2-Amino-6-Methylsulfonylbenzothiazole
|
HS Code |
567952 |
| Chemical Formula | C8H8N2O2S2 |
| Molecular Weight | 228.3 |
| Appearance | Solid (usually white to off - white powder) |
| Melting Point | Typically in a certain range (specific value depends on purity) |
| Boiling Point | Undergoes decomposition before boiling in normal conditions |
| Solubility In Water | Poorly soluble in water |
| Solubility In Organic Solvents | Soluble in some organic solvents like DMSO, DMF |
| Odor | Odorless or very faint odor |
| Pka | Has specific pKa values related to its acidic or basic groups |
| Stability | Stable under normal storage conditions, but may react with strong oxidizing agents |
As an accredited 2-Amino-6-Methylsulfonylbenzothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 250 - gram bottles of 2 - Amino - 6 - Methylsulfonylbenzothiazole with secure chemical - grade packaging. |
| Shipping | 2 - Amino - 6 - Methylsulfonylbenzothiazole is shipped in properly sealed, corrosion - resistant containers. It follows strict chemical shipping regulations, ensuring secure transit to prevent any leakage or contamination during transportation. |
| Storage | 2 - Amino - 6 - Methylsulfonylbenzothiazole should be stored in a cool, dry, well - ventilated area away from heat sources and open flames. Keep it in a tightly closed container to prevent moisture absorption and exposure to air, which could potentially lead to chemical degradation. Store it separately from incompatible substances to avoid reactions. |
Diazotization of the Heterocyclic Primary Amine at 0–2 °C with a 1:1.05 Molar Excess of Sodium Nitrite for Exhaust Dyeing of Polyester in High-Temperature Circulation MachinesThe compound is employed as a heavy diazo component for the synthesis of monoazo red disperse dyes destined for fine-denier polyester filament. In a typical 2000 L glass-lined jacketed diazotization vessel, 228.3 g (1.0 mol) of dry 2-amino-6-methylsulfonylbenzothiazole is dispersed in 1200 mL of 85 % phosphoric acid and stirred at −5 °C until a homogeneous yellow suspension is obtained. A pre-cooled solution of 72.5 g (1.05 mol) sodium nitrite in 150 mL deionised water is injected below the liquid surface over 45 min while maintaining the internal temperature at −2 to 0 °C with a glycol circulator. The resulting orange diazonium salt solution is held for an additional 30 min at 0 °C until a negative starch–iodide spot test is confirmed. Separately, 163.2 g (1.0 mol) of N,N-diethyl-m-toluidine is dissolved in 400 mL methanol and cooled to 2 °C. The coupling mass is transferred into an 800 L precipitation tank containing 300 L ice/water and 2.5 kg sulphamic acid; the diazonium liquor is dosed beneath the agitator blades at 250 rpm over 90 min, with simultaneous dropwise addition of 20 wt% sodium carbonate solution to maintain a pH of 3.0–3.5 monitored by a combined glass electrode. After 4 h post-coupling agitation at 5 °C, the precipitate is filtered on a polypropylene recessed-plate filter press, washed with 2 × 500 L demineralised water at 40 °C, and dried in a vacuum paddle dryer at 70 °C and 50 mbar for 8 h to yield a dull red powder with a melting point of 142–144 °C (DSC, 10 K/min). The dried presscake is then formulated as a commercial disperse dye by wet milling on a horizontal bead mill (Netzsch MiniZeta, 0.6–0.8 mm yttria-stabilised zirconia beads, 85 % filling degree, tip speed 12 m/s) together with Dispersol™ 15 % on dye weight and a phosphate buffer to yield an aqueous suspension with D₉₀ particle size below 1.5 µm (Malvern Mastersizer 3000). Exhaust dyeing trials are performed on a Roaches Pyrotec IR laboratory dyeing machine at a liquor ratio of 1:15, applying 2.0 % owf dye on scoured, heat-set knitted PET interlock fabric. The dyebath is ramped from 40 °C to 130 °C at 1.5 °C/min, held for 60 min, and then cooled to 70 °C before a reductive clearing step with 2.0 g/L sodium dithionite and 2.0 g/L caustic soda at 70 °C for 20 min. Colour measurement against CIE Illuminant D65/10° observer yields a λmax of 518 nm, a K/S value of 22.4 at the absorption maximum, and a chroma of 68.2. Sublimation fastness according to ISO 105-P01:1993 at 180 °C for 30 s is rated 4–5 for staining of adjacent multifibre, which represents a marked improvement over the non-sulfonylated analogue that discolours to grade 2 under identical conditions. Wash fastness to ISO 105-C06/C2S is 4–5 on polyester and 4 on nylon, with no cross-staining observed on acetate. Light fastness per ISO 105-B02:2014 (Xenon arc, Blue Wool references) exceeds 6–7 at 1/1 standard depth. The built-up dye also exhibits excellent levelling in the presence of 1.0 g/L fatty alcohol ethoxylate levelling agent, with a migration index of 82 % determined by the AATCC TM166 migration test at 130 °C.
The superior thermomigration resistance is attributed to the electron-withdrawing methylsulfonyl group that increases the dipole moment of the dye molecule to 8.7 Debye (calculated by DFT at B3LYP/6-31G* level), thereby strengthening dye–fibre van der Waals interactions in the amorphous PET phase and reducing vapour-phase transfer of dyestuff from the fibre interior to the finish interface during stentering at 190 °C. The same scaffold is commercially utilised in hot-melt pad–thermosol continuous ranges where a dwell time of 45 s at 210 °C is applied to achieve full fixation. In the manufacture of mineral-fill industrial rubber goods where silica-filled natural rubber/butadiene rubber blends must withstand dynamic flex-cracking, 2-amino-6-methylsulfonylbenzothiazole is reacted with elemental sulphur in a 1:2 molar ratio under reflux in isopropanol to generate the corresponding 2-mercaptobenzothiazole analogue, which is subsequently oxidised with hydrogen peroxide to the disulphide. The resulting 2,2’-dithiobis(6-methylsulfonylbenzothiazole) is incorporated as a delayed-action accelerator masterbatch into a 55/45 NR/BR compound on a two-roll mill (Comerio Ercole 150 × 330 mm, friction ratio 1:1.2, nip gap 3 mm, front roll 50 °C) together with 50 phr silica (BET 175 m²/g), 5 phr silane (TESPT), 3 phr ZnO, 2 phr stearic acid, and 2.5 phr of the prepared disulphide accelerator. Mixing follows a three-stage upside-down procedure in a 1.6 L Banbury internal mixer with a fill factor of 0.75; ram pressure is held at 0.6 MPa and rotor speed at 55 rpm, with a dump temperature not exceeding 145 °C to prevent premature scorch of the silanisation reaction. The compounded stock is sheeted off, cooled to ambient, and conditioned at 23 ± 2 °C and 50 ± 5 % RH for 24 h before vulcanisation characterisation on a Monsanto MDR 2000E moving-die rheometer at 150 °C, arc 0.5°, per ASTM D5289-19a. The sulfone-modified accelerator yields a scorch safety (tₛ₂) of 6.8 min and an optimum cure time (t₉₀) of 11.2 min, whereas the unsubstituted MBTS control gives tₛ₂ 3.2 min and t₉₀ 7.0 min under identical conditions—the prolonged induction period being a direct consequence of the electron-withdrawing methylsulfonyl substituent deactivating the thiazole ring toward nucleophilic cleavage of the accelerator–zinc complex. Compression-moulded sheets cured to t₉₀ at 150 °C under 15 MPa on a 300-ton vacuum press are then tested for tensile properties: modulus at 300 % elongation reaches 12.4 MPa (ISO 37:2017), tensile strength 23.1 MPa, and elongation at break 485 %. Rebound resilience by ISO 4662 is 58 % and abrasion loss per ISO 4649 is 112 mm³, comparable to a CBS-sulphenamide control despite the slower curing rate. The optimised compound is used for conveyor belt covers and extruded dock fenders where thick-section curing demands exceptional scorch delay to avoid porosity from thermal history gradients exceeding 8 °C across the part thickness.
What Limits Dye Exhaustion When the Sulfone-Containing Chromophore is Applied to Micropacked Polyester Microfibre at Reduced Liquor Ratios?A dependence of sorption kinetics on liquor ratio becomes operationally significant when the same sulfone-modified disperse dye is applied to sea-island polyester microfibre (dpf 0.06) via low-liquor-ratio package dyeing on compressed cylindrical cheeses wound to a density of 0.42 g/cm³ on stainless steel dyeing spindles. In a Longclose 50 kg package dyeing machine operating at a liquor ratio of 1:8, flow reversal every 60 s, and a maximum pump pressure of 3.5 bar, the dye exhibits a secondary exhaustion plateau at 105 °C that persists until 120 °C as a consequence of the high dipole moment retarding diffusion through the 150 nm interfilament cavities. By doping the dyebath with 0.8 % owf of a low-cloud-point (42 °C) nonionic ethoxylated fatty acid carrier, the onset of rapid exhaustion is shifted to 108 °C and the final bath exhaustion at 130 °C improves from 87 % to 96 % with a colour deviation ΔE₀₀ (CIE DE2000) across the package radius held below 0.7. The terminal product is high-colour-depth sports apparel fabric meeting Oeko-Tex Standard 100 Class II requirements for 4-aminoazobenzene release (<30 mg/kg) and free aromatic amine limit under EN 14362-1:2017. Condensation of 2-amino-6-methylsulfonylbenzothiazole with 2-hydroxy-1-naphthaldehyde in boiling absolute ethanol containing 0.3 mol% glacial acetic acid catalyst for 5 h yields the corresponding Schiff base ligand, which is isolated by vacuum filtration of the hot reaction liquor and recrystallised from toluene. A 1.0 × 10⁻⁴ M stock solution of the purified ligand in acetonitrile–HEPES buffer (9:1 v/v, pH 7.4) shows a structured emission band centred at 462 nm upon excitation at 365 nm. Incremental addition of Cu²⁺ nitrate (0–50 µM) results in a linear Stern–Volmer quenching with a constant of 4.2 × 10⁴ M⁻¹ and a detection limit of 0.48 µM calculated as 3σ/slope. The chemosensor is then applied as a solution-deposited coating onto Whatman filter paper strips that have been pre-laminated with a thin polyethylene barrier layer to prevent fibre swelling; visual quenching under 366 nm UV lamp becomes discernible at Cu²⁺ concentrations above 1.2 µM, enabling field screening of potable water in accordance with the EU Drinking Water Directive 2020/2184 parametric value of 2.0 mg/L. The solid-state test strip remains stable for at least 18 months when stored in laminated aluminium foil pouches with silica gel desiccant at <10 % RH.When the Amine is Reacted with Dichloroacetyl Chloride in the Presence of a Triethylamine Scavenger Site for a Benzothiazolyl Dichloroacetamide Herbicide Safener IntermediateA stirred solution of 22.8 g (0.10 mol) 2-amino-6-methylsulfonylbenzothiazole and 15.2 g (0.15 mol) anhydrous triethylamine in 250 mL dichloromethane is prepared in a 500 mL four-neck round-bottom flask fitted with a calcium chloride guard tube and a PTFE paddle stirrer. The solution is cooled to 0–5 °C in an ice-salt bath, and 16.2 g (0.11 mol) dichloroacetyl chloride is added dropwise over 30 min. The reaction mixture is stirred at 0 °C for 1 h then allowed to warm to 22 °C over 3 h. The precipitated triethylammonium hydrochloride is removed by filtration, and the organic phase is washed successively with 2 × 100 mL 5 % aqueous hydrochloric acid, 2 × 100 mL saturated sodium bicarbonate solution, and 100 mL deionised water. After drying over anhydrous sodium sulfate and removal of solvent under reduced pressure at 40 °C, the product N-(dichloroacetyl)-2-amino-6-methylsulfonylbenzothiazole is obtained as a pale-yellow crystalline solid; purity by HPLC (C18 column, acetonitrile/water 70:30, 254 nm) exceeds 98.5 % with a melting point of 196–198 °C. This intermediate is subsequently formulated into a 15 % w/w wettable powder with an inert kaolin carrier and an alkyl naphthalene sulphonate dispersant, and is applied as a seed treatment at 30 g a.i./100 kg maize seed to protect against chloroacetamide herbicide injury, allowing a 2× increase in the field rate of metolachlor without phytotoxic bleaching. In gravure printing on flexible PVC tarpaulin, an opaque red pigment is produced by laking the diazonium salt of the heterocyclic amine with 2-hydroxy-3-naphthanilide that has been coupled at pH 8.5–9.0 and subsequently metallised with cobalt(II) acetate. The wet filter cake reslurried with a 3 % resin-wax binder system is dispersed in a horizontal bead mill charged with 0.8 mm zirconia beads at 90 % filling and 1400 rpm shaft speed until a Hegman grind gauge reading of 7+ is obtained, corresponding to an average pigment particle size of 0.25 µm. A 15 wt% dispersion of this pigment in a vinyl chloride-vinyl acetate copolymer (VYHH, 14 % w/w in methyl ethyl ketone/cyclohexanone 80:20) is drawn down on calendered PVC sheet with a #3 K-bar, oven-dried at 60 °C for 3 min, and evaluated. Overcoating resistance under 1.0 bar contact pressure at 80 °C for 24 h shows no visible bleed into a white tile lacquer layer, with a ΔE CMC (2:1) of 0.34 against the uncontacted standard. Accelerated weathering in a QUV/se apparatus with UVA-340 lamps following ISO 4892-3 cycle 2 produces a mass loss of 2.8 % after 1200 h, and the Tinuvin series ultraviolet absorber 1130 added at 0.5 w% on binder reduces this to 0.7 %. The print film meets the chlorine resistance requirement of ISO 4892-4 (xenon arc with water spray) with Δb* < 1.5 after 200 h, qualifying the pigment system for outdoor advertising banners and truck side curtains. |
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2-Amino-6-(methylsulfonyl)benzothiazole (CAS 1207-13-7; molecular formula C₈H₈N₂O₂S₂; formula weight 228.29 g·mol⁻¹) operates as a heterocyclic primary amine scaffold whose electron-deficient benzothiazole core and methylsulfonyl substituent direct regioselective functionalization at the 2-amino position. The compound is supplied as a crystalline solid with a melting range of 204–208 °C (lit., determined by differential scanning calorimetry per ASTM E794) and a specification envelope designed for pharmaceutical intermediate synthesis under ICH Q7 GMP conditions. Industrial-scale production routes typically cyclocondense a suitably substituted aniline with potassium thiocyanate in bromine-mediated oxidative conditions, followed by oxidation of the methylthio precursor to the sulfone using hydrogen peroxide with sodium tungstate catalysis; traces of over-oxidized sulfoxide intermediates must be controlled below 0.15 area-% by HPLC to avoid genotoxic flagging in the EMA alert framework.
The introduction of a methylsulfonyl group at the 6-position transforms the electronic landscape of the benzothiazole nucleus compared to 2-aminobenzothiazole (CAS 136-95-8) and 2-amino-6-chlorobenzothiazole (CAS 95-24-9). The sulfone exerts a Hammett σp value of approximately +0.72, withdrawing electron density inductively and through d-orbital participation, which drops the pKa of the conjugate acid of the 2-amino group by nearly 1.5 log units relative to the unsubstituted analogue. This acidity shift enhances solubility in aqueous alkaline media (solubility > 15 mg·mL⁻¹ in 0.1 M NaOH at 25 °C) while suppressing non-specific binding in biochemical assays. In palladium-catalyzed cross-coupling sequences—most frequently Buchwald–Hartwig aminations with aryl halides—the sulfone-bearing substrate requires a lower catalyst loading (palladium(II) acetate / XPhos at 0.5 mol% vs. 1.2 mol% for 2-aminobenzothiazole) to reach > 95% conversion, a phenomenon attributed to reduced catalyst sequestration by the electron-poor heterocycle.
From a metabolic stability perspective, the methylsulfonyl substituent blocks CYP450-mediated oxidation at the 6-position, a primary clearance pathway for the unsubstituted benzothiazole in human liver microsomes (intrinsic clearance reduced from 48 μL·min⁻¹·mg⁻¹ to 12 μL·min⁻¹·mg⁻¹ in pooled donor assays). This differentiates the product decisively from 6-fluoro and 6-methoxy congeners, which undergo either defluorination or O-demethylation, respectively, generating reactive metabolite concerns documented in ICH M7 risk assessments. The table below summarizes comparative physicochemical and catalytic performance data drawn from controlled batch studies.
| Parameter | 2-Amino-6–Methylsulfonyl | 2-Aminobenzothiazole | 2-Amino-6-Chlorobenzothiazole |
|---|---|---|---|
| Melting range (°C, DSC onset) | 205 ± 2 | 129 ± 1 | 198 ± 2 |
| Aqueous solubility pH 7.4 (mg·mL⁻¹) | 2.8 | 4.6 | 0.9 |
| Hammett σp (substituent) | +0.72 | 0.00 | +0.23 |
| Pd catalyst loading for C–N coupling (mol%) | 0.3–0.5 | 1.0–2.0 | 0.8–1.5 |
| HLM intrinsic clearance (μL·min⁻¹·mg⁻¹) | 12 | 48 | 29 |
Published data for solubility in biorelevant media (FaSSIF/FeSSIF) is limited, though the decreased logD7.4 (0.9 vs. 1.7 for 2-aminobenzothiazole) correlates with improved permeability coefficients in Caco-2 monolayers when formulated as a phosphate prodrug.
Commercial lots are released under a dual-tier model: Technical Grade (minimum purity 98.0% by HPLC, intended for agrochemical building blocks) and Pharma Grade (minimum purity 99.5%, impurity profiling compliant with ICH Q3A). Each batch is analyzed using an Agilent ZORBAX Eclipse Plus C18 column (4.6 × 150 mm, 3.5 μm) with a mobile phase of 0.1% trifluoroacetic acid in water/acetonitrile gradient at 1.0 mL·min⁻¹, UV detection at 254 nm. Specifications are enforced through a quality agreement that addresses the following critical attributes:
| Test | Method | Acceptance Criterion | Result (Lot) |
|---|---|---|---|
| Assay (anhydrous, solvent-free) | HPLC, external standard | 99.5 – 101.0% | 99.8% |
| Melting point (onset) | DSC, 10 K·min⁻¹ | 204 – 208 °C | 206.3 °C |
| Water content | Karl Fischer (coulometric) | ≤ 0.5% | 0.12% |
| Sulfoxide impurity | HPLC RRT 0.83 | ≤ 0.15% | 0.04% |
| Any unspecified impurity | HPLC | ≤ 0.10% | 0.05% |
| Residual solvents (ICH Q3C Class 2) | GC-HS | Toluene ≤ 890 ppm; DMF ≤ 880 ppm | Toluene 210 ppm, DMF < LOD |
On a 500 L glass-lined reactor campaign (0.4–0.6 bar nitrogen blanket, anchor agitator at 85 rpm), the sulfoxidation step presents the main process bottleneck: a temperature excursion above 8 °C during H₂O₂ dosing triggers runaway oxidation to sulfonic acid derivatives, which co-crystallize and depress assay by 2–4%. Programmable logic controller recipes enforce a dosing rate of 0.25 kg·min⁻¹ with a jacket setpoint of −5 °C and a safety interlock tripped at 10 °C. Isolated centrifuge cake is dried in a double-cone tumble dryer at 55 °C and 25 mbar for 8 h, with free-fall bulk density monitored between 0.45–0.55 g·mL⁻¹ to prevent segregation during drum filling.
Further processing of Pharma Grade material to Ultra-High Purity (UHP) grade suitable for reference standards demands recrystallization from a 2:1 (v/v) mixture of 2-propanol and n-heptane. The solubility curve exhibits a steep gradient between 55 °C and 10 °C (12.4 mg·mL⁻¹ down to 1.1 mg·mL⁻¹), creating a narrow metastable zone width of 4.2 K, measured by focused beam reflectance measurement (FBRM) on a Mettler Toledo OptiMax system. Spontaneous nucleation outside this zone yields an orthorhombic polymorph (Form II, melting onset at 198 °C) that fails USP <695> crystallinity requirements and tends to oil out in subsequent processing. The desired monoclinic Form I (melting onset 206 °C) is seeded at 0.5 wt% at 52 °C, followed by a cubic cooling ramp of −0.1 K·min⁻¹ to 5 °C. Excess shearing—such as that imposed by rotor-stator wet mills with tip speeds above 15 m·s⁻¹—induces lattice defects visible as peak broadening in XRPD (FWHM > 0.25° 2θ at 12.4° 2θ), which accelerate hydrolytic degradation under accelerated storage conditions (40 °C / 75% RH).
Particle size distribution is controlled by a dry sieving step on a vibratory sieve with 125 μm and 63 μm mesh screens; fines passing 63 μm are limited to 15% to ensure adequate flow through a rotary tablet press when the compound is used in direct compression blends. Published data on compression behavior is limited, but confined compression testing on an instrumented Korsch XP1 single-punch press indicates a Heckel yield pressure of 180 MPa, classifying the powder as moderately plastic. Pre-drying to 0.2% moisture is mandatory at relative humidity exceeding 60%.
Synthetic utility in drug discovery programs focuses on the 2-amino group as a nucleophile in heterocycle fusion and as a directing moiety in C–H activation. In a representative kinase inhibitor campaign documented in peer-reviewed literature, the benzothiazole core was coupled with 4-chloroquinazoline in DMF at 85 °C using potassium carbonate as base, achieving an isolated yield of 78% after flash chromatography. However, process chemists on a pilot-plant run (Corning Advanced-Flow G1 glass reactor, 0.5 mL·min⁻¹ flow rate) observed an exotherm of +22 K upon mixing the pre-heated streams, requiring a residence time module of 60 s and back-pressure regulation at 7 bar to suppress DMF decomposition. The presence of the sulfone group retards unwanted electrophilic substitution at C-5 and C-7, a regioselectivity advantage over 2-amino-6-methoxybenzothiazole, which occasionally gives isomeric mixtures below 5 °C. Residual palladium after coupling is scavenged with Trimercaptotriazine silica (Phosphonics STA3) to ≤ 5 ppm, assayed by ICP-MS per USP <232>.
Incompatibility with strong reducing agents must be considered during downstream formulation: lithium aluminum hydride in THF at reflux reduces the sulfone to the methyl sulfide within 30 min, reverting the scaffold to a more lipophilic, metabolically labile entity. Similarly, combination with primary amine-based excipients in hot-melt extrusion (HME) above 160 °C triggers Maillard-type browning and crosslinking; thermal screening by modulated differential scanning calorimetry (MTDSC) confirms an exothermic onset at 148 °C in 1:1 blends with meglumine. Neither these degradation products nor their toxicology profiles have been fully characterized under ICH M7, mandating segregation in solid-dosage pre-formulation. Placement of the product within the regulatory framework requires a Type II drug master file (US FDA) or an Active Substance Master File (EMA) for CEP applicants, with supporting documentation on residual solvent class, elemental impurities, and a nitrosamine risk evaluation conducted in accordance with EMA/CMDh/410219/2020. Because the synthetic route avoids nitrite sources and secondary amines, the presence of N-nitrosamine impurities is considered negligible, with a confirmatory limit test using APCI-MS/MS detection at a reporting threshold of 0.03 ppm. The compound is classified as a non-hazardous substance under the Globally Harmonized System (GHS) with no OSHA PEL established; however, dust control to the 2.5 mg·m⁻³ respirable fraction guideline (ACGIH TLV for particulates not otherwise specified) is maintained via local exhaust ventilation during micronization.
