Benzothiazole-2-Acetonitrile

Product Name Benzothiazole-2-Acetonitrile
Alias 2-(Benzothiazol-2-yl)acetonitrile
Einecs EINECS 244-323-4
Mininmum Order 1G
Factory Site West Ujimqin Banner, Xilingol League, Inner Mongolia, China
Price Inquiry sales9@bouling-chem.com
Manufacturer Bouling Chemical Co., Limited
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In terms of specification, Benzothiazole-2-Acetonitrile is supplied with purity (≥98% by GC) and melting point (84–86 °C), making it suitable for use as a key building block in heterocyclic synthesis for pharmaceutical R&D.

Specifications

HS Code	603436
Chemical Formula	C9H6N2S
Molar Mass	174.22 g/mol
Appearance	Solid
Melting Point	104 - 108 °C
Solubility In Water	Insoluble
Solubility In Organic Solvents	Soluble in common organic solvents like ethanol, acetone
Odor	Typical organic compound odor
Stability	Stable under normal conditions

As an accredited Benzothiazole-2-Acetonitrile factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	Benzothiazole - 2 - Acetonitrile packaged in 1 - kg containers for easy handling.
Shipping	Benzothiazole - 2 - Acetonitrile, a chemical, is shipped in sealed, corrosion - resistant containers. Special handling precautions are taken due to its chemical nature. Shipments follow strict regulations to ensure safety during transit.
Storage	Benzothiazole - 2 - Acetonitrile should be stored in a cool, dry, well - ventilated area, away from heat sources and open flames as it may be flammable. Keep it in a tightly closed container to prevent moisture absorption and exposure to air. Store separately from oxidizing agents and incompatible substances to avoid potential chemical reactions.

Application of Benzothiazole-2-Acetonitrile

The cyano-methyl substituent at the 2-position of benzothiazole activates the heterocycle toward condensations where the methylene bridge participates in Knoevenagel-type additions. Production-scale experience in multi-purpose glass-lined reactors (typically 2000–5000 L capacity, jacket temperature control ± 1.5°C) reveals that exothermic runaway risk intensifies when the base catalyst charge exceeds 0.8 mol% relative to the nitrile. A standard operating envelope for downstream dye synthesis therefore limits the semi-batch addition rate of benzothiazole-2-acetonitrile to 0.35 kg/min per cubic metre of solvent, maintaining the reaction mass at 78–82°C in anhydrous ethanol. Foaming induced by trace water hydrolysing the nitrile to amide is suppressed by pre-drying the solvent over 3Å molecular sieves to moisture content ≤ 150 ppm. When these conditions are observed, the intermediate arylidene derivative precipitates directly upon cooling and centrifugation with a purity of ≥ 98.2% (HPLC area%, C18 column, acetonitrile/water 70:30 mobile phase), suitable for the next azo coupling step without recrystallisation. The dominant commercial pathway channels this reactivity into cationic azo dyes for polyacrylonitrile fibre—a segment where the benzothiazole chromophore shifts the absorption maximum bathochromically by 18–25 nm compared to analogous benzimidazole dyes, a technologically significant offset when targeting deep navy and black shades on acrylic.

When Benzothiazole-2-Acetonitrile Enters the Penultimate Step of a Thiazole Carboxamide Fungicide

Transformation of the nitrile into a thiazole-4-carboxamide pharmacophore proceeds through a three-step sequence that has been scaled to 800 kg batch size in Hastelloy C-276 autoclaves. Benzothiazole-2-acetonitrile is first hydrolysed under acidic conditions at 105–110°C with 65 wt% sulphuric acid, giving the corresponding acetic acid derivative; over-hydrolysis leading to decarboxylation must be avoided by terminating the quench when residual nitrile falls below 0.7% by GC. The acid is then converted to the acid chloride using thionyl chloride with catalytic DMF (0.3 wt%) under reflux in toluene, a step that generates corrosive off-gases requiring caustic scrubbing rated for 1.2 × the maximum theoretical HCl and SO₂ load. The terminal amidation with 1.05 equivalents of 2-aminothiazole in dichloromethane at 0–5°C delivers the target carboxamide, which after flash chromatography (silica gel, ethyl acetate/hexane 1:1) shows broad-spectrum activity against Ascomycete pathogens in greenhouse trials. Commercial registrants under OECD guideline 506 batch data have reported yields of 76–81% over the three chemical transformations. The entire process stream is governed by GHS classification for skin sensitisation (H317) of the nitrile starting material, mandating closed-loop transfer and local exhaust ventilation with a capture velocity ≥ 0.5 m/s at all charging ports.

Fluorescent Whitening Agent 368: The Consequence of Molar Extinction Coefficients and Food Contact Migration Limits

4,4′-Bis(benzothiazol-2-yl)stilbene-type optical brighteners utilise benzothiazole-2-acetonitrile as the heterocycle donor in a double Knoevenagel condensation with terephthalaldehyde. The reaction is carried out in dimethyl sulfoxide at 120°C in the presence of piperidine acetate catalyst (2 mol%) and proceeds to completion within 3.5 h as monitored by the disappearance of the aldehyde C–H stretch at 2720 cm⁻¹ in FTIR process analytics. A critical quality parameter is the E/Z isomer ratio: the desired E,E-isomer exhibits maximum fluorescence quantum yield (Φ = 0.88 in dichloromethane at 10⁻⁵ M) while the Z-isomers are essentially non-emissive. Post-reaction isomerisation is forced by adding catalytic iodine (0.1 wt%) and irradiating the suspension with a 400 W high-pressure mercury lamp until the Z-content drops below 2% by HPLC. The finished brightener is incorporated into polyethylene terephthalate (PET) bottle-grade resin at 120–180 ppm, where compliance with EU Regulation 10/2011 Annex I requires specific migration testing for the brightener to remain below the detection limit of 0.01 mg/kg food simulant. Long-term masterbatch storage under Southern European warehouse conditions (> 35°C ambient, 80% RH) revealed a shelf-life limitation: agglomerate formation after 8 months due to the hygroscopicity of the brightener powder, which necessitates foil-lined 25 kg fibre drums re-sealed under nitrogen purge.Direct nucleophilic displacement routes to 2-substituted benzothiazole pharmacophores often require the free benzothiazole-2-carbonitrile as a precursor, a compound that must be generated in-house by an oxidative conversion of benzothiazole-2-acetonitrile that has proven capricious on scales exceeding 50 kg. The transformation employs manganese dioxide (10 equivalents, activated grade, 5 µm particle size) in refluxing benzene, conditions that produce a mixture of the desired nitrile and unreacted starting material that co-elute on silica. Distillation under reduced pressure (115–118°C at 0.8 mbar ) through a wiped-film evaporator achieves a separation factor of 1.35, requiring a reflux ratio of 4:1 and a column of at least 15 theoretical plates to isolate product of > 99% purity. The purified benzothiazole-2-carbonitrile subsequently serves as the electrophilic C2-building block in the synthesis of riluzole analogues where the cyano group is displaced by trifluoromethoxy-substituted aniline nucleophiles. A documented process deviation at a CDMO facility in 2021 highlighted the hazard of localised overheating in the distillation sump, where accumulated benzothiazole-2-carboxamide impurities decomposed exothermically, triggering a pressure surge. Subsequent hazard evaluation under the UN Manual of Tests and Criteria Section 11 recommended a maximum sump temperature of 130°C and continuous monitoring by differential scanning calorimetry for trace peroxide contaminants.

What Limits the Synergistic Performance of Benzothiazole-Derived Accelerators in a Sulphenamide-Cure Truck Tyre Tread Compound?

