The Biginelli reaction is a one-pot (three-component) procedure that in the presence of an acid catalyst, converts a β-keto ester, an aryl aldehyde, and urea to a hexahydropyrimidine derivative. First, urea reacts with the aldehyde affording an aminal, which dehydrates to an N-acyliminium ion. The enol form of the β-keto ester then attacks the N-acyliminium intermediate, making an open chain ureide, which cyclizes to a hexahydropyrimidine derivative.

• Reagents: Catalytic Acid (HCl, H₂SO₄, TsOH, LiBr, etc.), Alcohol Solvent (e.g. Ethanol)
• Reactant: β-Keto Ester, Aryl/Heteroaromatic/Aliphatic Aldehyde, Urea (Monosubstituted, Thiourea)
• Product: Hexahydropyrimidine Derivative
• Type of Reaction: Condensation

Mechanism

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Related Compounds