Microscale – Paal-Knorr synthesis of 2,5-dimethyl-1-phenylpyrrole

Written by J.A Dobado | Last Updated on April 22, 2024

Objective

To synthesize at microscale a heterocyclic compound, in particular, 2,5-dimethyl-1-phenylpyrrole using the Paal-Knorr synthesis.

Synthesis of 2,5-dimethyl-1-phenylpyrrole by Paal-Knorr reaction
Microscale – Synthesis of 2,5-dimethyl-1-phenylpyrrole by Paal-Knorr reaction

Background

Among different types of cyclization reactions for preparing nitrogen heterocycles, one of the most popular methods for the synthesis of substituted pyrroles is known as the Paal-Knorr synthesis. In this experiment, a 1,4-dicarbonyl compound is heated with a primary amine to produce a pyrrole derivative.

Microscale experimental procedure

In a round-bottom flask fitted with a reflux condenser, add 186 mg (2.0 mmol) of aniline, 228 mg (2 mmol) of hexane-2,5-dione, 0.5 ml of MeOH, and 1 drop of HCl (conc.). Heat the mixture at reflux for 15 min, and then add 5.0 ml of HCl 0.5 M (keep the mixture cool in an ice bath). Collect the crystals by means of vacuum filtration, and recrystallize from 1 ml of a mixture of MeOH/water (9:1). The yield is approximately 52% (178 mg).

Isolation Scheme of theSynthesis of 2,5-dimethyl-1-phenylpyrrole by Paal-Knorr reaction
Isolation Scheme of the Synthesis of 2,5-dimethyl-1-phenylpyrrole by Paal-Knorr reaction

Physico-chemical properties

This table collects data for the molecular weight (Mw), melting point (M.p.) boiling point (B.p.) and density of the reactives and compounds used in this laboratory experiment.

Name Mw (g/mol) M.p. (ºC) B.p. (ºC) Density (g/ml)
Aniline93.13-61841.022
HCl 36.46-30>1001.200
Hexane-2,5-dione114.146191 -
MeOH32.04-9864.70.791
2,5-Dimethyl-1-phenyl-1H-pyrrole171.2448-52156-160 -

GHS pictograms

Hazard pictograms form part of the international Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and are collected in the followinf Table for the chemical compounds used in this experiment.

Name GHS
Aniline ghs05  Danger Warning Corrosive cat. 1 pictogram ghs06  Danger Toxic cat. 1–3 pictogram ghs08  Danger Warning Systemic health hazards pictogram ghs09  Warning (for cat. 1) (for cat. 2 no signal word) Environmental hazard pictogram
HCl ghs05  Danger Warning Corrosive cat. 1 pictogram ghs07  Warning Toxic cat. 4 Irritant cat. 2 or 3 Lower systemic health hazards pictogram
Hexane-2,5-dione ghs08  Danger Warning Systemic health hazards pictogram ghs07  Warning Toxic cat. 4 Irritant cat. 2 or 3 Lower systemic health hazards pictogram
MeOH ghs02  Danger Warning Flammable pictogram ghs06  Danger Toxic cat. 1–3 pictogram ghs08  Danger Warning Systemic health hazards pictogram
2,5-Dimethyl-1-phenyl-1H-pyrrole Non-hazardous

International Chemical Identifier

The IUPAC InChI key identifiers for the main compounds used in this experiment are provided to facilitate the nomenclature and formulation of chemical compounds and the search for information on the Internet for these compounds.

AnilinePAYRUJLWNCNPSJ-UHFFFAOYSA-N
HCl VEXZGXHMUGYJMC-UHFFFAOYSA-N
Hexane-2,5-dioneOJVAMHKKJGICOG-UHFFFAOYSA-N
MeOHOKKJLVBELUTLKV-UHFFFAOYSA-N
2,5-Dimethyl-1-phenyl-1H-pyrroleJNXIFVSGXLGULI-UHFFFAOYSA-N

References

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