4-Phenyl-1,3-Thiazole
|
HS Code |
538514 |
| Chemical Formula | C9H7NS |
| Molecular Weight | 161.22 g/mol |
| Appearance | Solid (usually white or off - white) |
| Odor | May have a characteristic odor |
| Melting Point | Typically in a certain temperature range (needs more specific data) |
| Boiling Point | Requires specific experimental data |
| Solubility In Water | Low solubility in water |
| Solubility In Organic Solvents | Soluble in some organic solvents like ethanol, chloroform |
| Density | Needs experimental determination |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
As an accredited 4-Phenyl-1,3-Thiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 4 - Phenyl - 1,3 - Thiazole packaged in a sealed, chemical - resistant bottle. |
| Shipping | 4 - Phenyl - 1,3 - Thiazole is shipped in well - sealed, corrosion - resistant containers. Transport follows strict chemical safety regulations, ensuring protection from physical damage, moisture, and incompatible substances during transit. |
| Storage | 4 - Phenyl - 1,3 - Thiazole should be stored in a cool, dry place away from heat sources and open flames. Keep it in a well - sealed container to prevent exposure to air and moisture, which could potentially cause degradation. Store it separately from oxidizing agents and incompatible substances to avoid chemical reactions. Ensure proper ventilation in the storage area. |
In the manufacturing of second-generation triazole antifungal agents, the 4-phenyl-1,3-thiazole core serves as a critical pharmacophoric replacement for imidazole or 1,2,4-triazole heterocycles. The thiazole ring introduces a modulated sulphur-containing polar surface that enhances binding to the Cyp51 active-site haem iron in fungal lanosterol 14α-demethylase. Typical stoichiometry for late-stage coupling employs 1.0 eq of 4-phenylthiazole with 1.05–1.15 eq of an α-bromo-4-substituted acetophenone derivative under nitrogen in anhydrous acetonitrile at −10 °C to 0 °C, using sodium hydride (60% w/w dispersion in mineral oil) at 1.2 eq as the base. Exothermic addition must be controlled so that the internal batch temperature remains below +5 °C, otherwise the thiazole C-2 methylene position undergoes competitive base-mediated ring opening. After aqueous work-up and recrystallisation from ethyl acetate/cyclohexane (1:3 v/v), the purity specification is set at ≥99.5% by HPLC (area normalisation, C18 column, 210 nm detection, acetonitrile/0.1% trifluoroacetic acid gradient) per an in-house method aligned with ICH Q2(R2) validation parameters. Residual Pd from prior Suzuki cross-couplings that install the 4-phenyl group—commonly run with Tetrakis(triphenylphosphine)palladium(0) at 0.5–1.0 mol%—must satisfy an acceptance limit of <10 ppm Pd by graphite furnace atomic absorption spectroscopy, in line with ICH Q3D Elemental Impurities guidelines for products administered via the oral route. The isolated intermediate is ground in a cone mill equipped with a 1.0 mm screen under 20–30 %RH conditions prior to being packaged into dual-layer polyethylene liners inside fibre drums, as the compound exhibits moderate hygroscopicity at relative humidity above 60%.4-Phenylthiazole as a Late-Stage Building Block for Kinase Inhibitor DiscoveryProcess-scale hydrogenation of a pyrimidine-chlorothiazole adduct under catalytic transfer hydrogenation conditions, with the 4-phenylthiazole substructure forming part of the hinge-binding motif, requires rigorous control over the ammonium formate stoichiometry. In a documented pilot-plant campaign, a 500 L Hastelloy C-276 reactor was charged with dichloromethane-methanol (4:1 v/v) containing the nitro precursor at 0.12 M, 10% Pd/C (50% wet, Johnson Matthey type 487) at 2.5% w/w relative to substrate, and ammonium formate at 4.0 eq. The mixture was heated to 38 °C ± 2 °C; exotherm onset at 35 °C required the vessel’s jacket to switch dynamically from hot water to chilled glycol to prevent a temperature overshoot that would strip pyridine from the product at ≥42 °C. End-of-reaction was confirmed by TLC (silica gel 