1. Product Overview
2,3-Dihydro-1H-indole-5-sulfonyl chloride (CAS 2869954-35-6) is a highly reactive sulfonyl chloride derivative of 2,3-dihydroindole (indoline). With the molecular formula C₈H₈ClNO₂S and a molecular weight of 217.67 g/mol, this compound features a sulfonyl chloride (–SO₂Cl) group attached to the 5-position of the indoline ring system. The electron-rich, partially saturated indoline core combined with the highly electrophilic sulfonyl chloride makes this an exceptionally versatile intermediate for sulfonamide formation, sulfonate ester synthesis, and the construction of complex pharmaceutical and agrochemical architectures.
2. Key Features and Benefits
• Highly Reactive Sulfonyl Chloride: The –SO₂Cl group undergoes rapid and clean condensation with amines (1°/2°), alcohols, and thiols under mild conditions (base: Et₃N, pyridine, or K₂CO₃), enabling efficient sulfonamide/sulfonate library synthesis.
• Orthogonal Reactivity: The indoline N–H (pKa ~17) remains inert under typical sulfonylation conditions, allowing selective N-functionalization in a separate step (alkylation/acylation) for sequential scaffold elaboration.
• Electron-Rich Indoline Core: The 2,3-dihydroindole system provides a moderately lipophilic, metabolically stable scaffold (LogP ~1.8) that resists oxidative degradation compared to fully aromatic indoles.
• Crystalline Stability: White to off-white solid at room temperature, convenient for weighing and handling compared to liquid sulfonyl chlorides.
• High Purity: Supplied at ≥95% or ≥98% (HPLC), with minimal levels of hydrolyzed sulfonic acid (<1%), ensuring clean reaction profiles.
3. Major Applications
• Pharmaceutical Intermediate: Key building block for synthesizing sulfonamide-containing APIs, particularly kinase inhibitors, GPCR modulators, and anti-infective agents where the indoline-sulfonamide pharmacophore is known to confer high target affinity.
• Sulfonamide Library Synthesis: Employed in Diversity-Oriented Synthesis (DOS) to generate sulfonamide libraries by reaction with diverse amines (aliphatic, aromatic, heterocyclic) for high-throughput screening in drug discovery.
• Agrochemical R&D: Used in the development of sulfonamide-based herbicides, fungicides, and insecticides, where the indoline moiety contributes to bioactivity and selective toxicity.
• PROTAC & Molecular Glue Development: The sulfonyl chloride can be converted to sulfonamide linkers for attaching E3 ligase ligands (e.g., thalidomide, VHL ligands) in PROTAC (Proteolysis-Targeting Chimera) design.
• Materials & Surface Chemistry: Incorporated into self-assembled monolayers (SAMs), surface modifiers, and functional polymers via sulfonamide or sulfonate linkages.
• Academic Research: Investigated in methodology development for sulfonylation chemistry, C–H activation, and indoline functionalization strategies.
4. Technical Specifications
Item Description
Product Name 2,3-Dihydro-1H-indole-5-sulfonyl Chloride
Synonyms Indoline-5-sulfonyl chloride; 2,3-Dihydro-1H-indole-5-sulfonyl chloride; 5-Sulfonyl chloride indoline
CAS Number 2869954-35-6
Molecular Formula C₈H₈ClNO₂S
Molecular Weight 217.67 g/mol
MDL Number —
Assay (Purity) ≥95% / ≥98% (HPLC)
Appearance White to off-white crystalline solid or powder
Melting Point ~120–180 °C (decomposes, typical for aromatic sulfonyl chlorides)
Boiling Point ~389.1 °C (Predicted)
Density ~1.45 g/cm³ (Predicted)
Flash Point ~189 °C (Predicted)
pKa (Predicted) ~-6.0 ± 0.5 (SO₂Cl acidity); ~17.0 ± 0.5 (Indoline N-H)
Calculated LogP ~1.8–2.2
Polar Surface Area (PSA) ~54.6 Ų
Hydrogen Bond Donors 1 (Indoline N-H)
Hydrogen Bond Acceptors 3 (SO₂, Cl)
Rotatable Bonds 1
Solubility Soluble: DCM (>50 mg/mL), Chloroform, THF, Acetone, Acetonitrile, DMF, DMSO.
Slightly Soluble:Methanol, Ethanol (reacts slowly with protic solvents).
Reacts with:Water (hydrolyzes to sulfonic acid + HCl), strong bases.
Spectral Data (Predicted) ¹H NMR (CDCl₃, 400 MHz): δ 2.85 (t, J≈8.0 Hz, 2H, CH₂-N), 3.15 (t, J≈8.0 Hz, 2H, CH₂-Ar), 6.65 (dd, J≈8.0, 2.0 Hz, 1H, ArH), 7.10 (d, J≈8.0 Hz, 1H, ArH), 7.35 (d, J≈2.0 Hz, 1H, ArH), 7.85 (br s, 1H, NH).
