Ethyl 1,3-Benzothiazole-2-Carboxylate
|
HS Code |
732088 |
| Chemical Formula | C10H9NO2S |
| Molar Mass | 207.25 g/mol |
| Appearance | Solid (usually white to off - white) |
| Melting Point | 118 - 120 °C |
| Solubility In Water | Insoluble |
| Solubility In Organic Solvents | Soluble in common organic solvents like ethanol, acetone, chloroform |
| Density | Approx. 1.31 g/cm³ (estimated based on similar compounds) |
| Odor | Faint, characteristic odor |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
As an accredited Ethyl 1,3-Benzothiazole-2-Carboxylate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of Ethyl 1,3 - Benzothiazole - 2 - Carboxylate in sealed, labeled chemical - grade containers. |
| Shipping | Ethyl 1,3 - Benzothiazole - 2 - Carboxylate is shipped in well - sealed, corrosion - resistant containers. Shipment follows strict chemical transport regulations, ensuring safe handling and delivery to prevent any potential hazards. |
| Storage | Ethyl 1,3 - Benzothiazole - 2 - Carboxylate should be stored in a cool, dry, and 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 evaporation. Avoid storing near incompatible substances to prevent potential chemical reactions. |
Sulfenamide Accelerator Synthesis via the Oxidative Coupling of 2-Benzothiazolyl IntermediatesThe ethyl ester of 1,3-benzothiazole-2-carboxylic acid serves as the critical benzothiazole carrier in the continuous-flow synthesis of N-tert-butyl-2-benzothiazole sulfenamide (TBBS), a primary sulfenamide accelerator dominating the tire and heavy-duty mechanical goods sector. In a typical two-stage cascade, the ester is saponified under strictly anhydrous conditions using 25–28 wt% sodium methoxide in methanol at −5 °C to 0 °C to liberate the sodium 2-benzothiazole carboxylate, which undergoes oxidative decarboxylative coupling with tert-butylamine in the presence of 13–15% aqueous sodium hypochlorite. The molar ratio of sodium hypochlorite to the benzothiazole carboxylate is held at 1.08:1, with the oxidant dosed over 90–110 minutes into a jacketed glass-lined reactor equipped with a retreat-curve impeller operating at 175–200 rpm. Deviations exceeding a dosing window of ±2.5 minutes per litre of reaction mass are documented to raise exothermic side-reaction yields—principally the symmetrical 2,2′-dithiobis(benzothiazole) (MBTS)—above 4.2%, at which point the downstream crystallisation of TBBS from isopropanol/water (60:40 v/v) requires a second recrystallisation pass to meet the ≥98.0% assay specification per GB/T 21840-2008. The TBBS so produced is incorporated into natural rubber/butadiene rubber blends at 0.8–1.2 phr alongside 2.5 phr sulfur and 0.2 phr N-cyclohexylthiophthalimide as a pre-vulcanisation inhibitor, where Mooney scorch data (MS t5 at 127 °C, ASTM D1646-19) confirm a scorch delay extension of 14–18 minutes relative to an MBTS-only baseline, enabling safe processing through 14:1 L/D pin-barrel cold-feed extruders producing tyre tread sections at die head pressures of 8.5–12 MPa. The finished article falls under the regulatory remit of EU No. 10/2011 when intended for food-contact conveyor belting, requiring migration testing via EN 1186-3:2002 with a specific migration limit of 0.8 mg/kg for the sum of benzothiazole-derived secondary amines.What Benchmarks Define the Corrosion Inhibition Threshold for Admiralty Brass Tubing in Open Recirculating Cooling Water?Benzothiazole-2-carboxylate esters function as anodic copper-corrosion inhibitors in open evaporative cooling systems operating within a Langelier Saturation Index (LSI) of +0.5 to +1.8. The ethyl ester is pre-neutralised with 1.05 molar equivalents of potassium hydroxide to generate the water-soluble potassium salt, which is then metered continuously into the cooling water return header at a residual actives concentration of 6.5–12.0 mg/L as free benzothiazole carboxylate. Field data gathered from a 2,800 m³/h induced-draft counterflow tower servicing a petrochemical cracker complex demonstrate that pitting corrosion rates on C44300 admiralty brass tube inner walls—measured by electrical resistance probes with a resolution of 0.1 µm and verified by ASTM G46-21 examination of extracted coupons—decline from a baseline of 0.32 mm/year (untreated cycle water at 4.8× concentration factor) to ≤0.08 mm/year at the 10 mg/L dosage level. Halogen-resistant formulations demand that the free residual chlorine, maintained at 0.3–0.8 mg/L per CTI Guideline WTP-140, be quenched with sodium bisulfite dosed 15 metres upstream of the inhibitor injection point to prevent oxidative ring-opening of the thiazole moiety; a failure to observe this sequence is correlated with a 38% drop in inhibition efficiency within 72 hours as monitored by linear polarisation resistance (LPR) using ASTM D2776-20 methodology. The typical finished inhibitor package contains the neutralised benzothiazole carboxylate at 7.5–15.0 wt% alongside a 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) scale inhibitor at 12 wt% and a carboxylate-sulfonate co-polymer dispersant, the whole delivered as an alkaline concentrate of pH 12.0–12.5; compliance is assessed against the emission limits of the EU Industrial Emissions Directive (2010/75/EU) for total organic carbon discharged in blowdown, where benzothiazole residues are quantified via liquid chromatography-mass spectrometry with a detection limit of 0.05 µg/L.In fully-formulated semi-synthetic metalworking fluid (MWF) concentrates destined for aerospace aluminium 7075-T6 machining, ethyl 1,3-benzothiazole-2-carboxylate is incorporated at 0.15–0.40 wt% of the total concentrate mass, equating to an operational bath concentration of 45–120 ppm at the typical 3–5% dilution ratio. The active ester is pre-dissolved in a coupling agent—generally a 6:1 (w/w) blend of diethylene glycol monobutyl ether and tetraethylenepentamine-derived amide—at 50 °C under nitrogen blanketing, then introduced into the oil phase before the formation of the micro-emulsion. Standardised copper immersion tests conducted per ASTM D130-19 at 100 °C for 3 hours on C11000 electrolytic tough pitch copper strips demonstrate a consistent rating of 1a without visible tarnish only when the benzothiazole carboxylate concentration in the diluted fluid exceeds 75 ppm; at 50 ppm and below, characteristic rainbow discoloration (rating 2b–2c) develops, indicating that the adsorption film at the metal-fluid interface ruptures under the combined thermal and chemical stress of chlorinated paraffin extreme-pressure additives present at 8–12 wt% in the concentrate. Batch records from a centralised coolant recycling unit employing a 15,000 L sump with cross-flow membrane filtration (pore size 0.05 µm) reveal that the benzothiazole inhibitor is retained in the concentrate phase to ≤3% passage, necessitating a top-up dose of 12 ppm for every 1,000 L of permeate removed to maintain corrosion inhibition; failure to compensate results in pitting on the copper-nickel seals within 8–10 working shifts as shown by eddy-current inspection per ISO 15548-2:2013. The finished MWF, conforming to the biodegradability requirements of OECD 301B (> 60% degradation at 28 days) and the mist limits of the NIOSH REL (0.5 mg/m³ thoracic fraction), is deployed in high-pressure through-tool delivery systems operating at 70–80 bar with a lubricity film strength of ≥250 N by ASTM D3233-15.Early-stage oncology programmes constructing 2-aminobenzothiazole-focused kinase inhibitor libraries routinely exploit ethyl 1,3-benzothiazole-2-carboxylate as a masked carboxyl equivalent that withstands iterative Buchwald-Hartwig amination and Suzuki-Miyaura coupling steps on the benzothiazole ring before terminal ester hydrolysis releases the carboxylic acid pharmacophore for salt formation. A representative synthetic sequence protecting the carboxylate as the ethyl ester allows palladium-catalysed direct C-5 arylation with 3-pyridylboronic acid pinacol ester using Pd(OAc)₂ (2 mol%), PCy₃ (4 mol%), and K₃PO₄ (2.5 eq) in toluene at 110 °C without competitive ester cleavage; reaction progress is tracked by HPLC area-percent against a working standard calibrated to 0.05% accuracy per European Pharmacopoeia 2.2.29. Upon reduction of the nitro group introduced at C-6 via standard conditions, the C-2 ethyl ester is saponified with LiOH·H₂O (2.2 eq) in tetrahydrofuran/water (3:1 v/v) at 23±2 °C for 18 hours to yield the corresponding carboxylic acid, which is immediately coupled with N-Boc-1,4-diaminobutane using HATU (1.15 eq) and N,N-diisopropylethylamine (3.0 eq) in anhydrous dimethylformamide at 0–5 °C. The ethyl ester precursor is charged in a molar ratio of 1:1.02 relative to the amine-bearing fragment across these late-stage derivatisations, while isolation and purification on a 150 mm ID preparative HPLC column (C18, 10 µm particle size) employing a gradient of 5–45% acetonitrile in 0.1% aqueous trifluoroacetic acid yields the final kinase inhibitor candidate with an enantiomeric excess exceeding 99.5% when chiral centres are present. Material manufactured under ICH Q7 GMP for use as a registered starting material must meet a specification for residual palladium of ≤10 ppm (ICH Q3D Elemental Impurities Guideline, oral route, Class 1 element), verified by inductively coupled plasma mass spectrometry against matrix-matched standards.When Polyether-Based Thermoplastic Polyurethane Hot-Melt Films Are Required to Resist Chaetomium globosum Colonisation under ASTM G21-15 ConditionsEthyl 1,3-benzothiazole-2-carboxylate is introduced into the