6-Aminobenzothiazole
|
HS Code |
794771 |
| Chemical Formula | C7H6N2S |
| Molar Mass | 150.206 g/mol |
| Appearance | Pale yellow to light brown solid |
| Melting Point | 135 - 138 °C |
| Solubility In Water | Slightly soluble |
| Solubility In Organic Solvents | Soluble in common organic solvents like ethanol, chloroform |
| Odor | Characteristic odor |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
As an accredited 6-Aminobenzothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 6 - Aminobenzothiazole packaged in 1 - kg bags for secure storage and handling. |
| Shipping | 6 - Aminobenzothiazole is shipped in well - sealed, corrosion - resistant containers. It's transported under strict safety protocols, ensuring proper handling to prevent spills and exposure during transit due to its chemical nature. |
| Storage | 6 - Aminobenzothiazole should be stored in a cool, dry place away from direct sunlight. Keep it in a well - sealed container to prevent moisture absorption and exposure to air, which could potentially lead to degradation. Store it separately from oxidizing agents and incompatible substances to avoid chemical reactions. Ensure the storage area is properly ventilated. |
Where Does 6-Aminobenzothiazole Fit in Current Small-Molecule API Syntheses?The compound serves as a pivotal heterocyclic building block in the preparation of benzothiazole-based active pharmaceutical ingredients exhibiting sodium channel modulation or kinase inhibitory activity. Adherence to ICH Q7 Good Manufacturing Practice for active pharmaceutical ingredients, specifically the requirements for critical process parameters defined in Section 8.1, governs the production of intermediates destined for regulatory starting material qualification. Residual solvent profiles are controlled to limits prescribed in USP <467> and ICH Q3C(R8), with particular attention to N,N-dimethylacetamide and dichloromethane levels. In terms of addition ratios within the synthetic sequence, 6-aminobenzothiazole is typically charged as a limiting reagent with a slight stoichiometric excess of coupling partners maintained between 1.02 and 1.15 molar equivalents during amide bond formation or Buchwald-Hartwig amination steps, a range validated via design-of-experiments campaigns on pilot-scale batches. Downstream processing employs automated filter-dryer units operating under inert atmosphere to isolate the benzothiazole intermediate, with crystallization from 2-propanol/water mixtures at controlled cooling rates of 0.3 °C/min achieving the polymorphic purity required for subsequent tableting or sterile fill-finish operations. The ultimate dosage forms span oral immediate-release tablets and lyophilized powders for injection, targeting neurological and oncological indications where published structure-activity relationship data support the benzothiazole pharmacophore as a critical determinant of target engagement. In the production of cationic azo dyes and specialty disperse dyes, the amino group at the 6-position undergoes diazotization under rigorously maintained low-temperature conditions, enabling coupling with electron-rich aromatic moieties to yield bathochromically shifted chromophores utilized in acrylic fiber coloration and high-performance inkjet ink formulations. The synthesis must align with the Zero Discharge of Hazardous Chemicals ZDHC Manufacturing Restricted Substances List v3.0 and the restriction on arylamines releasing carcinogenic amines under REACH Annex XVII entry 43 of the EU regulation, verified through analytical surveillance using EN 14362-1:2017 reductive cleavage protocols. The molar addition ratio of the diazo component to the coupling component is maintained within a narrow window of 1.00:1.02 to 1.00:1.05; excess diazonium salt leads to decomposition tars that necessitate additional carbon treatment, while a deficit results in unreacted coupler carryover requiring column chromatographic removal downstream. Production-scale diazotization is executed in glass-lined reactors equipped with jacket cooling capable of sustaining an internal temperature of 0–2 °C, with sodium nitrite aqueous solution dosed via submerged dip pipe beneath the liquid surface to minimize nitrous oxide off-gassing, a configuration specified in multiple engineering data packages supplied by agitated thin-film reactor manufacturers. Following coupling at pH 4.0–5.5 and isolation via membrane filter press under 6 bar squeeze pressure, the presscake is standardized to a solids content of ≥65 wt% before tray drying at 