Rapid Carbanionic and Oxyanionic Polymerizations Transferred to Continuous Microfluidic Systems: Recent Results and Perspectives Holger FreyAdrian Natalello, Jan Morsbach, Andreas Friedel, Christoph Tonhauser, Daniel WilmsUniversity of MainzInstitute of Organic and Macromolecular ChemistryDuesbergweg 10-14 55099 Mainz, GermanyDecember 4, 2014, Paris

*Hessel, V.; Serra, C.; Lwe, H.; Hadziioannou, G. Chem. Ing. Tech. 2005, 77, 1693. Polymerization Reactors

*Review ArticlesD. Wilms, J. Klos, H. Frey, Macromol. Chem. Phys. 2008, 209(4), 343-356.C. Tonhauser, A. Natalello, H. Lwe, H. Frey, Macromolecules 2012, 45, 9551-9570.

*OutlineCarbanionic / Oxyanionic Polymerization in Continuous Flow Living Carbanionic Polymerization: Introduction Use of Micromixing Devices for Carbanionic Polymerization End-Functional Polymers Synthesis of Block Copolymers by Carbanionic Polymerization Controlled Polydispersity via Microfluidic Strategies Oxyanionic Polymerization in Microfluidic Devices Conclusion and Perspectives

* Micromixer: Fast Mixing, Excellent Heat Dissipation, Continuous Problems: Mixing, Heat Dissipation, Sensitivity, Reaction Times?Living Carbanionic PolymerizationCharacteristics: Precise Control over Molecular Weight (via M/I), Low Polydispersity Mostly Rapid Polymerization, even at Low Temperatures Living Character Various Macromolecular Architectures Inherently Sensitive to Impurities Commonly Highly Exothermic Living Anions on Tap

Polymerization in Continuous FlowTonhauser, C.; Natalello, A.; Lwe, H.; Frey, H. Macromolecules. 2012, 45 (25), 95519570.Jhnisch, K.; Hessel, V.; Lwe, H.; Baerns, M. Angew. Chem. Int. Ed. 2004, 43, 406-446. Wilms, D.; Klos, J.; Frey, H. Macromol. Chem. Phys. 2008, 209, 343-356. Wurm, F.; Wilms, D.; Klos, J.; Lwe, H.; Frey, H. Macromol. Chem. Phys. 2008, 209, 1106-1114. *Effective mixingHigh surface-to-volume ratioSmall internal volumeHigh chemical and mechanical resistance

Multilamination Mixing Device *Slit Interdigital Micromixers: Laminar Mixing

ParameterSIMM-V2Mixing principlesMulti-laminationSize (L x B x H) / mm30 x 40 x 30Temperature / C-40 220Pressure stability / bar100Inner volume / L8

*Living Anionic Polymerization of StyreneHigh Rate Constants (Dependent on Solvent, Temperature, Concentration)Wurm, F.; Wilms, D.; Klos, J.; Lwe, H.; Frey, H. Macromol. Chem. Phys. 2008, 209, 11061 .Solvent: Cyclohexane Non-Polar Reaction Medium

*Carbanionic Polymerization in Non-Polar MediumSEC (THF) RI DetectionFlow Rates: 1 3.5 mL/minResidence Times:40 120 sNarrow Molecular Weight DistributionConvenient Adjustment of Molecular Weight at Varying Flow Rate Ratios

SampleMn (theor.) Mn (SEC) Mw/Mn (SEC)PS-15005701.25PS-22,0003,0001.09PS-33,0003,3001.10PS-46,0008,0001.08PS-520,00024,0001.11PS-630,00032,0001.21

*Carbanionic Polymerization in Non-Polar Medium1H-NMR (CDCl3)MALDI-ToF MSFull Conversion (NMR spectroscopy)Quantitative Functionalization (MALDI-ToF-MS)

SampleMn (theor.)Mn (SEC)Mw/Mn (SEC)PS-15005701.25PS-22,0003,0001.09PS-33,0003,3001.10PS-46,0008,0001.08PS-520,00024,0001.11PS-630,00032,0001.21

