2-Bromobenzothiazole
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HS Code |
608182 |
| Chemical Formula | C7H4BrNS |
| Molecular Weight | 214.08 |
| Appearance | Yellow to brown solid |
| Melting Point | 63 - 67 °C |
| Boiling Point | 284 - 286 °C |
| Solubility In Water | Insoluble |
| Solubility In Organic Solvents | Soluble in common organic solvents like ethanol, chloroform |
| Density | 1.72 g/cm³ |
| Flash Point | 125 °C |
| Odor | Characteristic |
As an accredited 2-Bromobenzothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 250g of 2 - Bromobenzothiazole packaged in a sealed, chemical - resistant bottle. |
| Shipping | 2 - Bromobenzothiazole is shipped in accordance with strict chemical transportation regulations. It's packaged securely in suitable containers to prevent leakage, ensuring safe transit to destinations, following all relevant safety and handling guidelines. |
| Storage | 2 - Bromobenzothiazole should be stored in a cool, dry, well - ventilated area, away from heat sources and ignition points. Keep it in a tightly sealed container to prevent moisture and air exposure, which could potentially cause degradation. Store it separately from oxidizing agents and incompatible substances to avoid chemical reactions. |
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In the industrial synthesis of sulfenamide accelerators for sulfur-vulcanized rubber, the purity of the mercaptobenzothiazole precursor exerts a measurable influence on the scorch safety margin defined by the moving-die rheometer curve at 160 °C per ISO 6502-2. The ex-aniline route to 2-mercaptobenzothiazole (MBT) can introduce residual aniline and carcinogenic N-nitrosamines, which has driven a search for alternative halogenated precursors that eliminate amine carry-over. 2-Bromobenzothiazole is charged into a high-pressure nucleophilic substitution with aqueous 20 wt% sodium hydrosulfide at a molar ratio of 1:1.1 (2-bromobenzothiazole:NaSH) inside a hastelloy-clad, magnetically driven autoclave stirred at 800 rpm. The reaction mass is heated to 190—200 °C under an autogenous pressure of approximately 1.8—2.2 MPa and held for 10 h until in-process GC analysis confirms residual 2-bromobenzothiazole below 0.1 area%. The resulting sodium MBT solution is acidified with 30% sulfuric acid to precipitate crude MBT, which, after vacuum drying at 60 °C and −0.09 MPa, exhibits a melting point of 178—180 °C and an assay ≥ 97% by HPLC (area normalization). Regulatory compliance for the intermediate aligns with REACH Annex XVII entries concerning N-nitrosatable substances and the purity thresholds of ASTM D4817 for sulfenamide accelerator precursors. Downstream, this MBT is oxidized with sodium hypochlorite to 2,2′-dibenzothiazyl disulfide (MBTS) or reacted with cyclohexylamine under alkaline conditions to yield N-cyclohexyl-2-benzothiazolesulfenamide (CBS). In a carbon-black-filled natural rubber truck tread formulation, CBS is incorporated at 1.2—1.8 phr, while MBTS is pre-dispersed in an internal mixer at a fill factor of 0.75 and a dump temperature of 140—150 °C; the optimal cure time t90 shifts by approximately 30 s per 0.1 wt% variation in MBT purity due to differences in amine content, which is monitored on a production-scale intermeshing twin-screw extruder (L/D 36) during final pelletizing. The terminal product range includes CBS, TBBS, and MBS granules, directly consumed in the manufacture of heavy-duty tyre treads and steel-cord conveyor belts where a delayed-action cure is mandatory. When copper alloy heat exchangers in open-recirculating cooling systems exhibit general corrosion rates exceeding 0.25 mm/yr under ASTM G31-72 conditions, the shift to a benzothiazole-based film-forming inhibitor becomes a mitigation necessity requiring high-purity 2-mercaptobenzothiazole (MBT) derived from 2-bromobenzothiazole. The