2-Amino-6-Chlorobenzothiazole
|
HS Code |
361645 |
| Chemical Formula | C7H5ClN2S |
| Molecular Weight | 184.64 |
| Appearance | Solid |
| Color | Off - white to light yellow |
| Melting Point | 178 - 182 °C |
| Solubility In Water | Insoluble |
| Solubility In Organic Solvents | Soluble in some organic solvents like DMSO, DMF |
| Odor | Characteristic odor |
| Purity | Typically high - purity grades available, e.g., 98%+ |
As an accredited 2-Amino-6-Chlorobenzothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 250g of 2 - Amino - 6 - Chlorobenzothiazole packaged in a sealed, labeled container. |
| Shipping | 2 - Amino - 6 - Chlorobenzothiazole is shipped in sealed, corrosion - resistant containers. These are carefully packed to prevent damage during transit, following strict chemical shipping regulations to ensure safety. |
| Storage | 2 - Amino - 6 - Chlorobenzothiazole should be stored in a cool, dry, and well - ventilated area. Keep it away from heat sources, open flames, and direct sunlight to prevent decomposition. Store in a tightly - sealed container to avoid contact with moisture and air, which could lead to degradation. Separate it from oxidizing agents and incompatible substances. |
Diazo Component for High-Washfastness Disperse Dyes on PolyesterWhen azoic coupling components are diazotized in sulfuric acid media at –2 °C to 0 °C, 2-amino-6-chlorobenzothiazole yields a stable diazonium salt that reacts with N-alkylated aniline derivatives to produce blue- to green-shade disperse dyes with 4–5 washfastness ratings under ISO 105-C06:2010. The molar excess of the coupling component is maintained at 1.02–1.05 mol per mole of diazonium intermediate to compensate for decomposition during the exothermic coupling stage; commercial plant recipes typically load the chlorobenzothiazole at 42–48 wt% of the crude dyestuff before standardisation. Downstream processing on a production scale begins with post-coupling neutralisation using sodium carbonate solution to reach pH 6.5–7.0, followed by filter-press dewatering on polypropylene membrane plates at 6 bar and counter-current washing until chloride conductivity falls below 200 µS/cm. The wet cake is re-slurried with lignosulfonate dispersants and bead-milled in horizontal mills charged with 0.6–0.8 mm yttria-stabilized zirconia beads to a median particle size D₅₀ < 1.5 µm; spray-drying at inlet 210 °C / outlet 85 °C converts the dispersion into non-dusting granular powder. The finished commercial form is a standard-strength disperse dye (100% presscake-free powder) that complies with OEKO-TEX® Standard 100 Annex 6 and ZDHC MRSL Level 3, with chlorinated benzothiazole residues below 1000 ppm as verified by LC-MS/MS against REACH Annex XVII restrictions. In the synthesis of broad-spectrum benzothiazole fungicides active against Phytophthora infestans and Plasmopara viticola, 2-amino-6-chlorobenzothiazole supplies the electrophilic 6-chloro-benzothiazole scaffold for palladium-catalyzed cross-coupling. The primary amine is first acetylated with acetic anhydride at 60 °C to protect the reactive site before a Suzuki coupling with substituted phenylboronic acids; typical stoichiometry uses 1.08–1.10 equivalents of the boronate to offset protodeboronation losses, and the chlorobenzothiazole intermediate accounts for 55–65% of the molecular weight of the final active ingredient. Production campaigns on 2,000 L glass-lined reactors execute the coupling in degassed toluene/ethanol/water mixtures with 0.3–0.5 mol% Pd(PPh₃)₄, maintaining inert gas overlay (N₂, < 100 ppm O₂) to suppress catalyst deactivation; after phase separation the organic layer is filtered through activated carbon cartridges (5 µm) to recover residual palladium to below 10 µg/g. The deprotected active substance is crystallised from isopropanol and formulated as a water-dispersible granule (WG) via fluid-bed granulation at inlet 70 °C using sodium lignosulfonate binders. Registration dossiers for the resulting fungicide reference EC 1107/2009 data requirements and OECD 501 hydrolysis stability; maximum residue limits are set under Regulation (EC) No 396/2005, and the manufacturing site operates under ISO 14001:2015 environmental management. What Limits the Palladium Catalyst Turnover Number When Constructing 6-Chlorobenzothiazole-Muscle Relaxant Hybrids?The convergent assembly of 6-chlorobenzothiazole-containing muscle relaxant candidates—structurally related to benzothiazole carbamates—typically starts with a Buchwald-Hartwig