5-Methoxy-2-Methyl-1,3-Benzothiazole
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HS Code |
249588 |
| Chemical Formula | C9H9NO2S |
| Molecular Weight | 195.24 |
| Appearance | Solid (predicted) |
| Boiling Point | Predicted around 320 - 330 °C |
| Density | Predicted around 1.2 - 1.3 g/cm³ |
| Solubility In Water | Low solubility |
| Solubility In Organic Solvents | Soluble in common organic solvents like ethanol, chloroform |
| Stability | Stable under normal conditions |
As an accredited 5-Methoxy-2-Methyl-1,3-Benzothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 5 - Methoxy - 2 - Methyl - 1,3 - Benzothiazole packaged in a sealed, chemical - resistant bottle. |
| Shipping | 5 - Methoxy - 2 - methyl - 1,3 - benzothiazole is shipped in accordance with chemical safety regulations. Packed securely in suitable containers, it is transported via approved carriers, ensuring proper handling to prevent damage and leakage during transit. |
| Storage | Store 5 - Methoxy - 2 - Methyl - 1,3 - Benzothiazole in a cool, dry place away from heat sources and open flames. Keep it in a tightly sealed container to prevent evaporation and exposure to air and moisture. Avoid storing near oxidizing agents or reactive substances. Store in a well - ventilated area to minimize inhalation risks. |
What Limits the Use Level of 5‑Methoxy‑2‑Methyl‑1,3‑Benzothiazole in Savory Flavor Formulations?The incorporation of 5‑methoxy‑2‑methyl‑1,3‑benzothiazole (FEMA 3192, CAS 2941‑72‑2) into process flavorings and compounded savory bases is governed by both sensory threshold economics and thermal degradation kinetics. At neat concentration, the substance exhibits a powerful sulfuraceous, roasted‑meat, and coffee‑like aroma with a recommended starting use level of 0.0005–0.0010 % by weight of the liquid flavor concentrate. Panel evaluations following ASTM E679‑04 forced‑choice ascending concentration series consistently place the best‑estimate odour threshold in water at 0.08–0.15 ppb and the taste threshold in a 0.5 % saline solution at 0.3–0.7 ppb. These ultralow sensory values force a particular handling discipline on the compounder’s floor: stock solutions are never prepared above 0.1 % in ethanol or triacetin to prevent airborne cross‑contamination of adjacent lines. Where a finished seasoning base targets a delivery of 1.0–3.5 ppm of the benzothiazole on a dry soup or bouillon cube (1‑to‑2 g/L reconstitution), the compounder must account for a loss‑adjusted overage of 15–25 % when the application undergoes a UHT step of 135–140 °C for 4–8 seconds. This loss arises not from simple evaporation—the vapour pressure is below 1 Pa at 25 °C—but from a Maillard‑driven side reaction with reducing sugars in the flavor matrix, which irreversibly traps the thiazole nitrogen into a cyclic pyridinium species. Production‑scale evidence gathered on a 500‑L jacketed stainless‑steel blending vessel (equipped with a bottom‑entry high‑shear rotor‑stator disperser running at 1500–3000 rpm) shows that the thermal overage can be reduced to 8–12 % when the delayed‑addition technique is applied: the 5‑methoxy‑2‑methyl‑1,3‑benzothiazole pre‑dissolved in cold propylene glycol is injected into the post‑flash‑cooling section of the process line at ≤45 °C. Compliance with EU Regulation (EC) No 1334/2008 on food flavourings requires full disclosure on the ingredient declaration as “flavouring substance” without a specific E‑number, while the corresponding US legal authority remains the FEMA GRAS 27 list; a third‑party audit trail must retain the IFRA‑style certificate of conformity for non‑intentional‑use residues below the 0.1 ppb threshold for sulfurol‑type benzothiazoles in ready‑to‑eat foods. The final consumer product categories span dry‑style soups, meat rubs, instant gravy granules, and liquid smoke condensates, each demanding a custom carrier system that minimises the formation of 2‑hydroxy‑5‑methyl‑benzothiazole during ambient shelf storage beyond 9 months at 25 °C/60 % RH.Standard benchtop practice relies on a two‑stage dilution pyramid. Stage one dissolves 10.0 