2-Amino-4-Chlorobenzothiazole
|
HS Code |
624302 |
| Chemical Formula | C7H5ClN2S |
| Molecular Weight | 184.64 |
| Appearance | Solid |
| Color | Off - white to light yellow |
| Melting Point | 178 - 182 °C |
| Solubility In Water | Insoluble |
| Solubility In Organic Solvents | Soluble in some organic solvents like ethanol, DMSO |
| Odor | Weak, characteristic |
| Stability | Stable under normal conditions |
As an accredited 2-Amino-4-Chlorobenzothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 250 - gram bottle of 2 - Amino - 4 - Chlorobenzothiazole, tightly sealed for safety. |
| Shipping | 2 - Amino - 4 - Chlorobenzothiazole is shipped in well - sealed containers, compliant with chemical transportation regulations. Packaging ensures protection from moisture and external factors during transit to maintain its quality. |
| Storage | 2 - Amino - 4 - Chlorobenzothiazole should be stored in a cool, dry, and well - ventilated area. Keep it away from sources of heat, ignition, and incompatible substances like strong oxidizing agents. Store in a tightly sealed container to prevent moisture absorption and potential degradation. Avoid exposure to direct sunlight. This storage method helps maintain its chemical stability. |
Diazotization of 2-amino-4-chlorobenzothiazole in a jacketed glass-lined vessel at 0–2 °C generates an electrophilic diazonium salt that couples with N-substituted aniline derivatives to produce monoazo disperse dyes absorbing in the 580–620 nm region. The process starts by dispersing 1.0 mol of the dry amine in 3.5–4.0 L of 30 % hydrochloric acid per kilogram of amine, cooling the suspension with brine circulation, and then feeding a 40 % aqueous sodium nitrite solution at a rate that keeps the temperature below 3 °C; endpoint is determined by starch–iodide paper and absence of nitrous fumes. After clarifying filtration through a 0.5 µm polypropylene depth filter, the diazonium liquor is added dropwise to a coupling bath containing 1.02 mol of N,N-diethyl-m-toluidine dissolved in dilute acetic acid, with simultaneous metering of sodium acetate to hold the pH at 4.5 ± 0.3. The precipitated dye is stirred for another 2 h, isolated on a filter press, washed until conductivity falls below 50 µS cm⁻¹, and dried in a vacuum paddle dryer at 80 °C and –0.09 MPa. The resulting blue disperse dye is standardised to 200 % strength with lignin sulfonate dispersant and applied to polyester knitted fabric by high-temperature exhaust at 130 °C for 45 min in an Ahiba Nuance IR dyeing machine. Wash fastness tested per ISO 105‑C06 (C2S) regularly reaches grade 4–5, and light fastness per ISO 105‑B02 exceeds 6 for a 1/1 standard depth. A crucial compliance boundary is set by OEKO‑TEX Standard 100 Appendix 4, which forbids the release of chlorinated anilines above 20 mg kg⁻¹; therefore the final disperse dye undergoes LC‑MS screening for 4-chloroaniline residues, and the wet cake washing protocol is extended when ambient humidity surpasses 60 % RH to prevent hydrolytic deamination of any residual diazonium intermediate.What Differentiates a 4‑Chlorobenzothiazole Precursor in Carboxamide Fungicides?When 2‑amino‑4‑chlorobenzothiazole is employed as a building block for thiazole‑carboxamide fungicides, the chlorine substituent remains in the final active ingredient and modulates both systemic mobility within the plant xylem and binding affinity to succinate dehydrogenase (SDH). In a pilot‑scale synthesis of a representative SDHI candidate, the heterocyclic amine is reacted with 1.05 eq. of ethyl chlorooxoacetate in anhydrous tetrahydrofuran containing 1.2 eq. of triethylamine as acid scavenger, maintaining the batch at –5 °C during the first 30 min and then allowing it to warm to 22 °C over 3 h. The oxamate intermediate is isolated by drowning into ice‑water, filtered, and