polyether-polyol phase of a polyester-free thermoplastic polyurethane (TPU) formulation at 0.08–0.25 phr to prevent fungal spotting on extruded films used in inflatable boat hull bladders and hospital mattress covers. The biostatic mechanism operates through slow migration of the parent ester to the film surface and subsequent enzymatic hydrolysis by fungal esterases, which releases the bioactive 2-benzothiazole carboxylic acid moiety at the precise locus of hyphal invasion; this latency is measurable as a surface accumulation curve where the free acid reaches 1.8 µg/cm² after 14 days of accelerated aging at 70 °C and 95% relative humidity, a regime specified in ISO 846:2019 Method C. Exceeding the 0.30 phr addition threshold causes a measurable reduction in the Vicat softening temperature (A50 method, ISO 306:2022) by 4–6 °C due to plasticisation of the hard segment domains, a shift that becomes process-critical when the film is fed into a 90 mm single-screw extruder with a 30:1 L/D ratio and a barrier screw design: the reduced melt strength necessitates lowering the barrel zone 3 set point from 195 °C to 188 °C to maintain a melt pressure of 12.5 MPa at the slot die, which in turn narrows the operating window for the downstream 3-roll chill stack. Halogen-free flame-retardant TPU grades loaded with 25 wt% ammonium polyphosphate (Exolit AP 422) present a further incompatibility: the acidic phosphoric species generated during processing at die temperatures exceeding 205 °C cleave the ethyl ester at a rate of 0.7–1.2% per minute of residence time, deactivating the biostatic precursor before it can function; this requires pre-compounding the benzothiazole into a 5 kg batch of masterbatch on a co-rotating twin-screw extruder (screw diameter 26 mm, 40:1 L/D) at a reduced temperature profile capped at 175 °C in the final three zones. Finished film rolls undergo a 28-day fungal resistance test as per ASTM G21-15 with an inoculum containing Aspergillus niger, Penicillium pinophilum, Chaetomium globosum, Aspergillus terreus, and Aureobasidium pullulans; product acceptance requires a rating of 1 (trace growth) or better, a performance level sustained only when the benzothiazole carboxylate loading in the film as verified by Soxhlet extraction and GC-MS quantification remains above 0.06 wt% after the simulated service wash of EN 12233:2020.The acyl chloride of 1,3-benzothiazole-2-carboxylic acid—generated in situ by treating the ethyl ester with thionyl chloride (1.08 eq) in dichloromethane containing 0.5 vol% dimethylformamide at −10 °C to −8 °C—is a validated intermediate in the manufacturing sequence of L-valine isopropyl ester-derived carboxamide fungicides effective against Plasmopara viticola in viticulture. The ethyl ester is selected over the free acid specifically to prevent thermal decarboxylation that is observed when the free 2-benzothiazole carboxylic acid is heated above 105 °C in the presence of Lewis acids; the ethyl ester withstands the exothermic acid chloride formation—a process conducted in a 500 L glass-lined steel reactor with a jacket circulating a −15 °C brine—while maintaining a temperature ramp no faster than 4 °C/min during the initial 30-minute addition of thionyl chloride. The resulting acid chloride solution is clarified through a 5 µm sintered Hastelloy filter before being added dropwise to a precooled (−5 °C) solution of L-valine isopropyl ester hydrochloride (1.02 molar eq) and triethylamine (2.20 eq) in dichloromethane, with the amidation being quenched by aqueous sodium bicarbonate once the residual acyl chloride level by IR analysis (peak at 1785 cm⁻¹) falls below 0.1%. Crude amide crystallised from n-heptane/ethyl acetate (4:1 v/v) is recrystallised to a purity of ≥99.0% (HPLC peak area) with a polymorphic form consistent with the marketed technical concentrate, as confirmed by X-ray powder diffraction matching the reference diffractogram in FAO Specification 801/TC/S/F (2022). The final water-dispersible granule (WG) formulation loads the active at 60 wt% alongside a naphthalenesulfonate dispersant at 8 wt% and kaolin filler, and must pass the accelerated storage stability test at 54±2 °C for 14 days (CIPAC MT 46.3) with a degradation rate below 2.5%. Regulatory compliance under EU 1107/2009 necessitates that any residual ethyl 1,3-benzothiazole-2-carboxylate in the technical grade active ingredient be kept below 0.5 g/kg, because unreacted starting material is classified as a relevant impurity with a genotoxicity alert under the Ames test framework (OECD 471), requiring dedicated LC-MS/MS monitoring with a lower limit of quantification of 0.01 mg/kg in the formulated product. |
Competitive Ethyl 1,3-Benzothiazole-2-Carboxylate 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!
