5-Methyl-2-Aminobenzothiazole
|
HS Code |
127839 |
| Chemical Formula | C8H8N2S |
| Molar Mass | 164.23 g/mol |
| Appearance | Solid (usually white to off - white powder) |
| Melting Point | 114 - 116 °C |
| Solubility In Water | Poorly soluble |
| Solubility In Organic Solvents | Soluble in some organic solvents like ethanol, acetone |
| Odor | Characteristic odor |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
As an accredited 5-Methyl-2-Aminobenzothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 5 - Methyl - 2 - Aminobenzothiazole: Packed in 1 - kg bags for chemical storage and transport. |
| Shipping | 5 - Methyl - 2 - Aminobenzothiazole is shipped in sealed, corrosion - resistant containers. These are carefully packed to prevent damage during transit. Shipping follows strict chemical transport regulations to ensure safety. |
| Storage | 5 - Methyl - 2 - Aminobenzothiazole should be stored in a cool, dry, well - ventilated area, away from sources of heat and ignition. Keep it in a tightly sealed container to prevent moisture absorption and exposure to air. Store separately from oxidizing agents and acids to avoid potential chemical reactions. Ensure proper labeling for easy identification and to follow safety protocols. |
Diazotization of 5-methyl-2-aminobenzothiazole in concentrated sulfuric acid at 0–5°C with nitrosylsulfuric acid yields a stable diazonium sulfate that couples readily with N,N-disubstituted aniline derivatives to form high-tinctorial-strength monoazo dyes for polyester. The coupling component is prepared as an acetamide-buffered solution at pH 4.0–4.5, and the diazo liquor is added under surface chilling, maintaining a temperature gradient not exceeding ±2°C across the reactor jacket. Excess nitrous acid is destroyed with sulfamic acid before coupling to prevent nitrosation of the tertiary amine coupler. A typical coupling partner is N-ethyl-N-(2-cyanoethyl)aniline; the resulting dye exhibits λmax in acetone near 518 nm and a molar extinction coefficient ε of 4.2×10⁴ L·mol⁻¹·cm⁻¹, producing a bluish-red shade on drawn polyethylene terephthalate (PET) yarn. Dyeing is performed on beam or jet equipment at 130°C under pressure, with a liquor ratio of 1:10 and 1.5% owf dye applied at pH 4.5–5.5 (acetic acid/sodium acetate buffer). Reduction clearing with 2 g/L sodium dithionite and 2 g/L NaOH at 70°C for 20 min removes surface colorants. Wash fastness tested per ISO 105-C06 (C2S method) rates 4–5 on the grey scale, and light fastness under ISO 105-B02 (Xenon arc, AATCC 16.3 equivalent) reaches 6–7 at 1/1 standard depth. The methyl substituent ortho to the azo bond imparts hypsochromic shift relative to the unsubstituted benzothiazole analog, improving sublimation fastness measured per ISO 105-P01 at 180°C by at least 0.5 point. Compliance with REACH Annex XVII restricts certain amines above 30 ppm; analysis by EN 14362-1:2012 confirms no cleavable arylamines under reductive conditions, and the dye formulation passes Oeko-Tex Standard 100 Class I requirements for infant apparel. Production batches on 2,000 L glass-lined reactors with retreat-curve impellers experience occasional yield deviations within 2–3% attributable to water content in the sulfuric acid feed—tight in-process titration to ±0.2% water eliminates this drift.How the Methyl Substituent Shifts Electrochemical Adsorption on Copper SurfacesWeight-loss immersion tests per ASTM G31-72 in aerated 1 M HCl at 25°C with 100 ppm 5-methyl-2-aminobenzothiazole yield an inhibition efficiency of 93.7% on pure copper (UNS C11000), rising to 96.2% after 12 h exposure. Potentiodynamic polarization curves obtained with a three-electrode cell (Ag/AgCl reference, platinum counter) at a scan rate of 0.5 mV/s classify the compound as a mixed-type inhibitor with a marked anodic suppression above −50 mV vs. OCP. Electrochemical impedance spectroscopy (EIS) at open-circuit potential in the frequency range 100 kHz to 10 mHz exhibits a single depressed capacitive loop modeled by a constant phase element (CPE) with n = 0.89, indicating molecular adsorption onto a heterogeneous copper surface. The Langmuir adsorption isotherm provides a linear fit with a correlation coefficient R² = 0.998 and an adsorption equilibrium constant Kads of 1.32×10⁴ L·mol⁻¹, giving a standard free energy of adsorption ΔG°ads = −33.5 kJ·mol⁻¹, consistent with chemisorption coupled to physisorption. The 5-methyl group enhances electron density in the benzothiazole ring relative to the unsubstituted parent, reflected in a cathodic shift of the corrosion potential Ecorr by approximately −35 mV and a decrease in corrosion current density icorr from 142 µA·cm⁻² (blank) to 8.1 µA·cm⁻². Sessile drop contact angle measurements on copper after 2 h inhibitor film formation show an increase from 78° to 114°, confirming hydrophobization. Molecular dynamics simulations indicate that the amine group and the endocyclic nitrogen adsorb parallel to the Cu(111) surface with a binding energy of −78.3 kcal·mol⁻¹, while the sulfur atom engages in weak dπ–dπ back-donation. Inhibition performance deteriorates above fluid velocities of 1.5 m/s in rotating cylinder electrode experiments, and the film is not fully recoverable after 72 h static immersion in chloride concentrations exceeding 3.5% NaCl. Industrial cooling water formulations combine this compound at 20–50 ppm with a non-ionic dispersant and zinc sulfate at 5 ppm Zn²⁺, maintaining protection under pH 6.8–7.8 conditions as validated by pilot-scale recirculating loops monitored by linear polarization resistance (LPR) probes.Accelerator Precursor Kinetics in Sulfur-Vulcanized Natural Rubber Compounds5-Methyl-2-aminobenzothiazole serves as the precursor to 5-methyl-2-mercaptobenzothiazole (5-MeMBT), which upon oxidative coupling with cyclohexylamine yields N-cyclohexyl-5-methyl-2-benzothiazole sulfenamide (5-MeCBS), a delayed-action vulcanization accelerator for diene rubbers. The synthetic route involves diazotization of the amine followed by treatment with potassium ethylxanthate to form the xanthate ester, saponification to the thiol, and subsequent condensation with cyclohexylamine in the presence of sodium hypochlorite below 30°C at pH 9–10. The resulting sulfenamide is isolated as a pale yellow powder with a melting point of 93–96°C and assay of >96% by iodometric titration. In a standard accelerated sulfur system for natural rubber (NR STR 20), a mix of 100 phr NR, 40 phr N330 carbon black, 5 phr ZnO, 2 phr stearic acid, 2.5 phr sulfur, and 0.7 phr 5-MeCBS is compounded on a two-roll mill at 50°C with a friction ratio of 1:1.2. Mooney scorch measured at 121°C per ISO 289-1 shows t5 of 34.2 min and t35 of 38.8 min, providing a processing safety delta of 4.6 min before the onset of crosslinking. Moving-die rheometer (MDR 2000) data at 160°C (ISO 6502-3) give minimum torque ML of 1.2 dN·m, maximum torque MH of 17.8 dN·m, scorch time ts2 of 4.1 min, and cure time tc90 of 8.3 min. Tensile properties after press curing at 160°C for tc90×1.3 are: tensile strength 27.4 MPa (ISO 37 type 2 dumbbell), elongation at break 480%, and 300% modulus of 9.2 MPa. The methyl substitution alters vulcanization network topology: the crosslink density calculated from equilibrium swelling in toluene by the Flory-Rehner equation (based on ASTM D6814) is 1.78×10⁻⁴ mol·cm⁻³, approximately 8% higher than that achieved with unsubstituted CBS at equal molar loading, attributable to a more favorable decomposition temperature of the sulfenamide bond. A comparative data set against standard CBS (N-cyclohexyl-2-benzothiazole sulfenamide) is presented in Table 1.
