Organic Syntheses, CV 3, 405
Submitted by Joe T. Adams, Robert Levine, and Charles R. Hauser.
Checked by H. R. Snyder and John Mirza.
1. Procedure
This reaction should be carried out under a well-ventilated hood (Note 1).
A mixture of
30.0 g. (0.5 mole) of anhydrous isopropyl alcohol and
65.0 g. (0.5 mole) of freshly distilled ethyl acetoacetate is placed in a
500-ml. round-bottomed three-necked flask equipped with a mercury-sealed stirrer, a gas inlet tube terminating about 1 cm. above the surface of the liquid, a gas outlet tube connected with a calcium chloride drying tube, and a thermometer (Note
2). The gas inlet tube is connected to a
source of boron fluorides (Note
3), and an
ice bath is applied to the reaction flask; when the temperature of the stirred mixture has fallen to approximately 0° the stream of
boron fluoride is started and adjusted so that the temperature of the mixture does not exceed 7°. The addition of
boron fluoride is continued until the mixture is saturated and for 15 minutes thereafter (Note
4). The reaction mixture then is stirred at 28° for 2.5 hours (Note
5), at the end of which period it is poured slowly into a stirred mixture of
130 g. of hydrated sodium acetate, 100 ml. of water, and 200 g. of crushed ice. The beaker containing the resulting mixture is allowed to stand in an ice bath for 2 hours with occasional stirring.
The mixture is poured into a
1-l. separatory funnel. The beaker is rinsed with
300 ml. of ether, and this portion of solvent is shaken with the mixture in the separatory funnel. The phases are separated, and the aqueous solution is extracted twice with
100-ml. portions of ether. The combined
ether solutions are washed with saturated aqueous bicarbonate solution until
carbon dioxide no longer forms. The solution is transferred to an
Erlenmeyer flask and dried over about
25 g. of anhydrous sodium sulfate for 12 hours, after which it is decanted into another Erlenmeyer flask and dried over about
10 g. of Drierite for 6 hours.
A
125-ml. modified Claisen flask is arranged for distillation, but with a dropping funnel fitted in the neck intended for the ebullator tube. Portions of the dried
ether solution are introduced into the flask through the funnel while the flask is heated on the steam bath for continuous removal of the solvent. After all the
ether solution and the
ether washings from the last drying agent have been concentrated, the dropping funnel is replaced by an ebullator tube and distillation under diminished pressure is begun cautiously. Fractions are collected at 60–96°/20 mm. and at 96–98°/20 mm. The first fraction is redistilled to give an additional quantity of material boiling at
96–98°/20 mm. (Note
6). The combined product weighs
52–58 g. (
60–67%) (Note
7).
2. Notes
1. Although no definite data are available concerning the toxicity of
boron fluoride, users should exercise caution and avoid breathing the fumes. The toxic effects of
hydrogen fluoride and alkali fluorides are well known.
Boron fluoride reacts with moisture in the air, forming white fumes of
fluoboric acid and
boric acid which cause a choking sensation when breathed.
2. The entire apparatus is dried in an
oven at about 100° just before use.
4. The time required for saturation varies from 1 to 2 hours, depending upon the rate of addition. As the saturation point is approached, the fuming at the end of the exit tube increases rather sharply; the mixture is considered to be saturated when the fuming appears to have become constant.
5. The temperature and time at this point are critical and must be controlled carefully.
6. If the fractionation is conducted with a
30-cm. Vigreux column the redistillation of the fore-run is unnecessary.
3. Discussion
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