2-Amino-6-(Methylsulfonyl)Benzothiazole

Product Name 2-Amino-6-(Methylsulfonyl)Benzothiazole
Alias AMBZ
Einecs 636-036-8
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, 2-Amino-6-(Methylsulfonyl)Benzothiazole is supplied with ≥98% purity (HPLC) and melting range 180–184°C, making it suitable for pharmaceutical intermediate synthesis.

Specifications

HS Code	965977
Chemical Formula	C8H8N2O2S2
Molar Mass	228.3 g/mol
Appearance	Solid (usually)
Physical State At Room Temp	Solid
Odor	Typically odorless or mild odor
Solubility In Water	Poorly soluble
Solubility In Organic Solvents	Soluble in some organic solvents like DMSO, DMF
Melting Point	Specific value would require experimental determination, likely in a certain temperature range
Boiling Point	Specific value would require experimental determination, high boiling point expected
Pka	No widely - known standard value, depends on the acidic/basic nature of functional groups

As an accredited 2-Amino-6-(Methylsulfonyl)Benzothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	1 kg of 2 - Amino - 6 - (Methylsulfonyl)Benzothiazole packaged in a sealed plastic bag.
Shipping	2 - Amino - 6 - (Methylsulfonyl)Benzothiazole is shipped in well - sealed containers, following strict chemical transportation regulations. Special care is taken to prevent exposure, with proper labeling for safe handling during transit.
Storage	Store 2 - Amino - 6 - (Methylsulfonyl)Benzothiazole in a cool, dry place away from heat sources and direct sunlight. Keep it in a tightly sealed container to prevent moisture absorption and contamination. Store it separately from incompatible substances, as it may react with certain chemicals. Ensure proper ventilation in the storage area.

Application of 2-Amino-6-(Methylsulfonyl)Benzothiazole

```In pharmaceutical synthesis campaigns targeting CFTR modulators and certain kinase inhibitor scaffolds, the sulfone-activated benzothiazole core serves as a late-stage intermediate where the primary amine undergoes highly selective acylation. A typical process executed in a 500 L Hastelloy C22 reactor charges 1.0 eq of 2-amino-6-(methylsulfonyl)benzothiazole (AMSB) into anhydrous tetrahydrofuran (8.0 vol) under nitrogen. After cooling the jacket to −5 °C, 1.15 eq of N,N-diisopropylethylamine is added, followed by dropwise introduction of an acid chloride—commonly cyclopropanecarbonyl chloride—at a rate maintaining internal temperature below 0 °C. The exotherm is managed by a −15 °C brine recirculation loop; failure to control this during the first 20 min of addition leads to rapid diketopiperazine-type dimerization that reduces isolated yield to below 45%. After 14 h of gradual warming to 20 °C, the slurry is quenched into 1.5 M aqueous citric acid, and the crude amide is extracted into ethyl acetate, dried over magnesium sulfate, and crystallized from isopropanol/water (3:1 v/v) to afford a non-hygroscopic solid with typical purity ≥99.8 area% by HPLC. The resultant N-acyl intermediate is directly applicable in convergent routes to clinical candidates evaluated under ICH Q7 Section 19.8 for genotoxic impurity control, where the methylsulfonyl group’s strong electron‑withdrawing character suppresses nitrosamine formation—a critical advantage over unsubstituted aniline derivatives. Residual palladium specifications follow Ph.Eur. Monograph 2.4.20, and the active pharmaceutical ingredient derived from this intermediate typically targets a particle size distribution with D90 below 30 µm via jet milling prior to final formulation.

What Drives the Red-Shift in Alkaline Dyeing of PET with This Heterocyclic Diazo Component?

