| HS Code | 351688 |
| Productname | Chlorosulfonyl Isocyanate |
| Iupacname | Chlorosulfonyl isocyanate |
| Chemicalformula | CClNO3S |
| Molecularweight | 141.53 g/mol |
| Casnumber | 1189-71-5 |
| Ecnumber | 214-715-2 |
| Appearance | Colorless to light yellow liquid |
| Odor | Pungent, sharp |
| Boilingpoint | 107 °C at 760 mmHg |
| Meltingpoint | -44 °C |
| Density | 1.626 g/mL at 25 °C |
| Refractiveindex | n20/D 1.447 |
| Flashpoint | 10 °C closed cup |
| Vaporpressure | 10 mmHg at 20 °C |
| Watersolubility | Reacts with water |
| Storageconditions | Store at 2-8 °C under dry inert atmosphere |
| Hazardclassification | Corrosive, toxic, water-reactive |
| Unnumber | UN 3265 |
| Packinggroup | II |
| Synonyms | CSI; N-carbonylsulfamoyl chloride; chlorosulfonyl isocyanate |
As an accredited Chlorosulfonyl Isocyanate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Chlorosulfonyl Isocyanate supplied in 100 mL amber glass bottles, PTFE-lined caps, sealed in UN-approved moisture-resistant hazmat packaging. |
| Container Loading (20′ FCL) | Chlorosulfonyl Isocyanate in 20′ FCL: clean, dry container; palletized sealed drums; secured, labeled, moisture-protected, handled per IMDG dangerous goods. |
| Shipping | Chlorosulfonyl isocyanate is shipped as a hazardous, moisture-sensitive corrosive liquid under UN 3265, Class 8, Packing Group II. Use chemically resistant, sealed packaging with dry/inert atmosphere, compliant hazard labels, and documented emergency response. Follow IATA/IMDG/ADR/DOT rules; avoid water, heat, and incompatible materials. |
| Storage | Store chlorosulfonyl isocyanate in a cool, dry, well-ventilated area, preferably in a fume hood, inside a tightly sealed, corrosion-resistant container under dry nitrogen. Protect from moisture, water, alcohols, amines, bases, acids, and oxidizers. Use secondary containment, keep away from incompatible materials, and label clearly. Maintain container closed when not in use; refrigerate if required. Ensure adequate ventilation and appropriate spill-response equipment. |
| Shelf Life | Limited; stable for about two years when sealed under dry inert gas, refrigerated, and protected from moisture; hydrolyzes readily. |
Chlorosulfonyl isocyanate is charged as a 1.0–1.15 mol electrophile per mole of vinyl ethyl ether in anhydrous dichloromethane at a jacket temperature of −15 °C to −5 °C. The feed vessel is blanketed with dry nitrogen to keep solvent moisture below 100 ppm as measured by ASTM E203. A glass-lined reactor with a nominal volume of 2000 L is fitted with a PTFE-lined diaphragm pump and a vent scrubber containing 10% sodium hydroxide solution. The addition is exothermic; if the internal temperature rises above 0 °C, the vinyl ether undergoes acid-catalysed oligomerisation that reduces N-chlorosulfonyl-2-azetidinone recovery and increases the colour of the organic phase by normal-phase HPLC area percent. The reaction mass is held for 20–30 min after the dose, then quenched with 5% aqueous sodium bicarbonate at 0–5 °C to pH 7.0–8.0. The resulting N-chlorosulfonyl-4-ethoxyazetidin-2-one is retained as a dichloromethane solution for reductive hydrolysis to the corresponding azetidin-2-one. The terminal azetidin-2-one is a monobactam building block. Residual moisture in the reactor headspace is monitored by Karl Fischer titration before the next batch because hydrolysis of the chlorosulfonyl group produces sulfamic acid, which corrodes carbon steel utility lines.