crystallised from isopropanol to a purity exceeding 99.2 area‑% by HPLC (C18, 210 nm). Compliance with Regulation (EC) No 1107/2009 requires that the technical material passes a 5‑batch analysis demonstrating all individual unspecified impurities below 0.1 % and that the manufacturing site operates under a certified HACCP system. The final formulation, commonly a 200 g L⁻¹ suspension concentrate, is milled in a horizontal bead mill charged with 0.6–0.8 mm yttria‑stabilized zirconia beads until particle size D90 drops below 4 µm (laser diffraction, ISO 13320:2020). Residual organic solvents are controlled below the limits set in ICH Q3C Guideline Class 2 residual solvents, with tetrahydrofuran capped at 720 ppm. During field trials the fungicide applied at 150 g a.i. ha⁻¹ has shown activity against *Rhizoctonia solani* in rice paddies, and the residue definition for dietary risk assessment, established under Codex Alimentarius, includes the parent compound and the free 4‑chlorobenzothiazole amine metabolite, which is monitored by LC‑MS/MS with a limit of quantification of 0.01 mg kg⁻¹ in polished rice grain.Medicinal chemistry campaigns targeting constrained bicyclic heterocycles as kinase hinge‑binding motifs routinely exploit 2‑amino‑4‑chlorobenzothiazole to access analogues that would otherwise require multistep de novo ring construction. In a typical library synthesis, the primary amine is first protected with di‑*tert*‑butyl dicarbonate in dichloromethane at ambient temperature in the presence of 0.1 eq. of 4‑dimethylaminopyridine, affording the N‑Boc derivative after 12 h and a silica plug filtration. The chlorine atom then serves as a handle for palladium‑catalysed cross‑coupling: a Negishi reaction with 0.95 eq. of 2‑pyridylzinc bromide and 0.02 eq. of tetrakis(triphenylphosphine)palladium(0) in dry dioxane at 90 °C furnishes the 4‑heteroaryl analogue, which is deprotected with trifluoroacetic acid and purified by preparative reverse‑phase HPLC to > 95 % purity. Because these intermediates are destined for preclinical in‑vivo evaluation, the batch must be accompanied by a TSE/BSE declaration, a certificate of analysis reporting residual palladium by ICP‑MS (< 10 ppm per USP <232>), and a statement confirming absence of genotoxic impurities according to ICH M7 classifications—particularly residual 4‑chloroaniline, for which a TTC‑based limit of 1.5 µg day⁻¹ is enforced. The final drug‑like molecules synthesized from this scaffold have been profiled against a panel of 96 kinases at 1 µM ATP concentration, and selectivity scores are calculated from residual enzyme activity measured via a fluorescence resonance energy transfer assay. Storage stability studies indicate that the unprotected heterocycle undergoes minor oxidative dimerisation when held at 40 °C / 75 % RH for more than 14 days in an unsealed polyethylene liner; therefore the product is packed under nitrogen in aluminium‑laminated bags with a silica gel desiccant pouch.When Accelerator‑Modified NR/BR Truck Tyre Treads Require Scorch DelaySubstituting the standard 2‑mercaptobenzothiazole (MBT) accelerator with 2‑mercapto‑4‑chlorobenzothiazole, synthesised by reacting 2‑amino‑4‑chlorobenzothiazole with carbon disulfide and sodium hydroxide in a pressurised autoclave at 120 °C and 0.4 MPa, shifts the scorch safety margin of a natural rubber/butadiene rubber truck tread compound. In a 1.6 L Banbury mixer (Farrel BR1600) operated at 40 rpm rotor speed and 50 °C initial temperature, the base masterbatch of NR SMR 20 (70 phr) and BR CB22 (30 phr), reinforced with N234 carbon black (50 phr), is dumped at 145 °C. The sulfur curing package, added on a two‑roll mill at 60 °C, consists of 1.8 phr sulfur, 4.0 phr zinc oxide, 2.0 phr stearic acid, and 0.8 phr of the 4‑chloro‑MBT derivative. Moving‑die