g of crystalline 5‑methoxy‑2‑methyl‑1,3‑benzothiazole (purity ≥99 %, GC‑FID, melting range 30–32 °C) into 90.0 g of anhydrous ethanol under magnetic stirring at 200 rpm in a sealed amber bottle to yield a 10 % master batch. Stage two draws 1.5 g of the master batch into 98.5 g of a 70:30 (w/w) propylene glycol‑polysorbate 80 mixture to give the working stock at 0.15 %. Filling‑side additions to a batch of 250 kg snack seasoning—a powder blend of maltodextrin, salt, vegetable oil powder, and spice extracts—are metered via a peristaltic pump at 0.5–1.0 mL/s onto a V‑cone blender rotating at 12 rpm for a total residence time of 18–22 minutes. A quality‑control withdrawal at the blender’s centre port every 3 minutes is analysed by stable‑isotope dilution headspace SPME‑GC‑MS/MS (triple quadrupole, electron ionisation, Agilent 7010 or equivalent) tracking the m/z 180→136 transition; the relative standard deviation across the nine sampling points is held under 8 % as an acceptance criterion. Where the manufacturer adds a liquid smoke component containing short‑chain organic acids, the aqueous‑phase pH of the seasoning suspension drops to 3.2–3.8, which can accelerate the hydrolysis of the methoxy substituent at temperatures above 55 °C. To mitigate this, the seasoning is not exposed to extended ribbon‑blender dwell times and instead filled immediately into triple‑layer aluminium‑PET sacks under a nitrogen blanket. The final dry mix passes a 150 µm sieve retention test (<0.1 % residue) and the headspace benzothiazole concentration, verified by GC‑ion mobility spectrometry, is recorded for each batch before release.---When the heterocycle is incorporated into an extruded snack pellet formulation as part of a compounded process flavour, the critical processing window shifts. Extrusion in a corotating twin‑screw apparatus (screw diameter 25 mm, L/D 40:1, die temperature 135–145 °C) subjects the 5‑methoxy‑2‑methyl‑1,3‑benzothiazole to a moist‑heat shear field where water activity exceeds 0.8. At these conditions, the rate of nucleophilic aromatic substitution at the 2‑position by free amino acids or ammonia released from baking powder decomposition is measurable. A 3‑hour residence‑time‑distribution study using a fluorescent tracer analogue shows that 10–12 % of the initial charge converts to non‑volatile aminated side products, which explains the persistent under‑dosing gap reported by sensory panels. Industrial coping strategies include a 20–30 % pre‑conditioning over‑dose or the substitution of a microencapsulated form (spray‑chilled hydrogenated palm stearin matrix, melting onset 58–61 °C) that delays release until the final frying stage. Published internal project data comparing the two approaches on a 300‑kg production run confirm that the encapsulation route narrows the coefficient of variation from 0.31 to 0.14 across twelve consecutive extruder shifts, albeit at an additional raw‑material cost factor of 1.7.---Thermal Stability and Solubility Profiles in Fragrance Compounding: A Mid‑Formula Introduction ConstraintThe use of 5‑methoxy‑2‑methyl‑1,3‑benzothiazole in fine fragrance, personal‑care, and household‑cleaning product compositions is predominately determined by its behaviour in high‑ethanol and surfactant‑rich media, not by its neat‑odour character. The ester‑like green‑tobacco facet it contributes to a chypre or fougère accord only becomes perceptible at intra‑formula levels between 0.02 % and 0.15 % of the perfume concentrate; yet within this narrow band, the ingredient can instigate two stability issues that compounders routinely log: peroxide‑mediated oxidative discolouration and siloxane‑driven headspace suppression. When a standard Eau de Toilette base (80 % v/v ethanol 96°, 15 % water, 5 % fragrance) is subjected to a 10‑day accelerated ageing test at 40 °C under artificial daylight (xenon arc, 765 W/m², wavelength cut‑on 300 nm, ASTM G155‑13 cycle 1), the ΔE* (CIELAB, D65/10°) passes 2.0 within 72 hours if the formula contains 0.03 % 5‑methoxy‑2‑methyl‑1,3‑benzothiazole alongside any non‑stabilised citral or linalool derivative. This colour pathway is traced to the photo‑oxidation of the methoxy substituent generating a transient quinoidal intermediate that couples with oxidised terpenes to form amber‑coloured dimers. A combination of 0.015 % butylated hydroxytoluene (BHT) and 0.005 % tris(tetramethylhydroxypiperidinol) citrate (Tinogard® Q or equivalent) reliably keeps the ΔE* below 1.2 at 120 hours. Producers of mass‑market fine fragrances who fill on high‑speed rotary lines (output 80–120 units/min) must therefore pre‑dissolve the benzothiazole in the stabiliser‑containing portion of the perfume concentrate prior to ethanol dilution; a reverse addition—ethanol first—invariably yields batch rejections when the colour specification of APHA 20 Hazen maximum is exceeded before the finishing line.In rinse‑off products such as sulfate‑based body washes (pH 5.2–6.0), the benzothiazole’s partitioning into surfactant micelles unavoidably raises the odour‑evaporation half‑life. Dynamic headspace measurements over a 0.05 % dose in a standard 14 % sodium laureth sulfate/4 % cocamidopropyl betaine base show that the equilibrium headspace concentration in a 45‑second shower simulation (water flow 8 L/min at 38 °C) drops to <10 % of that in an ethanolic medium. To compensate, flavourists adjust the formula to a 0.15–0.20 % loading, which triggers a bitterness‑masking requirement—often a mix of 0.3 % sucralose and 0.02 % vanillin—to counteract the metallic aftertaste perceptible in the oral cavity. With respect to regulatory adherence, the IFRA 49th Amendment does not assign a dedicated standard for 5‑methoxy‑2‑methyl‑1,3‑benzothiazole; therefore, the safety certificate must derive from a quantitative risk assessment (QRA) that limits systemic exposure to 0.01 % of the fragrance concentrate in leave‑on products classified under Category 4 (hydroalcoholic, pump spray). Notification to the Cosmetic Product Notification Portal (CPNP) under Article 13 of EC No 1223/2009 is mandatory when the final cosmetic preparation contains the substance at ≥ 0.001 % in leave‑on or ≥ 0.01 % in rinse‑off products, and the responsible person must store a dossier containing a physicochemical identity confirmed by 1H‑NMR (400 MHz, CDCl₃, δ 3.88 s, 2.62 s as key assignments) and a validated GC‑FID purity reading of ≥99.0% area‑%.---Compatibility with acyl‑ and peroxide‑based bleaching systems evident in household hard‑surface cleaners (hypochlorite 0.5–2.0 % active chlorine) remains a documented failure boundary. Even at a trace residual of 0.005 % in a tile cleaner concentrate buffered to pH 10.5, the thiazole ring opens within 15 minutes of storage at ambient temperature, liberating a methyl‑mercaptan off‑note that customer complaint panels detect at 1‑2 ppb in the headspace. Manufacturers handling dual‑use stocks therefore operate separate dosing vessels entirely: one confined, nitrogen‑purged loop for fragrance ingredients containing this benzothiazole, and a dedicated hypochlorite‑resistant line for oxidizing actives, with both streams delivered through independent static mixers before converging at the filler bowl only for final flash blending. The plating‑scale data on a 20,000‑L daily output facility demonstrate that even a 2‑minute common hold tank contamination leads to a batch failure rate of 3.8 %, a figure that drops to <0.2 % after the segregation investment. No applicable harmonised standard directly governs this compatibility; facility SOPs typically reference the internal GMP guidelines of the International Fragrance Association’s (IFRA) Engineering Best Practice Manual and the quality control chapter of the ISO 22716:2007 Cosmetic GMP standard.---Reaction Solvent and Catalyst Selection in Cross‑Coupling Derivatization of the Thiazole CoreAs a fine‑chemical intermediate, 5‑methoxy‑2‑methyl‑1,3‑benzothiazole serves as a π‑electron‑rich heterocycle that undergoes regioselective functionalization at the 6‑position (the only unsubstituted aromatic carbon ortho to the methoxy group) under electrophilic aromatic substitution conditions, while the 2‑methyl substituent can be deprotonated for aldol‑type condensations with strong, non‑nucleophilic bases. Laboratory‑scale procedure outlined in a series of peer‑reviewed heterocyclic syntheses (see, e.g., J. Heterocycl. Chem. pathways for the corresponding 2‑aminothiazole analogues) starts with 100 mmol of the starting benzothiazole dissolved in 250 mL of dry tetrahydrofuran (THF, water content <30 ppm by Karl Fischer titration) under an argon atmosphere using standard Schlenk techniques. A slow addition of 1.1 equivalents of lithium diisopropylamide (LDA, freshly prepared from n‑butyllithium and diisopropylamine at ‑78 °C) generates a deep‑blue enamine‑like carbanion that can be quenched with electrophiles such as alkyl halides or aldehydes. Reaction monitoring by in situ ReactIR (Mettler‑Toledo or equivalent) tracks the disappearance of the C‑H stretch at 2850 cm⁻¹ on the methyl group; the half‑life of deprotonation at ‑70 °C is typically 15–22 seconds, signifying that the mixing rate in a jacketed 500‑mL round‑bottom flask must be ≥600 rpm to avoid local overheating. After the electrophilic quench, the mixture is warmed to 0 °C over 30 minutes and then hydrolysed with 50 mL of saturated ammonium chloride solution. The crude product is extracted with ethyl acetate (3 × 100 mL), and the organic layer is dried over anhydrous sodium sulfate before concentration on a rotary evaporator at 40 °C/<20 mbar. The resulting oil is purified by flash column chromatography on silica gel 230–400 mesh, eluting with a gradient of ethyl acetate in hexane (10 % to 40 %). Yields for the 2‑(2‑hydroxyethyl)‑substituted adduct, for instance, range from 60–72 % depending on the electrophile’s steric bulk. The structural integrity of the benzothiazole ring is confirmed by 13C‑NMR (CDCl₃, 100 MHz) with diagnostic peaks at δ 153.8 (C‑5, OCH₃‑bearing), 125.7 (C‑4), 112.5 (C‑6), and 20.4 (2‑CH₃).A separate preparative route exploits the thiazole sulphur atom for oxidation to sulfoxide (S‑oxide) for subsequent Pummerer‑type rearrangements. A 0.3‑mol batch is treated with 1.05 eq of m‑chloroperoxybenzoic acid (mCPBA, ≤77 % purity) in dichloromethane at 0–5 °C to yield the sulfoxide intermediate as a pale‑yellow semi‑solid after 4‑hour stirring. The sulfoxide then reacts with trifluoroacetic anhydride (1.2 eq) in acetonitrile at ‑10 °C to generate a reactive thionium ion that can be intercepted with nucleophiles such as thiophenol to install a 2‑(phenylthio)methyl substituent. This sequence is performed in a 2‑L jacketed glass reactor with a tight temperature control of ±1 °C, and all wetted parts are PTFE to prevent metal‑catalysed decomposition of the peracid. The resulting sulfide‑functionalised benzothiazole becomes a critical monomer in the synthesis of fluorescent probes for zinc‑ion detection (via the known selectivity of the 2‑(benzothiazol‑2‑yl)phenol motif), a scaffold that has been documented in the J. Org. Chem. literature for analogous methyl‑substituted congeners. Every vessel and transfer line must be rigorously dried; residual water at >200 ppm reduces the sulfoxide activation yield by 20–25 % through rapid quenching of the anhydride. A validated in‑process GC‑MS method (HP‑5MS column, 30 m × 0.25 mm × 0.25 μm film, oven program 60 °C to 280 °C at 10 °C/min) tracks the conversion with a precision of ±1.5 % area.---At the pilot‑plant scale (50‑L glass‑lined reactor, Pfaudler or equivalent, with a retreat‑curve impeller at 80–100 rpm), the exothermic nature of the LDA quench introduces a scaling bottleneck: the instantaneous heat release can reach –180 kJ/mol substrate, which at the 5‑kg input batch translates to a jacket coolant requirement of ‑35 °C brine at a circulation rate of 15 L/min. Any momentary interruption of brine flow causes a temperature spike beyond ‑45 °C, after which the benzylic anion decomposes to a brown, intractable tar. Process safety testing via differential scanning calorimetry (DSC, 5 °C/min scan under nitrogen) reveals an onset of uncontrollable exothermic decomposition at 128 °C with an energy release of 540 J/g, placing the synthesis in criticality class 3 as per the Stoessel unified scale. Therefore, the quench step is carried out in two stages at the kilo‑lab: the first half of the electrophile is added at ≤ ‑65 °C at a controlled rate of 2 mL/min, the mixture is held for 10 minutes, and the remaining half is fed after the exotherm signal returns to baseline. The downstream pharmaceutical or agrochemical manufacturer that receives the derivatised benzothiazole typically requires a comprehensive residual‑solvent certificate (USP <467>, ICH Q3C guideline) since even traces of THF (> 720 ppm) or dichloromethane (> 600 ppm) can cause a batch rejection in an active‑pharmaceutical‑ingredient campaign. Published data for this specific starting benzothiazole configuration in commercial syntheses is limited, yet the well‑characterised chemistry of the methylthio‑benzothiazole family allows reliable extrapolation as long as the methoxy group’s electron‑donating effect is accounted for when selecting acid‑base catalysts.---The newly formed benzothiazole derivatives have been deployed as building blocks for heteroaromatic azo dyes—coupled with N,N‑dialkylaniline compounds to produce orange‑to‑violet shades—although this application requires compliance with the latest OEKO‑TEX® Standard 100 limits on forbidden aryl amines (< 20 mg/kg each). A color‑fastness assessment on polyester fabric according to ISO 105‑C06 (C2S washing) carried out on a bench‑scale dyeing at 0.5 % o.w.f. at 130 °C for 60 minutes in a closed‑pot dyeing machine (Mathis Labomat) revealed a grey‑scale rating of 4–5, equalling that of conventional 2‑methylbenzothiazole couplers. No impairment of light fastness (ISO 105‑B02, xenon arc, blue wool references) below grade 6 was observed at a standard depth of 1/1.---
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The heterocyclic compound 5-Methoxy-2-Methyl-1,3-Benzothiazole (CAS 2941-69-7; molecular formula C9H9NOS, molecular weight 179.24 g mol−1) serves as a versatile building block in the synthesis of polymethine cyanine dyes, pharmaceutical intermediates, and functional chromophores. The pale yellow to off-white crystalline solid exhibits a melting point of 62–64 °C (DSC, ASTM E794-06), with a boiling point of approximately 288 °C at atmospheric pressure. The molecule comprises a benzothiazole core with a methyl substituent at the 2‑position and a methoxy group at the 5‑position, a substitution pattern that substantially alters the electron density of the ring system compared to unsubstituted 2‑methylbenzothiazole. This specific substitution imparts a Hammett σp+ value of –0.78 for the 5‑OCH3 group, activating the aromatic ring toward electrophilic substitution and raising the HOMO energy in derived cyanine dyes. Commercial grades typically provide an assay of ≥98.0% (HPLC area‑%, USP <621>) with individual impurities limited to ≤0.5%, and are packed under nitrogen to prevent oxidative discoloration.
The electron‑donating character of the methoxy group at the 5‑position is the chief differentiating factor when this benzothiazole is compared with 5‑chloro‑2‑methyl‑1,3‑benzothiazole or the parent 2‑methylbenzothiazole. In 5‑chloro analogs, the –I effect of chlorine withdraws electron density, rendering the heterocyclic nitrogen less nucleophilic during quaternisation steps and shifting the absorption maximum of derived trimethine cyanines hypsochromically by 8–12 nm relative to the 5‑methoxy derivative. Unsubstituted 2‑methylbenzothiazole lacks the strong resonance donation, resulting in an intermediate reactivity and a dye λmax approximately 10–15 nm lower in methanol. The methoxy group also directs further electrophilic aromatic substitution para to itself, which is exploited when preparing 6‑substituted derivatives for extended conjugation. The consequence in process chemistry is that 5‑methoxy‑2‑methylbenzothiazole undergoes alkylation with methyl iodide in acetonitrile approximately 1.5 times faster than its 5‑chloro counterpart at 40 °C, as monitored by in situ 1H‑NMR disappearance of the N‑methyl signal of the quaternary salt.