Benzothiazole-2-acetonitrile is not a direct accelerator but is exploited as a synthon for experimental sulphenamide accelerators where the nitrile side chain is elaborated into a sterically hindered amine. In tyre tread formulations based on solution-polymerised styrene-butadiene rubber (S-SBR, 35% styrene, 55% vinyl, T_g = –25°C) extended with 37.5 phr treated distillate aromatic extract oil, a sulphenamide derivative prepared from benzothiazole-2-acetonitrile and tert-octylamine was evaluated against N-cyclohexyl-2-benzothiazole sulphenamide (CBS). The experimental accelerator was incorporated at 1.0 phr together with 2.5 phr sulphur and 0.4 phr diphenylguanidine. Rheometer data (Monsanto MDR 2000, 160°C, 1° arc) showed a scorch time (t_s2) of 3.2 min versus 2.8 min for CBS, offering a wider processing safety margin for extrusion at 105°C die temperature. However, the 300% modulus measured according to ISO 37:2017 reached only 8.2 MPa, compared to 9.6 MPa for the CBS reference, a deficiency traced to incomplete grafting of the bulky amine onto the polymer backbone during early vulcanisation stages. This outcome defines the molecular design envelope: the molar volume of the amine capping group must not exceed 200 cm³/mol or accelerator migration to the rubber-silica interface is hindered, a finding confirmed by dynamic mechanical analysis (tan δ at 60°C, 10 Hz) that plateaued at 0.112 irrespective of silane coupling agent loading.A parallel development stream that requires no

header: benzothiazole-2-acetonitrile undergoes a Gewald-type thiophene annulation when heated with elemental sulphur (1.2 equivalents) and a ketone in N,N-dimethylformamide containing diethylamine (0.5 equivalent). The resulting 2-(thieno[2,3-d]thiazol-2-yl)acetonitrile scaffolds have an electron-accepting character that makes them attractive conjugated building blocks for non-fullerene organic photovoltaic acceptors. The critical processing window in the laboratory-scale synthesis—up to 20 g batch—is the slow addition of sulphur at 50°C, as faster addition precipitates insoluble polysulphide networks that entrain the product. After aqueous workup and column purification, the product demonstrates a lowest unoccupied molecular orbital (LUMO) energy of –3.91 eV as measured by cyclic voltammetry against a ferrocene/ferrocenium internal standard in anhydrous acetonitrile with 0.1 M tetrabutylammonium hexafluorophosphate electrolyte. The structural rigidity of the fused thienothiazole unit leads to a molar extinction coefficient of 4.8 × 10⁴ M⁻¹cm⁻¹ at 451 nm, satisfying the light-harvesting demands of bulk-heterojunction blends with poly(3-hexylthiophene) donors. Published data for this specific configuration in an inverted device architecture (ITO/ZnO/active layer/MoO₃/Ag) placed the power conversion efficiency at 4.7% with a fill factor of 0.62, figures limited primarily by the energetic offset between the donor HOMO and acceptor LUMO, which at 0.53 eV exceeds the empirical threshold for minimal voltage loss. Equipment corrosion remains under-documented; however, sulphur-based process residues are known to attack stainless steel 316L components in the reactor at the vapour-liquid interface, necessitating quarterly thickness testing by ultrasonic gauging per ASME B31.3 for continued service.
Comparative Process Parameters for Representative Downstream Transformations
Downstream Segment Key Reaction Step Catalyst / Reagent System Temperature Range (°C) Isolated Yield (%) Critical Purity Threshold
C.I. Basic Dye Intermediate Knoevenagel condensation with dimethylamino benzaldehyde Piperidine (0.5 mol%), anhyd. ethanol 78–82 85–88 ≥ 98.2% (HPLC)
Thiazole Carboxamide Fungicide Three-step: hydrolysis → acid chloride → amidation H₂SO₄ 65 wt%; SOCl₂/DMF; 2-aminothiazole 105–110; reflux; 0–5 76–81 (overall) Residual nitrile < 0.7%
FWA 368 Double Knoevenagel with terephthalaldehyde Piperidine acetate (2 mol%), DMSO 120 72–75 Z-isomer < 2% (HPLC)
Riluzole Analogue Precursor Oxidation to benzothiazole-2-carbonitrile MnO₂ (10 eq.), benzene reflux; distillation 80 (rxn); 115–118 (0.8 mbar) 65–70 > 99% (GC)
Sulphenamide Accelerator Prototype Oxidative coupling with tert-octylamine NaOCl (aq. 12%), isopropanol 0–10 68 MP 118–120°C
Regulatory Cross-Reference for End-Use Compliance of Benzothiazole-2-Acetonitrile Derivatives
Derivative Class Applicable Standard / Regulation Specific Requirement Typical Limit
Optical Brightener in PET Food Packaging EU 10/2011, Annex I; EN 1186-1:2002 Overall migration into food simulant D1 ≤ 10 mg/dm²
Sulphenamide Accelerator in Tyre REACH Annex XVII, Entry 50 (PAH); ISO/TS 21482:2019 Content of benzothiazole-2-thiol (free MBT) ≤ 0.5 wt%
Agrochemical Technical Concentrate FAO/WHO Manual (1st Revision, JMP); CIPAC MT 46.3 Wet sieve retention on 75 µm ≤ 2%
Bulk Cargo Sea Transport IMDG Code Amendment 41-22 Classification: UN 3077 Class 9 (Environmentally Hazardous) Marine pollutant: yes
Non-Fullerene Acceptor Research Chemical China MEE Order No. 12 (Inventory); USA TSCA Section 5(h)(4) exemption R&D volume exemption < 10 kg/year

