Continuous flow-microwave reactor: Where are we

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This is an author’s version published in: http://oatao.univ-toulouse.fr/20461

To cite this version : Estel, Lionel and Poux, Martine

and

Benamara, Nassima and Polaert, Isabelle Continuous

flow-microwave reactor: Where are we? (2017) Chemical Engineering

and Processing, 113. 56-64. ISSN 0255-2701

Official URL :

http://doi.org/10.1016/j.cep.2016.09.022

Continuous

flow-microwave

reactor:

Where

are

we?

Lionel

Estel

a,

_*

_,

_Martine

_Poux

b

_,

_Nassima

_Benamara

a

_,

_Isabelle

_Polaert

a

a_{LaboratoiredeSécuritédesProcédésChimiques(LSPC),INSARouen,NormandieUniversité,Saint-ÉtienneduRouvray,France} b_{LaboratoiredeGénieChimique,UniversitédeToulouse,CNRS,INPT,UPS,France}

Keywords:

Processintensification Continuousreactor Microwave

ABSTRACT

This article presentsthe different microwavecontinuousreactors existing, which are reportedin literaturetocarryoutchemicalsynthesiswithamoreefficientway.Itshowshowthemethodsandtools ofchemicalengineeringcanbeusefulandnecessarytodefine,characterizeandoptimizethemicrowave reactors. This review scans continuous microwave reactors, by describing the different types of microwavetechnologiesused(multimode,single-mode,coaxialorguidedtransmission ...).Itthen focusesonthevariousexistingreactorgeometriesandon thecontroloftheelectromagneticfield homogeneity.Theproblemoftemperaturemeasurementandoverallinstrumentationisalsoaddressed (inputpower,reflectedpower,continuousadaptation ...).

Thisreviewscansthemostefficientmicrowavecontinuousflowreactorsexistingintheliteratureand highlightshowthemicrowavetechnologyisusedaswellaschemicalengineeringtools.Itpointsoutthe reactorsgeometries,thecontroloftheelectromagneticfieldand themeasurementofthephysical parameters(Temperature,microwavepower,etc.).

Finally,thescale-upofcontinuous-flowmicrowavereactorsisexaminedthroughtheexistinglab-scale andsemiindustrialpilotplantsdescribedinliterature.

1. Introduction:towardscontinuousflowprocess

Sincetheapplicationofmicrowavestochemistrylaunchedby Gedye[1]andGuiguere[2]in1986,manyresearchersstudiedthe effectsofmicrowaveheatingonnumerouschemicalreactionsin batchsystems.Thenumberofarticlespublishedisvery impres-sive: more than 43,750 publications on MW-assisted reactions between 1986 and 2016! (Source Thomson Reuters, based on Scopus, keywords search on ‘microwave and reaction’). The enthusiasm ofthescientistsforthemicrowavesystemsremains alwaysstrongespeciallyinorganicsynthesis,extraction,polymer, biomass area. (respectively,19,700; 15,500; 10,800; 1050 pub-lications).

Themainbenefitsobtainedinchemistryconsistinanincrease the reaction rate, the reduction of the side-products, the improvement of the product purity compared to conventional heating.Chemistryundermicrowaveenablesthereductionofthe solventquantity,theuseofgreensolventsaswaterandsometimes synthesis underdrymediaconditionscanbecarriedout.These

advantageshavebeenlistedbymanyauthors[3–5]andmicrowave processesareknownnowasenvironmentallyfriendlyprocessand whichenablesenergysaving.

Themajorlimitofmicrowavesisthepenetrationdepthwhichis onlyafewcentimetresin usualsolventsand chemical environ-mentswithfavourablepropertiesthatexcludestheuseof high-volumereactors.

Couplingmicrowaveheatingandcontinuousflowtechnology eliminatesthemaindrawbacksofmicrowavesandcreatesavery promising way to produce highvalue added chemicals or key pharmaceuticalintermediatessinceunlikethebatch,the continu-ous_flowhasbeendemonstratedtofacilitateprocess intensifica-tionandcontributetoasafe,efficientandsustainableproduction

[1,4].

The _first systems coupling microwave and continuous _flow werestudiedinthe1980’sandconcernedthepolymerheatingand thesoliddrying[6,7].Inchemicalsynthesis,about780paperson thecontinuousreactorshavebeenpublishedsince30years,286 areinthe_fieldofmicrowave_flowchemistryand220dealswith microwavecontinuous reactorwhich described systems witha large range of size from some millimetres or less to some centimetres.Thecontinuous_flow undermicrowavesappearsin 1990’satthesametimethanflowchemistry.Thereactorconsisted * Correspondingauthor.

inaTefloncoilplacedinacommercialmicrowaveoven.Ithasbeen used for several organic syntheses, including preparative-scale samples,butthequantitiesremainsmallbecauseof thelimited volumeofthereactor(10mL!_).

In most papers published, theemphasis is onthe chemical reactionsandthepartdedicatedtothereactorconsistsgenerallyin abriefdescriptionofthesystems.Amongthe43,750articles,only 430 are identified in the area of chemical engineering that represents less than 1% of the papers! The percentage falls dramatically to 0,2% when using the key-words microwave; chemicalreactionandchemicalengineering.

Themainobjectiveofthisworkistopresentastateoftheartin theareaofthecontinuousmicrowavesystems,toprovideacritical analysis,tohighlighttheprocessparametersandtoproposesome toolsofchemicalengineeringusefulforthedevelopmentofmore efficientmicrowaveprocesses.

2. Aboutenergyandheating

Lightthatinteractswithmattercanbereflected,absorbedor transmitted,whereverabsorptionoccurs,heatenergyisgenerated. Aslight,microwavesareelectromagneticradiations(EMR),which aresynchronizedoscillationsoftheelectricandmagneticfields propagating at the speed of light through a vacuum. The oscillations of the two _fields are perpendicular to each other andperpendiculartothedirectionofenergyandwave propaga-tion,formingatransversewave.

Theenergyofthewaveisstoredintheelectricandmagnetic fields.Inthequantumtheoryofelectromagnetism, electromag-netic microwave radiations consist of photons, the elementary particlesresponsibleforallelectromagneticinteractions.

The quantum energy of microwave photons is in the range 0.000001to0.001eV(300MHzto300GHz)whichisintherange ofenergiesseparatingthequantumstatesofmolecularrotation andtorsion.Sincethequantumenergiesareamilliontimeslower than those of X-rays, they cannot produce ionization and the characteristictypesofradiationdamageassociatedwithionizing radiation.Theyalsocannotplayaroleinchemicalbondingwhere quantumenergyisatleastathousandtimesbigger.

Microwave heating is based on the electromagnetic energy conversionwhich requiresthe existenceof a direct interaction betweenthebulkandthemicrowavesandasufficientpenetration depth. For a givenfrequency, this interactionexistsonly ifthe dielectricpropertiesofthebulkaresuitable.Thelatterarevery sensitive toany change in composition or in temperature. The energy conversion can be due to several mechanisms such as dipolarpolarization,ionicconduction, Wagnereffect... Inthe caseof dielectricsystem heating,dipolarpolarization andionic conductionarethemostfrequentlyencounteredphenomena.Even withoutchemicalreaction,thespecificityofmicrowaveheating, resultsfromthetemperaturedependenceofdielectricproperties (Fig.1).Inmanycases,thecomplexdielectricpermittivitydepends on the temperature and the dynamic behaviour of microwave heatingisthengovernedbythisthermalchange[8].

Itisimportanttospecifythatforcontinuousflowapplications, thedielectricandthermalproperties,inthereactionvolumeare bothspatiallyandtemporallyvariable.Forexample,Fig.2shows the behaviour of dielectric properties during the reaction of decompositioninisothermalmode(89!_C)ofAIBN[2,20

-Azobis(2-methylproprionitrile)] in TMSN [Tetramethylsuccinonitrile] (Scheme1)[9].

Ontopofthatvariabilityofthepropertiesisnottheonlykey factor,foragoodcouplingoftheelectromagnetic_fieldwiththe medium.Thevalueitselfofthedielectricpropertiesisimportant, since the electric field propagation and amplitude depend respectively on the real and imaginary part of the dielectric

permittivity.Forexample,thehighertherealpartofthedielectric permittivity is, the more important reflexions are. For liquid mediumwitha priorifavourable properties,likewaterorionic solvents, when the imaginary part is propitious for heating, important reflexionscan dramaticallydecreasethe electromag-neticfieldintensityandtherebytheoverallefficiencyoftheenergy conversion.Whendipolarpolarizationisthemainphenomenon, dielectricheatinginvolvesunorganizedmovementsatmicroscale duetotheinabilityofmoleculeclusterstomoveexactlywiththe electric _field. This hysteresis phenomenon explains how the organised energy of electromagnetic _field is transferred as Brownianmovementintomatter,manyauthorscallthis phenom-enon“internalfriction”[10].Thecharacteristictimescaleofthis conversion issomepicoseconds[11],i.e. veryfastcompared to thermaldiffusionwhichisaroundsomeseconds.

Forthosereasons,itisexpectedthatahomogeneouselectric fieldgivesanisothermalmedium,whereasforfastheatingrates, classicthermaltransfersneedhighthermalgradientsatthesystem walls(Fig.3).Infact,thisabsenceofthermalboundarylayeratthe wall – sometimes called inversion of the thermal gradient comparedwithconventionalheating(whenthewallsarecolder thanthebulk)–givestheabilitytoraisetheheatsourceforfast homogeneousheating. Attheopposite,inhomogeneous electro-magneticfieldsproducelocalhighthermalgradientscalled“hot spots”.

Many surveys have shown that rapid heating and enhance-mentsofchemicalyieldsareachievedwithmicrowaves[12–15].In solidchemistryandinheterogeneoussolid-liquidsystems,many experiments led to significant differences in reaction rates obtainedbetweenconventionalandmicrowaveheating.Ifatleast oneofthecomponentsofareactionmixturecouplesverystrongly withmicrowaves,thenitispossibletousethatpropertytorapidly heat thereactionmixtureand therebyobtainthe _final product morequicklyandsometimeswithabetteryield.Inthespecialcase ofheterogeneousreactionswithsolidphaseoringeneralwhen dielectric propertiesincrease withcompositionor temperature, the absorption rate of microwave energy also increases,hence thermal runaway can result; at the opposite when properties decreasethe system isself-regulated. Consequently, controlling heatingrateandelectromagneticfieldhomogeneityareessential for both repeatabilityand industrial applications. Therefore, to achievetheseobjectives,onekeystepisthemeasurementofthe dielectric properties and another is the modelling of the electromagneticfield.

