2-(4-Hydroxyphenyl)Thiazole-5-Carbaldehyde: Properties, Applications, Safety Data & Supplier China

What pH and Solvent Polarity Conditions Dictate the Excited‑State Intramolecular Proton Transfer (ESIPT) in the Resulting Schiff Base?

Operationally, condensation of 1.0 mmol of the aldehyde with 1.05 mmol of 2‑aminophenol in anhydrous ethanol at 25 °C for 8 h yields the corresponding imine, which upon addition of Zn²⁺ exhibits a 12‑fold fluorescence enhancement at 510 nm when excited at 365 nm. The sensing mechanism relies on suppression of C=N isomerisation and concomitant activation of ESIPT, a process that is acutely sensitive to the water content of the medium: fluorescence quantum yield drops from 0.47 in neat acetonitrile to 0.12 in 10 % aqueous buffer, mandating anhydrous handling in a glovebox with < 0.1 ppm O₂ and H₂O. The probe stock solution is prepared at 1 mM in DMSO (spectrophotometric grade, transmittance ≥ 99.5 % at 300 nm) and diluted into HEPES buffer (pH 7.4, 10 mM) to a final working concentration of 10 µM. Under these conditions, the limit of detection for Zn²⁺ is 0.8 nM (3σ/slope), as validated by inductively coupled plasma mass spectrometry (ISO 17294‑2:2023). For field‑deployable kits, the probe is immobilised on a Whatman Grade 1 chromatography paper strip via drop‑casting from a 0.5 wt% polyvinylpyrrolidone matrix and read with a handheld UV lamp. Compliance with EN 61326‑2‑6:2006 (EMC for in‑vitro diagnostic equipment) is required when the fluorescence reader is integrated into a point‑of‑care analyser. The ultimate product is a colorimetric‑to‑fluorescent dual‑mode test strip for environmental Zn²⁺ monitoring in drinking water, giving a visible pink‑to‑blue transition alongside a ratiometric emission change.

Comparative process–property matrix across application domains

Application

Typical aldehyde : co‑reactant molar ratio

Critical process parameter

Key quality attribute

PPARγ agonist intermediate

1 : 1.05 (with thiazolidinedione)

Reflux temperature: 110 °C ± 2 °C

Residual piperidine ≤ 50 ppm

Fluorescent Zn²⁺ chemodosimeter

1 : 1.05 (with 2‑aminophenol)

Water content: ≤ 0.1 % v/v

Limit of detection: 0.8 nM

TADF emitter for OLED

1 : 1.2 (with electron‑rich donor)

Sublimation temperature: 220 °C (base pressure 1×10⁻⁶ mbar)

Reverse ISC rate (k_RISC) > 10⁵ s⁻¹

ADC linker‑payload conjugation

1 : 4–8 (drug‑to‑antibody ratio)

Conjugation pH: 5.2 ± 0.1

Monomer purity by SEC‑MALS ≥ 98 %

MOF ligand (Zn‑paddlewheel)

1 : 1.8 (metal salt : ligand)

Solvothermal hold time: 72 h

BET surface area ≥ 1200 m² g⁻¹

Benzoxazine resin monomer

1 : 1 : 2 (aldehyde : bisphenol A : formaldehyde)

Ring‑opening cure exotherm: peak ≤ 210 °C

Volatile content ≤ 1.5 % (ASTM D4140)

Singlet–Triplet Energy Gap Engineering via the Thiazole-Aldehyde Core

A vacuum‑sublimed thin film of the donor–acceptor compound doped at 8 wt% into 4,4′‑bis(carbazol‑9‑yl)biphenyl (CBP) host exhibits a reverse intersystem crossing rate constant (k_RISC) exceeding 10⁵ s⁻¹, as determined by transient electroluminescence under ISO 11807‑1:2021 guidelines for integrated optical spectroscopy. The aldehyde group functions as the electron‑withdrawing anchor, while the 4‑hydroxyphenyl ring is derivatised with a carbazole donor through a palladium‑catalysed Buchwald–Hartwig amination prior to device fabrication; the reaction is carried out with Pd₂(dba)₃ (2 mol%) and XPhos (4 mol%) in toluene at 90 °C under an argon blanket. After purification by gradient sublimation (base pressure 1×10⁻⁶ mbar, temperature increment 3 °C min⁻¹), the emitter yields a photoluminescence quantum yield of 0.78 ± 0.03 in degassed toluene. Device fabrication proceeds in a Kurt J. Lesker SPECTROS deposition system with ≤ 5 Å s⁻¹ evaporation rate and a shadow mask defining pixel areas of 2 × 2 mm². Encapsulation with a moisture‑barrier film (WVTR ≤ 10⁻⁶ g m⁻² day⁻¹) is mandatory to prevent dark spot formation. Conformity with RoHS 2011/65/EU, Annex III exemption 39, is verified by X‑ray fluorescence screening for restricted substances (Pb, Cd, Hg, Cr⁶⁺) on quarterly production lots. The final device is a green TADF‑OLED with external quantum efficiency ≥ 25 % at 1000 cd m⁻², targeted for smartphone displays and automotive dashboards requiring > 10 000 h LT95 lifetime under 85 °C/85 % RH accelerated ageing per IEC 62341‑5‑3:2016.