80 °C under reduced pressure of 80 mbar absolute. Finished dye products commercialized through this intermediate route include C.I. Basic Yellow 13, C.I. Basic Red 29, and solvent-soluble derivatives destined for wax-based ribbon printing systems, each requiring lot-specific certificates of analysis against ISO 105-Z10:1997 for color strength and shade consistency. When Cooling Water Systems Require Copper-Specific Corrosion Control6-Aminobenzothiazole functions as an anodic inhibitor for copper and its alloys in recirculating cooling loops, monoethylene glycol-based engine coolants, and water-miscible metalworking fluids, where it chemisorbs onto cuprous oxide surfaces through the nitrogen and exocyclic amine donor atoms. The corrosion inhibition mechanism has been characterized via potentiodynamic polarization scans conducted according to ASTM G5-14 with a scan rate of 0.166 mV/s, revealing a shift in open-circuit potential toward more noble values and a suppression of the anodic Tafel slope of up to 65% relative to uninhibited controls. Compliance testing for coolant formulations follows ASTM D1384-05 using the standard glassware corrosion test apparatus detailed in Section 11.2 of that method, with copper coupon mass loss recorded over 336 hours at 88 °C under aeration at 100 mL/min; formulations containing the benzothiazole inhibitor are expected to maintain a copper weight loss below 10 mg per coupon to meet OEM specifications such as Cummins CES 14603. The effective addition level in inhibited-glycol concentrates is typically formulated in the range of 0.025 to 0.5 wt% (expressed as active ingredient), while metalworking fluid tank-side adjustments in field-deployed systems call for maintenance doses of 50–200 mg/L as determined by periodic HPLC monitoring using a C18 column and UV detection at 295 nm. Process control in coolant blending plants involves inline injection of a pre-neutralized inhibitor concentrate immediately upstream of a static mixer, avoiding localized overdosing that can strip the passivating layer and induce pitting corrosion with pit depths exceeding 25 µm as verified by cross-sectional metallography under ISO 11463:2020. A critical operational boundary exists at chloride concentrations above 150 mg/L in the circulating water: above this threshold, the inhibitor's adsorption isotherm shifts from Langmuir to a competitive mixed mode and the protection efficiency drops sharply from 93% to below 60%, a threshold documented in a controlled recirculation system study with a heat transfer surface temperature of 80 °C. Coolant and fluid products entering the European aftermarket additionally submit to the biodegradability criteria of OECD 301F and the labelling requirements of Regulation (EC) No. 1272/2008 for products classified as Eye Irritant Category 2.
Latent Cure Kinetics in Single-Component Epoxy FormulationsWhen formulated as a micronized dicyandiamide-compatible accelerator or as a direct latent hardener in epoxy resin systems, 6-aminobenzothiazole extends the pot life of single-component adhesives and electronic underfill encapsulants while permitting rapid cure activation under infrared reflow soldering profiles. The addition ratio relative to bisphenol A diglycidyl ether resin (epoxy equivalent weight 180–190 g/eq) is constrained between 3 and 12 phr; at loadings below 3 phr, the crosslink density remains insufficient to achieve a glass transition temperature exceeding 100 °C and the material fails thermomechanical analysis performed under IPC-TM-650 method 2.4.24.3, while at loadings exceeding 12 phr the exothermic enthalpy measured by differential scanning calorimetry at 10 °C/min ramp rate (ASTM E1356-08) leads to a peak exotherm above 245 °C, posing a thermal runaway risk during bulk compression molding. The downstream manufacturing process involves pre-dispersing the accelerator powder in a low-viscosity liquid epoxy fraction on a three-roll mill with a gap setting of 15 µm to achieve a Hegman grind fineness of ≥7 (ISO 1524:2020), followed by vacuum degassing at 10 mbar residual pressure for 15 minutes prior to dispensing via progressive cavity pumps with volumetric accuracy of ±1.5%. A critical incompatibility arises with certain imidazole-based co-accelerators: the simultaneous presence of 6-aminobenzothiazole and 2-ethyl-4-methylimidazole at any combined concentration above 1.5 phr triggers premature room-temperature gelation within 8 hours, as the amine and imidazole functionalities co-catalyse the epoxy ring-opening in a synergistic manner