Imidazol-1-yl-acetic acid
[CAS# 22884-10-2]

Identification

• Classification: Biochemical >> Common amino acids and protein drugs
• Name: Imidazol-1-yl-acetic acid
• Synonyms: 2-(1H-Imidazol-1-yl)acetic acid
• Molecular Formula: C₅H₆N₂O₂
• Molecular Weight: 126.11
• CAS Registry Number: 22884-10-2
• EC Number: 607-175-8
• SMILES: C1=CN(C=N1)CC(=O)O

Properties

• Density: 1.3±0.1 g/cm³, Calc.^*
• Melting Point: 268-269 °C (decomp.) (Expl.)
• Index of Refraction: 1.588, Calc.^*
• Boiling Point: 392.1±25.0 °C (760 mmHg), Calc.^*
• Flash Point: 190.9±23.2 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Risk Statements: H315-H318-H335
• Safety Statements: P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P332+P313-P362-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Serious eye damage	Eye Dam.	1	H318
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312

Discovery and Applications

Imidazol-1-yl-acetic acid is a small organic compound containing an imidazole ring substituted at the nitrogen-1 position with an acetic acid moiety. Its molecular formula is C₅H₆N₂O₂, and it represents one of several derivatives in the class of imidazole-substituted carboxylic acids. The structure is defined by the presence of a five-membered aromatic imidazole ring linked through a methylene bridge to a carboxylic acid group.

The discovery and synthesis of imidazol-1-yl-acetic acid are closely related to broader studies on the chemistry of imidazoles, which began in the 19th century with the work of Heinrich Debus and others. Imidazole itself was first synthesized in 1858, and subsequent research led to a variety of functionalized derivatives including imidazol-1-yl-acetic acid. The compound can be synthesized by alkylating imidazole with haloacetic acids, most commonly chloroacetic acid, in the presence of a base such as sodium hydroxide. This reaction yields imidazol-1-yl-acetic acid via nucleophilic substitution at the halomethyl position.

Imidazol-1-yl-acetic acid is used in synthetic and pharmaceutical chemistry as a versatile intermediate. Its imidazole moiety contributes nucleophilic and basic properties, while the carboxylic acid group provides functionality for further derivatization. This dual functionality allows the compound to serve as a building block in the preparation of more complex molecules, particularly in the development of biologically active agents.

In pharmaceutical contexts, imidazole derivatives are known for their broad spectrum of bioactivity, including antifungal, antibacterial, and enzyme-inhibitory properties. While imidazol-1-yl-acetic acid itself is not widely used as a drug, it serves as a key intermediate in the synthesis of pharmacologically relevant compounds. For example, it has been utilized in the preparation of angiotensin-converting enzyme (ACE) inhibitors and analogs of histamine receptor ligands. The carboxylic acid group enables coupling reactions to other bioactive scaffolds, while the imidazole ring can engage in hydrogen bonding and metal coordination in target binding.

Beyond medicinal chemistry, imidazol-1-yl-acetic acid is also of interest in coordination and supramolecular chemistry. The imidazole ring’s nitrogen atoms can act as ligands to metal centers, forming complexes that are studied for catalytic or structural properties. Derivatives of this compound have been employed in ligand design for transition metal coordination, offering potential applications in homogeneous catalysis and materials science.

In biochemical studies, imidazol-1-yl-acetic acid and its derivatives are also used as probes or mimics of naturally occurring imidazole-containing compounds, such as histidine and histamine. The structural similarity to these biological molecules allows the compound to serve as a model for understanding enzyme-substrate interactions involving imidazole side chains.

The physicochemical properties of imidazol-1-yl-acetic acid, such as its solubility in polar solvents and its moderate acidity, make it suitable for aqueous-phase reactions and bioassays. Analytical methods for detecting and quantifying the compound include nuclear magnetic resonance spectroscopy, mass spectrometry, and chromatographic techniques such as HPLC.

Overall, imidazol-1-yl-acetic acid remains a compound of interest primarily due to its role as an intermediate in chemical synthesis. Its applications are well-established in the literature, particularly in the context of pharmaceutical development, organic synthesis, and coordination chemistry. The compound exemplifies the utility of imidazole derivatives in modern chemistry through its structural simplicity and functional versatility.

References

2022. Magnetic Graphene Oxide/Carboxymethyl-Imidazolium-Grafted Chitosan Schiff Base Nanocomposite: A New PdNPs Support for Efficient Catalytic Reduction of Hazardous Nitroarenes. Journal of Inorganic and Organometallic Polymers and Materials, 32.
DOI: 10.1007/s10904-022-02368-z

2022. Substituted-amidine derivatives of diazabicyclooctane as prospective β-lactamase inhibitors. Monatshefte für Chemie - Chemical Monthly, 153.
DOI: 10.1007/s00706-021-02888-3

2022. Synthesis and characterization of a novel Brönsted acidic dicationic ionic liquid based on piperazine and its application in the one-pot synthesis of various xanthenes under solvent-free conditions. Research on Chemical Intermediates, 48.
DOI: 10.1007/s11164-022-04666-0