A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1962, 42, 92
DOI: 10.15227/orgsyn.042.0092
[Pyrrole, 2,3,4,5-tetramethyl-]
Submitted by A. W. Johnson and R. Price1.
Checked by Virgil Boekelheide and M. Kunstmann.
1. Procedure
In a 2-l. three-necked flask fitted with a stirrer, thermometer, 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° (lit.,3 m.p. 112°).
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).
2. Notes
1. 3-Methylpentane-2,4-dione is prepared by the methylation of acetylacetone.4,5
2. It is essential that the zinc dust be stirred effectively or the reaction may become violent.
3. Tetramethylpyrrole must be prevented from blocking the condenser. From time to time the condenser is cleared by turning off the coolant water.
4. 2,3,4,5-Tetramethylpyrrole 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.
3. Discussion
2,3,4,5-Tetramethylpyrrole has been prepared by the action of sodium methoxide on 2,3,5-trimethylpyrrole,6 by the reduction of 2,3,5-trimethylpyrrole-4-aldehyde semicarbazone with sodium ethoxide,7 by the reduction of 2,3,4-trimethylpyrrole-5-aldehyde with sodium ethoxide and hydrazine hydrate,8 and by the reduction of 2,4-dimethylpyrrole-3,5-dicarboxylic acid with lithium aluminum hydride.9 Direct ring synthesis by the condensation of 3-aminobutan-2-one and butan-2-one in alkaline solution gave very poor yields, the principal product being 2,3,5,6-tetramethylpyrazine.3 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:

References and Notes
  1. Department of Chemistry, The University of Nottingham, Nottingham, England.
  2. W. L. Semon and V. R. Damerell, Org. Syntheses, Coll. Vol. 2, 204 (1943).
  3. H. Fischer and B. Walach, Ann., 447, 38 (1926).
  4. A. W. Johnson, E. Markham, and R. Price, this volume, p. 785.
  5. K. von Auwers and H. Jacobsen, Ann., 426, 161 (1921).
  6. H. Fischer and E. Bartholomäus, Z. Physiol. Chem., 80, 10 (1912).
  7. H. Fischer and W. Zerweck, Ber., 56, 519 (1923).
  8. M. Dennstedt, Ber., 22, 1924 (1889).
  9. A. Treibs and H. Derra-Scherer, Ann., 589, 188 (1954).
  10. A. W. Johnson, E. Markham, R. Price, and K. B. Shaw, J. Chem. Soc., 4254 (1958).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

diacetyl monoxime

acetic acid (64-19-7)

sodium hydroxide (1310-73-2)

nitrogen (7727-37-9)

sodium methoxide (124-41-4)

zinc (7440-66-6)

sodium ethoxide (141-52-6)

hydrazine hydrate (7803-57-8)

butan-2-one (78-93-3)

Acetylacetone (123-54-6)

lithium aluminum hydride (16853-85-3)

Pyrrole, 2,3,4,5-tetramethyl- (1003-90-3)

3-Methylpentane-2,4-dione (815-57-6)


2,3,5-trimethylpyrrole-4-aldehyde semicarbazone


2,4-dimethylpyrrole-3,5-dicarboxylic acid


2,3,5,6-tetramethylpyrazine (1124-11-4)

phosphorus pentoxide (1314-56-3)