- Reagent Availability
- Experimental User Friendliness
-The synthesis of unsymmetrical ethers by SN2 displacement of alkyl halides by alkoxides is called the Williamson ether synthesis. The reaction works best when the R group is primary.
-In certain cases such as trityl protection, the reaction proceeds by SN1 pathway.
–E2 elimination is the main competing reaction, which predominates for tertiary alkyl halides.
-SN2-promoting aprotic polar solvents such as acetonitrile and DMF are generally used.
-The leaving group is not limited to halides. Alkyl sulfonates are equally usable.
・Williamson, W. Liebigs Ann. Chem. 1851, 77, 37.
・Williamson, W. J. Chem. Soc. 1852, 106, 229.
・Dermer, O. C. Chem. Rev. 1934, 14, 385. DOI: 10.1021/cr60049a002
In SNAr type reactions, note that the reactivity decreases in the order of F > Cl > Br > I.
 J. R. Prous, ed. Drugs Fut. 1992, 17, 1093.
 J. R. Prous, ed. Drugs Fut. 2002, 27, 339.
 J. R. Prous, ed. Drugs Fut. 1990, 15, 1080.