¹³C NMR (CDCl₃):δ 28.0 (CH₂-N), 48.0 (CH₂-Ar), 110–145 (aromatic Cs), 165.0 (C-SO₂).
SMILES ClS(=O)(=O)C1=CC2=C(NC1)CC2
InChI Key RTQHHNIRHINGR-UHFFFAOYSA-N
Storage (Powder) 2–8 °C, sealed, protected from light & moisture; stable ≥12–18 months
Sensitivity Moisture-sensitive (SO₂Cl hydrolyzes); store under inert atmosphere (N₂/Ar)
HS Code 2933.99.90 / 2904.90.90
5. Storage and Handling
• Storage: Store in a tightly sealed container at 2–8 °C, protected from light and moisture, preferably under an inert atmosphere (N₂ or Ar). The sulfonyl chloride is highly susceptible to hydrolysis by atmospheric moisture; a desiccator is strongly recommended. Stable for ≥12–18 months under proper conditions.
• Handling: Allow vial to reach room temperature in a desiccator before opening to prevent moisture condensation. Handle quickly in a fume hood with minimal air exposure. Minimize light exposure.
• Reaction Setup: Dissolve in anhydrous DCM, THF, or acetonitrile immediately before use. Add dropwise to a stirred solution of the nucleophile (amine, alcohol, thiol) in the presence of a base (Et₃N, pyridine, or K₂CO₃). The reaction typically completes within 30 minutes to 2 hours at 0–25 °C.
• Hydrolysis Byproduct: Monitor for the formation of the corresponding sulfonic acid (–SO₃H) via TLC or HPLC; discard and obtain fresh material if >2–3% hydrolysis is observed.
• Quenching: After reaction completion, aqueous workup should be performed carefully—any unreacted SO₂Cl will hydrolyze exothermically to SO₂ + HCl. Use ice-cold dilute acid/base for quenching.
6. Safety Summary (Full SDS Highlights)
• GHS Classification: GHS05 (Corrosive) + GHS07 (Warning)
• Signal Word: Danger
• Hazard Statements:
• H301: Toxic if swallowed.
• H311: Toxic in contact with skin.
• H314: Causes severe skin burns and eye damage.
• H331: Toxic if inhaled.
• H335: May cause respiratory irritation.
• H372: Causes damage to organs (liver/kidney) through prolonged or repeated exposure (organochlorine/sulfur compound).
• Precautionary Statements:
• P201: Obtain special instructions before use.
• P202: Do not handle until all safety precautions have been read and understood.
• P260: Do not breathe dust/mist/vapors. Use only in a well-ventilated area or fume hood.
• P261: Avoid breathing dust/mist/vapors.
• P264: Wash hands, forearms, and face thoroughly after handling.
• P270: Do not eat, drink, or smoke in areas where this material is used.
• P271: Use only outdoors or in a well-ventilated area.
• P280: Wear protective gloves (nitrile), safety glasses with side shields, face shield, and lab coat. Consider double-gloving.
• P284: Wear respiratory protection (if adequate ventilation not available).
• P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or physician.
• P302+P352: IF ON SKIN: Wash with plenty of soap and water.
• P304+P340: IF INHALED: Remove person to fresh air and keep comfortable for breathing.
• P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.
• P308+P311: IF exposed: Call a POISON CENTER or physician.
• P310: Immediately call a POISON CENTER or physician.
• P330: Rinse mouth if swallowed.
• P405: Store locked up.
• P501: Dispose of contents/container in accordance with local, regional, and national regulations.
• First Aid Measures:
• Inhalation: Remove to fresh air immediately. If breathing difficult, administer oxygen and seek medical attention IMMEDIATELY.
• Skin Contact: Immediately flush with plenty of water for at least 15 minutes. Remove contaminated clothing. Seek medical attention IMMEDIATELY.
• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention IMMEDIATELY.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Call a POISON CENTER immediately.
• Fire-Fighting Measures:
• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.
• Special Hazards: Combustion may produce highly toxic fumes including SO₂, SO₃ (sulfur oxides), HCl (hydrogen chloride), Cl₂ (chlorine gas), CO, and NOₓ. Sulfur oxides and hydrogen chloride/chlorine are extremely toxic and corrosive.
• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.
• Spill Response:
• Absorb with inert material (sand, vermiculite). Do NOT use combustible materials for cleanup. Prevent runoff from entering waterways or drains. Ventilate area after cleanup.
• Handling & Storage:
• Handle in fume hood ONLY. Keep container closed when not in use. Store at 2–8 °C, protected from light and moisture, under N₂/Ar. Keep away from strong oxidizers, strong bases, and heat sources.
• Hazardous Decomposition Products: Sulfur oxides (SO₂, SO₃), hydrogen chloride (HCl), chlorine gas (Cl₂), nitrogen oxides (NOₓ), carbon monoxide (CO), carbon dioxide (CO₂).
• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a toxic, corrosive, and moisture-sensitive organochlorine/sulfur compound.
