4-Methyl-1,3-Thiazole-2,5-Diamine
|
HS Code |
457971 |
| Chemical Formula | C4H7N3S |
| Molar Mass | 129.184 g/mol |
| Appearance | Solid (presumed, based on similar compounds) |
As an accredited 4-Methyl-1,3-Thiazole-2,5-Diamine factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 500g of 4 - Methyl - 1,3 - Thiazole - 2,5 - Diamine packaged in air - tight plastic bags. |
| Shipping | 4 - Methyl - 1,3 - Thiazole - 2,5 - Diamine is shipped in well - sealed, corrosion - resistant containers. Packaging adheres to strict chemical transportation regulations to ensure safe transit, minimizing risk of leakage during handling and transport. |
| Storage | 4 - Methyl - 1,3 - Thiazole - 2,5 - Diamine should be stored in a cool, dry, and well - ventilated area. Keep it away from sources of heat, ignition, and direct sunlight. Store in a tightly sealed container to prevent contact with air and moisture, which could potentially cause degradation or reactivity. Separate from oxidizing agents and incompatible substances. |
|
In the formulation of oxidative permanent hair colorants classified under the EU Cosmetics Product Regulation (EC) No 1223/2009, the presence of a heterocyclic diamine such as 4-methyl-1,3-thiazole-2,5-diamine alters the redox cascade by establishing a primary intermediate with a significantly lower oxidation potential compared to p-phenylenediamine, which shortens the induction period for dye chromophore formation in the alkaline peroxide medium. The addition of this diamine at concentrations between 0.5% and 2.5% w/w of the total dye base, in combination with established couplers — typically resorcinol, m-aminophenol, and 5-amino-o-cresol — within a pH 9.8 ± 0.2 ammonium hydroxide/ammonium bicarbonate buffer system, yields indo- and indoaniline dyes exhibiting an absorption maximum in the 570–590 nm region, which is critical for achieving cool brown and natural black shades in Level 3 permanent coloration. The manufacturing process demands cold compounding at 5–15 °C in vacuum-equipped planetary mixers to suppress premature oxidative coupling, followed by packaging in aluminium laminate tubes under nitrogen blanket and subsequently performing an on-head mixing ratio of 1:1 with a 6% hydrogen peroxide developer immediately before application. Each production batch must satisfy the positive listing requirements of Regulation 1223/2009 Annex III and the SCCS/1533/14 opinion on heterocyclic diamines, with a maximum on-head concentration restricted to 2.0% as free base, and the intermediate must be screened via HPLC–MS against a validated threshold of 0.1 ppm for potentially genotoxic aromatic amine impurities — especially o-toluidine congeners — before release. Terminal products are permanent cream and liquid oxidation hair colours sold through professional salon channels, with mandatory skin sensitization pre-testing conducted under ISO 10993-10 on a panel of 30 human volunteers, where cumulative irritation indices below 0.5 are required to confirm dermal tolerance. Synthesis of N-heterocyclic active pharmaceutical compounds targeting the ATP-binding pocket of tyrosine kinases or dihydrofolate reductase employs 4-methyl-1,3-thiazole-2,5-diamine as a regioselective building block in a Buchwald–Hartwig cross-coupling step conducted under Current Good Manufacturing Practice (cGMP) per ICH Q7, using a molar ratio of 1.00–1.05 equivalents relative to the electrophilic coupling partner in anhydrous THF at 65 ± 3 °C with a Pd2(dba)3/XPhos catalyst system, affording an advanced intermediate that is subsequently converted to a hydrochloride salt and purified through preparative HPLC to an assay exceeding 99.5%, yielding a thiazole-containing API intended for oral solid dosage forms such as film-coated tablets. When the Epoxy Prepreg Processing Window Narrows Below 80 °CFormulators adopting this diamine as a latent hardener for DGEBA-based aerospace prepregs encounter a processing window that is critically constrained by the compound’s exceptionally low amine hydrogen equivalent weight — calculated as 32.3 g/eq (molecular weight 129.2 g/mol divided by 4 active hydrogens) — which drives a rapid viscosity build-up once the one-component system is heated above its melting range. When blended with a standard liquid epoxy resin of epoxy equivalent weight 190 g/eq