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Williamson Ether Synthesis: History
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Chemistry, Organic
Contributor: Helena Kang

The Williamson ether synthesis forms an ether by nucleophilic substitution of an alkoxide or phenoxide at an electrophilic carbon bearing a leaving group. The oxygen nucleophile is commonly generated by deprotonating an alcohol or phenol, after which it attacks an alkyl halide, sulfonate, or analogous substrate through an SN2 pathway [1]. Bond formation therefore occurs between oxygen and an sp3 carbon, with inversion at a stereogenic reacting center. Primary electrophiles are generally the defining substrates because steric hindrance slows bimolecular displacement, while secondary and especially tertiary electrophiles increasingly undergo competing elimination. Aryl and vinyl halides do not participate by the ordinary SN2 mechanism, although phenoxides can serve as nucleophiles. Intramolecular Williamson reactions generate cyclic ethers when nucleophile and electrophile are tethered [2]. The method is distinct from acid-catalyzed alcohol dehydration and from transition-metal-catalyzed aryl ether formation because its essential elementary step is direct nucleophilic substitution by an oxygen anion.

  • Williamson ether synthesis
  • alkoxide
  • nucleophilic substitution
  • ether formation

Organic Chemistry Synthesis Methods • Organic Chemistry • Chemistry • Physical Sciences

References

  1. Wang, Z. Williamson Ether Synthesis; Wiley: Hoboken, NJ, United States, 2010; pp. 3026-3030. [CrossRef]
  2. Arun Parikh; Hansa Parikh; Khyati Parikh. Williamson Ether Synthesis; Cambridge University Press (CUP): Cambridge, United Kingdom, 2006; pp. 430-434. [CrossRef]
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