10.3.98.104 At: 03:12 30 Sep 2021; For: 9781466561250, chapter3, 10.1201/b12252-4 Flow Reactors Microstructured in Synthesis Photochemical Microphotochemistry:

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