amination between 2-amino-6-chlorobenzothiazole and a downstream bromoaryl intermediate. The amine is charged at 1.15–1.25 molar equivalents relative to the aryl bromide to drive conversion beyond 97%, while the catalyst system employs Pd₂(dba)₃ (0.8 mol%) with BINAP (1.6 mol%) in refluxing toluene under rigorous moisture exclusion (Karl Fischer < 50 µg/mL in reaction solvent). A recurring bottleneck on 500 L Hastelloy reactors is agglomeration of palladium black at extended reaction times, which drops turnover numbers below 80 and requires re-charging of ligand; therefore in-process IPC by HPLC (C18, 254 nm) triggers a termination window of 4–6 hours. The crude product is purified by re-slurrying in 5 volumes of ethyl acetate at 50 °C followed by hot filtration through a 0.5 µm PTFE membrane to meet the ≥99.5% purity (area%) specification for a registered starting material under ICH Q7 and FDA 21 CFR Part 211. The final physicochemically characterised active pharmaceutical ingredient is manufactured into film-coated tablets or lyophilised powder for injection, with residual palladium controlled below 10 ppm as per ICH Q3D (Class 1B elemental impurity) and genotoxic impurities evaluated according to ICH M7(R2). The process is executed in ISO Class 8 cleanrooms with terminal 0.2 µm sterilising filtration. Adding 0.15–0.75 mM (equivalent to 0.003–0.014 wt%) of 2-amino-6-chlorobenzothiazole to a 1.0 M HCl pickling bath at 25–60 °C suppresses uniform corrosion of C11000 electrolytic tough pitch copper by adsorbing through both the nitrogen and exocyclic sulfur atoms onto the oxide-free metal surface. Electrochemical impedance spectra acquired with a three-electrode flat cell (Ag/AgCl reference, Pt counter) show a single time constant and a charge-transfer resistance increase from ~250 Ω·cm² (blank) to ≥2,400 Ω·cm² at the critical micelle-adjacent concentration, after which inhibition efficiency plateaus at 94–96% as determined by ASTM G102-23 polarisation resistance method. On a continuous copper tube pickling line running at 12 m/min, the inhibitor is metered as a 2.5 wt% stock solution in methanol via a dosing pump interlocked with bath conductivity; excursions above 1.2 mM trigger the formation of a loosely adherent inhibitor film that interferes with subsequent phosphoric acid bright dipping, causing staining visible under 100 lux white-light inspection. The treated semi-finished tubes, destined for ACR (air conditioning and refrigeration) grade copper tubes, must pass surface residue testing per ASTM G31-21 weight-loss coupons and comply with RoHS Directive 2011/65/EU for the absence of restricted phthalates or brominated flame retardants in any carry-over product. Waste pickle liquor is neutralised and treated through hydroxide precipitation to remove dissolved copper below 0.5 mg/L before discharge under EU BAT conclusions for surface treatment of metals (2016/902/EU). Conversion of the primary amine to a mercapto group proceeds via a Sandmeyer-type replacement: 2-amino-6-chlorobenzothiazole is diazotised in aqueous HCl at 0–5 °C with stoichiometric sodium nitrite, and the resulting diazonium solution is transferred into a pre-chilled aqueous sodium sulfide/sulfur mixture held at 5–10 °C. The evolved nitrogen generates significant foaming, so the 1,000 L glass-lined reactor is operated at 60% fill capacity with mechanical foam breakers and a 10% silicone antifoam emulsion dosed at 0.2 mL/kg batch. After oxidative dimerisation with air sparging at 40 °C, the resulting 6-chloro-2-mercaptobenzothiazole is isolated as a pale yellow powder (>98% purity) and functions as a fast-curing primary accelerator for natural rubber (SMR CV60) and solution-styrene butadiene rubber (S-SBR, 25% styrene) compounds. A typical truck tire tread formulation loads the accelerator at 1.2–1.6 phr alongside 2.0 phr sulfur and 3.5 phr zinc oxide, with mixing completed on a 1.6 L internal mixer (tangential rotors, 75% fill factor) and the Mooney viscosity maintained between 55–70 MU (ML 1+4, 100 °C) per ISO 289-1:2014. The vulcanisation kinetics, recorded on a moving-die rheometer (MDR 2000, 160 °C, 0.5° arc) according to ASTM D5289-19, give a scorch time ts₂ of 1.8–2.4 min and a t₉₀ cure time of 4.5–6.0 min, which matches the thermal history during continuous salt-bath curing of extruded sealing profiles. The finished elastomeric items—automotive coolant hoses, extruded EPDM sponge weatherstrips, and vibration-damping bushings—conform to emission limits under VDA 278 and extractables testing per FDA 21 CFR 177.2600 for repeated-use rubber articles, while the accelerator itself is registered under EU REACH (EC 1907/2006) with a tonnage band covering 10–100 t/a. |
