2-(Trifluoromethyl)-1,3-Benzothiazole

The compound serves as the critical benzothiazole heterocycle in a multi‑step convergent synthesis of a succinate dehydrogenase inhibitor (SDHI) active ingredient registered under FRAC code 7. In the penultimate step, 2-(trifluoromethyl)-1,3-benzothiazole undergoes regioselective lithiation at the 6‑position using lithium diisopropylamide (LDA, 1.05 equiv) in anhydrous tetrahydrofuran at −78 °C, followed by quench with solid carbon dioxide to furnish 2-(trifluoromethyl)-1,3-benzothiazole-6-carboxylic acid. The acid is converted to the corresponding acid chloride with thionyl chloride (1.2 equiv, catalytic DMF, reflux 4 h) and subsequently amidated under Schotten–Baumann conditions (water/dichloromethane biphasic, pH 9.0–9.5) with a substituted aniline — typically 4‑chloro-2‑(trifluoromethyl)aniline — at a molar ratio of acid chloride to amine of 1.0 : 1.10. The crude active ingredient is purified by recrystallisation from toluene/hexane (1 : 3 v/v) and must meet the technical material purity of ≥ 98.5 % by HPLC (CIPAC method 476/TC, UV detection 254 nm). Compliance with the FAO specification framework for the benzothiazole carboxamide class (provisional specification, clause 2.1) additionally requires a water content below 0.5 % (Karl Fischer) and an acetone‑insoluble matter limit of ≤ 0.2 %. The final end‑use product is a 500 g L⁻¹ suspension concentrate (SC) formulation, incorporating a naphthalene sulfonate‑formaldehyde condensate dispersant and a propylene glycol antifreeze. The SC must pass the CIPAC MT 184 suspensibility test (retention ≥ 90 % after 30 min) and is applied as a foliar spray at 0.8–1.2 L ha⁻¹ for the control of Pyrenophora teres and Septoria tritici on malting barley. Process‑scale synthesis is executed in a 2000 L glass‑lined reactor, with cryogenic lithiation requiring jacket temperature maintenance at −85 °C; batch‑to‑batch variance in the carboxylation yield (± 3 % absolute) is principally governed by dissolved CO₂ mass transfer efficiency and the exotherm during lithiation quench.

When a 2‑(Trifluoromethyl)benzothiazole Derivative Replaces 2‑Aminobenzothiazole in Antitumor Lead Optimization

The replacement of the genotoxic 2‑aminobenzothiazole substructure with the electronically distinct 2‑(trifluoromethyl)-1,3-benzothiazole core is a deliberate medicinal chemistry strategy to improve the developability profile of 2‑(4‑aminophenyl)benzothiazole‑based cytotoxic agents. A potent preclinical candidate, structurally analogous to DF 203 but bearing the ‑CF₃ substituent at C‑2, is constructed via a palladium‑catalysed Suzuki–Miyaura cross‑coupling. The key intermediate, 2‑(trifluoromethyl)-1,3-benzothiazole‑6‑boronic acid pinacol ester, is coupled with 4‑iodoaniline using Pd(PPh₃)₄ at 2 mol % loading in a degassed 1,4‑dioxane/water mixture (4 : 1 v/v) at 85 °C for 16 h; the molar ratio of boronate to aryl iodide is held at 1.0 : 1.25 to compensate for protodeboronation side reactions. The biaryl product is nitrated with a mixed acid (HNO₃/H₂SO₄ 1 : 3 v/v) at 0–5 °C exclusively at the 4′‑position to yield the nitro derivative, which is subsequently reduced with iron powder (4 equiv) and ammonium chloride (1 equiv) in ethanol/water (9 : 1) at 80 °C, affording the active pharmaceutical ingredient (API). The final API must satisfy ICH Q3A residual solvent limits: dioxane content ≤ 380 ppm, residual palladium ≤ 10 ppm (ICP‑MS), and no detectable 2‑aminobenzothiazole (limit of quantitation 0.05 ppb by LC‑MS/MS). The API is formulated as a lyophilised powder for injection; each 50 mg vial is reconstituted with 10 mL of sterile water for intravenous administration in Phase II metastatic melanoma trials. The synthesis eliminates the risk of mutagenic 2‑aminobenzothiazole carry‑over, which would otherwise trigger a threshold of toxicological concern (TTC) assessment under ICH M7(R1).

High‑Washfast Disperse Azo Dyes — 2‑(Trifluoromethyl)-6‑aminobenzothiazole as Diazo Component

Incorporation of the strong electron‑withdrawing ‑CF₃ substituent into the benzothiazole diazo moiety raises the molecular planarity and polarity of the azo chromophore, directly enhancing the sublimation fastness and thermal migration resistance of the final disperse dye on polyester. The diazo component is prepared by electrophilic nitration of 2‑(trifluoromethyl)-1,3-benzothiazole with a mixed acid (HNO₃ 40 %, H₂SO₄ 60 %) at 0–5 °C, affording the 6‑nitro isomer in ≥ 92 % regioisomeric purity; the mass ratio of mixed acid to substrate is 5 : 1. Catalytic hydrogenation in a 316L stirred autoclave over 5 % Pd/C (0.5 wt % relative to nitro compound) at 40 psi hydrogen and 50 °C in ethanol yields 2‑(trifluoromethyl)-6‑aminobenzothiazole. For the downstream azo coupling, the amine is diazotised in 30 % sulphuric acid with sodium nitrite (1.02 equiv) at 0–5 °C and coupled to an N,N‑diethyl‑m‑toluidine coupler in a 1 : 1.02 molar ratio at pH 3.5–4.0, maintained by sodium acetate addition. The crude dye press cake is desalted via membrane filtration, standardised to 33.0 % pure dye content with sodium lignosulphonate dispersant, and spray‑dried (inlet temperature 180 °C, outlet 85 °C). The terminal product, registered under a Colour Index designation for a high‑fastness disperse blue, must meet the AATCC TM61‑2A wash fastness requirement of grade 4–5 (staining on multifibre adjacent fabric) after 45 min at 49 °C with 0.15 % reference detergent. The dye is commercially applied to PET automotive upholstery using a high‑temperature exhaust process (130 °C, 30 min, liquor ratio 10 : 1) at 2.0 % o.w.f.

How Does 2‑(Trifluoromethyl)benzothiazole Quaternary Salt Inhibit N80 Steel Corrosion in 15 % HCl at 90 °C?

Acidizing operations in carbonate reservoirs routinely expose N80 carbon steel to 15 % hydrochloric acid at bottom‑hole temperatures exceeding 80 °C, demanding effective corrosion inhibition to prevent catastrophic tubing failure. 2‑(Trifluoromethyl)-1,3-benzothiazole is converted to the quaternary ammonium methosulphate salt via N‑methylation with dimethyl sulphate (1.1 equiv) in dry toluene at 110 °C for 6 h in a Hastelloy C‑276 reactor; the resulting N‑methyl‑2‑(trifluoromethyl)benzothiazolium methosulphate is then anion‑exchanged with potassium iodide to obtain the more surface‑active iodide salt. When formulated as a 25 % active solution in isopropanol, this quaternary salt is injected into the acid stream at addition rates of 0.2–0.5 wt % of the total acid volume. Corrosion inhibition performance is evaluated strictly according to NACE TM0169‑2012 using pre‑weighed N80 coupons (UNS G41530, surface area 28.6 cm²) immersed in aerated 15 % HCl for 6 h at 90 °C under static conditions. Weight‑loss measurements (converted to corrosion rate in mm y⁻¹) and electrochemical impedance spectroscopy reveal that the quaternary salt forms a persistent chemisorbed film obeying the Langmuir adsorption isotherm, with a standard free energy of adsorption ΔG^∘ of approximately −38 kJ mol⁻¹. The operational boundary is sharp: the inhibitor film destabilises at temperatures above 105 °C or when the acid concentration exceeds 20 %, requiring co‑addition of an acetylenic alcohol intensifier. Furthermore, the formulation is incompatible with ferric ion concentrations greater than 500 mg L⁻¹ arising from dissolution of iron scale, as such concentrations trigger localised pitting; a pre‑flush of 7.5 % HCl with 0.1 wt % citric acid is recommended to mitigate this risk. The end product is a ready‑to‑use corrosion inhibitor package meeting the acceptance criterion of ≤ 0.05 lb ft⁻² day⁻¹ (equivalent to 0.124 mm y⁻¹) for coiled tubing acidizing treatments in dolomite formations.

Note: Weight‑loss data obtained in 15 % HCl, 90 °C, 6 h, N80 coupon per NACE TM0169‑2012; each value is the mean of triplicate determinations.

Achieving a 30 % Increase in Scorch Time ts2 at 135 °C in NR/SBR Blends

The delayed‑action sulfenamide accelerator N‑cyclohexyl‑2‑(trifluoromethyl)benzothiazole‑2‑sulfenamide (CBTBS) is synthesised from 2‑(trifluoromethyl)-1,3-benzothiazole via conversion to the corresponding 2‑mercapto analogue by treatment with sodium hydrosulphide (1.5 equiv) in DMF at 120 °C, followed by oxidative coupling with cyclohexylamine and sodium hypochlorite (25 % active chlorine, 1.05 equiv) at 0–5 °C. The resulting accelerator contains less than 0.1 % free amine by GC, a critical purity specification to avoid premature scorch. In a typical tread compound based on NR 70/BR 30 with N234 carbon black at 45 phr, CBTBS is dosed at 1.2 phr alongside sulphur (1.8 phr), zinc oxide (3.0 phr), and stearic acid (2.0 phr); mixing is performed in a 1.6 L internal mixer (fill factor 0.75, rotor speed 60 rpm) with a dump temperature not exceeding 130 °C. Cure characteristics are evaluated at 150 °C on a moving‑die rheometer (MDR 2000, arc 0.5°, frequency 1.67 Hz) following ASTM D5289‑19a. Compared to a control compound with conventional N‑cyclohexyl‑2‑benzothiazole sulfenamide (CBS) at the same molar loading, CBTBS extends the scorch time t_s2 at 135 °C by 30 % while maintaining a similar t₉₀ value; the shift is attributable to the electron‑withdrawing ‑CF₃ group raising the N–S bond dissociation energy, thereby retarding the nucleophilic cleavage that generates the active mercaptobenzothiazole species. The compound must additionally comply with ASTM D3192‑09 for carbon black evaluation in NR, with tensile strength (dumbbell, ASTM D412‑16) exceeding 21 MPa and elongation at break ≥ 450 %. Storage stability of the pure CBTBS powder requires conditions below 30 °C and relative humidity below 50 % to prevent premature hydrolysis to the parent mercaptan; a one‑month open‑dish stability test at 40 °C/75 % RH results in a 2.5 % loss of assay. The final tread cap compound is applied in radial truck tyres, where the improved scorch safety enables higher extrusion throughput (+ 15 % screw speed) without risk of premature crosslinking in the die head.

Data generated on an MDR 2000 per ASTM D5289‑19a; tensile tested per ASTM D412‑16, die C.

Sulphonated 2‑(trifluoromethyl)-1,3-benzothiazole, obtained by direct treatment of the parent heterocycle with 20 % oleum at 60 °C for 4 h followed by neutralisation with 50 % sodium hydroxide to pH 8.5, serves as a dual‑function optical brightener and photostabiliser in low‑density polyethylene greenhouse films because its excited‑state intramolecular proton transfer (ESIPT) character absorbs UV‑A radiation while emitting visible blue fluorescence. Prior to extrusion, the sodium sulphonate salt is predispersed at 10 wt % in a linear low‑density polyethylene carrier resin using a co‑rotating twin‑screw extruder with an L/D ratio of 40 : 1 and screw speed 300 rpm; barrel temperatures are set at 140–170 °C. This masterbatch is let down into the base LDPE (MFI 0.3 g (10 min)⁻¹, 190 °C/2.16 kg) to achieve a final brightener loading of 0.05 phr, co‑added with a hindered amine light stabiliser (0.15 phr) and a phenolic antioxidant (0.05 phr). The compound must demonstrate compliance with European Regulation EU 10/2011 for plastic food contact materials: specific migration of the sulphonated benzothiazole moiety into the simulant 3 % acetic acid (10 days at 40 °C) must remain below 0.05 mg kg⁻¹. Film blow‑moulded to a thickness of 150 µm achieves a CIE whiteness index increase of 8 units and a 15 % enhancement in PAR transmittance relative to UV‑only stabilised controls, as quantified by ASTM E313‑20. Published data for long‑term field exposure in Mediterranean climate under this specific formulation are limited, but accelerated QUV testing (ASTM G154‑16, UVA‑340 lamps, 1000 h) indicates a tensile strength retention exceeding 85 % when the brightener is present, compared to 72 % for films containing HALS alone.