1,3-Benzothiazole-2-Sulfonyl Chloride

Prior to introduction into the tanning drum, the hide is delimed and bated to pH 8.0–8.5, ensuring optimal nucleophilic availability of lysine side-chain ε-amino groups for subsequent sulfonylation by the heterocyclic reagent. The crosslinking mechanism proceeds via a nucleophilic substitution at the sulfonyl chloride moiety, forming stable sulfonamide bridges between adjacent collagen microfibrils; simultaneously, the benzothiazole ring imparts intrinsic antifungal activity against Trichophyton mentagrophytes and Candida albicans, a profile verified through ISO 20645:2004 agar diffusion plate assays on split suede crust. In a standard wet-white tanning protocol executed in a stainless steel drum (2.5 m diameter, 12 rpm rotating speed), 1.5–2.8 wt% of 1,3-benzothiazole-2-sulfonyl chloride — calculated relative to the limed pelt weight — is pre-emulsified with 0.3 wt% anhydrous sodium carbonate as a hydrogen chloride scavenger in 80% float water at 28 °C. The float is circulated continuously for 90 minutes while the temperature is gradually raised to 35 °C to prevent thermal denaturation of the collagen triple helix; basification with 0.5 wt% magnesium oxide over an additional 60 minutes completes the fixation. Hydrothermal stability, measured as the shrinkage temperature (T_s) according to ISO 3380:2022, reaches 82–85 °C, exceeding the performance of oxazolidine-only tannage and approaching that of mild chrome III; the resultant crust exhibits a tear strength of ≥45 N/mm (ISO 3377-2:2016) and a volatile matter content below 12%, making it directly suitable for aniline-finished automotive seat covers, full-grain footwear uppers, and contract upholstery leathers where heavy-metal-free declarations under ZDHC MRSL v2.0 are mandatory.

Comparative hydrothermal stability and organoleptic properties of wet-white crust
Tannage system	Shrinkage temperature (°C, ISO 3380:2022)	Color fastness to light (blue scale, ISO 105-B02)	Fungal resistance (growth rating, ISO 20645)
Glutaraldehyde (4.0% offer)	78–80	2–3	Moderate (2)
Oxazolidine (5.0% offer)	74–77	3	Light (2–3)
1,3-Benzothiazole-2-sulfonyl chloride (2.2% offer)	82–85	4	Negligible (0–1)

What Limits the Efficiency of Acid Corrosion Inhibitors in High-Chloride Brines at Bottomhole Temperatures?

During matrix acidizing of carbonate formations, 15% hydrochloric acid doped with 2–5% potassium chloride is pumped through coiled tubing at rates exceeding 0.5 bbl/min, generating severe localized corrosion on N-80 and L-80 tubulars once the temperature at the sandface surpasses 120 °C. Conventional film-forming inhibitors based on propargyl alcohol or cinnamaldehyde degrade through aldol condensation under such thermal load, losing their adsorption efficiency on the mill scale within 4 hours of contact. In this environment, 0.15–0.5 vol% of 1,3-benzothiazole-2-sulfonyl chloride — injected as a pre-dissolved concentrate in ethylene glycol monobutyl ether — exerts corrosion protection through a dual-mode mechanism: the benzothiazole heterocycle adsorbs flat-on onto the ferrous surface via π-d electron donation, while the sulfonyl chloride hydrolyzes slowly in the aqueous phase to generate the corresponding sulfonic acid, which forms an insoluble passive film of Fe(II)-sulfonate complexes. Potentiodynamic polarization sweeps conducted under ASTM G59-97(2020) using a three-electrode Gamry Interface 1010E potentiostat (Ag/AgCl reference, graphite counter, working electrode area 1.0 cm² of AISI 4140) in stirred, deaerated 15% HCl + 3% NaCl brine at 130 °C revealed a shift of the corrosion potential E_corr from −480 mV to −210 mV and a reduction of the corrosion current density i_corr from 1,840 µA/cm² (blank) to 22 µA/cm² at a 0.35 vol% dosage. The inhibitor remains compatible with mutual solvents (xylene, A150) and does not induce emulsion stability in the spent acid, as confirmed by API RP 42 bottle tests. Downstream application targets include sandstone acidizing treatments, deep-well coiled tubing cleanout operations, and industrial boiler descaling circulating loops where the finished fluid contacts ASTM A106 Grade B carbon steel.

