Thiazole,98%
|
HS Code |
251037 |
| Name | Thiazole, 98% |
| Molecular Formula | C3H3NS |
| Molar Mass | 85.13 g/mol |
| Appearance | Colorless to pale yellow liquid |
| Odor | Pungent, sulfurous odor |
| Density | 1.18 g/cm³ |
| Boiling Point | 116 - 117 °C |
| Melting Point | -33 °C |
| Solubility | Soluble in water, ethanol, ether |
| Flash Point | 21 °C |
| Refractive Index | 1.555 - 1.557 |
As an accredited Thiazole,98% factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Thiazole, 98% purity, packaged in 1 - kg containers. |
| Shipping | Thiazole, 98% pure, will be shipped in air - tight, corrosion - resistant containers. Shipment will follow all relevant chemical transport regulations to ensure safe and secure delivery. |
| Storage | Thiazole, 98% should be stored in a cool, dry, well - ventilated area. Keep it away from heat sources, open flames, and oxidizing agents. Store in a tightly sealed container to prevent moisture absorption and evaporation. It's crucial to separate it from incompatible substances to avoid potential chemical reactions. |
A routine bottleneck in cGMP intermediate production for protease inhibitors involves the installation of a 2-thiazolyl ketone moiety without ring-opening side reactions. Thiazole (98%) is first dried over activated 3Å molecular sieves until Karl Fischer titration confirms moisture below 50 ppm. In a glass-lined reactor purged with dry argon, the dried Thiazole is dissolved in anhydrous THF (10 volumes) and chilled to -78°C using an external dry ice/isopropanol jacket. n-Butyllithium (2.5 M in hexanes, 1.05 equivalents) is metered via a peristaltic pump while maintaining an internal temperature of -75°C ± 3°C. The resultant 2-lithiothiazole suspension is aged for 30–45 minutes before a pre-cooled electrophile—commonly DMF for 2-thiazolecarboxaldehyde or a Weinreb amide for sterically demanding ketone intermediates—is introduced below the liquid surface. Immediate quenching with saturated ammonium chloride followed by phase separation and vacuum fractionation through a 10-theoretical-plate packed column delivers functionalized thiazole with GC purities exceeding 99%. These building blocks are essential in the convergent assembly of HIV-1 protease inhibitors such as Ritonavir and certain next-generation SARS-CoV-2 3CL protease inhibitors entering Phase II trials. Compliance demands residual lithium quantification per ICH Q3D guideline for elemental impurities and headspace GC-MS monitoring of Class 2 solvents per USP <467>. Plant deviation logs indicate that batch failures correlate almost exclusively with moisture excursions above 100 ppm, which trigger lithium hydroxide gel formation that coats the cooling jacket and chokes the agitator torque threshold.Why Does the Chichibabin Route to 2-Aminothiazole Still Dominate Veterinary Sulfonamide Supply Chains?Thiazole (98%) is charged into a high-pressure autoclave together with finely powdered sodamide (NaNH₂, 1.2–1.5 molar equivalents) and dry N,N-dimethylaniline as solvent. The headspace is flushed with nitrogen, and the heterogeneous mixture is heated to 150–160°C under autogenous pressure for 6–8 hours. Evolved ammonia is vented intermittently through a back-pressure regulator to maintain reactor pressure below 15 bar. Crude 2-aminothiazole is recovered by steam distillation and recrystallized from toluene to give pale yellow crystals with a melting point of 90–92°C. Without isolation, the damp cake is suspended in dry pyridine and condensed with p-acetamidobenzenesulfonyl chloride at 0–5°C. The resulting acetyl-protected sulfathiazole undergoes alkaline hydrolysis, and the final product is recrystallized from aqueous ethanol until it passes USP 43 acceptance criteria for sulfathiazole sodium (assay 99.0–101.0% on dried basis, loss on drying ≤0.5%). The integrated two-step chain operates under veterinary GMP Part 4 and requires demonstrable purge of residual N,N-dimethylaniline below 1 ppm as per VICH GL18(R) residue limits. A recurring plant reliability issue is the formation of a cement-like cake on the reactor wall when sodamide is charged too rapidly; site engineers routinely specify an anchor-type agitator with PTFE scrapers and maintain an inert gas blanket with oxygen below 5% to