For temperature and power control feedback, in a running process, one major problem results in the temperature Fig.1.Frequencyandtemperaturedependenceofdielectricproperties ofNaX zeolites[8].

measurement, since direct measurement under microwave is ratherdelicate.Theintroductionofametallicconductorinacavity caninterferewiththeelectromagnetic_fieldandgenerateantenna effects.Thus,temperaturemeasurementisveryoftencarriedout withfiberopticorIRsensorswhichrespectivelyprovidelocaland surface temperature. As discussed earlier, the heating of the reactorwallcanbeduetothethermaldiffusionfromthebulkorto aspecificinternalheatsourcedependingonwhetherthereactor wallsaretransparentornotformicrowaves.Thusintransient,IR sensorswillgiveaninaccuratevalueofthebulktemperature.The temperatureknowledgeisthefirststepinamicrowaveheating study,sincesuchastudyinvolvessolvingMaxwell’sequationsof electromagnetism and the heat conduction equation, as told before,whereallthermal,electricandmagneticpropertiesofthe materialarenon-linearlydependentonthetemperature.

3. Microwavecontinuousflowsystems:focusonthedesignof reactors

The easiestand most rapid wayto builda continuous flow microwavereactoratthelaboratoryscalewas tomodifyand to adaptsomeexistingsystemssuchasdomesticovens,multimode and single-mode microwave apparatus, firstly developed for a batchuse.Theresultsofthesechemicalsynthesiscarriedoutin suchreactorshavetobeconsideredasdemonstrativeexamples only;becauseofthenon-controlofthemainparametersgoverning the microwave heating and the flow, the results are almost dependingofthe systemusedand thereproducibility becomes difficultandquiteimpossible.

The reactors were designed according to the chemical applications; in most cases, they consist in a simple tube implementedinto themicrowave cavity. The diameterand the lengthofthechannelseemtobeselectedarbitrarilyandtheflow rateischoseninordertoobtaintherighttimeresidenceinrelation with thekinetics of the reaction. The hydrodynamics was not generallyconsideredas a parameter which couldinfluence the reactionrate.

Thus,thediameterofthechannels–madegenerallyinquartz orTeflon–couldvaryintherangeoffewhundredmicrometresto somecentimetresandthelengthbetweensomecentimetres to few dozen centimetres. In this last case, the channel consists generallyin a coil togeta compact design and tofacilitateits implementationintothemicrowavecavity.Thereactorcouldbe placedintomultimodecavitiesaswellasinsinglemodecavities operatingat2.45GHz.

3.1.Thecontinuousflowsystems:asolutiontoscale-upmicrowave batchreactors

Thedevelopmentofcontinuousflowsystemswasfirstinitiated with the aim topropose solutions to increase the quantity of production,toprovethatscale-upoftheprocessispossibleandto demonstrate that the synthesis under microwave could be integratedtoindustry.

Thefirstexperimentswerecarriedoutintolargepipereactors (diameters more than a centimetre) simply introduced into commercialmicrowaveovens.Thus,thepowerofthemicrowave generatorcouldreach1.7kWaccordingthesystems,thepressure Fig.2.Behaviourofelectricalpropertiesinisothermalmodeat89!_C[9].

N N

CN CN CN CN

Scheme1.ThermaldecompositionofAIBN.

until30bar,temperatureuntil240!_{Candtherangeoftheflowrate}

from1L/hto20L/h.

Toachieveheterogeneousaswellashomogeneousreactionsin ascaleofdozengrams,alargemicrowavecontinuous-flowrecycle reactorbased on a modified Maxidigest 350(Prolabo), using a 66mL quartz glass cylinder reactor was specially designed for carrying out solid-liquid reactions [16]. The reaction mixture entersupflowfromthebottombyapistonpumpwithvariable flowratesbetween30and335mL/minforresidencetimesof12s to2min.Thesystemcouldoperateinopenorclosedloopmode. Acontinuousflowfixedbedreactorwasinsertedhorizontally intoalargemicrowavemultimodeoven[17].Thereactor,aPyrex glasstubewith1.07cmi.dand39cmlength,wasstuffedwiththe catalyst,astronglyacidiccation-exchangeresin,andtestedwith two reactions (hydrolysis of sucrose, the homogeneous and heterogeneous esterification of benzoic acid with ethanol) at 140!_{Cand7barwithflowrateof1L/h[17,18].}

Manyflow reactorsarecommerciallyavailabletoscaleupin microwave process chemistry such as Milestone FlowSYNTH reactorwhichcanoperate underpressure(30bar).Itconsistsof a200mLPTFEtubeplacedverticallyinamicrowavemultimode cavity(upto1600W).Moseleyandco-workers[19–21]reported sixhomogeneousreactionsinvestigated(OrthoClaisen Rearrange-ment, Naphthofuran Formation, Heck Reaction, Nucleophilic AromaticSubstitution Reaction)successfully carried out in this systemwithproductionratesbetween1and6L/h.