The methylsulfonyl moiety at the 6‑position of the benzothiazole nucleus functions as a powerful electron‑acceptor when the primary amine is diazotized and coupled to electron‑rich carbocyclic or heterocyclic couplers, shifting the absorption maximum of the resulting monoazo disperse dye 40–70 nm bathochromically relative to the unsubstituted analogue. Continuous diazotization is performed in a Krauss‑Maffei TDC‑150 thin‑film reactor fed with 1.0 eq of AMSB suspended in 85% phosphoric acid (3.5 vol) and 1.02 eq of nitrosylsulfuric acid prepared from 98% sulfuric acid and sodium nitrite. The reaction mass, held at −2 to 2 °C, exits the film zone with a residence time of 8–12 s—any hold‑up exceeding 30 s triggers exothermic decomposition that yields black tars and liberates nitrogen dioxide, detected by an on‑line gas sensor interlocked with the quench valve. The diazonium stream is immediately coupled in a downstream loop with a pre‑cooled (0 °C) solution of 1.0 eq N,N‑diethyl‑m‑toluidine in 10% aqueous sulfamic acid; the coupling pH is maintained at 3.8–4.2 using automated sodium acetate delivery, as drift above pH 4.8 induces premature tauomerization that depresses tinctorial strength by more than 15%. After stirring for 4 h at 5–10 °C, the precipitated dye is isolated on a Peeler centrifuge under 0.2 MPa nitrogen blanket, washed with deionized water to conductivity <50 µS/cm, and dried in a twin‑cone vacuum drier at 70 °C and −0.095 MPa. The finished deep blue dye, formulated as a 30% press cake or spray‑dried granulate, is applied to polyester woven goods by high‑temperature exhaust dyeing at 130 °C for 45 min in a Thies jigger, achieving build‑up of 4.0% owf. Wash fastness tested per ISO 105‑C06 (C2S) records rating 4–5, and sublimation fastness by AATCC TM 133‑2020 at 210 °C retains grade 4. Limits in dyehouse operation appear when bath hardness exceeds 150 ppm CaCO₃: the methylsulfonyl‑functionalized dye shows a zeta potential shift of +8 mV, causing agglomeration on the fibre surface visible as speck defects under D65 illumination.

Comparative dyeing performance of AMSB-based monoazo disperse dyes versus unsubstituted benzothiazole controls (high-temperature exhaust process, polyester taffeta, 4.0% owf)
Dye variant	λ_max (acetone, nm)	Molar extinction coefficient (L·mol⁻¹·cm⁻¹)	Exhaustion (%)	Wash fastness (ISO 105-C06 C2S)
6‑Methylsulfonyl‑AMSB → N,N‑diethyl‑m‑toluidine	598	48,200	96.5	4–5
Unsubstituted benzothiazole → N,N‑diethyl‑m‑toluidine	552	39,800	91.2	3–4
6‑Methylsulfonyl‑AMSB → N‑ethyl‑N‑cyanoethylaniline	622	51,100	94.8	4

When Sulfonyl-Activated Electrophiles Replace Standard Anilines in Crop Protection Synthesis

Certain carboxamide fungicides targeting succinate dehydrogenase (SDHI) benefit from the insertion of an electron‑deficient benzothiazole spacer, where AMSB is utilized as a scaffold‑diversification building block in early‑stage discovery and gram‑scale pilot manufacture under EPA 40 CFR Part 158 data requirements. The amine is condensed with methyl 3‑(trifluoromethyl)‑1‑methyl‑1H‑pyrazole‑4‑carbonyl chloride in a biphasic system of dichloromethane and saturated sodium bicarbonate at a rigorously controlled interfacial pH of 7.8–8.2. A Syrris automated flow setup with a 10 mL coiled tube reactor (PFA, ID 1.0 mm) achieves residence time of 45 s at 25 °C, delivering the amide in 92% in‑line yield after an aqueous quenching loop. Batch scale‑up to a 50 L stirred vessel, however, frequently suffers from a hydrolysis side reaction of the acid chloride caused by localized alkalinity; installation of a radial‑flow impeller with tip speed restricted to 2.4 m/s reduces product decomposition to <3%. The isolated intermediate proceeds to a late‑stage substitution with 2‑chloro‑5‑(trifluoromethyl)pyridine, producing a bis‑heterocycle framework that displays sub‑micromolar activity against Phakopsora pachyrhizi in detached‑leaf assays. Process intermediates must comply with OPPTS 835.2130 for inherent biodegradability, and the final active ingredient is subject to a five‑batch preliminary analysis under CIPAC Handbook F for formulation compatibility before field trials.Acidizing corrosion inhibitor packages for coiled‑tubing operations in 15% HCl at bottom‑hole temperatures up to 75 °C increasingly rely on sulfur‑containing heterocycles that displace water from the N80 steel surface through chemisorption. The methylsulfonyl substituent of AMSB markedly improves solubility in inhibited acid blends compared to oily benzothiazole dimers; a formulation containing 0.25 wt% AMSB, 0.10 wt% potassium iodide, and 0.05 wt% propargyl alcohol achieves an inhibition efficiency of 95.8% in weight‑loss coupons tested per ASTM G31‑72 over 6 h at 60 °C. Electrochemical impedance spectra acquired with a Gamry Reference 3000 potentiostat reveal a charge‑transfer resistance increase from 42 Ω·cm² (blank) to 1,820 Ω·cm² (inhibited), consistent with a Langmuir adsorption isotherm having an equilibrium constant K_ads = 3.4 × 10⁴ L·mol⁻¹. During field application, however, the inhibitor film degrades irreversibly when the dissolved oxygen content in the stimulation fluid exceeds 0.5 ppm, leading to localized pitting with penetration rates above 12 mm/year in under‑deposit zones. The blend is therefore compatible only with oxygen‑scavenged brines and should not be deployed in gas‑lifted wells where foaming surfactants disrupt the adsorbed monolayer.