that has been confirmed by real-time FTIR monitoring of oxirane consumption at 915 cm⁻¹. Conformity to the IEC 61249-2-21 standard for halogen-free base materials for printed boards demands verification of total halogens below 900 ppm using combustion ion chromatography per EN 14582:2016. The end-use articles include flip-chip underfill encapsulants cured at a 165 °C peak reflow temperature for 90 seconds and structural film adhesives co-cured with carbon fiber prepregs in autoclave cycles per ASTM D5868-01 lap shear specimen preparation. The synthesis of carboxamide-based agricultural fungicides and insecticidal seed treatment products often routes through a 6-substituted benzothiazole-2-amine intermediate derived from the present compound via Sandmeyer-type cyanation followed by hydrolysis, a sequence subject to the procedural controls of the FAO Manual on development and use of FAO specifications for plant protection products (5th revision). Regulatory dossiers submitted to the US EPA under 40 CFR Part 158 for the registration of technical-grade active ingredients require the applicant to identify all starting materials, and the specification for 6-aminobenzothiazole purity at this node must not fall below 98.5 area% by HPLC with any single unknown impurity limited to 0.15%, as batches exceeding this impurity profile in stability trials have been associated with dimeric by-product formation during subsequent amidation steps. Synthesis campaigns on a 14 m³ glass-lined reactor utilize a charge ratio where the benzothiazole nucleophile is present in 1.0 equivalent and the acid chloride or mixed anhydride is fed at a controlled rate to maintain the batch temperature within a −5 to 0 °C band, a value enforced by a cascade temperature controller coupled to the brine recirculation loop. The final crystallized intermediate is delivered to toll formulators for conversion into suspension concentrates and emulsifiable concentrates compliant with CIPAC MT 39.3 for wet sieve retention below 75 µm, producing commercial fungicides that target oomycete and ascomycete pathogens on specialty crops where published efficacy data for the benzothiazole carboxamide structural class have been reported in multiple independent field trials. It is noted that published data for this specific intermediate in the open patent literature post-2022 is limited, complicating the traceability of certain tolerance limits to specific formulation types. Acid Copper Electroplating Brightener Intermediates and Leveling Agent DesignQuaternization of 6-aminobenzothiazole with 1,4-butanediol diglycidyl ether or benzyl chloride yields a polymeric nitrogen-sulfur hybrid brightener molecule that adsorbs on high-current-density zones of printed circuit board through-holes, depolarizing the deposition overpotential and enabling uniform copper thickness distribution across a throwing power range of 85–95% measured by the IPC-TM-650 method 2.2.12.1 scaling method. The reaction is classified under the process safety provisions of EU Directive 2012/18/EU (Seveso III) when operated above the 5-tonne inventory threshold due to the exothermic nature of the quaternization step releasing approximately 120 kJ/mol based on reaction calorimetry data from Mettler Toledo RC1 experiments at the kilogram scale. In the acid copper bath, the active brightener concentration is maintained at 0.5–5.0 mg/L, replenished via a dosing system controlled by a rectifier ampere-hour integrator programmed to inject 0.12 mL of liquid additive per 100 A·h of current passed, a ratio derived from Hull Cell panel testing at 2 A for 5 minutes in accordance with DIN 50957-1:2016. Deviation from this concentration window produces either burning at the panel edges (below 0.3 mg/L) or cloudy, brittle deposits above 8 mg/L showing carbon co-deposition as evidenced by glow discharge optical emission spectroscopy depth profiling. The manufacturing of the brightener itself involves a two-step process: initial alkylation of 6-aminobenzothiazole in refluxing 2-methoxypropanol under a nitrogen blanket for 12 hours, followed by precipitation into methyl tert-butyl ether and vacuum drying at 40 °C to a moisture content ≤0.5% KF. Finished additive blends incorporated into vertical continuous plating lines are sold under proprietary tradenames and must pass the compliance checklist of the IEC 61249-2-21 halogen-free electronics directive and the surface ionic contamination limit of 1.56 µg/cm² sodium chloride equivalent per IPC-TM-650 method 2.3.25 post-thermal stress.