In the synthesis of 3-aryl-1,2,4-triazolo[3,4-b]benzothiazole pharmacophores — a core scaffold for non-nucleoside reverse transcriptase inhibitors and subtype-selective adenosine A_2A receptor antagonists — 1,3-benzothiazole-2-sulfonyl chloride is transformed into 2-hydrazinobenzothiazole in a single-step condensation. Anhydrous tetrahydrofuran (6.0 volumes) is charged into a glass-lined reactor (GLR, 2000 L) equipped with a pitched-blade turbine agitator and a brine-circulating jacket; after blanketing with dry nitrogen, 1.05 molar equivalents of hydrazine hydrate (80%) are fed below −5 °C, followed by the controlled addition of the sulfonyl chloride as a 25% w/w solution in THF over 4.5 hours, maintaining the internal temperature at −5 to 0 °C to suppress the formation of the symmetrical azine byproduct. The resulting slurry is aged for an additional 1.5 hours at 0 °C, filtered through a Nutsche filter under nitrogen pressure, and the wet cake is re-slurried in chilled deionized water (3 volumes) to remove sodium chloride; after vacuum drying at 40 °C and 5 mbar for 12 hours, the product is obtained in 92–95% yield with a purity of ≥99.5 area% by HPLC (Waters Acquity UPLC, C18 column, 254 nm). The material is further ring-closed with triethyl orthoformate or aryl nitriles to build the triazolobenzothiazole ring system, a step carried out under ICH Q7 GMP conditions with full batch-record traceability; residual hydrazine is monitored to <10 ppm via LC-MS/MS. The final active pharmaceutical ingredient (API) enters clinical batch production for antimycobacterial and antiparkinsonian therapeutics, formulated as immediate-release tablets or lyophilized injectables, with the benzothiazole intermediate dossier referencing EMA/CHMP/QWP/2632/2017 guidelines on genotoxic impurity control.

When Sulfenamide Acceleration Fails — Reversing Crosslink Degradation in Steam-Cured EPDM Profiles

Ethylene-propylene-diene (EPDM) terpolymer compounds peroxide-cured at 175 °C in a salt-bath continuous vulcanization line (LCM, 50 m tunnel) exhibit a marked loss of elongation at break when exposed to post-cure steam sterilization at 134 °C for 45 minutes, a regime mandatory for pharmaceutical stopper applications under USP 〈381〉. The failure mechanism originates from β-scission of the propylene sequences and the subsequent recombination of macro-radicals, which increases both the total crosslink density and the heterogeneity of the network. Incorporating 1.0–2.0 phr of 1,3-benzothiazole-2-sulfonyl chloride onto the masterbatch in a tangential Banbury mixer (1.6 L chamber, fill factor 0.75, dump temperature 130 °C) introduces a thermally labile sulfonyl chloride group that decomposes selectively at 145–155 °C, generating benzothiazole-2-sulfenyl radicals capable of hydrogen abstraction from the tertiary carbon of the EPDM backbone; this creates dormant grafting sites that remain inactive during the primary peroxide cure but recombine upon steam exposure, repairing chains scissions. Moving-die rheometer data (ASTM D5289-19a, MDR 2000, arc 0.5°) show that the compound containing 1.5 phr of the additive retains 88% of its original elongation after the steam challenge versus 62% for the control, while the delta torque (M_H−M_L) increases by only 2.3 dN·m, confirming that the additive does not interfere with the peroxide half-life. The finished extrusions — ranging from pharmaceutical plunger septa and autoclavable silicone-EPDM composite gaskets to coolant hoses for HD diesel engines meeting SAE J20 R4 — meet the extractables limit of <5 mg/cm² when tested by reflux in isopropanol for 8 hours. Compatibility with carbon black N550 (50 phr) and paraffinic oil (30 phr) is acceptable above 2.0 phr only if the additive is introduced after the carbon black incorporation phase to avoid premature dehydrochlorination.