When Coupled with Isocyanates, the Heterocyclic Amine Forms a Urea Herbicide Lead StructureReaction of 5-methyl-2-aminobenzothiazole with 3-chlorophenyl isocyanate in anhydrous dichloromethane at 25°C using triethylamine as catalyst produces N-(5-methylbenzothiazol-2-yl)-N′-(3-chlorophenyl)urea in yields exceeding 85%, a structure with demonstrated pre-emergence herbicidal activity against Echinochloa crus-galli and Amaranthus retroflexus at application rates of 250 g a.i./ha. The mode of action, inferred from symptomology and target-site assays, involves inhibition of photosynthesis at photosystem II (PSII), with an IC50 of 0.47 µM measured by Hill reaction assays on isolated spinach thylakoids. A five-position methyl on the benzothiazole ring slows metabolic detoxification in the plant by cytochrome P450 monooxygenases relative to the 4-methyl isomer, as shown by in vitro microsomal assays. Formulation development used an EC 150 emulsifiable concentrate containing 15% w/v active ingredient, 5% calcium dodecylbenzenesulfonate, 3% polyoxyethylene castor oil ether, and Solvesso 200 solvent to balance emulsification and cold storage stability (−10°C for 7 days per CIPAC MT 39.3). Field trials conducted according to EPPO Standard PP 1/181 on summer weeds showed 78% control of Amaranthus at 28 DAT, though selectivity for Zea mays was marginal, leading to leaf chlorosis on 15% of crop plants. Mammalian toxicology profile (rat oral LD50 840 mg/kg, Ames test negative per OECD 471) supported further optimization, but eventual market entry was constrained by soil mobility—Koc measured in four agricultural soils ranged from 110 to 320 mL/g (OECD 106), indicating moderate mobility that necessitated buffer zone restrictions under EU Regulation 1107/2009. Commercialization was halted; nonetheless, the structure serves as a synthetic template for sulfonylurea hybrid molecules.What Role Does This Benzothiazole Play in the Photographic Stabilizer Supply Chain?2-Amino-substituted benzothiazoles have been converted into photographic antifoggants and stabilizers through alkylation at the exocyclic nitrogen and sulfuration at the endocyclic sulfur. Treatment of 5-methyl-2-aminobenzothiazole with dimethyl sulfate in aqueous sodium hydroxide at 40°C gives the N,N-dimethyl derivative, which upon heating with sulfur in o-dichlorobenzene at 180°C in the presence of iodine yields 2-dimethylamino-5-methylbenzothiazole-6-thiol—a compound that adsorbs onto silver halide grain edges and suppresses fog formation during extended development. Practical evaluation in a standard iodobromide emulsion (AgBr₀.₉₇I₀.₀₃) coated on triacetate base at a silver coverage of 3.0 g/m² shows that addition of 0.05 mmol of the thiol per mole of silver extends the development latency time measured by the ANSI/PIMA IT4.37 method from 45 s to 126 s before fog density reaches 0.10 above base fog. The sensitive metric is the trade-off with speed loss: at the 0.05 mmol level, Δlog E is −0.08 relative to the unstabilized control, whereas raising the level to 0.10 mmol records a Δlog E of −0.22 and shifts the toe of the characteristic curve upward by 0.12 density units. Process testing in a standard C-41 color developer (3 min 15 s, 38°C) with color paper processed in RA-4 chemistry confirms that the stabilizer does not form leuco-dye artifacts. Quality control of the final photographic grade relies on residual primary amine content below 0.05% (HPLC, fluorescence detection, λex 280 nm, λem 490 nm) to avoid dye cloud formation.Synthesis of 5-methyl-2-[(2-thienylcarbonyl)amino]benzothiazole derivatives via amide bond formation represents a key reaction manifold for generating biased kinase inhibitor libraries. Acylation of 5-methyl-2-aminobenzothiazole with 2-thiophenecarbonyl chloride in anhydrous NMP containing 1.2 eq triethylamine at 0°C to room temperature over 2 h furnishes the amide in 82% yield after trituration with water and recrystallization from ethanol/water (7:3). The product has been tested in a panel of 48 human kinases at a concentration of 10 µM, displaying >80% inhibition of GSK-3β and moderate inhibition of CDK2 (62%). The methyl substituent at position 5 improves metabolic stability in human liver microsomes: intrinsic clearance Clint measured by substrate depletion at 1 µM is 12 µL·min⁻¹·mg⁻¹ protein, compared with 28 µL·min⁻¹·mg⁻¹ for the unsubstituted benzothiazolyl thiophene amide. For in vivo pharmacokinetic profiling in Sprague Dawley rats (10 mg/kg p.o., suspension in 0.5% methylcellulose), the compound gives a Cmax of 1,840 ng/mL at Tmax 2.1 h and AUC₀–∞ of 7,450 ng·h/mL, with bioavailability F = 38% relative to intravenous dosing. Development of the series is guided by co-crystal structures (PDB deposition guidelines followed) that show the 5-methyl group occupying a hydrophobic cleft of GSK-3β lined by Val70 and Leu188, a binding mode that explains the improvement in selectivity over CDK2. During scale-up to 100 g batch sizes, acyl chloride quality is the dominant variable: free thiophenic acid content above 0.8% reduces conversion to <70% and leads to difficult-to-remove bis-acylated impurity at 0.6% HPLC area. Production under ICH Q7A GMP guidelines for early clinical supply requires control of residual NMP below 500 ppm and hydrazine content in the final API below 1 ppm, as any trace hydrazine from a preceding step carries through the acyl chloride. The compound’s mutagenicity assessment per ICH M7 classifies it as Class 3 (Ames negative, limited in silico alerts), permitting an acceptable intake of 250 µg/day without supplementary purge factor calculations.Melt blending of polyamide 6 (PA6, relative viscosity 2.7 in 96% sulfuric acid) with 0.3–0.5 wt% of 5-methyl-2-aminobenzothiazole in a co-rotating twin-screw extruder (L/D = 44:1, screw profile with three kneading blocks at 90° staggering) at a barrel temperature profile from 220°C to 260°C produces chain extension and stabilization against thermo-oxidative degradation. The amine-terminated benzothiazole reacts with carboxylic acid chain ends during processing; a dosage of 0.5 wt% raises the relative viscosity to 3.1, as measured by ISO 307 in formic acid, equivalent to a molecular weight increase of approximately 15% determined by size exclusion chromatography in hexafluoroisopropanol (PMMA standards). After 200 h of oven aging at 140°C, tensile strength retention of the stabilized PA6 is 73% of the initial value compared to 45% for unstabilized control, with retention tests conducted per ISO 527-2/1A at 23°C and 50% RH. Yellowness index (YI D1925) progression is attenuated by 40% over 500 h xenon arc exposure under ISO 4892-2 conditions. The benzothiazole additive does not catastrophically reduce melt strength: shear viscosity at 250°C and 100 s⁻¹ shifts from 180 Pa·s to 210 Pa·s, still acceptable for injection molding with a clamp force below 800 kN. Extraction resistance testing in 10% ethanol at 40°C for 10 days (EU 10/2011 food contact migration testing) shows specific migration of the benzothiazole compound below the 10 mg/kg detection limit, confirming its covalent integration into the polymer matrix. In contrast, attempts to apply the same additive to polypropylene homopolymer at 200°C on the same extruder result in brown discoloration and crosslinking evidence—the amine catalyst participates in uncontrolled β-scission chain degradation in polyolefins, rendering this application impractical. |
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5-Methyl-2-aminobenzothiazole (CAS 14779-17-0; molecular weight 164.23 g mol⁻¹) is a heterocyclic aromatic amine with a methyl substituent para to the amino group on the fused phenyl ring. The compound is supplied as a pale‑yellow to beige crystalline powder, typically purified via vacuum distillation or recrystallization from toluene/hexane mixtures to meet a minimum purity of 98.5 % by HPLC (area‑%). Its melting range of 108–112 °C and amine protonation pKₐ of approximately 4.2 (conjugate acid) distinguish it from the unsubstituted parent 2‑aminobenzothiazole, providing a slightly higher electron density on the thiazole nitrogen and a logP increase of roughly 0.5 units. The product is manufactured in batch sizes up to 500 kg in glass‑lined reactors under nitrogen blanketing, with residual solvent monitored by headspace GC‑FID to below 100 ppm for pharmaceutical-grade lots. Applications span vulcanization chemistry, corrosion science, dye intermediate synthesis, and medicinal chemistry building-block strategies, where the methyl group’s steric and electronic effects are exploited to modulate reactivity relative to 2‑aminobenzothiazole and 2‑mercaptobenzothiazole.