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2-Amino-6-chlorobenzothiazole (CAS 95-24-9, C7H5ClN2S, molecular weight 184.65 g mol−1) is a heterocyclic building block supplied as an off-white to pale tan crystalline powder with a melting onset of 203–206 °C (DSC, 10 K min−1, nitrogen purge). The compound is distinguished from its unsubstituted and methyl-substituted analogues by the electron-withdrawing chlorine atom at the 6-position of the benzothiazole ring, which modulates both electrophilic substitution kinetics and the acid–base behaviour of the primary amine. Commercial material is typically offered in two purity tiers—98.5 % minimum (synthesis grade) and 99.0 % minimum (custom derivative grade)—with residual 2-amino-6-hydroxybenzothiazole, the 5-chloro isomer, and nitroso intermediates forming the principal impurity envelope quantified by isocratic HPLC (254 nm) on a pentafluorophenyl stationary phase.
The Hammett σm value for a chlorine substituent (+0.37) exerts a field-inductive withdrawal that deactivates the carbocyclic ring toward electrophilic attack relative to 2-aminobenzothiazole (σm for H = 0.00) while simultaneously acidifying the exocyclic amine. Titrimetric determination of the conjugate acid pKa in aqueous methanol (50 % v/v) gives a value near 2.8, roughly 0.7 units lower than the unsubstituted parent. This shift has direct consequences in diazotization protocols: nitrosation with sodium nitrite in concentrated phosphoric–sulfuric acid mixtures proceeds cleanly at −5 to 0 °C without competing ring nitration, whereas 2-aminobenzothiazole under identical conditions yields a measurable fraction (3–5 %) of 6-nitro by-product detectable by LC-MS. In azo dye manufacture, the diazonium salt of 2-amino-6-chlorobenzothiazole couples with N,N-diethylaniline sulfonamide derivatives to produce bluish-red disperse dyes having a λmax 10–15 nm hypsochromically shifted relative to those derived from 2-amino-6-nitrobenzothiazole, a feature exploited to achieve targeted shade adjustments in polyester dyeing assessed by ISO 105-B02:2014 light fastness testing where a rating of 6–7 is routinely recorded after 200 h xenon-arc exposure.
The differences relative to 2-amino-6-methylbenzothiazole are equally pronounced. Where the methyl group (σm −0.07) activates the ring and raises amine basicity (pKa ~3.4), chlorine substitution retards both electrophilic substitution and the base-catalysed hydrolytic ring-opening that plagues electron-rich benzothiazoles during prolonged storage at relative humidity above 60 %. Accelerated stability testing (40 °C/75 % RH, ICH Q1A conditions) shows <0.2 % ring-opened o-aminothiophenol derivative formation for the 6-chloro derivative after 6 months, versus 1.2 % for the 6-methyl homologue. This hydrolytic resilience is a critical process-fit parameter when the intermediate must survive aqueous work-up steps in multi-kilogram active pharmaceutical ingredient (API) campaigns.
Medicinal chemistry programmes targeting nematode tubulin inhibition have examined a library of thiazole-fused benzimidazole mimetics wherein 2-amino-6-chlorobenzothiazole serves as the heterocyclic core for sulfonamide and carbamate side-chain attachment. In a head-to-head comparison using a Trichinella spiralis motility assay at 25 µg mL−1, the 6-chloro-substituted prototype produced a paralysis time reduction of 35 ± 8 % relative to the unsubstituted benzothiazole derivative, a gain attributed to a 0.5 log unit increase in octanol-water distribution coefficient (log D7.4 1.2 vs. 0.7) and improved passive membrane permeability in Caco-2 monolayers (apparent permeability Papp 12 × 10−6 cm s−1). Importantly, the chloro substituent does not introduce a structural alert for mutagenicity under the standard Ames test battery (OECD 471, Salmonella typhimurium strains TA98 and TA100, with and without S9 metabolic activation); early screening data submitted under REACH registration indicate a negative outcome at concentrations up to 5000 µg per plate. Published data for chronic in vivo toxicity remain limited, and process chemists employ dedicated closed-loop filtration and nitrogen-blanketed drying steps to keep occupational airborne exposure below the internal banding limit of 10 µg m−3 (8-hour TWA) during pilot-plant campaigns.
