2-Chlorothiophenol
[CAS# 6320-03-2]

Identification

• Classification: Chemical reagent >> Organic reagent >> Thiol/thiophenol
• Name: 2-Chlorothiophenol
• Synonyms: 2-Chlorobenzenethiol
• Molecular Formula: C₆H₅ClS
• Molecular Weight: 144.62
• CAS Registry Number: 6320-03-2
• EC Number: 228-667-5
• SMILES: C1=CC=C(C(=C1)S)Cl

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*, 1.277 g/mL (Expl.)
• Boiling point: 206.3±13.0 °C 760 mmHg (Calc.)^*, 253.1 - 254.2 °C (Expl.)
• Flash point: 88.3 °C (Calc.)^*, 88 °C (Expl.)
• Index of refraction: 1.606 (Calc.)^*, 1.603 (Expl.)

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

Safety Data

• Hazard Symbols: GHS05 Danger
• Risk Statements: H314
• Safety Statements: P260-P264-P280-P301+P330+P331-P302+P361+P354-P304+P340-P305+P354+P338-P316-P321-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Serious eye damage	Eye Dam.	1	H318
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin corrosion	Skin Corr.	1	H314
Acute toxicity	Acute Tox.	4	H302
Skin corrosion	Skin Corr.	1C	H314

• Transport Information: UN 3265

Discovery and Applications

2-Chlorothiophenol is an organosulfur compound with the molecular formula C₆H₅ClS. It consists of a benzene ring substituted with a thiol group (–SH) at the 1-position and a chlorine atom at the adjacent 2-position, giving it an ortho-substituted structure. The compound is a colorless to pale yellow liquid with a strong, unpleasant odor typical of low-molecular-weight thiols.

This compound is synthesized primarily by chlorination of thiophenol under controlled conditions or through nucleophilic aromatic substitution reactions involving chlorinated aromatic precursors and sulfur-based nucleophiles. It is not known to occur naturally and is typically prepared in the laboratory or industrial settings for use as an intermediate.

2-Chlorothiophenol is used in the synthesis of pharmaceuticals, agrochemicals, and other fine chemicals. The presence of both the thiol and chloro substituents on the aromatic ring allows for selective transformations. The thiol group can undergo oxidation, alkylation, or coupling reactions, while the chlorine atom may be displaced by nucleophiles in further substitution reactions. This versatility makes the compound a valuable building block for preparing more complex molecules.

In pharmaceutical research, chlorothiophenol derivatives have been studied for their potential bioactivity, including antimicrobial and enzyme-inhibitory effects. The thiol group is particularly important in interacting with metal ions or cysteine residues in proteins, while the chlorine can influence lipophilicity and electronic distribution within the molecule.

In material science and surface chemistry, aryl thiols like 2-chlorothiophenol have been used for the functionalization of gold surfaces due to the strong affinity of sulfur for gold. This allows the formation of self-assembled monolayers (SAMs), which are employed in sensors, nanotechnology, and interface studies.

From a safety perspective, 2-chlorothiophenol should be handled with caution. Thiophenols are known for their strong, persistent odors and potential toxicity. Exposure may cause skin or respiratory irritation, and the compound is flammable and reactive with oxidizing agents. Proper ventilation, use of gloves, and eye protection are recommended when working with this compound.

In summary, 2-chlorothiophenol is a synthetic aromatic thiol used as a versatile intermediate in organic synthesis. Its chemical reactivity makes it valuable in preparing pharmaceuticals, agrochemicals, and materials for surface modification, although it requires careful handling due to its odor and potential health hazards.

References

2021. Metal-Free Thiol-Ene Coupling with anti-Markovnikov Selectivity. Science of Synthesis.
URL: https://science-of-synthesis.thieme.com/app/text/?id=SD-235-00274

2012. Direct Sulfanylation of 4-Quinazolinone via C-OH Bond Activation: An Efficient Route to 2-Aryl-4-sulfanylquinazolines. Synthesis, 44(13).
DOI: 10.1055/s-0031-1289731

1970. New method for synthesis of arylthiols. Bulletin of the Academy of Sciences of the USSR, Division of chemical science, 19(3).
DOI: 10.1007/bf00848985