Wei-Ming Xu, Hong-Qiang He
Feb 2, 2010
Citations
0
Influential Citations
2
Citations
Journal
Organic Preparations and Procedures International
Abstract
2-Bromo-6-methoxynaphthalene (2) is an important intermediate in the preparation of non-steroidal anti-inflammatory agents,1,2 such as 4-(6-methoxy-2-naphthyl)2-butanone (nabumetone) and 2-(6-methoxy-2-naphthyl)propionic acid (naproxen). A survey of the literature indicates that several synthetic procedures1–8 already exist. Among them, methylation of 6-bromo-2-naphthol (1) to give 2-bromo-6-methoxynaphthalene (2) with dimethyl sulfate2,3 and methyl halides4–6 are most commonly used. Methyl chloride5 and methyl bromide6 are gases at room temperature and thus have a limited utility. However, other reagents (dimethyl sulfate and methyl iodide) present serious toxicological and carcinogenic risks due to their volatility and their ability to methylate nucleic acids in living organisms. Environmental and toxicological concerns have resulted in increased interest in new methylating reagents. As a consequence, Maras et al.7 developed an efficient synthesis of 2-bromo-6-methoxynaphthalene (2) using tetramethylammonium chloride as a methylating agent, but the reaction was carried out under microwave-assisted conditions. Alternatively, Raju et al.8 reported a site-directed nuclear bromination by two-phase electrolysis of 2methoxynaphthalene and sodium bromide to obtain 2. The high yield accompanied with high regioselectivity of the electrochemical method might prove promising for future industrial use. Recently, dialkyl carbonate and in particular dimethyl carbonate (DMC) was used as an environmentally benign substitute for methyl halides and dimethyl sulfate.9 Carbon dioxide and methanol, which can be easily removed from the reaction medium, are the only by-products formed.