Organic Syntheses, CV 4, 84
BENZOYLCHOLINE IODIDE AND CHLORIDE
[Choline, chloride benzoate, and Choline, iodide benzoate]
Submitted by A. H. Ford-Moore
1
Checked by R. L. Shriner and Calvin N. Wolf.
1. Procedure
A.
2-Chloroethyl benzoate. In a
500-ml. round-bottomed flask attached to a
100-cm. air condenser by a ground-glass joint are placed
80.5g. (66ml., 1 mole) of redistilled ethylene chlorohydrin (b.p.
128–129°) and
140.5 g. (115.5 ml., 1 mole) of benzoyl chloride. The apparatus is set up in a good
hood, and the mixture is warmed gently with a low flame until the reaction starts (Note
1). The source of heat is withdrawn until the reaction moderates and is then again applied for an additional 30 minutes, during which time the temperature rises to about 200–215°. The flask is fitted with a
short column (about 20 cm.) and arranged for distillation. After volatile material has been removed by evacuation with a
water pump at a bath temperature of 100–110° the residual liquid is fractionated under reduced pressure. The yield of
2-chloroethyl benzoate boiling at
101–104°/2 mm. is
165–168 g. (
89–91%),
nD19 1.5298.
B.
2-Iodoethyl benzoate. A mixture of
170 g. of anhydrous sodium iodide and
1.2 l. of methyl ethyl ketone (Note
2) is heated on a
steam bath for 1 hour with occasional shaking in a
3-l. round-bottomed flask fitted with a
water-cooled reflux condenser.
2-Chloroethyl benzoate (162 g., 0.88 mole) is added to the mixture, and heating is maintained for an additional 22–24 hours with occasional shaking. The mixture is cooled to room temperature and filtered through a
15-cm. Büchner funnel with suction. The inorganic salts on the filter are washed with
200 ml. of methyl ethyl ketone, and the filtrate is concentrated by distillation of about 1 l. of the solvent. The residue is poured into 1 l. of water contained in a
separatory funnel, which is shaken, and the lower layer is withdrawn. The latter is washed successively with
200 ml. of 10% sodium bisulfite solution,
200 ml. of 5% sodium bicarbonate solution, and 100 ml. of water. It is dried with anhydrous
magnesium sulfate (5–7 g.) and fractionated under reduced pressure. The yield of material boiling at
133–136°/2.5 mm.,
nD15 1.5820, is
190–196 g. (
78–81%).
C.
Benzoylcholine iodide. A solution of
194 g. (0.70 mole) of 2-iodoethyl benzoate in
200 ml. of dry acetone is treated with
270 ml. of a 19.5% solution of trimethylamine in
acetone (Note
3) in a
1-l. Pyrex reagent bottle which is closed with a tightly fitting rubber stopper wired in place. The solution is allowed to stand at room temperature for 24 hours (Note
4), and at the end of this time the quaternary salt is separated by filtration with suction, washed with
200 ml. of dry acetone, and air-dried (Note
5). The weight of the quaternary iodide melting with decomposition at 247° is
200–210 g. (
85–90%) (Note
6).
D. Benzoylcholine chloride. Silver chloride is prepared by dissolving
160 g. (0.94 mole) of silver nitrate in 500 ml. of boiling distilled water and adding
120 ml. of analytical reagent hydrochloric acid (sp. gr. 1.18) from a dropping funnel in a period of 15 minutes, with continuous stirring. The
silver chloride is washed by decantation with three 300-ml. portions of boiling distilled water. The moist
silver chloride is suspended in 750 ml. of water warmed to 50–60° in a
2-l. beaker, and
210 g. (0.63 mole) of benzoylcholine iodide is added in a period of 1 hour, with good mechanical stirring. After the addition is completed, stirring is continued for an additional 30 minutes without the application of heat. The mixture is cooled and filtered with suction. The silver salts on the filter are washed with 200 ml. of hot water (Note
7), and the combined filtrates are evaporated to dryness under reduced pressure (water pump). The residue is dried by twice distilling to dryness with
250 ml. of absolute ethanol and then once with
250 ml. of dry acetone, the last of the
acetone being removed under reduced pressure. The product is recrystallized by dissolving it in
240 ml. of isopropyl alcohol (Note
8) and allowing the solution to cool in a
refrigerator. It is filtered and dried, first at 100° and then in a
vacuum desiccator over
silica gel. The yield of pure product, m.p.
207° (dec.), is
125–132 g. (
82–87%) (Note
9).
2. Notes
1. Usually the reaction starts at a temperature of 55° to 60° as evidenced by liberation of
hydrogen chloride. If the reaction becomes too vigorous it may be moderated by applying a wet towel to the flask.
2. A
purified grade of methyl ethyl ketone should be used. The technical material may be purified by allowing it to stand over solid anhydrous
calcium chloride for 24 hours, decanting from the syrupy layer and solid through a filter, and then distilling; b.p. 79–80°.
4. Increasing the reaction period to 48 hours gives an additional
5 to 7 g. of product.
5. If this preparation is carried out during periods of high humidity it is best to place the product in a vacuum desiccator, which is evacuated several times in order to remove the solvent. Anhydrous
calcium chloride may be placed in the bottom of the desiccator.
6. This product is quite pure as shown by titration of iodide ion.
7. The silver residues are saved for the recovery of
silver4 and
iodine.
8. The submitter states that the compound may be recrystallized by boiling with
acetone under an upright condenser and adding
ethanol cautiously down the condenser until the solid just dissolves. The substance is appreciably soluble in the cold solvent mixture. It is necessary to distil the mother liquor and recrystallize the residue from
acetone-ethanol, for otherwise a considerable loss of product will occur. The checkers used
isopropyl alcohol for crystallization.
3. Discussion
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved