Ethyl 4(5)-imidazolecarboxylate

CAS Number 23785-21-9
Molecular Formula C₆H₈N₂O₂
Molecular Weight 140.14 g/mol
Purity ≥99.0%
Appearance White Crystalline powder

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Product Description

Ethyl 4(5)-imidazolecarboxylate, also known as Ethyl 1H-imidazole-4-carboxylate or 1H-Imidazole-4-carboxylic acid ethyl ester, is an organic compound features an imidazole ring structure and is an ethyl ester derivative of 1H-imidazole-4-carboxylic acid. Its defining characteristic is the tautomerism of its imidazole ring system, which makes it a valuable synthetic intermediate in chemical research and synthesis.

Relationship to Histidine

  • Amino Acid Connection: Ethyl 4(5)-imidazolecarboxylate is the ester derivative of the core heterocycle found in the amino acid L-Histidine, making it a key intermediate for synthesizing histidine-related compounds and studying its biochemistry.

Synthesis Methods

  • Esterification: Imidazole-4-carboxylic acid is reacted with ethanol in the presence of an acid catalyst (e.g., H₂SO₄ or HCl) under reflux.

  • Catalytic Methods: Using inorganic salt composites, starting from precursors like ethyl acetoacetate.

  • Reactions with Ethyl Acetylglycine: Involves reactions with ethyl acetylglycine.

  • Cycloaddition Processes: Involves cycloaddition processes with ethyl isocyanoacetate and imidoyl chlorides.

Uses

  • Primary Use: A versatile building block in organic synthesis and medicinal chemistry.

  • Pharmaceuticals: Precursor in the synthesis of H₂ and H₃ antihistamines and other drug candidates targeting histamine receptors.

  • Agrochemicals: Used in the synthesis of complex molecules containing the imidazole scaffold.

  • Chemical Research: Employed as a reagent in modifying dendritic polymers to alter material surface properties and catalytic performance.

  • Biochemical Role: The parent acid (1H-imidazole-4-carboxylic acid) plays a role in lanthanide metal-catalyzed phosphate ester hydrolysis reactions.

  • Pharmaceutical Intermediate: Structurally related imidazole derivatives (e.g., etomidate) are used as anesthetics.

  • Coordination Chemistry: Useful in imidazole-based coordination complexes and ligand design.

  • Peptide Coupling: Sometimes employed in peptide coupling reactions or biochemical derivatizations due to its imidazole functionality.

Structure and Tautomerism

  • Imidazole Ring: A 5-membered ring with two nitrogen atoms. One nitrogen is of the "pyrrole" type, and the other is of the "pyridine" type.

  • Tautomers: The hydrogen atom on the nitrogen can switch positions between the two nitrogen atoms, creating two interchangeable structures (4-tautomer and 5-tautomer) in dynamic equilibrium.

  • Simplified Tautomerization: Ethyl 1H-imidazole-4-carboxylate ↔ Ethyl 1H-imidazole-5-carboxylate

  • Canonical SMILES: CCOC(=O)C1=CN=CN1

  • InChI: 1S/C6H8N2O2/c1-2-10-6(9)5-3-7-4-8-5/h3-4H,2H2,1H3,(H,7,8)

Key Properties

  • Appearance: Typically a white to off-white crystalline powder or a colorless to light yellow liquid or crystalline solid.

  • Solubility: Soluble in common organic solvents (e.g., methanol, ethanol, dichloromethane, DMSO) with limited solubility in water.

  • Melting Point: ~156-160 °C

  • Physical State: Solid at room temperature

Safety and Handling

  • Classification: Combustible solid with a storage class of 11.

  • Water Hazard Class (WGK): 3 (severely hazardous to water).

  • Handling: Standard laboratory precautions should be followed, including proper ventilation and protective equipment.

  • Storage: Keep in a well-ventilated place, store locked up, and keep container tightly closed.

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