Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Patent
1999-03-04
2000-09-19
Padmanabhan, Sreeni
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
568390, 568393, 568634, 562406, C07C 3702
Patent
active
061215007
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
This invention relates to processes for preparing 6-bromo-2-naphthol and derivatives thereof from 1,6-dibromo-2-naphthol.
BACKGROUND
6-Bromo-2-naphthol is a compound which has particular value as an intermediate in the preparation of non-steroidal antiinflammatory agents, such as 4-(6-methoxy-2-naphthyl)-2-butanone (commonly known as nabumetone) and 2-(6-methoxy-2-naphthyl)-propionic acid (commonly known as naproxen), via 6-bromo-2-methoxynaphthalene.
As disclosed in British Patent 380,563 (I. G. Farbenindustrie), it is known that 6-bromo-2-naphthol can be prepared by the hydrodebromination of 1,6-dibromo-2-naphthol with an alkali metal sulfite in an aqueous or aqueous-alcoholic solvent. This process is commercially unattractive, however, because of its requiring long reaction times to achieve good yields, e.g., 12 hours at reflux temperature to obtain a 99% yield when potassium sulfite is used and 30 hours at reflux temperature to obtain only a 90% yield when sodium sulfite is employed.
It would be desirable to be able to utilize an alkali metal sulfite as the hydrodebrominating agent in the preparation of 6-bromo-2-naphthol and its derivatives without requiring the long reaction times of I. G. Farbenindustrie for the hydrodebromination reaction.
SUMMARY OF INVENTION
It has now been found that the reaction time needed for preparing 6-bromo-2-naphthol by the hydrodebromination of 1,6-dibromo-2-naphthol with an alkali metal sulfite can be reduced by conducting the reaction in a water-glycol mixture as the solvent. Thus, the invention resides in a process which comprises reacting 1,6-dibromo-2-naphthol with an alkali metal sulfite in a water-glycol solvent mixture to prepare 6-bromo-2-naphthol and subsequently, if desired, converting the 6-bromo-2-naphthol product to a 6-bromo-2-alkoxynaphthlene which may then be converted to a pharmaceutically-active derivative, such as nabumetone or naproxen. Embodiments of this invention include: 1,6-dibromo-2-naphthol with an alkali metal sulfite in a water-glycol solvent mixture, 6-bromo-2-naphthol which has been produced by reacting 1,6-dibromo-2-naphthol with an alkali metal sulfite in a water-glycol solvent mixture, and 6-bromo-2-methoxynaphthalene obtained from 6-bromo-2-naphthol which has been produced by reacting 1,6-dibromo-2-naphthol with an alkali metal sulfite in a water-glycol solvent mixture.
DETAILED DESCRIPTION
The alkali metal sulfite which is reacted with 1,6-dibromo-2-naphthol in the practice of the invention may be any suitable alkali metal sulfite but is usually one in which the alkali metal is sodium or potassium, preferably sodium. The amount employed may be any amount in the range of 1-2 mols per mol of 1,6-dibromo-2-naphthol, but optimum results are ordinarily obtained when the sulfite/1,6-dibromo-2-naphthol mol ratio is in the range of 1.4-1.5/1.
Because of cost and availability considerations, ethylene glycol is apt to be preferred as the glycol component of the solvent mixture. However, other glycols (e.g., propylene glycol, butylene glycol, diethylene glycol, and triethylene glycol) are also utilizable. Although economic considerations can make it desirable to minimize the amount of glycol used in conjunction with water to form the solvent mixture, it is important that this amount be large enough to permit good dissolution of the remainder of the reaction mixture. The optimum concentration of glycol in the reaction mixture may vary with the particular glycol employed but can easily be determined by routine experimentation. Ordinarily this amount is such as to provide a glycol/water mol ratio in the range of 0.1-0.5/1, preferably 0.3-0.5/1.
If desired, a base such as potassium carbonate may be used to catalyze the reaction between the sulfite and 1,6-dibromo-2-naphthol, e.g., when the sulfite/1,6-dibromo-2-naphthol mol ratio and/or the glycol/water mol ratio is lower than is normally preferred. However, it is ordinarily found that the utilization of a catalyst is unnecessary.
The novel sulfate/1,6-dibromo-2-naphthol
REFERENCES:
patent: 2576161 (1951-11-01), Thompson
patent: 5225603 (1993-07-01), Aslam et al.
patent: 5536870 (1996-07-01), Wu
Albemarle Corporation
Padmanabhan Sreeni
Spielman, Jr. E. E.
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