Presentation on theme: "H-Cube – The next generation in Hydrogenation"— Presentation transcript:
1H-Cube – The next generation in Hydrogenation Asynt Ltd.
2H-Cube – Continuous Flow Hydrogenator Reaction Cube ConceptIntegrated compact flow reactors designed to have FOUR main advantages over conventional reactors.Improved SafetyFaster OptimizationContinuous Flow AutomationReduced SizeDeveloped by Thales Nanotechnology (Partner company of Comgenex)
3H-Cube – Continuous Flow System ProductHPLC pump flows a continuous stream of solvent into reactor.Hydrogen generated from electrolysis of waterHydrogen is mixed with sample, heated and passed through a catalyst cartridge. Up to 100°C and 100 bar. (1 bar=14.5 psi)Hydrogenated product emerges continuously into reaction vial.
4H-Cube System-Monitoring Screen Touch Screen operatedEasy setting of pressure and temperatureControl flow rate of HPLC pumpDisplays safety messagesNo lengthy set-up/shut down procedure
5Hydrogenation Process H2/SubstrateMixerCatCart HeaterBubble DetectorCatCartHolderPressureDetectorBack-pressurevalvet=2 mint = 0
6Catalyst System Catalyst contained in sealed disposable cartridges No scale-up issuesNo filtration necessary10mg to 100 g scaleCatalysts used:10% Pd/C , 5% Pd/CRaney Nickel / Raney Cobalt20% Pd(OH)2/C10% Pt/C , 5% Pt/C Sulfided5% Rh/C , 5% Rh/Al2O35% Pd/CaCO3 with lead (Lindlar’s Catalyst)30mm
7How does H-Cube compare to Batch Reactor? Nitro reduction tried on H-Cube and batch reactor.2 minutes reaction time100% conversion with H-Cube vs. <2% with batch reactorHigher active surface with packed column cartridges
8Reductions Deprotection Deuteration Nitro group Nitrile group Imine Reaction ExamplesReductionsNitro groupNitrile groupImineHeterocycleC=C bondAlkyneDehalogenationDesulphurizationOximeDeprotectionN-benzylO-benzylcBzDeuteration
9Reaction Conditions0.05M – 0.2M Solution in organic solvent, acetic acid or NH3/MeOHChoose CatCart (Catalyst and size)Set flow rate between 1ml/min and 3ml/minSet Pressure 1bar – 100barSet Temperature CSet ModeControlled modeFull H2 modeNo H2 mode (introduce a different gas)How much throughput?If RMM = 200Worst case 1ml/min, 0.05M, 3mmol/hour (600mg)Best Case 3ml/min, 0.2M, 36mmol/hour (7.2g)
10Catalyst RecyclingH-Cube conditions: 0.1M, [50:50] EtOAc:EtOH, ~1 bar, 30 oC, 1 mL/min;Total material processed = 30x 10 fractions = 30 mmol = 4.85 g with 140mg Pd/C
12O-Debenzylation using the Thales H-Cube: a study of catalyst capacity & deactivation
13Automated High-throughput Hydrogenation H-Cube integrated into CAVRO work stationAutomated injection and collectionTimed injections, link to UV detector possible
14H-Cube vs Traditional Batch Systems ParameterH-CubeBatch SystemsTime to set-up reaction10 minutes30 minutesCatalyst SeparationNone requiredFiltration-HazardousReaction analysis2 minutesAfter reactionTime taken to set up new reaction5 minutes60 minutesHigh-throughput library capabilityPotential for automated systemNot possibleSpecialist Lab Required?Can use in normal laboratorySeparate hydrogenation laboratory
15Advantages of H-Cube Safer… Smaller… Faster… No hydrogen cylinders necessaryUses deionised waterNo filtration of catalyst necessaryOnly µmolar quantities react at any one timeSmaller…H-Cube footprint is less than 0.3m3Easy storageScaleable reactions from mg to 100gFaster…Monitor reaction progress after 2 minutes!30 reaction conditions can be validated in less than a half day.Simple to use, minimal training required
16Acknowledgements Richard Jones, Thales Nanotechnology Mark Ladlow, GSK Cambridge