Organic Syntheses, Coll. Vol. 3, p.757 (1955); Vol. 23, p.83 (1943).
While a current of dry nitrogen
is passed through the apparatus, 400 ml. of dry ether
and 6.9 g. (1 gram atom) of lithium
(in small pieces) (Note 1)
are placed in a 1-l. three-necked flask fitted with a dropping funnel, mechanical stirrer, and reflux condenser
protected from moisture. The stirrer is started, and 10–15 ml. of a solution of 79 g. (0.5 mole) of dry bromobenzene
in 100 ml. of dry ether
is added from the dropping funnel. The reaction usually starts immediately; if not, the flask may be warmed, and the remainder of the mixture is then added at such a rate that the ether
refluxes gently. The mixture is stirred until the lithium
disappears (Note 2)
Forty-six grams (0.5 mole) of α-picoline (Note 3)
is then added, and the mixture is stirred at room temperature for 1 hour, during which time the dark red solution of picolyllithium
is formed. The flask is then immersed in an ice-salt bath
, and when the mixture is thoroughly chilled the nitrogen
train is disconnected. Then 20 g. of dry acetaldehyde
in 50 ml. of dry ether (Note 4)
is slowly dropped into the mixture over a period of 20 minutes. The red color entirely disappears. After 15 minutes, 100 ml. of water is slowly added and then 100 ml. of concentrated hydrochloric acid
(sp. gr. 1.2). The aqueous layer is removed and poured, with stirring, into a warm solution of 300 g. of sodium carbonate decahydrate
in 100 ml. of water (Note 5)
. The crude reaction product separates as an oil and is taken up in 300 ml. of chloroform
. The precipitated lithium carbonate
is filtered, transferred to a beaker
, and stirred with four 200-ml. portions of chloroform
. The chloroform
extracts are decanted or filtered, and all the chloroform
solutions are combined (Note 6)
. The chloroform
is removed by distillation, and the residue is fractionated under reduced pressure through a good column
. The 1-(α-pyridyl)-2-propanol
boils sharply at 116–117°/17 mm.
). A small fore-run and a considerable amount of high-boiling residue are discarded. The yield is 30–34 g.
based on the α-picoline
) (Note 7)
and (Note 8)
. This product darkens on exposure to light, and it should be preserved in a brown glass bottle.
The most unsatisfactory operation of this preparation is cutting the lithium
. It may be finely divided by rubbing the metal against a coarse wood rasp and allowing the filings to drop through a large paper funnel
directly into the ether
while a rapid stream of dry nitrogen
is passed through the flask. This procedure is most convenient when a large piece of lithium
is available and the amount of filings can be determined by the loss in weight. Larger pieces, cut with a knife [Org. Syntheses Coll. Vol. 2, 518 (1943)]
, can be used equally well (Note 2)
. Bartlett, Swain, and Woodward1
have published a convenient method for the preparation of lithium
The time depends upon the size of the pieces; the solution may be stirred for 24 hours without affecting the yield.
The submitters used α-picoline, b.p. 128–130°, obtained from the Barrett Company
. The checkers used practical α-picoline
, b.p. 128–134°
, freshly distilled under reduced pressure. Samples of picoline
containing water should be carefully fractionated to remove the water as the α-picoline-water azeotrope
, b.p. 93°
Alternatively, the acetaldehyde
may be distilled into the flask through the nitrogen inlet. During this operation, the outlet must be kept well above the surface, to prevent clogging. The introduction of aldehyde is stopped when the red color has disappeared.
A solution of 111 g. of anhydrous sodium carbonate in 150 ml. of water
may be substituted.
If sodium hydroxide
is used to liberate the amino alcohol from its salt, extraction with chloroform
produces unworkable emulsions.
The submitters obtained yields as high as 43 g.
This preparation is referenced from:
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