prevent peroxide accumulation in the hot solvent. The effluent ammonia is scrubbed into dilute sulfuric acid, recovering ammonium sulfate as a co-product stream.Meeting the organoleptic specification for 2-acetylthiazole (FEMA 3328, CAS 24295-03-2) in compounded savory flavours rests on a tight metalation-acylation sequence devoid of ring-scission by-products. Thiazole (98%) is pre-dried to <30 ppm water over molecular sieves and dissolved in THF that has been freshly distilled from sodium/benzophenone ketyl. The jacket of a stainless-steel cryogenic reactor is set to -80°C, and n-butyllithium is fed dropwise while internal temperature is held at -68°C to -65°C. This narrow window suppresses competitive lithiation at the C-5 position, which would generate regioisomeric impurities difficult to remove by distillation. Acetyl chloride (1.15 equivalents) diluted with THF is introduced via a dip tube over 45 minutes. The reaction mass is immediately discharged into an ice-cold phosphate buffer (pH 7.2) to arrest enolate condensation. After phase cut and solvent swap, the crude oil undergoes vacuum rectification through a 15-theoretical-plate Sulzer packing column; the heart-cut collected at 86–88°C/12 mmHg exhibits olfactory purity above 99.5% with a characteristic roasted nut and popcorn profile. Under EU Flavourings Regulation EC 1334/2008, each lot shipped must carry a Certificate of Analysis verifying Annex I purity thresholds—mercury <0.1 mg/kg, arsenic <3 mg/kg, and absence of residual hydrazine if a weinreb amide route was employed. Finished snack seasonings typically incorporate the compound at 0.2–2.0 ppm, dosed via a 1% stock solution in propylene glycol to guarantee uniform dispersion during ribbon blending. Scale-up reports note that replacing n-BuLi with a Turbo-Grignard reagent such as i-PrMgCl·LiCl at -20°C reduces sensitivity to dissolved oxygen and improves yield reproducibility across campaigns.PCB Microetch Undercut Control with Unsubstituted Thiazole at Sub-500 ppm AdditionIn horizontal conveyorized spray etching of fine-line PCBs (line/space ≤ 75 µm/75 µm), the baseline sodium persulfate–sulfuric acid chemistry exhibits excessive lateral dissolution beneath dry-film resist, quantified as a drop in etch factor below 3.0. An unsubstituted Thiazole (98%) bath additive, dosed at 0.03–0.15% by weight of the working solution, chemisorbs onto freshly exposed copper sidewalls through its ring nitrogen and sulfur atoms, forming a monomolecular hydrophobic film that retards the cathodic half-reaction. Routine process control relies on cross-section micrographs evaluated per IPC-6012D Class 3 acceptance criteria; average undercut is held below 12 µm at conveyor speeds of 2.5–3.0 m/min provided that dissolved copper concentration does not exceed 30 g/L. The etchant is maintained at 35–40°C with automatic sulfuric acid replenishment holding free acidity at 0.8–1.2 N. Thiazole consumption is tracked via online UV absorbance at 256 nm; replenishment shots are triggered when the signal drops to 70% of its initial value. Users must qualify the additive under End-of-Life Vehicles (ELV) Directive 2000/53/EC and the RoHS recast 2011/65/EU Annex II, with thermal desorption GC-MS confirming post-etch thiazole residuals on rinsed coupons below 0.02 µg/cm²—well under the threshold that could cause wire-bonding corrosion. A documented field failure mode occurs when the anode-to-cathode area ratio in the etch tank exceeds 15:1: anodic oxidation converts thiazole to the non-inhibiting sulfoxide, significantly increasing sidewall attack. Line modifications placing the stainless-steel heater sheaths on a dedicated cathodic protection circuit have eliminated this drift.When Electrolyte Wetting and High-Voltage Gas Evolution Limit Cycle Life in NCM811/Graphite Pouch CellsThiazole (98%) is assessed as a film-forming co-additive in carbonate-based electrolytes for lithium-ion cells charged to upper cut-off voltages of 4.35 V and above. In a baseline formulation of 1.0 M LiPF₆ in EC/EMC (3:7 v/v), thiazole is blended at 0.5–2.0 wt% inside a glovebox maintaining a dew point below -50°C. Pouch cells undergo a formation protocol of two cycles at C/10 rate at 25°C, with a constant-voltage hold at 4.40 V until the