Microreactors in Organic Chemistry and Catalysis, Second Edition (2013)
7. Heterogeneous Reactions
7.2. Immobilization of the Reagent/Catalyst
Unfortunately, the widely used flow reactors (for example, microreactors, multi-cell flow reactors, and disk reactors) do not tolerate solid particulates and precipitates, which would clog the miniaturized flow devices. Therefore, immobilization of the reagents/catalysts by a solid support is of significant importance in this field. Hence, a broad range of solid supports have been employed to incorporate the reagent/catalyst into the reactors, including packed-beds, monoliths, and other systems that exploit the high surface-to-volume areas obtained in microchannel devices.
7.2.1 A Packed-Bed Reactor
A packed (fixed)-bed reactor is the simplest and most conventional method for immobilization of the catalyst/reagent . A reaction solution passes over the retained reagent/catalyst particles in the packed-bed reactor. The chemical reaction takes place on the surface of the solid. The advantage of using a packed-bed reactor is the increased conversion per weight of catalyst compared with the corresponding batch reactions. These reactors show increased yield with lower amounts of by-products compared with the corresponding batch reactions. Packed-bed reactors are the most important type of reactor for the synthesis of large-scale basic chemicals and intermediates in industry.
A packed-bed reactor is a tubular vessel such as a column tube or a metallic cartridge in which the solid reagent/catalyst particles are randomly filled. The particles do not move with respect to a fixed reference frame. Micro- or nano-sized powder of a solid reagent/catalyst itself, such as metal or metal oxide, can be packed in the reactors. Polymer beads grafted with a reactive or catalytic moiety are also available. Silica gel (SiO2), alumina (Al2O3), perovskites (CaTiO3), activated carbon, and organic polymers are generally used as a solid phase. Recently, polyurea matrices and functionalized dendrimers have also been utilized in the flow reactions.
Several variations of packed-bed columns have been used in flow reactions, as shown in Figure 7.1 . (a) In an early stage of heterogeneous flow chemistry, gravity-fed packed-bed columns, similar to those used for silica gel chromatography, were mainly used. Typically, the column would have a sintered glass frit to retain the beads and a tap to control the flow. (b) An alternative arrangement is the overflow-type reactor, which allows easy heating or cooling of the flow reaction vessel. (c) This type is essentially the same as the others, except that the reagent/catalyst particles are fixed in a pressure-resistant cartridge. Thus, the substrate phase can be continuously passed through the reactor by using a pump despite the high pressure.
Figure 7.1 Schematic representation of the different types of packed-bed reactors.
Although packed-bed reactors are convenient and rather cheap to prepare, there are some potential drawbacks. One is the swelling of the solid phase. If the swelling properties significantly change as the reaction proceeds, the bed volume will be changed and may lead to distract the packed-bed reactor. Another major problem is the homogeneity of a solid packing. Grain particles of 50–100 μm size are used and randomly fixed in the vessel for the common packed-bed reactors. When packing is irregular, these fixed beds show uncontrolled fluid dynamics that result in various disadvantages from a chemical reaction engineering standpoint. The formation of localized hot spots and clogging zones would cause broad residence time distribution, which could result in low process efficiency and selectivity due to poorly controlled fluid dynamics.
7.2.2 Monolith Reactors
To overcome the drawbacks of packed beds, numerous groups have focused on the use of macroporous monoliths in flow systems [19, 20]. A monolith is defined by IUPAC as a shaped, fabricated, intractable article with a homogeneous microstructure that does not exhibit any structural components distinguishable by optical microscopy. In general, a monolith comprises a honeycomb-like ceramic structure, covered by a thin (<50 μm, ideally 2–10 μm for a flow reactor) layer of a continuous uniform porous support material, which is prepared by precipitation polymerization of a functionalized monomer. Due to the high void volumes made by the extensive number of small pores or channels within a monolithic reactor, the pressure drop is commonly low during the passage of a fluid [21, 22]. The polymer particles can only swell and shrink in the pore volume available. The reactive moieties are packed not onto a solid support but on the inner walls of the microreactor itself. This generally solves the issue of localized hot spots and clogging zones. In addition, a large contact area of a reagent/catalyst with a substrate can be achieved .
