2-(Hydroxyphenylmethyl)benzimidazole
[CAS# 50-97-5]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Imidazoles
• Name: 2-(Hydroxyphenylmethyl)benzimidazole
• Synonyms: HBB; Hybendazole; NSC 31798; NSC 405; alpha-Phenyl-1H-benzimidazole-2-methanol
• Molecular Formula: C₁₄H₁₂N₂O
• Molecular Weight: 224.26
• CAS Registry Number: 50-97-5
• EC Number: 200-073-0
• SMILES: C1=CC=C(C=C1)C(C2=NC3=CC=CC=C3N2)O

Properties

• Solubility: Slightly soluble (2 g/L) (25 ºC), Calc.^*
• Density: 1.298±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*
• Melting point: 207-208 ºC^**

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

^** Porai-Koshits, B. A.; Zhurnal Obshchei Khimii 1955, V25, P2138-43.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H317-H412
• Precautionary Statements: P261-P272-P273-P280-P302+P352-P321-P333+P317-P362+P364-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin sensitization	Skin Sens.	1B	H317
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

Discovory and Applicatios

2-(Hydroxyphenylmethyl)benzimidazole is an organic compound belonging to the class of benzimidazole derivatives. Structurally, it consists of a benzimidazole ring substituted at the 2-position with a hydroxyl-containing benzyl group. The general framework of benzimidazole—a fused system comprising a benzene ring fused to an imidazole ring—serves as a privileged scaffold in medicinal chemistry due to its presence in a wide variety of biologically active molecules.

The synthesis of 2-(hydroxyphenylmethyl)benzimidazole has been described in the literature and typically involves the condensation of o-phenylenediamine with a hydroxybenzaldehyde, followed by reduction of the resulting Schiff base to yield the target compound. This method provides flexibility in the substitution pattern on the phenyl ring, allowing for derivatives bearing the hydroxyl group at various positions (ortho, meta, or para). Common reagents for the reduction step include sodium borohydride or catalytic hydrogenation under mild conditions.

The presence of both a benzimidazole moiety and a phenolic hydroxyl group imparts the compound with potential for diverse chemical reactivity and biological activity. The benzimidazole ring system can participate in hydrogen bonding and π-stacking interactions, making it a key pharmacophore in the design of ligands for enzymes and receptors. Meanwhile, the hydroxyl group contributes to solubility and the possibility of forming intramolecular hydrogen bonds, which may stabilize specific conformations and influence binding interactions with biological targets.

Although 2-(hydroxyphenylmethyl)benzimidazole itself is not a widely marketed drug, the structure is closely related to a number of benzimidazole-based pharmaceuticals and experimental compounds. Benzimidazole derivatives are known for their applications as antiviral, antibacterial, antifungal, anticancer, and anti-inflammatory agents. Compounds structurally similar to 2-(hydroxyphenylmethyl)benzimidazole have been investigated for their ability to inhibit protein kinases, DNA topoisomerases, and microbial enzymes.

In the field of medicinal chemistry, derivatives of this compound have been explored as inhibitors of histamine receptors, especially H₂ receptor antagonists, and as selective ligands for central nervous system targets. Structure–activity relationship (SAR) studies have shown that hydroxylated benzimidazole compounds can exhibit enhanced affinity and specificity for certain enzymes and receptors due to their ability to form additional polar interactions.

Analytical characterization of 2-(hydroxyphenylmethyl)benzimidazole typically involves techniques such as nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and mass spectrometry (MS). In the ¹H NMR spectrum, characteristic signals include those from the aromatic protons of both the benzimidazole and phenyl rings, as well as the methylene (–CH₂–) bridge between the two. The hydroxyl proton often appears as a broad singlet, depending on solvent and temperature conditions. IR spectroscopy confirms the presence of hydroxyl (–OH) and imidazole (N–H) functional groups, while MS provides the molecular ion peak and fragmentation pattern consistent with the compound's structure.

The compound is generally a solid at room temperature and exhibits moderate solubility in polar organic solvents such as methanol, ethanol, and dimethyl sulfoxide (DMSO). Its stability under ambient conditions allows for convenient storage and handling in laboratory settings. However, the phenolic hydroxyl group may be susceptible to oxidation upon prolonged exposure to air and light, so samples are typically stored in tightly sealed containers protected from moisture and UV radiation.

In summary, 2-(hydroxyphenylmethyl)benzimidazole is a benzimidazole derivative with a hydroxyl-functionalized benzyl substituent, offering a platform for the development of biologically active compounds. Its structural features make it an attractive intermediate or lead compound in medicinal chemistry, particularly in the design of therapeutic agents targeting enzymes and receptors within inflammatory, infectious, or neoplastic pathways.

References

2022. A quantitative high-throughput screen identifies compounds that lower expression of the SCA2-and ALS-associated gene ATXN2. The Journal of biological chemistry, 298(8).
DOI: 10.1016/j.jbc.2022.102228

2013. Synthesis, characterization, reactivity, identification of isomeric species and crystal structure of dinitrosylmolybdenum(0) complexes of 2-(α-hydroxyalkyl/aryl)benzimidazole. Transition Metal Chemistry, 38(5).
DOI: 10.1007/s11243-013-9721-9

1984. Antiviral Action of 2-(α-Hydroxybenzyl)-Benzimidazole (HBB). Targets for the Design of Antiviral Agents.
DOI: 10.1007/978-1-4684-4709-5_8