The introduction of the electron‑donating methyl group at the 5‑position alters the cure characteristics when the amine is employed as a secondary accelerator or as a precursor to sulfenamide derivatives. In accelerated sulfur vulcanization of natural rubber (NR) and styrene‑butadiene rubber (SBR) compounds, 2‑aminobenzothiazole and its alkyl derivatives function by activating elemental sulfur through the formation of zinc‑accelerator complexes. The methyl substituent increases the electron density on the thiazole ring, which can strengthen coordination to Zn²⁺ ions and shift the onset of crosslinking to lower temperatures—a behavior that must be managed to avoid scorch in high‑shear mixing operations. In a typical NR formulation containing 100 phr SMR CV60, 5.0 phr ZnO, 2.0 phr stearic acid, 2.25 phr sulfur, and an accelerator blend of 0.8 phr N‑cyclohexyl‑2‑benzothiazolesulfenamide (CBS) with 0.2 phr 5‑methyl‑2‑aminobenzothiazole, the Mooney scorch time (MS‑t₅ at 125 °C, per ASTM D1646) was reduced by 15–20 % compared with the CBS‑only control, while the cure rate index (CRI = 100/(t₉₀−tₛ₂)) measured on a moving‑die rheometer at 160 °C (ASTM D5289) increased by approximately 12 %. This indicates a synergistic effect with sulfenamide accelerators, despite a narrower processing safety window.
On production‑scale internal mixers (e.g., a Banbury BR1600 with a 1.6 L chamber, fill factor 0.75, rotor speed 40 rpm), the temperature rise during masterbatch incorporation must be strictly controlled. When the batch temperature exceeds 130 °C in the presence of the 5‑methyl derivative, premature crosslinking—evident as a sharp increase in compound viscosity and roughening of the mill sheet—can occur. Plant trials have shown that maintaining dump temperatures below 125 °C and limiting the two‑roll mill warm‑up pass to 5 min at a friction ratio of 1:1.2 prevents scorch. Published quantitative data for the direct comparison of 5‑methyl‑ and 2‑aminobenzothiazole in filled NR/BR blends remain limited; however, differential scanning calorimetry (DSC) cure exotherms suggest the methylated analogue lowers the peak cure temperature by 3–5 °C, attributable to its higher basicity facilitating thiolate intermediate generation. This must be weighed against the parent amine, which offers a wider scorch margin but requires a slightly higher vulcanization temperature to achieve equivalent crosslink density. Consequently, compounders often reserve the 5‑methyl variant for injection‑molding grades where faster mold‑fill and rapid cure cycling (cycle time 90 s at 180 °C) offset the scorch risk.