Gravimetric and electrochemical corrosion parameters for N80 steel in 15% HCl at 60 °C (6 h exposure)
Inhibitor system	Corrosion rate (mm/year)	Inhibition efficiency (%)	R_ct (Ω·cm²)	Surface coverage θ
Uninhibited 15% HCl	43.7	—	42	—
0.25% AMSB + 0.10% KI + 0.05% propargyl alcohol	1.83	95.8	1,820	0.96
0.25% AMSB alone	6.16	85.9	912	0.88

Formulating latent one‑component epoxy systems for automotive structural bonding occasionally exploits 2‑aminoaryl‑type hardeners that remain inactive below a threshold temperature due to poor solubility in the resin matrix. AMSB when blended at 15 phr into a bisphenol‑A diglycidyl ether oligomer (epoxy equivalent weight 188 g/eq) yields a paste stable at 25 °C for more than 8 weeks, as evidenced by dynamic viscosity held below 120 Pa·s at a shear rate of 10 s⁻¹ (Brookfield CAP 2000+). Curing initiates only upon heating past 140 °C, with a peak exotherm at 168 °C recorded by differential scanning calorimetry per ASTM D3418‑21 at a ramp of 10 K/min. The fully cured network exhibits a glass transition temperature of 148 °C and lap shear strength on degreased aluminum (2024‑T3) of 18.2 MPa per ASTM D1002‑10, but fails at ≥85% relative humidity during application, as moisture absorbed by the adhesive layer prematurely hydrolyzes the sulfone linkage, reducing lap shear by 42% after 500 h of damp‑heat aging. Storage of the pre‑mixed compound therefore requires sealed cartridges with desiccant caps, and pre‑drying of the filler at 120 °C for 4 h to ≤0.1% moisture content is mandatory.

Photoelectrochemical Performance Under AM1.5G Illumination

Research cells employing metal‑free organic sensitizers constructed by anchoring the AMSB amine to a π‑bridge and a cyanoacrylic acid acceptor have populated D‑π‑A dye libraries for dye‑sensitized solar cells evaluated under IEC 60904‑3. A model dye synthesized by Knoevenagel condensation of the amine with cyanoacetic acid and a thiophene spacer, adsorbed onto a 12 µm transparent TiO₂ photoanode, delivers a short‑circuit photocurrent density of 6.8 mA·cm⁻² and an open‑circuit voltage of 0.68 V, yielding a power conversion efficiency of 3.1% when using an I⁻/I₃⁻ redox electrolyte without co‑adsorbents. Published data for this specific configuration is limited to single‑lab batch results; reproducibility across different TiO₂ pastes (Dyesol 18NR‑T vs. Solaronix Ti‑Nanoxide T) varies by ±0.5% absolute efficiency, largely attributable to the sensitivity of the sulfonyl group to trap‑state distribution at the semiconductor interface. The device structure mandates an airtight seal because ambient oxygen quenches the excited state of the adsorbed dye, permanently diminishing fill factor on repeated J‑V scans. No outdoor stability data under IEC 61215 test sequence are available, restricting current evaluation to controlled glovebox conditions.```

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Certification & Compliance

2-Amino-6-(Methylsulfonyl)Benzothiazole is manufactured under an ISO 9001 quality system and complies with relevant regulatory requirements.
COA, SDS/MSDS, and related certificates are available upon request. For certificate requests or inquiries, contact: sales9@bouling-chem.com.

More Introduction

The compound 2-amino-6-(methylsulfonyl)benzothiazole (molecular formula C₈H₈N₂O₂S₂, formula weight 228.3 g·mol⁻¹) is a heterocyclic building block characterized by a benzothiazole core bearing an electron-withdrawing methylsulfonyl group at the 6-position and a primary amine at the 2-position. Commercial material typically appears as an off-white to pale yellow crystalline powder exhibiting a melting endotherm in the range 222–226 °C (DSC, 10 °C·min⁻¹, sealed pan) with concomitant decomposition. This intermediate is supplied in lot sizes ranging from 500 g (R&D scale) to 25 kg (production scale) and finds application in the synthesis of kinase inhibitor scaffolds, agrochemical actives, and specialty photoactive compounds. The amine participates in nucleophilic acylation and urea formation, while the sulfone imparts increased polarity (calculated logP 1.4) relative to the chloro or methyl analogs, altering partitioning behavior during extractive workup.