at a stoichiometric ratio of 0.17:1 hardener to resin, the initial mix viscosity measured on a Brookfield CAP 2000+ viscometer at 70 °C drops to approximately 800 mPa·s, yet gelation is observed within 45 min under isothermal DSC (ASTM E2890) at 120 °C, which necessitates a two-stage cure cycle of 2 h at 130 °C followed by 4 h at 200 °C under 3–5 bar autoclave pressure to achieve complete conversion without exothermic runaway. The methyl substituent at the 4-position decreases molecular symmetry sufficiently to suppress crystallinity, permitting dissolution in acetone and MEK at 35–40% solids by weight for hot-melt prepregging on a 30‑m tower with zone temperatures ramped from 60 °C to 110 °C; however, the resulting prepreg must be stored at ‑18 °C within sealed foil pouches and conditioned for 24 h at 23 °C with 20–30% relative humidity before lay-up to prevent entrapped moisture from plasticising the network during cure. The highly crosslinked network produced from this stoichiometry — with a theoretical crosslink density exceeding 2.8×10‑3 mol/cm³ — exhibits a glass transition temperature projected by the DiBenedetto equation to lie between 250 °C and 285 °C when measured by DMA at 1 Hz (ASTM D7028). Practical measurement of dry Tg on a cured neat resin plaque of 2 mm thickness in a TA Instruments Q800 in single cantilever mode at a ramp rate of 3 °C/min typically reveals a loss-modulus peak near 278 °C, although this value can drop by 25–30 °C after 48 h immersion in 70 °C distilled water, an observation attributed to the hydrophilic thiazole ring facilitating moisture uptake of 0.9–1.2% by Karl Fischer titration. This makes post-cure vacuum drying at 180 °C for 6 h mandatory for any structural laminate intended for service under hot-wet conditions. Moreover, the high crosslink density results in a tensile modulus above 4.8 GPa (ISO 527‑2) and a fracture toughness KIc at 23 °C of only 0.6–0.8 MPa·m½ (ASTM D5045), indicating that this hardener is best suited for compression-dominated primary structures — such as engine nacelle frames or stiffened fuselage panels — where high compressive strength at elevated temperature outweighs the penalty in impact damage tolerance. Incompatibilities arise when the diamine is combined with amine-functionalised toughening agents (e.g., ATBN or CTBN) before cure, as the competing primary amine reactions accelerate gelation prematurely; therefore, any toughening strategy must employ preformed core‑shell rubber particles dispersed in the resin phase prior to hardener addition.
Handling protocols require pre-drying the diamine crystals at 60 °C and 10 mbar for 12 h before blending because the aromatic amine groups readily adsorb moisture above 60% relative humidity, leading to micro-voiding in the cured laminate. Dispersion on a co-rotating twin-screw extruder with an L/D ratio exceeding 40 and a screw profile composed of 70% kneading blocks operating at 200–250 rpm has been demonstrated to reduce the occurrence of unreacted hardener agglomerates to below 0.1 mm² per square metre of prepreg, assessed by ultrasonic C-scanning (ASTM E2580). Batch-to-batch consistency is monitored by FTIR quantification of residual nitrile or amine peaks in the B-staged prepreg, and any lot showing a deviation in the normalised absorbance ratio beyond ±0.05 from the production reference is rejected. The terminal product is a class‑critical, flame‑retardant prepreg meeting the FAR 25.853 vertical burn test and suitable for out‑of‑autoclave processing using vacuum‑bag‑only curing, ultimately yielding monolithic carbon‑fibre‑reinforced laminates for Class 2 aircraft secondary structures. How Does Tetrazotisation Selectivity Impact Tinctorial Strength on Wool Substrates?Controlled tetrazotisation of 4-methyl-1,3-thiazole-2,5-diamine in hydrochloric acid at 0–5 °C produces a bis-diazonium salt that, upon sequential coupling first with 2-naphthol-6-sulphonic acid (acid condition) and then with 1‑naphthol‑4‑sulphonic acid (alkaline condition) in the presence of sodium acetate buffer, yields a symmetric trisazo structure with an extinction coefficient above 45,000 L·mol⁻¹·cm⁻¹ at the λmax of 580–610 nm. The tinctorial strength and build‑up profile on scoured wool fabric are highly sensitive to the extent of mono‑ vs. bis‑diazotisation: GC‑MS