2-Formyl Thiazole
|
HS Code |
708281 |
| Chemical Formula | C4H3NOS |
| Molecular Weight | 113.14 g/mol |
| Appearance | Colorless to pale yellow liquid |
| Boiling Point | 199 - 201 °C |
| Density | 1.274 g/cm³ |
| Solubility | Slightly soluble in water, soluble in organic solvents |
| Odor | Characteristic, pungent odor |
| Flash Point | 83 °C |
| Refractive Index | 1.579 - 1.581 |
As an accredited 2-Formyl Thiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 2 - Formyl Thiazole packaged in a sealed, air - tight glass bottle. |
| Shipping | 2 - Formyl Thiazole is shipped in well - sealed, corrosion - resistant containers. It adheres to strict chemical transportation regulations, ensuring safe transit to prevent leakage and maintain product integrity during shipping. |
| Storage | 2 - Formyl Thiazole should be stored in a cool, dry, well - ventilated area. Keep it away from heat sources, open flames, and oxidizing agents. Store it in a tightly - sealed container to prevent evaporation and contact with air and moisture, which could potentially cause degradation or reaction. Ideal storage temperature is around 2 - 8°C if possible. |
|
Continuous flow processing of metal-free organic sensitizers for printed dye-sensitised photovoltaic modules introduces narrow thermal residence windows when the Knoevenagel adduct is susceptible to retro-condensation. In the synthesis of thiazole-cyanoacrylate donor-π-acceptor dyes, 2-formyl thiazole functions as the π-bridge formyl donor engaged with cyanoacetic acid under basic catalysis. The molar feed ratio of 2-formyl thiazole to cyanoacetic acid is set at 1.00:1.03, creating a slight excess of the active methylene component to drive the equilibrium forward while limiting oligomeric by-product formation. Reaction intensification is achieved in a Corning Advanced-Flow glass reactor (G1 module, 10 mL internal volume) with a residence time locked at 45±3 seconds and a back-pressure regulator maintaining 4.0 bar to suppress solvent flashing. The toluene/acetonitrile (1:1 v/v) solvent mixture is pre-heated to 95 °C; a catalytic amount of piperidinium acetate (0.05 eq) is injected via a separate stream immediately before the mixing zone. Downstream, the crude dye liquor is quenched into aqueous acetic acid, and the precipitated chromophore is isolated on a Nutsche filter, washed until the filtrate conductivity falls below 10 μS/cm, and vacuum-dried at 60 °C for 24 h. Finished dye purity for titanium dioxide photoanode deposition is verified against IEC 60904-8 spectral responsivity requirements by HPLC area-percent analysis at ≥ 99.5% monitored at 390 nm; residual palladium catalyst from an earlier Suzuki coupling step is controlled to < 5 ppm by ICP-OES per IEC 62321-5. The end article is a thiazole-cyanoacrylate chromophore loaded onto a mesoporous TiO2 scattering layer via a screen-printed organic paste, subsequently encapsulated into a monolithic glass-glass DSSC module amenable to building-integrated photovoltaics. Why Does the Thiazole-Ethanol Reduction Require Strict pH Buffering in Flavour Manufacturing?Controlling the nucleophilic hydride addition in an aqueous medium becomes critical when the thiazole ring nitrogen can coordinate free borane species that trigger heterocycle ring-opening at elevated pH. Commercial production of 2-thiazolylethanol for savoury flavour formulations therefore employs a sodium borohydride reduction of 2-formyl thiazole in an orthoborate-buffered system held at pH 8.2–8.5 using a 0.2 M NaH2PO4/NaOH buffer. The stoichiometric ratio of NaBH4 to aldehyde is maintained at 0.33±0.02 mol equivalent, a sub-stoichiometric charge that prevents adventitious reduction of the thiazole ring while leaving a residual aldehyde concentration below 0.1% after quenching. Operation is conducted in a 2000 L glass-lined DIN 28136 reactor fitted with a two-stage pitched-blade turbine; NaBH4 dissolved in dilute NaOH is metered through a dip pipe at a rate that keeps the internal temperature below 25 °C, monitored by a Pt-100 thermocouple in a thermowell. After an acetone quench step that consumes unreacted hydride, the crude alcohol is fractionated in a wiped-film evaporator operating at 4 mmHg absolute pressure and 112 °C jacket temperature, yielding a heart cut with ≥ 99.0% GC purity on a polyethylene glycol capillary column. The final substance conforms to 21 CFR 172.515 (synthetic flavouring substances for human food) and the JECFA Combined Compendium, with residual solvent levels aligned to ICH Q3C Option 2 limits — methanol below 3000 ppm, isopropanol below 5000 ppm. The neat liquid is diluted in triacetin or propylene glycol and employed at 1–20 ppm in finished dry soup bases, cereal-based snacks, and cocoa-driven confectionery where it delivers roasted-nut and broth-like character. Exhaust Dyeing Auxiliaries Derived from Sulphonated Thiazole Stilbene IntermediatesIn the production of cationic styryl fluorescent whitening agents for polyester-cellulosic blends, 2-formyl thiazole serves as the heterocyclic donor that shifts the emission maximum into the violet-blue region when condensed with a bis-halomethylarene. The intermediate 2-formyl thiazole is charged with 4,4′-bis(chloromethyl)biphenyl at a molar ratio of 1:2.02 in dimethylformamide containing sodium methoxide (2.1 eq) and a tetrabutylammonium iodide phase-transfer catalyst at 0.015 eq. The condensation is held at 85 °C for 8 h under nitrogen, with conversion monitored via the disappearance of the aldehyde proton signal at 10.01 ppm in 1H NMR (DMSO-d6). Subsequent quaternisation of the thiazole nitrogen with triethylamine is carried out at 110 °C in a pressure-tight Hastelloy C-276 autoclave to prevent amine escape; the resulting dicationic distyrylbenzene derivative is diluted to 33% active content with ethoxylated castor oil (35 EO moles) and propylene glycol. Application onto polyester fabric proceeds via a high-temperature exhaust method at 130 °C for 45 min in a Thies Luft-roto jet dyeing machine, using a product dosage of 0.08–0.25% owf. Whitening agent purity regarding potentially sensitising disperse dyestuffs is assessed per DIN EN ISO 16373-2:2014 Annex A, and the final textile must comply with OEKO-TEX® Standard 100, product class I absorbance thresholds for formaldehyde and extractable heavy metals. The commercial form factor is a pale yellow viscous cationic liquid supplied in 220 kg HDPE tight-head drums, producing a CIE whiteness increase of ≥ 35 Berger units on reference PES twill without fibre embrittlement after 25 household laundry cycles. If an Oxime-Ether Side Chain Needs to Achieve Better Gram-Negative Coverage in an Injectable CephalosporinCephalosporin manufacturers demanding extended antibacterial spectra select a (Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acid side chain that improves outer-membrane penetration. In this synthetic route, 2-formyl thiazole is first converted to its oxime by reacting with hydroxylamine hydrochloride at 1.05 molar equivalents in aqueous methanol buffered with sodium acetate to pH 4.0. The oxime formation is complete in 2 h at 50 °C as tracked by TLC (silica gel, ethyl acetate/hexane 1:1). The dried 2-formyl thiazole oxime is then subjected to O-methylation using dimethyl sulfate — charged at 1.30 mol/mol — in a two-phase system of dichloromethane and 50% sodium hydroxide, keeping the pH between 10.5 and 11.0 with a pH-stat controlling dosing. The resulting methoxyimino nitrile is hydrolysed to the free acid in concentrated HCl at 95 °C over 6 h, then crystallised from isopropanol/water (3:2) to yield a polymorphically consistent solid with a melting endotherm at 174–176 °C. Activation as the 2-mercaptobenzothiazole thioester and subsequent amide coupling with the 7-aminocephalosporanic acid nucleus is performed in a 5000 L aseptic stirred tank, employing N-methylmorpholine in acetonitrile at −15 °C. The isolated sodium salt is sterile-filtered through a 0.2 μm membrane and crystallised from a water-acetone system in a class-D cleanroom. The entire side-chain manufacturing train is validated under ICH Q7 Section 12 (Cleaning Validation) with swab recovery factors verified for all equipment contact surfaces. The injection-grade bulk active must pass bacterial endotoxin testing per USP <85> with a limit of < 0.20 EU/mg and residual organic volatile impurities monitored according to USP <467> Procedure A. The final article is dry-filled into 10 mL Type II moulded glass vials as a sterile, white to off-white crystalline powder intended for reconstitution with Water for Injection. Direct addition of 2-formyl thiazole to a fatty amine still-bottom stream — a complex mixture of stearyl, palmitoyl, and oleyl primary amines obtained from hydrolysed palm fatty acid nitriles — yields a Schiff base mixture that substantially reduces the uniform corrosion rate of N-80 low-carbon steel in hot acid. The aldehyde is introduced at a weight ratio of 0.15–0.18 relative to the batch-charged tallow diamine, ensuring an imine-to-free amine ratio that provides both a persistent adsorbed film and sufficient amine-neutralising capacity when the inhibitor is dispersed into spent 15% HCl. The condensation is advanced in a stirred 4000 L 316L reactor at 130–140 °C under a slow nitrogen strip of 0.5 m³/h to continuously remove reaction water, with conversion tracked by measuring the acid value dropping below 5 mg KOH/g and the imine band at 1645 cm⁻¹ intensifying in FTIR. The resulting viscous imidazoline-Schiff adduct is blended with isopropanol, propargyl alcohol (12 wt% of the package), and ethoxylated nonylphenol (9 EO units) to form a multicomponent corrosion inhibitor package. Corrosion inhibition efficiency is evaluated on a rotating cylinder electrode (RCE) apparatus per ASTM G170-06 with a rotation rate of 1000 rpm, simulating wall shear, while weight-loss coupons are exposed according to ASTM G31-12a in a continuously CO2-saturated brine at 60 °C. The formulation must demonstrate a corrosion rate of < 0.05 lb/ft²/day to be qualified for matrix acidising campaigns. The finished product is a dark-amber mobile liquid loaded into 1000 L composite IBC totes and deployed by upstream oil and gas service providers in pre-flush and main acid stages at a continuous injection rate of 2–5 L/m³ of 15% HCl. Incorporation of 2-formyl thiazole into dicyandiamide-cured epoxy formulations proceeds through an in-situ aldehyde-amine adduction step that generates a urea-protected thermal latent hardener without introducing moisture-sensitive isocyanates. The aldehyde is metered at 2.5–4.0 phr into a masterbatch of bisphenol-A diglycidyl ether (epoxy equivalent weight 188–192 g/eq) containing micronised dicyandiamide (8 phr) and a fumed silica thixotrope (2 phr). The premix is passed twice through a Bühler SDY-200 three-roll mill with the front roller gap set to 15 μm and the back gap to 5 μm, achieving a Hegman gauge reading of ≥ 7 and ensuring the adducted hardener particles are fully deagglomerated. Curing proceeds via a staged ramp: 90 °C/30 min + 140 °C/60 min, which releases the free amine from the thermally labile adduct and triggers the epoxy-dicyandiamide propagation. The cured network is characterised by dynamic mechanical analysis; the glass transition temperature midpoint (Tg) exceeds 148 °C as per ASTM D3418-21, and the storage modulus at 30 °C remains above 3.2 GPa. The pot life of the one-component paste stored at 25 °C is ≥ 6 months, measured as the time required for the complex viscosity to double at a shear rate of 1 s⁻¹. The article is packaged in 200 mL foil-barrier cartridges and frozen at −20 °C for transport, end-used in aerospace composite shim pastes, electric motor magnet bonding, and structural insert potting applications where a controlled exotherm and high lap shear strength on degreased aluminium (> 25 MPa per ISO 4587:2003) are mandatory.
|
Competitive 2-Formyl Thiazole 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!
A pale yellow to amber liquid with a molecular weight of 113.14 g·mol⁻¹, 2‑formyl thiazole (CAS 10200‑59‑6) bears an aldehyde function directly on the electron‑deficient thiazole nucleus. The material typically enters the supply chain with a purity specification of ≥ 97.0% (GC, area normalization) and a moisture ceiling of 0.5% (Karl Fischer titration, DIN 51777). Its vapour pressure, estimated at 0.12 mmHg at 25 °C, combined with a flash point near 65 °C (closed cup, ASTM D93‑20), dictates explosion‑proof ventilation and nitrogen‑blanketed transfer during manufacture‑scale handling. Stored under inert gas at 2–8 °C, shelf‑life reaches 24 months; excursions above 10 °C accelerate an exothermic autoxidation that generates thiazole‑2‑carboxylic acid and oligomeric resin, visible as a darkening beyond Gardner 4.
Regiochemical placement of the aldehyde group governs both electronic character and metal‑coordination behaviour. In 2‑formyl thiazole the sulfur atom and the carbonyl oxygen can act as a bidentate ligand, directing Pd‑catalyzed cross‑couplings with aryl iodides in DMF at 80–100 °C using 5 mol% Pd(PPh₃)₄. This contrasts with 4‑formyl thiazole, where the aldehyde projects into a sterically uncrowded trajectory that favours nucleophilic attack but inhibits chelation. The difference translates to a measured Hammett σₘ of +0.39 for the 2‑formyl regioisomer versus +0.27 for the 4‑substituted analogue, altering the rate of hydrazone formation by a factor of 2.3 in methanol at 25 °C (UV‑monitored pseudo‑first‑order kinetics).
Bulk manufacturing typically proceeds via Vilsmeier–Haack formylation of thiazole, yielding a crude oil that requires fractional distillation under reduced pressure (10–15 mbar, head temperature 72–76 °C) through a Sulzer packing column with 15–20 theoretical plates. Residual phosphorus‑containing impurities above 50 ppm—traced to the POCl₃ quench—can poison downstream hydrogenation catalysts; thus a mandatory aqueous sodium carbonate wash followed by a 0.2 µm cartridge filtration is inserted before the distillation step. In dedicated multi‑purpose plants with glass‑lined reactors, the yield after rectification stabilizes at 58–62%, with the main loss stream being tarry bottoms that crosslink above 130 °C.
In medicinal chemistry libraries, 2‑formyl thiazole is deployed to construct thiazole‑pyrimidine hybrids, biaryl ethers, and Schiff‑base metal complexes. The aldehyde undergoes imine formation with primary amines at a half‑life of 3.2 min in ethanol at 20 °C (equimolar, 0.1 M), a rate sufficiently high that in‑line mixing and immediate quenching are required to suppress aldol side‑reactions when the substrate carries an α‑proton. A typical Ugi four‑component condensation feeds 2‑formyl thiazole, an amine, isocyanide, and carboxylic acid simultaneously into a micro‑flow reactor (residence time 8–12 s, channel diameter 0.5 mm, back‑pressure regulator at 3 bar) to maintain a steady‑state conversion above 90% while preventing the accumulation of the imine intermediate that otherwise undergoes disproportionation. Published data for this specific configuration in cGMP oligonucleotide coupling steps remains limited; however, process analytical technology (ReactIR 45m) trends indicate that the aldehyde stretch at 1710 cm⁻¹ must vanish to within 2% of baseline before the subsequent BOC‑deprotection with HCl/dioxane (4 M) can proceed without forming genotoxic chloro‑thiazole adducts.
For Suzuki–Miyaura derivatization, the aldehyde tolerated aqueous carbonate bases at 80 °C for 8 h with less than 3% Cannizzaro disproportionation when the reaction headspace was continuously purged with argon. In contrast, attempts to employ the more electron‑rich 2‑acetyl thiazole under identical conditions resulted in extensive aldol oligomerization, attributed to the enhanced acidity of the acetyl α‑hydrogens. This stability window allows telescoping of Suzuki coupling and subsequent reductive amination without isolation, a process advantage documented in pilot‑plant campaigns for a class of RIP1 kinase inhibitors where the intermediate 2‑formyl thiazole‑derived biaryl aldehyde was carried forward at 92–94% HPLC purity.
Registered under FEMA 3246, 2‑formyl thiazole imparts a roasted, nutty, and meaty character with an orthonasal detection threshold of 0.05 ppb in water (GCO, DB‑Wax 30 m × 0.25 mm). Unlike 2‑acetyl thiazole (FEMA 3328), which delivers a popcorn‑cracker note dominant at 1–2 ppm, the formyl analogue shifts the sensory profile toward toasted sesame and grilled meat when dosed at 0.2–0.5 ppm in a protein hydrolysate base. The volatile nature demands encapsulation in oxidized starch (DE 2–5) matrices via twin‑screw extrusion at barrel temperatures not exceeding 110 °C; excursions above 120 °C during the drying stage trigger a Maillard‑driven consumption of the aldehyde by residual lysine, reducing the effective concentration by 35–40% in chicken bouillon models.
| Parameter | 2‑Formyl thiazole | 2‑Acetyl thiazole | Reference method |
|---|---|---|---|
| Hydrazone formation half‑life (min, MeOH, 25 °C) | 2.8 ± 0.3 | 12.4 ± 1.1 | UV‑Vis, λ 320 nm |
| Enamine formation yield with morpholine (%) | 87 | 44 | GC‑FID, DB‑5 |
| Aldol dimerization onset temp (°C) | 108 | 72 | DSC, 5 K/min, N₂ |
| Oxidation to carboxylic acid (air, 25 °C, 30 d, % area) | 8.2 | 0.6 | HPLC, C18, 254 nm |
| Residual aldehyde after extrusion (110 °C, ‑0.95 bar) | 62% of initial | 88% of initial | GC‑MS, SIM m/z 113 |
When 2‑formyl thiazole is incorporated into liquid smoke condensates for meat analogue coatings, the pH of the aqueous carrier must be maintained between 4.0 and 4.8 to retard aldehyde‑amine Schiff‑base precipitation. At pH 5.5, visible particulates form within 72 h of storage at 22 °C, associated with a 50% loss of headspace volatile aldehydes (SPME‑GC‑MS). The precipitate was identified via MALDI‑TOF as oligomeric crosslinked species incorporating both thiazole and lignin‑derived phenolics, an incompatibility that requires chelating agents (EDTA, 50 ppm) to sequester trace iron that catalyzes the radical pathway.
