Rapid Carbanionic and Oxyanionic Polymerizations
Transferred to Continuous Microfluidic Systems:
Recent Results and Perspectives
Holger Frey
Adrian Natalello, Jan Morsbach, Andreas Friedel, Christoph Tonhauser, Daniel Wilms
University of Mainz
Institute of Organic and Macromolecular Chemistry
Duesbergweg 10-14
55099 Mainz, Germany
December 4, 2014, Paris
Polymerization „Reactors“
Hessel, V.; Serra, C.; Löwe, H.; Hadziioannou, G. Chem. Ing. Tech. 2005, 77, 1693.
2
Review Articles
D. Wilms, J. Klos, H. Frey, Macromol. Chem. Phys. 2008, 209(4), 343-356.
C. Tonhauser, A. Natalello, H. Löwe, H. Frey, Macromolecules 2012, 45, 9551-9570.
3
Outline
Carbanionic / 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
4
Living Carbanionic Polymerization
Characteristics:
• 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
 Micromixer:
Problems: Mixing,
Fast Mixing,
Heat Dissipation,
Excellent Heat
Sensitivity,
Dissipation,
Reaction
Continuous
Times
?
SIMM-V2
HP-IMM
Living Anions “on Tap“
5
Polymerization in Continuous Flow
• Effective mixing
• High surface-tovolume ratio
• Small internal
volume
• High chemical and
mechanical
resistance
Tonhauser, C.; Natalello, A.; Löwe, H.; Frey, H. Macromolecules. 2012, 45 (25), 9551–9570.
Jähnisch, K.; Hessel, V.; Löwe, 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.; Löwe, H.; Frey, H. Macromol. Chem. Phys. 2008, 209, 1106-1114.
6
Slit Interdigital Micromixers: Laminar Mixing
Multilamination Mixing Device
Parameter
SIMM-V2
Mixing principles
Multi-lamination
Size (L x B x H) / mm
30 x 40 x 30
Temperature / °C
-40 – 220
Pressure stability / bar
100
Inner volume / µL
8
7
Living Anionic Polymerization of Styrene
High Rate Constants (Dependent on Solvent, Temperature, Concentration)
1 .Solvent: Cyclohexane  Non-Polar Reaction Medium
Wurm, F.; Wilms, D.; Klos, J.; Löwe, H.; Frey, H. Macromol. Chem. Phys. 2008, 209, 1106
8
Carbanionic Polymerization in Non-Polar Medium
• Narrow Molecular Weight Distribution
• Convenient Adjustment of Molecular
Weight at Varying Flow Rate Ratios
Sample
Mn
(theor.)
Mn
(SEC)
Mw/Mn
(SEC)
PS-1
500
570
1.25
PS-2
2,000
3,000
1.09
PS-3
3,000
3,300
1.10
PS-4
6,000
8,000
1.08
PS-5
20,000
24,000
1.11
PS-6
30,000
32,000
1.21
Flow Rates:
SEC (THF)
RI Detection
1 – 3.5 mL/min
Residence Times: 40 – 120 s
9
Carbanionic Polymerization in Non-Polar Medium
• Full Conversion (NMR spectroscopy)
• Quantitative Functionalization
(MALDI-ToF-MS)
Sample
Mn
(theor.)
Mn
(SEC)
Mw/Mn
(SEC)
PS-1
500
570
1.25
PS-2
2,000
3,000
1.09
PS-3
3,000
3,300
1.10
PS-4
6,000
8,000
1.08
PS-5
20,000
24,000
1.11
PS-6
30,000
32,000
1.21
MALDI-ToF MS
1H-NMR
(CDCl3)
10
Carbanionic Polymerization in Polar Medium
Solvent: THF  Polar Reaction Medium
•
Extremely Fast Kinetics; Control in Conventional Set-Up Only Possible at
Low Temperature
•
Fast Mixing and Excellent Heat Transfer in the Microstructured Reaction
Device Permit Continuous Synthesis of Well-Defined Polystyrenes at 25°C
11
Polar Medium (THF): Room Temperature (!)
Flow Rates:
0.8 – 2.6 mL/min
Residence Times: 1.6 – 5.0 s
Sample
Mn
(theor.)
