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Benzoisothiazole, also known as 1,2-benzisothiazole, is a fused heterocyclic compound comprising a benzene ring fused to a thiazole ring.
With diverse industrial and pharmaceutical relevance, this molecule exhibits significant biological activity and serves as a precursor in the synthesis of antimicrobial, antifungal, and anti-inflammatory agents.
This article explores benzoisothiazole in depth, from its chemical structure and physicochemical properties to its synthetic methods, applications, biological profile, toxicological assessments, and future research directions.
Detailed regulatory considerations and safety profiles are also addressed.
CAS Number: 95-14-7
Synonyms: Benzisothiazole, 1,2-Benzisothiazole, 1,2-benzothiazole
Introduction
Benzoisothiazole is a prominent member of nitrogen-sulfur heterocycles.
Due to its aromatic stability and electron-donating heteroatoms, it exhibits significant reactivity and binding potential in biological and material sciences.
Its structural versatility makes it valuable in drug discovery, dye manufacture, and agrochemicals. This compound has gained increasing attention due to its antibacterial, antifungal, and anticancer activities.
Chemical Identity
IUPAC Name: 1,2-benzothiazole
CAS Number: 95-14-7
Synonyms:
Benzisothiazole
1,2-Benzisothiazole
1,2-Benzothiazole
BZT
Benzo[d]isothiazole
Molecular Formula: C7H5NS
Molecular Weight: 135.18 g/mol
Structure: A bicyclic aromatic compound consisting of a benzene ring fused with a five-membered isothiazole ring.
Structure and Physicochemical Properties
Chemical Structure:
Physical Appearance: Colorless to pale yellow liquid
Boiling Point: 227–228°C
Melting Point: −30°C
Density: 1.24 g/cm³
Solubility: Slightly soluble in water; soluble in organic solvents such as ethanol, acetone, chloroform
LogP (octanol/water): 2.1
pKa: Approximately 5.5 (for the nitrogen atom)
Synthesis and Industrial Preparation
Laboratory Synthesis
Benzoisothiazole is commonly synthesized via the cyclization of 2-aminothiophenol with formaldehyde, or through oxidative cyclization of thiobenzanilides.
Example Reaction:
2-Aminothiophenol + Formaldehyde → Benzoisothiazole + H₂O
Industrial Production
Industrially, BZT is produced using:
Chlorosulfonation of aniline derivatives
Thermal cyclization of substituted thioureas
Sulfur and ammonia-based routes
These methods allow for high yields and are economically viable at scale.
Analytical Methods
Benzoisothiazole is characterized and quantified using the following analytical techniques:
Nuclear Magnetic Resonance (NMR): ¹H and ¹³C spectra confirm the aromatic and heterocyclic structure.
Mass Spectrometry (MS): Shows molecular ion peak at m/z 135.
Infrared Spectroscopy (FTIR): Peaks at ~3050 cm⁻¹ (C–H), ~1600 cm⁻¹ (C=N), and ~700–800 cm⁻¹ (C–S).
High-Performance Liquid Chromatography (HPLC): For quantitative analysis.
Gas Chromatography–Mass Spectrometry (GC-MS): Widely used for volatile derivatives.
Chemical Reactivity and Mechanisms
Electrophilic Substitution
Due to the electron-rich nitrogen and sulfur atoms, BZT undergoes electrophilic substitution primarily at the 3- or 6-position.
Nucleophilic Attack
The sulfur atom is susceptible to nucleophilic attack in oxidative conditions, leading to sulfoxides or sulfones.
Oxidation/Reduction
Can be oxidized to sulfone or sulfoxide.
Can undergo redox cycling in biological systems.
Applications
Pharmaceuticals
Used as a core structure in antipsychotic drugs like ziprasidone.
Acts as a lead compound for antifungal and antimicrobial drugs.
Scaffolds for anticancer agents.
