N. Bensel et al. / Tetrahedron Letters 43 (2002) 4281–4283
4283
tuted guaiacol derivatives using various amides,
carbamates, and aldehydes allows access to a wide
range of N-benzyl amides and carbamates. Moreover, it
shows that this original process involves inexpensive
and readily available starting materials, such as acet-
amide, paraformaldehyde, guaiacol, methanesufonyl
chloride, acetic and sulfuric acids, and can thus be
carried out on a kg scale without any difficulty.
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In summary, we have developed an original synthetic
pathway for the preparation of 5-substituted guaiacol
derivatives. This method relies on masking the phenol
into a deactivating group by converting it into the
corresponding mesyl ester. Amidomethylation leads to
the regioselective CꢀC bond formation at the guaiacol
5-position. Thus, 5-aminomethyl-guaiacol was obtained
in a four-step sequence and 75% overall yield. Exten-
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