4-Bromobenzo[D]Thiazole
|
HS Code |
390286 |
| Chemical Formula | C7H4BrNS |
| Molecular Weight | 214.08 |
| Appearance | Solid (usually white to off - white powder) |
| Melting Point | Typically in the range of 180 - 184 °C |
| Solubility In Water | Low solubility in water |
| Solubility In Organic Solvents | Soluble in some organic solvents like dichloromethane, chloroform |
| Purity | Can be found in various purity grades, e.g., 95%, 98% etc. |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
As an accredited 4-Bromobenzo[D]Thiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 4 - Bromobenzo[D]Thiazole packaged in a sealed, labeled chemical - grade vial. |
| Shipping | 4 - Bromobenzo[D]Thiazole is shipped in secure, airtight containers, following strict chemical transportation regulations. These containers are cushioned to prevent breakage during transit and stored away from heat and incompatible substances. |
| Storage | 4 - Bromobenzo[D]Thiazole should be stored in a cool, dry, well - ventilated area. Keep it away from heat sources, open flames, and oxidizing agents. Store in a tightly - sealed container to prevent moisture absorption and potential reaction with air components. Ensure the storage location is out of reach of children and unauthorized personnel. |
Within the synthesis cascade of heterocyclic carboxamide fungicides targeting succinate dehydrogenase (SDH; EC 1.3.5.1), 4-bromobenzo[d]thiazole participates as a key electrophile in a chemo-selective C–Br bond activation sequence. The bromide substituent at the 4-position of the benzothiazole scaffold exhibits a distinct reactivity profile under palladium-catalyzed cross-coupling, enabling direct attachment of an aryl or heteroaryl bioisostere required for optimal enzyme inhibition in the ubiquinone-binding pocket. Compliance with EU Plant Protection Product Regulation (EC) No 1107/2009 necessitates that all technical-grade intermediates meet purity specifications aligned with FAO Specification Guidelines, particularly with respect to halogenated dioxin and dibenzofuran content, which must remain below the limit of detection (LOD < 0.01 mg/kg) as measured by high-resolution GC-MS per EPA Method 1613B. In a representative kilogram-scale campaign, 4-bromobenzo[d]thiazole (1.0 equiv) is coupled with (4-fluorophenyl)boronic acid (1.15 equiv) using PdCl₂(dppf)·CH₂Cl₂ (0.03 equiv) and potassium phosphate (2.0 equiv) in a degassed 1,4-dioxane/water mixture (4:1 v/v) at 80–85°C for 6 hours under a nitrogen blanket in a glass-lined 200 L reactor. The exotherm upon Pd pre-catalyst activation is controlled by gradual dosing to maintain ΔT ≤ 5°C, avoiding dehalogenation side reactions that elevate 4H-benzothiazole impurity beyond the permissible 0.15% area threshold. Post-reaction extractive workup with toluene, charcoal treatment, and crystallization from n-hexane/ethyl acetate yields the biaryl intermediate in 86–89% isolated yield with a chromatographic purity of ≥98.5% (HPLC, 254 nm, C18 column, acetonitrile/0.1% phosphoric acid gradient). The resulting intermediate is subsequently acylated with 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl chloride in dichloromethane at 0–5°C in the presence of triethylamine (1.3 equiv) to form the final fungicidal active ingredient—a second-generation SDHI compound registered for foliar spray application on cereals at a field rate of 100 g a.i./ha. Residual palladium limits in the final agrochemical product are stringently controlled to < 20 mg/kg, verified by ICP-MS following microwave-assisted acid digestion in accordance with EPA Method 6020B. This process chain underscores that the 4-bromo substituent dictates the regiochemistry of biaryl coupling, a requirement that the 5- or 6-bromo isomers cannot satisfy due to unacceptable steric congestion with the thiazole sulfur in the enzyme’s binding cavity.What Makes 4-Bromobenzo[d]thiazole an Indispensable Suzuki Coupling Partner in Kinase Drug Discovery?The benzothiazole heterocycle constitutes a privileged scaffold in ATP-mimetic kinase inhibitor design, and placement of a bromine atom at the 4-position furnishes an orthogonal synthetic handle that withstands multi-step transformations involving organometallic reagents, strong bases, and elevated temperatures. Structure-activity relationship (SAR) explorations targeting the hinge region of receptor tyrosine kinases (e.g., VEGFR-2, PDGFR-β) frequently rely on 4-bromobenzo[d]thiazole as the starting point for constructing extended aromatic systems that engage a hydrophobic back pocket. All manufacturing of 4-bromobenzo[d]thiazole designated for GMP starting material use complies with ICH Q7 guidelines, and certificate of analysis (CoA) must include residual inorganic bromide content (limit < 0.05% w/w, titration per USP <221>), heavy metals (lead < 5 ppm, cadmium < 2 ppm, mercury < 1 ppm per USP <232>/<233>), and single largest organic impurity ≤ 0.10% area via HPLC equipped with a photodiode array detector (detection wavelength 254 nm, column: Zorbax Eclipse XDB-C18, 150×4.6 mm, 3.5 µm). For a typical medicinal chemistry campaign aimed at an allosteric Bcr-Abl inhibitor candidate, the synthetic route involves a one-pot borylation–Suzuki sequence: 4-bromobenzo[d]thiazole (100 mmol, 1.0 equiv), bis(pinacolato)diboron (1.2 equiv), potassium acetate (3.0 equiv), and Pd(dppf)Cl₂ (0.03 equiv) are stirred in anhydrous 1,4-dioxane at 100°C for 16 hours, after which the intermediate boronate ester is treated directly with 2-chloro-4-(trifluoromethyl)phenyl triflate (1.1 equiv), aqueous K₂CO₃ (2 M, 3.0 equiv), and an additional charge of Pd(PPh₃)₄ (0.02 equiv) at 80°C for 8 hours. This telescoped process is executed in a pressure-rated Hastelloy reactor under an argon atmosphere to avoid catalyst poisoning by sulfur-containing volatiles. Column chromatography on silica gel (hexane/ethyl acetate 9:1) yields the targeted 4-aryl benzothiazole core in 72% yield with >99.0% purity after trituration with methanol. The molecule ultimately progresses to IND-enabling toxicology studies where its genotoxicity is assessed via the bacterial reverse mutation test (Ames test; OECD TG 471) and chromosomal aberration assay (OECD TG 473), with the impurity profile of the 4-bromobenzo[d]thiazole-derived building block directly affecting the outcome of these assays. A recurring bottleneck observed during scale-up to 20 kg batch size stems from the incomplete consumption of 4-bromobenzo[d]thiazole (typically 2–3% remains) when the boronic acid coupling partner is sterically hindered; iterative addition of 0.01 equiv Pd catalyst is employed to drive the reaction without exceeding a total Pd content that would require a metal scavenger step (e.g., Si-thiol-functionalised silica, acceptable bed volume 5% of batch weight) to meet the residual Pd specification of < 10 ppm in the drug substance.
OLED Host Material Engineering with 4-Br-BenzothiazoleVacuum sublimation of 4-bromobenzo[d]thiazole-derived host intermediates constitutes the decisive purification step that separates a laboratory-grade building block from a device-qualified electronic material capable of sustaining long-term operational stability in phosphorescent organic light-emitting diodes. The precursor, typically a 4-(9H-carbazol-9-yl)benzo[d]thiazole derivative obtained through palladium-catalyzed C–N coupling, enters a custom-built three-zone horizontal tube sublimator at a pre-purified state of 99.5% area (HPLC-UV). The system is evacuated to a base pressure of < 5×10⁻⁷ mbar with a turbomolecular pump backed by a dry scroll pump, and high-purity argon is metered as carrier gas at a flow rate of 10 sccm. The evaporation boat is maintained at 215°C ± 2°C, while the first deposition zone is held at 140°C and the second at 110°C; a cold finger near the pump inlet is cooled to 25°C to trap volatile fragments. A single sublimation pass lasting 8–12 hours recovers 35–45% of the charged mass as transparent, needle-like crystals on the 140°C collector. Post-sublimation purity assessed by HPLC-MS (APCI+, selected ion monitoring) and differential scanning calorimetry (ASTM E794-06) routinely reaches 99.98% with a melting point depression of less than 0.5°C. The criticality of this process resides in the elimination of trace bromide-containing homologues and non-luminescent chromophores that function as triplet-exciton quenchers; residual bromine content above 50 ppm, quantified by combustion ion chromatography (ASTM D7359), correlates directly with a reduction in the host triplet energy level (ET measured via low-temperature phosphorescence spectroscopy at 77 K) and accelerates roll-off in device external quantum efficiency. When integrated into a green-emitting PhOLED stack with Ir(ppy)₃ as the emitter at 8 wt% doping, the host material deposited by thermal evaporation (5×10⁻⁷ mbar, deposition rate 0.5 Å s⁻¹) onto an ITO/PEDOT:PSS substrate allows a luminance of 1000 cd m⁻² and an LT95 lifetime exceeding 500 hours under constant current drive (encapsulated with a glass lid and epoxy seal inside a nitrogen-filled glovebox with O₂ < 0.1 ppm and H₂O < 0.1 ppm). Device endurance measurements are conducted according to IEC 62341-6-1:2017, and the spectral radiance is monitored with a calibrated spectroradiometer. An operational boundary that must be observed is the incompatibility of the benzothiazole host with certain p-dopants based on hexaazatriphenylene derivatives, which induce a charge-transfer absorption band that depletes the exciton population; this restricts hole injection layer formulation to MoO₃ or F4-TCNQ.If Nitroreductase-Responsive Triggers Are Required, 4-Bromobenzothiazole Delivers a Modular Fluorogenic CoreWhen deploying a turn-on fluorescent sensor for imaging hypoxia-associated nitroreductase (NTR) activity in solid tumor models, the electron-deficient benzothiazole nucleus acts as an efficient fluorescence quencher until the enzymatic reduction event releases intramolecular charge transfer. The synthetic route for a typical activatable probe begins with Sonogashira alkynylation of 4-bromobenzo[d]thiazole, where the bromide is replaced by a nitrophenylacetylene handle. In an anhydrous tetrahydrofuran/triethylamine mixture (3:1 v/v), 4-bromobenzo[d]thiazole (1.0 mmol), 4-nitrophenylacetylene (1.2 mmol), Pd(PPh₃)₂Cl₂ (0.05 mmol), and CuI (0.10 mmol) are stirred under argon at 60°C for 18 hours in a flame-dried Schlenk tube shielded from ambient light. The crude 4-((4-nitrophenyl)ethynyl)benzo[d]thiazole is purified by flash chromatography (silica gel, dichloromethane/petroleum ether 1:3) to afford a yellow solid in 68% yield. Quaternization with methyl iodide in acetonitrile at 80°C for 24 hours furnishes the water-soluble benzothiazolium salt that displays negligible fluorescence (Φ < 0.01 in phosphate-buffered saline, pH 7.4). Exposure to purified E. coli nitroreductase in the presence of NADH (500 µM) results in the reduction of the nitro group to an amino donor, causing a bathochromic shift and a 50-fold fluorescence enhancement with emission at 520 nm upon excitation at 405 nm. The limit of detection for NTR is established at 0.5 ng mL⁻¹ (signal-to-noise ratio 3:1), and selectivity is validated against a panel of biological reducing agents and thiols. For live-cell imaging applications in the biopharmaceutical industry, the probe is tested for cytotoxicity according to the MTT assay protocol aligned with ISO 10993-5:2009, and the working concentration is kept below 10 µM to maintain cell viability above 90% after 24 hours. Confocal laser scanning microscopy with a 405 nm diode laser and a 500–550 nm bandpass filter confirms cytoplasmic localization; co-staining with Hoechst 33342 verifies nuclear exclusion. An operational limitation is the susceptibility of the benzothiazolium probe to non-specific protein binding in serum-rich media, which elevates background fluorescence and necessitates a pre-wash step with bovine serum albumin-blocked coverslips. Published data for the long-term photostability of this specific 4-bromobenzothiazole-derived probe in hypoxic tumor spheroids beyond 48 hours remains limited, and users performing extended time-lapse studies are advised to validate signal stability against the corresponding acetoxymethyl ester protective-group variant.The emergence of A–D–A type non-fullerene acceptors (NFAs) with narrow bandgaps has positioned 4-bromobenzo[d]thiazole as a viable terminal acceptor building block owing to its strong electron-withdrawing character and planar benzothiazole geometry facilitating intermolecular π–π stacking. In a representative synthesis of an ITIC-like small-molecule acceptor, 4-bromobenzo[d]thiazole is first formulated via Vilsmeier–Haack conditions (POCl₃/DMF, 95°C, 4 hours) to install an aldehyde at the 2-position, a transformation that proceeds regioselectively because the 4-bromo substituent directs electrophilic substitution to the most electron-rich carbon of the thiazole ring. The 4-bromo-2-formylbenzo[d]thiazole is then subjected to Stille cross-coupling with a distannylated indacenodithiophene (IDT) core; the reaction uses Pd₂(dba)₃ (0.04 equiv) and P(o-tol)₃ (0.16 equiv) in anhydrous toluene at 110°C for 24 hours in a sealed pressure tube with rigorous freeze-pump-thaw degassing. Crude yield after aqueous workup approaches 60%, but the major challenge is the presence of mono-coupled and dehalogenated byproducts that co-elute during conventional chromatography. Purification to device-grade quality requires a three-step sequence: silica gel column chromatography (chloroform/toluene 3:1), size-exclusion chromatography on Bio-Beads S-X1 with toluene as eluent, and triple recrystallisation from chloroform/methanol. Only when the HPLC purity on a porous graphitic carbon column (operated at 150°C to resolve structural isomers) reaches ≥ 99.95% and the residual tin content measured by ICP-OES per ISO 11885 falls below 15 ppm is the material deemed fit for photovoltaic evaluation. Residual tin above this threshold catalyses photooxidative degradation of the active layer, manifesting as a rapid decrease in fill factor during maximum power point tracking. Photovoltaic devices are fabricated in an inverted architecture (ITO/ZnO/active layer/MoO₃/Ag) and tested under AM 1.5G illumination at 100 mW cm⁻² calibrated with a KG5-filtered silicon reference cell in compliance with IEC 60904-2. The external quantum efficiency spectrum recorded on a Bentham PVE300 system reveals that the terminal benzothiazole unit red-shifts the lowest-energy absorption band by approximately 40 nm relative to a benzotriazole analogue, a shift attributed to the increased electronegativity of the thiazole ring. An encapsulated device under continuous light soaking at 65°C exhibits a T80 lifetime exceeding 1200 hours when the active layer is processed from o-xylene in a nitrogen-filled glovebox, but this stability sharply degrades if the benzothiazole acceptor contains bromide-containing impurities exceeding 0.1% area, as confirmed by quantitative ¹H NMR with an internal standard. The bromine impurity creates deep trap states that accelerate non-radiative recombination, as evidenced by an increase in dark current measured with a Keithley 2400 source-measure unit under reverse bias.
Phosphine Ligand Synthesis via Electrophilic Bromine DisplacementThe direct conversion of 4-bromobenzo[d]thiazole into a sterically and electronically tuned monophosphine ligand proceeds through halogen-lithium exchange followed by electrophilic quenching with a chlorodiarylphosphine, a sequence that preserves the benzothiazole moiety’s capacity to coordinate metal centres while introducing a soft phosphorus donor atom. In a rigorously dried 500 mL jacketed reactor under an argon atmosphere, 4-bromobenzo[d]thiazole (50.0 mmol) is dissolved in anhydrous tetrahydrofuran (200 mL) and cooled to −78°C with a dry ice/acetone bath. A solution of n-butyllithium in hexanes (1.6 M, 32.8 mL, 1.05 equiv) is added dropwise over 30 minutes while maintaining the internal temperature below −70°C; the mixture turns deep red, indicative of the 4-lithiobenzothiazole intermediate. After stirring for an additional 45 minutes, chlorodiphenylphosphine (11.0 g, 50.0 mmol, 1.0 equiv) is introduced neat via syringe, and the cooling bath is allowed to warm gradually to ambient temperature over 12 hours. Quenching with degassed saturated ammonium chloride solution, extraction with toluene, and flash chromatography (silica gel, hexane/ethyl acetate 95:5) under nitrogen afford 4-(diphenylphosphino)benzo[d]thiazole as an air-sensitive white solid in 78% yield. The purity is assessed by ³¹P{¹H} NMR (δ +5.7 ppm in C₆D₆, referenced to 85% H₃PO₄) and elemental analysis (C 71.23% found, 71.45% calc.). This ligand, when combined with Pd₂(dba)₃ in a 1:1 P:Pd ratio, promotes the Buchwald–Hartwig amination of 4-bromobenzo[d]thiazole itself with secondary amines at room temperature, achieving a turnover frequency exceeding 1200 h⁻¹ for morpholine coupling. For international trade, 4-(diphenylphosphino)benzo[d]thiazole is classified under the IMDG Code as a Class 4.2 substance (spontaneously combustible) and must be shipped in sealed, nitrogen-flushed amber glass bottles packed within metal canisters containing vermiculite. Storage at −20°C under inert gas is mandatory, and the material must undergo ³¹P NMR re-certification before use if the container has been opened for more than 72 hours. An