Mn
(SEC)
Mw/Mn
(SEC)
PS-7
2,000
1,700
1.28
PS-8
3,000
2,300
1.14
PS-9
4,000
3,600
1.11
PS-10
5,000
6,400
1.10
PS-11
6,000
6,900
1.09
PS-12
10,000
10,500
1.14
PS-13
12,000
11,300
1.09
PS-14
15,000
17,000
1.10
PS-15
40,000
42,200
1.24
PS-16
60,000
71,000
1.25
SEC (THF) RI Detection
12
Conventional Approach vs. Micromixing
Living Carbanionic
Polymerization of
Styrenic Monomers:
Batch Reactor
vs.
Microstructured Reactor
Molecular Weights
Broad Range
Broad Range
Polydispersity
≤ 1.05
Mostly ≤ 1.15
Temperature
≤ - 60°C in Polar Solvents
≥ 25 °C
Hours
Seconds
One
Sample/Experiment
Several
Samples/Experiment
Reaction Times
Versatility
13
Versatile Synthesis of End-Functional Polymers
O
O
O
EEGE
EEGE
(Ethoxy Ethyl Glycidyl Ether)
• Conventional Access to End-Functional Polymers via Carbanionic
Polymerization
• Termination Agents: Chlorosilane, Diphenylethlene (DPE) and Epoxides
•
Epoxide Derivatives  Quantitative Functionalization (Quirk et al.)
Quirk, R. et al. Macromol. Symp. 2000, 161, 37-44.
Quirk, P. R.; Gomochak, D. L. Rubber Chem. Technol. 2003, 76, 812.
14
Synthesis of End-Functional Polystyrene
End-Functionalization of Polystyrene in THF (Polar Medium)
• Termination in Supplementary T-Junction
• Continuous Flow Process: Polymerisation-Termination Sequence
• Rapid and Quantitative Functionalization
15
Synthesis of End-Functional Polystyrene
Flow Rates:
0.5 – 1.5 mL/min
Residence Times: 5 – 15 s
Sample
Mn
(theor.)
Mn
(SEC)
Mw/Mn
(SEC)
PS-17
1,900
1,900
1.15
PS-18
2,900
3,000
1.14
PS-19
4,300
3,900
1.14
PS-20
4,500
6,400
1.18
PS-21
7,500
17,000
1.35
SEC (THF)
RI Detection
16
Synthesis of End-Functional Polystyrene
Flow Rates:
0.5 – 1.5 mL/min
Residence Times: 5 – 15 s
Sample
Mn
(theor.)
Mn
(SEC)
Mw/Mn
(SEC)
PS-17
1,900
1,900
1.15
PS-18
2,900
3,000
1.14
PS-19
4,300
3,900
1.14
PS-20
4,500
6,400
1.18
PS-21
7,500
17,000
1.35
MALDI-ToF MS
17
Functional Termination
C. Tonhauser, D. Wilms, F. Wurm, E. Berger-Nicoletti, M. Maskos, H. Löwe, H. Frey,
Macromolecules 2010, 43, 5582-5588
Synthesis of End-Functional Polystyrene
• Release of Hydroxyl Groups by Acidic Hydrolysis
• Semi-Continuous Approach to Hydroxy Functional Polymers
Facile Access to Precursors for Complex Macromolecular
Architectures (Blockcopolymers, Miktoarm Star Polymers)
19
Synthesis of Block Copolymers
Sample
S:t-BuOS
Mn
(theor.)
Mn
(SEC)
Mn
(MALLS)
Mw/Mn
(MALLS)
PS-17
0:20
3,600
3,700
4,200
1.21
PS-18
5:5
1,400
1,300
1,500
1.18
PS-19
10:5
1,900
1,900
2,100
1.22
PS-20
22:12
4,400
4,800
4,700
1.17
PS-21
80:30
13,600
13,100
13,600
1.15
PS-22
200:25
25,300
24,700
25,600
1.14
20
Change Mixing Pattern: Turbulent Mixing
4-Way Jet Mixing Device
Monomer
Initiator
21
Polymerization in Continuous Flow
Styrene in THF
sec-BuLi in hexane
Sample
2-Vinyl pyridine in THF
sec-BuLi in benzene
Total Flow / Mn (GPC) /
mL/min
g∙mol-1
PDI
Sample
Total Flow / Mn (GPC) /
mL/min
g∙mol-1
PDI
PS-7
8
2 200
1.09
P2VP-8
10
1 800
1.16
PS-8
9
4 700
1.08
P2VP-10
8
3 500
1.17
PS-10
7
32 200
1.08
P2VP-11
7
6 400
1.19
PS-11
8
42 500
1.08
P2VP-12
10
14 300
1.15
PS-14
10
74 200
1.05
P2VP-13
11
18 700
1.17
PS-15
11
104 200
1.04
P2VP-14
11
49 300
1.12
PS-16
12
148 700
1.04
P2VP-15
10
96 000
1.05
22
Polymerization in Continuous Flow
Comparison
PS and P2VP
Characteristics
Batch
Multilamination
Jet mixing
Effort
High
Middle
Low
Side reaction
Difficult to avoid
