Org. Synth. 1950, 30, 41
DOI: 10.15227/orgsyn.030.0041
5-ETHYL-2-METHYLPYRIDINE
[2-Picoline, 5-ethyl-]
Submitted by Robert L. Frank, Frederick J. Pilgrim, and Edward F. Riener
1,2.
Checked by R. S. Schreiber and T. L. Alderson.
1. Procedure
Two hundred and sixty-seven grams (296 ml., 4.38 moles) of 28% aqueous ammonium hydroxide,
207.5 g. (209 ml., 1.57 moles) of paraldehyde, and
5.0 g. (0.065 mole) of ammonium acetate are heated to 230° with continuous agitation in a
2-l. steel reaction vessel (Note 1), and the temperature is maintained at 230° for 1 hour
(Note 2). The
autoclave is then allowed to cool, and the two layers of the reaction mixture are separated
(Note 3). To the non-aqueous layer is added
60 ml. of chloroform, causing separation of water which is combined with the aqueous layer. The aqueous layer is extracted with three
50-ml. portions of chloroform, and the extracts are combined with the main portion of the
chloroform solution. After removal of the
chloroform by distillation at atmospheric pressure, fractional distillation under reduced pressure through a
30-cm. Fenske-type column3 gives a fore-run of water, paraldehyde, and
α-picoline, b.p.
40–60°/17 mm., followed by
72–76 g. (
50–53%) of
5-ethyl-2-methylpyridine, b.p.
65–66°/17 mm.;
nD20 1.4971
(Note 4).
2. Notes
1.
A steel reaction vessel of the type used for high-pressure catalytic hydrogenations is satisfactory. The pressure of the reaction mixture ranges from 800 to 3000 lb. A larger volume of reactants should not be used in a 2-l. reaction vessel.
2.
The reaction is exothermic and in some reaction vessels may cause the temperature to rise above 230° for a short period. This has no apparent effect on the yield of product. The temperature measured is that of a thermocouple inserted in a well in the cover of the autoclave and corresponds to about 250° if the thermocouple is in the wall of the autoclave.
3.
The mixture contains a small amount of solid material, apparently due to slight corrosion of the steel reaction vessel. If the solid causes the formation of an emulsion, it can be removed by filtration.
4.
The yield may be increased to
60–70% by use of an 8:1 molar ratio of
ammonium hydroxide to
paraldehyde, but this is generally inconvenient because of the greatly increased volume of the reaction mixture.
3. Discussion
5-Ethyl-2-methylpyridine (also known as "aldehyde-collidine") has been prepared by heating
aldehyde-ammonia;
4 aldehyde-ammonia and
acetaldehyde5,6,7 or
paraldehyde;
7,8,9 aldol-ammonia and
ammonia;
10 paraldehyde and
ammonia;
11,12,13 acetamide,
14 or
acetamide and
phosphorus pentoxide15 ethylene glycol and
ammonium chloride;
16 ethylidene chloride17,18 or bromide19 and
amonia;
ethylidene chloride and
acetamide,
ethylamine, or
n-amylamine;
16 crotonic acid and a
calcium chloride-ammonia complex;
20 and by passage of
acetylene21 or
acetaldehyde22 and
ammonia over
alumina and other catalysts.
A study has been made of catalysts for the present reaction,
23 and a mechanism for the synthesis of
pyridine and its derivatives by the Beyer-Chichibabin method has been published.
24
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
alumina
aldehyde-ammonia
aldol-ammonia
amonia
calcium chloride-ammonia complex
acetaldehyde (75-07-0)
acetylene (74-86-2)
Acetamide (60-35-5)
ammonia (7664-41-7)
ammonium acetate (631-61-8)
ammonium chloride (12125-02-9)
chloroform (67-66-3)
pyridine (110-86-1)
ethylene glycol (107-21-1)
ammonium hydroxide (1336-21-6)
crotonic acid (3724-65-0)
α-picoline (109-06-8)
ethylamine (75-04-7)
5-Ethyl-2-methylpyridine,
2-Picoline, 5-ethyl- (104-90-5)
ethylidene chloride (75-34-3)
phosphorus pentoxide (1314-56-3)
n-amylamine (110-58-7)
paraldehyde (123-53-7)
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