monitoring of the evolved gas during the diazotisation step is employed until the residual amine content is below 0.3 mol% (as determined by ion chromatography of the quenched aliquot), because under‑diazotised batches yield a brown residual colour base rather than the target navy‑black. The recommended feed ratio is 1.00 mol diamine to 2.05 mol sodium nitrite delivered as a 40% aqueous solution below the liquid surface, with the coupling step pH maintained within 5.0–5.5 for the first coupling and 8.5–9.0 for the second to maximise yields of the disazo product while suppressing isomerisation. After coupling, the resulting metal‑free acid dye is salted out with 15% sodium chloride, isolated in a filter press, and dried in a fluidised‑bed dryer with inlet air temperature set to 120 °C until moisture content reaches 4.0 ± 0.5%. The final dye is standardised with dextrin to a commercial strength of 200% vs. the reference standard using spectrophotometric matching against ISO 105‑J01 and subsequently subjected to a compliance screen under Oeko‑Tex Standard 100 (product class I) where the sum of all regulated aromatic amines — including any 4‑aminoazobenzene and benzidine congeners that can be liberated under reductive cleavage — must not exceed 20 mg/kg of dyed textile. Dyeing is carried out in a laboratory‑scale IR dyer set at a liquor ratio of 1:20 with 2.0% owf dye, 10% owf sodium sulphate, and 3% owf formic acid, ramped from 40 °C to 98 °C over 30 min and maintained for 60 min, giving a deep, fast‑to‑light navy shade with ISO 105‑B02 light fastness rating of 5‑6 on chlorinated wool. Production‑scale validation on a crease‑resistant wool challis woven at 250 g/m² demonstrates that the colourfastness to domestic laundering (ISO 105‑C06, test C2S) remains above grade 4‑5, confirming its applicability for upholstery and uniform textiles requiring heavy‑duty wash resistance. |
Competitive 4-Methyl-1,3-Thiazole-2,5-Diamine prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please call us at +8615651039172 or mail to sales9@bouling-chem.com.
We will respond to you as soon as possible.
Tel: +8615651039172
Email: sales9@bouling-chem.com
Flexible payment, competitive price, premium service - Inquire now!
4-Methyl-1,3-thiazole-2,5-diamine (CAS RN 6320-23-4) is a heterocyclic diamine that presents both an endocyclic nitrogen and two exocyclic primary amine sites on a thiazole scaffold bearing a methyl substituent at the 4-position. The compound is supplied as a crystalline solid with a molecular formula of C4H7N3S and a molecular weight of 129.18 g·mol⁻¹. Lot-controlled purity, determined by HPLC area percentage at 254 nm and 210 nm against an external standard, typically exceeds 98.5%; a melting endotherm onset recorded by differential scanning calorimetry per ASTM E794 at 10 K·min⁻¹ under nitrogen is observed in the range 137–142 °C. Amine value by non-aqueous perchloric acid titration falls between 860 and 875 mg KOH·g⁻¹, which correlates with the theoretical diamine equivalent weight of approximately 64.6 g·eq⁻¹. The product is hygroscopic and packages are purged with dry nitrogen to maintain residual moisture below 0.5 wt% by Karl Fischer titration (ASTM E203).
The presence of the 4-methyl group introduces both electronic induction and steric shielding of the adjacent 5-amino function. In uncatalyzed nucleophilic addition reactions with activated carbonyl reagents, the 5-NH2 site reacts preferentially; the methyl group raises the activation energy for Schiff base formation at this position by approximately 8–12 kJ·mol⁻¹ relative to the unsubstituted analogue, as inferred from Hammett σmeta parameters for methyl substitution. This modest deactivation is sufficient to improve chemoselectivity when competing acylation at the 2-NH2 group is desired, a limitation often encountered with 2,5-diaminothiazole where mixed di-acylated by-products can reach 15–20% under non-optimized conditions. The methyl substituent also alters the first pKa of the conjugate acid; spectrophotometric titration in aqueous ethanol (50% v/v) at ionic strength 0.1 M (NaClO4) yields a pKa1 near 3.8 ± 0.2, approximately 0.4 units lower than that of the des-methyl parent, shifting the solubility minimum in neutral pH buffers and affecting work-up protocols that rely on pH-controlled precipitation.