*Solvent: THF Polar Reaction MediumExtremely Fast Kinetics; Control in Conventional Set-Up Only Possible at Low TemperatureFast Mixing and Excellent Heat Transfer in the Microstructured Reaction Device Permit Continuous Synthesis of Well-Defined Polystyrenes at 25C Carbanionic Polymerization in Polar Medium

*Polar Medium (THF): Room Temperature (!)SEC (THF) RI DetectionFlow Rates: 0.8 2.6 mL/minResidence Times:1.6 5.0 s

SampleMn (theor.) Mn (SEC)Mw/Mn (SEC)PS-72,0001,7001.28PS-83,0002,3001.14PS-94,0003,6001.11PS-105,0006,4001.10PS-116,0006,9001.09PS-1210,00010,5001.14PS-1312,00011,3001.09PS-1415,00017,0001.10PS-1540,00042,2001.24PS-1660,00071,0001.25

*Conventional Approach vs. MicromixingLiving Carbanionic Polymerization of Styrenic Monomers:Batch Reactor vs. Microstructured Reactor

Molecular WeightsBroad RangeBroad RangePolydispersity 1.05Mostly 1.15Temperature - 60C in Polar Solvents 25 CReaction TimesHoursSecondsVersatilityOne Sample/ExperimentSeveral Samples/Experiment

*Versatile Synthesis of End-Functional PolymersConventional Access to End-Functional Polymers via Carbanionic PolymerizationTermination Agents: Chlorosilane, Diphenylethlene (DPE) and Epoxides Epoxide Derivatives Quantitative Functionalization (Quirk et al.)EEGE(Ethoxy Ethyl Glycidyl Ether)Quirk, R. et al. Macromol. Symp. 2000, 161, 37-44. Quirk, P. R.; Gomochak, D. L. Rubber Chem. Technol. 2003, 76, 812.

*Synthesis of End-Functional PolystyreneTermination in Supplementary T-JunctionContinuous Flow Process: Polymerisation-Termination SequenceRapid and Quantitative FunctionalizationEnd-Functionalization of Polystyrene in THF (Polar Medium)

*Synthesis of End-Functional PolystyreneSEC (THF) RI DetectionFlow Rates: 0.5 1.5 mL/minResidence Times:5 15 s

SampleMn (theor.) Mn (SEC) Mw/Mn (SEC)PS-171,9001,9001.15PS-182,9003,0001.14PS-194,3003,9001.14PS-204,5006,4001.18PS-217,50017,0001.35

*Synthesis of End-Functional PolystyreneFlow Rates: 0.5 1.5 mL/minResidence Times:5 15 sMALDI-ToF MS

SampleMn (theor.) Mn (SEC) Mw/Mn (SEC)PS-171,9001,9001.15PS-182,9003,0001.14PS-194,3003,9001.14PS-204,5006,4001.18PS-217,50017,0001.35

C. Tonhauser, D. Wilms, F. Wurm, E. Berger-Nicoletti, M. Maskos, H. Lwe, H. Frey, Macromolecules 2010, 43, 5582-5588Functional Termination

*Synthesis of End-Functional PolystyreneRelease of Hydroxyl Groups by Acidic HydrolysisSemi-Continuous Approach to Hydroxy Functional PolymersFacile Access to Precursors for Complex Macromolecular Architectures (Blockcopolymers, Miktoarm Star Polymers)

*Synthesis of Block Copolymers

SampleS:t-BuOSMn (theor.)Mn(SEC)Mn(MALLS)Mw/Mn(MALLS)PS-170:203,6003,7004,2001.21PS-185:51,4001,3001,5001.18PS-1910:51,9001,9002,1001.22PS-2022:124,4004,8004,7001.17PS-2180:3013,60013,10013,6001.15PS-22200:2525,30024,70025,6001.14

Change Mixing Pattern: Turbulent Mixing*4-Way Jet Mixing Device

Polymerization in Continuous Flow*Styrene in THFsec-BuLi in hexane2-Vinyl pyridine in THFsec-BuLi in benzene

SampleTotal Flow / mL/minMn (GPC) / gmol-1PDIPS-782 2001.09PS-894 7001.08PS-10732 2001.08PS-11842 5001.08PS-141074 2001.05PS-1511104 2001.04PS-1612148 7001.04