Selectivity in sulfamate ester formation from chlorosulfonyl isocyanate and a hindered secondary alcohol is governed by competing N-chlorosulfonyl carbamate hydrolysis and acetonide deprotection if the medium falls below pH 4.0. A reverse-addition sequence is used: chlorosulfonyl isocyanate is metered into a solution of the alcohol in anhydrous THF at −10 °C to +5 °C, with a chlorosulfonyl isocyanate-to-hydroxyl molar ratio of 1.05–1.20. Triethylamine is charged at 1.2–1.5 mol per chlorosulfonyl isocyanate to neutralise hydrogen chloride released during the quench. The pH is maintained between 7.0 and 8.5 using 5% aqueous sodium bicarbonate. The quench is performed below 10 °C to avoid cleavage of the acid-labile protecting groups. The sulfamate ester is extracted into ethyl acetate and dried to below 0.5% water before solvent swap to heptane. Terminal material is controlled for residual THF and ethyl acetate under ICH Q3C Class 2 and Class 3 limits. Glass-lined equipment is specified because stainless steel shows chloride stress corrosion after repeated exposure to the hydrolysed chlorosulfonyl residues.
Primary amines are transformed to N-chlorosulfonyl ureas when added to chlorosulfonyl isocyanate in dry acetonitrile at −5 °C to +5 °C. A molar amine-to-chlorosulfonyl isocyanate ratio of 0.98:1.0 is maintained so that the free isocyanate concentration in the reactor headspace remains below process control limits. The resulting N-chlorosulfonyl urea is not isolated at production scale because the chlorosulfonyl group is moisture-sensitive and the intermediate has poor ambient shelf life. The same vessel is charged with 2 N hydrochloric acid at 0–10 °C; hydrolysis of the chlorosulfonyl group yields the sulfamide. Alternatively, aqueous ammonia is used to quench to pH 8.0–9.0. The terminal sulfamide is a polar building block for medicinal chemistry screening libraries; published data for specific commercial sulfamide-containing products is limited. Process water is neutralised to pH 6.0–9.0 before discharge, with pH measured by ASTM D1293. The main production bottleneck is the need to prevent amine back-mixing in the feed line, which forms solid urea hydrochloride and blocks the dosing valve.
In continuous-flow format, chlorosulfonyl isocyanate and vinyl ether are fed as separate streams into a glass microreactor module with a static mixer and heat-transfer plate. The feed ratio is maintained at 1.05:1.0 chlorosulfonyl isocyanate to vinyl ether, and the reactor plate temperature is held at −5 °C to +5 °C. Residence time is 15–30 s under 2–3 bar back pressure to prevent dichloromethane vapour lock. The N-chlorosulfonyl-2-azetidinone stream is quenched in-line with 10% aqueous sodium bicarbonate. The advantage over batch operation is a lower working inventory of unreacted chlorosulfonyl isocyanate and improved removal of the cycloaddition exotherm. Fouling of the glass module occurs when the vinyl ether contains more than 0.1% water. The quenched dichloromethane stream is separated in a continuous centrifugal extractor and dried over molecular sieves. The terminal azetidin-2-one is equivalent to the batch product, but the flow configuration reduces operator exposure to chlorosulfonyl isocyanate vapour. Explosion-proof dosing equipment is applied in accordance with ATEX 2014/34/EU.
The chlorosulfonyl group retained in the intermediate can be displaced by morpholine, diethylamine, or sodium phenoxide to produce sulfonamide and sulfonate ester derivatives in the same reactor. When morpholine is used, 1.1–1.3 mol of nucleophile per chlorosulfonyl equivalent is added at 0–5 °C. The pH is held above 8.5 to prevent accumulation of hydrogen chloride. The sulfonamide product is extracted into dichloromethane and washed with 2% sodium bicarbonate. The terminal sulfonamides are used as building blocks in medicinal chemistry. Batch records show the main processing bottleneck is emulsification during the first water wash if the pH falls below 7.0. The displacement is run in glass-lined equipment; stainless steel is unsuitable because residual chloride promotes pitting corrosion.