rheometry (MDR 2000, ASTM D5289) at 160 °C records a minimum torque ML of 2.8 dNm, a maximum torque MH of 19.2 dNm, and a scorch time ts2 extended to 4.2 min compared with 2.9 min for the unsubstituted MBT control. This extended induction period is critical for avoiding premature crosslinking during the multi‑extruder shaping of tyre tread and sidewall components in a quadruplex extrusion line running at a die temperature of 95 °C. The stock must comply with the EU Tyre Label Regulation (EC) 1222/2009 and face no restriction under REACH Annex XVII Entry 50 for PAHs; therefore the 4‑chloro‑MBT raw material is recrystallised from toluene to guarantee benzo[a]pyrene content below 1 mg kg⁻¹ and total 8 PAH below 10 mg kg⁻¹ as determined by GC‑MS in selected ion monitoring mode. Post‑vulcanisation tensile properties tested on dumbbell specimens (ISO 37:2017 Type 2) show a modulus at 300 % elongation of 12.5 MPa and elongation at break of 490 %, values that satisfy the technical specifications of a major commercial vehicle tyre manufacturer. Furthermore, the chloro‑MBT derivative exhibits reduced bloom on the green compound surface after 72 h storage at 25 °C / 60 % RH, a property confirmed by attenuated total reflectance FT‑IR spectroscopy comparing the absorbance of the C=S stretching band at 1080 cm⁻¹ with the pristine stock.
Adsorption Layers on Cold‑Rolled Steel in Continuous Pickling LinesThe mixed‑type inhibition behaviour of 2‑amino‑4‑chlorobenzothiazole in hydrochloric acid arises from simultaneous physisorption of the protonated amine and chemisorption through the endocyclic sulfur and nitrogen lone pairs, which displace water molecules from the metal surface. Weight‑loss coupons of SAE 1010 cold‑rolled steel, polished to 600‑grit finish, are suspended in 1 M HCl at 25 ± 1 °C for 6 h according to ASTM G31‑21 protocol without aeration. When the inhibitor is dosed at 200 ppm, the corrosion rate falls from 7.2 mm year⁻¹ (blank) to 0.41 mm year⁻¹, and potentiodynamic polarisation scans from –250 mV to +250 mV vs. open‑circuit potential at 1 mV s⁻¹ reveal a shift in corrosion potential of less than 30 mV, confirming mixed inhibition. Electrochemical impedance spectra fitted to a Randles equivalent circuit show a charge‑transfer resistance that increases from 28 Ω cm² to 840 Ω cm² at the optimal concentration, a data set that guides the design of continuous pickling bath replenishment programmes for steel mills operating at line speeds of 80–120 m min⁻¹. A practical constraint emerges when ferric ion accumulates beyond 15 g L⁻¹ in the bath: the inhibitor undergoes oxidative decomposition, producing a dark precipitate that reduces its efficiency by nearly 60 %. Hence a side‑stream filtration loop with activated carbon is recommended, and the inhibitor concentrate is stored in HDPE drums at temperatures below 35 °C to prevent dechlorination. Compliance with EPA 40 CFR Part 433 for metal finishing effluent requires that spent pickle liquor be treated to remove residual organic inhibitor before discharge; adsorption onto organoclay followed by Fenton oxidation has been validated to lower dissolved organic carbon below the 50 mg L⁻¹ discharge threshold. A comparison of the 4‑chloro analogue with unsubstituted 2‑aminobenzothiazole under identical hydrodynamic conditions (rotating cylinder electrode at 2000 rpm) demonstrates that the chlorine substituent increases the adsorption equilibrium constant by a factor of 2.3, reflecting the electron‑withdrawing effect that strengthens the nitrogen‑to‑metal σ‑donation.In trace‑level spectrophotometric determination of palladium(II) in spent automotive catalyst leachates, 2‑amino‑4‑chlorobenzothiazole serves as a selective chromogenic ligand that forms a yellow 1:2 Pd‑ligand complex extractable into chloroform at a pH of 