No
No
Molecular
weights
Broad range
70 000
10 000
150 000
100 000
PDI
< 1.10
1.09 – 1.28
1.19 – 1.26
1.04 – 1.10
1.05 – 1.19
Temperature
≤ - 78°C
RT
RT
Versatility
One sample
Several samples
Several samples
Natalello, A.; Morsbach, J.; Friedel, A.; Alkan, A.; Tonhauser, C.; Müller, A. H.E., Frey, H.;
Org. Process Res. Develop., 2014, dx.doi.org/10.1021/op500149t
23
Influence of Mixing on Polydispersity
C. Serra et al., LAB ON A CHIP, 2008, 8,1682-1687
DOI: 10.1039/b803885f
24
Control of Polydispersity by Microreactor
Influence of PDI on polymer properties
•
Common mindset: “monodisperse polymers are good; polydisperse are bad”1
•
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
(1) Lynd N A, Meuler A J, Hillmyer M A. Polydispersity and block copolymer self-assembly. Progress in Polymer
Science 2008; 33; 875-893.
(2) 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.
25
Carbanionic polymerization
Microreactor
setup
T
M
Mixer
I
Pump 3:
Termination
reagent
Pump 1:
Monomer/Solvent
Flow rate: x
• Controlled living carbanionic
polymerization
Mixing device
 Well
defined polymer architectures
Pump 2:
Initiator/Solvent
Flow
Very
narrow
rate:
y
mass distributions possible (PDI < 1.10)
 Linear dependence of the achieved molecular weights DP = [M]/[I]
Turbulent mixing device – point of broadening
T
M
Mixer
I
sample
sample
Mmax(GPC, g mol-1)
PDI
flow rate (ml s-1)
PS03-01
PS03-01
3403
3403
1,15
1,15
8,0
PS03-02
3586
1,16
8,0
PS03-03
3283
1,22
7,0
PS03-03
PS03-04
3283
3233
1,22
1,22
7,0
6,2
PS03-05
PS03-04
3262
3233
1,22
1,22
5,4
6,2
3
PS03-06
PS03-05
3206
3262
1,26
1,22
4,8
5,4
2.8
PS03-07
3129
1,29
4,2
PS03-08
3162
1,28
3,6
PS03-02
PS03-06
PS03-07
PS03-09
3586
3206
3129
3111
1,16
1,26
1,29
1,34
8,0
8,0
4,8
2.6
4,2
2.4
3,2
1,28
1,33
3,6
2,8
PS03-11
PS03-09
3089
3111
1,45
1,34
2,4
3,2
PS03-12
PS03-10
3197
3453
1,56
1,33
2,0
PS03-13
3176
1,68
1,6
PS03-14
3193
1,75
1,2
2,4
1.4
PS03-12
PS03-15
3197
3387
1,56
1,83
2,0
0,8
1.2
PS03-16
PS03-13
3399
3176
1,95
1,68
0,4
1,6
PS03-17
PS03-14
3484
3193
2,21
1,75
0,3
1,2
PS03-15
3387
1,83
0,8
PS03-16
3399
1,95
0,4
PS03-17
3484
2,21
0,3
3089
1,45
PDI
3162
3453
PS03-11
Flow rate/
ml min-1
2.2
PS03-08
PS03-10
2,8
Pmax = 6600
Pmax = 3400
2
1.8
1.6
1
0
2
1000total
1000
4
flow rate /
6
8
ml 10000
min-1
-1
-1
molecular mass / g mol
10
8.0
8.0
8.0
8.0
7.0
7.0
6.2
6.2
5.4
5.4
4.8
4.8
4.8
4.2
4.2
3.6
3.6
3.2
3.2
2.8
2.8
2.4
2.4
2.4
2.0
2.0
1.6
1.6
1.2
1.2
0.8
0.8
0.8
0.4
0.4
0.3
0.3
Carbanions are still living:
-> Quantitative functionalization (MALDI-ToF)
T
M
Mixer
I
total flow = 0.8 ml/min
PDI (MALDI) = 1.10
total flow = 3.0 ml/min
PDI (MALDI) = 1.09
total flow = 4.0 ml/min
PDI (MALDI) = 1.07
total flow = 6.0 ml/min
PDI (MALDI) = 1.06
total flow = 10.0 ml/min
PDI (MALDI) = 1.05
+ 104 g/mol
Jan
Morsbach
PhD student
T
M
Summary
Mixe
r
I
• Systematic influence on the PDI of a polymerization at
8.0
8.0
7.0
6.2
5.4
4.8
4.2
3.6
3.2
2.8
2.4
2.0
1.6
1.2
0.8
0.4
0.3
constant molecular weights achieved
1000
• System can be transferred to other polymer systems
• Analysis how the properties are influenced are in progress
• Quantitative functionalized polymers enables further
investigations of block copolymer behavior
10000
molecular mass / g mol
-1
Hyperbranched Polymers & Microreactors
30
Hyperbranched Polyglycerol: Target Mn = 1,000 g/mol
SEC analysis (DMF)
