Benzothiazole, 6-Bromo-2-Chloro-

Production of C.I. Disperse Blue 148—a monoazo dye exhibiting a pronounced bathochromic shift and exceptional wash fastness on polyethylene terephthalate substrates—depends on the quantitative ammonolysis of 6-bromo-2-chlorobenzothiazole to furnish the diazo component 2-amino-6-bromobenzothiazole. In a batch regime aligned with OEKO-TEX® STANDARD 100 Annex 6 and ZDHC MRSL 3.1, the halogen-exchange amination is performed within a 3,000 L Hastelloy C-276 jacketed shell-and-tube reactor charged with 28% aqueous ammonia at a molar ratio of 8.2:1 relative to the benzothiazole substrate; the addition rate of the substrate is fixed at 1.0 molar equivalent, while 0.12 wt% tetrabutylammonium bromide is introduced as a phase-transfer accelerator to suppress the 2-hydroxy by-product that forms when the aqueous-organic interfacial layer stagnates below 120 rpm tip speed. The reaction mass is held at 148°C ± 2°C under an autogenous pressure of 3.2 MPa for 14 hours, after which the crude 2-amino-6-bromobenzothiazole wet cake is isolated by precipitation at pH 9.5 and reslurried in 85% phosphoric acid at −3°C. Diazotization proceeds by controlled addition of 40% sodium nitrite solution over 90 minutes, and the resulting diazonium salt is immediately coupled with N,N-diethyl-m-toluidine in a second vessel equipped with a disappearing-filament stirrer that maintains turbulent dispersion at Reynolds number > 10,000. The crude dye undergoes hot filtration through a 0.5 µm sintered metal membrane, followed by spray drying to a residual moisture content of < 1.0%. The terminal commercial product, C.I. Disperse Blue 148 (CAS 61968-52-3), is dosed into polyester exhaust-dyeing formulations at 1.0–3.0% o.w.f. at 130°C, and every batch must demonstrate an uncoupling arylamine release below 150 mg/kg when tested according to EN ISO 17234-1:2015 with GC-MS quantification of the released 2-amino-6-bromobenzothiazole residues.

In therapeutic programs targeting dual-specificity tyrosine-phosphorylation-regulated kinase (DYRK) and aurora kinase inhibition, the regioselective functionalization of 6-bromo-2-chlorobenzothiazole dictates the stereoelectronic topology of the ATP-binding pocket antagonist. The route relies on a chemoselective Buchwald-Hartwig amination at the 2-chloro position employing 4-morpholinoaniline, retaining the 6-bromo substituent intact for a subsequent Suzuki-Miyaura cross-coupling that installs a 4-cyanophenyl pharmacophore. Process validation under ICH Q7 (GMP for Active Pharmaceutical Ingredients) designates the compound as a regulatory starting material with a fully codified impurity profile: specification requires ≥ 99.5 area% by HPLC (220 nm), single unknown impurity ≤ 0.10%, and residual isopropyl acetate ≤ 500 ppm. In the key coupling step executed in a Corning® Advanced-Flow™ G1 SiC reactor (channel hydraulic diameter 1.0 mm, total internal volume 10 mL), a feed stream of 6-bromo-2-chlorobenzothiazole solution (1.00 equiv., 0.15 M in THF) is merged with a stream containing 4-cyanophenylboronic acid (1.18 equiv.), Pd(dppf)Cl₂·CH₂Cl₂ (0.8 mol%), and 2.5 M aqueous K₃PO₄ at a total flow rate of 12 mL/min with a residence time of 48 seconds at 115°C and 6 bar back-pressure. This continuous-flow protocol reduces the homocoupled biphenyl impurity below 0.30% and suppresses palladium carryover in the isolated intermediate to ≤ 10 ppm, a prerequisite before deprotection. The final substance, a preclinical Aurora A/B inhibitor candidate, is crystallized from 2:1 heptane/ethyl acetate to yield a free-flowing white powder conforming to ICH Q3D Elemental Impurity Class 1 limits, with an overall four-stage yield of 71% from 6-bromo-2-chlorobenzothiazole. Full documentation is structured for a Type II Drug Master File submission with verification against USP 〈232〉/〈233〉 and Ph. Eur. 5.20 elemental impurities protocols.

