Organic Syntheses, CV 5, 918
Submitted by R. L. Kidwell, M. Murphy, and S. D. Darling
1.
Checked by R. E. Ireland, J. W. Tilley, and C. Kowalski.
1. Procedure
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. (
73–81%) 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°.
2. Notes
1.
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]
2. 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. (
73–88%), m.p.
101.5–103°.
3. 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.
4. Water added at this point hydrolyzes the arylboronic ester extremely rapidly to 2-methoxynaphthalene.
5. The reaction is exothermic. Except for a darkening of the product, no apparent harm results if occasionally the temperature rises to 10–15°.
3. Discussion
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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