SampleTotal Flow / mL/minMn (GPC) / gmol-1PDIP2VP-8101 8001.16P2VP-1083 5001.17P2VP-1176 4001.19P2VP-121014 3001.15P2VP-131118 7001.17P2VP-141149 3001.12P2VP-151096 0001.05

ComparisonPolymerization in Continuous FlowNatalello, A.; Morsbach, J.; Friedel, A.; Alkan, A.; Tonhauser, C.; Mller, A. H.E., Frey, H.;Org. Process Res. Develop., 2014, dx.doi.org/10.1021/op500149t*PS and P2VP

CharacteristicsBatchMulti-laminationJet mixing EffortHighMiddleLowSide reactionDifficult to avoidNo NoMolecular weightsBroad range70 000 10 000150 000 100 000PDI< 1.101.09 1.281.19 1.261.04 1.101.05 1.19Temperature - 78CRTRTVersatilityOne sampleSeveral samplesSeveral samples

C. Serra et al., LAB ON A CHIP, 2008, 8,1682-1687 DOI: 10.1039/b803885f Influence of Mixing on Polydispersity*

*Control of Polydispersity by MicroreactorInfluence of PDI on polymer propertiesCommon mindset: monodisperse polymers are good; polydisperse are bad1

Mainly theoretical investigations but only a few experimental contributions2

Most experimental studies are based on mixing of several polymer samples3

Key issue:

No controllable parameter to tailor polydispersity is available

Lynd N A, Meuler A J, Hillmyer M A. Polydispersity and block copolymer self-assembly. Progress in Polymer Science 2008; 33; 875-893. Leibler L. Theory of microphase seperation in block copolymers. Macromolecules 1980;13:1602-17.(3) Noro A, Cho D, Takano A, Matsushita Y. Effect of molecular weight distribution on microphase seperated structures from block copolymers. Macromolecules 2005;38;4371-6.

Carbanionic polymerizationControlled living carbanionic polymerization Well defined polymer architectures Very narrow mass distributions possible (PDI < 1.10) Linear dependence of the achieved molecular weights DP = [M]/[I]Microreactor setup

Turbulent mixing device point of broadeningFlow rate/ml min-1

sampleMmax(GPC, g mol-1)PDIflow rate (ml s-1)PS03-0134031,158,0PS03-0235861,168,0PS03-0332831,227,0PS03-0432331,226,2PS03-0532621,225,4PS03-0632061,264,8PS03-0731291,294,2PS03-0831621,283,6PS03-0931111,343,2PS03-1034531,332,8PS03-1130891,452,4PS03-1231971,562,0PS03-1331761,681,6PS03-1431931,751,2PS03-1533871,830,8

sampleMmax(GPC, g mol-1)PDIflow rate (ml s-1)PS03-0134031,158,0PS03-0235861,168,0PS03-0332831,227,0PS03-0432331,226,2PS03-0532621,225,4PS03-0632061,264,8PS03-0731291,294,2PS03-0831621,283,6PS03-0931111,343,2PS03-1034531,332,8PS03-1130891,452,4PS03-1231971,562,0PS03-1331761,681,6PS03-1431931,751,2PS03-1533871,830,8PS03-1633991,950,4PS03-1734842,210,3

sampleMmax(GPC, g mol-1)PDIflow rate (ml s-1)PS03-0134031,158,0PS03-0235861,168,0PS03-0332831,227,0PS03-0432331,226,2PS03-0532621,225,4PS03-0632061,264,8PS03-0731291,294,2PS03-0831621,283,6PS03-0931111,343,2PS03-1034531,332,8PS03-1130891,452,4

sampleMmax(GPC, g mol-1)PDIflow rate (ml s-1)PS03-0134031,158,0PS03-0235861,168,0PS03-0332831,227,0PS03-0432331,226,2PS03-0532621,225,4PS03-0632061,264,8

sampleMmax(GPC, g mol-1)PDIflow rate (ml s-1)PS03-0134031,158,0

sampleMmax(GPC, g mol-1)PDIflow rate (ml s-1)PS03-0134031,158,0PS03-0235861,168,0PS03-0332831,227,0PS03-0432331,226,2PS03-0532621,225,4PS03-0632061,264,8PS03-0731291,294,2PS03-0831621,283,6PS03-0931111,343,2PS03-1034531,332,8PS03-1130891,452,4PS03-1231971,562,0PS03-1331761,681,6PS03-1431931,751,2PS03-1533871,830,8PS03-1633991,950,4PS03-1734842,210,3