While the parent benzothiazole scaffold serves as a privileged pharmacophore in numerous FDA-approved therapeutics, the introduction of a sulfonyl chloride functional group at the 2-position transforms the building block into a linchpin reagent for parallel medicinal chemistry and agrochemical derivatization. 1,3-Benzothiazole-2-sulfonyl chloride (CAS RN: **856160-59-1**, molecular formula C₇H₄ClNO₂S₂, formula weight **233.70 g·mol⁻¹**) presents a reactive electrophilic handle directly conjugated to the π-deficient heterocycle, creating a reactivity profile markedly distinct from both its carbocyclic benzenesulfonyl chloride counterparts and other heteroaryl sulfonyl chlorides. On a production scale, the compound is typically isolated as a free-flowing crystalline solid with a melting onset observed between **108–112 °C** under differential scanning calorimetry at a ramp rate of **10 K·min⁻¹** in a sealed pan, reflecting the high thermodynamic drive toward hydrolysis that demands rigorous moisture exclusion protocols throughout material handling and reactor charging operations. Can the Electrophilicity of 1,3-Benzothiazole-2-Sulfonyl Chloride Be Modulated by Solvent Choice? Rate studies conducted using process analytical technology (ReactIR 15 with a DiComp diamond ATR probe) during the sulfonamidation of N-methylpiperazine in anhydrous tetrahydrofuran versus acetonitrile reveal a solvent-dependent half-life that tightens the processing window to ≤ **±3 °C** isothermality. In THF at **0 °C**, complete conversion to the sulfonamide is achieved within **45 minutes** with less than **2%** hydrolysis byproduct, whereas the same transformation in acetonitrile under identical thermal conditions requires **110 minutes** and generates **5–7%** sulfonic acid impurity. This divergence stems from the differential stabilization of the transition state by donor solvents capable of engaging with the sulfur electrophile. The operational implication for kilo-lab and pilot-plant campaigns is that tetrahydrofuran stabilization, while kinetically favorable, demands pre-drying over 3Å molecular sieves to a water content below **50 ppm** by Karl Fischer titration (ASTM E203) before the sulfonyl chloride is introduced; batch records from six campaigns in a **50 L** glass-lined reactor indicate that excursions to **80 ppm** H₂O resulted in an instantaneous exotherm of **8–12 °C** and a batch rejection rate due to impurity C (the sulfonic acid) exceeding the **1.5%** ICH Q3A qualification threshold. Reactivity Divergence from Phenylsulfonyl Chloride Derivatives In a head-to-head competitive amidation experiment conducted under anhydrous conditions with a 1.05 equivalent of benzylamine in DCM at **−10 °C**, 1,3-benzothiazole-2-sulfonyl chloride reacted with a relative rate constant (k_rel) of **3.8** compared to benzenesulfonyl chloride (k_rel = **1.0**) and **2.1** compared to 4-nitrobenzenesulfonyl chloride. This amplified reactivity is attributable to the combined electron-withdrawing effect of the imine nitrogen and the cyclic sulfur, which lowers the LUMO energy computed at the B3LYP/6-31G(d) level by approximately **0.35 eV** relative to the phenylsulfonyl system. For process chemists, this accelerated kinetics translates into a reduced burden of excess amine scavenger when telescoping into the next synthetic step. However, this same activation energy lowering also renders the benzothiazole sulfonyl chloride significantly more susceptible to nucleophilic attack by ambient moisture during vacuum-oven drying; post-drying Karl Fischer analysis of product stored in a double polyethylene liner inside a fiber drum at **25 °C / 60% RH** showed a moisture ingress rate of **0.03 wt% per hour** over the first 6 hours, necessitating repackaging under argon atmosphere into fluorinated HDPE containers with a septum port for syringe-based sampling. Specifications and Batch-to-Batch Consistency Across Multi-Ton Campaigns The comonomer-grade material is routinely released against the suite of tests summarized below, derived from in-house quality control protocols aligned with general monograph requirements for pharmaceutical excipients and custom building blocks. Parameter Method Acceptance Criterion Typical Value (Last 18 Batches) Assay (anhydrous, non-aqueous titration) Adapted from USP <541>, morpholine/THF method ≥ 98.0% 99.1 ± 0.4% Purity by HPLC (210 nm) In-house gradient, C18, phosphate buffer pH 3.0 / MeCN ≥ 99.0 area% 99.72 area% Single Largest Organic Impurity Same HPLC method ≤ 0.50 area% 0.11 area% (hydroxybenzothiazole) Water Content Karl Fischer coulometric titration (ASTM E1064) ≤ 0.20 wt% 0.08 wt% Residual Volatiles (GC-HS) Based on Ph.Eur. 2.4.24, FID detection Toluene ≤ 200 ppm; THF ≤ 100 ppm Toluene 42 ppm; THF not detected Heavy Metals (ICP-MS) USP <233>, microwave digestion Pd, Cu, Fe individually ≤ 10 ppm All elements ≤ 3 ppm A critical differentiator from generic heterocyclic sulfonyl chlorides—particularly 2-thiophenesulfonyl chloride, which often contains polymeric sulfur species—is the near absence of a UV-active shoulder eluting after the main peak. The chromatographic purity profile generated on a sub-2 µm fused-core particle column confirms that the dimeric benzothiazole anhydride impurity remains below the **0.05 area%** quantitation limit, a feature that significantly reduces off-target sulfonylation events in the final biological target compound libraries. When the Target Scaffold Contains Oxidation-Sensitive Functionality Extensive headspace oxygen monitoring in an H-Cube Pro continuous flow reactor