initial synthesis follows the same high-pressure thiolation pathway—2-bromobenzothiazole and 20 wt% NaSH at a 1:1.05 molar ratio, 195 °C, 2.0 MPa—but the post-acidification MBT cake is subsequently neutralized with 30% sodium hydroxide to form a 50% active 2-mercaptobenzothiazole sodium salt solution (MBT-Na), with the final pH adjusted to 10.5—11.0. This conversion bypasses the residual aniline burden of conventional MBT and meets the heavy-metal limits of EN 15028:2012 for corrosion inhibitors used in drinking water additives. Industrial formulations dose MBT-Na into glycol-water coolants or open-loop cooling towers at a maintenance concentration of 20—50 mg/L as active benzothiazole, where it forms a chemisorbed film of 5—20 nm thickness verified by spectroscopic ellipsometry. The inhibition efficiency is benchmarked via linear polarisation resistance per ASTM D1384-13, with a target copper dissolution rate below 0.5 µm/yr. The terminal products are liquid concentrates containing 30—50% MBT-Na, often blended with tolyltriazole and phosphonates, and packaged in IBC 1000 L totes for direct injection into evaporative cooling circuits serving petrochemical plants and data centre HVAC loops. Can Palladium-Catalyzed Cross-Coupling of 2-Bromobenzothiazole Streamline GMP-Compliant Lead-Optimisation of Benzothiazole-Derived Kinase Inhibitors?Small-molecule oncology programs exploiting the benzothiazole pharmacophore frequently rely on Suzuki-Miyaura cross-coupling to construct 2-arylbenzothiazole libraries, where 2-bromobenzothiazole serves as the electrophilic partner. In a standard pilot-scale reaction compliant with ICH Q7 Good Manufacturing Practice for APIs, 2-bromobenzothiazole (1.0 mol) is dissolved in 1,4-dioxane/water (3:1 v/v, 8 L/kg substrate) together with the appropriate arylboronic acid (1.25 mol), and the mixture is degassed with subsurface nitrogen for 45 min. The catalytic system employs PdCl₂(dppf)·CH₂Cl₂ at a loading of 1.5 mol% and potassium carbonate (2.5 mol) as base. The stirred suspension is heated to 85 °C and maintained for 14 h, at which point conversion normally exceeds 95% by UPLC. The crude 2-arylbenzothiazole is extracted into ethyl acetate, treated with a silica-bound trimercaptotriazine scavenger to reduce residual palladium below the 10 µg/g limit mandated by ICH Q3D for elemental impurities, and recrystallised from methanol to yield an off-white solid with purity ≥ 99.0% (HPLC, 210 nm). The entire process is executed under an ICH M7 mutagenic impurity control strategy that classifies 2-bromobenzothiazole as a Class 3 alerting structure, requiring purge factor calculations verified by spiking studies at the 1-ppm threshold. The terminal agents—examples being 2-(4-amino-3-methylphenyl)benzothiazole and its N-acetyl prodrug forms—are advanced into preclinical solid-tumour models targeting CYP1A1-expressing cancers, with the prodrug approach exploiting the differential metabolism first published in J. Med. Chem. and subsequently evaluated under US FDA IND 105,493. Phase-Transfer-Catalyzed TCMTB Biocide Production Compliance with BPR Article 582-(Thiocyanomethylthio)benzothiazole (TCMTB) is a broad-spectrum industrial microbicide registered for wood preservation, leather tanning, and paper mill slimicide under the EU Biocidal Products Regulation (BPR) Article 58 active substance review programme. The synthetic route starts from MBT obtained via the high-pressure thiolation of 2-bromobenzothiazole: the dried MBT cake (assay ≥ 97%) is suspended in toluene at a concentration of 0.8 mol/L, and tetrabutylammonium bromide is added as a phase-transfer catalyst at 3 mol% relative to MBT. Chloromethyl thiocyanate (TCNMA) is then metered in at a molar ratio of 1.1:1 (TCNMA:MBT) while maintaining the reaction temperature at 40—45 °C; the pH of the aqueous phase is held