Submitted by P. S. Pinkney
Checked by Louis F. Fieser and T. L. Jacobs.
1. Procedure
A
3-l. three-necked, round-bottomed flask is fitted with a
mercury-sealed mechanical stirrer (Note
1), a
250-cc. dropping funnel, and a
reflux condenser protected from the air by means of a
calcium chloride tube. In the flask are placed
23 g. (1 gram atom) of sodium and
250 cc. of dry toluene (Note
2). The stirrer is started, and
202 g. (1 mole) of ethyl adipate (p. 264) is added from the dropping funnel at such a rate that the addition is complete in about two hours. The reaction usually starts immediately on addition of the
ethyl adipate. The temperature of the
oil bath is maintained at 100–115° during the addition and for about five hours longer. Dry
toluene is added through the condenser from time to time in order to keep the reaction mixture fluid enough for efficient stirring (Note
3). Between
750 cc. and 1 l. of toluene is added in this manner.
The reaction mixture is cooled in an
ice bath and slowly poured into
1 l. of 10 per cent acetic acid cooled to 0° (ice-salt mixture). The
toluene layer is separated, washed once with water, twice with cooled
7 per cent sodium carbonate solution, and again with water. The
toluene is removed by distillation at ordinary pressure, and the residue is distilled under reduced pressure. The yield is
115–127 g. (
74–81 per cent of the theoretical amount) of a product boiling at
83–88°/5 mm. or
79–84°/3 mm. (Note
4) and (Note
5).
2. Notes
1. The Hershberg
1 stirrer, shown in part in
f.htmig. 4, provides very efficient agitation of this or other pasty mixtures. Two glass rings are sealed to the end of a stirrer shaft at right angles to one another, and each is threaded with B. and S. No. 18 Chromel or Nichrome wire (in the drawing the wire is shown only for the lower ring; the upper wire is not provided with a cross brace). The stirrer is easily introduced and removed through a narrow opening, and in operation it follows the contour of the flask. It is convenient to use glass tubing for the stirrer shaft and to provide it with a pair of small ball bearings slipped on over short sections of rubber tubing (one of these bearings is shown in the drawing).
Fig. 4
The yields reported were obtained using this stirrer; with various other stirrers it was seldom possible to duplicate the results.
3. If the reaction mixture is allowed to become too thick for efficient stirring, or if the temperature of the oil bath is raised above 115–120°, the solid
sodium derivative will cake on the sides of the flask. This makes the complete removal of the reaction mixture from the flask and the decomposition of the sodium derivative more difficult.
4. According to the literature,
2,
3 the product obtained in this manner may contain
ethyl adipate. To remove this, the product is cooled to 0° and run slowly into
600 cc. of 10 per cent potassium hydroxide solution maintained at 0° with ice-salt. Water is added until the salt which separates has dissolved, and the cold alkaline solution is extracted twice with
200-cc. portions of ether. The alkaline solution, kept at 0°, is run slowly into
900 cc. of 10 per cent acetic acid solution with stirring, the temperature remaining below 1° (ice-salt). The oil which separates is taken up in
400 cc. of ether, and the aqueous solution is extracted with four
250-cc. portions of ether. The
ether extract is washed twice with cold
7 per cent sodium carbonate solution and dried over
sodium sulfate. After removal of the
ether the residue is distilled, b.p.
79–81°/3 mm. The recovery is only
80–85 per cent, and in a well-conducted preparation the
ethyl adipate eliminated amounts to less than 1 per cent of the total product. Unless the preparation has proceeded poorly the tedious purification ordinarily is best omitted.
If material free from all traces of
ethyl adipate is desired, time and material can be saved by omitting the first distillation (observation of the checkers). The
toluene solution of the crude
2-carbethoxycyclopentanone is cooled to 0° and added slowly with stirring to
300 cc. of 10 per cent potassium hydroxide solution maintained below 1°. Cold water is added until the slightly soluble potassium salt has dissolved. The
toluene layer is then separated and washed twice with
150-cc. portions of cold, 10 per cent potassium hydroxide solution. After each washing, cold water is added to dissolve any solid which separates. The
toluene solution, now very light yellow in color, is finally washed twice with 150-cc. portions of cold water. The aqueous solutions are combined, extracted with
250 cc. of ether, and treated as described for the alkaline solution above. The yield is
100–115 g. (
64–74 per cent).
5. The following procedure gives slightly better yields.
A
3-l. round-bottomed flask, which contains
50 g. of "molecular" sodium, is fitted with a reflux condenser protected from the air by means of a calcium chloride tube, and
1250 cc. of benzene, dried by distilling over
sodium, is added.
Three hundred and three grams (1.5 moles) of ethyl adipate is then added, in one lot, followed by
3 cc. of absolute alcohol. The flask is warmed on the
steam bath until, after a few minutes, a vigorous reaction commences and a cake of the sodio-compound begins to separate. During this stage the flask is kept well shaken by hand. After the spontaneous reaction has abated, the mixture is refluxed on the steam bath overnight, then cooled in ice. The product is decomposed with ice and
6 N hydrochloric acid, the acid being added until Congo red paper is turned blue. The
benzene layer is separated, and the aqueous layer is extracted once with
200 cc. of benzene. The united extract is washed with
200 cc. of 5 per cent sodium carbonate solution and 300 cc. of water. The solution is placed in a
3-l. distilling flask and the
benzene and water are removed by distillation under ordinary pressure. The residue is fractionated under reduced pressure. The yield is
185–192 g. (
79–82 per cent of the theoretical amount) of a product boiling at
108–111°/15 mm. On redistillation the product boils at
102°/11 mm.
The significant features of this procedure are the addition of alcohol, which eliminates or greatly reduces the induction period, and the excess of
sodium, which contributes to the completeness of the reaction. The
benzene, used as a solvent, may be replaced by
petroleum ether (b.p.
60–80°).
The once-distilled
carbethoxycyclopentanone is sufficiently pure for ordinary synthetic purposes; it gives a 93 per cent yield of the Cmethyl derivative. (R. P. Linstead and E. M. Meade, private communication.
4 Checked by R. L. Shriner and N. S. Moon.)
3. Discussion
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