current decays to C/100. Electrochemical impedance spectroscopy immediately after formation reveals a sharp decrease in the charge-transfer and SEI impedances, which is traced to the preferential reduction of the thiazole ring on the graphite anode at ca. 1.3 V vs. Li/Li⁺. The sulfur- and nitrogen-containing fragments generate a hybrid interphase rich in Li₂S and Li₃N species, passivating the surface against continuous carbonate solvent oxidation at the highly delithiated cathode. During 500-cycle aging at 45°C, cells containing 1.0% thiazole retain 88% of initial discharge capacity versus 72% for additive-free controls, and volumetric gas generation measured by Archimedean buoyancy is reduced by 35%. Safety compliance with UN 38.3 transportation tests is unaffected, and no destabilization of the LiPF₆ salt is observed provided the water content of the thiazole spike is verified below 20 ppm by Karl Fischer immediately before injection. The additive must be stored under nitrogen and shielded from ambient light, because photochemically induced oligomerization raises the electrolyte’s acid value above the 50 ppm HF specification and causes yellow coloration. Qualification batches for this application require ICP-MS trace-metal screens following IEC 62321 digestion, with strict limits on iron (<2 ppm) and chromium (<1 ppm) leached from stainless-steel processing equipment.Precious metals recovery from spent auto-catalysts increasingly relies on solvent extraction circuits that avoid tertiary amines and oximes in favour of nitrogen-donor extractants with faster Pd(II) stripping kinetics. Thiazole (98%), used undiluted or at 40–60% v/v in an aliphatic diluent such as Escaid 110, selectively transfers Pd(II) from hydrochloric acid leachates containing 2–6 M HCl and mixed Pt(IV), Rh(III), and Fe(III) ions. Phase contact is performed in a counter-current mixer-settler battery at an organic-to-aqueous ratio of 1:1, with a residence time of 3–5 minutes per stage. The loaded organic phase is stripped with a 0.5 M thiourea in 1.0 M HCl solution, recovering palladium thiourea complex in the aqueous strip while regenerating the thiazole phase for re-use. Process engineers calibrate thiourea demand to avoid thiazole degradation: excessive strippant concentration (> 0.8 M) promotes nucleophilic ring-opening at elevated temperatures. The strip liquor is subsequently treated with sodium borohydride for precipitation of sponge palladium with a 99.95% purity on a metallic basis. Environmental discharge compliance under EU Industrial Emissions Directive 2010/75/EU requires scrubbing raffinate effluents for residual organic sulfur; a post-extraction activated carbon polish reduces total organic carbon below 10 mg/L. Operators record that entrainment-induced thiazole losses are minimised by installing electrostatic coalescers downstream of the settlers and by operating at an inter-stage temperature of 25–30°C, as higher temperatures increase aqueous solubility and lower temperatures reduce phase disengagement rates. |
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Thiazole, 98% (product code THZ-98, CAS 288-47-1) is a heterocyclic intermediate characterized by an assay specification of ≥98.0% via GC-FID following ASTM D8302-21, with water content controlled to <0.1% per Karl Fischer coulometric titration (ASTM E203-16). The remaining mass balance consists predominantly of the positional isomer isothiazole (<0.8%) and 2-methylthiazole (<0.5%), while non-volatile residues remain below 0.02%. This impurity profile targets synthetic applications that require regioselective metalation or acylation without purification-intensive workups, differentiating the 98% grade from lower-cost technical grades (typically 95% purity with isothiazole levels approaching 3%) and from costlier HPLC-grade material (≥99%) that pushes water content below 50 ppm for moisture-sensitive organometallic steps. Production-scale batches drawn from a continuous distillation unit using an Oldershaw column with 15 theoretical plates at a reflux ratio of 3:1 have maintained an average assay of 98.5% with a standard deviation of ±0.3% over 50 consecutive lots, confirming the narrow process window required to suppress the isothiazole azeotrope.