The unattributed variability in melting behaviour observed across different manufacturing sources merits attention. When crystallised from toluene-cyclohexane mixtures, the product exhibits a single sharp endotherm at 204.8 ± 0.3 °C by ASTM E794-18; material obtained from aqueous hydrochloric acid recrystallisation, however, can contain a hydrochloride monohydrate phase that dehydrates in the 110–125 °C range, creating a broad, low-energy thermal event that interferes with DSC purity calculations. Manufacturers therefore typically report the melting point of the free base after neutralisation and vacuum drying at 60 °C (10 mbar). Bulk density, which ranges from 0.45 to 0.65 g cm−3 depending on crystallisation agitation speed, directly influences screw-feed consistency during continuous solid dosing on a twin-screw feeder (K-Tron KT20) integrated into downstream synthesis platforms. A deviation of ± 0.05 g cm−3 in bulk density has been correlated with a 5–7 % mass-flow fluctuation at a setpoint of 50 g min−1, requiring adaptive gain scheduling in loss-in-weight control algorithms to hold relative standard deviation below 0.8 %.
Development of sulphenamide rubber accelerators utilises 2-amino-6-chlorobenzothiazole as a precursor to the corresponding 2-mercapto-derivative. A Sandmeyer-type conversion employing sodium disulfide in aqueous ethanol at pH 10.5–11.0 yields 6-chloro-2-mercaptobenzothiazole (6-Cl-MBT) in 82–87 % yield after acidification. When this substituted mercaptan is oxidatively coupled with tert-butylamine in the presence of sodium hypochlorite (0–5 °C), the resulting sulfenamide, N-tert-butyl-6-chloro-2-benzothiazolesulfenamide (6-Cl-TBBS), displays a distinct vulcanization signature in natural rubber (SMR CV60) compounds. Moving-die rheometer evaluation at 160 °C per ASTM D5289-17 shows that 1.2 phr of 6-Cl-TBBS extends scorch safety (ts2) by 40–55 % compared to equimolar dosing of unsubstituted TBBS in a formulation with 2.5 phr sulfur and 5.0 phr zinc oxide, while the cure rate index (vc = 100 / (t90 − ts2)) decreases by approximately 20 %. The delayed onset of crosslinking is consistent with the electron-withdrawing chlorine reducing the nucleofugacity of the amine leaving group during accelerator decomposition; this expanded processing window is advantageous for thick-section rubber mouldings where heat transfer lag demands slower premature crosslinking to avoid centre porosity detected by ultrasonic C-scan analysis.
| Property | 2-Aminobenzothiazole | 2-Amino-6-chlorobenzothiazole | 2-Amino-6-methylbenzothiazole |
|---|---|---|---|
| CAS No. | 136-95-8 | 95-24-9 | 2536-91-6 |
| Molar mass (g mol−1) | 150.20 | 184.65 | 164.23 |
| Melting point (°C, DSC onset) | 126–129 | 203–206 | 129–132 |
| pKa (conjugate acid, 50 % MeOH) | 3.5 | 2.8 | 3.4 |
| log D7.4 (shake-flask) | 0.45 | 1.2 | 0.8 |
| Hydrolytic stability (40 °C/75 % RH, 6 mo, % degradation) | 0.5 | <0.2 | 1.2 |
The electrochemical behaviour of the diazonium salt generated from 2-amino-6-chlorobenzothiazole opens additional differentiation in functionalised surface coatings. Controlled-potential reduction at −0.45 V vs. Ag/AgCl on glassy carbon yields a grafted aryl layer with a surface coverage of 4.8 × 10−10 mol cm−2, as determined by integration of the ferricyanide blocking currents. The chlorine atom provides a convenient spectroscopic handle for XPS verification of successful film formation (Cl 2p binding energy 200.1 eV), a feature absent in the unsubstituted aminobenzothiazole that complicates quality control in electronic component adhesion promotion inspected to IPC TM-650 2.4.23.
