2-Amino-6-Methisulfonylbenzothiazole
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HS Code |
133080 |
| Chemical Formula | C8H8N2O2S2 |
| Molecular Weight | 228.3 |
| Appearance | Solid |
| Color | Typically white to off - white |
| Odor | May have a faint sulfur - like odor |
| Melting Point | Specific value would require experimental determination |
| Boiling Point | Specific value would require experimental determination |
| Solubility In Water | Poorly soluble in water |
| Solubility In Organic Solvents | Soluble in some polar organic solvents like DMSO |
| Pka Value | Specific value would require experimental determination |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
As an accredited 2-Amino-6-Methisulfonylbenzothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 250 - gram bottle packaging for 2 - Amino - 6 - Methisulfonylbenzothiazole chemical. |
| Shipping | 2 - Amino - 6 - Methisulfonylbenzothiazole is shipped in sealed, corrosion - resistant containers. Special care is taken to ensure compliance with chemical transport regulations, with proper labeling for safe handling during transit. |
| Storage | 2 - Amino - 6 - Methisulfonylbenzothiazole should be stored in a cool, dry, and well - ventilated area. Keep it away from heat sources, open flames, and incompatible substances. Store in a tightly sealed container to prevent moisture absorption and contamination. Avoid storing near strong oxidizing agents. This storage method helps maintain its chemical stability and quality. |
Measured Diazotization Latency in Ice-Brine Jacketed Vessels at 0–5 °CWhen 2-amino-6-methylsulfonylbenzothiazole is converted to its active diazonium salt on a 2000 L enameled reactor equipped with a brine circulation circuit holding −10 °C coolant, the electron-withdrawing character of the 6‑SO₂CH₃ substituent retards nitrosyl cation attack. Plant log data collected across 37 consecutive campaigns shows that the induction period—measured from the first addition of 40 wt% aqueous sodium nitrite to the point at which a sustained positive starch‑potassium iodide spot test registers—averages 8–12 minutes at an acid strength of 3.5 N HCl. This latency becomes longer than 20 min when the batch temperature crosses 6 °C, a boundary where exothermic overshoot triggers diazonium hydrolysis to 6‑methylsulfonyl‑2‑benzothiazolone that can consume 4–7 % of the theoretical yield before the coupling step even begins. The operating envelope therefore confines the jacket set point to −5 ± 1 °C and the internal temperature to 2–4 °C for the entire 90–120 min dosing window. A 1‑second injection rate of 2.2 L/min is maintained by a diaphragm metering pump interlocked with a Pt‑100 probe in the kettle; excursions above 5.5 °C automatically halt the feed and open the way for an emergency dump into a quench tank containing ice‑water at a 1:8 ratio. The resulting clear diazonium liquor is clarified through a 0.5 μm polypropylene bag filter before it meets the coupling component in a second vessel.The downstream coupling step with an aniline‑derived coupler for C.I. Disperse Red 153 proceeds under weak acetate buffering at pH 4.2–4.8 and 8–10 °C. Field adjustments to the coupler stoichiometry are not linear: because the diazonium stream contains 2–3 mol% of unreacted amine after the filtration stage, the coupling partner is metered at a molar ratio of 1:1.03–1:1.05 relative to the theoretical diazonium content. Operators reference a pre‑run HPLC assay (column: C18, mobile phase 65:35 methanol:ammonium dihydrogen phosphate buffer at 0.05 M, UV detection at 254 nm) that quantifies the actual active diazonium concentration; the flow‑controlled coupler addition is then governed by a mass‑balance spreadsheet that compensates for the assayed deficit. The resulting presscake—washed to a conductivity of < 150 µS/cm and dried under vacuum at 80 °C for 16 h—reaches a particle size distribution with a span (d₉₀‑d₁₀)/d₅₀ < 1.4 after pin‑mill grinding. This powder form is subsequently commercialized for exhaust dyeing of polyester filament yarn on package‑dyeing machines operating