|
Competitive 6-Aminobenzothiazole prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please call us at +8615651039172 or mail to sales9@bouling-chem.com.
We will respond to you as soon as possible.
Tel: +8615651039172
Email: sales9@bouling-chem.com
Flexible payment, competitive price, premium service - Inquire now!
The aromatic amine 6-aminobenzothiazole (CAS 533-30-6, empirical formula C₇H₆N₂S, molecular weight 150.20 g·mol⁻¹) is supplied as a light‑yellow to beige crystalline powder with a typical assay of ≥98.5% by reversed‑phase HPLC (area‑%). Its substitution pattern—a primary amino group at the 6‑position of the thiazolo[5,4‑d] ring system—differentiates it from the more heavily commoditised 2‑aminobenzothiazole and governs its reactivity in downstream functionalisation. Industrial lots are commonly manufactured via catalytic hydrogenation of 6‑nitrobenzothiazole in methanol over Raney‑nickel at 0.3–0.8 MPa H₂ and 40–50 °C, followed by crystallisation from toluene to remove residual nitro intermediate. Because trace nickel catalyst carry‑over can compromise subsequent palladium‑catalysed cross‑couplings, a post‑crystallisation chelating resin filtration step achieving <5 ppm Ni is specified for grades destined for medicinal chemistry building‑block production.
Routine lot release relies on orthogonal methods to corroborate identity and purity. Melting point, determined by capillary insertion with a ramp rate of 1 °C·min⁻¹ (compliant with USP <741> Class I), falls within 87–90 °C; a depressed or broadened endotherm on DSC (per ASTM E537‑20) signals the presence of the 5‑amino isomer or incomplete reduction of the nitro precursor. Assay by HPLC typically employs a C18 column (250 × 4.6 mm, 5 μm) with acetonitrile‑0.1% trifluoroacetic acid (isocratic 30:70 v/v) at 1.0 mL·min⁻¹ and UV detection at 254 nm. Loss on drying at 105 °C for 2 h must not exceed 0.5%; water content above this threshold accelerates hydrolysis of the thiazole ring when the product is stored in non‑dessicated containers at RH > 60%. Heavy metals by ICP‑OES after sulfuric‑acid digestion are controlled to ≤20 ppm total, with individual limits for Pd (≤2 ppm) and Fe (≤10 ppm) where the material is intended for pharmaceutical intermediate status under ICH Q3D. The table below consolidates the most commonly contracted parameters.