T = 120°C
Continuous flow
Mn ~ 750 g/mol
Throughput: 1 – 5 ml/min
Mw/Mn = 1.6
Reaction time: several minutes
D. Wilms, J. Nieberle, J. Klos, H. Löwe, H. Frey, Chem. Eng. Technol. 2007, 30(11), 1519-1524.
Hyperbranched Polyglycerol: Target Mn = 1,000 g/mol
1H-NMR
analysis
Repeat units
Hydroxyl groups
Initiator core
Methanol-d4
O CH2 CH2 O
O CH2 CH2 CH3
Mn = 1,100 g/mol
5.0
4.5
4.0
3.5
3.0
2.5
Chemical Shift (ppm)
2.0
1.5
1.0
0.5
DPn= 16
Hyperbranched Polyglycerol: Initiator attachment?
Confirmation of initiator core incorporation
 MALDI-ToF analysis
800
1000
1200
1400
Mass/Charge
Complete core incorporation
(Independent of flow rates)
14
1600
Hyperbranched Polyglycerol: Variation of Flow Rates
Sample
Target Mn
[g/mol]
Flow Rate
Monomer [ml/min]
Flow Rate
Initiator [ml/min]
Molar Ratio
Initiator:Monomer
Mn
1
( H-NMR)
PG-1
1,000
0,87
1
1 : 10,7
1100
PG-2
1,000
1,74
2
1 : 10,7
1300
PG-3
1,000
2,17
2,5
1 : 10,7
1600
SEC analysis (DMF)
D. Wilms, J. Nieberle, J. Klos, H. Löwe, H. Frey, Chem. Eng. Technol. 2007, 30(11), 1519-1524.
Hyperbranched Polyglycerol: Variation of Flow Rates
Sample
Target Mn
[g/mol]
Flow Rate Monomer
[ml/min]
Flow Rate
Initiator [ml/min]
Molar Ratio
Initiator:Monomer
Mn
(1H-NMR)
PG-4
1,000
0,87
1
1 : 10,7
1100
PG--5
1,020
0,91
1
1 : 12,0
1600
PG-6
1,100
1,97
2
1 : 13,0
1200
PG-7
2,000
1,81
1
1 : 25,0
3200
SEC analysis (DMF)
Mn ~ 150,000 g/mol
Isolation
by
Dialysis
16
Mw/Mn ~ 1.1
Standards)
(PS
Conclusion & Perspectives
Polymer Synthesis in Microreactors:
Carbanionic and Oxyanionic Techniques
•
•
•
•
•
Efficient Continuous Flow Process for Living Carbanionic Polymerization
Facile and Fast Processes Serve to Optimize Reaction Parameters
Convenient Molecular Weight Adjustment
Tailoring of the Polydispersity of Living Polymer Cabanions
Quantitative Implementation of Various End-Groups at Polymers
• Facile Extension to Complex Polymer Architectures
(Star Polymers, Block Copolymers)
36
Conclusion & Perspectives
Pending 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
37
Acknowledgments
Prof. Holger Löwe
Elena Berger-Nicoletti
Michael Maskos
Monika Schmelzer
Institut für
Mikrotechnik Mainz
POLYMAT
38
Conclusion & Perspectives
Pending 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
39
Multilamination Flow Pattern
Micromixer Inlay
Mulitlamination Flow Pattern
• Hydrodynamic Focusing
• Jet Formation in the Slit-Shaped Interdigital Micromixer
Method of Operation
Hessel, V. et al. AIChE Journal 2003, 49, (3), 566-577.
Löb, P. et al. Chemical Engineering Science 2006, 61, (9), 2959-2967.
40