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Benzothiazole-2-Acetonitrile is manufactured under an ISO 9001 quality system and complies with relevant regulatory requirements.
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More Introduction

What Differentiates a Methylene-Spaced Nitrile from a Directly Attached Cyano Group?

The introduction of a single methylene unit between the benzothiazole heterocycle and the terminal nitrile function fundamentally alters the electronic landscape of the molecule. In benzothiazole-2-carbonitrile, the electron-withdrawing nature of the nitrile is conjugated directly with the thiazole ring, deactivating the 2-position toward nucleophilic attack and lowering the LUMO energy primarily on the heterocycle itself. Benzothiazole-2-acetonitrile (CAS 56278-50-3) decouples this conjugation. The methylene bridge acts as an insulator, localizing the nitrile’s inductive effect on the adjacent carbon and preserving the benzothiazole ring’s capacity for electrophilic substitution at the 6- and 4-positions. This structural nuance, confirmed by DFT calculations comparing Fukui indices for both compounds, makes the acetonitrile derivative a more versatile intermediate in step-economic syntheses of kinase inhibitors and fluorescent probes where simultaneous functionalization at the 2-methylene and the aromatic ring is required. Purity benchmarks for commercially relevant grades are tightly controlled. Typical product models include B2AC-97 (technical grade) and B2AC-99 (high-purity grade). The 99% assay, determined by HPLC with UV detection at 254 nm using a C18 column and acetonitrile/water (70:30 v/v) mobile phase, corresponds to a melting point range of 62.0–64.0 °C as measured by differential scanning calorimetry per ASTM E794-06 (reapproved 2018). Moisture content, determined by Karl Fischer titration per ASTM E203-16, is specified at ≤ 0.3% for the B2AC-99 grade and ≤ 0.8% for the technical variant. Sulfated ash, measured according to USP <281>, is held below 0.05%. Residual solvent profiles—typically ethanol or ethyl acetate depending on the crystallization train—are quantified by headspace GC-FID with reporting limits of 50 ppm for Class 2 solvents as defined by ICH Q3C(R8). These thresholds are not arbitrary; batch records from a cGMP intermediate producer show that residual ethyl acetate above 120 ppm in the B2AC-99 lot correlates with a melting point depression of 0.4 °C and a slight broadening of the endothermic peak, flagging inadequate drying cycle parameters.

