Organic Syntheses, CV 3, 408
Submitted by Charles R. Hauser and David S. Breslow.
Checked by R. L. Shriner, W. M. Hoehn, and Vera A Patterson..
1. Procedure
In a
clean, dry, 500-ml. three-necked flask, fitted with a mechanical stirrer, a 250-ml. separatory funnel, and a reflux condenser (Note
1), the upper end of which is protected by a
calcium chloride drying tube, is placed
40 g. (0.62 gram atom) of powdered zinc (Note
2).
A solution of
83.5 g. (0.50 mole) of ethyl bromoacetate (Note
3) and
65 g. (0.61 mole) of benzaldehyde (Note
4) in
80 ml. of dry benzene and
20 ml. of absolute ether is placed in the separatory funnel. About 10 ml. of this solution is added to the
zinc, and the flask is warmed until the reaction starts (Note
5). The mixture is then stirred and the rest of the solution added at such a rate that the reaction mixture refluxes, care being taken that the reaction does not become too vigorous. The addition should take about an hour. The reaction mixture is refluxed for 30 minutes on a
water bath after the addition of the solution is complete.
The flask is then cooled in an
ice bath and the reaction mixture hydrolyzed by the addition of
200 ml. of cold 10% sulfuric acid with vigorous stirring during the addition. The acid layer is drawn off and the
benzene solution extracted twice with
50-ml. portions of 5% sulfuric acid. The
benzene solution is washed once with
25 ml. of 10% sodium carbonate solution, then with
25 ml. of 5% sulfuric acid (Note
6), and finally with two 25-ml. portions of water. The combined acid solutions are extracted with two
50-ml. portions of ether, and the combined
ether and
benzene solutions are dried with
5 g. of magnesium sulfate or Drierite. The solution is filtered, the solvent removed by distillation at atmospheric pressure from a
steam bath, and the residue fractionated under reduced pressure. The ester is collected at
151–154°/11–12 mm. (
128–132°/5–7 mm.). The total yield is
59–62 g. (
61–64%) (Note
7).
2. Notes
1. An
efficient reflux condenser is necessary to prevent loss of solvent. The same precautions as to cleanliness of apparatus and absence of moisture should be observed in carrying out Reformatsky reactions as in reactions involving the Grignard reagent.
3.
Ethyl bromoacetate is a powerful lachrymator, and care should be exercised in handling it. A
10% solution of ammonium hydroxide should be kept available to neutralize any of the bromo ester which may be spilled.
6. The acid extraction should be continued until no white precipitate of
zinc hydroxide is formed on extraction with
sodium carbonate. This step is important, since the zinc complex hydrolyzes much less readily than the corresponding magnesium complex. A small amount of unhydrolyzed complex forms at the interface of the
benzene and acid solutions. It is most readily separated during the first alkaline extraction.
3. Discussion
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