microwave-assisted polymer synthesis: a new technology...
TRANSCRIPT
Microwave-assisted Polymer Synthesis:
A New Technology at its Outset
Frank Wiesbrock, Richard Hoogenboom, Ulrich S. Schubert
Laboratory of Macromolecular Chemistry and NanoscienceEindhoven University of Technology & Dutch Polymer Institute
OutlineOutline
IntroductionPolymerizations under microwave heating (MWH)
Polymerization of 2-ethyl-2-oxazolineLivingness / First-order kinetics / Bulk polymerization / High molecular weights
Polymerization of other 2-oxazolinesLivingness / First-order kinetics / Bulk polymerization / High molecular weights
Diblock copoly(2-oxazolines)Motivation / Library synthesis / Characterization by GPC and NMR / Surface energy
Conclusions and Outlook
Polymerizations under MWHPolymerizations under MWH
Results from the search “microwave (AND) polymerization”
in the SciFinder database on October 18th, 2004.
1960 1970 1980 1990 20000
102030405060708090
100
Number of publications on microwave-assisted polymerizations, sorted by year
?
F. Wiesbrock, R. Hoogenboom, U. S. Schubert, Macromol. Rapid Comm. 2004, 25, 1739-1764.
Results from the search “microwave (AND) polymerization”
in the SciFinder database on October 18th, 2004.
1960 1970 1980 1990 20000
102030405060708090
100
Number of publications on microwave-assisted polymerizations, sorted by year
?
Polymerizations under MWHPolymerizations under MWH
Polyethers and C-C-coupling reactions
Controlled-radicalpolymerizations
Living cationicring-opening
polymerizationof 2-oxazolines
(→ libraries)
Step-growth polymerization reactions
carried out for polyamides and
polyimides
Ring-opening polymerization reactions
performed (almost) exclusively on
caprolactones and -lactames
Radical polymerizations:Focus on
MMA and styrene
Polymerization of 2Polymerization of 2--ethylethyl--22--oxazolineoxazoline
S OO
O
ON+
ON
O
N
ON+
N
O
n Initiation Propagation Termination OHN
O
n
water
+
TsO− TsO−
F. Wiesbrock, R. Hoogenboom, C. H. Abeln, U.S. Schubert, Macromol. Rapid Comm. 2004, 25, 1895-1899.
Poly(2Poly(2--ethylethyl--22--oxazolineoxazoline): Livingness): Livingness
0 20 40 60 80 1000
1000
2000
3000
4000
5000
6000
Mn
conversion (%)
80 °C 100 °C 120 °C 140 °C 160 °C 180 °C
[ ] [ ] [ ] MPk *pdt
Md ⋅⋅=−
[ ][ ] [ ] t Ikln 0pMM
t
0 ⋅⋅=⇒
0 10 20 30 40 50 600
1
2
3
4
5
ln ([
M0 ]
/[ M
t ])
→
t / min →
180 °C 160 °C 140 °C 120 °C 100 °C 80 °C
Poly(2Poly(2--ethylethyl--22--oxazolineoxazoline): Kinetics): Kinetics
2.2 2.3 2.4 2.5 2.6 2.7 2.8
-7
-6
-5
-4
-3
-2
-1
EA = 73.4 kJ mol-1
ln k
p
T−1 (103 K−1)
eAk RTAE
p−⋅=
Alnlnk T1
RE
pA ⋅−=⇒
Poly(2Poly(2--ethylethyl--22--oxazolineoxazoline): Bulk ): Bulk polympolym..
4 5 6 7 8 9 100
2000
4000
6000
Mn: single measurements
Mn
c (mol L-1)
1.05
1.10
1.15
1.20
1.25
PD
I
PDI: single measurements PDI: arithmetic mean with error bars
(at 2σ-niveau)
7 8
t / min
c / mol L-1
9.90 7 5
Poly(2Poly(2--ethylethyl--22--oxazolineoxazoline): Higher): Higher MMnn
0 200 400 600 800 1000
0100002000030000400005000060000700008000090000
100000
PDI
Mn
[M] / [I]
Mn and PDI values (solvent, calibration)
DMF, PEG DMF, PMMA CHCl3, PEG theoretical
1.21.62.02.42.8
12 14 16 18 20 22
t / min
ratio [M]/[I0] 50 150 300 1000
Other 2Other 2--oxazolinesoxazolines: Livingness: Livingness
0 20 40 60 80 1000
1000
2000
3000
4000
50002-Methyl-2-oxazoline
Mn
→
conversion / % →
180 °C 160 °C 140 °C 120 °C 100 °C theor.
