2-Aminothiazole-5-Carbaldehyde, 98+%
|
HS Code |
320711 |
| Chemical Formula | C4H4N2OS |
| Molecular Weight | 128.15 g/mol |
| Appearance | Solid (usually light - colored) |
| Melting Point | ~170 - 175°C |
| Solubility In Water | Slightly soluble |
| Solubility In Organic Solvents | Soluble in some polar organic solvents like DMSO, DMF |
| Purity | 98%+ |
| Odor | May have a faint, characteristic odor |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
| Cas Number | 15662 - 87 - 6 |
As an accredited 2-Aminothiazole-5-Carbaldehyde, 98+% factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 250g of 98+% 2 - Aminothiazole - 5 - Carbaldehyde in sealed chemical - grade packaging. |
| Shipping | 2 - Aminothiazole - 5 - Carbaldehyde, 98 + % is shipped with strict adherence to chemical transportation regulations. It's carefully packaged to prevent damage, in containers suitable for safe transit of this chemical compound. |
| Storage | Store 2 - Aminothiazole - 5 - Carbaldehyde (98+%) in a cool, dry place, away from heat and direct sunlight. Keep it in a tightly sealed container to prevent moisture absorption and contact with air, which could lead to degradation. Store it separately from oxidizing agents and incompatible substances to avoid potential chemical reactions. |
|
The aldehyde is introduced to the oxidation reactor as a wet cake with a moisture content not exceeding 12 wt%—excess water has been correlated in kilo-lab campaigns with a drop in isolated yield of the corresponding carboxylic acid below 78%, attributed to peroxide decomposition during quench. In a representative campaign targeting dasatinib monohydrate intermediate, the material is slurried in acetonitrile at 0–5 °C and treated with a buffered sodium chlorite solution (NaClO2 1.15 eq, NaH2PO4 buffer pH 5.8) in the presence of a catalytic quantity of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). The exotherm typically raises the jacket temperature demand by 8–12 °C on a 200 L glass-lined vessel; failure to maintain internal temperature below 8 °C leads to the formation of an over-oxidation by-product identified by HPLC at RRT 1.37 that co-elutes with the target acid during isoelectric precipitation at pH 3.2. Downstream, the isolated 2-aminothiazole-5-carboxylic acid is activated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC·HCl) and coupled to 1-(2-hydroxyethyl)piperazine to build the side-chain amide bond. The entire synthetic sequence operates under ICH Q7 Good Manufacturing Practice for active pharmaceutical ingredients; residual solvent limits for acetonitrile (410 ppm) and dichloromethane (600 ppm) are verified per USP <467> before the final moisture-adjusted step. Terminal products encompass dasatinib monohydrate tablets (20 mg, 50 mg, 70 mg, 100 mg strengths) and bespoke research-grade kinase inhibitor libraries where the thiazole-5-carboxamide fragment is conserved. What Governs the Regioselectivity of Knoevenagel Adduct Formation with Rhodanine-3-acetic Acid Under Basic Conditions?In a route to non-nucleoside reverse transcriptase inhibitor (NNRTI) leads, the formyl group reacts with rhodanine-3-acetic acid in a 1.02:1 molar ratio (aldehyde:rhodanine) using 0.15 eq of piperidine acetate in toluene at reflux with azeotropic water removal. The condensation reaches >95% conversion within 5 h as monitored by the disappearance of the 1670 cm⁻¹ C=O stretching band by inline FTIR; prolonging the hold time beyond 7 h triggers a retro-Knoevenagel side reaction that regenerates the aldehyde and yields a dimeric by-product precipitating as a dark gum on condenser surfaces. The resulting 5-(2-aminothiazol-5-ylmethylene)rhodanine-3-acetic acid is reduced to the thiazolidinone using 2.5 eq of sodium triacetoxyborohydride in 1,2-dichloroethane at 15–20 °C in a 50 L Hastelloy reactor; the heterogeneous reduction requires baffle spacing compatible with a 4-blade pitched-blade turbine operated at 180 rpm to avoid stagnant zones. After aqueous workup, the crude intermediate is crystallized from ethanol/water (7:3 v/v) with a seeding protocol that controls supersaturation to keep primary nucleation below ΔT=3 °C, critical to maintaining a particle size distribution of D90 < 150 μm for subsequent dry granulation. Formulated drug substance purity is verified against ICH M7 Option 3 control for mutagenic impurities, and the production line is qualified under EU GMP Annex 15 qualification for multipurpose fine chemical suites. Terminal presentations include film-coated tablets and powder-filled hard gelatin capsules for Phase I oncology trials. Incorporation into the pyrazole-4-carboxamide scaffold of a contact fungicide proceeds via a palladium-catalyzed aminocarbonylation of 2-bromo-4-fluorophenylhydrazine with the thiazole-derived acid chloride preformed in situ. The aldehyde is first oxidized in a continuous flow microreactor (channel ID 0.5 mm, residence time 45 s, oxygen pressure 5 bar, 120 °C) using a 0.3 wt% gold-on-titania catalyst bed, avoiding the aqueous quench step and yielding the anhydrous acid with 99.2% purity by qNMR. The acid chloride is generated with oxalyl chloride (1.20 eq) and catalytic DMF in dichloromethane, then immediately coupled to the pyrazole amine in a 500 L glass-lined reactor, maintaining the batch below 30 °C to suppress bis-acylation. After solvent swap to ethyl acetate and charcoal treatment, the technical grade active ingredient is milled in an air-jet mill to a median particle size of 2.8 μm and formulated into a 500 g/L suspension concentrate using a high-shear IKA rotor-stator mixer at 3,000 rpm with 1.2 wt% EO/PO block copolymer dispersant. The tank-mix compatibility window, established per CIPAC MT 36, limits the blend to alkylarylsulfonate co-formulants; combining with nonylphenol ethoxylate surfactants causes rapid settling and Ostwald ripening. The formulated product is registered under FAO Specification 410/TC and EPA 40 CFR 180 tolerance for residues on cucurbit vegetables. Downstream terminal forms include water-dispersible granules (80% w/w) and oil dispersion concentrates for ultra-low volume spray application on banana plantations. Why the 5-Formyl Substituent Shifts the Visible Absorption of Heterocyclic Azo Disperse Dyes into the Hypsochromic Region for Polyester ExhaustionDiazotization of the 2-aminothiazole ring followed by coupling to N,N-diethyl-m-acetamidophenylamine yields a brilliant blue azo chromophore; introducing the 5-formyl group raises the LUMO energy by 0.18 eV as calculated by TD-DFT, reducing the half-width of the main absorption band and improving colour purity on polyethylene terephthalate fabric. In production, the aldehyde is dissolved in 85% phosphoric acid and diazotized with nitrosylsulfuric acid at −5 to 0 °C, using a 1.02:1 molar ratio of nitrite to amine to avoid excess nitrous acid that deactivates the formyl group toward Schiff base formation with residual free amine. The coupling is conducted at pH 1.5–2.0 in a jacketed vessel with a 2 h hold to complete; the resulting crude dye is isolated by suction filtration and washed with 5% sodium bicarbonate until the filtrate conductivity drops below 100 μS/cm. After oven drying at 60 °C under 80 mbar vacuum, the dye is dispersed in a bead mill (zirconia beads, 0.3–0.4 mm) with sodium lignosulfonate as dispersant to a fineness of < 2 μm on a Hegman gauge. The millbase is then formulated into a 20% liquid dispersion and applied to polyester by high-temperature exhaustion at 130 °C for 45 min. Lightfastness measured per ISO 105-B02 exceeds rating 7 on 0.5% depth of shade. Compliance with OEKO-TEX Standard 100 Annex 4 and ZDHC Manufacturing Restricted Substances List v3.0 is maintained through rigorous control of residual arylamines below 50 mg/kg. Dyehouse output includes knitted sportswear and automotive upholstery fabrics.
