Synthesis of Diaryl Ethers, Diaryl Thioethers, and Diarylamines Mediated by Potassium Fluoride-Alumina and 18-Crown-6: Expansion of Scope and Utility(1).
An efficient alternative to the Ullmann ether synthesis of diaryl ethers, diaryl thioethers, and diarylamines involving the S(N)Ar addition of a phenol, thiophenol, or aniline to an appropriate aryl halide, mediated by potassium-fluoride alumina and 18-crown-6 in acetonitrile or DMSO, is described. Expansion of the reaction conditions to include DMSO as solvent has resulted in a far greater range of substitution patterns permitted on the electrophile. For example, it was found that electronically unfavorable 3-chlorobenzonitrile could be condensed with 3-methoxyphenol to form the corresponding diaryl ether in 66% yield, a combination not normally amenable to Ullmann coupling. Electron-withdrawing groups present on the electrophile may be as diverse as nitro, cyano, formyl, acetyl, ester, amide, and even aryl. The method features a simple reaction procedure that provides products in generally good to excellent purified yields.
Sawyer
J. Scott
JS
The Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Schmittling
Elisabeth A.
EA
Palkowitz
Jayne A.
JA
Smith
William J.
WJ