Toscaleupchemicalsynthesistokilogramscale,apilotplant microwavereactorwasbuiltbyMLSGmbH(ETHOSPILOT4000)

[22]. The system consistsin a verticaltubularreactor of0.88L (700mm length) placed on a multimode microwave cavity equippedwithfourmagnetronsthatdeliveramicrowavepower up to 200W and two truncated pyramids mode stirrers. This systemcanoperatewithapressureupto60barand240!_Cwith

flowratesbetween0.2–20L/h[22,23].FourIRsensorsandtwo Ni-Cr/Nithermocouplesareusedtorecordthetemperature respec-tivelyalong the tubular reactorand at theoutput of both the reactorandthecooler.Theesterificationoflinaloolwasperformed inthisETHOSPILOT4000ata25kgscalewith2.2L/h_flowrate

[24].

AninterestingapparatuswasintroducedbyMorschhäuseretal. abletooperatesafelyathightemperature/pressure(310!_C/60bar)

witha production onan industrial scale (up to20L/h)[25]. It consistsinacylindricalreactor(75cm#1cmi.d)madeof

g

-Al2O3,

transparenttomicrowavesinsertedintoasinglemodecylindrical waveguide.Thisreactorhasbeenvalidatedasasafeandenergy efficient instrument using four chemical transformations with flowratesof3.5–6.0L/h.

Inserts(helicalcoil)madeofPTFEimpregnatedwithcarboneC/ PTFEwereaddedintoaglasstubecontinuousmicrowavereactor located into a microwave single mode unit (Biotage) to assist heatingmicrowavelow-absorbantsolvantsandtoincreasemixing

[26].AwindowinthemicrowavecavitypermitstheuseofanIR cameratorecordthesurfacetemperatureofthereactor.Chemical reactionswereconductedinlow-microwave-absorbantsolvantsas theradicalallylationofaniodolactoneincarbontetrachloride.A 78%yieldwasachieved(at100!_{Cand6bar)howevertherewasa}

temperaturegradientfromthecentertothesurfaceofthereactor ($6–9!_C).

Inordertoincreasetheproductionto1kg/day,theconceptof parallelization of reactors was followed. A multitubular milli-reactor/heatexchangerconsistingofacylindricalframe(1.2cmi.d and13.7cmlength)containingsevenquartztubes(166mmlength, 2mmi.d)wasdeveloped.Fiberopticsensorswereusedtomeasure thetemperature of thereactionmixtureand thecoolingliquid

[27].Thissystemwastestedsuccessfullyontheproductionof 1,3-diphenyl-2-propynyl piperidine catalyzed by Cu that has been

depositedontheinnerwallsofthetubes.Theenergyuniformityin the tubular reactors was studied by measuring the microwave powerabsorbedbyeachtube_filledwithaspecifiedsolvent.This systemwasconceivedfollowingapreviousstudythathighlighted the importance of the design of both the reactor and the microwaveequipmenttoachieveagoodperformance[28]. 3.2.Continuousflowsystems:towardsthereactorminiaturization

Coupling microwave heating and micro-reactors is a very promisingapproachfromthepointofviewprocessintensification. Many systems have been developed since few years involving micro or milli-channels with diameters from some hundred micrometrestomorecurrentlysomemillimetres.

Generally, the running conditions require a flow rate range (110mL/h) inferior than those used for channels with large diameter.Themicrowavepowerisalsoinferior(generallyabout 10–100Wmax).Insomeoftheproposedsystems,pressurecould reach70barandtemperature,450!_C.

3.2.1.Narrowchannels

Inthesefollowingstudies,themicroreactorsaregenellaryused as demontrative toolsfor chemical reactionsunder microwave irradiation. Because of the small channels diameter, they are limitedtosomemilligramsofproduct.

In2003,aglassmicro-reactor(fromMicroChemicalSystems) implementedintoacommercialsinglemodesynthesizer (Discov-er-CEM) has been used to perform the Suzuki cross-coupling reactionusingthecontrolledlocalizedheatingofaPd-supported catalyst.The temperatureat thebaseof the micro-reactorwas measuredwithanIRsensorplacedinthebottomofthecavity.The rateconversionoftheSuzukireactionswasaround50–99%witha residencetimelessthan60sandamicrowavepowerof5–7W.On thesamebasisasthepreviousreactor,theauthorsproposedin 2004anewmicro_flowcellbasedontheprincipleofheatinglocally thecatalyst.TheflowcellwasaUglassflowcapillaryreactorwith aninternaldiameterof800

m

m,and138mmlong,coatedwitha gold_film atthe baseof thereactortopromotethe microwave heating.Theauthorsfoundthatheatabsorbedbythethinlayerof goldmetalincreasedthereactionrateandproductyieldknowing thatthecontactbetweenthecatalystandthereactantswasless than60s[29].

