Continuous flow-microwave reactor: Where are we

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Continuous flow-microwave reactor: Where are we

Lionel Estel, Martine Poux, Nassima Benamara, Isabelle Polaert

To cite this version:

Lionel Estel, Martine Poux, Nassima Benamara, Isabelle Polaert. Continuous flow-microwave reactor:

Where are we. Chemical Engineering and Processing: Process Intensification, Elsevier, 2017, 113, pp.56-64. �10.1016/j.cep.2016.09.022�. �hal-01844762�

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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

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Continuous fl ow-microwave reactor: Where are we?

Lionel Estel^a,*,Martine Poux^b,NassimaBenamara^a,IsabellePolaert^a

aLaboratoiredeSécuritédesProcédésChimiques(LSPC),INSARouen,NormandieUniversité,Saint-ÉtienneduRouvray,France

bLaboratoiredeGénieChimique,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.Thenumberofarticlespublishedisveryimpres- 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 chemicalenviron- mentswithfavourablepropertiesthatexcludestheuseofhigh- volumereactors.

Couplingmicrowaveheatingandcontinuousflowtechnology eliminatesthemaindrawbacksofmicrowavesandcreatesavery promising way to produce highvalue added chemicals or key pharmaceuticalintermediatessinceunlikethebatch,thecontinu- ousflowhasbeendemonstratedtofacilitateprocessintensifica- tionandcontributetoasafe,efficientandsustainableproduction [1,4].

The first systems coupling microwave and continuous flow werestudiedinthe1980’sandconcernedthepolymerheatingand thesoliddrying[6,7].Inchemicalsynthesis,about780paperson thecontinuousreactorshavebeenpublishedsince30years,286 areinthefieldofmicrowaveflowchemistryand220dealswith microwavecontinuous reactorwhich described systems witha large range of size from some millimetres or less to some centimetres.Thecontinuousflowundermicrowavesappearsin 1990’satthesametimethanflowchemistry.Thereactorconsisted

* Correspondingauthor.

E-mailaddress:Lionel.Estel@insa-rouen.fr(L.Estel).

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 andperpendiculartothedirectionofenergyandwavepropaga- 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,foragoodcouplingoftheelectromagneticfieldwiththe 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 dramaticallydecreasetheelectromag- neticfieldintensityandtherebytheoverallefficiencyoftheenergy conversion.Whendipolarpolarizationisthemainphenomenon, dielectricheatinginvolvesunorganizedmovementsatmicroscale duetotheinabilityofmoleculeclusterstomoveexactlywiththe electric field. This hysteresis phenomenon explains how the organised energy of electromagnetic field is transferred as Brownianmovementintomatter,manyauthorscallthisphenom- 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,inhomogeneouselectro- 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 caninterferewiththeelectromagneticfieldandgenerateantenna 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.

Fig.3. Thermalboundarylayer(conventionalheating).

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].

Manyflowreactorsarecommerciallyavailabletoscaleupin microwave process chemistry such as Milestone FlowSYNTH reactorwhichcanoperate underpressure(30bar).Itconsistsof a200mLPTFEtubeplacedverticallyinamicrowavemultimode cavity(upto1600W).Moseleyandco-workers[19–21]reported sixhomogeneousreactionsinvestigated(OrthoClaisenRearrange- 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].FourIRsensorsandtwoNi- Cr/Nithermocouplesareusedtorecordthetemperaturerespec- tivelyalong the tubular reactorand at theoutput of both the reactorandthecooler.Theesterificationoflinaloolwasperformed inthisETHOSPILOT4000ata25kgscalewith2.2L/hflowrate [24].

AninterestingapparatuswasintroducedbyMorschhäuseretal.

abletooperatesafelyathightemperature/pressure(310^!C/60bar) witha production onan industrial scale (up to20L/h)[25]. It consistsinacylindricalreactor(75cm#1cmi.d)madeofg-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].Thissystemwastestedsuccessfullyontheproductionof1,3- diphenyl-2-propynyl piperidine catalyzed by Cu that has been

depositedontheinnerwallsofthetubes.Theenergyuniformityin the tubular reactors was studied by measuring the microwave powerabsorbedbyeachtubefilledwithaspecifiedsolvent.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 2004anewmicroflowcellbasedontheprincipleofheatinglocally thecatalyst.TheflowcellwasaUglassflowcapillaryreactorwith aninternaldiameterof800mm,and138mmlong,coatedwitha goldfilm 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 (270mL) is located and an aluminumsectionsheltering,thecoolingmicrochannel(600mL).

Thereactorwastestedfortheoxidationofbenzylalcoholwithflow 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 usedwitharangeofinternaldiameterbetween200and1150mm tocarryoutsyntheseswithvariableflowratesof2–40mL/minto obtaintheresidencetimeneededforreaction.Crosscouplingand ring-closingmetathesiswithmetalcatalysts,nucleophilicaromat- icsubstitutionandheterogeneousWittigreactionswerecarried out.Itwaspointedthattheconversionratewasdependentofmany parameters, such as flow rate, the internal diameter of the capillary,thepowerlevel,etc.Ontheconceptofnumberingup,a flowmulti-reactorsystemcomposedoffourcapillarytubeswasset