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二.放大工艺操作和合成路线选择1ChangshengZheng,Ph.D.LinkedIn2.Scale-upOperationandRouteSelection大纲21.放大设备与操作2.合成路线选择▪绿色化学原则▪路线选择标准3.生产成本计算4.合成路线选择实例1-1OperationComparisoninLabandPlant3OperationLabPlantCommentsTimeShort(hours)Long(days)DryingextractsDesiccantNa2SO4DesiccantavoidazeotropingConcentratingTodrynessTransferandthermaldecompositionareconcernsTrituratingReslurryingsolidsDecantingSiphoning,Dip-tubeActivatedcarboncommonIn-linefilterCleaningissueTumbledryerOragitateddryerCommon1-2PilotPlantEquipmentTrainRecommended(notlisted):scrubber,Dean-starkapparatus,vacuumcontrolvalve,reactorVolumelevelsensor,temperaturerecorder,etc1-3Batchstirred-tankreactorBafflescanbeusuallyinstalledtoprevent“swirling”andimprovemixingefficiencyBafflescanhousetemperaturesensors,pHprobes,oractasdiptubesforgasinjectionorsamplecollectionInternalcoolingcoilcanbeaddedtoimproveheattransfer1-4Reactors-MaterialofConstructionGlass-linereactor,entirelymadeofglassGlass-linesteelreactor,steelvesselscoatedinsidewithhigh-temperaturefiredglassenamelMetalreactor,common316stainlesssteelHastelloyreactor,greaterresistancetoacidsandchemicallyresistantnickelalloy▪Foragitationdependentprocess,parameters(mixingspeed,impellergeometry,etc,developedatbenchinscale-downexperimentsshouldbeappliedidentically▪Atscale,impellertipspeed,πRD,canbeusedinscale-downexperiments1-5MixinginProcess▪Laminarmixingiscausedbyfluidlayersmovingovereachother▪Turbulentmixingisthetumblingandre-tumblingofeddies(mostchemicalprocess)▪TheReynoldNumber(Re).FlowandmixingmechanismdependentonRe.Re5000,turbulentRe=DVvoru/ρDimpellerdiameterVvelocityvkinematicviscosityutrueviscosityρdensityP=NpρN3D5/gc▪MixingpowerNppowernumberNrotationnumbergcgravitationalconstantTraditionalPopularHeattransferViscosityliquidemulsificationSolidsuspension1-6ReactorAgitation91-7ChargingRawMaterials➢SolventandsolutionLowvacuumPumpHazardliquidreagents➢GasSubsurfacebydip-tube➢SolidandPowder▪FireorexplosionhazardPreventtheformationofdustcloud;RemoveoxygenbyinertingthesystemoreliminatingthesourceofheatandsparkHazardsolide.g.LiAlH4inspecialdissolvingplasticbag▪Wheneverpossible,preparesolidreagentbydissolvingthemfirstorPreparingaslurry,sinceliquidadditionismucheasilycontrolled.101-8ReactionControlTheresultofareactionisdeterminedbykineticsandthermodynamics.Needtomaximizeyieldandproductpurity.▪KineticsTemperature,concentrationdependence▪ThermodynamicsReactioncouldbereversibleorinvolveparallelandsidereactions▪ObjectivesmustbeclearlyinplaceHowthereactionendpointwillbedetermined?Doestheyieldpeakandthenbegintodecline?IfthereactionisprelongedtomaximizeyieldWhatistheeffectontheimpurityprofile?111-9ExothermicReaction▪Controlthereactionratesothatitismatchedtotheheatremovalcapacityofthereactor.▪Themostcommonmethodofdoingsoisbycontrolledadditionofalimitingreagent.▪Beawareofthepossibilitythatunreactedreagentcanaccumulateinthereactorifthereactionrateisslow.Nomorethan10%oftheunreactedreagentshouldbeallowedtoaccumulateinthereactor.▪Sometimeitissafertorunthereactionatahighertemperaturebecauseitreducedthepossibilityofreagentaccumulation(e.g.operatingatreflux)121-10WorkupReactionQuench▪Addingthequenchtothebatchorpouringreactionintoquenchsolution?▪Commonquenchingagentsincludingcitricacid,bisulfate,variousbufferExtractionandphaseseparation▪Raglayerinplant▪Acid-baseflip-flop▪ImmiscibleorganicsolventmakesaneffectiveextractphaseDealingwithemulsion▪Mixlongeratlowerspeed▪Applyheatorcyclethetemperatureupanddown▪Addasmallamountofco-solvent,suchasmethanol▪Addsalt▪Applyvacuumorpressure▪Polishfiltrationtoremovefineparticulates▪pHadjustment131-11PolishFiltration/Decolorization/WaterRemovalPolishFiltration:▪Passthesolutionthroughafine-poredfilter▪Poresize5µisadequateforgeneralchemicalprocessing,▪Solutionwith0.1%solid;100-Lbatch10-inchcartridgeDecolorization/drying▪Lab:activecarbon/soliddryingagents▪Plant:Notdesirablewithactivecarbon/soliddryingagents▪Filtration,pre-coatthefilterwithCelite,silicaorusefilterwithporesizeof0.1µor0.2µ141-12DistillationVacuumvs.AtmosphericPressure▪Lab:Rotovap(vacuumdistillation);quick,convenientandsimple▪Plant:VacuumdistillationismorecostlyanddifficulttocontrolSolventExchange▪OnesolventisbettersuitedforrunningareactionandanotherisbettersuitedforcrystallizationOperatingTips▪Knowthepressurelimitsofthecondenserandthrottletheoperatingpressureofcoolantloop▪Payattentiontothemeltingpointofsolventorsolventmixture.Eg.Cyclohexanemp6°C.▪Beawareoftheneedforsecondarycondensation▪Usingvacuum,establishthedesiredpressureinthereactorfirstandthenslowlyapplyheat,whichhelptominimizefoaming1-13SafetyforDistillation•Theun-distilledmaterial,thedistilledproduct,andthepotresidueshownothermallyinitiateddecompositionbyDSC.•MaintainthedistillationJackettempatleast50℃belowtheonsettemperatureofdecomposition.1516Compoundsmayigniteattheirauto-ignitiontemperatureinairintheabsenceofanignitionsource▪Acetone:465°C,with-20°Cfpand2.5-12.8%LEL-UEL▪ether:160°C,with-45°Cfpand1.9-48.0%LEL-UELThefactthatauto-ignitiontemperaturemaybesignificantlyhigherthantheflashpointundersco