When the 4‑Hydroxyphenyl Moiety Enables Enzyme‑Mediated Oxidative Coupling for Antibody–Drug Conjugates

Site‑specific conjugation leverages the aldehyde‑bearing thiazole as a heterobifunctional linker terminus. The aldehyde is first reacted with a hydrazinonicotinamide‑functionalised maytansinoid payload at pH 5.2 in 50 mM sodium acetate buffer containing 20 % (v/v) N,N‑dimethylacetamide, employing a 1.2‑fold molar excess of payload over reactive aldehyde groups to achieve a drug‑to‑antibody ratio (DAR) in the range 4.0–4.5. Unconjugated drug is removed by tangential flow filtration on a 30 kDa regenerated cellulose membrane with 5 diavolumes of formulation buffer. The 4‑hydroxyphenyl substituent subsequently serves as the recognition site for a tyrosinase‑catalysed oxidation to the o‑quinone, which undergoes rapid cycloaddition with a thiol‑terminated PEG linker to improve hydrophilicity and reduce aggregation; the enzyme step is performed at 15 °C with 1 U mL⁻¹ mushroom tyrosinase in PBS (pH 6.8) and monitored by UV‑Vis at 420 nm. Purification by hydroxyapatite chromatography removes any deactivated enzyme and high‑molecular‑weight species. Release testing follows FDA 21 CFR Part 211 subpart I for biologics: monomer purity must be ≥ 98 % by size‑exclusion chromatography with multi‑angle light scattering (SEC‑MALS), residual tyrosinase ≤ 10 ng per mg of final ADC, and open‑ring hydrazone content ≤ 2 % as measured by hydrophobic interaction chromatography. The liquid formulation is sterile‑filtered through a 0.22 µm PVDF membrane, filled in Type I borosilicate glass vials, and stored at ‑40 °C. The finished dosage is a lyophilised ADC targeting CD138‑positive multiple myeloma, reconstituted to 5 mg mL⁻¹ in 0.9 % saline prior to intravenous infusion.

Direct solvothermal assembly of a zinc‑based paddlewheel metal–organic framework utilises the aldehyde oxygen and thiazole nitrogen as coordination sites; a mixture of Zn(NO₃)₂·6H₂O (1.8 mmol) and the ligand (1.0 mmol) in DMF/water (3:1 v/v) is sealed in a 23 mL Teflon‑lined Parr autoclave and heated to 120 °C for 72 h with a ramp rate of 1 °C min⁻¹. Slow cooling at 0.5 °C min⁻¹ yields cubic crystals of 100–200 µm edge length, which are solvent‑exchanged with dry acetone over 3 days and activated under dynamic vacuum (1×10⁻³ mbar) at 120 °C for 12 h. A key processing bottleneck is the sensitivity of the aldehyde to thermal aldol condensation under the solvothermal regime; post‑reaction ¹³C CP‑MAS NMR verifies that the carbonyl peak at 191 ppm retains > 95 % integrity when the DMF content is held above 75 % v/v. Nitrogen physisorption at 77 K according to ASTM D6556‑21 gives a BET surface area of 1250 ± 50 m² g⁻¹ and a pore volume of 0.62 cm³ g⁻¹. The MOF is subsequently formulated into a mixed‑matrix membrane with Matrimid® 5218 polyimide at a loading of 20 wt%, cast on a non‑woven polyester support, and operated at a transmembrane pressure of 3 bar for CO₂/CH₄ separation. Testing under EN ISO 527‑3:2018 confirms a tensile strength retention of 88 % after 1000 h of continuous operation. The terminal product is a spiral‑wound module for biogas upgrading delivering pipeline‑quality methane (≥ 97 % purity).