0 20 40 60 80 1000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
2-Phenyl-2-oxazoline
Mn
→
conversion / % →
200 °C 180 °C 160 °C 140 °C 120 °C 100 °C theor.
0 20 40 60 80 1000
100020003000400050006000700080009000
100001100012000
2-Nonyl-2-oxazoline 140 °C 130 °C 120 °C 110 °C 100 °C theor.
Mn
→
conversion / % →
The number average molecular weights depend linearly on the monomer conversion.
R. Hoogenboom, F. Wiesbrock, M. Leenen, M.A.R. Meier, U.S. Schubert, submitted.
Other 2Other 2--oxazolinesoxazolines: First: First--order kineticsorder kinetics
0 10 20 30 40 50 600
1
2
3
4
5
6
2-Methyl-2-oxazoline
ln ([
M0]/[
Mt])
→
t / min →
180 °C 160 °C 140 °C 120 °C 100 °C
0 20 40 60 80 100 1200
1
2
3
4
5
2-Phenyl-2-oxazoline
ln ([
M0]/[
Mt])
→
t / min →
200 °C 180 °C 160 °C 140 °C 120 °C 100 °C
0 10 20 30 40 50 600
1
2
3
4
5
62-Nonyl-2-oxazoline
ln ([
M0]/[
Mt])
→
t / min →
140 °C 130 °C 120 °C 110 °C 100 °C
Kinetic analysis
F. Wiesbrock, R. Hoogenboom, M. Leenen, U.S. Schubert, submitted.
Polymerization of 2Polymerization of 2--oxazolinesoxazolines
Monomer Frequency factor A
1011 L mol−1 s−1
Activation energy EAkJ mol−1
2-Methyl-2-oxazoline
18.0 75.4
2-Ethyl-2-oxazoline
7.17 73.4
2-Phenyl-2-oxazoline
53.8 84.4
2-Nonyl-2-oxazoline
4030.2 78.5
OHN
O
n
OHN
O
n OH
N
O
n
OHN
O
n
ON+
N
R O Rn
22--oxazolinesoxazolines: Bulk polymerization: Bulk polymerization
1 2 3 4 5 6 7 8 9 10 11 12
0
1000
2000
3000
4000
5000
2-Methyl-2-oxazoline
PDI
→
Mn
→
M / mol L−1 →
1.01.11.21.31.41.5
1 2 3 4 5 6 7 8
0
2000
4000
6000
8000
10000
12000
PDI
→
Mn
→
M / mol L−1 →
1.01.11.21.31.41.5
2-Phenyl-2-oxazoline
1 2 3 4 5
02000400060008000
100001200014000
Mn
→
M / mol L-1 →
1.0
1.1
1.2
2-Nonyl-2-oxazoline
PD
I →
Reduced solvent amounts
22--oxazolinesoxazolines: Higher : Higher MMnn
High molecular weight polymers
0 200 400 600
0
10000
20000
30000
40000
50000
PDI
→
Mn
→
[M] / [I] →
Mn and PDI values (solv., calibr.) DMF, PEG DMF, PMMA theor.
1.01.52.02.5
2-Methyl-2-oxazoline
0 100 200 300 400 500 600 700
0
20000
40000
60000
80000
100000
120000
PDI
→
Mn
→
[M] / [I] →
Mn and PDI values (solv., calibr.) DMF, PEG DMF, PMMA CHCl3, PEG theor.
1.01.21.41.61.82.0
2-Phenyl-2-oxazoline
0 100 200 300 400 500
01000020000300004000050000600007000080000 Mn and PDI values (solv., calibr.)
CHCl3, PEG theor.