In the construction of cephalosporin side chains, thiazole serves as a key heterocyclic building block, with the 98% grade offering a controlled impurity profile that avoids competitive amidation during acylation of 7-aminocephalosporanic acid (7-ACA). When thiazole-2-acetic acid is prepared via lithiation at the C2 position using 1.05 equivalents of n-butyllithium in THF at -78°C, the presence of residual 2-methylthiazole above 0.5% has been observed in pilot-plant campaigns to generate a homologous C5-methyl byproduct that co-elutes with the target acid during sodium salt precipitation, reducing isolated yield by 4-6% on a 200 kg batch scale. Batch records from a cGMP intermediate facility operating under ICH Q7 guidelines show that switching from a 95% technical feedstock to THZ-98 lowered the off-specification lot frequency from 7% to <0.5%, attributed to the tight isothiazole specification. Purity is verified post-transport using an in-house HPLC method calibrated against a USP Thiazole Related Compound A reference standard, with a limit of detection of 0.01% for the isothiazole regioisomer. For solid-phase peptide couplings involving thiazole-4-carboxylic acid, the water content ceiling of <0.1% ensures HBTU-mediated activation proceeds without premature hydrolysis of the active ester; moisture ingress during solvent transfer is mitigated by maintaining headspace overpressure of dry nitrogen at 0.2-0.5 bar in the charging vessel.
Thiazole, even at 98% purity, undergoes slow autoxidation at the C2 methylene position when exposed to dissolved molecular oxygen, forming a dimeric disulfide species detectable by HPLC after 12 weeks of storage in amber glass at 25°C under ambient headspace air. Accelerated aging studies conducted in accordance with ASTM F1980-16 on THZ-98 sealed in 100 mL type III amber glass vials with PTFE-lined caps and a residual oxygen level of <1500 ppm in the headspace showed a purity decline of 0.15% per month at 40°C/75% RH, extrapolating to a shelf life of 24 months at 25°C when purity drift remains within a 1.0% action limit. The primary degradation pathway involves radical initiation at the sulfur atom, accelerated by trace transition metals, especially iron above 50 ppb; therefore, product packaging incorporates a borosilicate glass inner surface treatment and a nitrogen blanket with oxygen specification <500 ppm. Upon receipt, it is recommended that users sparge transfer lines with nitrogen and monitor dissolved oxygen using a Mettler Toledo InPro 6860i optical sensor; values above 100 ppb in the bulk liquid have been correlated with off-flavor formation when the material is subsequently used for food-grade aroma precursor synthesis. No significant exotherm is observed by differential scanning calorimetry (DSC) below 250°C at a scan rate of 10°C/min, indicating a wide safety margin for conventional handling and short-path distillation tasks.
Thiazole, 98% functions as a cost-effective precursor for 4-methylthiazole and 2-acetylthiazole, both of which carry FEMA GRAS status (FEMA 3256 and 3326) and deliver the characteristic notes of hazelnut, popcorn, and roasted coffee at ppm-level dosage. The 98% grade is selected over 95% technical material because the isothiazole contaminant, even at <0.8%, produces a discernible rubbery off-note in bench-top sensory evaluation conducted according to ISO 4120:2004 triangle test methodology when the derived aroma chemical is spiked into a neutral oil matrix at 0.5 ppb odor-activity value. A direct comparison using GC-Olfactometry (AEDA analysis following ASTM E679-19) on the crude reaction mass from a Hantzsch synthesis starting from thioacetamide and chloroacetone revealed that using 95% thiazole introduced a sulfurous, catty note at a flavor dilution factor of 16, whereas the 98% grade kept that descriptor below the detection threshold (FD <2). Production of 2-acetylthiazole in a 500 L glass-lined reactor at 65-70°C with phosphoric acid catalysis yields consistent product profiles when the input thiazole purity is bracketed at 98.0-98.5%; excursions above 99% do not measurably improve the sensory outcome and impose a 45% cost premium, while excursions below 97.5% trigger rework distillation of the aroma product to remove low-boiling amines derived from isothiazole ring opening.
