Albemarle Corporation

Brian F Becnel

Mahmood Sabahi

Kevin J Theriot

In producing nabumetone or precursor thereof, use is made of 2-bromo-6-methoxynaphthalene formed by (a) methylating 6-bromo-2-naphthol with methyl bromide or methyl chloride, in a halogen-free liquid solvent comprising at least about 40% by weight of one or more compounds of the formula RZ where R is a hydrogen atom or an alkyl group, and Z is a hydroxyl group or a cyanide group with the proviso that if Z is a cyanide group, R is an alkyl group, and in the presence of at least one strong base; and (b) recovering and purifying 2-bromo-6-methoxynaphthalene so formed. The 6-bromo-2-naphthol in turn is preferably formed by reacting 1,6-dibromo-2-naphthol with hydrogen in a halogen-containing liquid solvent comprising at least about 50% by weight of (A) at least one liquid organic halide solvent in which the halogen content has an atomic number of 35 or less or (B) a mixture of water and at least one such liquid organic halide solvent, and in the presence of catalytic amounts of (i) a tungsten carbide-based catalyst, and (ii) at least one phase transfer catalyst, most preferably while purging HBr from the reaction mixture as it is formed. In this way, the quantities of by-products formed in the overall operation are reduced, the need for use of excess iron and/or dimethyl sulfate as reaction components is avoided, and the overall efficiency of plant operation is improved especially when conducted on a large scale.

Production of nabumetone or precursors thereof

In producing (.+-.)-2-(6-methoxy-2-naphthyl)propionic acid or precursor thereof from 2-bromo-6-methoxynaphthalene, use is made of 2-bromo-6-methoxynaphthalene formed by (a) methylating 6-bromo-2-naphthol with methyl chloride in a solvent comprising one or more compounds, RZ, where R is a hydrogen atom or an alkyl group, and Z is --OH or --CN provided that if Z is --CN, R is alkyl, and in the presence of a strong base; and (b) recovering and purifying 2-bromo-6-methoxynaphthalene so formed. Preferably, the 6-bromo-2-naphthol is formed by (1) reacting 1,6-dibromo-2-naphthol with hydrogen, in a solvent comprising (a) organic halide in which the halogen has an atomic number of 35 or less or (b) a mixture of water and such organic halide, and in the presence of catalytically effective amounts of (i) a tungsten carbide-based catalyst, and (ii) phase transfer catalyst; and (2) separating 6-bromo-2-naphthol from the organic halide solvent so that the 6-bromo-2-naphthol is substantially free of halogen-containing impurities before use in the above methylation reaction. This technology makes possible reductions in quantities of co-products formed, eliminates need for use of excess iron and/or dimethyl sulfate as reaction components, and makes possible improvements in plant operating efficiency. Precursors of (.+-.)-2-(6-methoxy-2-naphthyl)propionic acid formed from such 2-bromo-6-methoxynaphthalene are Grignard reagent of 2-bromo-6-methoxynaphthalene, bis(6-methoxy-2-naphthyl)zinc, 6-methoxy-2-naphthylzinc halide, 6-methoxy-2-naphthyllithium, 6-methoxy-2-naphthylcopper(I), bis(6-methoxy-2-naphthyl)cadmium, 6-methoxy-2-naphthylcadmium halide, and 6-methoxy-2-vinylnaphthalene.

Growing community of inventors

Port Allen, LA, United States of America

Brian F Becnel