PDI
→
Mn
→
[M] / [I] →
1.01.11.21.31.41.5
2-Nonyl-2-oxazoline
NNN
O
O
O
N
O
N
O
N
O
N
O
N
O
N
O
N
O
N N N
O
O
O
N N
O
O
NNNN
O
O
O
O
NCH3
OOH
CH3-(EtOx)10-(NonOx)10-OH
Diblock copolyDiblock copoly(2(2--oxazolineoxazoline)s)s
F. Wiesbrock, R. Hoogenboom, M. Leenen, S.F.G.M. van Nispen, M. van der Loop, U.S. Schubert, in preparation.
DiblockDiblock copolymers: Motivationcopolymers: Motivation
hydrophobicblock
hydrophilicblock H2O
hydrophobicblock
hydrophilicblock
H2O
+ A (hydrophobic)
AA
AA
AA
AA
AA AAAA
A AA
AA
A
Micellar catalysis
CATEduct(s) Product(s)
drug drug
drug drug
drugdrug
drug
Drug delivery
Formation of micelles Micelles with hydrophobic agents
Diblock Diblock copolymer librarycopolymer library
N
O
n
N
O
n
N
O
n
N
O
n
CH3
OH
N
O
n
N
O
n
N
O
n
N
O
n
CH3
OH
N
O
n
N
O
n
N
O
n
N
O
n
CH3
OH
Each block is composed of 50 monomer units.
Synthesis of a 16-membered library of di block copolymers of the AB- and the AA-type
Copolymerization: OverviewCopolymerization: Overview
General Procedure: Each first block prepared six times
1
2
3
4
5
6
Characterization of the first propagation step
Characterization of the first propagation step
+ MeOx
+ EtOx
+ NonOx
+ PheOx
Characterization
of the diblock
copolymers
General Procedure: Each first block prepared six times
1
2
3
4
5
6
Characterization of the first propagation step
Characterization of the first propagation step
+ MeOx
+ EtOx
+ NonOx
+ PheOx
Characterization
of the diblock
copolymers
Synthesis: OverviewSynthesis: Overview
Chemspeed Platform or fumehood (*) Single-mode microwave reactor
1. Preparation of a stock solution, transfer to the reaction vials
(*) depending on the number of experiments
2. Synthesis ofthe first block
3. Addition of the second monomer
4. Incorporationof the second
block5. Analysis ofthe (set of)
diblockcopolymers
GPC characterizationGPC characterization
Poly(2-ethyl-2-oxazoline) as first block; GPC measurements
7 8
CH3-(EtOx)50-OH CH3-(EtOx)50-(EtOx)50-OH CH3-(EtOx)50-(NonOx)50-OH CH3-(EtOx)50-(PheOx)50-OH
retention time / min
in DMF in CHCl3
Reliable number average molecular weights can be obtained only for the mono block polymers and the diblock copolymers of the AA-type. Diblock copolymers of theAB-type can be characterized by 1H-NMR (combined with the analysis of the
first block by GPC measurements).