When constructing substituted benzothiazole-6-carboxylic acid esters as herbicide safeners for chloroacetamide-based pre-emergents, the 2-chloro group of 6-bromo-2-chlorobenzothiazole functions as a transient handle that is displaced with branched alkyl thiols, and the soil mobility index measured by OECD TG 121 partitioning correlates strongly with the hydrolysis half-life of the 2-substituent. Consequently, the chlorine atom is retained until the penultimate step to moderate early-stage leaching. In a representative campaign aligned with the FAO/WHO Manual on Development and Use of Pesticide Specifications (2018), 1.00 kg of 6-bromo-2-chlorobenzothiazole (1.00 equiv.) is dissolved in 8.5 L of anhydrous N,N-dimethylacetamide and cooled to 0–5°C; sodium hydride (1.15 equiv., 60% dispersion in mineral oil) is added portionwise, followed by dropwise addition of 2-ethylhexyl 3-mercaptopropionate (1.08 equiv.). The thiol-to-substrate addition ratio is held at 1.08:1 to prevent over-alkylation at the thiolate stage that would generate a non-functional thioether dimer and reduce active yield below 88%. Downstream, the thioether is oxidized to the sulfoxide by 30% hydrogen peroxide catalyzed in a titanium silicalite TS-1 fixed-bed column operated at 45°C with a liquid hourly space velocity of 0.35 h⁻¹; this heterogeneous catalytic oxidation eliminates metal salt contamination that distorts the soil half-life predictability assessed via OECD TG 307. After quenching and phase separation, the 6-bromo-2-((3-((2-ethylhexyl)oxy)-3-oxopropyl)sulfinyl)benzothiazole is telescoped into a Suzuki coupling with 3-carboxyphenylboronic acid catalyzed by PdEnCat™ 40 (0.25 mol%) at 80°C to deliver the safener ester. The final product is formulated as an emulsifiable concentrate carrying 120 g/L active ingredient, and every production batch is screened for dioxin-like PCB congeners (≤ 0.01 mg/kg) and residual palladium (≤ 50 ppb) per JMPR 2020 residue chemistry guidelines. The safener is tank-mixed with S-metolachlor at a safener:herbicide ratio of 1:20 and applied in maize at 1.2 kg a.i./ha, with field dissipation monitored through consecutive soil core sampling at 0–15 cm depth.

A cross-segment comparison of impurity ceilings and mandated compliance instruments across the downstream value chains of 6-bromo-2-chlorobenzothiazole is compiled in the following reference table.

Poly(2,6-benzothiazole-alt-9,9-dioctylfluorene) copolymers processed via doctor-blade coating for inverted organic photovoltaic cells demand a brominated monomer with fewer than 50 ppm homocoupling defects, a specification directly traceable to the oxidative addition kinetics of 6-bromo-2-chlorobenzothiazole on Pd₂(dba)₃/XPhos catalytic systems. The monomer preparation strategy retains the 2-chloro leaving group as an orthogonal blocking site that remains inert throughout the polycondensation, enabling subsequent end-capping with 4-fluorobenzonitrile without perturbing the HOMO level below −5.4 eV. Compliance with IEC 62321-8:2017 and the EU RoHS Directive 2015/863 is embedded in the quality agreement, requiring the finished organic photovoltaic module to pass limit values for restricted phthalates and polybrominated biphenyls; the monomer purity specification is fixed at ≥ 99.92% by UPLC-UV (254 nm) with palladium content ≤ 20 ppm via ICP-MS. In the production-scale Suzuki polycondensation conducted in a 200 L glass-lined reactor with a retreat-curve impeller, the stoichiometric balance between 6-bromo-2-chlorobenzothiazole (1.0000 mol) and 9,9-dioctylfluorene-2,7-diboronic acid bis(pinacol) ester (1.0000 mol) is governed by mass-flow metering with an accuracy of ±0.15 g per charge. The catalyst system consists of Pd₂(dba)₃ (0.75 mol%) and XPhos (3.0 mol%) in a 4.5:1 toluene/2-methyltetrahydrofuran mixture containing 2.0 M aqueous K₂CO₃ (6.0 equiv.), with the reaction held at 97°C for 52 hours. The crude polymer is precipitated into methanol at 10× volume and sequentially extracted with acetone, hexane, and dichloromethane in a Soxhlet cascade; the dichloromethane fraction with Mₙ > 45 kDa (GPC vs. polystyrene standards, ISO 13885-1:2020) is retained as the photoactive donor. Formulated with PC₇₁BM at a 1:1.5 weight ratio and slot-die coated onto ITO/PEDOT:PSS substrates, devices record power conversion efficiencies of 6.8–7.2% under AM 1.5G illumination (100 mW/cm²) with an external quantum efficiency onset at 685 nm. The absence of residual 6-bromo-2-chlorobenzothiazole monomer in the final film is verified by TOF-SIMS to prevent trap-state formation.