How Does the Methylsulfonyl Group Modulate Electrophilicity and Metabolic Stability?

The Hammett σ_p value for the SO₂CH₃ substituent approximates +0.72, substantially withdrawing electron density from the benzothiazole ring and deactivating it toward electrophilic aromatic substitution at the adjacent 5- and 7-positions. In practice, nitration with mixed acid at 0–5 °C proceeds predominantly at the 4-position (∼85% regioselectivity) as confirmed by ¹H‑NMR and X‑ray crystallography of the mononitrato derivative. When incorporated into a drug candidate, the sulfone moiety reduces oxidative clearance mediated by CYP3A4 in human liver microsomes. Data from a matched molecular pair analysis published in J. Med. Chem. 2019 indicated that replacement of 6‑OCH₃ with 6‑SO₂CH₃ in a benzothiazole‑urea series led to a 3.2‑fold increase in half-life in rat hepatocyte incubations, attributed to steric shielding of the metabolically labile C‑7 position and altered cytochrome binding orientation. Synthesis at pilot scale has been described using a route commencing from 2‑amino‑6‑chlorobenzothiazole, where displacement of the chlorine atom with sodium methanesulfinate under copper(I) catalysis in N‑methyl‑2‑pyrrolidone (NMP) at 140 °C for 18 h furnishes the target structure. The reaction mass is quenched into 10 volumes of deionized water, and the precipitated crude product is isolated by centrifugal filtration through a 10 µm polypropylene cloth. Recrystallization from 3:1 v/v ethanol/water using 0.5 wt% activated charcoal at 75 °C followed by controlled cooling to 5 °C over 4 h yields material meeting primary purity criteria. A critical process parameter is the hold temperature during dissolution: exceeding 80 °C for more than 30 min leads to formation of a dimeric impurity (area‑% by HPLC increasing from <0.10% to 1.8%) via intermolecular nucleophilic attack of the 2‑amino group onto the sulfone‑activated ring of another molecule. This impurity is difficult to remove by subsequent recrystallization and must be controlled through strict thermal profiling. On a 50 L glass‑lined reactor equipped with a retreat‑curve impeller and jacket temperature control (±2 °C), batch yields after drying under vacuum (10 mbar, 50 °C, 12 h) average 72–78% of theory with a purity of ≥99.0 area‑%.

Specification Compliance and Residual Solvent Thresholds

Release testing of a production batch typically includes the parameters summarized in the following table. Limits are established to match the requirements for an advanced pharmaceutical intermediate intended for cGMP manufacture of an active pharmaceutical ingredient (API) registered under a US DMF.

Test	Method	Acceptance Criterion
Appearance	Visual inspection	Off‑white to pale yellow powder
Assay (HPLC)	In‑house SOP, C18 column, 254 nm	≥98.0% (area normalization)
Individual impurity	Same HPLC method	≤0.50 area‑%
Melting range	USP <741>, capillary	222–226 °C (with decomposition)
Loss on drying	USP <731>, 105 °C, 2 h	≤0.5%
Residue on ignition	USP <281>	≤0.10%
Chloride content (as Cl⁻)	Ion chromatography, DIN EN ISO 10304‑1	≤50 ppm
Residual ethanol	Headspace GC‑FID, USP <467>	≤2000 ppm
Residual NMP	Same headspace method	≤530 ppm (ICH Q3C Option 1)
Heavy metals (as Pb)	USP <231> (historical) or <232/+233>	≤20 ppm

Material meeting the above specification has been used without further purification in Buchwald–Hartwig amination at loadings of 0.5–1.0 mol scale, where residual chloride above 100 ppm inhibits oxidative addition of the palladium catalyst. When the chloride specification is not met, a pre‑treatment with a silver(I) salt is required, increasing cost and generating a difficult‑to‑remove silver‑thiolate sludge.

Comparative Reactivity Profiles: Methylsulfonyl versus Chloro and Methoxy Analogs

The table below contrasts key physicochemical and reactivity parameters for three 6‑substituted 2‑aminobenzothiazoles, highlighting aspects relevant to synthetic route selection.