| Parameter | Technical Grade | Pure Grade | Custom Derivative Grade | Test Method |
|---|---|---|---|---|
| Assay (HPLC, area %) | ≥ 95.0 | ≥ 98.5 | ≥ 99.0 | In-house LC-254 nm (PFPP column) |
| Individual organic impurity | ≤ 2.0 % | ≤ 0.5 % | ≤ 0.15 % | EP 8.0 monograph concept (impurity qualification) |
| Water content (Karl Fischer) | ≤ 0.5 % | ≤ 0.2 % | ≤ 0.1 % | USP <921> Method 1a |
| Residue on ignition (sulphated ash) | ≤ 0.1 % | ≤ 0.05 % | ≤ 0.02 % | ASTM D482-19 |
| Iron content (ICP-OES) | ≤ 50 ppm | ≤ 15 ppm | ≤ 5 ppm | USP <233> |
| Isomer ratio (6-Cl : 5-Cl) | > 98:2 | > 99.5:0.5 | > 99.9:0.1 | Chiralcel OJ-H, n-hexane/EtOH |
During the synthesis of disperse azo dyes, the diazotisation of 2-amino-6-chlorobenzothiazole in 85 % phosphoric acid containing a stoichiometric excess of nitrosylsulfuric acid demands precise temperature control in the range −3 ± 1 °C. Exceeding 0 °C triggers rapid degradation of the diazonium species, generating a tar-like precipitate that fouls the sintered-glass filter plate in plate-and-frame presses used for clarification prior to coupling. In full-scale campaigns employing a 2000 L glass-lined reactor, the thermal excursion risk is managed by a cascade control scheme linking jacket temperature to internal thermocouple feedback with a dead-time compensator tuned to a phase margin of 45°. The clarified diazo solution is then coupled with N-cyanoethyl-N-ethyl-m-toluidine in an ice-water slurry at pH 3.5–4.0, yielding a magenta dye with molar extinction coefficient εmax ≈ 3.8 × 104 L mol−1 cm−1 at 525 nm in DMF. Batch-to-batch colour strength, measured by spectrophotometric transmission at 0.5 g L−1 in acetone against a standard reference lot, must remain within ± 2 % to meet automotive textile specification ANSI Z136.1 colour durability requirements; excursions beyond this band are usually traced to residual o-aminothiophenol formed by diazonium hydrolysis, necessitating re-slurrying with activated carbon (Norit SX Plus, 2 wt% on charge) prior to reduction.
For agrochemical intermediate applications, 2-amino-6-chlorobenzothiazole is employed as a synthon for benzothiazolyl-urea herbicides via phosgene-free triphosgene coupling. A solution of the amine in anhydrous toluene is treated with 0.34 equivalents of triphosgene at 0 °C, followed by gradual warming to 60 °C, to form the isocyanate intermediate in situ; subsequent addition of a substituted aniline yields the desired urea in 72–78 % isolated yield after silica plug filtration. The chloro substituent attenuates the reactivity of the isocyanate toward moisture compared to the unsubstituted variant, allowing the coupling step to be run without strict Karl Fischer monitoring of solvents—an operational advantage in toll manufacturing facilities where storage conditions are not validated to Class 100 cleanroom standards. The resulting urea derivatives exhibit herbicidal activity on Echinochloa crus-galli with an ED50 of 18 g ha−1 in post-emergence greenhouse trials; substitution of 2-aminobenzothiazole in the same structure causes a drop in activity (ED50 > 50 g ha−1), ascribed to faster metabolic N-demethylation in the target weed.
Commercial logistics must account for the substance’s classification under the Globally Harmonized System (GHS) as Acute Toxicity Category 4 (oral, H302) and Skin Sensitisation Category 1 (H317), based on REACH-registered dossier data. Packaging in fibre drums with a conductive polyethylene inliner prevents static charge accumulation during pneumatic transfer, while warehouse storage is specified at temperatures not exceeding 30 °C with exclusion of direct sunlight per ICH Q1A(R2) photostability guidance. The compatibility with common elastomeric seals used in isotainer discharge ports has been evaluated; ethylene-propylene-diene monomer (EPDM) gaskets show +3.2 % mass swell after 72-hour immersion in saturated toluene slurry at 25 °C, remaining within the acceptable limit of <5 % set by the plant’s mechanical integrity programme. No incipient exothermic activity is observed in accelerating rate calorimetry (ARC) below 250 °C under nitrogen, classifying the material as thermally benign for standard unit operations.
