Thiol RAFT agents

RAFT polymerization can be performed simply by adding a chosen quantity of an appropriate RAFT agent to an otherwise conventional radical polymerization. Generally, the same monomers, initiators, solvents and temperatures are used. The only commonly encountered functionalities that appear incompatible with RAFT agents are primary and secondary amines and thiols. 

Also, Kerep and Ritter reported a radical chain transfer agent as a dual initiator, FRP-1 [45]. The first step builds on the fact that hydroxyl groups are much better nucleophiles in enzymatic ROP than thiols. Due to the chemoselectivity of the enzyme, PCLs with predominantly thiol endgroups were obtained, which were subsequently used as macroinitiator for styrene. The authors report that the reaction yield can be further increased by microwave irradiation. Although thiols provide less control over the radical polymerization than RAFT agents, the subsequent radical polymerization successfully leads to the synthesis of PCL-Z -PS. 

Ideally, to avoid odor issues with the RAFT agent and polymer the Z , and preferably the R(S) groups, should be based on non-volatile thiols (e.g. dodeca-nethiol for Z in 5). RAFT agents of this type already described in the literature include... 

RAFT agents based on volatile thiols (e.g. 12,13) can be odorous. 

Winnik and coworkers [11] utilized an azide functional RAFT agent to synthesize azide functional linear PNIPAM followed by a thiol-ene Michael addition reaction with propargyl acrylate, producing a-alkyne-ou-azide PNIPAM. Consequently, the cyclization reaction by CuAAC was achieved in water with CUSO4 and ascorbic acid as the catalyst (Scheme 33). Further, the solution properties showed that the cyclic PNIPAM had higher phase transition temperature due to the endless chain structure of the cycUc compared to the linear counterpart with the same molecular weight. 

Very recently, Monteiro and Jia [85] reported a thiol-ene reaction for the preparation of cyclic polymer with inherent alkyne functionality from RAFT polymerization. An alkyne-hydroxyl-RAFT agent, through post-polymerization functionalization, was used to introduce an acrylate to the polymer via the reaction of the hydroxyl group with acryloyl chloride. Through the successive aminolysis of the RAFT and thiol-ene reaction between the acrylate group and thiol group, which was generated from aminolysis under hexylamine, alkyne functional monocyclic PSTY, PDMA, PNIPAM, and P BA were obtained (Scheme 37). 

Transesterification (thiol exchange by reaction of a dithioe-ster with a thiol). Thioglycolic acid-based dithioesters are poor RAFT agents. FFowever, they can serve as precursors to other RAFT agents as they undergo facile reaction with other thiols to provide new dithioesters. For example, reaction of dithioester 86 with benzylmercaptan provides benzyl dithiobenzoate (103) in high yield (Scheme 25). ... 

Reaction of thiochloroformate with thiol The esterification of the appropriate thiol with a thiochloroformate (Scheme 28) has been used in the synthesis of phenyl xanthates and phenyl trithiocarbonates. This method was also used to synthesize the T-RAFT agent 173. " The thiochloroformate may be replaced with the corresponding imidazole to avoid use of thiophosgene. ... 

In solution polymerization the RAFT agent should be selected for solubility in the reaction medium. In protic media some RAFT agents show hydrolytic sensitivity which increases with RAFT agent activity (dithiobenzoates > trithiocarbonates aliphatic dithioesters). " ° " ° RAFT agents are also susceptible to nucleophilic attack by primary and secondary amines and thiols. 

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