Multi-component reaction in water (Passerini reaction)


To develop a multi-component reaction (MCR), as an example of a high-atom-economy reaction. Also, in this special case, the Passerini reaction is performed in aqueous medium, which means dramatically reducing the environmental impact of the process.

Multi-component reaction in water (Passerini reaction)
Multi-component reaction in water (Passerini reaction)


MCRs are reactions in which three or more molecules interact with each other to give a single compound that incorporates most of the atoms from each of the starting materials, so that these reactions have high atom economy.
The three types of compounds involved in the Passerini reaction are an isocyanide, an aldehyde (or ketone), and a carboxylic acid. It is usually performed in an organic solvent such as CH2Cl2 or MeOH. Reaction times are typically on the order of a day, so it is unusual to conduct such reactions in a practice session, because this takes far longer than a typical laboratory session. However, this reaction can be conducted in an aqueous medium and not only is a green alternative but also represents a reduced reaction time while offering excellent yields at room temperature. This method is more environmentally friendly than traditional, since water is non-toxic and safe and it is not necessary to heat using volatile and flammable organic solvents.

Experimental procedure

In a 50 ml Erlenmeyer flask, add 20 ml of water, benzoic acid (0.61 g, 0.50 mmol) and benzaldehyde (0.51 ml, 0.50 mmol). Stir the mixture for a few minutes, and then add tert-butyl isocyanide (0.57 ml, 0.50 mmol). After adding all reagents, stir the reaction vigorously at room temperature until the appearance of a white precipitate (approximately 25 min).
Collect the white solid from the reaction crude by vacuum filtration. Transfer the solid to a round-bottom flask and dissolve in hot EtOH at reflux. The addition of water leads to the formation of a white solid compound that is analytically pure and is isolated by vacuum filtration. Dry, weigh, and calculate the yield. The typical yield of this reaction in water ranges from 85 to 95 %.

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)
Benzaldehyde 106.12 -26 178-179 1.044
Benzoic acid 122.12 125 249 1.08
EtOH 46.07 -114.1 78.5 0.790
tert-Butyl isocyanide 83.13 - 91

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
Benzaldehyde ghs07  Warning Toxic cat. 4 Irritant cat. 2 or 3 Lower systemic health hazards pictogram
Benzoic acid ghs05  Danger Warning Corrosive cat. 1 pictogram ghs07  Warning Toxic cat. 4 Irritant cat. 2 or 3 Lower systemic health hazards pictogram
EtOH ghs02  Danger Warning Flammable pictogram
tert-Butyl isocyanide ghs02  Danger Warning Flammable pictogram ghs06  Danger Toxic cat. 1–3 pictogram

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.