Org. Synth. 1929, 9, 16
Submitted by C. S. Marvel and W. A. Lazier.
Checked by J. B. Conant, J. S. Andrews, and C. O. Tongberg.
In a 5-l., two-necked, round-bottomed flask
, fitted with an efficient reflux condenser (Note 1)
, is placed a mixture of 130 g. (131 cc., 1.64 moles) of dry pyridine (Note 2)
and 3 l. of absolute alcohol
(see Note 2 on p. 249
). During the course of forty to fifty minutes 450 g. (19.6 atoms) of sodium
is added gradually. The sodium
is added in as large pieces as can be inserted through the second opening in the flask. One and one-half liters of absolute alcohol
is now added and the mixture heated over an oil bath
for two to three hours until the sodium
disappears. It is desirable not to allow the reaction mixture to cool (Note 3)
at this point but to separate the piperidine
immediately. The condenser is set for distillation and a separatory funnel
is inserted through the stopper in the second opening of the flask. The alcohol
is then distilled using an oil bath (Note 4)
. The addition of a piece of zinc
facilitates an even distillation. During this procedure, water to the amount of 1700–1800 cc. is added to the reaction mixture through the separatory funnel, slowly at first and later as rapidly as possible. At the beginning, this addition must be very cautious as the heat evolved causes a very distillation of alcohol
. After about 200 cc. of water has been added, the mixture begins to solidify and remains semi-solid until most of the water has been added. The distillation is continued until practically all the alcohol
has distilled (three to four hours). At the end of this time there remains in the distilling flask
about 1500 cc. of residue, which is discarded. The distillate is about 5 l. in volume. To this is added 200 cc. of concentrated hydrochloric acid
(sp. gr. 1.19) and the mixture is then returned to the distilling flask. The alcohol
is removed by distillation on a steam bath
until the residual volume in the flask amounts to about 600–800 cc.; this requires two to three hours.
The residue is then transferred to a 2-l. round-bottomed flask fitted with a mechanical stirrer and separatory funnel. The mixture is treated with stirring with a solution of 186 g. of technical sodium hydroxide or 170 g. (4.25 moles) of c.p. sodium hydroxide in about 300 cc. of water. With continuous stirring 235 g. (1.67 moles) of benzoyl chloride is now added during the course of one hour, keeping the temperature down by cooling with running water. After the addition, the reaction mixture is cooled, the amide separated (Note 5), washed with a little water (Note 6) and distilled (Note 7) under reduced pressure. The product boils at 180–184° /20 mm., 191–194° /27 mm., 240–244° /130 mm., and weighs 240–250 g. (77–81 per cent of the theoretical amount).
Benzoyl piperidine thus obtained is a straw-colored viscous liquid. Upon long standing or seeding with crystalline benzoyl piperidine, the compound crystallizes in long, colorless needles which melt at 44°. The literature reports 48° as the melting point of the pure material.
Using 180 g. of pyridine in place of the 130 g. suggested, and a corresponding increase in the other chemicals except the sodium and alcohol, a yield of 300–326 g. of benzoyl piperidine is obtained. This is a smaller percentage yield (70–75 per cent of the theoretical amount) but the actual yield more than repays for the excess of pyridine used (Note 8).
A reflux condenser 180 cm. long with inner tube 2 cm. in diameter
is recommended. If a smaller condenser is employed, the reaction cannot be run as rapidly as is desirable to give the best results. If the reaction is not run rapidly sodium ethoxide
separates in the flask.
Unless the purity of the pyridine
is known, it should be dried with solid sodium hydroxide
and distilled before use. For this work a fraction boiling at 112–117° was used.
If the alcohol
solution is allowed to cool before the addition of the water, it solidifies and is remelted only with difficulty. If it is desired to suspend the process, the water should be added first and then the solution will not solidify.
In distilling the piperidine
from the strong alkaline solution, the flask must be suspended in the oil bath. Direct heating raises the temperature of the flask to such a point that the alkali rapidly etches through it.
A troublesome emulsion sometimes results after benzoylation. This usually may be broken up by the addition of more strong sodium hydroxide
solution. In case an emulsion is formed which cannot be broken it is possible to extract the product with benzene
Any sodium hydroxide
carried into the distilling flask causes decomposition of the benzoyl piperidine
during distillation and consequently a considerably lower yield results. For this reason it is well to wash the product carefully in the separatory funnel with a little water after the alkaline solution has been drawn off.
is much given to superheating, making distillation difficult.
is available, benzoyl piperidine
for use in the preparation of pentamethylene bromide (p. 428)
may be prepared by direct benzoylation. A mixture of 105 g. of sodium hydroxide (2.6 moles)
, 170 g. of piperidine (2.0 moles)
), and 800 cc. of water is treated with 280 g. (2 moles) of benzoyl chloride
using the apparatus and procedure described above; the temperature is kept at 35–40°. The oily product is separated after dilution with 250 cc. of benzene
if necessary (Note 5)
, dried with a small quantity of potassium carbonate
and distilled. The portion boiling at 172–174° /12 mm.
weighs 330–345 g.
per cent of the theoretical amount). The first few cubic centimeters of the distillate may be colored by a reddish impurity, in which case a forerun is collected separately.
can be prepared by the action of benzoyl chloride
in the presence of alkalies.1
This preparation is referenced from:
Chemical Abstracts Nomenclature (Collective Index Number);
potassium carbonate (584-08-7)
hydrochloric acid (7647-01-0)
sodium hydroxide (1310-73-2)
benzoyl chloride (98-88-4)
Piperidine, 1-benzoyl- (776-75-0)
sodium ethoxide (141-52-6)
pentamethylene bromide (111-24-0)
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved