5-Bromo-1,3-Benzothiazole-2(3H)-Thione

Systemic Activity in Oomycete Control — A 5-Bromo Derivative Profile

5-Bromo-1,3-benzothiazole-2(3H)-thione functions as a building block for thiophosphoryl fungicides targeting oomycete pathogens in high-value horticultural crops. The bromine substituent elevates lipid solubility relative to the parent benzothiazole-2-thione, enabling acropetal transport across the xylem when formulated as a suspension concentrate. Downstream synthesis typically involves condensation with O,O-diethyl phosphorochloridothioate under alkaline biphasic conditions, yielding an S-(benzothiazol-2-yl) phosphorodithioate active ingredient with an LC₅₀ below 2.0 mg/L against Phytophthora infestans zoospore motility in detached leaf disc assays. The formulated product must comply with EU 1107/2009 dossier requirements and FAO Specification 59/WP/-(2020) for wettable powder physical stability. Field application rates for grape downy mildew (Plasmopara viticola) range from 180 g a.i./ha to 320 g a.i./ha, applied in 7–10 day intervals during the véraison stage. Manufacturing process quality hinges on wet-milling the technical concentrate through a horizontal bead mill charged with 0.6–0.8 mm yttria-stabilized zirconia media until a particle size distribution with D₉₀ ≤ 4.5 μm is achieved, as verified by laser diffraction per ISO 13320:2020. A naphthalene sulfonate formaldehyde condensate dispersant at 2.5–4.0 wt% on active ingredient prevents Ostwald ripening during 24-month ambient storage. Tank-mix compatibility limitations exist: combination with copper-based formulations must be avoided due to formation of insoluble copper-thiolate complexes that clog flat-fan nozzles at pressures below 3.0 bar. End-use products reach the market as pre-measured water-soluble sachets or high-concentrate suspension for drip irrigation injection in protected strawberry cultivation.

A notable production bottleneck observed on pilot-scale fluid energy mills is the material’s low melting onset at 162–164°C, which precludes jet milling under adiabatic compression temperatures exceeding 85°C; thus, cryogenic milling with liquid nitrogen cooling is mandated when targeting D₅₀ below 1.0 μm for seed treatment slurries. Residue analytical methods for MRL compliance rely on QuEChERS extraction followed by LC-MS/MS in negative electrospray mode, with a limit of quantitation of 0.01 mg/kg in grape must per EN 15662:2018. The compound’s environmental fate profile indicates moderate soil adsorption (K_oc estimated at 320–480 L/kg for the parent thione, based on model structures of analogous chlorinated benzothiazole thiols; published empirical data for the exact 5-bromo congener under OECD 121 batch equilibrium is limited), necessitating buffer zone restrictions within 15 metres of surface water in Northern European authorization zones. Registration holders in Brazil must supplement the standard IBAMA ecotoxicology package with acute oral honeybee data ( Apis mellifera ) showing contact LD₅₀ > 100 μg/bee to secure pollinator hazard classification Grade III.

What Makes a Benzothiazole Thione Effective as a Sulfur Donor in EPDM Extrusion?

Incorporation into an EPDM compound as a sulfur donor requires precise control over the dissociation kinetics of the thione C=S bond. The bromine atom inductively withdraws electron density from the heterocycle, shifting the onset of sulfur release to 132–138°C as measured by differential scanning calorimetry under a nitrogen atmosphere at a 10 K/min ramp rate—a window approximately 8–12 K lower than that of the unsubstituted 2-mercaptobenzothiazole. This temperature aligns with the barrel zone settings of a 90 mm cold-feed pin–barrel extruder processing low-Mooney EPDM (ML 1+4 at 125°C of 45–55 MU) for automotive weatherseal profiles. The compound is dosed at 2.0–3.2 phr alongside a secondary sulfenamide accelerator (e.g., N-cyclohexyl-2-benzothiazolesulfenamide at 0.8–1.2 phr) to balance scorch safety with crosslink density. Mixing proceeds in an intermeshing tangential internal mixer with a fill factor of 0.72, drop door set to 125–130°C. A single-pass addition sequence is critical: EPDM masticated for 45 seconds, followed by carbon black (N550, 80 phr) and paraffinic oil (55 phr), with the thione donor introduced at the 35-second mark after oil incorporation to prevent localized hot spots that accelerate premature sulfur bridge formation around carbon black agglomerates. Rheometer data (moving die rheometer arc 0.5° at 180°C per ASTM D5289-19a) typically show a minimum torque (M_L) of 1.8–2.3 dN·m and a maximum torque (M_H) of 14.5–17.0 dN·m, with t_s2 ranging from 1.9–2.6 minutes and t₉₀ from 6.8–8.4 minutes. The resulting network yields a crosslink density ν_e of 1.0–1.4 × 10⁻⁴ mol/cm³, fitting a bimodal chain-length distribution that improves compression set resistance at 125°C by 22–28% compared to an equivalent sulfur/TMTD donor system.

Extrusion die swell ratios at a shear rate of 150 s⁻¹ are maintained below 14% when the die land length is kept at 6× the gap opening. Premature crosslinking in the head zone arises if the melt temperature overshoots 146°C, a failure mode traced to an exothermic decomposition cascade initiating at bromine–sulfur heterolytic cleavage; thus, the head thermocouple setpoint must not deviate from 138±3°C. Drying of the compound pellet is required when the adsorbed moisture content exceeds 0.07 wt%, achieved via a fluidized-bed drier operating at 55°C with a dew point of −35°C for a residence time of 25–35 minutes. Incompatibilities are observed with zinc-free activator systems reliant on calcium oxide alone: the absence of zinc stearate (0.5–1.0 phr) retards the formation of the active sulfurating complex, extending t₉₀ beyond 12 minutes and resulting in under-cured corner sections in molded glass run channel joints. Finished profile compliance is assessed via ISO 188:2011 hot air ageing at 100°C for 72 hours, requiring retention of elongation at break above 65% of the unaged value.

5-Bromo-1,3-benzothiazole-2(3H)-thione serves as a neucleophilic partner in transition metal-catalyzed carbon–sulfur bond-forming sequences aimed at constructing 2-alkylthio- or 2-arylthiobenzothiazole cores with anti-tubercular activity against drug-resistant Mycobacterium tuberculosis strains. The thione sulfur attacks an activated electrophile—most commonly a propargyl bromide or a 2-chloro-N-phenylacetamide derivative—in the presence of anhydrous potassium carbonate in N,N-dimethylformamide at 50–60°C under a nitrogen blanket, achieving isolated yields above 75% after silica-gel column chromatography with hexane:ethyl acetate (8:2 v/v). Subsequent oxidation of the thioether to the sulfone with m-chloroperbenzoic acid (2.5 equivalents) in dichloromethane at 0–5°C generates a crystalline intermediate with melting point 192–194°C, whose X-ray diffraction pattern confirms the p-bromophenyl ring torsion angle essential for enoyl-ACP reductase (InhA) inhibition. The synthetic route falls under ICH Q7 GMP guidance when the final API is destined for Phase II clinical supply, requiring residual palladium levels below 10 ppm as quantified by USP <233> inductively coupled plasma mass spectrometry. A typical laboratory-scale campaign at 5.0 kg batch size employs a 20 L jacketed glass reactor with pitched-blade turbine agitation at 200 rpm, and the product is isolated by centrifugation in a Hastelloy C-22 basket centrifuge washed with chilled isopropanol (2 × 1.5 L). Published toxicity and efficacy data for the specific brominated thione building block are limited, but structure-activity relationship models for the benzothiazole scaffold suggest that the electron-withdrawing bromine at C-5 reduces metabolic N-glucuronidation rates in human liver microsomes by a factor of 3–4 relative to the unsubstituted analog, potentially extending the plasma half-life in preclinical murine models.

When Tannery Soak Liquor Requires Phenol-Free Preservation

Hypochlorite-free beamhouse operations processing salted bovine hides adopt a brominated benzothiazole thione as a broad-spectrum bactericide and fungicide in the main soak float. The compound’s thione group disrupts the proton gradient across the microbial cytoplasmic membrane, achieving a 3 log₁₀ reduction in total viable mesophilic count within 6 hours at an addition rate of 0.08 wt% on soaked hide weight, as per IULTCS/IUC 4 dipslide methodology. An in-process pH of 8.2–8.8 maintained with sodium carbonate (0.3–0.5%) minimizes the ionization of the thione proton, preserving the lipid-permeable undissociated form required for membrane penetration. Hide moisture regain is not adversely affected due to the absence of surfactant co-formulants that could strip natural fats; the 24-hour soak weight increase remains at 28–32% of green-salted mass, comparable to a quaternary ammonium biocide control. Compliance with ZDHC MRSL 3.1 is verified via an independent screening of the commercial product lot against the directive’s Section A restricted substances list, with a detection limit of 5.0 mg/kg for free phenol by EN ISO 17070:2006 (GC-MS). Downstream deliming and bating processes at pH 8.0–8.5 do not inactivate the residual active, which partitions into the flesh splits at a concentration of 120–180 mg/kg (dry weight) after splitting and shaving—levels that provide continued fungistatic protection through wet-blue storage at 25–30°C and 75% relative humidity for up to 14 days without additional re-chroming liquor dosing.

Running the soak drum—a stainless steel diameter 3.6 m Y-shaped vessel with 8 rpm rotation—requires pre-dilution of the thione agent in 20 litres of water at 35°C before addition into the 200% float volume to avoid localized concentration spikes that can cause hair slip at the epidermis interface on belly regions. Published data for this exact brominated thione in pickle liquor applications is limited; however, redox potential monitoring in pilot-scale trials suggests incompatibility with hydrogen peroxide-based sulfide oxidation units if carry-over exceeds 0.01 g/L, as the thione consumes peroxide at a stoichiometric ratio of 1:4 (thione:H₂O₂), lowering the oxidation-reduction potential below the +450 mV threshold required for efficient sulfide destruction. Finished wet-blue is subsequently evaluated for grain tightness and collagenase stability via ISO 5402:2014 flexometer resistance, with acceptance criteria set at 50 000 dry flexes without grain cracking.