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Chlorosulfonyl isocyanate (ClSO₂NCO, CAS 1189-71-5) is supplied as a neat liquid reagent in two common assay bands: reagent grades at ≥98.0% and high-purity grades at ≥99.0%. Vendor-specific model codes such as CSI-98 and CSI-99 are not standardized under ISO, but they typically denote gas chromatographic assay and hydrolyzable chloride limits rather than formulation differences. The molecule has a molar mass of 141.53 g/mol and combines an isocyanate terminus with a sulfonyl chloride group, producing a bifunctional electrophile used for cycloaddition, sulfamoylation, and sulfonylurea intermediate formation. At ambient pressure, the material is a colorless to pale yellow lachrymatory liquid with a boiling point near 107 °C and a density near 1.626 g/mL at 25 °C.
The physical property envelope below applies to neat, unstabilized material. Batch certificates should be consulted for supplier-specific acceptance ranges because residual chloride, color, and water content vary with packaging and storage history.
| Property | Typical value or range | Test method or basis |
|---|---|---|
| Molecular mass | 141.53 g/mol | Calculated from CClNO₃S |
| Boiling point at 101.3 kPa | 107 °C | OECD 103 distillation comparison |
| Density at 25 °C | 1.626 g/mL | ASTM D4052 |
| Refractive index nD20 | 1.447 | ASTM D1218 |
| Flash point, closed cup | 18 °C | ASTM D3828 |
| Vapor pressure at 25 °C | 18 mmHg | Safety data sheet reported value |
| Assay, reagent grade | ≥98.0% | Gas chromatography, TCD |
| Assay, high-purity grade | ≥99.0% | Gas chromatography, TCD |
| Water, high-purity vendor specification | ≤0.05% | Karl Fischer titration |
| Color, vendor specification | APHA ≤100 | Visual or instrumental APHA |
The flash point and vapor pressure indicate that vapor-phase accumulation in closed process areas is a credible ignition and inhalation hazard. Closed-transfer equipment with dry nitrogen padding is therefore specified for production-scale handling.
Chlorosulfonyl isocyanate reacts with primary or secondary alcohols to form N-chlorosulfonyl carbamates, and with ammonia or amines to form sulfamide and sulfonylurea precursors after displacement of the chloride. In olefin substrates, the reagent participates in a [2+2] cycloaddition to yield N-chlorosulfonyl β-lactams, which can be reductively desulfonylated to the free β-lactam. The electron-withdrawing sulfonyl group increases the electrophilicity of the isocyanate carbon beyond that of alkyl or aryl isocyanates. This property is used in pharmaceutical and agrochemical sequences where methyl isocyanate or p-toluenesulfonyl isocyanate is insufficiently reactive.
Published procedures for β-lactam formation commonly specify anhydrous dichloromethane or diethyl ether, substrate concentrations between 0.2 mol/L and 1.0 mol/L, and controlled addition of chlorosulfonyl isocyanate at 0–5 °C over 60–120 min. The reaction exotherm is immediate. For a 2000 L glass-lined reactor, jacket temperature is typically set at -10 °C, and the reactor headspace is blanketed with nitrogen at 0.2–0.5 bar. At solvent moisture levels above 50 ppm by Karl Fischer titration, hydrolysis competes with the desired cycloaddition and produces sulfamic acid derivatives plus carbon dioxide. The resulting off-gas reduces the assay of the reactive intermediate and raises headspace pressure.
In sulfonylurea intermediate production, staged addition of chlorosulfonyl isocyanate to an amine produces an N-chlorosulfonyl urea intermediate, which is then treated with aqueous ammonia or methylamine. The N-chlorosulfonyl group functions as a leaving group for nucleophilic displacement. Because the reagent is more electrophilic than chlorosulfonic acid, it permits sulfamoylation of sterically hindered alcohols that are inert under conventional sulfonating conditions. However, the same reactivity makes moisture exclusion and stoichiometric control more critical than with p-toluenesulfonyl isocyanate.
