Org. Synth. 1957, 37, 6
DOI: 10.15227/orgsyn.037.0006
3-BENZOYLPYRIDINE
[Ketone, phenyl 3-pyridyl]
Submitted by Frank J. Villani and Mary S. King
1.
Checked by Max Tishler and Matthew A. Kozlowski.
1. Procedure
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. (90–96%), nD26 1.6088.
2. Notes
1.
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 and
benzene 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.
2.
Satisfactory results were obtained with
nicotinic acid from either Eastman Organic Chemicals or Matheson, Coleman and Bell.
3.
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.
4.
The
ether extractions remove any
diphenyl sulfoxide that is formed.
5.
About
800–1000 ml. of 50% sodium hydroxide is required.
6.
4-Benzoylpyridine can be obtained by this procedure from
isonicotinic acid in yields of
87–90%. This product is recrystallized from
hexane, m.p.
72–73°.
3. Discussion
The described method of preparing
3-benzoylpyridine is a modification of that of Wolffenstein and Hartwich.
2 Other methods of preparing this compound are by the addition of
phenylmagnesium bromide to
3-cyanopyridine,
3 the addition of
3-pyridyllithium to
benzonitrile,
4 the
chromic acid oxidation of
phenyl-3-pyridylcarbinol,
5 and the decarboxylation of
β-benzoylpicolinic acid obtained from
quinolinic acid anhydride and
benzene.
6
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
hydrochloric acid (7647-01-0)
Benzene (71-43-2)
ether (60-29-7)
benzonitrile (100-47-0)
sodium hydroxide (1310-73-2)
thionyl chloride (7719-09-7)
chloroform (67-66-3)
aluminum chloride (3495-54-3)
chromic acid (7738-94-5)
Phenylmagnesium bromide (100-58-3)
Nicotinic acid (59-67-6)
aluminum hydroxide
hexane (110-54-3)
3-Benzoylpyridine,
Ketone, phenyl 3-pyridyl (5424-19-1)
diphenyl sulfoxide (945-51-7)
4-Benzoylpyridine (14548-46-0)
3-cyanopyridine (100-54-9)
3-pyridyllithium
phenyl-3-pyridylcarbinol
β-benzoylpicolinic acid
quinolinic acid anhydride
isonicotinic acid (55-22-1)
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved