RAFT General Procedures

RAFT POLYMERISATION

RAFT Polymerisation

Conventional free radical polymerisation produces polymers with broad polydispersity (Mw/Mn ) > 1.5, dead polymer chains and poor MW control. (Figure 1)

Figure 1.

RAFT polymerization (Figure 2) can be performed by simply adding a chosen quantity of an appropriate RAFT agent to a conventional free-radical polymerization. The same monomers, initiators, solvents, and temperatures are used. This produces a polymer with controlled molecular weight, narrow polydispersity (Figure 3), built in functionality through the choice of R group, and as the RAFT group is retained it allows for further chemical manipulation of the polymer.

Figure 2.

 

 

 

 

 

 

 

 

Figure 3. Typical molecular weight distributions for a conventional (broad) and RAFT polymerization (narrow). [1]

As the RAFT group is retained it allows for further chemical manipulation of the polymer, RAFT therefore offers the ability to design and manufacture complex, multi-functional polymers with unique properties, blocks, stars, and complex molecular architectures are accessible (Figure 4).

 

 

 

 

 

 

 

Figure 4. Polymer Architectures

Solvents and Initiators

The same solvents and initiators that are used in conventional free-radical polymerization can be used in RAFT polymerisation, common solvents include water, toluene, benzene, acetonitrile, acetone, ethyl acetate, methanol and DMF. RAFT polymerisations can also be carried out in bulk.

RAFT polymerization is usually carried out with conventional radical initiators such as azo-initiators (AIBN, VAZO-88/ACHN, ACP or K2S2O8 are used. Styrene polymerization may be initiated thermally between 100 and 120◦C. Peroxide initiators may oxidise RAFT agents.

Calculated Molecular Weight

Molecular weights in RAFT polymerization can be predicted, [monomer] and [RAFT] are the initial monomer and RAFT agent concentrations, Mw monomer and Mw RAFT are the molar masses of monomer and RAFT agent, and X is the monomer conversion determined gravimetrically. (Equation (1)).

 

Standard procedures for RAFT polymerisation.

 

Standard procedure for laboratory scale solution polymerisation of methyl methacrylate at 90 °C with cyano-4-(dodecylsulfanylthiocarbonyl)sulfanylpentanoic acid (BM1432): an aliquot (2 mL) of a stock solution composed of MMA (14 mL), azobis-(1-cyclohexanenitrile) (9.8 mg), and organic solvent (6 mL) was added to each of a series of ampoules containing the weighed amounts of (BM1432). The contents were degassed, the ampoules sealed and heated at 90°C for 6 hours. The polymer was isolated by exhaustive evaporation of monomer or precipitation in methanol and conversions were determined gravimetrically. Molecular weight and conversion data are shown in below.

Table 1. Molecular weights and polydispersities for PMMA formed by polymerization of MMA (6.55 M) with 1,1 -azobis(1-cyclohexanenitrile) (0.0018 M) as initiator and RAFT agent (BM1432) for 6 h at 90 °C.[2]

Standard procedure for laboratory scale preparation of poly(N,N-dimethyl acrylamide) PDMA using cyanomethyl 3,5-dimethyl-1H pyrazole-1-carbodithioate (BM1481) at 100 °C. A solution containing N,N-dimethyl acrylamide (0.618 mL, 3 M), azobis-(1-cyclohexanenitrile) (2.93 mg, 0.006 M), 18 (12.68 mg, 0.03 M), trioxane (10 mg; internal standard) and acetonitrile (1.382 mL) was prepared in a 5 mL microwave vial. The resulting mixture was degassed, sealed and heated at 100 °C by microwave irradiation for 1 h. The volatiles were removed in vacuo to give poly(DMA) at 99% conversion of DMA (determined by 1H NMR), with Mn 12 100, Đ 1.07.[iv]

Standard procedure for laboratory scale preparation of poly(N,N-dimethylacrylamide)-co-poly(vinylacetate) P(DMA-co-VAC) using cyanomethyl 3,5-dimethyl-1H-pyrazole-1-carbodithioate (BM1481) at 100 °C. A solution containing N,N-dimethylacrylamide (0.010 mL, 0.048 M), vinylacetate (0.553 mL, 3 M), azobis-(1-cyclohexanenitrile) (5.86 mg, 0.012 M), BM1481 (20.28 mg, 0.048 M), and ethyl acetate (1.437 mL) was prepared in a 5 mL microwave vial. The resulting mixture was degassed, sealed and heated at 100 °C via microwave irradiation for 12 hours. The volatiles were removed in vacuo to give poly(DMA-co-VAc) at 55% conversion (>99% of DMA and 54% VAc), with Mn=4700, Đ 1.23.5

Standard procedure for laboratory scale preparation poly(N-isopropylacrylamide-b-N,N-dimethylaminoethylacrylamide) P(NIPAAm-b-DMAEAm) with 4-cyano-4-(dodecylsulfanylthiocarbonyl)sulfanyl pentanoic acid (BM1432). Homo-pNIPAAm polymer with a target molecular weight of 15 kDa was polymerized by dissolving in a round-bottom flask 2 g (17.7 mmol) of NIPAAm, 54 mg (0.134 mmol) of BM1432, and 2.2 mg (13.4 µmol) of 2,2′-Azobis(2-methylpropionitrile) in 4 g p-dioxane. The flask was purged with N2 for 30 min and heated at 60 °C for 12 h, followed by precipitation into pentane. The product was dried under vacuum, dialyzed against DI water at 4 °C, and freeze-dried. The diblock extension was performed by dissolving in a round-bottom flask 1.32 g (83 µmol) of the ∼15 kDa homo-pNIPAAm (macroCTA), 0.2258 g (1.59 mmol) of DMAEAm, 0.18 g (1.59 mmol) of NIPAAm, 1.4 mg (8.3 µmol) of AIBN in 8 mL of MeOH. This resulted in a [DMAEAm]:[NIPAAm]:[mCTA]: [initiator] ratio of 18:18:1:0.1. The flask was purged with N2 for 30 min, followed by heating at 60 °C for 18 h. The MeOH was removed by rotary evaporation, and the product was dissolved in 5 mL of THF and precipitated thrice into pentane. The precipitate was dried under vacuum, dissolved in DI water, purified by PD-10 desalting column, and freeze-dried.[v]

 

[1] Data shown are from GPC analysis of polystyrene prepared by thermal polymerization of styrene at 110◦C for 16 h (Mn 324000, Mw/Mn 1.74, 72% conversion) and a similar polymerization in the presence of cumyl dithiobenzoate (0.0029 M) (Mn 14400, Mw/Mn 1.04, 55% conversion). G. Moad, J. Chiefari, J. Krstina, A. Postma, R. T. A. Mayadunne, E. Rizzardo, S. H. Thang, Polym. Int., 2000, 49, 993-1001. doi:10.1002/1097-0126(200009)49:9 3.0.CO;2-6

[2] Moad, G.; Chong, Y. K.; Postma, A.; Rizzardo, E.; Thang, S. H., Polymer, 2005, 46, 8458−8468.

[iii] Xiaodong Zhou, Peihong Ni, Zhangqing Yu, Polymer, 2007, 48, 6262-6271.

[iv] James Gardiner, Ivan Martinez-Botella, John Tsanaktsidis, Graeme Moad, Polym. Chem., 2016, 7, 481-492.

[v] Michael A. Nash, Paul Yager, Allan S. Hoffman, and Patrick S. Stayton, Bioconjugate Chem., 2010, 21, 12, 2197-2204.