Organic Syntheses, Coll. Vol. 5, p.918 (1973); Vol. 49, p.90 (1969).
A 2-l. Three-necked flask
equipped with a condenser
and containing 27 g (1.1 mole) of magnesium
is flame-dried and the atmosphere replaced with nitrogen
. A 200-ml. portion of tetrahydrofuran (Note 1)
is added along with several lumps, totaling about 95 g., of 6-bromo-2-methoxynaphthalene (Note 2)
and a small crystal of iodine
. The mixture is heated to reflux until the boiling becomes spontaneous. An additional 600 ml. of tetrahydrofuran
is added with more of the bromide to maintain a vigorous reflux, until 237.4 g. (1 mole) of 6-bromo-2-methoxy-naphthalene
has been added. After the spontaneous reflux has subsided, the dark solution is heated to reflux for 20minutes.
A 5-l. three-necked flask
fitted with a paddle stirrer
, a Claisen adapter
containing a thermometer well
and nitrogen inlet
, and a dropping funnel
is flame-dried and placed under nitrogen
. Into the flask are introduced 125 ml. (1.1 mole) of trimethyl borate (Note 3)
and 600 ml. of tetrahydrofuran
. This solution is cooled to −10° with an all-encompassing ice-salt bath
or a dry ice-carbon tetrachloride bath
. The dropping funnel is charged with the Grignard solution which is added over 30 minutes to the borate solution while stirring rapidly and maintaining the temperature between −10° and −5°. A white sludge separates from the solution during the addition. After stirring for an additional 15 minutes, 86 ml. (1.5 mole) of chilled acetic acid (Note 4)
is added all at once. This is followed by the addition of a cold solution of 112 ml. (1.1 mole) of 30% hydrogen peroxide
in 100 ml. of water, dropwise over 15 minutes, while maintaining the temperature below 0° (Note 5)
and stirring vigorously.
The mixture is allowed to warm up over 20 minutes and is poured into a 2-l. separatory funnel
. The purplish solution is washed with a saturated ammonium sulfate solution (about 1.5 l)
containing ferrous ammonium sulfate
until the rust-brown ferric color is no longer produced. The organic layer is dried over magnesium sulfate
and concentrated, leaving a dark solid. Purification of the solid by high-vacuum short path distillation gives 127–142 g.
) of a pinkish or tan-colored product, b.p. 148–150° (0.15 mm.)
, m.p. 145–147°
. It may be further purified by sublimation, or recrystallization from benzene-hexane
, m.p. 148–149°
Reagent grade tetrahydrofuran (Mallinckrodt)
has been used directly. The formation of the Grignard reagent starts readily and no precipitates are formed. Tetrahydrofuran
obtained from the Quaker Oats Company in 1-gal. cans
has also been used; the reaction, however, is slower to start, a cloudy precipitate is formed, and the yield is slightly lower. [Caution! See P. 976]
This starting material is obtained conveniently from the bromination 2
and methylation of 2-naphthol
. The procedure is modified by not removing the tin salts.
After bromination of 144 g. (1 mole) of 2-naphthol
, the hot solution is poured into water and filtered. The dry precipitate is mixed with a solution of 200 ml. of concentrated sulfuric acid
in 500 ml. of technical methanol
and heated to vigorous reflux for 4 hours. An oily layer separates during the heating period. The hot mixture is poured into 3 l. of ice and water, and the solids are removed by filtration. The moist solid is triturated with 1 l. of hot 5% sodium hydroxide
. After chilling the mixture to solidify the oil, it is filtered and the product is washed and dried. The 6-methoxy-2-bromonaphthalene
is purified by distillation, b.p. 114–118° (0.2 mm.)
. After distillation the product is most conveniently handled by remelting and pouring it into a mold to solidify. The overall yield is 173–208 g.
), m.p. 101.5–103°
Commercial trimethyl borate
contains an appreciable amount of methanol
. It is removed by adding anhydrous lithium chloride 3
to the bottle and allowing the mixture to stand with occasional shaking. The upper layer is decanted off and fractionated, b.p. 68–69°. The product must be protected from moisture.
Water added at this point hydrolyzes the arylboronic ester extremely rapidly to 2-methoxynaphthalene.
The reaction is exothermic. Except for a darkening of the product, no apparent harm results if occasionally the temperature rises to 10–15°.
The classic caustic fusion of sulfonic acid salts has been used for preparing 2,6-dinaphthol 4
and its derivatives. Other more recent procedures have employed the direct hydrolysis of aryl bromides 5
and the oxidation of aryl Grignard reagents.6
The indirect oxidation of an aryl Grignard reagent through a boronic ester nearly doubles the yield of phenol
obtained by direct oxidation and decreases the reaction time. Tetrahydrofuran
is the preferred solvent. It facilitates the dissolution of the bromide, which is relatively insoluble in diethyl ether
, solvates the Grignard reagent, and renders the oxidation reaction homogeneous.
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