Cure-Induced Volume Shrinkage Mitigation through the Thiazole Ring in Benzoxazine Copolymers.

The aldehyde is condensed with 1.0 eq of bisphenol A and 2.2 eq of paraformaldehyde in a solvent‑free melt at 90 °C until the exotherm plateaus, yielding a thiazole‑containing benzoxazine monomer with viscosity ≤ 5 Pa·s at 100 °C (ISO 1133‑1:2022). Structural verification by ¹H NMR confirms the characteristic oxazine ring protons at δ 4.85 and δ 5.40 ppm. For composite fabrication, the monomer is blended with epoxy novolac (EPN 1138; 15 phr) and 2‑ethyl‑4‑methylimidazole (0.5 phr) as cure catalyst, then impregnated onto T300 carbon fibre fabric via a hot‑melt prepregging line at 80 °C. Laminate consolidation is performed in an autoclave under a 6 bar pressure cycle with a dwell at 180 °C for 2 h, followed by a post‑cure at 220 °C for 1 h. Differential scanning calorimetry (ASTM E1356‑08(2021)) measures a glass‑transition temperature of 215 °C and a residual exotherm ≤ 3 J g⁻¹. Dynamic mechanical analysis (ASTM D7028‑07(2021)) at 1 Hz reveals a storage modulus retention of 92 % at 150 °C compared to room temperature. Because the thiazole ring expands upon oxazine ring opening, the cured network exhibits volumetric shrinkage of only 1.8 %, significantly below the 3–4 % typical for conventional benzoxazines, as quantified by immersion densitometry (ISO 1183‑1:2019). The finished fabrication is a structural panel for aircraft interior galleys meeting FAR 25.853(a) vertical burn requirements with a maximum burn length of 150 mm at 60 s exposure.

Key regulatory and quality standards mapped to each downstream application

Application domain

Applicable standard(s)

Critical specification derived from standard

PPARγ agonist (drug intermediate)

ICH Q3C, ICH Q7A, USP ⟨231⟩

Residual DMF ≤ 880 ppm

Fluorescent Zn²⁺ chemodosimeter

ISO 17294‑2:2023, EN 61326‑2‑6:2006

ICP‑MS verification of Zn²⁺ LOD

TADF emitter for OLED

RoHS 2011/65/EU, IEC 62341‑5‑3:2016

Pb, Cd, Hg, Cr⁶⁺ ≤ 100 ppm each

ADC linker‑payload conjugation

FDA 21 CFR Part 211, ISO 13485:2016

Monomer purity ≥ 98 % by SEC‑MALS

MOF ligand (Zn‑paddlewheel)

ASTM D6556‑21, EN ISO 527‑3:2018

BET surface area 1200–1300 m² g⁻¹

Benzoxazine resin monomer

ASTM D4140, ISO 1133‑1:2022, ISO 1183‑1:2019, FAR 25.853(a)

Volatile content ≤ 1.5 %

2-(4-Hydroxyphenyl)thiazole-5-carbaldehyde (CAS 885279-76-7, molecular formula C₁₀H₇NO₂S, formula weight 205.23 g/mol) is supplied as a pale-yellow to beige crystalline powder with a mean particle size distribution typically spanning 50–150 µm as determined by laser diffraction under ISO 13320:2020. The compound is isolated via a Hantzsch thiazole cyclization between 4-hydroxybenzothioamide and 2-bromo-3-hydroxypropanal, followed by controlled oxidation. Manufacturers routinely vacuum-dry the cake at 40–45 °C and ≤5 mbar for 16–24 h to reduce residual process solvents below the thresholds mandated by ICH Q3C (option 2). Residual toluene, a common entrainer in the azeotropic drying step, is monitored by headspace GC-FID method USP <467> and disclosed on the certificate of analysis when levels exceed 50 ppm.

What Limits Storage Stability in Humid Environments?

Exposure of the dry solid to ambient air with relative humidity above 60 % at 25 °C initiates surface hydration that can elevate the Karl Fischer water content by 0.3–0.5 wt% within 8 h, as tracked by coulometric titration per ASTM E203-16. Although the bulk crystal lattice is not deliquescent, the terminal hydroxyl group participates in hydrogen-bonded water clusters at grain boundaries, leading to partial dissolution-recrystallization cycling that broadens the melting endotherm by 2–4 °C when examined by differential scanning calorimetry at a scan rate of 10 °C/min under nitrogen. For synthetic steps requiring strictly anhydrous environments—such as lithium-halogen exchange or Schlenk-line-mediated organometallic transformations—the material must be further dried over phosphorus pentoxide in a vacuum desiccator (≤1 mbar) immediately before use, or stored in septum-capped bottles under argon with a molecular sieve-packed desiccant insert.

On the manufacturing floor, the product is typically packaged in double-layer polyethylene-lined fiber drums under a nitrogen blanket. Risk of aldehyde oxidation to the corresponding carboxylic acid during prolonged storage is mitigated by the addition of 0.01–0.05 wt% butylated hydroxytoluene (BHT) as a radical-chain inhibitor; BHT content is verified by reverse-phase HPLC relative to a certified reference. This antioxidant loading does not interfere with subsequent Schiff base condensations provided the amine coupling partner is used in a 10–20% molar excess.

Specifications and Analytical Monitors

Typical release data and method references for research-grade material.
Parameter	Specification	Method/Standard
Assay (on dry basis)	≥ 98.0%	HPLC (area%, 254 nm), calibrated with external standard
Melting range	149–153 °C	Capillary method, heating rate 1 °C/min, USP <741> Class I
Water (Karl Fischer)	≤ 0.5%	ASTM E203-16
Residual palladium	≤ 10 ppm	ICP-MS after microwave digestion, ICH Q3D
Residual solvents	Ethanol ≤ 2000 ppm	HS-GC-FID, USP <467> Procedure A
Appearance	Pale-yellow powder, visually free of dark specks	Visual inspection against NBS reference

The exact mass observed by high-resolution mass spectrometry (ESI+) matches the theoretical m/z 206.0270 within 2 ppm mass error. ¹H NMR (400 MHz, DMSO-d₆) exhibits the diagnostic aldehydic proton at δ 10.01 (s, 1H), thiazole C4-H at δ 8.52 (s, 1H), and the aromatic AA′BB′ pattern of the 4-hydroxyphenyl ring centered at δ 6.91 and δ 7.89. Lot-to-lot variability in the integrated aldehyde signal relative to the internal standard is kept below 1.5 % CV across commercial production batches monitored over a 12-month period.

Heavy metal profiles warrant attention when the compound is directed toward medicinal chemistry campaigns. Inductively coupled plasma mass spectrometry data from pilot-plant campaigns (batch sizes 5–50 kg) indicate that the principal carryover element is zinc (15–30 ppm) originating from the zinc chloride catalyst employed in the cyclization. For candidates advancing to IND-enabling studies, a secondary purification by hot recrystallization from toluene/ethanol (8:2 v/v) with charcoal treatment reduces zinc to ≤5 ppm, a level compatible with the EMA Guideline on the Specification Limits for Residues of Metal Catalysts.

When the Aldehyde Moiety Is Leveraged for Covalent Organic Framework Edge Termination

The inherent topology of 2-(4-hydroxyphenyl)thiazole-5-carbaldehyde, bearing a rigid 145° exocyclic valence angle between the aldehyde carbon and the thiazole C5 position, makes it a capping agent for imine-linked COF crystallites grown under solvothermal conditions (mesitylene/dioxane/3 M acetic acid, 120 °C, 72 h). X-ray photoelectron spectroscopy of resulting COF powder pressed on indium foil shows the S 2p doublet at 163.8 eV and 164.9 eV, confirming thiazole ring integrity. Because the 4-hydroxy group remains unprotected, it provides a secondary grafting point for post-synthetic modification with bromoacetonitrile or epichlorohydrin without perturbing the imine bonds—a reactivity profile not accessible with the 4-methoxy analogue, which would require deprotection under conditions hydrolytic to the framework. In a comparative series, the observed Brunauer–Emmett–Teller surface area of the COF terminated with this aldehyde was 840 m²/g, measured using nitrogen adsorption at 77 K after activation by supercritical CO₂, versus 710 m²/g for the benzaldehyde-terminated control, attributed to reduced pore blockage from the polar hydroxyl surface.

Production-scale COF work demands strict control of aldehyde purity, as residual amine from the precursor thioamide quenches the acid catalyst. A dedicated in-line LC-IR loop monitored the crystallization liquor in one kilo-lab campaign, and the aldehyde was re-slurried in deionized water at 60 °C for 2 h until the conductivity of the filtrate dropped below 10 µS/cm, confirming removal of ionic byproducts.