Organic materials based on polystyrene- or polyacrylate-based copolymers and inorganic materials based on silica gel, zeolites, or carbon are available for the preparation of monoliths. Recently, metal-organic frameworks (MOFs) have received much attention as a new-generation monolith. Among them, organic monoliths are the most popular solid phase for heterogeneous reagents/catalysts in a flow mode. Three important strategies for the preparation of polymer-based monolithic reactors are as follows.
1. Copolymerization of more than two monomers in the presence of porogens (Fréchet-type monoliths) [21–26].
2. Preparation of diblock copolymers in which a well-defined cylindrical and degradable polymer is embedded inside a second polymer followed by selective removal of the degradable polymer .
3. Polymerization of a monolithic polymeric phase wedged inside the microchannel pore system of an inert support such as glass and other preformed inorganic materials .
The third concept, the PASSflow (polymer-assisted solution phase synthesis) technique, was originally developed by Kunz and Kirshning and has been utilized in a variety of heterogeneous reactions under both batch and flow conditions. The monolith consists of a chemically functionalized and highly porous polymer–glass composite. This monolith was synthesized by precipitation polymerization of styrene and a functionalized vinylic monomer with 2,2′-azobis(2-methylpropionitrile) (AIBN) within porous glass rods. For example, functionalized monoliths bearing a quaternary ammonium moiety were prepared by treatment of copolymer that was prepared from vinylbenzyl chloride with styrene, with triethylamine. Various monoliths bearing a functional group such as sulfonic acid, amine, pyridine, and imidazole have been reported. As will be shown later, these materials can be utilized in the continuous-flow reactions.
Macklay, Ley, and coworkers reported a different process for the preparation of a flow multi-channel microreactor in which the internal wall was coated by palladium catalyst. The disc-shaped plastic micoreactors, termed microcapillary films (MCFs), contain 19 parallel microchannels, each with a mean internal diameter of 142 ± 10 μm. The material was prepared using a melt extrusion process from an ethylene-vinyl alcohol copolymer (EVOH) . Immobilization of palladium(0) on the wall surface inside the MCFs was performed by simple chemical deposition techniques (Scheme 7.3). The palladium-coated capillaries were used for transfer hydrogenation of ketones, imines, nitro compounds, alkenes, and alkynes with triethylsilane under flow conditions . Microcapillaries whose inside surfaces were coated with copper or gold were also utilized for the continuous-flow reactions .
Scheme 7.3 Wall surface functionalization of microcapillaries (EVOH-MCF) inside and schematic illustration of a wall-coated microcapillary.
Recently, magnetic nanoparticles have received attention as a new class of solid supports. Such particles, which consist of magnetic elements such as iron and nickel compounds, can be easily removed from a reaction mixture by applying an external magnetic field. In addition, the nanoparticles offer inductive heating of the reaction mixture in the presence of an electromagnetic field. Kirschning et al. reported continuous-flow reactions using a flow packed-bed reactor that was filled with magnetic nanoparticles (Fe2O3/Fe3O4) coated with silica gel (Scheme 7.4) [31, 32]. Their results suggested that inductive heating can be compared with microwave heating with respect to rate acceleration. They utilized functionalized silica-coated Fe2O3/Fe3O4 nanoparticles ligated to Pd(0) in flow hydrogenation and cross-coupling reactions.
Scheme 7.4 Unfunctionalized and functionalized magnetic nanoparticles, and a schematic illustration of the inductive heating-assisted microreactor.
The polymeric catalytic membrane is utilized for biphasic laminar flow synthesis. Uozumi and coworkers developed membrane-installed microflow devices, in which a self-assembled polymeric Pd nanoparticle membrane was installed, for several important chemical transformations. The polymer membrane was precipitated at the laminar interface between the two parallel flows (Scheme 7.5). There is no doubt that the vast interfacial surface of the catalytic membrane with substrates and reactants in the biphasic flows would improve the rate of chemical transformation. And in fact, Suzuki–Miyaura coupling , allylic arylation , and hydrodehalogenation  were achieved with significant efficiency by using the microflow devices with Pd-nanoparticle membranes installed.
