Org. Synth. 1962, 42, 92
Submitted by A. W. Johnson and R. Price1
Checked by Virgil Boekelheide and M. Kunstmann.
In a 2-l. three-necked flask
fitted with a stirrer
, and reflux condenser
are placed 250 ml. of glacial acetic acid
, 54.5 g. (0.84 g. atom) of zinc dust
, and 52.5 g. (0.46 mole) of 3-methylpentane-2,4-dione (Note 1)
. The contents of the flask are stirred vigorously (Note 2)
, and a solution of 42 g. (0.415 mole) of diacetyl monoxime2
in 150 ml. of glacial acetic acid
is added from a separatory funnel
at a rate to maintain the temperature of the mixture at 65–70°. The addition takes 1 hour. When the addition is complete, the mixture is refluxed with stirring for an additional 30 minutes. The flask is then fitted for distillation with steam under nitrogen
; 500 ml. of water is added and steam is introduced. Steam distillation (Note 3)
is continued until no more tetramethylpyrrole
comes over. This takes 1–2 hours and the distillate amounts to 1–2 l. The tetramethylpyrrole
crystallizes from the steam distillate and is collected by filtration, washed with water, and dried over phosphorus pentoxide
in a vacuum desiccator
. There is obtained 15–18 g.
of white plates, m.p. 110–111°
By neutralizing the filtrate with sodium hydroxide solution, a second crop of 4–5 g. of tetramethylpyrrole, m.p. 109–110°, is obtained. The total yield is 20.5–22.5 g. (40–44%) (Note 4).
is prepared by the methylation of acetylacetone
It is essential that the zinc
dust be stirred effectively or the reaction may become violent.
must be prevented from blocking the condenser. From time to time the condenser is cleared by turning off the coolant water.
is very readily oxidized in the air to a green resinous substance. If it is not used immediately, it should be stored under nitrogen
or sealed in a glass vial under vacuum.
has been prepared by the action of sodium methoxide
by the reduction of 2,3,5-trimethylpyrrole-4-aldehyde semicarbazone
with sodium ethoxide
by the reduction of 2,3,4-trimethylpyrrole-5-aldehyde
with sodium ethoxide
and hydrazine hydrate
and by the reduction of 2,4-dimethylpyrrole-3,5-dicarboxylic acid
with lithium aluminum hydride
Direct ring synthesis by the condensation of 3-aminobutan-2-one
in alkaline solution gave very poor yields, the principal product being 2,3,5,6-tetramethylpyrazine
The above modification of direct ring synthesis avoids this side reaction.10
4. Merits of Preparation
The present method possesses these advantages over those reported earlier:5,6,7,8
it is less laborious, in that it is a single-stage preparation, and it gives a better over-all yield.
This preparation is referenced from:
Chemical Abstracts Nomenclature (Collective Index Number);
acetic acid (64-19-7)
sodium hydroxide (1310-73-2)
sodium methoxide (124-41-4)
sodium ethoxide (141-52-6)
hydrazine hydrate (7803-57-8)
lithium aluminum hydride (16853-85-3)
Pyrrole, 2,3,4,5-tetramethyl- (1003-90-3)
phosphorus pentoxide (1314-56-3)
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