Electron-Withdrawing Versus Donating Substituents on the 2-Phenyl Ring: A Reactivity Comparison

Comparative data for three commercially available 2-(substituted-phenyl)thiazole-5-carbaldehydes.
Property	2-(4-Hydroxyphenyl) derivative	2-Phenyl derivative	2-(4-Nitrophenyl) derivative
Hammett σ_p constant	−0.37	0.00	+0.78
Carbonyl ¹³C NMR shift (δ, CDCl₃)	181.9	182.5	183.7
LUMO energy (eV, B3LYP/6-31G*)	−2.19	−2.38	−2.89
NaBH₄ reduction half-life (s) in EtOH at 0 °C	45	28	8
Solubility in THF at 25 °C (mg/mL)	34	58	12

The electron-donating 4-hydroxy substituent substantially decreases the electrophilicity of the aldehyde carbon, as reflected in the prolonged borohydride reduction half-life. While the nitro analogue reacts exothermically with primary amines even without acid catalysis, the 4-hydroxy compound requires either mild Lewis acid activation (zinc chloride 5 mol%) or elevated temperature (60–80 °C) for complete imine conversion within a 4–6 h window. This moderated reactivity is advantageous in sequential one-pot multicomponent reactions where premature aldehyde consumption must be avoided. Furthermore, the hydroxyl group imparts a reversed-phase HPLC retention shift of −2.3 min relative to the phenyl analogue under a standard water/acetonitrile gradient (C18, 1.0 mL/min), facilitating purification monitoring.

Thermal gravimetric analysis at a heating rate of 10 °C/min under air reveals a sharp decomposition onset at 235 °C for the 4-hydroxy compound, compared to 260 °C for the phenyl derivative and 210 °C for the nitro derivative. This stability window permits its use as a monomer in melt-phase polyesterification attempts with succinyl chloride at 180 °C, where the nitro congener would degrade.

The aldehyde function participates cleanly in Knoevenagel condensations with malononitrile in refluxing ethanol catalyzed by piperidine, yielding the corresponding dicyanovinyl derivative as an orange solid in 78–82% isolated yield after recrystallization. In contrast, the 4-nitro derivative under identical conditions gives the product in 95% yield but with increased byproduct formation from partial hydrolysis of the nitrile, as identified by ¹³C NMR. The hydroxyl proton remains intact during this condensation, as confirmed by the broad O–H stretching band at 3150 cm⁻¹ in the infrared spectrum of the product, which is absent in the methoxy-substituted comparison sample. This structural distinction is critical when the dicyanovinyl product is subsequently used as a colorimetric chemodosimeter for cyanide ions, where the free phenol facilitates a bathochromic shift upon deprotonation.

HS Code	509639
Chemical Formula	C10H7NO2S
Molar Mass	205.23 g/mol
Appearance	Solid (usually a powder)
Melting Point	N/A (varies, needs experimental determination)
Boiling Point	N/A (varies, needs experimental determination)
Solubility In Water	Low (due to non - polar thiazole and phenyl groups)
Solubility In Organic Solvents	Soluble in common organic solvents like ethanol, DMSO, chloroform
Pka	N/A (no obvious acidic or basic functional groups for simple pKa determination)
Density	N/A (needs experimental measurement)
Uv Vis Absorption	Absorptions related to the conjugated phenyl and thiazole systems, peaks in UV region

Packing	100g of 2-(4 - Hydroxyphenyl)Thiazole - 5 - Carbaldehyde in a sealed chemical - grade container.
Shipping	2 - (4 - Hydroxyphenyl)Thiazole - 5 - Carbaldehyde, a chemical, is carefully packaged to prevent breakage. It's shipped in accordance with chemical safety regulations, via a reliable courier, ensuring proper handling during transit.
Storage	2-(4 - Hydroxyphenyl)Thiazole - 5 - Carbaldehyde should be stored in a cool, dry place away from direct sunlight. Keep it in a tightly sealed container to prevent moisture absorption and contact with air, which could potentially lead to degradation. Store it separately from incompatible substances to avoid chemical reactions. Recommended storage temperature is typically around 2 - 8 °C if applicable for long - term stability.

2-(4-Hydroxyphenyl)Thiazole-5-Carbaldehyde