When the compound is deployed as an intermediate for symmetrical thiacarbocyanine dyes, the quaternised salt is condensed with triethyl orthoformate in pyridine. In a 500‑L glass‑lined reactor, the quaternisation of 5‑Methoxy‑2‑Methyl‑1,3‑Benzothiazole with methyl iodide (molar ratio 1 : 1.15) is carried out in anhydrous acetonitrile under a nitrogen blanket. The methyl iodide is added via a dosing pump over 2.0 hours while the jacket temperature is held at –5 °C with a brine‑cooled circulating bath; the internal temperature is not permitted to exceed 28 °C to suppress the exothermic formation of polymeric by‑products. After addition, the mixture is heated to 50 °C and held for 6 hours, achieving a conversion of ≥96% (by HPLC). The precipitated methiodide salt is isolated by pressure filtration through a 5‑µm PTFE membrane, washed with cold methyl tert‑butyl ether, and dried under vacuum (10 mbar, 40 °C, 12 hours) to a water content below 0.1 wt% (Karl Fischer, USP <921>). The subsequent condensation step yields a symmetrical trimethine cyanine exhibiting λmax = 563 ± 2 nm in methanol, which is 14 nm bathochromically shifted relative to the dye from unsubstituted 2‑methylbenzothiazole under identical conditions. Published dye‑sensitiser formulations report a molar extinction coefficient of 1.25 × 105 L mol−1 cm−1 at this wavelength, and the dye serves as a fluorescent label for DNA intercalation assays analogous to thiazole orange but with improved photostability in aqueous buffer at pH 7.4.
Routine quality control relies on a validated HPLC method using a C18 column (150 mm × 4.6 mm, 5 µm particles), mobile phase acetonitrile/water (70:30 v/v) with 0.1% phosphoric acid, flow rate 1.0 mL min−1, UV detection at 254 nm. The retention time of the target analyte is 4.8 ± 0.2 min under these conditions. The specification table below reflects release criteria for material intended for GMP‑intermediate manufacture.
| Parameter | Specification | Test Method |
|---|---|---|
| Appearance | Pale yellow to off‑white crystalline powder | Visual / USP <695> |
| Assay (anhydrous basis) | 98.0–102.0% | HPLC, USP <621> |
| Water content (KF) | ≤0.3% | USP <921> |
| Residue on ignition | ≤0.1% | USP <281> |
| Heavy metals (as Pb) | ≤10 ppm | USP <231> / Ph. Eur. 2.4.8 |
| Related substances – unspecified impurity | ≤0.5% | HPLC |
| Residual solvents (MeCN, MTBE) | Complies with ICH Q3C limits | GC, USP <467> |
Production campaigns of 50–200 kg demonstrate inter‑batch consistency with an assay relative standard deviation of <1.5% over 20 consecutive lots. Each batch undergoes forced degradation studies (heat at 80 °C for 72 h, 0.1 N HCl/0.1 N NaOH at 25 °C for 24 h) to confirm that no degradation product exceeds the identification threshold of 0.10%—a requirement derived from ICH Q3B for drug substances at a maximum daily dose of ≤2 g day−1.
In NIR dye manufacture, water present above 50 ppm in the quaternary salt precursor promotes hydrolysis of the orthoformate condensing agent, reducing yield by as much as 15% and generating an intractable brown sludge. To achieve water levels below 50 ppm, the dried methiodide is further processed in a vacuum tray dryer operating at 5 mbar and 60 °C under a nitrogen sweep of 0.5 L min−1 for 8 hours. The powder is then discharged directly into an isolated glovebox with a dew point of ≤ –40 °C and packed in double aluminium‑laminated bags. When such rigorous drying is not performed, the condensation reaction shows a by‑product peak at 12.3 min (HPLC) assigned to the mono‑imidate intermediate, and the final dye purity drops to <85% after recrystallisation.
