ABC Triblock Terpolymers with Orthogonally Deprotectable Blocks: Synthesis, Characterization, and Deprotection

Abstract

The development and availability of new protecting groups are vital for all branches of synthetic chemistry. Equally vital is the facile and selective removal of these groups, leaving intact other protecting groups which are to be cleaved later. Herein we demonstrate this concept of orthogonal deprotection by combining three different forms of protected methacrylic acid (MAA) in the same terpolymers. One of these protected monomers was 2-(pyridin-2-yl)ethyl methacrylate (PyEMA), recently developed by us, whose units can be readily converted to MAA units either under alkaline hydrolysis conditions or thermally. The second monomer was tetrahydro-2H-pyran-2-yl methacrylate (THPMA) which can be cleaved either via acidic hydrolysis or by thermolysis. The third form of protected MAA was benzyl methacrylate (BzMA) which can be subjected to hydrogenolysis. Two ABC triblock terpolymers based on all three of these monomers were successfully synthesized—one by reversible addition–fragmentation chain transfer (RAFT) polymerization and the other by group transfer polymerization (GTP)—thus proving the feasibility of these demanding three-stage syntheses via both polymerization methods. The molecular weight characteristics and compositions of the terpolymers were determined by gel permeation chromatography and proton nuclear magnetic resonance spectroscopy (1H NMR), respectively. Subsequently, the ABC triblock terpolymers were sequentially subjected to conditions of alkaline hydrolysis, acidic hydrolysis, and hydrogenolysis, leading to the selective cleavage of the PyEMA, the THPMA and the BzMA units, respectively, without affecting the remaining types of protecting groups, according to analysis using 1H NMR spectroscopy. Similarly selective was the acidic hydrolysis followed by alkaline hydrolysis. Thermal treatment at 130 °C of the terpolymers led to the conversion of both the PyEMA and the THPMA units to MAA units, without affecting the BzMA units, yielding amphiphilic diblock copolymers whose self-assembly properties in water were investigated.