Scheme 7.5 (a) Preparation of polymeric Pd-nanoparticle membrane-installed devices, (b) a catalytic biphasic reaction under laminar flow conditions, (c) Pd-cross-linking formation as a catalytic membrane.
Microreactors katika Organic Chemistry na Catalysis, Toleo la Pili (2013) 7. Heterogeneous athari 7.2. Kwa bahati mbaya, reactors mtiririko sana kutumika (kwa mfano, microreactors, multi-cell mtiririko reactors, na diski reactors) si kuvumilia chembe ngumu na precipitates, ambayo ingekuwa clog kifaa miniaturized mtiririko. Kwa hiyo, immobilization ya reagents / catalysts na msaada imara ni ya umuhimu mkubwa katika uwanja huu. Kwa hiyo, mbalimbali ya msaada imara wamekuwa kutumika kuingiza reagent-katalista katika reactors, ikiwa ni pamoja na packed-kitanda, monoliths, na mifumo mingine ambayo kutumia juu ya uso-kwa-kiasi maeneo kupatikana katika vifaa microchannel. 7.2.1 A packed-kitanda Reactor A packed (fasta) kitanda Reactor ni rahisi na zaidi ya kawaida mbinu kwa immobilization ya kichocheo-reagent. Suluhisho la athari hupita juu ya chembechembe zilizowekwa za reagent / catalyst katika kichocheo cha kitanda kilichofungwa. Mmenyuko wa kemikali hufanyika juu ya uso wa kitu kigumu. Faida ya kutumia packed-kitanda reactor ni kuongezeka kwa kubadilisha kwa uzito wa kichocheo ikilinganishwa na majibu yanayolingana ya kundi. Vituo hivi vinaonyesha uzalishaji ulioongezeka na kiasi kidogo cha bidhaa za chini ikilinganishwa na athari zinazolingana za kundi. Reactors packed-kitanda ni aina muhimu zaidi ya reactor kwa ajili ya synthesis ya kemikali ya msingi ya kiwango kikubwa na kati katika sekta. Reactor ya kitanda kilichofungwa ni chombo cha bomba kama vile bomba la safu au cartridge ya chuma ambayo chembe ngumu za reagent au catalyst zimejazwa kwa nasibu. Chembe hizo hazihami kuhusiana na mfumo wa kumbukumbu uliowekwa. Micro au nano-size poda ya reagent imara mwenyewe, kama vile chuma au chuma oksidi, inaweza kuwa packed katika reactors. Polima beads grafted na reactive au catalytic sehemu pia zinapatikana. Silika gel (SiO2), alumina (Al2O3), perovskites (CaTiO3), kaboni iliyoamilishwa, na polima za kikaboni hutumiwa kwa ujumla kama awamu ngumu. Hivi karibuni, matrix za polyurea na dendrimers za kazi pia zimetumiwa katika athari za mtiririko. Aina mbalimbali za nguzo za kitanda cha kuunganishwa zimetumika katika athari za mtiririko, kama inavyoonyeshwa katika Mchoro 7.1. (a) Katika hatua ya mapema ya heterogeneous mtiririko kemia, mvuto-kulishwa packed-kitanda nguzo, sawa na wale kutumika kwa silica gel chromatography, walikuwa hasa kutumika. Kwa kawaida, nguzo hiyo ingekuwa na friti ya kioo iliyochomwa ili kuhifadhi shanga na bomba la kudhibiti mtiririko. (b) Mpangilio mbadala ni reactor overflow-aina, ambayo inaruhusu rahisi joto au baridi ya mtiririko athari chombo. (c) Aina hii ni kimsingi sawa na wengine, ila kwamba reagent-catalytic chembe ni fasta katika cartridge shinikizo sugu. Hivyo, awamu substrate inaweza kuendelea kupita kupitia reactor kwa kutumia pampu licha ya shinikizo la juu. Picha ya 7.1: Mfano wa aina mbalimbali za nyenzo za kutengeneza mafuta. Ingawa mitambo ya kutengeneza nyuklia yenye vitambaa vingi ni rahisi na ni ya bei nafuu, kuna mambo fulani yasiyofaa. Moja ni uvimbe wa awamu thabiti. Kama swelling mali kwa