Below is a comparative survey of selected thiazole diamines available in research-grade bulk, highlighting the influence of the substitution pattern on the amine equivalent weight and the melting behavior that governs handling in continuous solid-dosing equipment.
| Compound | CAS RN | Amine equiv. wt. (g·eq⁻¹) | Melting range (°C) | Typical HPLC purity (%) |
|---|---|---|---|---|
| 4-Methyl-1,3-thiazole-2,5-diamine | 6320-23-4 | 64.6 | 137–142 | ≥98.5 |
| 1,3-Thiazole-2,5-diamine | 5845-54-7 | 57.6 | 105–110 | ≥97.0 |
| 4,5-Dimethyl-1,3-thiazol-2-amine | 2288-27-7 | 128.2 (monoamine) | 93–96 | ≥98.0 |
| 2-Amino-5-methyl-1,3-thiazole-4-carboxamide | 7032-93-1 | — | 218–222 (dec.) | ≥95.0 |
Operational boundaries are defined by thermal gravimetric analysis and reaction calorimetry. At 160 °C a slow exothermic decomposition is detectable with an onset near 148 °C by TGA under air at a heating rate of 5 K·min⁻¹, corresponding to a mass loss of 2% over 60 min. This limits short-path distillation to vacuum levels below 0.5 mbar where the boiling point falls below the decomposition threshold. Incompatibility with strong oxidizing agents—including peroxides, hypochlorites, and concentrated nitric acid—has been confirmed by adiabatic calorimetry (ARC), which recorded a pressure rate rise exceeding 20 bar·min⁻¹ above 100 °C in the presence of 30% H₂O₂; mixing with oxidizers is therefore contraindicated.
When formulated as a latent or ambient-cure hardener for bisphenol A diglycidyl ether (DGEBA, EEW 188–192 g·eq⁻¹), 4-methyl-1,3-thiazole-2,5-diamine introduces a step-change in pot life relative to aliphatic polyamines. Isothermal DSC at 25 °C per ASTM E1356 on a stoichiometric mixture (amine-hydrogen‑to‑epoxy ratio 1:1) yields a first exotherm peak top at 12.3 min for the neat diamine dispersed in DGEBA, compared with 4.7 min for 1,3-thiazole-2,5-diamine under identical conditions. The extended latency is attributed to the steric shielding of the 5-amino group, which retards the initial nucleophilic ring-opening. The difference in gel time, measured by a thermoset cure rheometer (parallel plate geometry, 0.5 mm gap, 1 Hz oscillation) per ASTM D4472, is even more pronounced: gelation at 40 °C occurs at 42 ± 3 min for the methylated diamine, versus 18 ± 2 min for the non-methylated counterpart. This window is narrow enough that batch-to-batch variation in amine particle size distribution, when dispersed rather than dissolved, can shift gel time by up to ±8 min unless wet-milled to a median particle diameter D50 below 10 µm using a bead mill operated at 1500–2000 rpm.
Real-time infrared monitoring of the oxirane consumption at 915 cm⁻¹ during isothermal cure at 50 °C confirms that the 5-NH2 addition rate is suppressed, while the 2-NH2 reaction proceeds at a rate comparable to that of aniline. The resulting network exhibits a glass transition temperature (Tg) of 128 °C by DMA (tensile mode, 1 Hz, 3 K·min⁻¹ ramp) after a post-cure cycle of 2 h at 80 °C plus 1 h at 120 °C. This Tg is approximately 15 °C lower than that achieved with 1,3-thiazole-2,5-diamine under the same protocol, consistent with increased free volume introduced by the methyl side group. The crosslink density calculated from rubbery plateau modulus by the theory of rubber elasticity yields a value of 2.8 × 10⁻³ mol·cm⁻³, lower than the 3.5 × 10⁻³ mol·cm⁻³ obtained with the des-methyl analogue. For applications requiring Vicat softening temperatures above 120 °C per ASTM D1525, blends with aromatic polyamines, such as 4,4′-diaminodiphenyl sulfone, have been explored; however, published data for these specific binary amine blends remain limited, and phase separation in the uncured state has been observed at DDS loadings above 20 phr when mixing is conducted without solvent.