Alkylation and Condensation Reactivity in Pharmaceutical Scaffold Construction

The acidity of the methylene protons (pKa ~ 16–18 in DMSO, estimated from Bordwell tables for comparable arylacetonitriles) permits smooth deprotonation with a range of bases, enabling C-alkylation, Michael addition, and Knoevenagel condensation pathways. Sodium hydride (60% dispersion in mineral oil) at 0.2–0.5 mol% loading in anhydrous DMF at 0–5 °C generates a nucleophilic carbanion that can be quenched with primary alkyl halides to install diverse side chains. In one published protocol for a CRTH2 antagonist intermediate, benzothiazole-2-acetonitrile was alkylated with 2-bromomethyl-4-fluorophenylacetic acid methyl ester in the presence of potassium carbonate and tetrabutylammonium bromide in toluene at 70 °C, yielding 87% after recrystallization from isopropanol. The methylene nitrile also participates in condensation with aromatic aldehydes under piperidine-catalyzed conditions, forming α,β-unsaturated nitriles with the benzothiazole moiety in the β-position. These adducts exhibit absorption maxima between 330 nm and 380 nm, making them suitable for subsequent cyclization to aminopyrimidines or aminopyrazoles. Processing on pilot-plant scale requires careful exotherm management. When performing large-batch alkylations (≥50 kg input of benzothiazole-2-acetonitrile) in a 500 L glass-lined reactor equipped with a retreat-blade impeller, the deprotonation step with sodium hydride generates a temperature rise of 8–12 °C over a 15-minute addition period. A jacket temperature setpoint of -5 °C and a controlled dosing rate of 0.3 kg/min for the alkyl halide solution are necessary to maintain internal temperature below 10 °C, avoiding competitive elimination pathways. Published data for this specific configuration is limited, but internal process safety reports from a contract manufacturer indicate that exceeding an internal temperature of 18 °C during the alkylation of benzothiazole-2-acetonitrile with benzyl chloride results in a 3–5% increase in the dibenzylated impurity, which co-elutes with the product under normal-phase flash chromatography conditions. Vigorous exclusion of moisture is critical throughout. While the compound itself is not classified as water-reactive, the carbanion generated in situ is rapidly quenched by water, recovering starting material and generating hydroxide ions that can catalyze nitrile hydrolysis. For manufacturing campaigns where ambient relative humidity exceeds 60%, the solid starting material should be pre-dried in a vacuum tray dryer at 45 °C and 10 mbar for 4 hours before charging. Reactor headspace should be purged with nitrogen (99.999%) to maintain a dew point below -40 °C. These precautions, while adding approximately 5 hours to the campaign timeline, are substantially less costly than reprocessing a batch with >2% of the corresponding amide hydrolysis byproduct.

Comparing Performance with 2-Benzothiazoleacetic Acid and Other C2 Synthons

The acetonitrile derivative occupies a distinct reactivity niche relative to its oxidized and reduced counterparts. 2-Benzothiazoleacetic acid (CAS 29182-45-8), the corresponding carboxylic acid, is often favored for amide coupling via carbodiimide-mediated activation, but the additional deprotonation and alkylation pathways of the nitrile are inaccessible. Reduction of benzothiazole-2-acetonitrile with borane-tetrahydrofuran complex or catalytic hydrogenation over Raney nickel at 40 psi H₂ pressure yields 2-(2-aminoethyl)benzothiazole, a primary amine building block used in the synthesis of translocator protein (TSPO) ligands. The nitrile thus serves as a masked amine synthon, offering an orthogonal strategy to the traditional nitro-reduction or azide-hydrogenation sequences that are incompatible with sulfur-containing heterocycles due to catalyst poisoning. The following table summarizes key physical and handling distinctions between the acetonitrile, the carbonitrile, and the acetic acid analog, as these frequently appear together on a synthetic chemist’s shortlist during scaffold optimization.

Property	Benzothiazole-2-acetonitrile	Benzothiazole-2-carbonitrile	2-Benzothiazoleacetic acid
Melting point (°C)	62–64	150–152	102–105
pKa of acidic proton	~17 (methylene, DMSO)	N/A	4.2 (carboxyl, water)
Typical reactive sites	Methylene carbanion, nitrile, ring positions 4/6	Ring positions, nitrile hydrolysis	Carboxyl, ring positions
Moisture sensitivity in synthesis	High (carbanion formation step)	Moderate	Low
Packing standard	25 kg fiber drum with inner PE liner	50 kg steel drum	25 kg fiber drum

In head-to-head amidation studies, the nitrile is not a direct substitute for the carboxylic acid. The nitrile can be transformed into the corresponding primary amide under moderately acidic hydration conditions (e.g., sulfuric acid 90%, 40 °C, 2 hours), but the yield of isolated 2-benzothiazoleacetamide rarely exceeds 75% due to competing ring sulfonation. The acetic acid route via EDC/HOBt coupling with primary amines in dichloromethane at ambient temperature routinely delivers amides in 85–92% yield without ring modification. This insurmountable gap in efficiency means the nitrile is retained for strategies where late-stage functionalization relies on the methylene nucleophilicity rather than the carbonyl electrophilicity.

