5-(Difluoromethoxy)-2-mercapto-1H-benzimidazole
[CAS# 97963-62-7]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Imidazoles
• Name: 5-(Difluoromethoxy)-2-mercapto-1H-benzimidazole
• Molecular Formula: C₈H₆F₂N₂OS
• Molecular Weight: 216.21
• CAS Registry Number: 97963-62-7
• EC Number: 619-308-7
• SMILES: C1=CC2=C(C=C1OC(F)F)NC(=S)N2

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Melting point: 239 - 243 °C (Expl.)
• Boiling point: 360.9±50.0 °C 760 mmHg (Calc.)^*
• Flash point: 172.1±30.1 °C (Calc.)^*
• Index of refraction: 1.644 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411

Discovery and Applications

5-(Difluoromethoxy)-2-mercapto-1H-benzimidazole is a heterocyclic organic compound featuring a benzimidazole core substituted at the 5-position with a difluoromethoxy group (-OCHF₂) and a thiol (-SH) group at the 2-position. Its molecular formula is C₈H₅F₂N₂OS, and the compound combines the biological relevance of the benzimidazole scaffold with the unique properties imparted by the fluorinated ether and mercapto substituents.

Benzimidazole derivatives are widely studied for their pharmacological and agrochemical applications due to their versatile bioactivities, including antimicrobial, antifungal, antiviral, and anticancer effects. The mercapto group at the 2-position is a reactive site often involved in coordination with metals or formation of disulfide bonds, contributing to biological activity and chemical reactivity. The difluoromethoxy substituent is known to influence lipophilicity, metabolic stability, and binding affinity by introducing electronegativity and modulating electronic distribution in the molecule.

This compound is generally synthesized via cyclization reactions starting from o-phenylenediamine derivatives and appropriate fluorinated reagents to introduce the difluoromethoxy group, followed by thiolation to install the mercapto functionality. The synthesis may involve multi-step procedures under controlled conditions to maintain the integrity of sensitive groups.

In medicinal chemistry, 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole and related analogs have been investigated as potential therapeutic agents. The combination of benzimidazole and fluorinated groups often enhances binding to biological targets such as enzymes or receptors, improving potency and selectivity. The mercapto group may contribute to enzyme inhibition by interacting with active site cysteine residues or metal cofactors.

In agricultural chemistry, compounds of this type have been studied for fungicidal or pesticidal activity. The benzimidazole nucleus is a well-known pharmacophore in fungicides, and fluorinated substituents can improve environmental stability and bioavailability. The mercapto group may also provide unique modes of action through thiol-mediated biochemical interactions.

The physicochemical properties of 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole include moderate solubility in organic solvents and potential sensitivity to oxidation due to the thiol group. Proper storage under inert atmosphere and avoidance of oxidizing agents are recommended to preserve compound stability.

Safety data are limited but general precautions for thiol-containing and fluorinated aromatic compounds should be followed. These include use of gloves, eye protection, and working in well-ventilated areas to minimize exposure.

In summary, 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole is a fluorinated benzimidazole derivative with potential applications in pharmaceutical and agrochemical research. Its structural features confer unique chemical reactivity and biological activity, making it a compound of interest in the development of novel therapeutic and pesticidal agents.

References

2020. Synthesis and Antimicrobial Activity of Novel Bis-1,2,3-triazol-1H-4-yl-substituted Aryl Benzimidazole-2-thiol Derivatives. Russian Journal of General Chemistry, 90(8).
DOI: 10.1134/s1070363220080186

2012. Control of the agglomeration of crystals in the reactive crystallization of 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole. Frontiers of Chemical Science and Engineering, 6(4).
DOI: 10.1007/s11705-012-1211-7

2005. Metabolism of pantoprazole involving conjugation with glutathione in rats. The Journal of pharmacy and pharmacology, 57(3).
DOI: 10.1211/0022357055669