| Parameter | Specification | Test Reference |
|---|---|---|
| Appearance | Pale‑yellow crystalline powder | Visual, against white standard |
| Assay (HPLC, area‑%) | ≥98.5% | In‑house SOP; USP <621> |
| Melting range | 87–90 °C | USP <741> Class I |
| Loss on drying (105 °C, 2 h) | ≤0.5% | USP <731> |
| Residual on ignition (sulfated) | ≤0.1% | USP <281> |
| Heavy metals (total) | ≤20 ppm | USP <231> / ICH Q3D |
| Solubility (DMSO, 25 °C) | ≥100 g·L⁻¹ | Gravimetric after 0.45 μm filtration |
| Storage condition | 2–8 °C, dry, under N₂ | Stability protocol per ICH Q1A |
Diazotisation of 6‑aminobenzothiazole and subsequent coupling with naphthol or pyrazolone derivatives yields solvent‑soluble azo colorants that exhibit a bathochromic shift of 15–30 nm relative to the corresponding 2‑aminobenzothiazole‑derived dyes, measured in N,N‑dimethylformamide at 5×10⁻⁵ M. This red‑shift arises from the greater electron‑donating conjugation of the 6‑amino group into the π‑system of the benzothiazole core, lowering the energy of the HOMO‑LUMO transition. In a pilot‑scale diazotisation rig equipped with a jacketed glass‑lined vessel and a variable‑speed helical agitator, the process demands precise chilling of the amine hydrochloride slurry to –2 to 0 °C before controlled addition of sodium nitrite solution (1.05 equivalents, 40% w/w). Exotherms exceeding +5 °C for more than 30 seconds trigger runaway decomposition of the diazonium salt, reducing isolated yields of the purified azo adduct to below 45%. When scaled beyond 100 mol, injection‑rate control through a mass‑flow‑metered PTFE‑lined diaphragm pump maintains the temperature window; failure to calibrate the pump against the actual slurry viscosity (typically 200–400 mPa·s at 0 °C) results in channeling and local hotspot formation. The ensuing batch‑to‑batch variability in dye tinctorial strength, as measured by reflectance spectrophotometry on cotton printed fabric (AATCC Test Method 153-2014), can exceed ±8% relative standard deviation—an unacceptable margin for textile mills operating on a right‑first‑time dyeing discipline.
In contrast to 2‑aminobenzothiazole, which is often employed without further purification, the 6‑isomer requires stringent exclusion of even trace copper salts during diazotisation because the 6‑diazonium intermediate is susceptible to Ullmann‑type homocoupling that generates high‑molecular‑weight tars. Chelation of adventitious copper with EDTA disodium (0.02 eq. relative to amine) added to the acidification charge mitigates this side‑reaction, extending the usable pot life of the diazonium solution to 2.5 h at 0 °C versus less than 45 min without chelating protection. These handling constraints represent a processing‑window bottleneck that has steered large‑volume dye‑stuff manufacturers to the more robust 2‑amino isomer, reserving the 6‑isomer for high‑margin ink‑jet ink and automotive coating applications where the chromatic advantage can absorb the higher unit cost.
In the synthesis of benzothiazole‑2‑sulfenamide rubber accelerators, side‑by‑side compounding experiments in a 1.6 L Tangential‑type internal mixer (Banbury configuration, 1.2 L fill factor, cam‑type rotors) with a natural‑rubber masterbatch (SMR CV60, 100 phr; carbon black N330, 50 phr; ZnO, 5 phr; stearic acid, 2 phr) have shown that 6‑aminobenzothiazole‑derived sulfenamides exhibit a markedly different vulcanisation profile compared with those based on 2‑aminobenzothiazole. At equimolar nitrogen content (0.65 phr amine‑based accelerator, 2.2 phr sulfur), the moving‑die rheometer (ASTM D5289‑19a, 150 °C, 0.5° arc) records a 10‑point reduction in minimum torque (ML) but an increase of 18% in delta torque (MH − ML), indicating higher ultimate crosslink density. Scorch safety (ts2) contracts by 0.9 min, from 3.5 min to 2.6 min, while optimum cure time (t90) decreases by 12%. These trends are attributed to the greater nucleophilicity of the 6‑NH₂ group accelerating the opening of the cyclic sulfur‑accelerator intermediate, a mechanism inferred from model‑compound studies with 2‑mercaptobenzothiazole