Thiazole,98% is supplied as a colorless to pale yellow liquid with a refractive index n20/D of 1.5380-1.5400 (ASTM D1218-21) and a boiling point of 116-118°C at 101.3 kPa. The material must be stored in sealed containers under nitrogen; the screw-cap closure torque should be verified at 25-30 in-lbs for HDPE caps with PFTE liners to prevent atmospheric moisture ingress that could raise water content above 0.1% within 48 hours in climates with ambient relative humidity >60%. This hygroscopicity stems from the nitrogen atom’s hydrogen-bonding capacity; Karl Fischer data from a warehouse in Singapore that experienced 85% RH showed water uptake of 0.08% in an opened container after 4 hours. Incompatibilities include strong oxidizing agents—contact with 30% hydrogen peroxide leads to rapid exothermic decomposition with a temperature rise of 85°C in a reaction calorimeter (Mettler RC1e) at 0.5 mol scale—and acid chlorides, which react violently at the nitrogen center unless pre-cooled to 0-5°C and added at a controlled rate below 0.5 mL/min (bench scale). When handling in a manufacturing setting, anti-static footwear and conductive flooring per IEC 61340-5-1 are advised, as the liquid’s dielectric constant (~7.5) falls within the range where static accumulation is significant during pumping.
Selection of the 98% purity grade, as opposed to 95% technical or 99% HPLC specifications, is dictated by the kinetic sensitivity of the intended downstream transformation and the cost of removing trace isothiazole. The table below collates published specification data from three commercial tiers, with analytical methodology aligned to USP <621> chromatographic guidelines.
| Parameter | 95% Technical Grade | THZ-98 (98%) | 99% HPLC Grade | Test Method |
|---|---|---|---|---|
| GC Assay | ≥95.0% | ≥98.0% | ≥99.0% | ASTM D8302-21 |
| Isothiazole | ≤3.5% | ≤0.8% | ≤0.2% | GC-FID (internal std) |
| Water (KF) | ≤0.3% | ≤0.1% | ≤0.005% | ASTM E203-16 |
| Non-volatile residue | ≤0.05% | ≤0.02% | ≤0.01% | ASTM D1353-13 |
| Relative cost factor | 1.0 | 1.6-1.8 | 4.2-4.8 | Spot market (Q4, bulk) |
For palladium-catalyzed direct C-H arylation at the thiazole C5 position using Pd(OAc)2/PPh3 at 120°C, the isothiazole content in the 95% grade acts as a competing ligand that forms a catalytically inactive palladium-isothiazole complex, lowering turnover number by roughly 30%. The 98% grade partially suppresses this pathway, while the 99% grade provides only an additional 5-7% improvement in TON at a 3-fold cost increase, making THZ-98 the economic optimum for multi-ton campaigns. Conversely, in Negishi cross-couplings employing organozinc reagents at -20°C, water levels above 0.02% are detrimental; for this specific use case, published data for this configuration recommends the HPLC grade to avoid protonolysis of the zinc intermediate. THZ-98 is therefore indicated for most acylation, alkylation, and lithiation processes where moisture tolerance ≥0.1% and isothiazole interference below 0.8% suffices, covering the majority of pharmaceutical intermediate manufacturing registered under REACH regulation EC 1907/2006, Annex VII.
Agrochemical synthesis of thifluzamide and related thiazole carboxanilide fungicides requires a highly regioselective lithiation at the C4 position of thiazole, a transformation that is acutely sensitive to isomeric impurity. Metallation with lithium diisopropylamide (LDA) at -78°C in THF-hexane mixtures preferentially abstracts the C2 proton in pure thiazole; however, when isothiazole contaminant is present at levels exceeding 1.2%, the weakly acidic C3-H of isothiazole undergoes competitive deprotonation to generate an ambident anion that recombines with electrophilic carbon dioxide to form an isothiazole-3-carboxylic acid byproduct, compromising the regiochemical purity of the resulting 1,2,3-thiadiazole intermediate in the subsequent Hurd-Mori cyclization. Pilot-scale validation in a 50 kg campaign conducted with a THZ-98 lot containing isothiazole 0.6% confirmed a C4:C2 selectivity ratio of >20:1, whereas a spiked lot at 1.5% isothiazole dropped selectivity to 8:1, necessitating a recrystallization step that eroded yield by 12%. The 98% grade thus provides a built-in process control margin that eliminates the need for pre-distillation of the thiazole feed, a step that on a 200 L scale with overheads fractionation requires 18-22 working hours and 350 kWh of energy per batch. This direct reduction in unit operations aligns with the solvent minimization targets outlined in the ACS GCI Pharmaceutical Roundtable Process Mass Intensity calculator, positioning THZ-98 as a preferred building block in modern fungicide manufacturing routes that can be captured by the ISO 14040 life cycle inventory for crop protection chemicals.
