alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol
[CAS# 24155-42-8]

Identification

• Classification: Analytical chemistry >> Standard >> Pharmacopoeia standards and magazine standards
• Name: alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol
• Synonyms: 1-(2,4-Dichlorophenyl)-2-(1-imidazolyl)ethanol
• Molecular Formula: C₁₁H₁₀Cl₂N₂O
• Molecular Weight: 257.12
• CAS Registry Number: 24155-42-8
• EC Number: 246-042-5
• SMILES: C1=CC(=C(C=C1Cl)Cl)C(CN2C=CN=C2)O

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Melting point: 134 ºC (Expl.)
• Boiling point: 468.5±45.0 ºC 760 mmHg (Calc.)^*, 468.5 ºC (Expl.)
• Flash point: 237.1±28.7 ºC (Calc.)^*
• Index of refraction: 1.626 (Calc.)^*
• Water solubility: 1300 g/L (20 ºC)

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

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Warning
• Hazard Statements: H302-H312-H315-H319-H332-H335-H371-H400-H411
• Precautionary Statements: P260-P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P308+P316-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Specific target organ toxicity - single exposure	STOT SE	2	H371
Specific target organ toxicity - single exposure	STOT SE	3	H335
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Reproductive toxicity	Repr.	2	H361

Discovory and Applicatios

α-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol is a synthetic organic compound that belongs to the class of substituted imidazoles. Structurally, it features a five-membered imidazole ring substituted at the 1-position with a hydroxyethyl group and at the α-position with a 2,4-dichlorophenyl group. Its molecular framework combines an aromatic halogenated ring, a heterocyclic base, and a polar hydroxyl functionality, which together influence both its chemical reactivity and potential biological activity.

The imidazole ring is a key heteroaromatic moiety found in numerous naturally occurring and synthetic bioactive molecules. This structure, containing two nitrogen atoms at nonadjacent positions, contributes to both hydrogen bonding and coordination chemistry, making it an important motif in medicinal and coordination chemistry. The presence of a hydroxyethyl side chain on the nitrogen increases solubility in polar solvents and adds an additional site for hydrogen bonding, potentially enhancing interactions with enzymes or receptors.

The dichlorophenyl substituent at the α-position refers to a phenyl ring with chlorine atoms substituted at the 2- and 4-positions. Chlorination of aromatic rings often enhances lipophilicity and can increase the compound's binding affinity for biological targets by promoting hydrophobic interactions. The electron-withdrawing effect of the chlorine atoms also modulates the electronic density on the phenyl ring, which can influence the compound’s reactivity in electrophilic substitution reactions and metabolic stability.

This compound is synthesized using methods typical for substituted imidazoles. A common route involves the reaction of 2,4-dichlorophenylacetonitrile or 2,4-dichlorophenylacetic acid derivatives with glyoxal, ammonia (or ammonium salts), and an aldehyde or ketone to form the imidazole ring via a multicomponent condensation reaction. The hydroxylated ethyl side chain can be introduced by nucleophilic substitution or reduction of a corresponding ketone precursor.

In terms of physical properties, α-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol is typically a crystalline solid at room temperature. It has moderate solubility in organic solvents such as ethanol, methanol, or dimethyl sulfoxide (DMSO), and limited solubility in water. Its melting point varies depending on purity and crystallization method, and it is generally stable under ambient storage conditions when kept away from moisture and light.

Functionally, compounds of this type are frequently studied in pharmaceutical chemistry. The combination of a halogenated aromatic ring and an imidazole base is a structural hallmark in several therapeutic classes, including antifungal, antibacterial, and enzyme-inhibiting agents. Specifically, imidazole derivatives are known to interfere with fungal cytochrome P450 enzymes, disrupting ergosterol biosynthesis, which is essential for fungal cell membrane integrity. While α-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol itself is not an approved drug, its structural similarity to antifungal agents such as miconazole or econazole makes it a useful model or synthetic intermediate in medicinal research.

Analytical characterization of this compound includes standard techniques such as nuclear magnetic resonance (NMR) spectroscopy for elucidating the substitution pattern on both the imidazole and phenyl rings. Proton and carbon-13 NMR spectra typically show characteristic chemical shifts for the imidazole protons, aromatic ring protons, and the hydroxyl and methylene groups in the side chain. Infrared (IR) spectroscopy is used to confirm the presence of hydroxyl and imidazole functional groups, with typical absorptions around 3,200-3,500 cm⁻¹ for the O-H stretch and in the region of 1,500-1,600 cm⁻¹ for the C=N and aromatic stretches. Mass spectrometry is used to determine the molecular ion peak and fragment patterns that confirm the molecular structure.

Derivatives and analogs of α-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol are also valuable in structure-activity relationship (SAR) studies. By systematically varying the positions or nature of the substituents on the imidazole or phenyl rings, chemists can investigate how these changes affect biological activity and pharmacokinetics.

In conclusion, α-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol is a structurally significant imidazole-based compound that combines features of aromatic chlorinated rings, polar hydroxyl groups, and nitrogen-containing heterocycles. Its well-defined structure and chemical versatility make it a compound of interest in synthetic organic chemistry and pharmaceutical development, particularly in the design of antifungal or enzyme-targeting molecules.

References

2024. Synthesis of Proline-Derived Helical Copolyacetylenes as Chiral Stationary Phases for HPLC Enantioseparation. Chinese Journal of Polymer Science, 42(11).
DOI: 10.1007/s10118-024-3249-7

2024. Synthesis of hybrid compounds containing tetraoxane and triazole or imidazole moieties and their fungicidal activity. Russian Chemical Bulletin, 73(5).
DOI: 10.1007/s11172-024-4248-0

2019. An Easy, Efficient and Improved Synthesis of Sertaconazole Nitrate. Russian Journal of Organic Chemistry, 55(8).
DOI: 10.1134/s1070428019080219