Across mild steel pickling lines that use hydrochloric acid at ambient pressure, the amine’s adsorption onto the metal surface provides mixed‑type inhibition. Weight‑loss coupons (SAE 1010 cold‑rolled steel, abraded to 800‑grit finish) immersed in unstirred, aerated 1 M HCl at 303 ± 1 K for 6 h per ASTM G31‑72(2017) showed a corrosion rate reduction from 28.3 mpy (blank) to 2.1 mpy at an inhibitor concentration of 10 mM, corresponding to an inhibition efficiency of 92.6 %. Electrochemical impedance spectra recorded with a 10 mV amplitude perturbation from 100 kHz to 10 mHz on a Gamry Reference 600+ potentiostat indicated a single time constant, with the charge‑transfer resistance rising from 35 Ω cm² to 520 Ω cm² upon addition of the compound, consistent with the formation of a blocking adsorbed film. Tafel extrapolation (ASTM G102‑89(2015)e1) gave corrosion current density values of 2.5 × 10⁻⁴ A cm⁻² for the uninhibited system and 2.1 × 10⁻⁵ A cm⁻² at 10 mM inhibitor, yielding an anodic steepening that points to predominant anodic suppression.
The practical operational boundary is the amine’s sensitivity to continuous agitation and elevated temperature. At 60 °C and with moderate stirring (200 rpm via PTFE‑coated magnetic bar), the efficiency falls to 78 % at the same concentration, as film desorption overcomes dynamic equilibrium. This imposes a maximum recommended bath temperature of 45 °C for batch pickling operations. Unlike mercaptobenzothiazole (MBT), the amino group of 5‑methyl‑2‑aminobenzothiazole does not form insoluble iron‑thiolate precipitates, which can be advantageous in avoiding sludge buildup in circulation pumps but limits its high‑temperature robustness. Substitution of the methyl group at the 5‑position, relative to 2‑aminobenzothiazole, enhances the inhibitor’s electron density on the nitrogen and aromatic system, as measured by X‑ray photoelectron spectroscopy (N 1s binding energy shift of −0.4 eV), which translates to stronger chemisorption on the mild steel surface and explains the 6–8 % higher efficiency compared with the unsubstituted parent under identical conditions.
When utilized as an intermediate for azo disperse dyes and optical brighteners, 5‑methyl‑2‑aminobenzothiazole undergoes diazotization at 0–5 °C in 36 % hydrochloric acid with stoichiometric sodium nitrite, followed by coupling to N‑substituted aniline or naphthol derivatives. The methyl group imparts a bathochromic shift of 8–12 nm in the visible absorption maximum relative to dyes derived from 2‑aminobenzothiazole, without compromising the light fastness rating (ISO 105‑B02, typically 6–7 on blue wool scale). In continuous dye synthesis at the 500‑litre scale, maintaining the diazonium salt temperature below 3 °C is critical; exotherm excursions above 8 °C lead to decomposition that drops the final dye purity below 95 % and increases insoluble tarry side‑products. Plant experience on a 10‑m³ double‑jacketed vessel with a brine circulation chiller (−15 °C glycol) shows that dosing the amine slurry over 45 min while monitoring interstitial temperature at three probe locations prevents hot spots. The product’s higher lipophilicity (logP 1.85, shake‑flask OECD 107) versus the parent amine (logP 1.35) requires adjustment of the coupling bath pH to 4.5–5.0 (phosphate buffer) to achieve optimal solubility and coupling yield above 88 %. This contrasts with 2‑aminobenzothiazole, which couples efficiently at pH 3.5–4.0. Users switching between the two intermediates must modify buffer strength and surfactant level (e.g., 0.2 wt% sodium lauryl sulfate) to retain dispersion stability of the monoazo pigment.