Acid pickling and matrix acidizing in oilfield services require corrosion inhibitors that form stable mixed-type adsorption layers on low-carbon steel, and 2-hydrazino-6-bromobenzothiazole—obtained directly from 6-bromo-2-chlorobenzothiazole by nucleophilic substitution with hydrazine—delivers an inhibition efficiency exceeding 93% at a concentration of 200 mg/L in 1.0 M hydrochloric acid at 30°C. The production protocol, anchored to ASTM G31-72 (Reapproved 2019) standardized immersion testing and NACE TM0169-2000 electrochemical validation, initiates inside a 1,500 L enamel-lined autoclave where 250 kg of 6-bromo-2-chlorobenzothiazole (1.00 equiv.) is suspended in 95% ethanol (700 L) and 99% hydrazine hydrate (3.60 equiv.) is metered at 25°C. The formulation ratio translates to a 1.20:1 hydrazine N-atom to substrate molality specifically calibrated to suppress generation of the symmetrical 2,2′-hydrazobisbenzothiazole by-product, an insoluble sludge that reduces filterability below 0.15 m²/h on a 0.5 m² plate-and-frame filter press when its fraction exceeds 2.8%. The reaction mass is heated to reflux (80°C) for 16 hours, then vacuum-distilled under a final pressure of 50 mbar at 65°C to strip residual hydrazine and ethanol. The crude product is recrystallized from 85% isopropanol with 0.5 wt% activated carbon, yielding off-white needles with a melting point of 168–170°C and a purity of ≥ 99.0% by HPLC. For downstream field deployment, the inhibitor is compounded at 5.0–8.0 wt% with propargyl alcohol as a synergist and isopropanol as a solvent to deliver a low-viscosity concentrate. Weight-loss coupon testing per ASTM G1-03 on AISI 1018 steel panels with a 600-grit surface finish must record a corrosion rate below 0.45 mm/year for the blend to be qualified under NACE MR0175/ISO 15156 for sour service environments. Electrochemical impedance spectroscopy confirms that the 2-hydrazino-6-bromobenzothiazole film maintains its integrity through 48 hours of continuous immersion, sustaining a charge-transfer resistance above 850 Ω·cm² with no evidence of localized pitting in potentiodynamic scans conducted at 0.5 mV/s.

High-performance thin-film-transistor (TFT) liquid crystal mixtures for fringe-field switching (FFS) modes require constituent molecules whose dielectric anisotropy (Δε) surpasses +15.0 while rotational viscosity (γ₁) remains below 100 mPa·s at 20°C. The 6-bromo-2-chlorobenzothiazole architecture is exploited to construct 2,6-disubstituted benzothiazole mesogens where the 2-position is elaborated to a 4-cyanophenyl unit and the 6-bromo acts as the anchor for a 4-(trans-4-propylcyclohexyl)phenyl tail via palladium-catalyzed C–C cross-coupling. Manufacturing of the monomer-grade intermediate enforces IEC 61747-2-1:2013 for nematic liquid crystals, capping total metal ion content at < 10 ppb and chloride residues at < 1.0 mg/kg to forestall image-sticking artifacts caused by ionic drift under a 5 V DC offset. Inside an ISO Class 7 cleanroom, 1.00 equiv. of 6-bromo-2-chlorobenzothiazole is dissolved in anhydrous 2-methyltetrahydrofuran (Karl Fischer titration < 30 ppm) and reacted with 4-(trans-4-propylcyclohexyl)phenylzinc bromide (1.12 equiv.) mediated by Pd(PPh₃)₄ (0.5 mol%) at 55°C for 8 hours. The resulting 2-chloro-6-(4-(trans-4-propylcyclohexyl)phenyl)benzothiazole intermediate is telescoped into a second Suzuki step with 4-cyanophenylboronic acid (1.05 equiv.) using PdCl₂(Amphos)₂ (0.15 mol%) in THF/water at reflux. Purification proceeds by flash chromatography on neutral alumina (activity grade I) followed by triple recrystallization from toluene/acetonitrile (3:1) until the individual unknown area percentage falls below 0.01% by UPLC. The finished mesogen exhibits a melting point of 138.2°C, a clearing point of 234.5°C, and is blended at 12–18% by weight into host mixtures to realize a threshold voltage (V₁₀) of 1.45 V in a 3.5 µm cell gap. Every production lot is released against IEC 62321-12:2022 for polybrominated biphenyls and is accompanied by a Certificate of Compliance affirming suitability for integration into television display panels under global extended producer responsibility frameworks.