Agrochemicals
Intermediate in pesticide synthesis (e.g., fungicides and herbicides).
Functions as a plant growth regulator.
Dyes and Pigments
Precursor for sulfur-based dyes and UV stabilizers.
Used in the manufacture of heat-sensitive pigments.
Polymers and Materials
Acts as a corrosion inhibitor.
Incorporated in materials for flame retardancy.
Biological Activity and Pharmacology
Antimicrobial Activity
Active against E. coli, S. aureus, and Candida albicans.
Mechanism: Disruption of microbial cell walls and enzyme inhibition.
Anticancer Properties
Derivatives show inhibition of topoisomerases and DNA synthesis.
Active in vitro against breast and prostate cancer cell lines.
CNS Activity
Benzoisothiazole derivatives bind dopamine and serotonin receptors.
Ziprasidone is a well-known antipsychotic with this scaffold.
SAFETY INFORMATION ABOUT BENZOISOTHIAZOLE
First aid measures:
Description of first aid measures:
General advice:
Consult a physician.
Show this safety data sheet to the doctor in attendance.
Move out of dangerous area:
If inhaled:
If breathed in, move person into fresh air.
If not breathing, give artificial respiration.
Consult a physician.
In case of skin contact:
Take off contaminated clothing and shoes immediately.
Wash off with soap and plenty of water.
Consult a physician.
In case of eye contact:
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
Continue rinsing eyes during transport to hospital.
If swallowed:
Do NOT induce vomiting.
Never give anything by mouth to an unconscious person.
Rinse mouth with water.
Consult a physician.
Firefighting measures:
Extinguishing media:
Suitable extinguishing media:
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas
Advice for firefighters:
Wear self-contained breathing apparatus for firefighting if necessary.
Accidental release measures:
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment.
Avoid breathing vapours, mist or gas.
Evacuate personnel to safe areas.
Environmental precautions:
Prevent further leakage or spillage if safe to do so.
Do not let product enter drains.
Discharge into the environment must be avoided.
Methods and materials for containment and cleaning up:
Soak up with inert absorbent material and dispose of as hazardous waste.
Keep in suitable, closed containers for disposal.
Handling and storage:
Precautions for safe handling:
Avoid inhalation of vapour or mist.
Conditions for safe storage, including any incompatibilities:
Keep container tightly closed in a dry and well-ventilated place.
Containers which are opened must be carefully resealed and kept upright to prevent leakage.
Storage class (TRGS 510): 8A: Combustible, corrosive hazardous materials
Exposure controls/personal protection:
Control parameters:
Components with workplace control parameters
Contains no substances with occupational exposure limit values.
Exposure controls:
Appropriate engineering controls:
Handle in accordance with good industrial hygiene and safety practice.
Wash hands before breaks and at the end of workday.
Personal protective equipment:
Eye/face protection:
Tightly fitting safety goggles.
Faceshield (8-inch minimum).
Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection:
Handle with gloves.
Gloves must be inspected prior to use.
Use proper glove
removal technique (without touching glove's outer surface) to avoid skin contact with this product.
Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
Full contact:
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
Splash contact
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
It should not be construed as offering an approval for any specific use scenario.
Body Protection:
Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection:
Where risk assessment shows air-purifying respirators are appropriate use a fullface respirator with multi-purpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls.
If the respirator is the sole means of protection, use a full-face supplied air respirator.
Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so.
Do not let product enter drains.
Discharge into the environment must be avoided.
Stability and reactivity:
Chemical stability:
Stable under recommended storage conditions.
Incompatible materials:
Strong oxidizing agents:
Hazardous decomposition products:
Hazardous decomposition products formed under fire conditions.
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas.
Disposal considerations:
Waste treatment methods:
Product:
Offer surplus and non-recyclable solutions to a licensed disposal company.
Contact a licensed professional waste disposal service to dispose of this material.
Contaminated packaging:
Dispose of as unused product