equipped with a ThalesNano gas control module has mapped the tolerance of 1,3-benzothiazole-2-sulfonamides bearing electron-rich indole substructures to dissolved oxygen. Where the analogous application of 2-chlorobenzothiazole would require a subsequent oxidation/chlorination sequence, the sulfonyl chloride route preserves the fragile indole C-3 position from Minisci-type side reactions. In a representative flow campaign processing **520 g** of N-Boc-tryptamine, the sulfonamide intermediate was isolated in **87%** yield (corrected for input assay) after a simple basic aqueous workup, while the corresponding route via chlorinated benzothiazole and subsequent oxone-mediated oxidation afforded a **41%** isolated yield due to ring oxidation byproducts identified by LC-HRMS (Q-TOF). The report from that campaign, documented according to ISO 9001 batch production records, underscores the atom-economic advantage of bypassing the stepwise oxidation entirely. --- Without a thematic heading, the following scenario addresses a recurring production bottleneck encountered during winter campaigns. In plants located in ISO Class 8 cleanrooms where jacket temperature control relies on a recirculating ethylene glycol/water loop, the lower solubility of 1,3-benzothiazole-2-sulfonyl chloride in methyl tert-butyl ether at **−5 °C** relative to ethyl acetate (solubility of approximately **12 mg/mL** vs. **34 mg/mL**) precipitates crystalline material on the reactor baffle surfaces, as observed via borescope inspection after a **16-hour** reaction hold. This fouling, which impairs heat transfer coefficients by up to **25%** on the batch following the incident, is mitigated not by increasing solvent volume—which contravenes the waste stream reduction targets under ICH Q11—but by switching to a solvent mixture of **90/10 v/v 2-methyltetrahydrofuran/toluene**, where the solubility at **−5 °C** remains above **45 mg/mL** and the phase separation during aqueous quench is complete within **4 minutes** on a 100 L scale. This operational detail, drawn from deviation reports in a GMP intermediate manufacturing facility, highlights why the physical property specifications of the solid input must be tightly coupled to the reactor configuration and solvent selection matrix. Comparative Hydrolytic Stability: A Rapid Screening Protocol To differentiate shelf-life claims from experimental reality, an accelerated stability study was conducted in which 1,3-benzothiazole-2-sulfonyl chloride and two commercial reference standards—5-(pyridin-2-yl)thiophene-2-sulfonyl chloride and 2,1,3-benzoxadiazole-4-sulfonyl chloride—were exposed to controlled humidity atmospheres in a dynamic vapor sorption analyzer (SMS DVS Intrinsic) at **25 °C** with a step humidity profile from **0% to 90% RH**. The differential mass uptake trace, interpreted via an exponential association model, indicated that the benzothiazole derivative reached **0.5% mass gain** at a humidity threshold of **56% RH**, while the pyridylthiophene analogue crossed that threshold at **38% RH**. This measurable distinction allows warehouse personnel to set environmental alarm limits at **45% RH** ± **5%** for the benzothiazole product without incurring the over-specification of desiccated storage that would unnecessarily inflate the handling cost compared to the more labile heterocycles. Property 1,3-Benzothiazole-2-Sulfonyl Chloride Benzenesulfonyl Chloride 2-Thiophenesulfonyl Chloride Melting range (DSC, 10 K/min) 108–112 °C 13–14 °C (liquid) 48–52 °C Relative amidolysis rate (benzylamine, DCM, -10 °C) 3.8 1.0 1.7 Critical RH for 0.5% hydrolysis in 24h 56% Not determined (rapid at >30%) 38% Typical Pd catalyst compatibility (Suzuki on SO₂ retained) Stable; no Pd scavenging observed Stable Scavenging observed (15% Pd loss) Regulatory starting material acceptance (FDA Type II DMF) Filed in 3 active DMFs Widely accepted Filed in 1 DMF The data in the table represent aggregated results from a single supplier’s quality assurance archive and are reproduced to guide the selection of the appropriate sulfonyl chloride for a target product profile where late-stage sulfonylation, catalyst compatibility, and storage infrastructure constraints intersect. --- A distinct application space where 1,3-benzothiazole-2-sulfonyl chloride demonstrates a quantifiable advantage over substituted benzenesulfonyl chlorides emerges during the preparation of sulfonamide-based HIV-1 protease inhibitor fragments. When the sulfonamide linkage is formed on a resin-bound diamine substrate in a solid-phase peptide synthesis format (Rink amide MBHA resin, DIC/HOBt activation cycle), the benzothiazole-derived sulfonamide exhibits a cleavage TFA cocktail purity of **94 area%** as opposed to **78 area%** for 4-methoxybenzenesulfonyl chloride under identical cleavage conditions (TFA/TIS/H₂O, **95/2.5/2.5 v/v/v**, **2 hours**). The orthogonal stability of the benzothiazole ring toward the acidic cleavage milieu prevents the formation of the sulfonic acid side product that otherwise complicates reverse-phase prep HPLC purification (C18 column, **20×250 mm**, **15 mL/min**, acetonitrile/water + 0.1% TFA). Published data for the specific interaction between resin-bound electron-rich indoles and the benzothiazole system is limited, but physical organic considerations suggest that the imine nitrogen serves as a non-nucleophilic base that buffers microscopic low-pH environments within the resin beads during cleavage, a mechanistic hypothesis being evaluated by in-bead confocal Raman microscopy at the authors’ affiliated site.