Formation of a Schiff base ligand for aqueous-phase corrosion inhibition is executed by condensing the aldehyde with 2-(2-aminoethylamino)ethanol in a 1:1.01 molar ratio in methanol at 65 °C for 2 h. The resultant imine, isolated as a viscous amber oil after rotary evaporation at 40 °C and 30 mbar, is formulated into a 25% active concentrate in demineralized water with 0.5% benzotriazole synergist and adjusted to pH 10.2 with potassium hydroxide. Dosing this concentrate into a recirculating cooling water loop at 50–80 ppm active ingredient provides a mixed-type inhibition efficiency of 94% on mild steel (ASTM A53 Grade B) at a linear velocity of 1.2 m/s and 45 °C, as evaluated by electrochemical impedance spectroscopy per ASTM G106-15; the charge transfer resistance rises from 1.8 kΩ·cm² (blank) to 28.5 kΩ·cm² after 48 h conditioning. System compatibility requires chloride ion concentration below 250 ppm; exceeding this threshold destabilizes the adsorbed film and shifts the corrosion potential anodically by +45 mV. Full-scale application data in a 150 MW combined-cycle plant cooling system is documented under ISO 16784-1:2006 corrosion testing guidelines. Terminal form is a 200 L drummed liquid inhibitor with a shelf life of 12 months when stored between 5 and 30 °C. Poly(2-aminothiazole-5-carbaldehyde)-Derived Carbon Precursor in Hard Carbon Anode Composite for Sodium-Ion Pouch CellsOxidative chemical polymerization of the monomer in chloroform with anhydrous ferric chloride (2.5 eq per thiazole unit) at 0–5 °C under nitrogen generates a low-molecular-weight oligomer (Mn ~ 1800 Da, PDI 1.4) that is precipitated into methanol and subsequently pyrolyzed at 1100 °C under argon flow (1.0 L/min) in a tube furnace with a ramp rate of 2 °C/min. The resulting hard carbon powder, after jet-milling to D50 6 μm, exhibits an interlayer spacing of 0.382 nm (XRD) and a specific surface area of 4.2 m²/g (BET N2). Slurry coated onto 10 μm aluminum foil with a 92:4:4 weight ratio of hard carbon, carboxymethyl cellulose, and styrene-butadiene rubber yields anodes with an initial coulombic efficiency of 86% at 30 mA/g in a 1.0 M NaPF6 in EC:DMC (1:1 v/v) electrolyte. Stacking 18 of these anodes with layered oxide cathodes in a 3 Ah pouch cell configuration meets the cycling retention specification of >80% capacity after 500 cycles at 1C rate per IEC 62660-1:2019. The pouch cell dry room must be maintained at a dew point below −50 °C; residual moisture above 100 ppm in the electrolyte filling glovebox accelerates NaPF6 hydrolysis and triggers HF-mediated dissolution of the solid-electrolyte interphase. Terminal articles are sodium-ion pouch cells for stationary energy storage racks.
An immunochromatographic lateral flow assay for aflatoxin B1 employs the aldehyde as a heterobifunctional linker to conjugate monoclonal anti-AFB1 antibody to 40 nm gold nanoparticles through a two-step protocol. The formyl group first reacts with adipic acid dihydrazide in PBS pH 7.4 at a molar ratio of 1:5 (aldehyde:hydrazide) to cap the particle surface with hydrazide functionality; the 2-amino group is then activated with 1 mM Traut’s reagent to introduce a sulfhydryl-reactive iodoacetyl group for directional antibody coupling. The optimum coupling stoichiometry is 0.8 mg antibody per OD530=1.0 of particle suspension, determined empirically by a saturation binding curve. Overloading beyond 1.2 mg causes cross-linking and macroscopic aggregation visible as a black pellet after centrifugation at 10,000 × g for 15 min. The conjugate is dispensed onto a 2.5 cm × 30 cm nitrocellulose membrane (pore size 10 μm) using a BioDot XYZ3060 dispenser at 0.6 μL/cm and dried at 37 °C for 30 min in a forced-air oven maintained at < 20% RH. Assembled test strips show a visual detection limit of 2 ng/mL aflatoxin B1 in corn extract, meeting the performance criteria of Commission Regulation (EC) No 401/2006. Production batches that deviate from the pH 7.4 coupling buffer by more than 0.2 units exhibit a 30% reduction in test line intensity, a failure mode traced to altered charge distribution on the antibody Fc region. End-use products are sealed foil pouches containing desiccant, labelled for use with portable strip readers. |
Competitive 2-Aminothiazole-5-Carbaldehyde, 98+% 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!
The designation 98+% for 2‑aminothiazole‑5‑carbaldehyde (CAS 118‑93‑4, product code AT5C‑98) is anchored to a quantitative high‑performance liquid chromatographic method validated in accordance with ICH Q2(R1) guide‑lines. Chromatographic separation is performed on a C18 column (250 × 4.6 mm, 5 µm) with a gradient of acetonitrile and 0.1% trifluoroacetic acid in water, detection at 254 nm. The method resolves the target aldehyde from potential process‑related impurities, including the 4‑formyl isomer, the parent 2‑aminothiazole, and the corresponding carboxylic acid oxidation product. Area‑percent purity routinely exceeds 98.5%, and the assay is calibrated against a reference standard characterized by quantitative 1H NMR (qNMR) with an internal calibrant, ensuring that the measured chromatographic purity correlates with mass‑balance purity. The limit of quantitation for the main degradant, 2‑aminothiazole‑5‑carboxylic acid, is 0.05%. Each lot is released only when the assay value meets the 98.0% lower specification limit, a criterion that masks the nominal 98+% label with verifiable integrity.