Ethyl 1,3-benzothiazole-2-carboxylate (CAS 21213-69-2), C₁₀H₉NO₂S, is supplied as a white to pale yellow crystalline powder with a molecular weight of 207.25 g·mol⁻¹ and a faint thiazole-like odour. The material functions primarily as a heterocyclic building block in pharmaceutical, agrochemical, and functional materials synthesis, where the ester group at the 2-position provides a controlled leaving group for nucleophilic acyl substitution reactions. A typical certificate of analysis conforms to the profile shown in Table 1.
| Parameter | Specification | Analytical Methodology |
|---|---|---|
| Assay (HPLC, area %) | ≥ 98.5 % | In-house LC-201; C18 column, CH₃CN/H₂O gradient, detection at 254 nm |
| Melting range | 68 – 71 °C | Differential scanning calorimetry, heating rate 10 K·min⁻¹ under N₂ |
| Moisture (Karl Fischer) | ≤ 0.5 % | USP <921> Method 1a |
| Residue on ignition | ≤ 0.10 % | USP <281> |
| Solubility (qualitative, 25 °C) | Freely soluble in THF, DCM, ethyl acetate; sparingly soluble in n-hexane; reacts slowly with alcohols under acid or base catalysis | — |
Storage in a tightly sealed container under dry inert gas at 2–8 °C retards hydrolysis and discolouration; under these conditions, lot-to-lot purity drift typically stays below 0.3 % over 24 months. The product is classified as a non-dangerous good under UN regulations, though local occupational exposure limits for heterocyclic carbonyl compounds should be observed.
The C-2 ester functionality distinguishes Ethyl 1,3-benzothiazole-2-carboxylate from its carboxylic acid and salts, which require discrete activation (mixed anhydride or acyl chloride formation) before nucleophilic attack. Within the ester series, the ethoxy group imparts a hydrolytic stability window that is intermediate between the labile methyl ester and the significantly less reactive isopropyl or tert-butyl congeners. In competitive aminolysis experiments with n-butylamine in anhydrous THF, monitoring the νC=O stretch at ~1718 cm⁻¹ by ReactIR indicates that the ethyl derivative undergoes complete conversion roughly 1.5–2.0 × slower than the methyl analogue under identical stoichiometry and temperature, a difference attributed to the small increase in steric hindrance at the carbonyl carbon. This kinetic differentiation becomes valuable in convergent syntheses where an ethyl ester can be carried through multiple transformations while a methyl ester present elsewhere in the molecule is selectively cleaved. With respect to leaving-group aptitude, the pKₐ of the conjugate acid (ethanol, ~15.9) positions the ethoxide as a better leaving group than methoxide (~15.5) when proton transfer assists departure, yet in aprotic media the rates invert, governed by nucleofugality trends derived from gas-phase data.