In the system described by Jachuck et al. [30], the reaction vesselisdividedintotwosections:amicrowavetransparentPTFE section where the reactionchannel (270

m

L) is located and an aluminumsectionsheltering,thecoolingmicrochannel(600

m

L). Thereactorwastestedfortheoxidationofbenzylalcoholwith_flow ratesof 1–5mL/mincorrespondingtoresidencetimesof3–17s under different microwave intensities (0–39W). An optimal conditionforthisreactionwasdeterminedandtheauthorsstate thatthisreactorhasawiderankofimplications.

Singleandmulti-parallelcapillaryflowreactorswereusedto performmicrowaveorganicsynthesisinacommercialmicrowave synthesizer[31,32].Thefirstonewasasingleglasscapillarytube attachedtoastainlesssteelmixingchamberwiththreeinletports and locatedintothecommercialsingle-modemicrowavecavity (BiotageSmithCreatorSynthesizer).Asetofcapillarytubeswas usedwitharangeofinternaldiameterbetween200and1150

m

m tocarryoutsyntheseswithvariableflowratesof2–40

m

L/minto obtaintheresidencetimeneededforreaction.Crosscouplingand ring-closingmetathesiswithmetalcatalysts,nucleophilic aromat-icsubstitutionandheterogeneousWittigreactionswerecarried out.Itwaspointedthattheconversionratewasdependentofmany parameters, such as flow rate, the internal diameter of the capillary,thepowerlevel,etc.Ontheconceptofnumberingup,a flowmulti-reactorsystemcomposedoffourcapillarytubeswasset

outtoimplementparallelreactionsatamilligramscalebasedon thepreviousdevelopedreactor.

3.2.2.Straightmillireactors

Inordertooperateathightemperatures,abackpressuresystem hasbeen introducedintoa microwavecontinuous_flow tubular reactor in order so as to conduct high temperature/pressure reactionswitheitherpolarornotpolarreactionmixtures[33,34]. Thesystemconsistsinacylindricaltube(1.75mmi.dand17cm length) positioned vertically at the end of thewaveguide of a modifiedBiotageInitiatorSynthesizer.Thereactorvolumeinthe hotzoneis103.4

m

Landisoperatingathightemperature/pressure uptoatleast73barand450!_{Cwithflowratesupto1mL/min.The}

efficiencyofthereactorwasevaluatedbyusingtworeactionswith high transition-statebarriers(Claisenrearrangement and benz-imidazolesynthesis).

Whenthe loadtobe heatedis stronglyabsorbentof micro-waves, it becomes difficult to control the heating, especially knowing that the permittivity varies during the course of the reaction.Onewaytoovercomethisproblemconsistsinusinga milli-reactor/heatexchanger[35].Thereactorwasaquartztubular reactor(3mmi.d)putinashell(7mmi.d)whereacoolant_flow (toluene)toavoid theoverheatingof thereactionmixture.The dimensions of thereactorweredefined aftera study basedon simulations performedwithCOMSOL Multiphysics. In a second step, thesimulation oftheelectromagnetic field and theliquid circulationwasdoneshowingthatthetemperatureprofilesinthe reactorarehighlydependingonthevelocityoftheliquidespecially onmillimetersizesreactors.Besidesabuoyancyeffectduetothe horizontalpositionofthereactor,stagnantlayerswereformedat thereactorwallsbecausethe_flowinthereactorwasratherlaminar

[36].

A tube made of quartz with a variable inner diameter (4– 11mm)putverticallyinasingle-modecavity(SAIREM)wasused as reactor at _flow rates between 15 and 100mL/min. The microwaveenergyabsorbedwascalculatedbyanindirectmanner bya heatbalanceonthereactorassumingheatlossisdoneby naturalconvection.Theheatingefficiencyincreasedlinearlywith theloaddiameterreachingamaximumof78%andwasrestricted bythepropagationdiameter.Thetemperaturedoesnotincrease uniformlythroughouttheaxialdirectionoftheloadsuggestingthe presenceofnon-uniformelectromagneticfieldintensity[28].

The placement of several microwave single-mode cavities serially connected all, to only one generator has been also investigatedforscale-upthemicrowavecontinuousflowsynthesis inasingle-modecavity[37].

Operatingatelevatedpressuresupto100bar,areactionvessel – a cylindrical quartz tube (1.5mm i.d, 100mm length) was introducedintoacylindricalsingle-modecavity(TM10)[38].The temperaturerecordedusingaradiationthermometerismonitored byaresonancefrequencyauto-trackingfunction.Thereactorwas successfully testedwithacontinuoussynthesisofcopper nano-particles, operating at elevated temperature and pressure increasesthereactionratetherebyenhanceproductionscale.

Toperformheterogeneousreactions,thesynthesisofCuInSe2 nanocrystals,atubularmicrowavesegmented_flowreactor(PTFE tubeof1.59mmi.d)wasimplementedintoasinglemodecavity, connectedtoperistalticpumpsthroughaT-mixer[39].Toprevent thedepositionofnanocrystalsonthewallofthereactorhencethe riskofsparking,astreamofsegmentedgas-liquidallowsbetter mixing of the heteregeneous medium. The use of microwave heating combined with flow technology resulted into the synthesisofhighqualitynanoparticlesinashorttimeandata lowercost.