at 8.0—8.5 by the gradual addition of 20% sodium carbonate solution. After 6 h of agitation in a glass-lined reactor, the organic layer is washed, dried, and concentrated, furnishing TCMTB with a typical purity of 95% (GC-FID, DB-5 column). The final formulated product is a 30 wt% emulsifiable concentrate stabilized with an anionic-nonionic surfactant package, which is diluted on-site to a 0.2—0.5% w/w active working solution for vacuum-pressure impregnation of timber. Efficacy must be validated according to EN 113 against basidiomycete decay fungi, while the leaching behaviour and inherent biodegradability are characterised under EN 84 and OECD 302B protocols, respectively. Terminal commercial products based on this TCMTB concentrate include Cooper’s Busan® 30WB and Lanxess Preventol® A 12-D, which are applied in industrial wood-treatment cylinders operating at 12-bar pressure cycles for utility poles and railway sleepers. Disperse Red Chromophore Synthesis via Diazotization of 2-Aminobenzothiazole and Coupling to N,N-Diethyl-m-toluidinePolyester coloration with medium-energy disperse dyes is served by azo chromophores derived from 2-aminobenzothiazole, which is manufactured from 2-bromobenzothiazole through a copper-catalyzed ammonolysis. 2-Bromobenzothiazole is charged into a 316L stainless-steel autoclave with 25% aqueous ammonia at a molar ratio of 1:12 and cuprous oxide (0.5 mol%) and heated to 200 °C for 8 h; after cooling, the precipitated 2-aminobenzothiazole is filtered, washed to neutrality, and dried at 50 °C under vacuum to obtain a light-beige powder with a purity ≥ 98.5% (HPLC) and melting point 126—129 °C. The diazotization is carried out by dissolving the amine in 85% phosphoric acid and adding 40% nitrosylsulfuric acid dropwise at 0—5 °C, maintaining a slight excess of nitrous acid detectable on starch-iodide paper; the resulting diazonium salt is immediately coupled to N,N-diethyl-m-toluidine at a molar ratio of 1:1.02 (diazonium:coupler) in ice-water, with the pH adjusted to 3.5—4.0 by sodium acetate. The precipitated dye is filtered, washed, and bead-milled to a particle size distribution with D90 ≤ 1 µm for exhaust dyeing of polyester at 130 °C. Formulation compliance is verified against the ZDHC MRSL v3.1 and OEKO-TEX Standard 100 Annex 4 limits for banned amines and chlorophenols. In a typical high-temperature dyeing cycle, the milled presscake is dosed at 1.0—3.0% on-weight-of-fabric, and the resultant dyeing meets the fastness benchmarks of ISO 105-C06 (C2S washing) and ISO 105-B02 (xenon arc, rating ≥ 6). The terminal product is sold as C.I. Disperse Red 152, packaged in 25-kg moisture-proof fibre drums, and used for woven polyester sportswear and automotive upholstery where identical shade reproducibility across international supply chains is non-negotiable. |
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2-Bromobenzothiazole (CAS 615-20-3, synonym 2-benzothiazolyl bromide) is supplied as a white to pale-yellow crystalline solid with a melting range of 61–64 °C (capillary method, open glass) and a molecular weight of 214.08 g·mol⁻¹. Catalog listings—e.g., Sigma-Aldrich 562440, TCI B3389—typically deliver product at ≥98% purity (GC, FID area%) with a ≥99% grade available on request. In the halogenated benzothiazole series the C2 bromine atom occupies a reactivity midpoint: oxidative addition to Pd⁰ proceeds 1.7–2.3‑fold faster than that of the 2‑chloro congener (CAS 615‑21‑4), while the 2‑iodo analogue offers still higher rates but at 3–5‑fold greater procurement cost and markedly poorer photostability. This balance directs its use in discovery-phase medicinal chemistry, agrochemical intermediate synthesis, and the preparation of benzothiazole-based ligands for photonic applications where catalyst economy and shelf‑life are primary optimisation parameters.
