Laboratory Methods of Organic Chemistry - Sciencemadness Dot Org

362 HANTZSCH'S COLLIDINB SYNTHESIS
extracts, after being shaken again with water in order to remove
most of the alcohol, are dried for a short time with potassium carbonate.
The ether is then evaporated and the residue is distilled in
a vacuum. Boiling point 175°-178°/12 mm. Yield 15 g. of ester
of collidine dicarboxylic acid from 20 g. of dihydro-ester.
Potassium Collidinedicarboxylate.—Purified potassium hydroxide
(30 g.) is dissolved in 100 c.c. of absolute alcohol by boiling for a long
time in a round-bottomed flask (capacity 250 c.c.) under reflux on a
wire gauze, 15 g. of ethyl collidinedicarboxylate are added, and the
solution is refluxed for three to four hours on a vigorously boiling
water bath. The salt produced is sparingly soluble in alcohol and
gradually separates in the form of a crystalline crust. When the
hydrolysis is over the crystals are separated from the cooled solution
at the pump and washed, first twice with alcohol and then with
ether. Yield 12-14 g.
Collidine.—The carboxyl group is removed by heating the potassium
salt with slaked lime. The salt is thoroughly mixed with twice
its weight of calcium hydroxide by grinding in a mortar, and the
mixture is poured into a combustion tube (about 60 cm. long)
closed 10 c.c. from the end with an asbestos plug. By means of
another loosely fitting asbestos plug the mixture is kept in position
and one end of the tube is tightly corked. The other end is connected
with a receiver by means of an adapter and the tube is placed
with the closed end uppermost in an inclined combustion furnace.
After a moderately deep channel has been produced over the mixture by
tapping the tube is warmed by small flames. Then, beginning at
the elevated end of the tube, the flames are raised more and more
until, with closed tiles, a bright red heat is finally reached. The
collidine which distils is dissolved in ether, and the solution dried
with a little potassium hydroxide ; the ether is evaporated and the
collidine distilled. Boiling point 172°. Yield 3-4 g.
If a nitrogen cylinder is available, the mixture of potassium salt
and lime is heated in a slow stream of the gas.
The synthesis of the pyridine ring from ethyl acetoacetate, aldehydes,
and ammonia proceeds extraordinarily readily. The mechanism is as
follows. In the first phase the aldehydes react with the acetoacetic
ester to form alkylidene bis-acetoacetic esters. The 1 : 5-diketone derivatives
so formed undergo ring closure by introduction of a molecule of
ammonia and elimination of two molecules of water :