The 2,5-diamine architecture of the thiazole ring functions as a bifunctional nucleophile in cyclocondensation reactions with 1,3-dielectrophilic reagents. With diethyl ethoxymethylenemalonate, the 5-amino group attacks the activated β-carbon, followed by ring closure involving the 2-amino group to form a fused pyrimidothiazole scaffold. The 4-methyl substituent exerts a directive effect that reduces regioisomeric by-products: HPLC analysis of the crude reaction mixture from a refluxed suspension in ethanol (reaction time 6 h) shows a single dominant peak accounting for 94% area, compared with 85% area for the unsubstituted congener. The higher regiochemical purity simplifies the downstream chromatography, and the product precipitates upon cooling to 0–5 °C with a recovery of 78–82% after filtration and cold ethanol wash. This is a critical advantage in medicinal chemistry libraries where the 4-methyl group also occupies a hydrophobic pocket often explored in kinase inhibitor design.
The diamine is also used as a precursor for diazotization: the 5-amino group can be converted to the corresponding diazonium salt at 0–5 °C in 2 M HCl with sodium nitrite, enabling subsequent Sandmeyer-type substitutions or azo coupling. Because the 2-amino group remains protonated under these conditions, it is protected in situ, avoiding double diazotization that would otherwise necessitate selective protection–deprotection sequences. Thermal hazard assessment by reaction calorimetry (Mettler Toledo RC1e, isothermal at 5 °C) reveals a specific heat release of approximately −180 kJ·mol⁻¹ (based on NaNO₂ addition), and the accumulation of diazonium intermediate beyond 2 mmol in the reactor must be avoided; the semi-batch dosing protocol limits nitrite addition to maintain a maximum accumulation of <5% of the instantaneous charge.
The thiazole nitrogen and the two primary amine groups provide a tridentate ligand framework that has been examined for immobilization of late transition metals onto crosslinked chloromethylated polystyrene beads. A suspension of beads (Merrifield resin, 1.0–1.5 mmol Cl·g⁻¹) in DMF at 80 °C with 3 equivalents of the diamine and potassium carbonate yields a loading of approximately 0.4–0.6 mmol N·g⁻¹ after 24 h, as quantified by elemental analysis. The methyl substituent at the 4-position reduces the tendency for secondary crosslinking through the 5-amino group during grafting, which is a documented complication with the sterically unhindered parent diamine that leads to intra-bead gelation and poor metal dispersion. Subsequent complexation with PdCl₂ in methanolic solution produces a heterogeneous catalyst active in Suzuki-Miyaura couplings at 0.5 mol% palladium loading, retaining >90% conversion over five recycles when tested with 4-bromoanisole and phenylboronic acid in ethanol-water at 60 °C. Leaching of palladium into the organic phase, determined by ICP-OES after each cycle, averages <3 ppm, meeting the thresholds of the European Pharmacopoeia monograph 2.4.20 for elemental impurities in residual metal classes.
When the diamine is employed as a ligand in homogeneous catalysis, pre-drying of the solvent system to a water content below 50 ppm is necessary to prevent competing protodemetalation pathways; molecular sieves 4A dried at 300 °C for 12 h are added directly to the reaction mixture. Published mechanistic data for this exact coordination environment remains sparse, but the steric parameter derived from X-ray crystal structures of analogous thiazole-amine palladium complexes suggests that the methyl group restricts the accessible conformations of the five-membered chelate ring, which may rationalize the lower turnover frequencies compared with the des-methyl analogue at room temperature yet higher selectivity for the cross-coupled product over homo-coupling side products at elevated temperature.
| Ligand precursor | Pd loading (mol%) | Conversion at 60 °C, 4 h (%) | Selectivity to cross-coupled product (%) | Pd leaching cycle 5 (ppm) |
|---|---|---|---|---|
| 4-Methyl-1,3-thiazole-2,5-diamine | 0.5 | 94 | 98 | 2.6 |
| 1,3-Thiazole-2,5-diamine | 0.5 | 91 | 92 | 8.1 |
| 2-Aminothiazole | 0.5 | 78 | 86 | 15.4 |
Regulatory handling is governed by classification under Regulation (EC) No 1272/2008 (CLP) as a skin irritant Category 2 (H315) and eye irritant Category 2 (H319). No endocrine-disrupting properties have been identified in the screening data submitted under REACH for substances with this structural motif, but full toxicological profiling remains incomplete; thus the precautionary principle mandates the use of local exhaust ventilation at 0.5 m·s⁻¹ face velocity during open handling. Waste streams containing residual diamine are quenched with 10% aqueous acetic acid to protonate the amines before discharge into dedicated organic nitrogen waste containers compliant with local regulations.