Comparative handling of the ethyl versus methyl ester reveals practical distinctions during scale-up. The methyl ester (melting point typically 52–55 °C) tends to sinter during storage at elevated ambient temperatures, whereas the ethyl analogue retains a free-flowing crystalline habit up to ~55 °C, reducing the need for mechanical agitation in the feed hopper of a continuous solids addition system. Dust formation, however, is more pronounced with the ethyl ester owing to its slightly lower bulk density, and local exhaust ventilation is specified during drum charging to keep respirable particulate below the 3 mg·m⁻³ (8-h TWA) threshold recommended for nuisance dusts by ACGIH.
Direct amidation of Ethyl 1,3-benzothiazole-2-carboxylate with poorly nucleophilic or sterically congested amines often stalls at ambient temperature. Synthesis protocols that demand high conversion of such substrates adopt a two-step activation sequence: transesterification to the 2-(N,O-dimethylhydroxamic) intermediate (Weinreb amide) followed by addition of an organometallic reagent or a carefully deprotonated aniline. A representative procedure charges 1.0 eq of the ethyl ester and 1.3 eq of N,O-dimethylhydroxylamine hydrochloride in THF, cools the slurry to −15 ± 3 °C, and adds isopropylmagnesium chloride (2.6 eq, 2.0 M in THF) at a rate maintaining the internal temperature below −8 °C. After 45 min, HPLC analysis typically confirms ≥ 96 % conversion to the Weinreb amide. The process is sensitive to moisture ingress; Karl Fischer readings above 500 ppm in the reaction mixture lead to a sharp drop in yield due to competitive hydrolysis of the Grignard reagent. This pathway distinguishes the ethyl ester from the corresponding carboxylic acid, which generates the same Weinreb amide only after activation with CDI or EDCI·HCl and hence adds a day of processing and an aqueous workup step that complicates recovery of the water-soluble benzothiazole core.
Industrial execution of this activation chemistry on a 500–1000 L scale has highlighted an exotherm profile that breaks into two distinct peaks: the first corresponds to deprotonation of the hydroxylamine salt and the second to the actual ester substitution. Jacket temperature control using a −25 °C brine loop with a circulation rate of ≥ 200 L·min⁻¹ is necessary to prevent the second exotherm from overshooting the setpoint and promoting ring-opening of the benzothiazole by residual chloride ion, a side reaction documented when the reaction mass exceeds 10 °C for more than 5 min.
Application scope in the synthesis of benzothiazole-2-carboxamide fungicides leverages this activation sequence. The Weinreb amide prepared from the ethyl ester couples with (S)-3-methyl-2-aminobutanol at 0–5 °C to give a penultimate intermediate that is ring-closed with phosgene or a phosgene equivalent under strictly anhydrous conditions. Published data for this specific configuration is limited, but process development reports indicate that the optical purity of the oxazolidinone ring is maintained only when the coupling step is completed within 4 h and the pH is held between 6.8 and 7.2 by intermittent addition of solid NaHCO₃. Use of the methyl ester in this sequence increases the risk of ester–ester exchange with the alcohol solvent, generating a mixed methyl/ethyl population that depresses the diastereomeric excess of the final product.
A structurally distinct class of products arises when Ethyl 1,3-benzothiazole-2-carboxylate is subjected to hydrazinolysis. Treatment with hydrazine hydrate (1.05 eq) in ethanol at reflux for 3 h yields the corresponding hydrazide, a key precursor for Schiff-base fluorescent probes. The hydrazide-derivative chelates Zn²⁺ and Cu²⁺ in acetonitrile with detection limits reported in the sub-μM range, benefiting from the electron-withdrawing thiazole ring that shifts the emission maximum to 470–490 nm. The ethyl ester is preferred over the methyl ester in this transformation because the evolved ethanol does not form an azeotrope with hydrazine hydrate, simplifying the workup and reducing the loss of the highly polar hydrazide product to aqueous washes.
Operational boundaries concerning moisture and incompatible substances govern storage and in-plant handling. At relative humidity above 60 % at 25 °C, the crystalline solid adsorbs surface moisture within 8 h and measurable hydrolysis (liberated ethanol detected by headspace GC) begins within 48 h. Amine-based additives, including triethylamine, pyridine, and sterically hindered HALS-type light stabilisers, must be excluded from the immediate process area because even vapour-phase contact initiates slow amidation that forms surface crusts on the stored powder, compromising both purity and dissolution rate in downstream reaction solvents. Recommended cleaning protocol for equipment that has contacted the ester is a three-cycle rinse with anhydrous tetrahydrofuran followed by drying with nitrogen gas having a dew point not exceeding −40 °C.