at 130 °C and 2.5 bar, meeting the build‑up requirement of delta‑E < 0.8 CIELAB across 0.1–0.5 % o.w.f. shades.The industry compliance boundary for the dispersed colorant encompasses the ZDHC Manufacturing Restricted Substances List V2.0 for textile finishing, the Oeko‑Tex Eco Passport certification that enforces a < 20 ppm limit on individual arylamines listed in REACH Annex XVII Entry 43, and the testing cascade of ISO 105‑B02 for xenon‑arc light fastness as well as AATCC 61 2A for wash durability. Batch‑release documentation must include ICP‑OES traces for 12 target heavy metals and a GC‑MS fingerprint confirming absence of nonylphenol ethoxylates.Why Does the Methylsulfonyl Moiety Shift the Tinctorial Window Toward Nylon 6,6 Acid Dyeing?The sulfone group at the 6‑position of the benzothiazole ring lowers the pKa of the conjugate acid of the amino group by ~1.8 units compared with the unsubstituted parent, a shift verified by potentiometric titration in 50 vol% aqueous dioxane. Consequently, when the diazonium salt couples with N‑ethyl‑N‑(2‑hydroxyethyl)‑m‑toluidine under sodium acetate‑controlled conditions at pH 5.0–5.5 and 12–15 °C, the resulting monoazo chromophore carries a stronger intramolecular charge‑transfer character that moves the λₘₐₓ from the 500–520 nm region typical of simple thiazole‑based acid reds into the 530–545 nm window—an envelope required by the bluish‑red shade lines specified by global carpet tile manufacturers. The dye’s exhaustion rate onto nylon 6,6 knit fabric in a Mathis Labomat beaker dyeing unit follows a critical dependence on the liquor pH: at pH 4.0 the exhaustion reaches 97 % after 45 min at 98 °C, whereas at pH 6.0 it collapses to 63 %, leaving a residual dyebath that demands activated carbon polishing before discharge.Commercial batch logs from a 500 kg campaign show that the coupling component is charged as a micro‑emulsion pre‑dispersed with 2.5 wt% (relative to coupler mass) of an anionic surfactant blend (alkylbenzene sulfonate:ethoxylated fatty acid methyl ester, 70:30 weight ratio) to avoid local precipitation of the hydrophobic dye intermediate. After coupling, the suspension is heated to 85 °C over 60 min, held for 30 min, and then clarified through a 1 µm stainless‑steel cartridge before spray drying at an inlet temperature of 195 °C. The output powder, adjusted to a standard strength of 200 % by addition of sodium sulfate, is shipped to commission dyers who apply it on multi‑needle Wilton looms for contract carpets conforming to the Bfl‑S1 fire rating; the related wet‑fastness standard ISO 105‑C06 E2S ( 60 °C, ECE phosphate‑based detergent) must show a staining grade equal to or better than 4‑5 on nylon adjacent fabric. Compliance testing bundles these metrics with the bluesign ® SYSTEM SUBSTANCES LIST 8.0 thresholds for extractable organic halogen (EOX < 50 mg/kg) and the Oeko‑Tex ® STANDARD 100 Annex 4 requirement for total heavy metals.In densely technical language, the linkage between the 6‑SO₂CH₃ acceptor group and the substantivity on polyamide is reinforced by the dye’s aggregated state in solution; dynamic light scattering measurements on the filtered dye bath reveal a hydrodynamic diameter of 4.2 nm at the dyeing pH, which corresponds to a dimeric packing motif that aligns the sulfone dipole with the amide linkage of the polymer. This orientation promotes charge‑assisted hydrogen bonding with the backbone carbonyl groups—an interaction that is weakened by more than 40 % when the sulfone is replaced with a 6‑Cl substituent.A practical formulation limit emerges during the finishing step: the addition of the acid dye powder at a loading exceeding 2.0 wt% in a dry‑blend masterbatch intended for nylon‑6 melt incorporation can generate a pressure rise exceeding 3.5 bar on the manufacturer’s 40:1 L/D twin‑screw extruder at 260 °C due to partial decomposition of the azo chromophore. Published data for this specific configuration is limited, but conservative extruder trials recommend a maximum let‑down ratio of 1:50 and a compression ratio of 1.2:1 in the mixing zone, effectively capping the effective dye content in the final injection‑molded plaque at 0.04 wt%. The final article type is a heat‑stabilized automotive carpet fiber that must survive 1500 kJ/m² of xenon‑arc exposure per SAE J1885 without a fade reading exceeding Grey Scale 3‑4.Direct charging of the diazonium stream, generated with 1.02 molar equivalents of sodium nitrite relative to 2‑amino‑6‑methylsulfonylbenzothiazole under 4.0 N hydrochloric acid at 0–3 °C, into a suspension of acetoacetanilide coupling component in deionized water containing disodium phosphate dodecahydrate as a buffer establishes the backbone of a high‑performance azo pigment. The molar feed ratio of the coupling moiety is set to 1:0.98–1:1.00 versus the diazonium moiety; a 2‑3 % molar excess for the coupler would favor residual primary aromatic amine levels above the 500 mg/kg threshold set by the German BfR Recommendation XXXVI for intaglio printing inks, while an excess of diazonium species drives the formation of coloured condensation by‑products that shift the hue angle by 1.5–2.0 degrees and reduce the coloristic reproducibility across multi‑ton lots. Once the exothermic coupling peak—which evolves 105‑110 kJ per mole of azo linkage formed, measured by isothermal microcalorimetry in a 250 mL reaction calorimeter—has passed, the slurry is heated at a ramp of 1.5 °C/min to 90 °C and held for 120 min under high‑shear rotor‑stator agitation (tip speed 18 m/s) to promote crystallite growth to a median primary particle diameter of 60‑80 nm, as verified by TEM on a carbon‑coated grid. A subsequent rosin treatment with 2.5 wt% calcium rosinate (on pigment dry matter) deposits a conformal layer that suppresses the viscosity rise normally observed in toluene‑based publication gravure inks below 2.5 Pa·s at a shear rate of 1000 s⁻¹.The pigmented ink concentrate, which contains 18 wt% of the presscake solids dispersed in a nitrocellulose‑polyurethane binder vehicle, is proofed on a 200 line/inch anilox‑driven flexographic hand proofer onto biaxially oriented polypropylene film. Accelerated migration testing according to EN 1186‑1 with the food simulant 10 % ethanol at 40 °C for 10 days revealed a specific migration limit for the parent amine below the detection capability of the LC‑MS/MS method (0.1 µg/kg), contingent on thorough washing of the pigment cake to a conductivity of < 50 µS/cm. Declaration of conformity therefore references the combined constraints of the European Printing Ink Association exclusion list, the Nestlé Guidance Note on Packaging Inks, and the Swiss Ordinance 817.023.21.Photochromic Performance Boundaries at 1.5–3.0 wt% in CR‑39 MatricesSubstitution of the primary amine with a diazo‑derived indolinospirobenzopyran moiety generates a photochromic molecule whose open‑form absorption extends to 585 nm. When this functional dye is dissolved in diallyl diglycol carbonate (CR‑39) monomer at a loading of 1.5–3.0 wt% prior to the addition of 2.5 wt% diisopropyl peroxydicarbonate initiator, the subsequent cast‑polymerization in a glass‑gasketed mold must follow a temperature‑step profile: 48 h ramp from 40 °C to 75 °C, followed by 4 h post‑cure at 95 °C. The thermal limit of 95 °C is non‑negotiable because differential scanning calorimetry traces show an exothermic decomposition onset at 107 °C for the spiro‑compound, leading to irreversible yellowing that increases the yellowness index (ASTM E313) of a 2.0 mm lens blank from 0.8 to 3.2 units.The photosensitivity at the target tint neutral‑grey shade is quantified by the half‑darkening time under illumination from a 450‑W xenon lamp filtered to 1.2 sun irradiance; a batch record achieving τ½ < 35 s at 23 °C requires that the dye be pre‑dissolved in 15 wt% of the CR‑39 monomer together with 0.05 wt% of the free‑radical scavenger 2,6‑di‑tert‑butyl‑4‑methylphenol and passed through a 0.2 µm PTFE membrane to remove undissolved particulates that would otherwise nucleate premature photofatigue. Finished planks are surfaced, hardened via a polysiloxane top‑coat, and cut into lenses that must meet the minimum luminous transmittance specification of ANSI Z80.3 and the traffic‑signal recognition clause of ISO 12312‑1:2022. The compliance docket incorporates a REACH dossier for the spiro‑dye as a “monomer under controlled factory conditions” and aging validation according to the 200 h QUV‑B test with a fading threshold of ΔE*₀₀ < 2.5.Within the framework of a cGMP intermediate supply agreement, 2‑amino‑6‑methylsulfonylbenzothiazole is delivered with a purity specification of ≥ 99.0 % (HPLC area‑percent, reverse‑phase C8 column, UV detection at 260 nm) and a residual solvent profile compliant with ICH Q3C Option 2 limits for Class 2 solvents—typically methanol < 3000 ppm, dichloromethane < 600 ppm, and acetone < 5000 ppm. Its role as a pharmaceutically active intermediate hinges on the regioselective introduction of a leaving group at the 2‑amino position via diazotization‑Sandmeyer conversion to the 2‑bromo analogue, which then serves as an electrophilic coupling partner in a palladium‑catalyzed Suzuki‑Miyaura cross‑coupling with a boronic acid‑bearing heterocycle. The scale‑up protocol at a 50‑L pilot‑scale batch level starts with diazotization under a 5‑fold molar excess of concentrated hydrobromic acid at −5 to 0 °C, quenching the diazonium stream into a 35 wt% solution of cuprous bromide in hydrobromic acid over 75 min, and then hydrolyzing the crude bromo product. The molar conversion efficiency is tracked via in‑line FTIR monitoring of the diazonium absorption at 2260 cm⁻¹; a decline in the peak area to < 0.2 % of its maximum signals complete consumption before the cuprous bromide is added.Genotoxic hazard control is structured around the ICH M7(R2) addendum for mutagenic impurities. Process capability analysis on 15 consecutive GMP lots shows that the intrinsic content of potential alkylating residues falls below the individual threshold of toxicological concern of 1.5 µg/day when the intermediate’s use in the final drug substance results in a daily intake of up to 300 mg of the API. A quantitative structure‑activity relationship evaluation using Derek Nexus 6.2 and Sarah Nexus 3.2 flags the 2‑bromo intermediate as a potential Alerting Structure class 3; consequently, a dedicated liquid chromatography‑high‑resolution mass spectrometry method with a limit of quantitation of 0.1 ppm relative to the API is filed in the drug master file under US DMF Type II and EU ASMF. The terminal dosage form to which this intermediate contributes is an extended‑release tablet containing a kinase inhibitor with a benzothiazole‑isoquinoline chemotype, manufactured by roller compaction at a ribbon density of 1.15 g/cm³ on a Gerteis Mini‑Press pathway before tablet pressing at a hardness of 80 – 85 N.UV Absorber Migration Kinetics in Polyurethane CoatingsThe heterocyclic amine is converted into a 2‑(2‑hydroxyphenyl)‑6‑methylsulfonylbenzothiazole‑based ultraviolet absorber via diazo‑coupling with 4‑methoxyphenol followed by demethylation with pyridine hydrochloride at 180 °C. Incorporation of this absorber into a solvent‑borne two‑pack polyurethane clearcoat at a loading of 0.3 – 0.8 wt% (on resin solids) demands a pre‑dissolution step in xylene‑butyl acetate ( 60:40 weight ratio) at 60 °C for 4 h to prevent crystallization‑driven haze during film curing. The formulation is applied over a silver metallic basecoat on a cold‑rolled steel panel; the clearcoat is force‑dried at 80 °C for 30 min and then exposed to cyclic SAE J2527 accelerated weathering. After 3000 h, the retained specular gloss measured at a 20° geometry stands at 77 % of the original value, compared with 52 % for the unstabilised control.The migration‑limiting property is probed by sectioning the film with a cryo‑microtome and profiling the absorber concentration versus depth via confocal Raman microscopy at the 1355 cm⁻¹ band (C‑N stretch of the benzothiazole). The gradient at the coating‑substrate interface remains below a depletion depth of 2.5 µm after 500 h at 90 °C under a thermal aging oven conditioned to 30 % relative humidity, a performance edge attributed to the strong dipole moment of the methylsulfonyl group anchoring the molecule to the urethane hard segment through dipole‑dipole interaction with the residual N‑H groups. Compliance with FDA 21 CFR 178.3297 for indirect food additives limits the maximum migration into fatty food simulants to < 1.0 mg/dm² as defined by the overall migration test of EU 10/2011; results from a 30‑day contact test with 95 % ethanol at 60 °C place the extracted fraction at 0.32 mg/dm², well within the boundary.---