Purity specifications for laboratory‑ and pilot‑scale supply are determined by a suite of pharmacopoeia‑derived and in‑house methods. The table below summarises the certificate‑of‑analysis criteria applied to bulk lots released for custom synthesis programmes. Water content is measured by coulometric Karl Fischer titration following ISO 760:1978; residual solvent profiling is available upon request using headspace GC‑FID per USP〈467〉 methodology. Single‑crystal X‑ray diffraction (SXRD) data confirm the absence of the oxybis‑benzothiazole impurity that can arise from adventitious hydrolysis during prolonged storage above 25 °C.
| Parameter | Specification | Test Method |
| Appearance | White to pale‑yellow crystalline powder | Visual inspection under D65 light |
| Purity (GC) | ≥ 98.0% (area‑%) | GC‑FID, DB‑5 column (30 m × 0.25 mm × 0.25 μm) |
| Melting range | 61 – 64 °C | Capillary method, heating rate 1 °C/min |
| Water (w/w) | ≤ 0.50% | Karl Fischer titration (ISO 760:1978) |
| Identity | Conforms to reference 1H NMR, 13C NMR, and IR spectra | FT‑IR (KBr disk); NMR in CDCl₃, 400 MHz |
| Storage recommendation | Keep at 2–8 °C, protected from light and moisture | Stability data batch LC‑012‑B |
The bromine atom in 2‑bromobenzothiazole presents an activation barrier for oxidative addition that is sufficiently low to permit efficient Pd‑catalysed cross‑coupling at catalyst loadings routinely achievable in pilot‑plant operations (0.1–0.5 mol% Pd with modern dialkylbiarylphosphine ligands). In a representative set of screening conditions—Pd(OAc)₂ (0.5 mol%), SPhos (1.0 mol%), K₂CO₃ (2.0 equiv.), toluene/EtOH/H₂O (7:2:1 v/v/v), 80 °C, 16 h)—the conversion hierarchy for Suzuki–Miyaura coupling with 4‑methoxyphenylboronic acid is captured in the following table. The 2‑bromo substrate delivers isolated yields within 10–15 percentage points of the iodo analog while requiring only one‑fourth to one‑third the catalyst loading that a comparable 2‑chloro coupling demands, reflecting the established Ar‑Br oxidative addition rate advantage over Ar‑Cl.
| 2‑Halobenzothiazole | Conversion (GC area‑%, t = 4 h) | Isolated yield (%) |
| 2‑Bromo | 97 | 88 |
| 2‑Chloro | 38 | 32 |
| 2‑Iodo | >99 | 92 |
In Buchwald–Hartwig aminations the same trend holds: 2‑bromobenzothiazole couples with primary and secondary aliphatic amines at 70–80 °C with BrettPhos‑precatalyst systems, whereas the 2‑chloro analog typically requires 90–100 °C and longer reaction times to reach comparable conversion. The bromo substrate can also participate in direct nucleophilic aromatic substitution with thiolates and imidazole under mild heating (60 °C, DMF) without metal catalysis, though competing thiazole ring‑opening becomes significant at pH > 10. Published data for Sonogashira alkynylation indicate that 2‑chlorobenzothiazole is essentially unreactive under standard conditions (Pd(PPh₃)₄/CuI, Et₃N, THF, 25 °C), whereas 2‑bromobenzothiazole furnishes the 2‑ethynyl derivative in 70–78% yield; the 2‑iodo congener reaches 82–90% but requires careful exclusion of ambient light to prevent radical debromination.
Handling protocols in kilo‑lab operations emphasise rigorous exclusion of moisture: even at 25 °C and 60% RH, unpackaged 2‑bromobenzothiazole can darken within 72 h as a surface hydrolysis film forms, detectable by ion chromatography as an increase in free bromide from < 50 ppm to > 300 ppm. Storage in amber‑glass containers under nitrogen at 2–8 °C suppresses this degradation for at least 24 months; Karl Fischer titration after 6‑month intervals typically shows water content remaining below 0.60%. When the compound must be handled in air, pre‑drying of solvents to ≤ 50 ppm H₂O and use of molecular sieves (3 Å) are employed to sustain reagent integrity across multi‑step sequences. Reported incompatibilities include strong bases (ring‑opening) and prolonged contact with primary amines in neat state, which can give rise to the 2‑aminobenzothiazole thermodynamically at temperatures exceeding 120 °C even in the absence of a catalyst.