Carbanions are still living:-> Quantitative functionalization (MALDI-ToF)

SummarySystematic influence on the PDI of a polymerization at constant molecular weights achievedSystem can be transferred to other polymer systemsAnalysis how the properties are influenced are in progressQuantitative functionalized polymers enables further investigations of block copolymer behavior

*Hyperbranched Polymers & Microreactors

Mn ~ 750 g/molMw/Mn = 1.6T = 120CContinuous flowThroughput: 1 5 ml/minReaction time: several minutesSEC analysis (DMF)Hyperbranched Polyglycerol: Target Mn = 1,000 g/molD. Wilms, J. Nieberle, J. Klos, H. Lwe, H. Frey, Chem. Eng. Technol. 2007, 30(11), 1519-1524.

1H-NMR analysisMn = 1,100 g/molDPn= 16Initiator coreRepeat unitsHydroxyl groupsMethanol-d4Hyperbranched Polyglycerol: Target Mn = 1,000 g/mol

MALDI-ToF analysisConfirmation of initiator core incorporationComplete core incorporation(Independent of flow rates)14Hyperbranched Polyglycerol: Initiator attachment?

Hyperbranched Polyglycerol: Variation of Flow RatesSEC analysis (DMF)D. Wilms, J. Nieberle, J. Klos, H. Lwe, H. Frey, Chem. Eng. Technol. 2007, 30(11), 1519-1524.

SampleTarget Mn [g/mol]Flow Rate Monomer [ml/min]Flow RateInitiator [ml/min]Molar RatioInitiator:MonomerMn (1H-NMR)PG-11,0000,8711 : 10,71100PG-21,0001,7421 : 10,71300PG-31,0002,172,51 : 10,71600

Isolation by DialysisMn ~ 150,000 g/molMw/Mn ~ 1.1 (PS Standards)SEC analysis (DMF)16Hyperbranched Polyglycerol: Variation of Flow Rates

SampleTarget Mn [g/mol]Flow Rate Monomer [ml/min]Flow Rate Initiator [ml/min]Molar Ratio Initiator:MonomerMn(1H-NMR)PG-41,0000,8711 : 10,71100PG--51,0200,9111 : 12,01600PG-61,1001,9721 : 13,01200PG-72,0001,8111 : 25,0 3200

*Conclusion & PerspectivesPolymer Synthesis in Microreactors: Carbanionic and Oxyanionic Techniques

Efficient Continuous Flow Process for Living Carbanionic PolymerizationFacile and Fast Processes Serve to Optimize Reaction Parameters Convenient Molecular Weight AdjustmentTailoring of the Polydispersity of Living Polymer CabanionsQuantitative Implementation of Various End-Groups at Polymers

Facile Extension to Complex Polymer Architectures(Star Polymers, Block Copolymers)

*Conclusion & PerspectivesPending Questions

Unprecedented Polymer Structures?

Kinetic Control of Polymerization of Metastable Monomers? (Example: Vinyl Alcohol) Gradients, One-Step Block Copolymer Syntheses, Architectures by versatile multi-microfluidic systems

*AcknowledgmentsProf. Holger LweMichael MaskosElena Berger-NicolettiMonika SchmelzerPOLYMATInstitut fr Mikrotechnik Mainz

*Conclusion & PerspectivesPending Questions

Unprecedented Polymer Structures?

Kinetic Control of Polymerization of Metastable Monomers? (Example: Vinyl Alcohol) Gradients, One-Step Block Copolymer Syntheses, Architectures by versatile multi-microfluidic systems

*Multilamination Flow PatternHydrodynamic FocusingJet Formation in the Slit-Shaped Interdigital MicromixerHessel, V. et al. AIChE Journal 2003, 49, (3), 566-577.Lb, P. et al. Chemical Engineering Science 2006, 61, (9), 2959-2967. Micromixer InlayMulitlamination Flow PatternMethod of Operation

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