Organic Syntheses, CV 4, 136
Submitted by G. A. Page and D. S. Tarbell
1.
Checked by William S. Johnson, Shirley Rosenberg, and Robert D. Eberhardt.
1. Procedure
A.
o-Carboxycinnamic acid.
Eighty-eight grams (78 ml., 0.46 mole of peracid) of 40% peracetic acid (Note
1) is placed in a
250-ml. Erlenmeyer flask which is immersed in a
water bath maintained at 25–30°. A
150-ml. dropping funnel is mounted so that the stem enters the flask to within about 4 cm. of the liquid surface. With mechanical stirring (Note
2), a cold solution of
20 g. (0.14 mole) of β-naphthol (Note
3) in
100 ml. of glacial acetic acid is added dropwise over a period of 4 hours to the
peracid. With the appropriate rate of addition, the temperature of the reaction mixture slowly rises to 30–35° and should not exceed 40°. Solid material begins to separate from the orange solution when one-third or more of the
naphthol solution is introduced. When the addition is complete, the mixture is stirred for 1 hour and the flask is allowed to stand in the water bath until the exothermic reaction ceases (usually 6–8 hours), then at room temperature for 4 days (Note
4). The solid material is collected by suction filtration and washed on the filter with sufficient
(10–20 ml.) acetic acid to remove colored impurities. Drying in the air gives
19.6–20.1 g. of crude
o-carboxycinnamic acid as a pale yellow crystalline solid (Note
4) and (Note
5).
The crude acid is purified by dissolving in
360–400 ml. of cold 5% sodium bicarbonate solution, filtering, and acidifying the filtrate with sufficient excess of mineral acid to turn Congo red paper blue. The product is separated by suction filtration, washed with water to remove mineral acid, and air-dried. Material thus obtained weighs
17.9–18.7 g. (
67–70% yield). It melts generally (Note
6) between
202° and 205°, and is sufficiently pure (Note
7) for most practical purposes.
B.
β-(o-Carboxyphenyl)propionic acid. In an open
1-l.wide-mouthed round-bottomed flask are placed
18 g. (0.094 mole) of o-carboxycinnamic acid and
550 ml. of 10% sodium hydroxide solution. The mixture is warmed to 90° (Note
8) on a
steam bath and stirred mechanically. The steam bath is then removed while
54 g. (Note 9) of nickel-aluminum alloy (Raney catalyst) powder is added through the open neck of the flask in small portions (from the end of a
spatula) at frequent intervals (Note
10). When addition of the alloy is complete (about 50 minutes), the mixture is stirred and maintained at 90–95° for 1 hour by warming on a steam bath. Distilled water is added as needed to maintain the total volume at approximately 550 ml. The hot mixture is filtered with suction, and the metallic residue is washed with
50 ml. of hot 10% sodium hydroxide solution and two 50-ml. portions of hot water in such a manner that the solid is always covered with liquid (Note
11). The cooled filtrate and washings are added dropwise with mechanical stirring to
300 ml. of concentrated hydrochloric acid (sp. gr. 1.19) in an open
2-l. beaker at such a rate that the temperature does not exceed 80–85° (Note
12). Separation of crystalline material begins almost immediately and is complete when the beaker contents have cooled to room temperature. The
β-(o-carboxyphenyl)propionic acid is separated by suction filtration, washed with water, and air-dried (Note
13). The yield is
16.8–17.3 g. (
92–95%), m.p.
165.5–167° (Note
14).
2. Notes
1.
Commercial 40% (w/w) peracetic acid is available from the Becco Sales Corporation, Buffalo 7, New York. The use of a 3.3 molecular proportion of the
peracid results in slightly higher and more consistent yields of product than when the theoretical 3.0 proportion is employed. The procedure gives the same yield (percentage) of product when using proportionately smaller quantities of reactants.
2. The operator should be protected by means of a safety shield. A
glass (propeller-blade) stirrer passing through the open neck of the Erlenmeyer flask is convenient; rapid stirring is not essential.
3.
β-Naphthol of C.P., U.S.P., or N.F. grade has been used with equal success.
4. After 15 hours' standing,
15.0–16.8 g. of crude
o-carboxycinnamic acid may be recovered by filtration, washing, and drying.
6. On melting,
o-carboxycinnamic acid cyclizes to give the
lactone of β-hydroxy-β-(o-carboxyphenyl)propionic acid (phthalideacetic acid), m.p.
153°. If the melting point is taken too slowly, or if the diacid is not washed completely free of mineral acid, it may therefore melt considerably below 200°. The reduction step (part
B), however, proceeds normally with such material.
7. The acid may be recrystallized from aqueous
ethanol to give small, white, felted prisms, m.p.
205°.
8. It is advisable to insert a
thermometer only at intervals since the alkaline mixture attacks glassware to an appreciable extent on prolonged contact.
9. Using less than 50 g. of the alloy results in the same yield of final product, which, however, contains small amounts of unchanged
o-carboxycinnamic acid. Equally good results are obtained when proportionately smaller quantities of reactants are used.
10. If excessive foaming is encountered it may be controlled as required by the addition of a few drops of
octyl alcohol.
11. The metallic residue may ignite if allowed to dry on the filter. Disposal can be carried out by dissolving the residue in dilute
nitric acid.
(Caution! Vigorous reaction.)
12. With this order of addition, aluminum salts remain in solution, thus simplifying the procedure. External cooling may be applied in order to save time.
13. Extraction of the filtrate with
ether gives an additional
0.4–0.5 g. of the crude acid after removal of solvent by distillation. It may be purified by conventional means to give an additional
0.25–0.35 g. of the pure product.
3. Discussion
This preparation is referenced from:
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