Presentation on theme: "H-Cube – The next generation in Hydrogenation"— Presentation transcript:
1 H-Cube – The next generation in Hydrogenation Asynt Ltd.
2 H-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)
3 H-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.
4 H-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
5 Hydrogenation Process H2/SubstrateMixerCatCart HeaterBubble DetectorCatCartHolderPressureDetectorBack-pressurevalvet=2 mint = 0
6 Catalyst 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
7 How 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
8 Reductions Deprotection Deuteration Nitro group Nitrile group Imine Reaction ExamplesReductionsNitro groupNitrile groupImineHeterocycleC=C bondAlkyneDehalogenationDesulphurizationOximeDeprotectionN-benzylO-benzylcBzDeuteration
9 Reaction 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)
10 Catalyst 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
12 O-Debenzylation using the Thales H-Cube: a study of catalyst capacity & deactivation
13 Automated High-throughput Hydrogenation H-Cube integrated into CAVRO work stationAutomated injection and collectionTimed injections, link to UV detector possible
14 H-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
15 Advantages 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
16 Acknowledgements Richard Jones, Thales Nanotechnology Mark Ladlow, GSK Cambridge