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2-Amino-6-methylsulfonyl-1,3-benzothiazole (commonly referenced in industrial supply chains as 2-Amino-6-Methisulfonylbenzothiazole) is a heterocyclic aromatic sulfone derived from the benzothiazole scaffold, bearing a primary amine at position 2 and an electron-deficient methylsulfonyl group at position 6. The molecular formula C8H8N2O2S2 yields a molecular weight of 228.29 g/mol. The sulfone moiety introduces a Hammett σp constant of approximately +0.72, which deactivates the fused phenyl ring toward electrophilic substitution and modulates the nucleophilicity of the exocyclic amine, affecting both condensation reaction kinetics and the thermal lability of derived sulfenamides. The product is supplied as a free-flowing crystalline powder ranging in color from off-white to pale beige, with lot-dependent particle size distributions determined by pin milling or jet milling post-drying. Primary packaging is sealed in fiber drums with antistatic polyethylene liners compliant with DIN EN 61340-5-1, holding net weights of 25 kg or 50 kg, with desiccant sachets inserted when ambient relative humidity at the point of shipment exceeds 60 %.
Substitution at position 6 of the benzothiazole ring critically influences the electron density on the thiazole nitrogen and the reactivity of the amino group. In 2-amino-6-fluorobenzothiazole (CAS 348-38-5) the inductive effect predominates, whereas the nitro congener (2-amino-6-nitrobenzothiazole, CAS 6285-57-0) introduces a strong resonance-withdrawing effect that positions the amine as a significantly weaker nucleophile. The methylsulfonyl group combines both inductive and resonance withdrawal, yet its sulfone geometry — a tetrahedral sulfur centre — prevents the coplanar conjugation that the nitro group achieves. This structural distinction manifests in three operational differences observed during downstream derivatisation: (a) sulfenamide-forming condensation with 2-mercaptobenzothiazole proceeds with an activation energy approximately 8–12 kJ/mol lower than that of the nitro analogue, enabling complete conversion at 45 °C in toluene within 3 hours versus the 60 °C and 6 hours required for the nitro derivative; (b) the sulfone is resistant to reductive side-reactions under hydrogenation conditions that strip halogens from 6-chloro or 6-bromo variants when Raney nickel is used; (c) solubility in methanolic ammonia at 25 °C is approximately 2.8 g/100 mL, compared to 0.9 g/100 mL for the nitro compound, simplifying purification of amidation products by controlled crystallization. Differential scanning calorimetry across heating rates of 10 K/min (ASTM E793) reveals a sharp endothermic melt for the methylsulfonyl derivative, typically 174–177 °C, whereas the 6-chloro analogue melts at 197–199 °C and the 6-nitro analogue at 252–254 °C with concurrent decomposition. These thermal disparities influence melt-phase processing windows when the compound is dispersed directly into polymer matrices.
Model variants are offered to accommodate divergent regulatory and performance requirements across application domains. The pharmaceutical intermediate grade (designation AMS-P) is controlled for residual palladium content below 5 ppm (determined by ICP-OES per USP <232>), while the technical grade destined for rubber compounding (AMS-T) applies a limit of 20 ppm. Purity is determined by reversed-phase HPLC with UV detection at 254 nm using a C18 column (4.6 × 150 mm, 3.5 μm particle size) and methanol/water (70:30 v/v) mobile phase at 1.0 mL/min. The following table presents the release criteria for the two primary model designations.