4.0–5.5. The analytical procedure calls for adding 2 mL of a 0.1 % (w/v) reagent solution in ethanol to an aqueous palladium sample buffered with acetate, shaking with 5 mL of chloroform for 2 min, and measuring the absorbance of the organic layer at 420 nm against a reagent blank. Beer’s law is obeyed in the range 0.5–8.0 µg mL⁻¹, with a molar absorptivity of 1.6 × 10⁴ L mol⁻¹ cm⁻¹ and a Sandell sensitivity of 0.0066 µg cm⁻². Common base metals found in autocatalyst digests—iron, nickel, chromium—do not interfere when masked with 0.5 % EDTA, and the method accuracy, verified against certified reference material SRM 2557, falls within ± 2 % relative error. The ligand’s sensitivity to light, however, means that prepared reagent solutions older than 48 h must be discarded unless stored in amber glass under refrigeration; otherwise a baseline drift exceeding 0.020 AU is observed. |
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2-Amino-4-chlorobenzothiazole (IUPAC: 4-chloro-1,3-benzothiazol-2-amine, CAS 19952-47-7) is supplied as a white to pale yellow crystalline powder with a molecular formula C7H5ClN2S and a molecular weight of 184.65 g/mol. The compound’s melting point, determined by differential scanning calorimetry in accordance with ASTM E793, falls within the range 207–210 °C, and its purity by reverse-phase HPLC (C18, 254 nm, USP <621>) routinely exceeds 98.5 area%. Industrial interest centers on its role as a reactive heteroaromatic amine scaffold for pharmaceutical intermediates, agrochemical building blocks, and specialty vulcanization accelerators. The electron-withdrawing chlorine substituent at the 4-position, in conjunction with the 2-amino group, creates a regiochemically differentiated benzothiazole system whose nucleophilicity and cross-coupling behavior deviate markedly from those of the parent 2-aminobenzothiazole and from the 5-, 6-, or 7-chloro isomers.
| Parameter | Specification | Test Method |
|---|---|---|
| Assay (HPLC, area %) | ≥ 98.5 | USP <621>, C18, 254 nm |
| Melting range | 207–210 °C | ASTM E793 (DSC) |
| Loss on drying (105 °C, 2 h) | ≤ 0.5% | USP <731> |
| Sulfated ash | ≤ 0.2% | USP <281> |
| Regioisomeric impurity (2-amino-6-chlorobenzothiazole) | ≤ 0.3% | HPLC, chiral/achiral trace |
| Heavy metals (as Pb) | ≤ 10 ppm | USP <231> |
Beyond pharmacopeial monographs, synthetic chemists track the isomeric impurity profile by calibrated HPLC-MS because the 4-chloro isomer can co-elute with the 6-chloro congener under certain gradients (e.g., 0.1% TFA in water/acetonitrile). A method validated per ICH Q2(R1) with a resolution of Rₛ ≥ 2.0 is necessary when the compound is deployed in an active pharmaceutical ingredient synthesis where ICH Q3A thresholds for unspecified impurities apply.
In Suzuki–Miyaura coupling of 2-amino-4-chlorobenzothiazole with arylboronic acids, the chloro substituent occupies the electronically deactivated 4-position of the benzothiazole ring, yet oxidative addition to Pd(0) proceeds smoothly under mild heating. A representative protocol employing Pd(PPh3)4 (2 mol%), K2CO3 (2.0 eq.) in DMF/H2O (4:1 v/v) at 85–90 °C yielded the 4-aryl derivative in 87% isolated yield after 18 h. By contrast, the unsubstituted 2-aminobenzothiazole requires longer reaction times (≥ 24 h) and generates 6–8% of debromination by-product when brominated substrates are used, reflecting the influence of the 4-chloro group on the electron density at the carbon–chlorine bond. Process safety assessments from pilot-plant campaigns in glass-lined reactors (Pfaudler-type, 500–1000 L) note that the coupling exotherm typically raises the jacket temperature setpoint by 3–5 °C within the first 15 min, necessitating a temperature ramp limited to 1.5 °C/min to avoid overshoot beyond 95 °C, above which palladium black formation accelerates.
