Rapid microwave-assisted cleavage of methyl phenyl ethers: New method for synthesizing desmethyl precursors and for removing protecting groups

摘要

A new microwave-enhanced method for rapid demethylation of methyl phenyl ethers using neat methanesulfonic acid (CH3SO3H) is presented. Using a monomodal microwave cavity, cleavage of anisole (1), used as model compound, to phenol (2) was achieved with high conversions (ca 80%) in very short reaction times (10-20 s). The feasibility of cleaving one or both of two methoxy groups was illustrated with 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD153035, 3). High conversions (< greater-than-or-equal-to >82%) of 3 were attained with four different conditions (i.e. combination of input effect (35-125 W) and time (15s-2min)). 4-(3-Bromoanilino)-7-hydroxy-6-methoxyquinazoline (4), 4-(3-bromoanilino)-6-hydroxy-7-methoxyquinazoline (5) and 4-(3-bromoanilino)-6,7-dihydroxyquinazoline (6), the possible mono- or di-demethylated compounds, were obtained. Methods for rapid demethylations are of interest in radiochemistry for post-labeling deprotections of hydroxyl containing aromatic rings andalso provide a more direct route for synthesizing precursor compounds for labeling by alkylation. Copyright < copyright > 2002 John Wiley & Sons, Ltd.