Understanding Acid-Promoted Polymerization of <i>N</i>-Phenoxycarbonyl <i>N</i>-Substituted Glycine: Differences among Methyl, Ethyl, and Butyl Substituents

Polymerization of N-phenoxycarbonyl N-substituted glycines (NNPCs) is a promising approach toward functional polypeptoids due to the excellent tolerance to nucleophilic impurities. However, side reactions in NNPC polymerization are hard to avoid, and the mechanism has not been understood. In the present work, well controlled polymerizations of N-ethyl glycine NPC (NEG-NPC) and N-butyl glycine NPC (NBG-NPC) catalyzed by acetic acid are successfully carried out with designable molecular weights and low dispersities (D̵ < 1.11). The severe side reaction in sarcosine NPC (Sar-NPC, a.k.a. N-methyl glycine NPC) polymerization is inhibited by maintaining low initiator concentration. A kinetic investigation reveals the differences among Sar-NPC, NEG-NPC, and NBG-NPC as well as the mechanism of the side reaction, i.e., oligomers backbite to form 1,4-dialkylpiperazine-2,5-dione (DAP), which is further validated by a density functional theory study. Block and statistical copolymerizations of Sar-NPC with NEG-NPC and NBG-NPC are conducted, producing the corresponding copolypeptoids with designed compositions. In the copolymerization of Sar-NPC with NEG-NPC, the reactivity ratios are 1.133 (Sar-NPC) and 0.969 (NEG-NPC), and in the case of Sar-NPC with NBG-NPC, they are 1.067 (Sar-NPC) and 1.038 (NBG-NPC). The approximately equal values confirm the essentially statistical copolymerization and the ideal random distributions of the two repeating units in polypeptoids. Poly(sarcosine-r-N-butyl glycine)s possess lower critical solution temperatures, and their cloud point temperatures (Tcps) are tunable between 37 and 82 °C with the sarcosine molar fractions from 58% to 70%.