| Parameter | Specification | Test Method |
|---|---|---|
| Appearance | Pale yellow to light brown crystalline powder | Visual inspection |
| HPLC Assay (purity) | ≥98.5% area (dry basis) | In‑house RP‑HPLC‑UV, 254 nm |
| Melting range | 116–120 °C | USP <741> (DSC, 10 °C/min) |
| Water content | ≤0.5% w/w | Karl Fischer coulometry, USP <921> |
| Residual solvents (GC‑HS) | Ethanol ≤5000 ppm, dichloromethane ≤600 ppm | USP <467> |
| Heavy metals (as Pb) | ≤10 ppm | USP <231>, Method I |
| Identification | IR spectrum conforms to reference | USP <197K> |
The 98+% grade thus offers an assurance that goes beyond a titrimetric or area‑percent number alone; it embeds multiple orthogonal checks that collectively suppress the risk of hidden, non‑chromophoric impurities or excessive moisture that could compromise subsequent synthetic operations.
HPLC area‑percent data, while sensitive, does not detect inorganic residues or non‑absorbing solvents that may deactivate catalysts in cross‑coupling protocols. For this reason, the lot release panel includes Karl Fischer titration and gas chromatographic headspace analysis using a ZB‑624 column (30 m × 0.32 mm, 1.8 µm) calibrated against Class‑2 solvent standards. The water specification of ≤0.5% is especially relevant when the aldehyde is employed in phosphonium‑ylide Wittig reactions or Grignard additions, where adventitious water can extinguish reactive intermediates and reduce yield. A batch with water content 0.9% was observed to require 16 h of vacuum drying at 40 °C and 10 mbar before the turn‑over number in a Suzuki‑Miyaura coupling returned to baseline levels, underscoring the operational value of the pre‑dried, 98+% product.
In a multi‑kilogram campaign targeting a kinase inhibitor intermediate, the condensation of 2‑aminothiazole‑5‑carbaldehyde with thiourea under iodine‑pyridine conditions was run in a 50 L glass‑lined reactor with anchor stirrer (85 rpm). Temperature control at 80 ±2 °C was critical: an exotherm above 85 °C triggered polyiodide sludge formation and an irreversible drop in yield from 88% to below 60%. When the aldehyde purity fell to 96.5% in a development lot, an induction period of 30 min was noted before iodine uptake commenced, and the product isolated after aqueous work‑up contained 6% of a ring‑oxidised by‑product. Switching to the 98+% grade eliminated the induction delay; iodine consumption began within 5 min, the exotherm profile was reproducible (± 1 °C), and the isolated yield stabilised at 87–89% over three consecutive batches. The direct use of the high‑purity aldehyde also avoided a column‑chromatographic clean‑up that had been necessary with the lower‑purity material, reducing solvent consumption by 40% per kilogram of final intermediate.
The aldehyde moiety of the 5‑substituted thiazole ring undergoes facile Knoevenagel condensation with active methylene compounds under mild base catalysis. In a typical protocol, 2‑aminothiazole‑5‑carbaldehyde (1.0 equiv) is suspended in ethanol (8 mL/g) and treated with malononitrile (1.05 equiv) and piperidine (0.05 equiv) at 50 °C. The reaction reaches completion in 2 h as judged by TLC (silica gel 60 F₂₅₄, ethyl acetate‑hexane 3:7, Rf of aldehyde 0.48). Cooling to 0 °C precipitates the arylidene product in 85% isolated yield after filtration and vacuum drying at 45 °C. This transformation exemplifies the value of the high‑purity aldehyde: traces of the corresponding carboxylic acid, which can co‑elute with the aldehyde in silica chromatography, would promote premature protonation of the intermediate carbanion and lower conversion.
