Abstract
A simple and efficient method for α-brominating lactones that affords α-bromolactones under mild conditions using tetraalkylammonium hydroxide (R4N+OH−) as a base was developed. Lactones are ring-opened with Br2 and a substoichiometric amount of PBr3, leading to good yields of the corresponding α-bromocarboxylic acids. Subsequent intramolecular cyclization over 1 h using a two-phase system (H2O/CHCl3) containing R4N+OH− afforded α-bromo lactones in good yields. This method can be applied at the 10 mmol scale using simple operations. α-Bromo-δ-valerolactone, which is extremely reactive and difficult to isolate, could be isolated and stored in a freezer for about one week using the developed method. Optimizing the solvent for environmentally friendly large-scale syntheses revealed that methyl ethyl ketone (MEK) was as effective. In addition, in situ-generated α-bromo-δ-valerolactone was directly converted into a sulfur-substituted functional lactone without difficulty by reacting it with a sulfur nucleophile in one pot without isolation. This new bromination system is expected to facilitate the industrial use of α-bromolactones as important intermediates.
Highlights
Lactones are important heterocycles in the organic chemistry, materials science, and medicinal chemistry fields, and bromolactones are important synthetic intermediates for selectively, effectively, and practically introducing lactone units into organic molecules [1-18]
We begin by first discussing the properties and stabilities of industrially important five- and six-membered lactones. γ-Butyrolactone and its α-brominated derivative are both stable at room temperature; α-bromo-γ-butyrolactone is readily synthesized by brominating the five-membered lactone under basic conditions
We developed a facile and efficient method for α-brominating lactones using tetraalkylammonium hydroxide (R4N+OH−) as the base under mild conditions
Summary
Lactones are important heterocycles in the organic chemistry, materials science, and medicinal chemistry fields, and bromolactones are important synthetic intermediates for selectively, effectively, and practically introducing lactone units into organic molecules [1-18]. The α-bromolactone, in which the bromine atom is located at the Beilstein J. Α-Bromolactones are widely used as synthetic intermediates for functional materials and pharmaceuticals, as well as initiators in atom-transfer living radical polymerization (ATRP) reactions and functional polymer synthesis [29-34]. The main process for the bromination of δ-valerolactone (1a) was treating the lactone with lithium diisopropylamide (LDA) at −78 °C to first generate the corresponding enolate, trapping it with trimethylsilyl chloride (TMSCl) to form the enol silyl ether, followed by reaction with bromine (Scheme 1a) [37,38]. While the industrial demand for α-bromolactones has grown in recent years, the above-mentioned laboratory-level synthetic methods are not suitable for scale-up because LDA, TMSCl, and enol silyl ethers are sensitive to moisture and air, as well as being expensive for large-scale syntheses. The development of an innovative, cost-effective method for the production of α-bromolactones in large quantities is highly desirable
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