| Attribute | Method | AMS-P (Pharma) | AMS-T (Technical) |
|---|---|---|---|
| Assay (HPLC, area%) | Ph. Eur. 2.2.29 | ≥ 99.0 % | ≥ 97.0 % |
| Water (Karl Fischer) | ASTM E203 | ≤ 0.5 % w/w | ≤ 0.5 % w/w |
| Sulphated Ash | Ph. Eur. 2.4.14 | ≤ 0.1 % | ≤ 0.3 % |
| Heavy Metals (as Pb) | USP <231> | ≤ 10 ppm | ≤ 30 ppm |
| Melting Range | ASTM E324 | 174–177 °C | 172–176 °C |
| Residual Solvents (Class 2) | ICH Q3C Headspace GC | Conform | — |
| Appearance | Visual vs. standard | Off-white to pale beige crystalline powder | Off-white to light tan powder |
Trace mutagenic impurities such as sulfonate esters are monitored via LC-MS/MS with a reporting threshold of 1.5 μg/g for the pharma grade, aligning with the staged TTC concept outlined in ICH M7(R2). For rubber-grade material, the specification includes a sieve residue limit of ≤ 0.5 % retained on a 75 µm screen (ASTM D4577) to minimise undispersed domains during compounding.
The preparation of delayed-action sulfenamide accelerators via oxidative condensation of 2-Amino-6-Methisulfonylbenzothiazole with 2-mercaptobenzothiazole yields a molecule whose solubility parameters differ markedly from those of the common N-cyclohexyl-2-benzothiazolesulfenamide (CBS, CAS 95-33-0) and N-tert-butyl-2-benzothiazolesulfenamide (TBBS, CAS 95-31-8). The methylsulfonyl substituent raises the Hansen polarity parameter δP to approximately 8.2 MPa½, compared to 5.1–5.5 MPa½ for CBS and TBBS, reducing compatibility with natural rubber (δP ≈ 2–3 MPa½) and ethylene-propylene-diene terpolymer (EPDM) grades with ethylene content above 55 %. This mismatch imposes practical constraints on processing: when the accelerator is introduced at loadings exceeding 2.0 phr into an EPDM formulation based on ENB-cure sites in a Banbury BR1600 internal mixer (tangential rotors, fill factor 0.75, drop temperature 135 °C), undissolved crystalline residues have been observed on the mill at the dump stage, requiring a second pass on a two-roll mill with a friction ratio of 1.25:1 and a nip gap of 0.8 mm to achieve dispersion quality below ASTM D7723 rating 3. The scorch safety, however, is significantly extended. A model truck-tread formulation of 100 phr NR (SMR 20), 50 phr N330 carbon black, 5 phr ZnO, 2 phr stearic acid, and 1.5 phr insoluble sulphur cured at 150 °C yields the comparative cure behaviour shown in the following table.
| Accelerator (1.5 phr) | Mooney Scorch t5 at 121 °C (min) | MDR t90 at 150 °C (min) | Tensile Strength (MPa) | Elongation at Break (%) | 300% Modulus (MPa) |
|---|---|---|---|---|---|
| 2-Amino-6-methylsulfonylbenzothiazole-derived sulfenamide | 31.2 | 14.8 | 23.7 | 480 | 12.4 |
| CBS | 24.4 | 11.2 | 25.1 | 445 | 13.1 |
| TBBS | 20.7 | 9.6 | 24.9 | 430 | 13.8 |
Testing performed in accordance with ASTM D5289 (MDR) and ISO 37 (tensile properties, type 2 dumbbells). The data indicate a pronounced extension of processing safety, allowing thicker cross-sections to be cured without reversion — a relevant attribute for solid tyre press-curing where centre porosity is a documented rejection mode. The trade-off is a reduction in 300% modulus of approximately 5–10%, which must be compensated by adjusting sulphur and carbon black loadings in the recipe.
A further operational boundary arises from the moisture sensitivity of the unreacted 2-Amino-6-Methisulfonylbenzothiazole intermediate. Storage of opened containers in mill rooms where relative humidity routinely exceeds 75 % leads to agglomeration of the fine powder by capillary condensation at particle contacts; when such material is dosed gravimetrically by an automated weighing system with a loss-in-weight feeder, bridging in the hopper cone has been observed at powder flow function values exceeding FF = 5.0 (determined by Schulze ring shear tester per ASTM D6773). Pre-drying in a vacuum oven at 50 °C for 2 hours restores acceptable flow, but the additional unit operation must be factored into batch-cost calculations.
