Submitted by R. H. Kimball, George D. Jefferson, and Arthur B. Pike.
Checked by C. R. Noller
1. Procedure
The apparatus consists of a
1-l. three-necked flask with a
mercury-sealed mechanical stirrer and a
6-mm. inlet tube reaching to the bottom of the flask. In the third neck is a
cork bearing a low-temperature thermometer and a tube containing phosphorus pentoxide on glass wool, and calcium chloride. The inlet tube is connected to
three 20-cm. drying towers,
two containing phosphorus pentoxide on glass wool, and
one containing calcium chloride. To the last tower is connected a
2-l. Florence flask fitted as a
wash bottle with a safety tube and containing 1 l. of concentrated sulfuric acid. The Florence flask is connected to the
hydrogen chloride generator described in
Org. Syn. Coll. Vol. I, 1941, 293, in which a single charge of
1.5 l. of concentrated sulfuric acid and
800 cc. of hydrochloric acid is sufficient for this preparation. A
pressure equalizer should be provided between the
generating flask and the funnel.
After the inlet tube is removed from the reaction flask,
400 cc. of absolute alcohol (Note
1) and
161 g. (1 mole) of dry α-phenylacetoacetonitrile (m.p.
88.5–89.5°)
(p. 487) are added. The neck is temporarily closed by a cork, and the nitrile is dissolved by warming with stirring. The flask is then surrounded by a freezing mixture, and the solution vigorously stirred, so that any nitrile which crystallizes will be finely divided. When the temperature reaches −10°, the inlet tube is inserted and a stream of dry
hydrogen chloride passed through, with moderate stirring, at such a rate that the bubbles rising from the 6-mm. tubing in the sulfuric acid wash bottle can just be counted. This is continued for five to eight hours until the mixture is saturated (Note
2). The
ice bath is then removed, stirring continued until all the solid has dissolved (about one hour), and the flask allowed to stand overnight (Note
3).
Most of the excess
hydrogen chloride is removed by adding porous tile and evacuating the flask with a
water pump for a half hour, while it is surrounded by a water bath maintained at about 40°.
Two hundred grams of sodium carbonate is dissolved in 1.2 l. of water in a
5-l. flask, and 2 l. of cracked ice added. Into this solution the reaction mixture is poured in a thin stream with vigorous shaking, and the solution is extracted at once with three
500-cc. portions of ether. The
ether extracts are washed countercurrently with four
250-cc. portions of ice-cold 5 per cent sodium chloride solution to remove the alcohol and then combined in a
3-l. flask placed in an ice bath.
A solution of
100 g. of c.p. concentrated sulfuric acid in 700 cc. of water is prepared in a 5-l. flask, 1.5 l. of cracked ice added, and the mixture shaken until ice forms on the outside of the flask. After about half of this solution has been poured into the cold
ether solution of the imino ether, using a funnel to remove the excess ice, the mixture is shaken for exactly fifteen seconds (Note
4), allowed to settle, and the layers separated. The remaining acid is added to the
ether layer in two portions, the mixture each time being shaken for fifteen seconds, and separated. Since the
ether solution, although now free of the imino ether, still contains a small amount of
ethyl phenylacetoacetate, it is saved to be combined with the main portion later.
The
sulfuric acid solution of the imino ether sulfate quickly turns cloudy because of the separation of
ethyl α-phenylacetoacetate. To complete the hydrolysis, the mixture is heated on the
steam bath for one-half hour at the temperature at which the
ether just boils (about 50°) (Note
5). It is then cooled, the ester layer separated, and the acid extracted once with
250 cc. of ether. The
ether solution is washed once with 100 cc. of water which is recombined with the acid. The acid solution is replaced on the steam bath and heated for forty-five minutes after the temperature reaches 80–90°. After the solution is cooled and extracted as before, all
ether extracts, including the original from which the imino ether was removed, are combined and washed once with
250 cc. of 5 per cent sodium bicarbonate solution, once with 250 cc. of water, and then dried over
20 g. of anhydrous sodium sulfate (Note
6). The
sodium sulfate is removed by filtration and washed with
ether, the
ether removed from the filtrates, and the residue fractionated
in vacuo from a
250-cc. Claisen flask having a 25-cm. fractionating side arm. The main fraction boils at
139–143°/12 mm., or
130–134°/5 mm., and weighs
103–167 g. (
50–81 per cent of the theoretical amount). By fractional distillation of the fore-run, main fraction, and residue, a product boiling over a one- to two-degree range may be obtained with no change in the yield (Note
7).
2. Notes
2. More rapid saturation lowers the yield appreciably.
3. A fine precipitate, probably
ammonium chloride, settles. The most successful runs showed little or none of this precipitate.
4. Any delay at this point results in hydrolysis of some of the imino ether to the product, which stays in the
ether layer.
5. Care should be taken in lifting the flask from the bath, since any mixing may cause the
ether to boil out of the flask.
6. Removal of product from time to time during the course of the hydrolysis seems to improve the yield.
7. The liquid ester is an equilibrium mixture, the enol content of which is increased by distillation and falls slowly, on standing, to
30 per cent.
1 The boiling point of
145–147°/11 mm., recorded in the literature, is higher than any noted in the present work.
3. Discussion
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