Living Radical Polymerization - ACS Publications

Chapter 13

Copper-Mediated Living Radical Polymerization Utilizing Biological and End Group Modified Poly(ethylene-co-butylene) Macroinitiators

Downloaded by NORTH CAROLINA STATE UNIV on September 21, 2012 | http://pubs.acs.org Publication Date: August 15, 2000 | doi: 10.1021/bk-2000-0768.ch013

David M. Haddleton, Adam P. Jarvis, Carl Waterson, Stefan A. F. Bon, and Alex M. Heming Department of Chemistry, University of Warwick, Coventry, CV4 7AL, United Kingdom ([email protected])

Summary : Copper mediated living radical polymerization can be used with a wide range of functional initiators to produce functional polymers. Block copolymers may be efficiently prepared using macroinitiators. This is demonstrated in this paper by synthesis and characterisation of a cholestrol based initiator and macroinitiators based on mono and difunctional polymers of ethylene and butylène. Polymerization of styrene and methacrylates using Schiff base ligands in conjunction with Cu(I)Br proceeds in a controlled manner yielding homopolymers, A - B diblock and A - B A triblock (co)polymers of defined molecular weight and low polydispersity. Polymers based on methacrylic acid, 2dimethylaminoethyl methacrylate and a random copolymer of methacrylic acid and methyl methacrylate have been synthesized by use of the cholestrol initiator to give resulting water soluble/dispersible polymers.

Introduction Synthetic polymers containing biologically active moieties and amphiphilic segments are understandably receiving significant attention. Such polymers play important roles in many biological processes and their potential in applications for medicinal uses is now being realised (1-3). Living radical polymerization, and more specifically atom transfer polymerization, allows control of the synthesis of polymers

182

© 2000 American Chemical Society

In Controlled/Living Radical Polymerization; Matyjaszewski, K.; ACS Symposium Series; American Chemical Society: Washington, DC, 2000.

183


whilst being inert to many types of useful functional groups. For example, Fukuda and co-workers (4) have synthesized glycopolymers by atom transfer polymerization, whilst Marsh et al have produced polymers incorporating a uridine monomer, 5'methacryloyluridine (5). Copper(I) mediated polymerization is proving a versatile technique for the synthesis of many different polymers (6-9) We have been ulitizing a range of SchifF base ligands used in conjunction with Cu(I)Br and an appropriate initiator has been established giving a versatile and extremely effective living polymerization system for acrylics and other vinyl monomers (10-13). Herein, we describe the synthesis and characterisation of a cholesterol derived initiator, for atom transfer polymerization which illustrates the versatility of this approach, giving a wide range of functionalised polymers. Block copolymer formation using macroinitiators synthesized by the esterification of Kraton L-1203™ and Kraton L-2203™, commercially available mono and dihydroxyl terminated copolymers of polyethylene and butylène, is also reported. These examples have been chosen so as to illustrate the potential diverse range of polymers which can be produced via the simple approach of transforming alcohols via esterification with 2-bromo-wobutyrylbromide into initiators for living radical polymerization.

Experimental

General Information. For general procedures and analysis techniques see previous publications (14). A l l reactions were carried out using standard Schlenk techniques under a nitrogen atmosphere. Methyl methacrylate and styrene were purified by passing down an activated basic alumina column so as to remove inhibitor, water and other protic impurities. Trimethylsilyl methacrylate ( T M S M A ) was purified by a trap-totrap distillation over C a H . Kraton liquids L-1203 and L-2203 were obtained from Shell Chemicals, Belgium and used without further purification. A l l other reagents were used as received without further purification. Cu(I)Br (Aldrich, 98%) was purified according to the method of Keller and Wycoff.(15). 2

Synthesis of cholesteryl-2-bromoisobutyrate, 1 Cholesterol (2.0 g, 5.17 mmol) was dissolved in anhydrous pyridine (15 ml) with 4-dimethylaminopyridine (0.26 mmol, 0.031 g), a solution of 2-bromo-2-methyl propionyl bromide (7.75 mmol, 0.96 ml) was added dropwise with stirring, the


