An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards 'clickable' biodegradable polylactide.

Abstract

2-Hydroxy-4-pentynoic acid (1) is a key intermediate towards 'clickable' polylactide which allows for efficient introduction of a broad range of pendant functional groups onto polymers from a single monomer via convenient 'click' chemistry with organic azides. The incorporation of various pendant functional groups could effectively tailor the physicochemical properties of polylactide. The reported synthesis of 1 started from propargyl bromide and ethyl glyoxylate. However, both of starting materials are expensive and unstable; especially, propargyl bromide is shock-sensitive and subjected to thermal explosive decomposition, which makes the preparation of 1 impractical with high cost and high risk of explosion. Herein, we report a simple, economical and safe synthetic route to prepare 1 using cheap and commercially available diethyl 2-acetamidomalonate (4) and propargyl alcohol. The desired product 1 was obtained via alkylation of malonate 4 with propargyl tosylate followed by a one-pot four-step sequence of hydrolysis, decarboxylation, diazotization and hydroxylation of propargylic malonate 5 without work-up of any intermediate.

• Authors: Quanxuan Zhang, Hong Ren, Gregory L Baker
• Journal: Beilstein journal of organic chemistry (Beilstein J Org Chem) Vol. 10 Pg. 1365-71 ( 2014) ISSN: 1860-5397 [Print] Germany
• PMID: 24991290 (Publication Type: Journal Article)