Year: 2026
Type: article
Abstract: dehydration of 4-pentenoic acid with excess acetic anhydride, which yielded the desired product in >99% purity following fractional distillation. Recycling of unreacted anhydride and acetic acid byproduct for use in future batches introduces an element of chemical circularity. Reaction of E2 with the resulting anhydride proceeded at room temperature to afford the desired diester in 96% isolated yield. Purification is restricted to a simple aqueous workup, with no column chromatography and no need to separate out carbodiimide-derived urea impurities. Importantly, the resulting monomer was then subjected to photoinitiated thiol-ene step-growth copolymerization with 1,3-propane dithiol and it showed equivalent polymerization behavior when directly compared to the chemically identical monomer made by Steglich esterification. Under identical conditions, these two pro-E2 monomers polymerized to give practically indistinguishable molecular weight distributions and glass-transition temperatures. Substrate scope was further explored by esterification of the natural product boldine with pentenoic anhydride. This also resulted in high yield and purity by crystallization, with no chromatography needed. In contrast, the conventional DIC-mediated synthesis of boldine dipentenoate required dichloromethane and extensive silica-gel chromatography, consuming approximately 1 L of organic solvent and 125 g of spent silica gel per gram of product. These results demonstrate that carboxylic anhydrides can provide a practical alternative to carbodiimide-mediated esterification for polymerizable pro-drug synthesis while simultaneously reducing hazardous reagents, solvent use, purification burden, and solid waste.
Source: RSC Advances
DOI: 10.1039/d6ra09163f
Institution: Rensselaer Polytechnic Institute
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,042
OpenAlex ID: W7225322676