The problem of the N-demethylation of quaternary ~onium salts has bee a perennial one in organic chemistry. The classical method for demethylatio
Involves the pyrolysis of ammonium halides, which may however lead to extens deoomposition.
2 Refluxing ethanolamine has also been used for purpqeee of demethylation, 3 but this reagent can lead to predominantly Hofmann elimlnatil and when methoxy groups arw present, 0-demethylation can also take place. 'D examples where these side reactions overshadow N-demethylation are the conversion of magnoflorine Iodide (I) and isocorydlne methiodlde (II) to the diphenolic phenanthrene derivative III. 4 Finally, N-demethylation conditions Involving the use of LIAlH, In a refluxing high boiling solvent such as THF or dioxane usually fail whenever one or more phenolic group Is present, so that salts I and II are recovered unchanged. 5
We now wish to report that the ideal method of N-demethylation.mey turn out to involve the use of thiophenoxide anion in refluxing 2-butonona.
The reaction is of the simple SW2 type, and consists of attack by the thlophenoxlde anion on the N-methyl group. In Table I it con be seen that the