Thiol-reactive functional poly(meth)acrylates: multicomponent monomer synthesis, RAFT (co)polymerization and highly efficient thiol–para-fluoro postpolymerization modification

Abstract

A novel class of thiol-reactive (meth)acrylate monomers and the quantitative postpolymerization modification of their RAFT-made (co)polymers with aromatic, glycosidic, and aliphatic thiols are presented. A set of 6 different N-functional 2-(meth)acryloyloxy-2-(pentafluorophenyl)acetamide monomers bearing pentafluorophenyl groups was prepared by a Passerini three-component reaction of (meth)acrylic acid, 2,3,4,5,6-pentafluorobenzaldehyde, and various isocyanides in water in up to near-quantitative isolated yields. RAFT polymerization was used to produce well-defined homopolymers and copolymers with methyl methacrylate, tert-butyl methacrylate, poly(ethylene glycol) methyl ether (meth)acrylate, and pentafluorophenyl acrylate, with low polydispersity indices of generally Đ_M ≤ 1.23. In the presence of base, (co)polymers underwent selective para-fluoro substitution reactions with thiols in the absence of any side reactions observable by ¹H and ¹⁹F NMR spectroscopy and size exclusion chromatography. The selection of employed thiols included various alkanethiols, a thiolated glucose derivative, mercaptopropionic acid, L-cysteine and the drug captopril. ¹⁹F NMR kinetic measurements indicated quantitative thiol–para-fluoro substitutions after <3–80 min at 25–45 °C using 1–1.1 equiv. of thiol, depending on the reactivity of the employed thiol (aromatic, glycosidic > primary aliphatic > secondary aliphatic > tertiary aliphatic) and the choice of a suitable base (triethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)). The versatility of thiol-reactive (meth)acrylate species is demonstrated by the examples of a thermoresponsive copolymer showing a thiol-sensitive lower critical solution temperature (LCST) and the selective sequential modification with thiols and amines of a doubly reactive copolymer containing activated pentafluorophenyl esters.