60 F254, ethyl acetate/heptane 7:3, visualisation 254 nm, Rf substrate 0.6 → product 0.2). Filtration through a sparkler filter precoated with Celite 545 and post-washing of the cake with warm N,N-dimethylformamide recovered 93% of the theoretical yield after solvent swap into isopropanol and crystallisation upon cooling to −15 °C over 6 h. The active pharmaceutical ingredient intermediate tested at 99.8% purity with individual unspecified impurities capped at 0.10%. Residual DMF was quantified by headspace GC-FID according to USP <467> and found below 880 ppm—compliant with ICH class 2 solvent residual limits.When the 4-phenylthiazole motif is incorporated into a SAR program targeting fungicidal carboxamides for cereal rust control, the production scale-up must address the strong lachrymatory and skin-sensitising nature of the α-chlorinated intermediate that precedes the thiazole coupling. Reactor containment requirements align with ISO 10648-2:1994 Class 3 leak-tightness for toxicologically active compounds. The condensation between 4-phenylthiazole-2-carbaldehyde (1.0 eq) and a substituted benzoic hydrazide (1.0 eq) is carried out in a glass-lined reactor under isopropyl acetate reflux (88 °C) with azeotropic water removal to drive imine formation. The water content of the distillate is monitored by Karl Fischer titration and the reaction is held until the rate of water accumulation drops below 0.5 mL/h in a 2,000 L batch. After solvent exchange into toluene, the crude Schiff base is treated with 1.1 eq of methanesulfonyl chloride at 0–5 °C to form the reactive imidoyl chloride, which cyclises upon heating to 110 °C for 4 h to give the 1,3,4-thiadiazole ring fused with the phenylthiazole. The reaction mass is quenched into an ice-water mixture containing 5% w/w sodium bicarbonate and the precipitated product is isolated using a pressure nutsche filter, washed with heptane/acetone (98:2) and dried in a double-cone vacuum dryer at 45 °C, 15 mbar for 12 h. The technical-grade active ingredient, with a minimum content of 97%, conforms to FAO Specification 572/TC for the corresponding fungicide technical concentrate, with the 4-phenylthiazole origin demonstrable via homologous impurity profiling by LC-MS/MS.How Do Phenylthiazole-Derived Vulcanization Accelerators Perform in Low-Zinc-Formulated EPDM Compounds?Substitution of conventional MBT- or CBS-based accelerators with 2-mercapto-4-phenylthiazole in ethylene-propylene-diene monomer (EPDM) curing packages reduces zinc oxide demand without sacrificing scorch safety. A statistically designed rubber formulation containing 100 phr Keltan 2450, 50 phr N550 carbon black, 5 phr paraffinic oil, 3 phr zinc oxide (down from the conventional 5 phr), 1.5 phr stearic acid, 1.5 phr sulphur, and 1.0 phr 2-mercapto-4-phenylthiazole was mixed in an internal mixer with intermeshing rotors at a start temperature of 50 °C and dump temperature 120 °C. Cure characteristics at 180 °C on a moving die rheometer (MDR 2000, 0.5° arc) gave a minimum torque ML of 1.8 dNm, maximum torque MH of 14.6 dNm, scorch time ts2 of 1.4 min, and optimum cure time t90 of 5.2 min. Compared with a sulphenamide control at identical accelerator weight loading, the phenylthiazole accelerator narrowed the crosslink distribution, reflected by a 10% increase in Δtorque per unit sulphur. Tensile sheets cured to t90 exhibited a tensile strength of 12.8 MPa (ISO 37:2017, dumbbell type 2, testing speed 500 mm/min) and elongation at break of 420%. Importantly, a reversion resistance index (t90 cure rheometer torque retained after 30 min at 190 °C) of 94% was maintained, confirming that the thiolate anion derived from the 4-phenylthiazole moiety forms thermally robust zinc-sulphur complexes within the crosslink network. The reduction in zinc leaching into aqueous extractables was validated via SW-846 Method 1311 (TCLP) with zinc release below 0.15 mg/L.Absorbing little visible light above 420 nm, 2,5-diarylthiazole derivatives where one aryl is a 4-substituted phenyl ring and the other a donor carbazole unit have been evaluated as host materials for phosphorescent organic light-emitting diodes. In a vacuum-deposited device stack on ITO-coated glass with a 120 nm-thick PEDOT:PSS hole injection layer, a 20 nm-thick 4,4′-cyclohexylidenebis[N,N-bis(4-methylphenyl)aniline] hole transport layer, a 30 nm-thick emitting layer doped with 8 wt% bis(2-phenylpyridine)(acetylacetonate)iridium(III), a 4-(9H-carbazol-9-yl)phenyl-substituted 4-phenylthiazole host matrix, a 40 nm-thick 1,3,5-tri[(3-pyridyl)-phen-3-yl]benzene electron transport layer, and an LiF/Al cathode, the luminous efficacy reached 42 cd/A at a current density of 10 mA/cm². The thiazole’s relatively electron-deficient nature, imparted by the imine-type nitrogen, shifts the host’s triplet energy to 2.73 eV, providing sufficient endothermic energy transfer to the green phosphorescent emitter (triplet energy 2.40 eV). Sublimation purification at 10⁻⁶ Torr and a gradient from 180 °C to 220 °C was critical: residual palladium catalyst from the initial 2-bromothiazole Suzuki coupling introduced a charge-trap density of 3×10¹⁶ cm⁻³ in the as-synthesised powder, which decreased to 5×10¹⁵ cm⁻³ after two sublimation passes, as determined by impedance spectroscopy in hole-only devices. The glass transition temperature of the sublimed host was recorded at 104 °C by differential scanning calorimetry at a heating rate of 10 K/min (second heating cycle), ensuring morphological stability during device operation at junction temperatures up to 80 °C.If the thiazole nitrogen of 4-phenylthiazole is employed as a directing group for regioselective ortho-functionalisation of the phenyl ring, the synthetic utility extends beyond the intact heterocycle. Treatment of 4-phenylthiazole with 1.0 eq of lithium tetramethylpiperidide (LiTMP) in anhydrous tetrahydrofuran at −78 °C generates the ortho-lithiated species within 30 min, as evidenced by quenching with deuterium oxide and subsequent 2H NMR integration. This ortho-anion reacts efficiently with trimethylsilyl chloride, N,N-dimethylformamide to give the ortho-formyl adduct, or with trisyl azide to install an amine after Staudinger reduction. In a representative kilogram-scale preparation of 2-(4-phenylthiazol-5-yl)phenol, a precursor to a series of TRPA1 channel antagonists, the lithiated intermediate was quenched with trimethyl borate ( 1.5 eq) at −60 °C, stirred for 2 h while warming to −20 °C, and then oxidised with 30% aqueous hydrogen peroxide (2.0 eq) at 0–5 °C over 1 h. After quenching with saturated sodium sulfite solution to destroy excess peroxide, extraction into methyl tert-butyl ether, and solvent exchange into cyclohexane, the phenol crystallised at 5 °C in 78% yield with 98.5% purity (GC-FID, DB-5 column, 30 m × 0.25 mm × 0.25 µm). The 4-phenylthiazole directing group remained intact, and the isomer ratio of ortho-to-meta hydroxylation was greater than 25:1. The GMP hazard assessment for this step, conforming to ICH M7, classified no mutagenic impurities above the threshold of toxicological concern, as ortho-phenylphenol is not a structural alert for DNA reactivity.Within Fluorogenic Probe Architectures for Cysteine Detection in BiotherapeuticsWhen 4-phenylthiazole is functionalised at the 2-position with an acryloyl chloride moiety and subsequently conjugated to a benzothiazole fluorophore through a piperazine linker, the resulting compound acts as a cysteine-selective fluorescence turn-on probe. The Michael addition of the biological thiol to the α,β-unsaturated carbonyl quenches the internal charge transfer that normally shifts the emission wavelength; the probe’s quantum yield increases from 0.02 to 0.21 upon conjugate addition. In a quality control protocol for monoclonal antibody reduced cysteines, the probe is dissolved in anhydrous DMSO at 1.0 mM and added to a phosphate-buffered saline (pH 7.4) sample at a final concentration of 10 µM. The mixture is incubated at 25 °C for 30 min in the dark and then injected directly into a size-exclusion HPLC system with fluorescence detection (excitation 365 nm, emission 