incompatibility of note is the rapid decomposition of the free ligand in the presence of chlorinated solvents, particularly dichloromethane, which produces a phosphonium impurity that severely retards catalysis; all handling is conducted in toluene or tetrahydrofuran.The exceptional photostability of 2-(2-hydroxyphenyl)benzo[d]thiazole (HBT) derivatives places 4-bromobenzo[d]thiazole-based intermediates at the center of high-performance UV absorber design for engineering thermoplastics subjected to prolonged outdoor weathering. The bromine atom at the 4-position is a strategic precursor for the synthesis of asymmetrical HBT analogues in which one arm carries a polymerizable methacrylate group for covalent anchoring into polycarbonate or poly(methyl methacrylate) matrices. A scaled production campaign in a 100 L glass-lined reactor illustrates the condensation pathway: 4-bromobenzo[d]thiazole is first converted to the corresponding 2-aminothiophenol via alkaline hydrolysis under pressure (2 M NaOH, 150°C, 10 bar), followed by cyclization with 2-hydroxy-4-methoxybenzaldehyde in methanol under acidic conditions (catalytic sulfuric acid, reflux 6 hours). The resulting 4-bromo-2-(2-hydroxy-4-methoxyphenyl)benzo[d]thiazole is isolated in 82% yield and subjected to Suzuki coupling with 4-vinylphenylboronic acid to install the polymerizable handle. After purification and recrystallisation from toluene, the methacrylate-functionalized UV absorber (melting point 182–184°C) is introduced into polycarbonate via twin-screw extrusion at a loading of 0.5 wt% using a co-rotating extruder with L/D 44:1, barrel temperatures 260–290°C, and screw speed 300 rpm. The compounded pellets are injection-molded into 3.2 mm plaques and exposed to xenon-arc accelerated weathering per ISO 4892-2:2013 (filtered xenon radiation, 0.51 W m⁻² nm⁻¹ at 340 nm, black-standard temperature 65°C, water spray cycle). After 1500 hours of cumulative exposure, the yellowness index measured according to ASTM E313-20 exhibits a delta YI of < 2.0, outperforming the benzotriazole benchmark under identical conditions. A formulation caveat documented during compounding is the antagonistic interaction with hindered amine light stabilizers (HALS) containing secondary amino groups; the combination reduces the active HBT tautomer population via acid-base adduct formation, and the recommended stabilizer package should substitute non-basic NOR-HALS or employ an acid scavenger such as calcium stearate at 0.1 wt%. Regulatory compliance for food-contact applications is assessed via overall migration testing per EU 10/2011 (simulant D1, 40°C, 10 days), where the specific migration limit of the unreacted 4-bromobenzo[d]thiazole precursor is controlled to < 0.01 mg kg⁻¹ simulant, necessitating exhaustive extraction of the functionalized polymer before use in multi-layer laminate structures. |
Competitive 4-Bromobenzo[D]Thiazole 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!
| Parameter | 4-Bromobenzo[D]Thiazole | 5-Bromobenzo[D]Thiazole | 2-Bromobenzo[D]Thiazole |
|---|---|---|---|
| CAS Registry Number | 767-70-1 | 62037-52-9 | 767-70-1 (note: isomer designated 2-bromo) |
| Molecular Weight (g/mol) | 214.08 | 214.08 | 214.08 |
| Melting Range (°C) | 38–42 | 48–52 | 8–11 (low-melting solid) |
| t90 Suzuki Conversion (min) | 42 ± 3 | 8 ± 1 | 110 ± 12 |
| Oxidative Addition Barrier ΔG‡calc (kcal/mol) | 23.4 | 20.8 | 26.1 |
| Typical Purity Specification | ≥98.5% (GC) | ≥97.0% (GC) | ≥96.0% (GC) |
| Key Commercial Differentiator | tunable reactivity window for consecutive couplings | highest intrinsic activity for single-step derivatization | requires strong π‑acidic ligands; prone to ring-opening |
| Attribute | Research Grade (BT4-RG-100) | Intermediate Grade (BT4-IG-1K) | cGMP Grade (BT4-GMP-5K) |
|---|---|---|---|
| Purity (GC-FID, area%) | ≥98.5 | ≥99.0 | ≥99.5 |
| Water (KF, ISO 760) | ≤0.1% | ≤0.1% | ≤0.05% |
| Residual Palladium (ICP-MS) | ≤20 ppm | ≤10 ppm | ≤5 ppm |
| Alkyl Bromides (GC-MS headspace) | Not tested | ≤10 ppm | ≤5 ppm (EMA genotoxic) |
| Endotoxins (USP <85>) | Not tested | Not tested | <0.25 EU/mg |
| Packaging | 100 g amber vial, nitrogen | 1 kg HDPE bottle in foil laminate, nitrogen | 5 kg or 25 kg UN 1A2 fibre drum, VPCI-lined |
| Regulatory Compliance | ISO 9001:2015 | ISO 9001:2015, REACH | ICH Q7, FDA 21 CFR 210/211, EXCiPACT |