184 reaction was left overnight at room temperature. The product was isolated by first removal of insolubles by filtration and a C H C 1 solution was washed with sodium bicarbonate and water. The organic layer was dried over magnesium sulfate, fliltered and the solvent removed to yield the product as a yellow solid which on washing with methanol resulted in a white solid. Yield = 2.20g (79.4%), pure by T L C . Calcd. for C i H i B r 0 : C, 69.51; H , 9.60. Found: C, 69.48; H 9.54. 2


3

5

2

2

Synthesis of Kraton L-1203 Macroinitiator, 2 Kraton L-1203 168.15 g (0.04 mol) was dissolved in anhydrous tetrahydrofuran 600 mL. Triethylamine 8.4 m L (0.06 mol) was added to the mixture followed by the addition with stirring of 2-bromo-2-methyl propionyl bromide 7.4 mL (0.06 mol). The reaction was allowed to stir overnight at room temperature. The product was isolated by filtration followed by rotary evaporation. The resulting viscous product was dissolved in CHC1 500 m L and the solution was sequentially washed with saturated N a H C 0 solution and water. The CHC1 layer was dried with M g S 0 filtered and the solvent was removed to leaving a clear colourless viscous liquid. Yield = 165.9 g 3

3

3

4

Synthesis of the difunctional macroinitiator based on Kraton L-2203,3 Kraton L-2203 192.14g (0.06 mol) was dissolved in anhydrous tetrahydrofuran 600 mL. Triethylamine 25.2 m L (0.18mol) was added to the mixture followed by the addition with stirring of 2-bromo-2-methyl propionyl bromide 23.1 mL (0.18 mol). The reaction was allowed to stir overnight at room temperature and the workup followed the same procedure as for Kraton L-1203 to give a pale yellow viscous liquid. Yield = 170.8 g.

Polymerization of Methyl Methacrylate with 1 as initiator; [MMA]/[I]/[Cu]/[L] = 100/1/1/2 in 66% toluene solution Initiator 1, (0.268 g, 0.5 mmol) Cu(I)Br (0.072 g, 0.5 mmol) and a magnetic follower were placed in a Schlenk tube. Deoxygenated toluene (10.6 mL) and N-npropyl-2-pyridylmethanime (0.180 g, 1.15 mmol) were added. The solution was deoxygenated via three freeze pump thaw cycles and the solution heated to 90 °C. Deoxygenated inhibitor free M M A (10.6 mL) was then added (t = 0). Samples were removed periodically for analysis, via syringe. Polymerization of other monomers with 1 were carried out under similar conditions.


185


Polymerization of Methyl Methacrylate with 2 and 3 as initiator; [MMA]/[I]/[Cu(I)]/[Ligand] = 90/1/1/2 Macroinitiator, 2 (4.35 g , 1 mmol) , Cu(I)Br (0.1433 g , 1 mmol) and a magnetic follower were placed in an oven dried Schlenk tube. Deoxygenated xylene 20.4 m L , N-«-octyl-2-pyridylmethanimine (0.4380 g , 2 mmol) and deoxygenated M M A 9.6 m L (90 mmol) were added to the Schlenk tube. The resulting solution was deoxygenated via four freeze pump thaw cycles and the reaction was placed in a thermostatically controlled oil bath at 90°C. Samples were removed periodically for conversion and molecular weight analysis. Conversions were carried out by gravimetry and molecular weight analysis was carried out by G P C analysis or *H N M R analysis. Polymerizations with other monomers utilised a similar regime as described above.

Quaternisation of Poly(2-(dimethylamino)ethyl methacrylate), P(DMAEMA) To a solution of P ( D M A E M A ) in T H F was added a 3-fold excess of methyl iodide at room temperature. The quaternised polymer precipitated from solution after stirring for 24 hours. The solid was filtered and purified by soxhlet extraction with THF and dried under vacuum for 24 hours.

