ATRP: Complete Tools for the Synthesis of Well-Defined, Functionalized Polymers

Synthesis of functional polymers via ATRP

Atom transfer radical polymerization (ATRP) provides a simple route to many well-defined (co)polymers with predetermined molecular weight, narrow molecular weight distribution, and high degree of chain end functionality.^1-4 It has been effectively applied to the preparation of polymers with precisely controlled functionalities, topologies, and compositions.^{5, 6} ATRP is a radical process and is much more tolerant of functional groups than ionic polymerizations. This broadens the range of unsaturated molecules that can be polymerized or copolymerized via ATRP and opens the possibilities of straightforward introduction of various functionalities into the polymer structure. Numerous (co)polymers can be formed with a wide-ranging spectrum of properties. As presented in Figure 1, there are four major strategies for the synthesis of telechelic polymers with functional groups via ATRP:⁷

1. Use of functional initiators
2. Substitution of the terminal halogen atom
3. Direct polymerization of functional monomers
4. Polymerization of "protected" monomers, followed by post-polymerization chemical transformations

The first two approaches yield end-functionalized polymers whereas the last two yield polymers with multiple functionalities along the backbone (Figure 1).

Functional initiators for ATRP

ATRP uses simple initiators, mainly alkyl halides R-X (X = Cl, Br).^{1, 8, 9} The number-average molecular weight (Mn) of polymers prepared by ATRP depends on the initial concentration ratio of monomer (M) to initiator as well as the monomer conversion:
Mn = ([M]₀ / [RX]₀) × conversion × MW(M). The alkyl halides used as initiators can contain one or more halogen atoms. Depending on the exact initiator structure and the number of halogen atoms, the architecture of the prepared polymers can be varied from linear (using alkyl halides with a single halogen atom), to star-like or brush-like (multiple halogen atoms in the initiator). Star polymers can be generated using initiators with alkyl halide groups attached to a single core (Figure 2).

The alkyl halides used as initiators may also contain various functional groups. The main advantages of using functional initiators in the synthesis of polymers via ATRP are the following:

• Direct functionalization
• No post-polymerization modification required
• Yields α-telechelic polymers
• Multiple applicable functionalities (more than those attainable via nucleophilic substitution of ω-end halogen atom)

Figure 3 illustrates structures of alkyl halide functional initiators that yield end-functionalized polymers. Groups such as hydroxyl in the structure of the ATRP initiator (I) are suitable for the synthesis of polymers that can react with molecules, or surfaces with carboxylic acid / isocyanate groups. Polymers synthesized with initiators containing azide or alkyne groups are able to participate in click chemistry-type functionalizations. Allyl group-containing initiators (III) yield polymers that can undergo hydrosilylation or thiolene reactions with molecules or surfaces containing Si-H or S-H bonds, respectively. Trichlorosilyl groups react with surfaces containing hydroxy or amine groups (including Si-OH bonds, such as those on the surface of silica particles or glass).

Finally, disulfide-containing difunctional initiators (IV) yield polymers containing a functional group able to react with gold surfaces, and gives the ability to degrade in reducing environments. It should be noted that polymers prepared by ATRP contain two chain ends: the α-end derived from the initiator and the ω-end, which is normally bromide or chloride. Alkyl halides (II and V)can participate in a number of nucleophilic substitution reactions, which expands the types of end-functional polymers accessible through ATRP.⁹

Ligands for highly active ATRP catalysts

One drawback of the classical ATRP method is the use of large amounts of the CuX / ligand catalyst complex required.^{2, 11} The obtained polymers require tedious purification to remove the catalyst. Although various methods for catalyst removal have been developed, the extra purification step is associated with longer time needed to obtain the final product, and generates chemical waste.¹²

The use of very active ligands tris[2-(dimethylamino)ethyl]amine (Me₆TREN, Prod. No. 723142) and tris(2-pyridylmethyl)amine (TPMA, Prod No. 723134) alleviates this problem (Figure 4a). These ligands can be used in new techniques called Activators ReGenerated by Electron Transfer (ARGET)^{13, 14} and Initiators for Continuous Activator Regeneration (ICAR),¹⁵ which decreases the amount of catalyst needed to only a few (often single-digit) ppm. For comparison, 1,000 to 10,000 ppm of catalyst were used in traditional ATRP. Both techniques employ a reducing agent, a radical initiator such as AIBN¹⁵ in ICAR ATRP or tin(II) ethylhexanoate,^{13, 14, 16-18} ascorbic acid,¹⁹ glucose,¹⁴ hydrazine,¹⁵ or Cu(0),²⁰ in ARGET ATRP. These reducing agents allow for the regeneration of the lower oxidation state metal complex, which would normally be irreversibly converted to the higher oxidation state complex due to radical termination (Figure 4b).