Org. Synth. 1947, 27, 38
DOI: 10.15227/orgsyn.027.0038
4-ETHYLPYRIDINE
[Pyridine, 4-ethyl-]
Submitted by Robert L. Frank and Paul V. Smith
1.
Checked by Homer Adkins and Robert H. Jones.
1. Procedure
In a 3-l. three-necked round-bottomed flask fitted with a Hershberg stirrer and a thermometer are placed 1500 ml. of acetic anhydride and 300 g. (306 ml., 3.80 moles) of dry pyridine (Note 1). Three hundred grams (4.6 gram atoms) of zinc dust (Note 2), in amounts of 5–10 g., is added with stirring over a period of 3 hours. Heat is evolved almost immediately, and a cooling bath of water may be necessary. The reaction mixture becomes green after about 20 minutes. The temperature of the contents of the flask should be maintained between 25° and 30°. After the addition of the first 300-g. portion of zinc, 300 ml. of acetic acid is added to the reaction mixture and a reflux condenser is attached to the flask. Then 120 g. (1.83 gram atoms) of zinc dust is added in small portions. Heat is evolved during the addition, and the reaction may become rather violent. The mixture is refluxed with stirring for 30 minutes. A third portion of 180 g. (2.75 gram atoms) of zinc dust is added all at once, and refluxing is continued for an additional half hour. The solution is now orange-brown.
The flask is allowed to cool, and the contents are transferred to a 5-l. round-bottomed flask. The mixture is cautiously neutralized with 2 l. of a 40% aqueous solution of sodium hydroxide. The mixture is steam-distilled until 3 l. of distillate is collected, after which the residue is discarded. The distillate, which separates into two layers, is saturated with 1.5–1.8 kg. of solid potassium carbonate (Note 3). The organic layer is removed by decantation; the remaining water layer is divided into two portions, and each is extracted once with 150 ml. of chloroform. The chloroform extracts are combined with the organic layer.
The mixture is distilled using an efficient fractionating column (Note 4). There is a large fore-run of chloroform, pyridine, and water (Note 5), after which the temperature rises and 145–167 g. of material, b.p. 145–165°/760 mm., is collected. This is refractionated, and 135–155 g. (33–38%) of 4-ethylpyridine, b.p. 163–165°/760 mm., n20D 1.5010, is obtained (Note 6).
2. Notes
1.
The
pyridine is dried over
calcium oxide and redistilled.
2.
The
zinc is activated before use by stirring
830 g. of zinc dust in 300 ml. of 10% hydrochloric acid for 2 minutes, filtering, and washing the
zinc with 600 ml. of water, then with
200 ml. of acetone.
3.
An equal weight of
sodium chloride may be used instead of
potassium carbonate.
4.
A
Fenske-type column 30 cm. in length and 18 mm. in diameter packed with glass helices gave satisfactory separations.
5.
It does not appear feasible to recover the
pyridine from the mixture of
chloroform, water, and
pyridine.
6.
This procedure has been employed by Arens and Wibaut
2 to prepare other 4-alkyl derivatives of pyridine. The yields tend to decrease as the molecular weight of the anhydride increases. The boiling points are as given below:
4-propylpyridine 189°,
4-n-butylpyridine 207–209°,
4-isobutylpyridine 197–199°,
4-isoamylpyridine 222–223°, and
4-n-octylpyridine 265–268°.
3. Discussion
4-Ethylpyridine has been prepared by heating
N-ethylpyridinium iodide in a
sealed tube at 300°;
3 by heating
pyridine with
ethyl iodide;
4 from
4-ethylpyridinecarboxylic acid through distillation from lime;
5 and in small amounts by distilling
brucine with
potassium hydroxide.
6 Pyridine when heated with
ferric chloride in an autoclave gives a mixture of alkylated pyridines from which
4-ethylpyridine can be isolated.
7 A general method for 4-alkylpyridines involves heating 5-(γ-pyridyl)-5-alkylbarbituric acids with alkali followed by an acid cleavage to remove the
carbon dioxide.
8 4-Ethylpyridine has been isolated from California petroleum.
9 The most useful method involves the treatment of
pyridine with
acetic anhydride and
zinc.
10,11
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
potassium carbonate (584-08-7)
hydrochloric acid (7647-01-0)
acetic acid (64-19-7)
acetic anhydride (108-24-7)
sodium hydroxide (1310-73-2)
chloroform (67-66-3)
sodium chloride (7647-14-5)
carbon dioxide (124-38-9)
acetone (67-64-1)
pyridine (110-86-1)
potassium hydroxide (1310-58-3)
zinc (7440-66-6)
ferric chloride (7705-08-0)
calcium oxide
brucine
Ethyl iodide (75-03-6)
Pyridine, 4-ethyl-,
4-ethylpyridine (536-75-4)
4-propylpyridine (1122-81-2)
4-isobutylpyridine (4810-79-1)
4-isoamylpyridine
N-ethylpyridinium iodide
4-ethylpyridinecarboxylic acid (4021-13-0)
4-n-butylpyridine (5335-75-1)
4-n-octylpyridine
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