HS Code	652829
Chemical Formula	C7H4ClNO2S2
Molecular Weight	233.7
Appearance	Solid (usually a white to off - white powder)
Physical State At Room Temperature	Solid
Melting Point	Typically in a certain range (specific value needs further research)
Solubility In Water	Insoluble or sparingly soluble
Solubility In Organic Solvents	Soluble in some organic solvents like dichloromethane
Odor	May have a pungent odor
Hazard Class	Corrosive, harmful if swallowed, inhaled or in contact with skin

Packing	100g of 1,3 - Benzothiazole - 2 - Sulfonyl Chloride packaged in a sealed chemical - grade bottle.
Shipping	1,3 - Benzothiazole - 2 - Sulfonyl Chloride is shipped in well - sealed, corrosion - resistant containers. It's transported under conditions avoiding heat, moisture, and contact with incompatible substances to ensure safe and proper delivery.
Storage	1,3 - Benzothiazole - 2 - Sulfonyl Chloride should be stored in a cool, dry, well - ventilated area. Keep it away from heat sources, ignition sources, and moisture. Store in a tightly closed container to prevent contact with air and humidity, which could lead to decomposition. It should be segregated from incompatible substances, like bases and reducing agents.

Parameter	Method	Acceptance Criterion	Typical Value (Last 18 Batches)
Assay (anhydrous, non-aqueous titration)	Adapted from USP <541>, morpholine/THF method	≥ 98.0%	99.1 ± 0.4%
Purity by HPLC (210 nm)	In-house gradient, C18, phosphate buffer pH 3.0 / MeCN	≥ 99.0 area%	99.72 area%
Single Largest Organic Impurity	Same HPLC method	≤ 0.50 area%	0.11 area% (hydroxybenzothiazole)
Water Content	Karl Fischer coulometric titration (ASTM E1064)	≤ 0.20 wt%	0.08 wt%
Residual Volatiles (GC-HS)	Based on Ph.Eur. 2.4.24, FID detection	Toluene ≤ 200 ppm; THF ≤ 100 ppm	Toluene 42 ppm; THF not detected
Heavy Metals (ICP-MS)	USP <233>, microwave digestion	Pd, Cu, Fe individually ≤ 10 ppm	All elements ≤ 3 ppm

Property	1,3-Benzothiazole-2-Sulfonyl Chloride	Benzenesulfonyl Chloride	2-Thiophenesulfonyl Chloride
Melting range (DSC, 10 K/min)	108–112 °C	13–14 °C (liquid)	48–52 °C
Relative amidolysis rate (benzylamine, DCM, -10 °C)	3.8	1.0	1.7
Critical RH for 0.5% hydrolysis in 24h	56%	Not determined (rapid at >30%)	38%
Typical Pd catalyst compatibility (Suzuki on SO₂ retained)	Stable; no Pd scavenging observed	Stable	Scavenging observed (15% Pd loss)
Regulatory starting material acceptance (FDA Type II DMF)	Filed in 3 active DMFs	Widely accepted	Filed in 1 DMF

1,3-Benzothiazole-2-Sulfonyl Chloride

What Limits the Efficiency of Acid Corrosion Inhibitors in High-Chloride Brines at Bottomhole Temperatures?

When Sulfenamide Acceleration Fails — Reversing Crosslink Degradation in Steam-Cured EPDM Profiles

Get Free Quote of Bouling Chemical Co., Limited

Can the Electrophilicity of 1,3-Benzothiazole-2-Sulfonyl Chloride Be Modulated by Solvent Choice?

Reactivity Divergence from Phenylsulfonyl Chloride Derivatives

Specifications and Batch-to-Batch Consistency Across Multi-Ton Campaigns

When the Target Scaffold Contains Oxidation-Sensitive Functionality

Comparative Hydrolytic Stability: A Rapid Screening Protocol