Within fine chemical synthesis routes to benzothiazole-containing active pharmaceutical ingredients, this amine functions as a strategic building block for forming amide, sulfonamide, and urea linkages. The presence of the sulfone is utilised to increase the logP of the final molecule while introducing a polar surface area contribution of 60.0 Ų per fragment, thereby maintaining permeability class within the rule-of-five thresholds. In a described process for a kinase inhibitor intermediate, coupling of the amine with an activated carboxylic acid is performed in DMF at 0–5 °C using HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate) as the coupling agent; the yield after chromatography-free isolation by drowning in water and reslurrying in ethanol at 50 °C is 82–85 %, with residual DMF below 880 ppm (limit per ICH Q3C option 1). The primary difference from the analogous 6-methoxy derivative in this application is the sulfone’s resistance to metabolic O-demethylation, which eliminates a common toxicophore and simplifies the genotoxic impurity strategy for the sulfonate counter-ion.
Batch records specify in-process controls for sulfonate ester formation, given the reactivity of the sulfone moiety under acidic alcohol conditions. A validated UPLC-MS method with a limit of quantification of 0.5 ppm for methyl methanesulfonate is applied to every campaign, and no lot is released for human-use synthesis without passing this limit. Published data comparing mutagenic profile of the sulfone versus the 6-trifluoromethyl analogue in the Ames assay (TA98 and TA100 strains, with and without S9 metabolic activation, OECD 471) shows no positive response up to 5000 µg/plate for the methylsulfonyl compound, whereas the trifluoromethyl congener exhibits a borderline increase in revertants at the highest dose, a difference attributed to the absence of metabolic defluorination pathways for the sulfone. This constitutes a critical selection criterion when designing a starting material for a development phase where later mutagenic flags cannot be mitigated.
Diazotisation of the amine and subsequent coupling to naphthol AS-type couplers yields azo pigments with absorption maxima bathochromically shifted by 15–25 nm relative to the corresponding 6-methylbenzothiazole derivatives, due to the electron-withdrawing sulfone acting as an auxiliary chromophore. Accelerated weathering of prints on cotton poplin (pigment printing paste with copolymer binder) conducted according to ISO 105-B02 at a controlled irradiance of 0.35 W/m² at 340 nm (xenon arc, filtered to daylight) reveals a blue wool rating of 6 after 200 hours for the sulfone-containing pigment, versus 4–5 for the non-sulfonated 6-methyl analogue. The improvement in photostability is attributable to stabilisation of the excited state through the sulfone’s electron sink capacity, reducing hydrogen abstraction from the binder matrix. The downside in this application segment is the pigment’s lower alkali fastness; the sulfone undergoes partial hydrolysis to the sulfonic acid sodium salt when printed goods are subjected to hot alkaline scour at 80 °C and pH 11.5, causing a colour strength loss of approximately 12–15 % (ISO 105-C10, test solution C). This liability restricts its use to non-chloride-bleached home laundry applications and necessitates a caution statement on the technical data sheet.
Functionalisation of glassy carbon electrodes with a self-assembled monolayer of 2-Amino-6-Methisulfonylbenzothiazole via diazonium electrografting produces a sensor capable of complexing Cu(II) and Pb(II) at concentrations down to 10⁻⁹ M. Cyclic voltammograms recorded in 0.1 M acetate buffer (pH 4.5) and acetonitrile (80:20 v/v) at a scan rate of 50 mV/s show a quasi-reversible wave at +0.32 V vs. Ag/AgCl, with a peak current enhancement of 340 % upon addition of 50 µM Cu(NO₃)₂. The sulfone’s differentiation from other amino-benzothiazoles in this detection scheme stems from its resistance to oxidative polymerisation during the grafting step: under the potentiostatic conditions employed (−0.6 V for 120 s in 0.5 mM diazonium salt), the 6-unsubstituted and 6-methyl derivatives form insulating multilayers that suppress the electron-transfer kinetics (ΔEp > 200 mV), whereas the sulfone yields a film of 2.5–3.0 nm thickness (ellipsometric measurement) with near-ideal blocking behaviour for ferricyanide but facile ion-gated permeation for the target metals. Published data on this sensor configuration are limited to proof-of-concept laboratory cells; no data from continuous-flow electrochemical reactors operating under industrial wastewater conditions are publicly available.
