Process plant design : project management from inquiry to acceptance

370 Pages·2011·3.2 MB·English

by  Frank P Helmus

Editedby
IanHouson
ProcessUnderstanding
Related Titles
Helmus,F.P. Vogel,G.H.
ProcessPlantDesign ProcessDevelopment
ProjectManagementfromInquiryto FromtheInitialIdeatotheChemical
Acceptance ProductionPlant
2008 2005
ISBN:978-3-527-31313-6 ISBN:978-3-527-31089-0
Bro¨ckel,U.,Meier,W.,Wagner,G.(eds.) Wiley-VCH(ed.)
ProductDesignand Ullmann’sProcesses and
Engineering Process Engineering
BestPractices
2004
2007 ISBN:978-3-527-31096-8
ISBN:978-3-527-31529-1
Koolen,J.L.A.
Rao,S.
DesignofSimpleandRobust
TheChemistryofProcess ProcessPlants
Developmentin FineChemical
2001
andPharmaceuticalIndustry
ISBN:978-3-527-29784-9
2007
ISBN:978-0-470-31995-6
Zlokarnik,M.
Scale-upin Chemical
Engineering
2006
ISBN:978-3-527-31421-8
Edited by Ian Houson
Process Understanding
For Scale-Up and Manufacture of Active Ingredients
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V
Contents
Preface XV
ListofContributors XVII
1 QualitybyDesign 1
VinceMcCurdy
1.1 History 1
1.2 DefiningProductDesignRequirementsandCriticalQuality
Attributes 3
1.3 TheRoleofQualityRiskManagementinQbD 6
1.4 DesignSpaceandControlStrategy 12
1.5 QualitySystems 14
References 15
2 RouteandProcessSelection 17
DavidJ.Ager
2.1 Introduction 17
2.2 RouteEvaluation 20
2.3 FactorstoConsider 24
2.3.1 Timing 24
2.3.2 Costs 25
2.3.2.1 RemovalofaChromatographyStep 26
2.3.3 Safety,Health,andEnvironment(SHE) 26
2.3.3.1 SaferProcesses 28
2.3.3.2 GreenChemistry 33
2.3.4 Legal 37
2.3.5 OtherConsiderations 38
2.3.5.1 Throughput 40
2.3.5.2 Solvents 42
2.3.5.3 RawMaterials 43
2.3.5.4 Intermediates 43
2.4 RouteSelection 43
2.4.1 Sildenafil 48
VI Contents
2.5 ProcessSelection 49
2.5.1 Pregabalin 51
2.5.2 NK1ReceptorAntagonist 53
2.5.3 Data 55
2.6 Summary 56
References 57
3 CriticalStagesofSafetyAssessmentinProcessDesign
andScale-Up 59
StephenRowe
3.1 ReactionSafetyConcepts 59
3.1.1 WhatIstheHazard? 60
3.1.2 TheCriticalEffectsofScale-UponThermalBehavior 60
3.1.3 SafetyFeaturesofaReaction 62
3.1.4 StagesofSafetyAssessment 64
3.2 Pre-LaboratorySafetyStudies 65
3.2.1 PredictingReactionSafetyCharacteristics 65
3.2.2 SelectingInherentlySaferProcessingConditions 68
3.3 TheSynergiesofSafetyandOptimization – Together 69
3.3.1 TestingofPotentiallyExplosiveCompounds 69
3.3.2 ThermalStabilityAssessment 70
3.3.3 ReactionThermodynamic,Kinetic,andGas-Generation
Quantification 71
3.3.4 DevelopingFault-TolerantProcesses – byDesign 74
3.4 EstablishingaReliableBasisofSafetyforScale-Up 75
3.4.1 HazardousScenarioIdentification 76
3.4.2 DeterminingtheConsequencesofHazardousScenarios 77
3.4.3 ExperimentalSimulation – AdiabaticCalorimetry 77
3.4.4 SpecifyandImplementSafetyMeasures 79
3.4.5 Large-ScaleProduction 80
3.5 FlammabilityHazards 80
3.5.1 AssessingPilot-ScaleFlammabilityHazards 82
3.6 Summary 84
References 85
4 UnderstandingtheReaction 87
JohnAtherton,IanHouson,andMarkTalford
4.1 Introduction 87
4.2 ProcessComplexity 88
4.2.1 NumberofPhases 88
4.2.2 PhysicalandDynamicComplexity 89
4.2.2.1 LengthScales 89
4.2.2.2 Time 90
4.2.2.3 Solubility 90
4.2.2.4 Density 90
Contents VII
4.2.2.5 Rheology 90
4.2.2.6 HeatTransfer 90
4.2.2.7 MassTransfer/InterfacialArea 90
4.2.2.8 MixingTime 91
4.2.3 ChemicalComplexity 91
4.3 TopicsforDataAcquisition 91
4.4 ReactionProfiles 92
4.5 ReactionPictures 93
4.6 IonicEquilibriaandReactionSelectivity 95
4.6.1 Nitration 95
4.6.2 Acylation 96
4.6.3 AssociationEquilibria – LithiumDiethylamide(LDA) 99
4.7 Kinetics 99
4.7.1 OrderofReaction 99
4.8 CatalyzedProcesses 102
4.9 TheRate-DeterminingStep 102
4.10 MixinginChemicalReactors 105
4.11 MixingTheory 106
4.11.1 MixingRegimes 108
4.11.2 Micromixing 109
4.11.3 Macromixing 110
4.11.4 Mesomixing 110
4.11.5 DeterminingMixingSensitivityintheLaboratory 111
4.11.6 CommentsonScalabilityofMixing 111
4.12 MultiphaseProcesses 112
4.13 MassTransferTheory 113