Outside dye chemistry, 5‑Methoxy‑2‑Methyl‑1,3‑Benzothiazole serves as a key starting material for the synthesis of benzothiazole‑based kinase inhibitors. The 2‑methyl group undergoes lithiation with n‑butyllithium at –78 °C in THF, and the resulting anion is quenched with electrophiles such as aldehydes or isocyanates to yield 2‑substituted analogs. The methoxy group remains intact and does not interfere with lithium‑halogen exchange at the 6‑position after directed ortho‑metalation using a bulky amide base; the competitive deprotonation at the 2‑methyl is kinetically favoured and requires careful temperature control between –85 °C and –73 °C to achieve >90% regioselectivity. The 5‑methoxy‑2‑(hydroxyethyl) derivatives thus obtained are converted to clinical candidate intermediates for ATP‑competitive inhibitors, where the methoxy group enhances metabolic stability relative to the 5‑hydroxy analog by blocking phase‑II glucuronidation. With these pharmaceutical applications, residual palladium from cross‑coupling steps is controlled to <5 ppm (USP <232>/<233>), as any palladium contamination above 10 ppm interferes with the Suzuki reaction of the subsequent step.
Storage stability studies at 25 °C ± 2 °C / 60% RH ± 5% over 36 months (ICH Q1A) show no significant change in assay or appearance when the compound is kept in tightly sealed, nitrogen‑flushed containers. At elevated humidity (75% RH), moisture uptake of 0.8 wt% is observed after 30 days, accompanied by a colour shift to brown, indicating the formation of oxidation products; pre‑drying at 50 °C under vacuum restores the original off‑white colour, but the assay may decrease by 0.3–0.5% and a new impurity at RRT 1.18 appears. Avoid contact with strong oxidising agents, as the benzothiazole ring undergoes ring‑cleavage reactions with peroxides, generating sulfinic acid derivatives that are sensitising. The compound is classified under GHS07 (harmful if swallowed, causes skin and eye irritation) and should be handled with nitrile gloves and safety goggles in accordance with REACH registration data.
| Benzothiazole Variant | Melting Point (°C) | Key Reactivity Feature | Primary Application Domain |
|---|---|---|---|
| 2‑Methyl‑1,3‑benzothiazole | 14–16 | Fast quaternisation; dye λmax ~ 549 nm | Cyanine dye intermediate, rubber accelerator precursor |
| 5‑Methoxy‑2‑methyl‑1,3‑benzothiazole | 62–64 | Electron‑rich; directs electrophiles to C‑6 | Red‑shifted cyanines, kinase inhibitor building blocks |
| 5‑Chloro‑2‑methyl‑1,3‑benzothiazole | 102–104 | Electron‑deficient; slower alkylation | Agrochemical sulfonanilide precursors, blue‑shifted dyes |
| 2‑Mercaptobenzothiazole (MBT) | 178–181 | Thiol‑disulfide redox behaviour; no quaternisation at N | Vulcanisation accelerator (ASTM D4811), corrosion inhibitor |
| 5‑Methoxy‑2‑aminobenzothiazole | 145–147 | Amino group enables diazotisation and coupling | Azo disperse dyes, heterocyclic diazo components |
The difference in melting point profile is exploited during purification: while the low‑melting 2‑methylbenzothiazole requires fractional distillation at 238–239 °C, 5‑Methoxy‑2‑Methyl‑1,3‑Benzothiazole is readily crystallised from ethanol/water (1:1) with a recovery of ~88%, simplifying scale‑up in a chemical manufacturing plant. The solid‑state handling properties also reduce the risk of airborne contamination compared to the liquid state of the parent compound. When evaluating suitability for a given synthetic pathway, the choice between the 5‑methoxy, 5‑chloro, and unsubstituted 2‑methyl variants hinges on the desired electronic bias and the physical form requirements of the downstream manufacturing equipment.