The 2‑bromobenzothiazole scaffold provides a direct entry to the benzothiazole‑based pharmacophore that appears in approved drugs such as Riluzole (2‑amino‑6‑trifluoromethoxybenzothiazole, EMA‑approved for amyotrophic lateral sclerosis). While industrial production of Riluzole relies on a thiocyanation‑cyclisation route, the 2‑bromo intermediate enables late‑stage diversification at the C2 position through palladium‑catalysed Buchwald‑Hartwig coupling with a library of amines, alcohols, and thiols, a strategy exploited in SAR studies for mGluR5 allosteric modulators and TRPV1 antagonists. In addition, the bromine atom serves as a traceless director in sequential C–H borylation at the 5‑position of the benzothiazole ring, which can be protodebrominated to yield 5‑substituted analogues with functionality arrayed for kinase inhibitor programmes.
For agrochemical discovery, 2‑bromobenzothiazole is a precursor to the benzothiazole‑2‑carboxylate series that features in systemic fungicides. A two‑step sequence—palladium‑catalysed alkoxycarbonylation under CO (10 bar) employing Xantphos (2 mol%) and Pd(OAc)₂ (1 mol%) at 100 °C in DMF, followed by saponification—provides the 2‑carboxylic acid in 75–82% overall yield. The 2‑chloro substrate under identical conditions requires 20 bar CO and 120 °C to reach 65% conversion, further illustrating the activation benefit of the bromine leaving group. Pilot‑scale runs in a 50‑L Hastelloy autoclave have confirmed robustness of the carbonylation protocol when residual oxygen is kept below 50 ppm in the headspace.
In the construction of benzothiazole‑containing ligands for dye‑sensitised solar cells (DSSCs) and phosphorescent OLED emitters, material cost becomes a critical decision factor once the target compound advances beyond the milligram‑scale discovery phase. 2‑Iodobenzothiazole, while delivering the highest cross‑coupling yields, carries a unit price approximately 4‑fold that of the bromo analog and exhibits a shelf‑life limited to 6–9 months at –20 °C under argon before onset of discoloration and decomposition to a complex mixture of di‑benzothiazolyl sulfides. Process chemists substituting 2‑bromobenzothiazole in a model Sonogashira–Suzuki cascade—first coupling with (triisopropylsilyl)acetylene, then with a carbazole‑cored boronate ester—observed an overall yield of 64% after chromatography, compared with 81% for the iodo route; nevertheless the cost per gram of purified ligand was reduced by 58%. The moderate yield drop was traced to a 12‑hour incipient induction period in the first step that could be shortened to 4 h by using XPhos‑Pd‑G3 (1.5 mol%) instead of Pd(PPh₃)₄, underscoring the necessity of ligand screening when the less reactive halogen is installed.
Under the thermal and photochemical conditions of device fabrication—vacuum deposition at 10⁻⁶ mbar, source temperature 220–250 °C—the 2‑bromobenzothiazole‑derived ligands showed no statistically significant difference in OLED device lifetime (T50 at 1000 cd·m⁻²) relative to their iodo‑derived counterparts, provided the final ligand purity exceeded 99.5% by HPLC (C18, MeCN/water 80:20, 254 nm). Thus, the economic advantage can be preserved without compromising end‑device reliability when purification protocols are aligned with the slightly higher impurity burden of the bromo pathway.
Occupational exposure scenarios for 2‑bromobenzothiazole are governed by GHS classification H315 (skin irritation) and H319 (eye irritation). Engineering controls—local exhaust ventilation, closed‑loop transfer in drum‑scale operations—are prescribed for quantities exceeding 500 g. Waste streams containing brominated benzothiazole by‑products must not be combined with amine‑based scavengers during neutralisation because of risk of exothermic quaternisation; instead incineration in a 1100 °C afterburner with a residence time of ≥ 2 s is the recommended destruction pathway as described in Safety Data Sheet section 13. The compound is not registered under EU REACH for ≥ 1 tonne·year⁻¹ at the time of writing, and its inclusion in any new process at industrial scale would require a full chemical safety assessment per Article 14 of Regulation (EC) No 1907/2006.