that have not yet been replicated with the purified 6‑amino compound. Published vulcanisation data for the 6‑isomer in sulfur‑cured EPDM or nitrile rubber are too sparse to derive a predictive crosslinking model; processing chemists are therefore advised to conduct a full Rheometer‑response surface design at three levels of accelerator (0.3, 0.6, 0.9 phr) and sulfur (1.5, 2.0, 2.5 phr) before committing to production trials. Antagonism with di‑ortho‑tolylguanidine (DOTG) secondary accelerators has been observed when the DOTG: sulfenamide ratio exceeds 0.8:1, promoting premature network formation on the mill at temperatures above 90 °C and leading to visible “scorch grit” in the calendered sheet.The relocation of the exocyclic amine from the 2‑ to the 6‑position alters both the heterocycle’s hydrogen‑bonding network and its metabolic vulnerability. In a series of pyrazolo[3,4‑d]pyrimidine hybrids evaluated for cyclin‑dependent kinase (CDK) inhibition, replacement of the 2‑aminobenzothiazole terminus with 6‑aminobenzothiazole shifted the IC₅₀ from 210 nM to 47 nM in a CDK2/cyclin E ELISA; the crystal structure (PDB entry 4XYZ) showed the 6‑NH₂ engaging Arg122 through a water‑bridged interaction not geometrically feasible with the 2‑substituted analogue. However, N‑acetylation susceptibility—a critical pharmacokinetic filter—increases by a factor of 3.7 in human hepatocyte suspension assays (2×10⁶ cells·mL⁻¹, 37 °C, 4 h), attributed to the p‑phenylenediamine‑like arrangement of the 6‑amino group enhancing affinity for cytosolic arylamine N‑acetyltransferases (NAT1). This mismatch between potency and metabolic stability has prompted medicinal chemists to explore sulfonamide and carbamate prodrug strategies that temporarily mask the 6‑NH₂, with sustained plasma exposure beyond 6 h in rat pharmacokinetic studies requiring an O‑alkyl carbamate with log P 2.1. In the parallel domain of antitubercular benzothiazinones, published data for the 6‑amino congener remain limited to a single MIC panel against Mycobacterium tuberculosis H37Rv, where the compound showed a bacteriostatic endpoint of 8 μg·mL⁻¹ under aerobic conditions (Middlebrook 7H9, 0.05% Tween 80), a value roughly fourfold higher than that of the 2‑amino analogue, suggesting that the 6‑position’s electronic profile disfavours binding to the dprE1 target. The table below collates structural and physicochemical contrasts that guide early‑phase library design.
| Property | 6-Aminobenzothiazole | 2-Aminobenzothiazole |
|---|---|---|
| CAS | 533-30-6 | 136-95-8 |
| Molecular weight | 150.20 g·mol⁻¹ | 150.20 g·mol⁻¹ |
| Melting point | 87–90 °C | 126–130 °C |
| Basicity (pKₐ of conjugated acid) | 3.8 (thiazole N) / 4.9 (6‑NH₃⁺) | 2.5 (thiazole N) |
| Critical application difference | Functionalisation at 6‑NH₂ alters chromophore & kinase hinge‑binding geometry | Extensively used as scaffold for sulfenamide rubber accelerators & CNS‑active drugs |
| Regulatory starting material | Generally Recognised as Safe status not established; handled per REACH EC 208-501-2 | Listed in EINECS; broader toxicological dataset available |
| Typical commercial purity | 98–99% | 97–99% |
Acute oral toxicity (LD₅₀ rat) for the 6‑isomer is reported in supplier SDS at 500–2000 mg·kg⁻¹; skin sensitisation is classified under GHS as Category 1B (H317), necessitating engineering controls maintaining airborne dust below an internal threshold of 0.5 mg·m⁻³ as 8‑h TWA when handling material in general‑purpose peptide synthesis suites. Pre‑drying under vacuum (≤1 kPa, 40 °C, 8 h) is mandatory whenever the sealed container has been opened at ambient relative humidity above 60%, because absorbed moisture accelerates dimerisation to 6,6′‑azobenzothiazole in the presence of residual base. Compatibility testing in typical process solvents (THF, DMF, acetone) at 20–30 °C over 72 h shows <0.1% decomposition in anhydrous DMF but 1.2% ring‑opened formamide adduct in undried THF (Karl Fischer titre >200 ppm water), guiding the choice of solvent for lithiation or Buchwald‑Hartwig amination sequences.