Film-Forming Inhibition on Mild Steel in Acidic Flow-Lines

The compound adsorbs onto low-carbon steel (AISI 1018) surfaces from 15 wt% hydrochloric acid at 60°C via the thione sulfur and the bromine-substituted aromatic ring, forming a coherent chemisorbed monolayer that suppresses both anodic iron dissolution and cathodic hydrogen evolution. Electrochemical impedance spectroscopy in a standard three-electrode flat cell (ASTM G106-89(2020), with a platinum counter electrode and a silver/silver chloride reference) at a frequency range of 100 kHz–10 mHz and an AC amplitude of 10 mV reveals a charge-transfer resistance increase from 45 Ω·cm² (uninhibited) to 1 840 Ω·cm² at a dosage of 400 mg/L. Weight-loss coupons ( 50 × 25 × 2 mm, polished to 600 grit) exposed for 6 hours per ASTM G31-72 show a corrosion rate reduction from 38.2 mm/year to 1.7 mm/year , translating to inhibitor efficiency exceeding 95% . Potentiodynamic polarization scans at a sweep rate of 0.166 mV/s from −250 mV to +250 mV vs. open circuit potential classify the brominated thione as a mixed-type inhibitor with a predominant effect on the anodic Tafel slope, which steepens from 68 mV/dec to 122 mV/dec, suggesting blocking of active sites at the metal-solution interface. Conventional stimulation vessel batch records from a Permian Basin field trial (Well A-23, dolomite formation, bottomhole static temperature 82°C) indicate that a treatment fluid containing 0.3 vol% of a formulated inhibitor package based on the bromo-thione plus propargyl alcohol synergist maintained a rate of metal loss below 0.05 lb/ft² over 8 hours of shut-in, as measured by electrical resistance probe corrosion monitoring with a resolution of 0.01 mils/year.

The application window narrows significantly when organic acids replace mineral acids: inhibition efficiency in 10 wt% formic acid at 70°C collapses to 42% at the same inhibitor loading unless augmented with 50 ppm of potassium iodide, which shifts the pitting protection potential above +300 mV versus SCE per ASTM G61-86(2018) cyclic potentiodynamic polarization. Operational boundaries exclude contact with fluids containing hydrogen sulfide partial pressures exceeding 0.05 psi, as the thiophilic nature of the dissolved H₂S results in desorption of the inhibitor film and precipitation of insoluble metal thiolate scales on the N80 tubing wall. The neat technical solid must be shipped and stored under nitrogen blanketing in UN-rated 1H2 plastics drums with moisture absorbers; exposure to air at relative humidity above 65% for over 48 hours initiates hydrolytic debromination detectable as a discoloration shift from pale yellow to amber and a 4–6% decline in active content measured by iodometric titration per an internal QA/QC method validated against ASTM E298-17a for organic thiols.

Alkylation of 5-bromo-1,3-benzothiazole-2(3H)-thione with 2-ethylhexyl bromide in the presence of sodium methoxide yields a S-(2-ethylhexyl) thioether that exhibits ultraviolet absorption maximum at 315 nm with a molar extinction coefficient suitable for stabilizing polypropylene homopolymer films against photo-initiated chain scission. Compounding into polypropylene extruded cast film (thickness 50 μm) at 0.15 wt% additive loading is performed on a co-rotating twin-screw extruder with L/D 40:1 using a melt temperature of 230°C at the die. Accelerated weathering under ASTM G154-23 Cycle 1 (UVB-313 lamps, 0.63 W/m² at 310 nm, 60°C black panel temperature) for 1 000 hours shows retention of tensile strength at yield above 87% , compared to 48% for an unstabilized control. Migration kinetics determined by HPLC analysis of ethanol food simulant (EN 1186-1:2002, 10 days at 40°C) show total extractives below 2.5 mg/dm² , which falls within the specific migration limit established in EU Regulation 10/2011 for an unlisted substance requiring an additive evaluation via EFSA threshold of toxicological concern. The stabilizer system is generally co-formulated with a hindered amine light stabilizer (HALS) of the 2,2,6,6-tetramethylpiperidine type at a ratio of 1:2 (thioether:HALS) to address both thermo-oxidative and photo-oxidative degradation during outdoor service of agricultural silage wrap. First-pass film production using a chill-roll cast film line with a 300 mm width slot die at a haul-off speed of 15 m/min exhibits no die-lip build-up over 8-hour continuous runs when the additive is pre-dispersed in a polypropylene carrier resin via a 30 wt% masterbatch. Published specific migration data for the exact 5-bromo-substituted thioether into fatty food simulants is limited; therefore, a confirmatory EN 13130-1:2004 screening using olive oil at 40°C for 10 days is recommended before packaging-grade approval.