Results and Discussion

Synthesis of initiators 1,2 and 3 The cholesterol derived initiator, cholesteryl-2-bromoisobiityrate (1, scheme 1) was synthesized via reaction of 2-bromo-wo-butyrylbromide with cholesterol. Addition of the 2-bromoisobutyryl group was confirmed by ATR-FTIR and N M R . The Kraton derived macroinitiators (2 & 3, scheme 1) were synthesized via the esterification of Kraton L-1203 and Kraton L-2203. Introduction of the initiator species onto the hydroxyl termini of the Kraton L-2203 was clearly seen by both ATR-FTIR (\)c=o 1738 c m and loss of 1)O-H 3342 cm" ), Figure 1. Esterification of the hydroxyl groups upon Kraton L-2203 was quantitative by *H N M R , Figure 2. *H N M R demonstrated two types of hydroxyl end termini. The triplet at δ 3.7 (A), H O CflU (CH ) is due to an ethylene end terminus and the doublet at δ 3.3 (Β), HOCHiCH ( C H C H ) corresponds to a butylène end terminus. Upon functionalisation both resonaces moved downfield to δ 4.22 and 3.91 respectively. Interestingly the monofunctional derivative only contained ethylene end termini resulting in a triplet resonance. It was also noted that the methyl signal of the ester groups was split into 4

2

1

3

2

3



Kraton L-1203

Scheme 1


187


Before Functionalisation

After Functionalisation

Figure 1. FT-IR Analysis of Kraton L-2203™ Before and After Functionalisation

(ppm)

]

Figure 2. HNMR

Analysis of Kraton L-2203 Before (a) and After φ) Functionalization


188 two separate signals (C and D), again being attributed to two different end group environments.


Polymerization of methyl methacrylate initiated by 1 Polymerization of methyl methacrylate using a Sehiff base ligand in conjunction with Cu(I)Br and 1 as an initiator proceeds in a controlled manner to give polymers with M close to that predicted with relatively narrow molecular weight distributions, Table 1. The incorporation of the cholesterol moiety within the polymer, including the retention of the vinyl group is confirmed by Ή N M R , Figure 3. n

ι ι ι ι) ι ι ι ι I ι ι ι ι ι ι ι ι ι

5

ιI

4

I I

I I 1 ι ι ι

ι

I I M I f )) i [ 1 M 1 i I )

3

2

1

I

1 [ I t I 1 I I I I I [ I I ) I

0

(ppm)

Figure 3. ^NMR

spectrum of ΡΜΜΛ initiated by 1 showing the retention of the vinyl proton at δ 5.30.

The number average molar mass increases linearly with conversion following an apparent lack of control at the beginning of the reaction, Figure 4. This might be exlpained by insufficient Cu(II) at the beginning of the reaction or deviation away from the P M M A calibration in the SEC most evident at low mass. The C N M R spectrum of the polymer shows the aHerminal end group which, as expected after atom transfer polymerization, contains a tertiary bromide. Resonances at δ 58.93, 58.43 and 58.35 are characteristic of meso and racemic end group stereochemistry, 1 3


189 corresponding to resonances obtained from a model compound, methyl-2bromoisobutyrate, [(CH ) C(C0 Me)Br] δ 55.4 (16).


3

2

2

Conversion

Figure 4. Evolution of molecular weight for the polymerization of MMA initiated by 1; [MMA]/[I]/[Cu]/[L] = 100/1/1/2

Table 1. Selected data for the atom transfer polymerization of vinyl monomers in toluene for initiator 1. MJM Reaction M (theory) Conversion Mi time (hours) (g/mol) (g/mol) MMA" 1.20 6.85 9840 9510" 93 Styrene 1.23 7.00 34 3940 4460 1.20 DMAEMA" 3050 2.00 100 3040 TMSMA" 2.73 2540 2910 84 TMSMA/MMA 4.83 2450 98 2990 Polymerizations carried out at 90 °C. Polymerizations carried out at 110°C. M (theory) = ([M ]o/[I] χ MW ) * conversion + MW where MW is the molecular weight of monomer, where MW iu tor is the molecular weight of the cholesterol initiator and [M ]o/[I] is the initial concentration ratio of monomer to initiator. M obtained from GPC with molecular weights being calibrated using poly(methyl methacrylate) standards. M„ obtained from GPC with molecular weights being calibrated using poly(styreyie) standards. ^ M„ obtained from HNMR spectroscopy. Monomer

c

a

n

b

e

f

f

a

f

a

b

c

n

monomer

0

monomer

inHiator>

monomer

in

monomer

a

0

d

n

e

!


190 Polymerization of styrene initiated by 1


The M n again increases linearly with conversion, and unlike the polymerization of methyl methacrylate, control is observed throughout the reaction, Figure 5. A s expected, the rate of polymerization is slower than that observed for the polymerization of methyl methacrylate.

4000-1 3500 3000 ^

2500

V W tt, 2000 §

1500 1000 5000 Ά 0.00

1

1 0.05

«

1 0.10

«

1 0.15

·

1 0.20

·

1 0.25

1

1 ' 0.30

1 0.35

R _

0.40

Conversion

Figure 5. Evolution [Styrene]/[I]/[Cu]/[L]

of M for the polymerization = 100/1/1/2. n

of styrene initiated by 1;

Synthesis of water soluble polymers initiated with 1 We are particuarly interested in the synthesis of amphiphilic block copolymers containing hydrophilic-hydrophobic moieties. These polymers form micelles in aqueous solution, with the hydrophobic blocks aggregating to form the core and the hydrophilic blocks in the solvated outer layer (17-19). Water soluble polymers were synthesized by two methods. The first was the polymerization of (2(dimethylamino)ethyl methacrylate) (DMAEMA) using atom transfer polymerization. The P ( D M A E M A ) synthesized typically gave low polydispersity indexes (MJM = 1.20) with *H N M R spectroscopy giving excellent agreement for M with the theoretical values calculated, Table 1. A n increase in the hydrophilicity of P ( D M A E M A ) is achieved by quaternisation with methyl iodide, Figure 6. n

n



191

Figure 6. Quaternisation of P(DMAEMA) with methyl iodide.

l

H N M R spectroscopy confirmed quantitative quaternisation of the amine group in the polymer chain enhancing water solubility dramatically compared with the unquaternised polymers. The *H N M R spectrum of unquaternised P ( D M A E M A ) in C D C I 3 confirms the presence of both the cholesterol and D M A E M A units. On changing the solvent to D 0 , the cholesterol resonances are suppressed for both the quaternised and unquaternised polymers. This suggests the hydrophobic cholesterol moiety is poorly solvated; possibly indicating the existence of micelle formation. 2

The second method performed was polymerization of trimethylsilyl methacrylate ( T M S M A ) by atom transfer polymerization with 1. Deprotection of the trimethylsilyl group to free acid was achieved via the hydrolysis of the polymer in methanol at 60 °C forming poly(methacrylic acid). Removal of the trimethylsilyl group was confirmed by *H N M R spectroscopy. The incorporation of methyl methacrylate into poly(methacrylic acid) to form a statistical copolymer was also studied to form polymers with varying degrees of hydrophilicity. The synthesis of a statistical copolymer containing 50 mol % T M S M A and 50 mol % M M A gave a composition and M (obtained from *H N M R spectroscopy) close to that expected (Micaic = 2520, M eo = 2500). These poly(methacrylic acid) polymers form aggregates with hydrophilic-hydrophobic domains in basic aqueous solution. n

nth


192 Polymerization of M M A and BzMA initiated by 2 Polymerization of methyl methacrylate and benzyl methacrylate with 2 as macroinitiator proceeds in a controlled manner to give A - B block copolymers with M close to that predicted and narrow molecular weight distribution, Table 2. The kinetic plots for the polymerization of M M A and B z M A are shown in Figure 7. The rate is first order with respect to monomer concentration and is linear indicating a 'living'or 'pseudo-living' process. The M increases linearly with conversion and agree well with expected values. The initial points in the molecular weight plot are low in comparison to the theoretical M with this being due to Kraton L-1203 not being available with an hydroxyl functionality of exactly 1.0. A s a consequence the samples taken from the reaction contain small amounts of the unfunctionalised Kraton. This observation has also been noted in the work of Batsberg et al for the A B block copolymerization of styrene (9). n


n

n

The incorporation of the P M M A block is demonstrated in Figure 8 where the G P C for the macroinitiator has shifted to higher mass upon block copolymerization with M M A . Kraton macroinitiators are viscous liquids and the Kraton-PMMA copolymer product was isolated as a white powder. The unfunctionalised Kraton was removed from the polymer by precipitation in 40 % ethanol /60 % hexane.