4.13.1 EffectofMassTransferonChemicalReactionRates 114
4.13.1.1 ChemicalRate-LimitedReaction 114
4.13.1.2 MassTransferRate-LimitedReaction 114
4.13.1.3 Solubility-LimitedReaction 114
4.13.2 PhaseEquilibria 115
4.13.2.1 Partitioning 115
4.13.2.2 ‘‘SaltingOut’’ 115
4.13.2.3 CommonIonEffect 115
4.14 MassTransferandMixingRequirementsinMultiphase
Systems 116
4.14.1 Liquid–LiquidSystems 116
4.14.2 Liquid–SolidSystems 118
4.14.3 Gas–LiquidSystems 118
4.14.4 Solid–Liquid–GasSystems 119
4.15 ConceptsofStructureandScaleforEquipmentSelection 120
4.15.1 WhatDoWeMeanby‘‘Structure’’? 120
4.15.2 Whatis‘‘Predictability’’? 121
4.15.3 Whatis‘‘Intensity’’? 121
4.15.4 ScalesofStructure 122
VIII Contents
4.15.5 HowSusceptibletoVariabilityistheProcess;WhenWouldDifferent
EquipmentHelp? 123
4.16 Conclusion 124
References 125
5 UseofModelstoEnhanceProcessUnderstanding 127
WilfriedHoffmann
5.1 Introduction 127
5.2 TheProcessCharacterizationElementsofaChemicalReaction 128
5.3 TheImpactofModeling 130
5.4 UnderstandingtheChemistry 131
5.4.1 ASimpleStart 131
5.4.2 GettingRealRateParameters 132
5.4.3 IntroductionofTemperatureDependence 135
5.4.4 IncludingReactionHeats 137
5.4.5 PuttingElementsTogether:Large-ScaleSimulations 138
5.4.6 ThermalProcessSafetySimulations 141
5.5 PhysicalRates(theElementsofMassTransfer) 144
5.5.1 Gas/LiquidMassTransfer 145
5.5.2 Solid/LiquidMassTransfer 149
5.6 SummaryandOutlook 152
References 153
6 Scale-UpofChemicalReactions 155
E.HughStittandMarkJ.H.Simmons
6.1 Introduction 155
6.2 CaseStudy – BatchHydrogenation 156
6.3 Scale-UpofStirredTankReactors(STRs) 159
6.3.1 FundamentalsofFlowRegimes,Turbulence,andTurbulent
Mixing 160
6.3.1.1 MixingMechanismsinLaminarFlows 161
6.3.1.2 MixingMechanismsinTurbulentFlows 162
6.3.1.3 EstimatingEnergyDissipationandMixingLengthScalesfrom
TurbulentFlowFields 164
6.3.2 StirredVesselDesignandScale-Up 166
6.3.2.1 ImpellerFlowPatterns 167
6.3.2.2 PowerInputandSpecificEnergyDissipationRate 167
6.3.2.3 MixingTimes 170
6.4 StirredTankScale-Up 171
6.4.1 ChoiceofCriterionforScale-UpinTurbulentFlow 171
6.4.1.1 ConstantMixingTime(ConstantN) 171
6.4.1.2 ‘‘Constant’’TurbulentMixingBehavior(Constant ε ) 172
T
6.4.2 HeatTransfer 172
6.4.3 MultiphaseSystems:Solid–LiquidSystems 174
6.4.3.1 ParticleSuspensionandFlowPatterns 175
Contents IX
6.4.3.2 Solid–LiquidMassTransfer 177
6.4.4 MultiphaseSystems:Gas–LiquidSystems 177
6.4.4.1 PowerConsumption 178
6.4.4.2 GasHold-UpandFlowPatterns 178
6.4.4.3 MassTransfer 179
6.4.5 Summary 180
6.5 ChemistryEffectsinScale-Up 181
6.5.1 ‘‘Fed-Batch’’Liquid-PhaseReactions 181
6.5.2 Liquid–SolidReactions 182
6.5.3 Gas–Liquid(–Solid)Reactions 183
6.5.3.1 GaseousReactant 183
6.5.3.2 GaseousProduct 183
6.5.3.3 Catalysis 184
6.5.4 Impurities 184
6.6 AchievingProcessUnderstandingforReactorScale-Up 184
6.6.1 ChemistryScale-UpSensitivity 185
6.6.2 OntheAcquisitionofRelevantChemicalInformation 186
6.6.3 OntheAcquisitionofRelevantReactorDesignInformation 187
6.7 ReactorSelection 188
6.7.1 SoWhichReactorCanIUse? 188
6.7.2 GenericDuty 189
6.7.3 CharacterizingMixingRate 189
6.7.4 CharacterizingSolidsSuspension 190
6.7.5 CharacterizingHeatTransfer 190
6.7.6 CharacterizingMassTransfer 191
6.8 ExploitingProcessUnderstandinginScale-Up 191
6.8.1 MixingRate-LimitedReactions 192
6.8.2 Solid–LiquidMixing-LimitedReactions 193
6.8.3 Heat-Transfer-LimitedReactions 193
6.8.4 Mass-Transfer-LimitedReactions 194
6.9 Conclusions 194
References 195
7 ProcessUnderstanding – Crystallization 199
LeroyCronin,PhilipJ.Kitson,andChickC.Wilson
7.1 Introduction 199
7.1.1 CrystalDefinitionandStructure – CrystalDefectsandBasics
ofCrystalGrowth 200
7.1.2 ThermodynamicsofCrystallization 202
7.1.3 KineticsofCrystalGrowth,Nucleation 204
7.1.3.1 MetastableStates 206
7.1.4 NucleationandCrystalGrowth 206
7.1.4.1 SupersaturationandMetastableZoneWidth 206
7.2 CrystallizationProcesses 208
7.2.1 CrystallizationfromtheMelt 208