Toincreasetheelectricfielddensityandtogetanhomogeneous temperature within a microwave continuous _flow reactor, a

particular riged waveguide optimized was developed [40]. The systemconsistsinanaxialridgedwaveguide(aridgeof4mmi.d) withaTE10modewhereonetoseveralverticalPTFEtubeswith

differentinternaldiameterswereputtroughtit.COMSOL Multi-physicswasusedasasimulationtooltocalculatetheelectricfield distribution.Theauthorsthenselectedtwomodelsofthereactors implementation as being the most efficient for a temperature between0and40!_C.

3.2.3.Coilmillireactors

Thecoilreactorwasdesignedtomakethebestuseofthecavity small spaceand maximize thereaction time by increasing the reactorlength.

Asetof26reactionsperformedinamicrowavecontinuousflow systemcomposedofaquartzorTefloncoil(atubingof3mmi.d, and3minlength)placedinamicrowaveovenwasreportedasone ofthefirstimplementationofmicrowavecontinuousflow[41,42]. A simple concept that operates at 200!_{C, under a pressure of}

140bar,witha_flowrateof15mL/minandoffersaresidencetimeof 1–2min. In the same way, early in 1990, Chen et al. [43,44]

reportedamicrowavecontinuousflowsystemtocarryoutsafely chemicalreactionsonascalehigherthan20g.Thereactionvessel wasaTefloncoilofabout10mLplacedinamodifiedcommercial microwavemultimodeovenandfedwithanHPLCstandardpump. Five reactions(esterification, racemization,hydrolysis, substitu-tionand cyclization)weresuccessfullycarriedoutatmorethan 20gscaleinthisreactor.

Anisothermalcontinuous_flow reactor,20mm diametercoil madeofquartz(3mmi.d)envelopedwithaPTFEheatexchanger insertedinasinglemodecavitywaspresentedbyMatsuzawaetal.

[45].Fiber-opticprobeswereusedtorecordthetemperatureat differentpointsofthereactor.Tooptimizethedesignofthereactor and the applicator for a better efficiency, experiments and simulations wereperformed todetermine theinfluence of the materialsformingthereactorandthevelocityoftheliquidsonthe temperature.TheSuzuki-Miyauracouplingsynthesiswasusedto evaluatethereactorperformances.

A_flowcellcoilwasalsousedinordertosafelyscaleupcertain chemicalreactionstomultigramquantitiesinacommercial single-modecavity(EmrysSynthesizer)[46].Itconsistsofaborosilicate glassprotectivewrap(100mm#10mm)containingaborosilicate glasscoil (i.d.3mm)with a totalvolume of 4mL.A varietyof reactionsatflowratesbetween0.25–1mL/minweresuccessfully scaleduptoequalorhigher yieldswhencompared withthose obtained under conventional heating (aromatic nucleophilic substitution,esterification,andtheSuzukicross-coupling). 4. Characterizationofmicrowavescontinuous-flowsystems 4.1.Temperaturemeasurement,powermeasurement,electromagnetic field

The knowledge of the temperature is a key data, which is essentialinanyprocessundermicrowavefirstbecauseitallows maintaining a constant temperature inside the system by regulatingoftheincidentpoweroftheMWgenerator.Inchemical flowsynthesis,temperaturebecomesacontrolparameterofthe processandthechoiceofitslocationintothesystemiscrucial. Temperaturemeasurementcanbecarriedoutintothesystemby implementingsomespecificsensors.Ithasbeenshowninprevious workthatinternalsensorssuchasopticalfibersarepreferredto externalsystemsuchasinfraredprobe[47]becausetheygivea valueofthemediumtemperatureinsteadofawalltemperature. Note that in the literature, many enhancements in chemical reactionshave been reportedas a microwave effect, which, in reality,wereonlyduetoawrongtemperaturemeasurement.

The measurement of the absorbed power is also a crucial parameter which could berealized indirectlyby implementing bolometers(seeFig.4).Fromenergyefficiency,generallysystems runcorrectlywhena minimumof75%oftheincidentpoweris absorbed.

Localtemperatureandpowercanbeeasilymeasuredbutsome essentialinformation like theelectromagneticfielddistribution cannot be obtained experimentally. The calculation of the electromagnetic field distribution inside the channel provides information abouttheenergy distributionandthe temperature profile. Theycouldbe determinedusing commercialnumerical codessuchasCOMSOL,Quickwave,ANSYS... Theyareallbased ontheresolutionofMaxwell’sequations.Theinputdatainclude theelectromagneticpropertiesandthephysicalpropertiesofthe fluidandtheirvariationwithtemperature,thedimensionsofthe microwavecavityandtheincidentpower.

Electromagnetic_fieldpatternsareusefultoanalysehowthe energyisdissipatedintothematerial,andallowstoverifyifthe sampletoheat islocatedcorrectlyintothecavity,ataposition wheretheelectricfieldreachitsmaximum(Fig.5).Information abouttheabsorbedpowerisalsoavailable.

