Organic Syntheses, CV 3, 300
Submitted by H. L. Holmes and L. W. Trevoy.
Checked by Cliff S. Hamilton and Carol K. Ikeda.
1. Procedure
A.
Ester condensation. A suspension of
9.40 g. (0.41 gram atom) of powdered sodium1 in
100 ml. of absolute ether is placed in a
1-l. three-necked flask (Note
1) fitted with a
reflux condenser,
dropping funnel, and a
calcium chloride tube. A solution of
23.8 ml. (0.41 mole) of absolute ethanol (Note
2) in
50 ml. of absolute ether is added through the dropping funnel, and the mixture is refluxed on a
steam bath for 10–11 hours. The reflux condenser is replaced by a
mercury-seal stirrer. A
thermometer and a calcium chloride tube are fitted into the third neck of the flask. The suspension of
sodium ethoxide in absolute
ether is cooled to −10° to −15° in an
ice-hydrochloric acid bath, and a solution of
47.85 g. (0.19 mole) of ethyl γ-veratrylbutyrate (Note
3) and
29.6 g. (0.40 mole) of ethyl formate in
100 ml. of absolute ether is added dropwise through the dropping funnel with vigorous stirring (Note
4). The mixture is kept at −10° for 4 hours, and then the thermometer and calcium chloride tube are removed and the stirrer is replaced by a reflux condenser equipped with a calcium chloride tube. The mixture is allowed to come to room temperature and stand for 72 hours. During this time a gas is evolved and a pale yellow solid separates.
On digestion of this solid mass with 1 l. of ice and water, the
sodium salt of the enol dissolves in the water, and the unreacted ester is removed by extracting the aqueous layer with two
200-ml. portions of ether (Note
5). The formyl derivative settles out as an oil upon acidification of the aqueous layer with dilute
sulfuric acid. The oil is extracted with three
200-ml. portions of ether, and the ethereal extract is washed several times with water and dried over anhydrous
sodium sulfate. The
ether is distilled, and, to remove traces of
ethyl formate, the oil is heated on a steam bath under a pressure of 20–30 mm. for 1 hour. The remaining yellow formyl derivative weighs 27–29 g. (Note
6).
B.
Cyclization. The above oil is poured dropwise into a well-stirred mixture of
110 ml. of 90% phosphoric acid (sp. gr. 1.75) and
23.4 ml. of sulfuric acid (sp. gr. 1.83) which is kept at −10°. The temperature is allowed to rise to 0–10°, and the stirring is continued for 2 hours. The viscous reaction mixture is poured into 500 ml. of ice and water, and the acid is partially neutralized with
300 ml. of 40% sodium hydroxide solution with efficient cooling. The viscous cream-colored oil is extracted with three
150-ml. portions of ether; the
ether extract is washed well with water and
sodium bicarbonate solution to remove the last traces of acid and then dried over anhydrous
sodium sulfate. The cyclized ester, after removal of the
ether, is a red oil which solidifies upon cooling. The yield is 23–24 g.
C.
Saponification. The ester is saponified by refluxing for 5 hours with
75 ml. of a 10% sodium hydroxide solution containing
3 ml. of ethanol; it is then poured into 150 ml. of water and decolorized with
Norit. Upon acidification of the alkaline solution with dilute
hydrochloric acid,
18–19 g. (
40–43%) (Note
7) and (Note
8) of acid is obtained, melting at
191–193° (cor.).
2. Notes
1. It is suggested that a flask with a ground-glass joint be employed for the condensation as it leads to less discoloration of the formylation product.
4. The ethereal solution of the two esters should be added at such a rate that the addition is complete in about 1 hour.
6. The formylation product is too sensitive to purify by distillation even at pressures of 1–2 mm. of
mercury.
3. Discussion
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
ethanol (64-17-5)
sulfuric acid (7664-93-9)
hydrochloric acid (7647-01-0)
ether (60-29-7)
sodium hydroxide (1310-73-2)
sodium bicarbonate (144-55-8)
sodium sulfate (7757-82-6)
mercury (7439-97-6)
Norit (7782-42-5)
sodium (13966-32-0)
phosphoric acid (7664-38-2)
sodium ethoxide (141-52-6)
calcium oxide
ethyl formate (109-94-4)
γ-veratrylbutyric acid
6,7-Dimethoxy-3,4-dihydro-2-naphthoic acid,
2-Naphthoic acid, 3,4-dihydro-6,7-dimethoxy- (53684-50-7)
ethyl γ-veratrylbutyrate
magnesium ethoxide (2414-98-4)
β-(3,4-dimethoxybenzoyl) propionic acid
3,4-dihydro-2-naphthoic acid
7-methoxy-3,4-dihydro-2-naphthoic acid
6,7-dimethoxy-2-naphthoic acid
6-methoxy-3,4-dihydro-2-naphthoic acid
sodium salt (824-79-3)
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