In continuous flow diazotization for azo pigment formation, 2-amino-4-chlorobenzothiazole is dissolved in concentrated sulfuric acid (98%) at −5 to 0 °C and fed into a microreactor (channel ID 1.0 mm) simultaneously with nitrosyl sulfuric acid. The controlled residence time of 30 s and the isothermal profile of the silicon carbide reactor plate suppress thermal runaway and minimize premature decomposition of the diazonium salt. This stability is attributed to the 4-chloro group’s inductive electron withdrawal, which reduces the nucleofugacity of the diazonium moiety compared with the 2-aminobenzothiazole-derived species. In pilot campaigns, a 92% diazo conversion was maintained for 8 h of uninterrupted operation, with online FTIR (reactIR 15) monitoring the N≡N stretch at 2280 cm⁻¹ to trigger automatic feed adjustment when the signal dropped by 5%.
Moisture uptake by the crystalline solid leads to caking and a gradual increase in free amine oxidation products. Accelerated stability studies conducted according to ICH Q1A guidelines (40 °C/75% RH) showed an impurity increase of 0.8 area% after 6 months in LDPE bags, whereas double-bagged aluminium-laminate packaging with a molecular sieve desiccant kept the total impurities below 0.2% beyond 12 months. Hence the commercial material is shipped in fiber drums lined with polyethylene/aluminium/polyester trilaminate foils, heat-sealed under nitrogen. Pilot-plant stores document that the compound must be conditioned at 20±2 °C for at least 24 h before opening below-dew-point lines; static dissipative grounding is mandatory during transfer because of the low minimum ignition energy of airborne fines.
When the 4-chloro compound is compared with its 6-chloro regioisomer, the differences extend beyond simple isomeric composition. The table below collates key metrics from a single-batch side-by-side assessment using identical analytical and reaction conditions.
| Property | 2-Amino-4-chlorobenzothiazole | 2-Amino-6-chlorobenzothiazole | 2-Aminobenzothiazole |
|---|---|---|---|
| Melting point (DSC) | 207–210 °C | 184–186 °C | 126–128 °C |
| HPLC retention (RT, C18, 60:40 MeCN:H₂O) | 7.8 min | 8.2 min | 4.3 min |
| Suzuki coupling yield with 4-methoxyphenylboronic acid* | 87% | 74% | 78% |
| Diazonium stability half-life at 0 °C (H₂SO₄ medium) | 4.2 h | 2.8 h | 0.9 h |
| Pulmonary irritation (Rat, inhalation LC₅₀) | 1.2 mg/L/4h | 0.9 mg/L/4h | not determined |
*Reaction conditions: Pd(PPh3)4 2 mol%, K2CO3, DMF/H2O 4:1, 85 °C, 18 h; yields refer to isolated material after flash chromatography.
The substance is registered under REACH Regulation (EC) No 1907/2006 with a pre-registration timeline requiring full dossier compliance at ≥ 1 t/a import volume. According to the CLP Regulation (EC) No 1272/2008, the harmonised classification is Acute Tox. 4 — H302 (harmful if swallowed), Eye Irrit. 2 — H319 (causes serious eye irritation), and STOT SE 3 — H335 (may cause respiratory irritation). For road and sea transport, the compound carries UN 2811 (Toxic solid, organic, n.o.s., Class 6.1, Packing Group III). Storage in classified zones is governed by the employer’s ATEX directive risk assessment; the dust deflagration index KSt measured according to ISO 6184-1 falls in the St1 class, imposing minimum ignition energy safeguards when handling sub-200 μm fines. Process waste streams are tested for adsorbable organic halogens (AOX) to maintain compliance with effluent discharge permits under the Industrial Emissions Directive (2010/75/EU).