Fig.6 shows howa temperature sensor (here anoptic fiber introducedin a glass steelsleeve) caninteract and modifythe temperatureprofileintothereactorevenifthesensorisnotmuch sensibletothemicrowaves.Recently,thiseffectwasalsodescribed in [36] showing that any inside element could disturb the temperaturedistributionbydisturbingthe_flowpattern.

4.2.Hydrodynamiccharacterization 4.2.1.Flowregimeandmixing

The flowregime and themixing are twomain points tobe considered in order to increase the performances in terms of reaction rate, conversion and selectivity and to get more reproducibilitybetweenthereactions.Theflowregimedeveloped into the channel could be laminar or turbulent depending essentially on the _flow rate as the operating parameter. For Reynoldsnumbersinferiorto2300,theflowregimeislaminarand thevelocityprofileintothechannelbecomesparabolicwhenthe flow is fully developed which is not very suitable to getgood mixing(Fig.7).Thiscouldbeimprovedbyusingchannelswith specialgeometrieswherethedisturbancescreatedintotheliquid flowenhancetheradialmovement.Fig.7showstheinfluenceof thechannelshapeonthehydrodynamics;comparedtoastraight channel,thestreamlinesinacorrugatedchannelarenotparallelto Fig.4.Abolometertomeasureindirectlytheabsorbedmicrowavepower.

Fig.5.Simulationoftheelectricfieldintensityinthewaveguide[45].

Fig. 6.Modification of the temperature profile by the implementation of a temperaturesensor[48].

theflowaxisatthebendlevel.Thestreamlinescrossovereach other, indicating the fluid particles are being mixed in the tangential directionand a significantsecondary_flow isformed, whichisabletoprovidemixingcomparedwithaflowinastraight channel. Thissecondaryflow calledDeanvorticesis due tothe centrifugal forceencountered at thebend and tothe pressure gradientwhichgeneratecounter-rotatingvorticesinthechannel cross-section(Fig.8).

Mixing could be also improved by using microstructured channelswithspecialinternalstriations[49].

TurbulencecouldalsopromotemixingwhenRenumbersare higherthan104_{.Manystudiesbasedonexperimental}

measure-mentbyLasertechniquesandonCDFsimulationsreportonthe designofthechannelsandtheirimpactonflowfield[50].

In continuous-flow microwave systems, the length of the tubular reactor is generally _fixed and the _flow rate is often adaptedaccordingtothekineticsofthereaction.Acompromise betweenthevelocity(i.e.flowrate)andthetimeresidencehasto befound.Thegeometryof thechannelisgenerallyverysimple and often reduced to a simple tube. It is obvious that better reactionratesandconversioncouldbeobtainedifhydrodynamics isre-examined.

4.2.2.Pressuredrop

Thepressureofaliquidflowingintoachanneldecreasesdueto frictionbetweentheinteriorwallsofthechannelandthemoving fluid. An understanding of the pressure loss is essential in continuous flow reactors; it depends on the fluid velocity, the fluid characteristics and the geometry of the channel. The calculation of the pressure drop

D

P (Pa) involves the Fanning frictionfactor,f(%),whichrepresentstheratiobetweenthelocal shearstressandthelocalflowkineticenergydensityandwhichis function of the roughness of the channel and the level of turbulencewithintheliquidflow(Reynoldsnumber).Thepressure dropcanbecalculatedby:

D

P¼2f

r

u2_ReL

h

whereReh¼rudh

m ,Reynoldsnumber(%)

withuthefluidvelocity(ms%1_{);Lthechannellength(m);}

_r

_the

fluiddensity(kgm%3_);d

hthehydraulicdiameter(m);

m

thefluid

dynamicviscosity(Pas)

TheFanningfactorisdependingalsoonthegeometryof the channels.Itiswellknownthatforacylindricalchannel,itsvalueis 16/Reinlaminarflow.Moreauetal.[51]havereportedsomevalues oftheFanningfactorfordifferentmilli-structuredreactors. Fig.7. Streamlinesinacurvedreactor(Ansys-CFX)atRe:194.

Fig.8. (left)AxialvelocityprofileinthestraightregionandinthemiddleofthebendinareactoratRe:194–(right)velocityfieldforthecrosssectionatthemiddleofthebend withrecirculationloopsatRe:194.

4.2.3.Residencetimedistribution

TheresidencetimedistributionRTDisaprobabilitydistribution functionthatdescribesthetimethatthe_fluidelementsspendinto the reactor, thus giving information on hydrodynamics in particularontheaxial dispersionandmacromixing thatallows thecharacterizationof the reactorat a globallevel. The Peclet number(Pe=uL/Daxwithuthefluidvelocity(ms%1);Lthelength

ofthechannel(m);Daxthediffusioncoefficient(m2s%1))helpsto

determineifthereactorbehaviourisclosetoaperfectstirredtank or a plug flow reactor. In a plug flow reactor obtained when Pe>100,eachelementoffluidhasthesameresidencetimeandthe stagnant zones are avoided, that could be a key factor onthe selectivity of chemical reactions. The coefficient of the axial dispersionisobtainedbythedeconvolutionoftheDTScurve[52]. This graph reports the detection of a tracerat theexit of the reactor;onFig.9,thepeakdoesnotexhibitsometailsthatindicate theabsenceofdeadzones.