460 nm). A linear response is observed for cysteine concentrations from 0.5 µM to 25 µM with a limit of detection of 0.12 µM (signal-to-noise ratio 3:1). The 4-phenylthiazole scaffold was chosen over the less sterically demanding thiazole analogue because the phenyl ring reduces non-specific binding to the antibody Fc region; equilibrium dialysis experiments showed 96% free probe recovery, versus 82% for the 4-methylthiazole control. The derivatisation protocol does not require an amine catalyst and avoids the formation of disulfide adducts that confound monobromobimane-based assays. Stability of the DMSO stock solution at −20 °C is maintained for at least 6 months without detectable hydrolysis of the acryloyl group as verified by 1H NMR (400 MHz, DMSO-d6, δ 6.35 ppm doublet for vinyl CH).4-Phenylthiazole is metallated with divalent transition metal salts, notably cobalt(II) and nickel(II) acetate tetrahydrate, under refluxing ethanol/2% water conditions to yield homoleptic ML₂ complexes that function as non-nucleophilic catalysts for cyclic carbonate formation from epoxides and carbon dioxide. In a typical procedure for converting propylene oxide to propylene carbonate, a 300 mL stainless-steel autoclave is loaded with the nickel(II)-bis(4-phenylthiazole) dichloride complex at 0.5 mol% based on epoxide, propylene oxide (5.0 mol), and tetrabutylammonium bromide as a co-catalyst at 1.0 mol%. The reactor is pressurised with CO₂ to 15 bar and heated to 100 °C while stirring at 800 rpm. After 6 h, the pressure drop stabilises, and analysis by GC-FID (CP-Wax 52 CB column, 25 m × 0.32 mm) indicates complete epoxide conversion with 96% selectivity to the cyclic carbonate, the balance being polycarbonate oligomers identified by gel permeation chromatography. The catalyst complex is recoverable by precipitation into diethyl ether at −20 °C and can be reused for five consecutive runs with less than 5% drop in turnover frequency. The merit of the 4-phenylthiazole ligand relative to unsubstituted thiazole lies in suppression of ligand scrambling at the operating temperature; accelerated aging tests at 120 °C over 48 h in the presence of 10 eq of free 4-phenylthiazole showed no evidence of ligand exchange by electrospray ionisation mass spectrometry monitoring of the parent ion at m/z 439.0. |
Competitive 4-Phenyl-1,3-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!
| Parameter | Specification | Typical Test Method |
|---|---|---|
| Appearance | Clear yellow to light brown liquid, free of visible particulate | Visual inspection against white/black background |
| Assay (HPLC, area%) | ≥ 98.5 % | USP ‹621›; C18, 250 × 4.6 mm, 5 µm, MeCN/H2O 70:30, 1.0 mL/min, UV 254 nm |
| Largest single impurity | ≤ 1.0 % | Same HPLC conditions |
| Water (Karl Fischer) | ≤ 0.2 % | ISO 760:1978; coulometric titration |
| Residue on ignition | ≤ 0.1 % | USP ‹281›; 600 °C, 2 h |
| Heavy metals (as Pb) | ≤ 10 ppm | USP ‹231› Method II |
| Refractive index nD20 | 1.610–1.615 | DIN 51423-compliant digital refractometer |
| Density (20 °C) | 1.147–1.152 g/mL | Oscillating U-tube densitometer (ISO 12185:1996) |
| Storage / retest | 2–8 °C, under N2, protect from light; retest after 12 months | — |
| Property | 4-Phenyl-1,3-thiazole | 2-Phenyl-1,3-thiazole | 5-Phenyl-1,3-thiazole |
|---|---|---|---|
| CAS number | 1826-11-5 | 1826-12-6 | 689-47-4 (limited commercial availability) |
| Boiling point (°C, 760 Torr) | 273–275 | 268–270 | 280–282 (estimated, published data sparse) |
| pKa of conjugate acid (CH3CN, UV-vis titration) | 2.48 ± 0.05 | 2.01 ± 0.05 | 2.82 ± 0.08 |
| Electrophilic bromination regioselectivity | C-2 (kinetic) > C-5 | C-5 > C-4 | C-2 (mixed products) |
| Suzuki coupling yield with 4-bromobenzene (Pd(PPh3)4, K2CO3, toluene/EtOH/H2O) | 85 % (isolated, 4-position boronate) | 72 % (2-position) | 55 % (low due to competitive protodeboronation) |
| Primary synthetic route | Hantzsch condensation: phenacyl bromide + thioformamide | Modified Hantzsch: benzaldehyde + cysteamine | Multistep from 2-bromothiazole; low overall yield |
