Org. Synth. 1963, 43, 45
DOI: 10.15227/orgsyn.043.0045
N-ETHYLPIPERIDINE
[Piperidine, 1-ethyl-]
Submitted by J. Wollensak and R. D. Closson
1.
Checked by C. D. Ver Nooy and B. C. McKusick.
1. Procedure
A 1-l. three-necked flask equipped with a reflux condenser, an inlet for dry nitrogen, and a mechanical stirrer is flushed with dry nitrogen. It is then charged with 340 g. (4.00 moles) of piperidine (Note 1) 4.4 g. (0.19 g. atom) of sodium, and 5.0 g. (5.1 ml., 0.063 mole) of pyridine (Note 2). While a slow stream of nitrogen continues to pass through the flask, the solution is heated under reflux with high-speed stirring for approximately 10 minutes. During this time most of the sodium reacts without evolution of hydrogen, and the dispersion darkens. The dispersion, which contains some finely divided solids, is cooled and transferred to a 2-l. stirred autoclave (Note 3) under nitrogen. An additional 85 g. (1.00 mole) of piperidine is used to wash the last portions of the dispersion into the autoclave.
The autoclave is pressured with
ethylene (Note 2) to 400 lb./in.
2 with stirring
(Note 4). It is then heated to 100° with stirring, which causes the pressure to rise to about 555 lb./in.
2. It is maintained at 100° with stirring until a gradual drop in pressure ceases; this usually takes about 2.5 hours, but it may take as long as 10 hours
(Note 5). The autoclave is cooled to room temperature, and the excess
ethylene is vented. The reaction mixture is transferred to a
1-l. round-bottomed flask, the autoclave is rinsed with
100 ml. of methanol that is added to the flask, and the mixture is fractionated through a
90-cm. column packed with glass helices. After a fore-cut of 50–100 g. distilling at
55–129°,
434–468 g. (
77–83%) of
N-ethylpiperidine is collected; b.p.
129–130.5°;
nD20 1.443–1.444
(Note 6).
2. Notes
1.
Piperidine obtained from Eastman Kodak was fractionated through a
90-cm. column packed with glass helices, and the fraction distilling at
105° was used for this work. This material contained approximately 0.36 wt.% of
pyridine as indicated by vapor phase chromatography and ultraviolet analysis.
2.
Sodium from Ethyl Corporation,
pyridine from Eastman Kodak, and
C.P. ethylene from Matheson are suitable.
3.
The kind of stirrer is not important. The submitters obtained similar results with a
three-blade propeller turning at 600 r.p.m. and a
paddle stirrer turning at 78 r.p.m. They believe that a rocking autoclave could be substituted for a stirred one.
4.
Over half the
ethylene pressured into the autoclave dissolves in the
piperidine. It is essential to agitate the
piperidine during the pressuring operation so that the
piperidine will become saturated with
ethylene, for otherwise there will not be enough
ethylene for the reaction.
5.
The checkers found that it shortened the reaction time appreciably to repressure the autoclave to 400–500 lb./in.
2 whenever the pressure dropped below 350 lb./in.
26.
The checkers got the same results using half the quantities of reactants in a 1-l. stirred autoclave.
3. Discussion
The described procedure is essentially the method of Closson, Kolka, and Ligett.
2 Since
N-ethylpiperidine was first prepared by Cahours by reaction of
piperidine with
ethyl iodide,
3 a large number of synthetic methods have been used for its preparation. Reductive alkylation of
pyridine with
ethanol over Langenback or
Raney nickel catalyst gives
N-ethylpiperidine in high yield.
4 The compound may similarly be prepared by catalytic hydrogenation of
N-ethylpyridinium chloride with
platinum oxide as catalyst
5 and by the alkylation of
piperidine using
ethanol and
Raney nickel catalyst under hydrogenating conditions.
6 Other methods that have been used are electrolytic reduction of
N-ethylglutarimide,
7 interaction of
pentamethylene oxide and
ethylamine at high temperature over
aluminum oxide,
8 interaction of
ethylamine and
1,5-dibromopentane,
9 and reduction of
1-acetylpiperidine with
lithium aluminum hydride.
104. Merits of the Preparation
The procedure is illustrative of a general method of ethylating amines, wherein one reacts the amine with
ethylene using an alkali-metal salt of the amine as catalyst.
2 Di-n-butylamine and
n-hexylamine have been thus ethylated at 130–160°,
aniline,
o-toluidine, and
N-methylaniline at 240–275°. In general, higher olefins add to amines only sluggishly.
2
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
Ethyl Corporation
ethanol (64-17-5)
methanol (67-56-1)
aniline (62-53-3)
hydrogen (1333-74-0)
nitrogen (7727-37-9)
platinum oxide
Raney nickel (7440-02-0)
pyridine (110-86-1)
sodium (13966-32-0)
piperidine (110-89-4)
1,5-dibromopentane (111-24-0)
ethylene (9002-88-4)
pentamethylene oxide (142-68-7)
Ethyl iodide (75-03-6)
aluminum oxide (1344-28-1)
N-Methylaniline (100-61-8)
lithium aluminum hydride (16853-85-3)
ethylamine (75-04-7)
di-n-butylamine (111-92-2)
N-Ethylpiperidine,
Piperidine, 1-ethyl- (766-09-6)
N-ethylpyridinium chloride
N-ethylglutarimide
1-acetylpiperidine (618-42-8)
o-toluidine (95-53-4)
n-hexylamine (111-26-2)
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