Rapid microwave-assisted cleavage of methyl phenyl ethers: new method for synthesizing desmethyl precursors and for removing protecting groups
✍ Scribed by Anna Fredriksson; Sharon Stone-Elander
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- French
- Weight
- 209 KB
- Volume
- 45
- Category
- Article
- ISSN
- 0022-2135
- DOI
- 10.1002/jlcr.577
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
A new microwave‐enhanced method for rapid demethylation of methyl phenyl ethers using neat methanesulfonic acid (CH~3~SO~3~H) 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‐dimethoxy‐quinazoline (PD153035, 3). High conversions (⩾82%) of 3 were attained with four different conditions (i.e. combination of input effect (35–125 W) and time (15 s–2 min)). 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 and also provide a more direct route for synthesizing precursor compounds for labeling by alkylation. Copyright © 2002 John Wiley & Sons, Ltd.