Storage of chlorosulfonyl isocyanate in carbon steel is incompatible. Wetted materials for long-term service are glass, PTFE, or 316L stainless steel with attention to chloride-induced crevice corrosion. Moisture ingress through mechanical seals or vacuum lines is a dominant cause of batch failure. Intermediate bulk containers are padded with dry nitrogen at 0.3–0.7 bar, and emergency response should use dry-powder containment rather than direct water flushing because the liquid reacts violently with water.
The primary storage hazard is not thermal self-accelerating decomposition at ambient temperature; it is pressure generation from hydrolysis off-gases. Storage at 2–8 °C under dry nitrogen reduces vapor-phase condensation and moisture ingress. Freeze cycles are not recommended because the material solidifies below approximately -44 °C, and thawing can produce localized concentration gradients that complicate representative sampling. Feed systems to reactor vessels should use PTFE-lined diaphragm pumps or vacuum transfer with inert gas. Rotary vane pumps exposed to HCl off-gas show seal degradation within 3–6 months in continuous campaigns.
Differential scanning calorimetry data for chlorosulfonyl isocyanate–water mixtures show immediate exothermic response. Published adiabatic onset temperatures for specific process configurations are limited. Process safety reviews therefore require closed-vessel testing using ASTM E1981 or equivalent accelerating rate calorimetry before scale-up. Vent lines from reactors and storage tanks are routed through dilute caustic scrubbing to absorb HCl and CO₂ before reaching vacuum systems or atmospheric vents.
p-Toluenesulfonyl isocyanate (TSI, CAS 4083-64-1) has a higher molar mass of 197.25 g/mol and introduces a toluenesulfonyl group rather than a chlorosulfonyl group. The p-toluenesulfonyl group is more sterically hindered and less electrophilic, generally requiring longer reaction times or higher temperatures in sulfamoylation. Chlorosulfonyl isocyanate reacts rapidly at or below room temperature and installs a chloride-bearing sulfonyl group that is more readily displaced by ammonia or amines. In contrast to chlorosulfonic acid, chlorosulfonyl isocyanate adds the isocyanate function directly, avoiding the formation of free sulfuric acid and simplifying aqueous workup.
Methyl isocyanate is lower-boiling and more acutely toxic by inhalation; chlorosulfonyl isocyanate is less volatile but carries a skin corrosion and water-reactivity hazard profile that demands closed handling. Sulfuryl chloride is a chlorosulfonating agent but lacks the isocyanate group, so it cannot form carbamates or sulfonylureas without a separate phosgene or isocyanate step. The selection of chlorosulfonyl isocyanate over these alternatives is therefore driven by the need for a single reagent that delivers both sulfonyl chloride and isocyanate functionality under controlled, anhydrous conditions.
In pharmaceutical intermediate supply chains, chlorosulfonyl isocyanate is not a final drug substance and is not cleared for direct food-contact or pharmaceutical formulation use. Residual solvent and impurity limits are applied downstream under ICH Q3C and ICH M7 as part of the drug substance manufacturing process. Manufacturers requiring cGMP supply of chlorosulfonyl isocyanate typically request a technical dossier with residual heavy metals by ICP-MS, assay by gas chromatography with thermal conductivity detection, and water content by Karl Fischer titration. Batch release under a GMP starting-material program may include identity by FTIR, assay ≥99.0%, water ≤0.05%, and appearance not darker than APHA 100.
Transport classification under international maritime and road regulations generally assigns chlorosulfonyl isocyanate to a toxic corrosive liquid class. The exact proper shipping name and packing group must be confirmed against the current IMDG code and ADR tables because water reactivity can affect segregation. REACH registration dossiers list skin corrosion category 1 and acute inhalation toxicity category 3; the harmonized classification and labeling inventory should be checked for the current H-code set. No ACGIH threshold limit value or OSHA permissible exposure limit is established specifically for chlorosulfonyl isocyanate. Process control therefore relies on closed systems, dry inert gas padding, and continuous monitoring for HCl and isocyanate decomposition products.