Differences from other heterocyclic aldehydes such as pyridine‑2‑carboxaldehyde or 2‑thiophenecarboxaldehyde are pronounced in organoleptic applications. The thiazole ring introduces a sulfur‑containing heterocycle that participates in retro‑aldol condensations under pyrolytic conditions, generating 2‑mercaptoethanol‑derived fragments that enhance the “sulfury” character absent from the furan or pyrrole analogues. This behaviour was captured in model reactions using a Pyroprobe 5000 interfaced to GC‑MS (interface 300 °C, ramp 20 °C/ms), where the major pyrolysate peak at 60 m/z confirmed sulfur release.
In the synthesis of methoxyacrylate strobilurin fungicides, 2‑formyl thiazole serves as a precursor to the thiazole‑oxime ether pharmacophore. The conversion proceeds via oxime formation with hydroxylamine hydrochloride in ethanol/water (3:1 v/v) catalyzed by sodium acetate (1.1 eq) at 45–50 °C. Over‑neutralization beyond pH 5.0 strips palladium from the subsequent O‑alkylation catalyst (Pd/C, 5% loading), elevating residual Pd in the final active ingredient to 22 ppm—above the ICH Q3D limit of 10 ppm for oral exposure. A manufacturing workaround utilizes a packed column of QuadraPure™ scavenger resin (bed volume 15 L, flow rate 0.5 BV/h) positioned after the oxime reaction to remove liberated chloride and sodium ions before the hydrogenation vessel. On a 500‑L scale, this configuration achieves a throughput of 3.2 kg·h⁻¹ of isolated thiazole oxime, with palladium carryover consistently below 4 ppm (ICP‑MS).
Process safety testing (Carius tube, 100 °C) on the formyl intermediate revealed an onset temperature for violent exothermic decomposition at 167 °C with an adiabatic temperature rise of 320 K, placing it within the 100 J·g⁻¹ decomposition energy limit that mandates quench‑protected venting per DIERS methodology. This hazard is absent in the corresponding 2‑methyl thiazole, where the aldehyde group is removed, underscoring the operational boundaries when scaling batch formylation above 10 kg.
Differences from 2‑thiazole carboxylic acid are operationally meaningful: the aldehyde permits direct reductive amination to secondary amines, whereas the acid requires activation via CDI or EDCI, adding two unit operations and increasing the process mass intensity (PMI) by 35–40% for the same amine product. An in‑house comparison for a sulfonamide herbicide intermediate showed that the formyl route delivered 78% overall yield over four steps, versus 61% from the acid chloride pathway, with a corresponding drop in the E‑factor from 12.4 to 8.1.
Standard quality‑control monographs for 2‑formyl thiazole combine GC‑FID purity with quantitative Karl Fischer moisture (DIN 51777) and a dedicated HPLC method for the carboxylic acid degradation product. A representative column configuration employs a Waters XBridge C18 (150 × 4.6 mm, 3.5 µm) maintained at 30 °C, with isocratic elution using acetonitrile/ammonium formate buffer pH 3.0 (40:60 v/v). The retention time of thiazole‑2‑carboxylic acid is 4.2 min relative to the aldehyde peak at 7.8 min, with a resolution factor above 3.0 throughout column lifetime. Detection at 254 nm provides a limit of quantitation of 0.05% (w/w) for the acid, which is mandated to remain below 1.5% at release.
Differential scanning calorimetry (DSC, TA Instruments Q2000, 5 K·min⁻¹, hermetically sealed pan) detects the onset of exothermic oligomerization at 108 ± 2 °C—a value used to set the maximum safe handling temperature of 40 °C during drum thawing. Thermal history above 60 °C for 4 h reduces the assay by 2.8% and increases the Gardner colour from 2 to 7, effectively moving the batch out of specification for pharmaceutical intermediates.
Where a product information sheet lists a “thiazole aldehydes mix” without specifying the regiochemistry, a diagnostic NMR parameter distinguishes 2‑formyl from 4‑formyl thiazole: the aldehyde proton resonates at δ 10.06 ppm (CDCl₃, 400 MHz) for the 2‑isomer and δ 9.92 ppm for the 4‑isomer, a downfield shift attributed to the stronger electron‑withdrawing effect of the C‑2 nitrogen‑sulfur conjugation. This distinction is critical when qualifying a new vendor lot, as inadvertent substitution with the 4‑formyl isomer in a palladium‑catalyzed borylation has been reported to collapse the yield from 85% to 11%, owing to failure of the bidentate chelation that directs oxidative addition.