kiasi kikubwa kubadilisha kama athari inaendelea, kiasi kitanda itakuwa iliyopita na inaweza kusababisha distract reactor packed-kitanda. Tatizo jingine kubwa ni homogeneity ya ufungaji imara. Chembechembe za chembechembe za ukubwa wa 50-100 μm hutumiwa na kuwekwa kwa nasibu katika chombo kwa ajili ya reactors ya kawaida ya kitanda kilichofungwa. Wakati kufunga ni isiyo ya kawaida, hizi vitanda fasta kuonyesha uncontrolled fluid dynamics kwamba kusababisha hasara mbalimbali kutoka kemikali athari uhandisi mtazamo. Kuundwa kwa maeneo ya moto na maeneo ya kuziba kusababisha usambazaji wa muda wa makazi, ambayo inaweza kusababisha ufanisi wa mchakato wa chini na uteuzi kutokana na nguvu za kioevu zisizodhibitiwa vizuri. 7.2.2 Monolithic Reactors: Ili kushinda mapungufu ya mabwawa ya pakiti, makundi mengi yamezingatia matumizi ya monoliths ya macroporous katika mifumo ya mtiririko. Monolith ni kifungu cha muundo wa kipekee, ambacho ni kipengele cha muundo wa kawaida, ambacho kina muundo wa kawaida, na ambacho hakionyeshi sehemu yoyote ya muundo inayoweza kutofautishwa na microscopy ya macho. Monolith ni muundo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo wa udongo. Kwa sababu ya kiasi cha juu cha utupu uliofanywa na idadi kubwa ya pores ndogo au njia ndani ya reactor monolithic, kushuka kwa shinikizo kwa kawaida ni chini wakati wa kupita kwa kioevu [21, 22]. Chembe za polima zinaweza tu kuvimba na kupungua katika kiasi cha pore kinachopatikana. Sehemu zenye kutenda hazipakwi kwenye nguzo thabiti bali kwenye kuta za ndani za kichocheo hicho. Hii kwa ujumla hutatua suala la maeneo ya moto ya mahali na maeneo ya kuziba. Aidha, eneo kubwa la mawasiliano ya reagent / catalyst na substrate inaweza kupatikana. Vifaa vya kikaboni kulingana na polystyrene- au polyacrylate-msingi copolymers na vifaa vya asilia kulingana na silica gel, zeolites, au kaboni zinapatikana kwa ajili ya maandalizi ya monoliths. Hivi karibuni, mifumo ya chuma-organiki (MOFs) imepokea umakini mwingi kama monolith ya kizazi kipya. Miongoni mwao, monoliths kikaboni ni awamu ya imara maarufu zaidi kwa reagents heterogeneous / catalysts katika hali ya mtiririko. Mikakati mitatu muhimu kwa ajili ya maandalizi ya polymer-msingi monolithic reactors ni kama ifuatavyo. 1. Uwe na mtazamo wa kweli Copolymerization ya monomers zaidi ya mbili katika uwepo wa porogens (Fréchet-aina monoliths) [2126]. 2. Uwezekano wa kupata Kupanga diblock copolymers ambayo vizuri-kufafanuliwa cylindrical na degradable polymer ni embedded ndani ya polymer pili ikifuatiwa na kuondolewa kwa kuchagua ya polymer degradable. 3. Uwe na mtazamo wa kweli Polymerization ya monolithic polymeric awamu wedged ndani ya microchannel pore mfumo wa inert msaada kama vile glasi na nyenzo nyingine preformed asilia. Utaratibu wa PASS (polymer-assisted solution phase synthesis) ulianzishwa na Kunz na Kirschning na umekuwa ukitumika katika athari mbalimbali za heterogeneous chini ya hali ya mchanganyiko na mtiririko. Monolith inajumuisha kemikali functionalized na porous sana polima <unk> kioo composite. Monolith hii ilitengenezwa kwa polimerization ya mvua ya styrene na monomer ya vinylic iliyofanya kazi na 2,2′-azobis (2-methylpropionitrile) (AIBN) ndani ya vijiti vya glasi. Kwa mfano, monoliths functionalized kubeba