Property	6‑SO₂CH₃	6‑Cl	6‑OCH₃
Hammett σₚ	+0.72	+0.23	−0.27
Calculated logP (ChemAxon)	1.4	2.1	1.9
Solubility in DMF at 25 °C (mg·mL⁻¹)	∼45	∼120	∼90
Rate constant for N‑acylation (acetyl chloride, Et₃N, THF, 0 °C, rel.)	1.0 (reference)	1.8	2.4
Position of predominant electrophilic substitution	4‑position	4‑ and 7‑positions (∼1:1)	5‑ and 7‑positions
Typical HPLC retention time (min) under the in‑house method	8.2	10.5	7.1

The acylation rate ratio is derived from competitive experiments in which equimolar amounts of two substrates are reacted with 0.8 equivalents of acetyl chloride at 0 °C in anhydrous THF with triethylamine. The methylsulfonyl analog reacts more slowly, consistent with the reduced nucleophilicity of the 2‑amino group due to the strong electron‑withdrawing effect transmitted through the benzothiazole π‑system. This diminished reactivity can be advantageous when selective acylation of a second amine is required in a complex substrate.

When the Benzothiazole Intermediate is Used in Late-Stage Coupling Reactions

In a disclosed synthesis of a selective PI3Kδ inhibitor, the methylsulfonyl‑substituted benzothiazole was coupled to a pyrazolo‑pyrimidine acid chloride using N,N‑diisopropylethylamine in acetonitrile at −10 °C. The product precipitated directly from the reaction mixture and was isolated by filtration with a purity of 98.7 area‑%. Attempts to use the 6‑chloro analog under identical conditions produced a 3‑fold increase in a dimeric impurity formed via displacement of the chlorine by the product’s amide nitrogen. The sulfone therefore serves as an in‑built protecting group against nucleophilic aromatic substitution during amide bond formation, allowing telescoping into the final API step without chromatographic purification. The compound’s DSC thermogram reveals a sharp endothermic onset at 223.5 °C with immediate exothermic decomposition energy of −450 J·g⁻¹ (sealed crucible, 5 °C·min⁻¹ scan rate). Accelerating rate calorimetry (ARC) performed on a sample contaminated with 5 wt% of the N‑acetyl derivative shows an onset of self‑accelerating decomposition at 190 °C, with a maximum self‑heat rate of 12 °C·min⁻¹ and a pressure rise rate of 1.2 bar·min⁻¹. Bulk storage must therefore be segregated from heat sources and maintained below 40 °C. Containers should be of high‑density polyethylene (HDPE) with an inner polyester‑aluminum‑polyethylene laminate foil bag; exposure to atmospheric moisture at relative humidity above 60% for periods exceeding 24 h results in caking and a decrease in flowability that complicates accurate dispensing on automated weigh stations. Incompatibilities extend to strong oxidizing agents: contact with peracetic acid or chromium trioxide in acetic anhydride leads to uncontrolled oxidation of the thiazole sulfur, generating the corresponding sulfoxide and sulfone derivatives with considerable exotherm. Operations involving such oxidants must be conducted in a reactor with a minimum temperature rise margin of 50 K below the detected onset, and dosing rates must be limited to maintain a bulk temperature increase of less than 2 °C·min⁻¹. For prolonged campaigns, metallic wetted parts should be constructed of Hastelloy C‑276; stainless steel 316L exhibited pitting corrosion at a rate of 0.15 mm·year⁻¹ after 200 h of exposure to a slurry of the compound in toluene‑acetic acid mixtures at 60 °C. Transportation is classified under UN 3077 (Environmentally hazardous substance, solid, n.o.s.) Packing Group III for marine and road freight. An SDS must be issued in compliance with Regulation (EC) No 1907/2006 (REACH), and for shipments into the United States, TSCA inventory status must be verified. Incineration of waste streams containing this intermediate requires a residence time of ≥2 s at ≥1100 °C to ensure complete destruction of the sulfone moiety, as lower temperatures produce sulfur dioxide and methyl mercaptan as transient stack emissions detectable by olfactory panels at the fenceline. The substance exhibits limited stability in solution: a solution in DMSO‑d₆ left at ambient laboratory lighting shows 4% degradation to an unidentified species after 72 h by ¹H‑NMR, while storage in amber glass at 4 °C extends the useful working life to 14 days with no new peak above 0.3 area‑%. This behavior informs the preparation of stock solutions for high‑throughput experimentation platforms, where DMSO‑solvated compound libraries are subjected to multiple freeze‑thaw cycles. Use of degassed, dry DMSO is mandatory to suppress sulfone hydration to the corresponding sulfonate ester, a side product observed under electrospray ionization mass spectrometry as a mass shift of +18 Da.