16 17 18 19 20 21 22 23
retention time / min
CH3-(EtOx)50-OH CH3-(EtOx)50-(MeOX)50-OH CH3-(EtOx)50-(EtOX)50-OH CH3-(EtOx)50-(PheOX)50-OH
8 7 6 5 4 3 2 1 0
ppm
400150
OHCH3
N
O
N
O
50 50
11HH--NMRNMR
Diblock copoly(2-oxazoline)s:Measurements in CDCl3
8 7 6 5 4 3 2 1 0
ppm
400150
OHCH3
N
O
N
O
50 50
8 7 6 5 4 3 2 1 0
ppm
430 150
OHCH3
N
O
N
O
50 50
Block copolymer libraryBlock copolymer library
*N
O
CH3 n
OHN
O
* n OH
N
O
* n
MeMe [4]p.t. 400+400PDI ---/1.16
MeEt [4]p.t. 400+500PDI ---/1.17
OHN
O
* n
MePhe [4]p.t. 400+1800PDI ---/1.25
OHN
O
* n
MeNon [4]p.t. 400+400PDI ---/---
*N
O
CH3 n EtMe [4]
p.t. 500+400PDI ---/1.18
EtEt [4]p.t. 500+500
PDI 1.12/1.16
EtPhe [4]p.t. 500+1800PDI 1.27/1.19
EtNon [4]p.t. 500+400
PDI 1.15(*)/---
firstblock second
block
*N
O
CH3 n NonMe [2]p.t. 400+400PDI ---/---
NonEt [2]p.t. 400+500
PDI 1.70(*)/---
NonPhe [2]p.t. 400+1800PDI 1.14/---
NonNon [2]p.t. 400+400PDI 1.43/---
*N
O
CH3 n PheMe [3]
p.t. 1800+400PDI ---/1.18
PheEt [3]p.t. 1800+500PDI 1.35/1.19
PhePhe [3]p.t. 1800+1800PDI 1.27/1.16
PheNon [3]p.t. 1800+400PDI 1.28/---
[n]: concentration of the respective monomers in mol/L; p.t. preparation time (in s);
PDI values obtained from CHCl3 /DMF solutions; (*): GPC traces on next slide
Diblock copolyDiblock copoly(2(2--oxazolineoxazoline)s)s
6 7 8
PDI = 1.15
CH3-(EtOx)50-(NonOx)50-OH
retention time [min]7 8 9
PDI = 1.70
CH3-(NonOx)50-(EtOx)50-OH
retention time [min]
The order of incorporating the monomers
into the polymer chainmust be chosen
carefully!
The findings in the courseof the preparation of the
NonOx-EtOx polymerwere found to be reproducible and
independent of thesolvent (CH3CN, CH2Cl2)
NonOxPheOx
EtOxMeOx
MeO
x EtO
x
Phe
Ox
Non
Ox0
10
20
30
40
50
60
70
80
90
CA
diio
dom
etha
ne (d
eg)
Block 2Block 1
ContactContact--angle measurementangle measurement
Polar test liquid: Ethylene glycol
4 Measurements per Contact Angle
Apolar test liquid: Diiodo methane
4 Measurements per Contact Angle
NonOx PheOxEtOx
MeOx
MeO
x
EtO
x
Phe
Ox
Non
Ox0
10
20
30
40
50
60
70
80
90
100
CA
eth
ylen
e gl
ycol
(deg
)
Block 2 Block 1
S. Wijnans, B.-J. de Gans, F. Wiesbrock, R. Hoogenboom, U.S. Schubert, Macromol. Rapid Commun. 2004, 25, in press.
ContactContact--angle measurementangle measurement
Nonyl chains preferentially orient to surface → lower surface energy
Result of 70 min measuring time (128 contact angles: saves time by factor 10)
MeOxEtOx
PheOxNonOx
Non
Ox
Phe
Ox EtO
xM
eOx05
10
152025
30
35
40
45
50
Sur
face
ene
rgy
(mN
/m)
Block 2 Block 1
ConclusionsConclusions
A steadily growing number of polymer syntheses undergoes major improvements in terms of reaction times, purity and yields of the targeted product(s) under microwave irradiation.
The living cationic ring-opening polymerization of 2-oxazolines undergoes remarkable accelerations under the high temperatures in the course of the microwave irradiation; first-order kinetics and livingness are maintained.
Diblock copoly(2-oxazoline)s can be prepared in a convenient 2-step process. For the incorporation of 50 monomers (per block) into the polymer chain, the total reaction times span the range from 14 minutes (EtOx-EtOx) to 80 minutes (PheOxPheOx).
The molecular weight distributions are narrow before and after the addition of the second monomer (except for the polymers that contain a poly(2-nonyl-2-oxazoline) as first block).
N
O
n
N
O
n
N
O
n
N
O
n
CH3
OH
OutlookOutlook6464 TriblockTriblock copolymerscopolymers
AcknowledgementAcknowledgement
Prof. Dr. Ulrich S. Schubert
Richard Hoogenboom
Mark Leenen
Sjoerd van NispenMichel van der Loop
Sanne Wijnans Berend-Jan de Gans