quaternary ammonium sehemu walikuwa tayari kwa matibabu ya copolymer kwamba ilikuwa tayari kutoka vinylbenzyl kloridi na styrene, na triethylamine. Monoliths mbalimbali kubeba kundi kazi kama vile asidi sulfonic, amine, pyridine, na imidazole wameripotiwa. Kama itakavyoonyeshwa baadaye, vifaa hivi vinaweza kutumiwa katika athari za mtiririko wa kuendelea. Macklay, Ley, na wenzake waliripoti mchakato tofauti kwa ajili ya maandalizi ya mtiririko multi-channel microreactor katika ambayo ukuta wa ndani ilikuwa coated na palladium kichocheo. Micro-reactors ya plastiki ya disk, inayoitwa filamu za microcapillary (MCFs), ina microchannels 19 sambamba, kila moja na kipenyo cha ndani cha 142 μm. Vifaa vilitengenezwa kwa kutumia mchakato wa extrusion ya kuyeyuka kutoka kwa copolymer ya etylene-vinyl pombe (EVOH). Imobilization ya palladium (p) juu ya uso wa ukuta ndani ya MCFs ilifanywa na mbinu rahisi za kuhifadhi kemikali (Scheme 7.3). Vipuli vilivyofunikwa na palladium vilitumiwa kwa uhamisho wa hidrojeni ya ketoni, imini, nitro compounds, alkenes, na alkynes na triethylsilane chini ya hali ya mtiririko. Microcapillaries ambayo nyuso za ndani zilikuwa zimefunikwa na shaba au dhahabu pia zilitumiwa kwa athari za mtiririko wa kuendelea. Mfano wa kioo cha juu cha EVOH (Evoh-MCF) ndani ya kioo na mchoro wa kioo cha chini cha kioo. Hivi majuzi, nanoparticles za sumaku zimepokea uangalifu kama darasa jipya la msaada thabiti. Chembe hizo, ambazo zina elementi za sumaku kama vile chuma na nikeli, zinaweza kuondolewa kwa urahisi kutoka kwa mchanganyiko wa athari kwa kutumia uwanja wa sumaku wa nje. Kwa kuongezea, nanoparticles kutoa inductive joto ya mchanganyiko wa athari katika uwepo wa uwanja wa umeme. Kirschning et al. Mzunguko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiririko wa mtiriririko wa mtiririko wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiririko wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa mtiriringo wa m Matokeo yao yalionyesha kwamba joto inductive inaweza kulinganishwa na microwave joto kuhusiana na kasi ya kasi. Kwa mfano, nanoparticles za Fe2O3 na Fe3O4 zilizopakwa silika, ambazo zinaunganishwa na Pd0, zinatumiwa katika mtiririko wa hidrojeni na athari za kuunganisha. Schematic 7.4: Unfunctionalized na functionalized magnetic nanoparticles, na schematic mfano wa inductive joto-msaidizi microreactor. Polymeric catalytic utando ni kutumika kwa ajili ya biphasic laminar mtiririko synthesis. Uzoumi na wenzake waliendeleza vifaa vya microflow vilivyowekwa kwenye utando, ambapo utando wa nanoparticle ya Pd ya polymeric uliwekwa, kwa mabadiliko kadhaa muhimu ya kemikali. Polymer utando ilikuwa precipitated katika laminar interface kati ya mbili mtiririko sambamba (Scheme 7.5). Hakuna shaka kwamba kubwa interfacial uso wa catalytic utando na substrates na reactants katika mtiririko biphasic ingekuwa kuboresha kiwango cha mabadiliko ya kemikali. Na kwa kweli, Suzuki <unk> Miyaura kuunganisha, allylic arylation, na hydrodehalogenation walikuwa mafanikio na ufanisi mkubwa kwa kutumia vifaa microflow na Pd-nanoparticle utando imewekwa. Pd-nanoparticle membrane-installed vifaa vya kutayarisha (a) catalytic biphasic reaction chini ya hali laminar mtiririko (c) Pd-cross-kuunganisha malezi kama membrane catalytic.