Organic Syntheses, Coll. Vol. 4, p.88 (1963); Vol. 37, p.6 (1957).
In a 2-l. three-necked flask
, fitted with a sealed mechanical stirrer (Note 1)
, a reflux condenser protected with a calcium chloride tube
, and a dropping funnel
, is placed 123 g. (1 mole) of nicotinic acid (Note 2)
. The stirrer is started, and 500 ml. (818 g., 6.9 moles) of distilled thionyl chloride
is added in a slow stream over a period of 15–20 minutes (Note 3)
. After the addition is complete, the mixture is heated on the steam bath
with continuous stirring for 1 hour; then the reflux condenser is replaced by one set for downward distillation, and the excess thionyl chloride
is removed by distillation at reduced pressure as heating on the steam bath is continued (Note 1)
and (Note 3)
. After most of the thionyl chloride
has been distilled, 200 ml. of anhydrous benzene
is added, and the benzene
is distilled at reduced pressure. An additional 500 ml. of anhydrous benzene
is added; then the flask is fitted with a thermometer
and a reflux condenser and is placed in an ice-salt bath
. The stirrer is started, and 330 g. (2.5 moles) of anhydrous aluminum chloride
is added in portions over a period of 1 hour as the internal temperature is held between 5° and 10°. The ice bath
is removed, and the flask is permitted to warm to room temperature and is finally heated under reflux for 6 hours.
The dark red-brown reaction mixture is cautiously poured onto a mixture of 2 kg. of ice and 200 ml. of concentrated hydrochloric acid
. The organic layer is separated and discarded. The acid solution is extracted with three 500-ml. portions of ether (Note 4)
, which are discarded; then it is treated with 50% aqueous sodium hydroxide
until the aluminum hydroxide
which first forms redissolves (Note 5)
. After cooling, the organic material is extracted with five 300-ml. portions of chloroform
. The combined chloroform
extracts are washed with water, the solvent is removed by distillation on the steam bath, and the product is distilled. The yield of 3-benzoylpyridine (Note 6)
, b.p. 107–110°/0.3 mm.
or 141–145°/4 mm.
, is 165–175 g.
It is convenient to use a sealed stirrer, such as the Trubore stirrer
, which may be left in the flask during the distillation of thionyl chloride
at reduced pressure; however, the stirrer cannot be left running during this distillation, for it is stopped by the cake of acid chloride hydrochloride. The distillations are accomplished most conveniently if the dropping funnel is removed and replaced by a capillary and the stirrer is left in place but not running during the distillations.
Satisfactory results were obtained with nicotinic acid from either Eastman Organic Chemicals or Matheson, Coleman and Bell
The submitters used thionyl chloride from Hooker Electrochemical Company
. It was distilled and collected over a 1° range (78–79°). The first few drops of thionyl chloride
are added cautiously as the initial reaction may be quite vigorous. Recovered thionyl chloride
may be used for subsequent runs.
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