Table 2 Selected data for the A T P polymerization of vinyl monomers in xylene using the monofunctional macroinitiator Kraton L-1203 ™ Monomer Kraton L-1203 MMA MMA MMA MMA BzMA BzMA

[M]:[2]

45 :: 1 45 :: 1 90 :: 1 90 :: 1 50 : 1 50 : 1

C

e

0

Time / mins

Conv

/%

280 280 280 280 150 150

92.1 92.1 93.5 93.5 96.6 96.6

Mv/M

Mi (Theory) 4500

M, (Exp) 7170

11310a

10650" 11700" 14340" 15520" 13920" 14570"

15580a 15710a

b

n

1.04 1.11 1.11 1.15 1.11 1.15 1.16

a

M (Theory) =([Monomer]o/[Initiator] χ A/w mortomer)x ConV + Mwkraton A/\y Kraton ÎS a S S U m e d to be 7170 as obtained against PMMA calibration. M obtained from GPC against PMMA equivalent. Following precipitation. n

0

5

b

n

c


193

• [BzMA]:[2]:[Cu(ï)]:[Ligand]=50:1:1:2


ο [MMA]:[2]:[Cu(I)]:[Ligand]=90:1:1:2

150

350

200

Time (Mins)

Figure 7. First order rate plots for the copper mediated atom transfer polymerization of methyl methacrylate (MMA) and benzyl methacrylate (BzMA) utilising [Monomer]:[2]:[Cu(I)]:[Ligand] = 90:1:1:2 and 50:1:1:2 respectively

Polymerization of M M A and D M A E M A initiated by 3 Polymerization of M M A and 2-di(methylethyl)amino methacrylate using 3 as macroinitiator also proceeded in a controlled manner to give A - B - A block copolymers with M close to that predicted and narrow molecular weight distribution, Table 3. The M increases linearly with conversion with values of M agreeing well with predicted values. A value for k [pol *] of 2.17 χ 10" s for the 70 : 1 reaction agrees well with k [pol *] = 1.2 χ 10" s" for the 140:1 reaction. The resulting A - B - A block copolymers have a relatively narrow molecular weight distribution with M /M typically less than 1.25. Block copolymerization with the water soluble monomer dimethylaminoethyl methacrylate ( D M A E M A ) was also investigated. The first order rate plots for the A - B - A block copolymer are linear indicating little termination occurs. The polymerization involving D M A E M A : 3 = 89:1 was carried out by halving the concentration of macroinitiator whilst keeping the concentration of monomer the same. The value of k [pol *] = 2.84 χ 10" s" for the 44.5 : 1 reaction agrees well with k [pol *] = 1.46 χ 10" s" for the 89:1 reaction which is approximately half. The polydispersity index of the resulting block copolymers is relatively narrow typically M / M =1.20 n

n

n

4

_1

p

4

1

p

w

4

1

p

4

1

p

w

n


n

194 Kraton Macroinitiator, 2 Kraton/Ρ MMA Copolymer

(1

A\

1 1

•

• \ \ \

M 15520 PDi 1.11


n

;

M 7170 PDi 1.04 n

"l

\

i\

i y 1

·

10

»

V

J

1

'

•

14

12

1

·

1

16

18

Elution Time

Figure 8. GPC overlay demonstrating A-B block copolymer formation

Table 3. Selected data for the ATP polymerization of vinyl monomers in xylene using the difunctional macroinitiator Kraton L-2203 ™ Monomer

Kraton L-2203 MMA After Ppt MMA After Ppt DMAEMA DMAEMA

[M]:[3]

140: 1

Rxn Time (mins)

240

Conv (%)

78.5

Mv/M

Mn (Theory)

M (Exp)

3500

7380

18400"

17720 18490 14090 14660 16410 11791"

tt

e

1.11 e

e

70 : 1

240

95.5

14110"

e

e

89 : 1 44.5 : 1

240 240

86.0 98.2

15530" 10370"

n

a

a

1.20 1.16 1.23 1.16 1.19 1.20

M (Theory) =([Monomer]o/[Initiator] χ Mw monomer) x Conv + Mw kraton MwKmm is assumed c to be 7380 as obtained against P M M A calibration. Mw Kraton is taken to be 3500. M n obtained from G P C against P M M A equivalent M determined from H N M R spectroscopy. n

0

b

d

l

n


195


Conclusions Esterification of alcohols containing a range of functionality e.g. biological molecules containing an O H functionality, produces initiators containing the 2bromoisobutyrate fragment. This is a versatile and facile route for the synthesis of fimctionalised initiators for atom transfer polymerization. A range of functionalised polymers have been synthesized by initiation of cholesteryl-2-bromoisobutyrate 1. Living polymerization of methyl methacrylate and styrene afford polymers of controlled molecular mass and narrow molecular mass distributions. Water soluble polymers containing the cholesterol moiety have been synthesized by the hydrolysis of poly(trimethylsilyl methacrylate) and quaternisation of poly(2(dimethylamino)ethyl methacrylate). Esterification of the hydroxyl end functionalities of Kraton L-1203 and Kraton L-2203 with 2-bromo-2-methylpropionyl bromide is a simple and effective route to generating mono and difunctional macroinitiators based on copolymers of poly(butylene-co-ethylene). The subsequent use of these macroinitiators in atom transfer polymerization of methacrylates mediated with a Schiff base ligand and Cu(I)Br has been shown to be an effective method for producing A - B and A - B - A block copolymers with controlled molecular weight and narrow polydispersity. Taken together the examples chosen show the potential of this chemistry to synthesise end functional polymers and block copolymers from macroinitiators.

Acknowledgement We wish to thank B P (APJ), EPSRC ( A M H , C W ) for funding and Shell, Belgium for supplying the Kraton Liquid polymers

References 1. 2. 3. 4.

Spaltenstein, Α.; Whiteside, G . M . J. Am. Chem. Soc 1991, 113, 686. Wasserman, P. M . Science 1987, 235, 553. Miyata, T.; Nakamae, K . Trends in Polymer Science 1997, 5, 198-206. Ohno, K.; Tsujii, Y . ; Fukuda, T. J. Polym. Sci. Part a-Polym. Chem. 1998, 36, 2473-2481. 5. Khan, Α.; Haddleton, D . M.; Hannon, M . J.; Marsh, A . In Preparation 1999.



196 6. (a) Shipp, D . Α.; Wang, J.-L.; Matyjaszewski, K . Macromolecules 1998, 31. (b) Patten, T. E.; Matyjaszewski, K . Accounts of Chemical Research 1999, 32, 895. (c) Matyjaszewski, K . Chemistry-α European Journal 1999, 5, 3095. 7. Gaynor, S. G.; Matyjaszewski, K . Macromolecules 1997, 30, 4241. 8. Jankova, K.; Chen, X. Y.; Kops, J.; Batsberg, W. Macromolecules 1998, 31, 538541. 9. Jankova, K . ; Kops, J.; Xianyl, C.; Batsberg, W . Macromol. Rapid Commun. 1999,20,219. 10. Haddleton, D. M.; Jasieczek, C . B . ; Hannon, M . J.; Shooter, A . J. Macromolecules 1997, 30, 2190-2193. 11. Haddleton, D . M.; Waterson, C.; Derrick, P. J.; Jasieczek, C.; Shooter, A . J. Chem. Commun. 1997, 683. 12. Percec, V.; K i m , H . J.; Barboiu, B . Macromolecules 1997, 30, 8526-8528. 13. Haddleton, D . M.; Kukulj, D.; Duncalf, D . J.; Heming, A . H.; Shooter, A . J. Macromolecules 1998, 31, 5201. 14. Haddleton, D . M.; Crossman, M. C.; Hunt, Κ. H . ; Topping, C.; Waterson, C.; Suddaby, K . G. Macromolecules 1997, 30, 3992. 15. Keller, R. N.; Wycoff, H . D. Inorg. Synth. 1947, 2, 1. l6. Haddleton, D . M.; Heming, A . H.; Kukulj, D.; Jackson, S. G . J. Chem. Soc. Chem. Commun. 1998, 1719. 17. Butun, B . C.; Billingham, N. C.; Armes, S. P. Chem. Commun. 1997, 671. 18. Butun, B. C.; Billingham, N. C.; Armes, S. P. J. Am. Chem. Soc. 1998, 120, 11818. 19. Baines, F. L.; Billingham, N. C.; Armes, S. P. Macromolecules 1996, 29, 3416.


Living Radical Polymerization - ACS Publications

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