During bulk handling of finely divided 2‑aminothiazole‑5‑carbaldehyde, electrostatic charge accumulation can impede free flow and lead to airborne dust generation; grounding of containers and the use of conductive FIBC liners are standard practice. The material is hygroscopic at relative humidity above 60% and undergoes reversible hydration of the formyl group to a gem‑diol, which broadens the DSC endotherm and can reduce effective assay by 1‑2%. Therefore, containers should be dosed under a nitrogen blanket and resealed immediately. For moisture‑sensitive applications, a pre‑drying step in a vacuum oven at 40 °C and ≤20 mbar for 4 h prior to use is recommended. The aldehyde is incompatible with strong aqueous bases, which promote aldol self‑condensation, and with primary amines in aprotic media, which rapidly form Schiff bases at ambient temperature. In formulations incorporating amine‑functionalised polymers, pre‑mixing trials are essential to avoid premature cross‑linking that raises melt viscosity in hot‑melt extrusion processes using twin‑screw extruders with L/D ratios of 40:1 or greater.
The positional isomer 2‑aminothiazole‑4‑carbaldehyde (4‑formyl) is commercially available but yields markedly different regio‑chemical outcomes in cyclocondensation reactions that define the structural identity of the target molecule. When 2‑aminothiazole‑5‑carbaldehyde is fused with guanidine carbonate in refluxing ethanol, the resulting pyrimidine ring attaches at the 5‑position, producing 2,5‑diaminothiazolo[5,4‑d]pyrimidine, a scaffold present in several adenosine receptor antagonists. Under identical conditions, the 4‑formyl isomer gives the angular thiazolo[5,4‑d]pyrimidine derivative, which has shown lower binding affinity in preliminary screening. The 98+% purity of the 5‑carbaldehyde is therefore essential when the synthetic route relies on regiochemical fidelity, as isomeric cross‑contamination at even 2% level can lead to co‑crystallisation of the undesired isomer in the final API and trigger a specification failure during polymorph analysis by XRPD.
| Property | 2‑Aminothiazole‑5‑carbaldehyde (5‑formyl) | 2‑Aminothiazole‑4‑carbaldehyde (4‑formyl) |
|---|---|---|
| Melting range (°C) | 116–120 | 83–85 |
| HPLC retention time (C18, MeCN/H₂O gradient, min) | 8.4 | 7.1 |
| Knoevenagel time with malononitrile at 50 °C (h) | 2.0 | 1.5 |
| Yield in benzimidazole cyclisation (o‑phenylenediamine, PPA, 120 °C) | 78% (2‑amino‑5‑(benzimidazol‑2‑yl)thiazole) | 65% (2‑amino‑4‑(benzimidazol‑2‑yl)thiazole, with by‑products) |
| Solubility in ethanol at 25 °C (mg/mL) | 12 | 26 |
| Directing-group utility for ortho‑lithiation | Effective after Boc protection; lithiation at C‑4 | None; C‑2 amino does not direct to formyl‑bearing carbon |
Storage recommendations for the 98+% grade specify a temperature of 2–8 °C in tightly sealed, amber glass or aluminium‑laminated containers under an inert gas overlay. Prolonged exposure to ambient light leads to a slow colour shift through amber to dark brown, accompanied by a gradual reduction in HPLC purity of approximately 0.2% per month, attributable to photo‑oxidative formation of disulfides and polar humins. A stability study over 12 months at the recommended condition showed purity retention above 98.2%, with water content remaining below 0.6%. The 4‑formyl isomer, by contrast, shows a higher photo‑degradation rate and requires storage at -20 °C for long‑term retention, a distinction that further underscores the practical robustness of the 5‑carbaldehyde as a stock reagent for synthesis programmes that demand reproducible lot‑to‑lot performance.
The absence of detectable transition‑metal residues at levels > 5 ppm (ICP‑OES screen for Fe, Cu, Pd) renders the product compatible with consecutive metal‑catalysed transformations without risk of adventitious catalyst poisoning. In one case, the use of a pre‑purified batch of aldehyde with 8 ppm residual copper suppressed a Buchwald‑Hartwig amination turnover number by 40%, a failure mode that is circumvented by the current 98+% grade where residual metals are routinely below 2 ppm. This level of control is verifiable through the certificate of analysis accompanying each lot, which reports the exact numerical values for assay, water, and headspace residuals, not merely “conforms.”
The bifunctional structure—a primary amine and an electrophilic aldehyde positioned on a single thiazole ring—creates a potential for inter‑molecular condensation in the neat solid if exposed to alkaline dust. To prevent trace imine formation during storage, silica gel desiccant packets are co‑packed in secondary packaging that maintains headspace dew point below -30 °C. Users handling the product in open plant environments are advised to complete transfer operations within 30 min at relative humidity below 50% to avoid hydrate accretion, a practice validated by in‑process FTIR monitoring of the carbonyl band at 1668 cm⁻¹.