4.3.Couplinghydrodynamicsandelectromagneticfieldsimulation Numerical modellingof continuous flow microwave heating includescouplingofthreephysicsphenomena(electromagnetism, fluidflowandheattransfer),whichcanberealizedbysolvingthe following governing equations: Maxwell’s equations, Fourier’s energybalanceandNavier-Stokesequation.Thisnewapproachto designandtooptimizethecontinuousflowmicrowavesreactorsis noteasytoimplementanditrequiresalargeknowledgeinmany scientificfields,firsttoselecttherelevantinputdataandthento analysecorrectlythe results. Mostof thecommercialRF codes proposeusefulmodulestotakeinconsiderationallthecoupled phenomena and they have been used in most of cases for modellingMWbatchsystems[53].Studiesinvolvingcontinuous flowaremorerecent[54]andtherearestilllimited.

OneapproachconsistsinreplacingtheMaxwell’sequationby Lambert’slawwhichislessexpensiveintermsofcalculationtime

[55].Itisrecommendedwhenthevolumeoftheobjectislargeand reasonableresultsareobtained.

Usinga3Dmodellingofatubularmillireactor-heatexchanger, ithasbeenshownthatanimportanttemperaturegradientintothe channelcouldexistwhichisspeciallydevelopedintothestagnant zones[36].Thepresenceofinternalsandtheinfluenceofthe_fluid velocityonthetemperatureprofileshavebeenstudiedputtingin handtheimportanceofthehydrodynamicsontheheatingprocess whichprevailsaheadofthemicrowaveenergydissipation.

Recently, Salvi et al. [56] proposeda 3-D simulation of the continuousflowheatingofNewtonianandnon-Newtonianliquids usingdifferentmodelsavailableintoCOMSOL.Providetheuseofa correctlyrefinedmesh,theyshowthegoodpredictionofthemodel intermsofabsorbedpoweraswellasforthetemperature.

5. Conclusions

The main advantages for microwaves arerelated toa rapid increaseofthebulktemperature(10K/s),nohightemperatureat thevesselwall.Sometimesamoreorlessselectiveheatingofthe reactantsis indicated. Many otheradvantages havebeen listed previously but one question still remains, “whyso few imple-mentations in industry”? As pointed out before, one must be carefulwiththeequipmentused.Withthenumerousexamplesof theliterature,itisdifficulttorationalizetheresults,tobesureto getagoodhomogeneityinelectromagneticfieldandin tempera-ture.Inthemostofcases,thedesignofthereactorseemstobe completelyignored.Thisiscompletelyunrealisticwhenweknow howthehydrodynamicscouldmodifythereactionrate.

Apreliminarymodelingisessentialincombiningthedifferent existingphenomena.Determiningkinetics,hydrodynamics, phys-icochemical parameters and especially dielectric properties is crucial.Theglobalmodelingmusttakeintoaccountthedifferent componentswhicharethereactor,thechemicalmediumandthe microwave applicator. When the final design is achieved, the control of the process takes place. An accurate temperature measurement and power controlare needed to proceedunder controlledconditions.Inlinepowermeasurementsareveryrare, many equipment only gives a value of the input power and sometimes a global valueof the reflected power. A directional couplerallowsseparatemeteringofforwardandreversepower, when it is equipped withtwo bolometer detectors it gives an accurate measure of the power. Withthe latter sensor,energy optimizationandfinetuningarepossible.Thisisakeypointforthe economicaspectsandindustrialdevelopments,becausesafetyand energysavingplayanimportantrole.

For novel technologies, the costs related to the equipment purchase include research, tuning and adaptation. They are generally higher than equipment costs for traditional process. Aneconomic benefitis possibleonoperatingcostswhen some improvements are performed. For example, increased reaction rate, product selectivity and synthesis yield, improvement of safety,ofparametersofresidencetimecontrol.

IntheveryinterestingstudyofBenaskaretal.[57],twoactual chemicalproductionlineswereconsidered,2-acetoxybenzoicacid as aspirin and 4-phenoxypyridine as antibiotic precursor in Vancocin production. The mostrelevant general message from thispaperisthattheprocess-designneeds,inaholisticmanner, havetobetakenintoaccountratherthan focusingonlyonthe reaction.

Higherenergyefficienciescouldbeattainedusingsingle-mode microwave irradiation; however, at the moment, the energy contributiontotheoverallcostwas foundtobenegligible.The impactofanintegratedmicrowaveheatingandmicroprocessing system on profitability was demonstrated with respect to operational cost and chemical productivity. Other applicator concepts,like internaltransmission line[58] ortraveling wave

[59]areunderinvestigationinbatchprocesses,applicationswill certainlyfollowtocontinuousreactors.

Futuredevelopmentsshouldincludetheexpertiseof comple-mentaryscientificfields.Ofcoursechemistryremainsattheheart oftheproblem,modelling,measurementsofproperties, hydrody-namics,processcontrolandchemicalengineeringingeneralare nowessentialtogofurthertowardstheindustrialstage. References

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