When Trace Metal Profiles Dictate Product Specification for Electronic Applications

A niche yet technically demanding application area for high-purity benzothiazole-2-acetonitrile is as a precursor to benzothiazole-based hole-transport materials and fluorescent whiteners. In these applications, transition metal contamination—particularly iron, copper, and palladium—must be controlled to single-digit parts per million levels to avoid quenching of excited states or electromigration in thin-film devices. The B2AC-99 specification includes a trace metals panel quantified by inductively coupled plasma mass spectrometry (ICP-MS) after microwave digestion. Typical lot-specific data for a 99.7% assay lot shows iron at 4 ppm, copper at 1 ppm, zinc at 2 ppm, and palladium below the reporting limit of 0.5 ppm. Such profiles are achieved not through recrystallization from technical grade alone but via a sequence of activated carbon treatment in refluxing toluene, hot filtration over Celite, and two subsequent recrystallizations from ethanol/water mixtures. This processing train adds approximately 40% to the cost per kilogram compared to standard technical grade but is mandatory for optoelectronic polymer suppliers whose device performance specifications require total heavy metal content ≤10 ppm. Incompatibilities with amine-based reagents extend beyond synthetic concerns. Storage stability studies show that benzothiazole-2-acetonitrile packaged in fiber drums with amine-cured epoxy liners develops a yellow discoloration within 30 days at 40 °C/75% RH, accompanied by a 0.2% decrease in HPLC purity. This degradation pathway, attributed to nucleophilic addition of residual amines to the nitrile, is mitigated by the exclusive use of polyethylene liners without slip agents that contain erucamide or oleamide. Confirmed shipment stability for 24 months from the date of manufacture is supported by data from ICH Q1A(R2)-conformant long-term storage at 25 ± 2 °C and 60 ± 5% RH. The second and final table in this overview aligns the product’s documentation package with the harmonized standards expected in a pharmaceutical starting material audit.

Document/Specification	Reference Standard	Typical Value/Range for B2AC-99
Certificate of Analysis	ISO 17025:2017	Lot-specific, includes assay, moisture, residue on ignition
Residual Solvent Method	USP <467> / EP 2.4.24	Class 2 solvents all <100 ppm
Elemental Impurities	USP <232> / ICH Q3D	Class 1 and 2A elements compliant with oral PDE limits
Heavy Metals (as Pb)	USP <231> (historical) / Ph. Eur. 2.4.8	<10 ppm
Shelf Life Specification	WHO TRS 1010, Annex 10	24 months when stored in original unopened container
REACH Registration	EC No. 1907/2006	Pre-registered for >1 ton/year import volume

Operational boundaries are rigidly defined for the compound in fine chemical manufacturing. Contact with strong oxidizing agents leads to exothermic decomposition with a heat release of approximately 1.5 kJ/g as recorded by accelerating rate calorimetry; therefore, charging into reactors previously used for peroxide chemistry without an intermediate wash with a reducing solution of sodium metabisulfite is prohibited. Thermal decomposition onset in air is 210 °C by thermogravimetric analysis at 10 °C/min scan rate, so melt transinjeetion into reaction mixtures requiring temperatures above 190 °C must be performed under inert gas. No federal or state occupational exposure limit has been established, so engineering controls common to nitrile-containing fine powders—local exhaust ventilation, minimum ignition energy awareness below 10 mJ, and bonded/grounded conductive container systems meeting IEC 60079-32-2—are applied as a conservative layer of protection.