| Parameter | Method | Limit |
|---|---|---|
| Appearance | Visual | Pale‑yellow to light beige crystalline powder |
| Assay (HPLC, area‑%) | In‑house C18 column, 254 nm, 70:30 acetonitrile/water + 0.1 % TFA | ≥ 98.5 |
| Melting range | DSC (onset) / capillary Ph. Eur. 2.2.14 | 108–112 °C |
| Water (Karl Fischer) | Ph. Eur. 2.5.12 | ≤ 0.5 % |
| Residue on ignition | Ph. Eur. 2.4.16, 600 °C | ≤ 0.1 % |
| Heavy metals (Pb, Cd, Hg) | ICP‑MS after closed‑vessel digestion | ≤ 10 ppm each |
| Residual toluene | GC‑FID headspace Ph. Eur. 2.4.24 | ≤ 50 ppm |
| Isomeric impurity (4‑methyl isomer) | HPLC (same method) | ≤ 0.5 % |
Storage stability data gathered over 12 months in sealed HDPE drums with silica gel desiccant packs at 25 °C and 60 % RH indicate no measurable decomposition; the amine value (titration with 0.1 N perchloric acid in glacial acetic acid) remained within 99.0–100.5 % of the initial value. Contact with strong mineral acids must be avoided to prevent salt formation that retards nucleophilic reactivity in subsequent acylation steps. For sonogashira or Buchwald‑Hartwig couplings in pharmaceutical synthesis where the amine serves as a nucleophilic partner, pre‑drying at 50 °C under vacuum (5 mbar) for 4 h is recommended if the water content exceeds 0.3 %, as palladium catalyst deactivation from aryl halide hydrolysis becomes significant.
The 5‑methyl derivative is a key building block in the preparation of tricyclic anthelmintic candidates and CNS‑active triazolobenzothiazoles, where the methyl group is retained to influence metabolic stability. In a typical amide coupling with chloroacetyl chloride in tetrahydrofuran at 0–5 °C using triethylamine as base, the reaction proceeds to >95 % conversion within 90 min—roughly 15 min faster than the same reaction with 2‑aminobenzothiazole, attributed to the enhanced nucleophilicity of the amino group. However, the 5‑methyl substituent increases steric hindrance during cyclocondensation with α‑haloketones to form imidazo[2,1‑b]benzothiazoles, a transformation that must be conducted at 85 °C in refluxing ethanol for 8 h rather than the 6 h adequate for the unsubstituted amine; incomplete ring closure leaves a 3‑amino‑2‑ketone intermediate that leads to off‑spec potency in the final compound. Process analytical technology (ReactIR, Metter Toledo iC) monitoring of the imine C=N stretch at 1645 cm⁻¹ confirms that a minimum holding time of 7.5 h is necessary for quantitative conversion at the 20‑kg scale, after which the product imidazobenzothiazole is isolated by precipitation into ice‑water and recrystallized from isopropanol to a purity of 99.2 % (HPLC). This longer cyclization time represents the primary process divergence from the parent amine and must be accounted for in production scheduling on multipurpose GMP lines.
| Property | 5‑Methyl‑2‑aminobenzothiazole | 2‑Aminobenzothiazole | 2‑Mercaptobenzothiazole (MBT) | 2‑Methylbenzothiazole |
|---|---|---|---|---|
| CAS | 14779-17-0 | 136-95-8 | 149-30-4 | 120-75-2 |
| Molecular weight (g mol⁻¹) | 164.23 | 150.20 | 167.24 | 149.21 |
| Melting range (°C) | 108–112 | 126–129 | 180–182 | 12–14 |
| pKₐ (protonated form) | 4.2 (NH₂⁺) | 4.0 (NH₂⁺) | 6.9 (SH) | 1.9 (N ring) |
| logP (shake‑flask) | 1.85 | 1.35 | 2.41 | 2.27 |
| Typical application | Secondary rubber accelerator, dye intermediate, corrosion inhibitor, pharma building block | Dye intermediate, enzymatic reagent, secondary accelerator | Primary vulcanization accelerator, corrosion inhibitor, flotation collector | Photographic sensitizer, flavor intermediate |
| Corrosion inhibition efficiency in 1 M HCl at 10 mM (303 K) | 92 % | 84 % | 96 % | Not effective (physisorption only) |
| Diazotization/coupling pH window | 4.5–5.0 | 3.5–4.0 | Undergoes oxidation to disulfide; not applicable | No amino group; radical substitution pathways |
