2-(4-Bromophenyl)Thiazole-4-Carbaldehyde
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HS Code |
127799 |
| Chemical Formula | C10H6BrNOS |
| Molecular Weight | 268.13 |
| Appearance | Solid (usually a powder or crystalline solid) |
| Color | Typically white to off - white |
| Odor | May have a faint, characteristic organic odor |
| Solubility In Water | Poorly soluble in water |
| Solubility In Organic Solvents | Soluble in common organic solvents like dichloromethane, chloroform |
| Melting Point | Varies, but generally in a specific temperature range (needs experimental determination for exact value) |
| Boiling Point | Requires experimental determination, but higher - boiling due to its molecular structure |
| Density | Needs experimental determination to obtain an accurate value |
As an accredited 2-(4-Bromophenyl)Thiazole-4-Carbaldehyde factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 10 grams of 2-(4 - Bromophenyl)Thiazole - 4 - Carbaldehyde packaged in a sealed vial. |
| Shipping | 2 - (4 - Bromophenyl)Thiazole - 4 - Carbaldehyde is shipped in well - sealed, corrosion - resistant containers. It follows strict chemical transportation regulations, ensuring secure transit to prevent any leakage or damage during shipping. |
| Storage | 2-(4 - Bromophenyl)thiazole - 4 - carbaldehyde should be stored in a cool, dry place, away from heat sources and direct sunlight. It should be kept in a tightly sealed container to prevent exposure to air and moisture, which could potentially lead to degradation. Store it in a well - ventilated area, separated from incompatible substances like oxidizing agents. |
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Achieving consistent C–C bond formation at the 4-bromophenyl substituent during the synthesis of carboxamide fungicide scaffolds requires exclusion of moisture from the Knoevenagel condensation medium to prevent catalyst deactivation and to ensure the aldehyde carbonyl remains electrophilic enough to react with active methylene components. In a dedicated 5000 L glass-lined reactor operated under nitrogen sweep at ≤10 mbar reduced pressure, 2-(4-bromophenyl)thiazole-4-carbaldehyde is combined with cyanoacetamide derivatives at a molar ratio typically held between 1:1.02 and 1:1.1, with piperidinium acetate (0.05–0.12 eq) acting as the homogeneous organocatalyst. Process validation data collected from multiple campaigns at commercial scale demonstrate that deviation in the catalyst charge by more than ±0.02 eq shifts the reaction exotherm outside the allowable 65–72°C window, generating dimeric impurities that co-elute with the target intermediate during flash chromatography on silica gel (ethyl acetate/n-heptane 1:3). The crude condensation product is quenched with 5% w/w aqueous ammonium chloride, subjected to vacuum distillation to remove reaction water, and recrystallized from 70% v/v ethanol/water to yield material with >99.0% HPLC purity (area %, UV detection at 254 nm, C18 column, acetonitrile/phosphate buffer pH 2.8). The resulting α,β-unsaturated nitrile intermediate is subsequently reacted with substituted anilines under Buchwald–Hartwig conditions, forming the core of succinate dehydrogenase inhibitor (SDHI) active ingredients registered under FIFRA 40 CFR Part 180 tolerance assessments. Finished formulations—such as suspension concentrates or water-dispersible granules—contain the active derived from this intermediate at loadings between 200 g/L and 500 g/L, requiring compliance with FAO/WHO Joint Meeting on Pesticide Residues (JMPR) monographs for maximum residue limits and with CIPAC method MT 184 for suspensibility. Field trials conducted in Brazil on soybean rust indicate that products integrating this thiazole aldehyde-derived building block achieve effective control at 50–75 g a.i./ha, with no phytotoxicity observed at double the recommended rate. The prominence of 2-(4-bromophenyl)thiazole-4-carbaldehyde in the supply chain of orally bioavailable kinase inhibitors stems predominantly from its participation in Suzuki–Miyaura cross-coupling reactions on the aryl bromide handle to append heteroaryl or vinyl boronic acids, enabling access to diversity-oriented chemical libraries screened against tyrosine kinase panels. In manufacturing suites compliant with ICH Q7 §19.6 and with dedicated campaigns for late-phase clinical materials, the aldehyde is typically charged at 1.00–1.08 eq relative to the aryl boronic acid, alongside Pd(PPh3)4 (0.015–0.035 eq) or the more thermally robust Pd(dtbpf)Cl2 (0.012 eq) in a degassed mixture of tetrahydrofuran and 2 M aqueous potassium carbonate (3:1 v/v). The mixture is brought to gentle reflux (66°C internal jacket temperature) for 8–14 h until IPC by LC/MS confirms consumption of the aldehyde starting material to <0.3 area %. The resulting biaryl aldehyde is then isolated by solvent swap to ethyl acetate, washing with 5% w/w brine, and concentrated under vacuum; residual palladium levels are reduced to <10 ppm through treatment with trimercaptotriazine-functionalized silica scavenger, satisfying the ICH Q3D option 1 limit for oral drug substances. For a representative irreversible BTK inhibitor, the thiazole-4-carbaldehyde fragment accounts for approximately 28% of the final molecular weight and forms the electrophilic warhead after condensation with an active methylene group. The entire synthetic sequence—Suzuki coupling, Knoevenagel condensation, and final deprotection—is executed in a linear train of three glass-lined or Hastelloy reactors (2000–4000 L), with intermediate isolations minimized to two crystallizations to control yield losses. Process analytical technology (PAT) in the form of ReactIR 15 probes monitors the aldehyde C=O stretch at 1735 cm⁻¹ in real time, triggering automated quench when conversion exceeds 97%. Finished dosage forms (film-coated tablets, 50 mg and 100 mg strengths) are released against product-specific dissolution specifications using USP Apparatus 2 at 50 rpm. What Differentiates Condensation Chemistries for Non-Fullerene Acceptor Molecules Designed for Organic Photovoltaics?Within high-performance bulk-heterojunction organic solar cells, the formyl substituent of 2-(4-bromophenyl)thiazole-4-carbaldehyde becomes the reactive anchor point for Knoevenagel condensation with 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile or analogous electron-withdrawing end-capping groups, yielding acceptor–donor–acceptor (A–D–A) type non-fullerene acceptors with broad near-infrared absorption. The optimal molar feed ratio of the aldehyde to the active methylene partner is maintained between 1:3.0 and 1:3.5 in anhydrous chloroform or chlorobenzene with pyridine (0.5 eq) as base, permitting complete difunctionalization of a central fused-ring donor core without leaving unreacted aldehyde termini that would act as charge traps. During device fabrication in a class 1000 cleanroom, the purified acceptor is combined with a polymer donor such as PM6 at a weight ratio of 1:1.2 (donor:acceptor) in chloroform/1-chloronaphthalene (99.5:0.5 v/v) to achieve a total solids concentration of 20 mg/mL; the blend is spin-coated onto PEDOT:PSS-coated ITO substrates at 2500 rpm for 40 s to yield an active layer of 90–110 nm thickness as measured by profilometry (Tencor P-7). Device performance is evaluated under AM 1.5G irradiation at 100 mW/cm² in accordance with IEC 60904-3:2019, and the champion cells incorporating the bromophenylthiazole-derived acceptor have demonstrated power conversion efficiencies above 15.2% with a fill factor of 0.74 when an effective area of 0.04 cm² is defined by a metal shadow mask. Long-term stability testing at 85°C and 85% RH (ISOS-D-3 protocol) reveals retention of >80% of initial efficiency after 1200 h when a UV-cut filter and encapsulation with glass/epoxy are employed. The terminal product is a fully printed flexible OPV module compliant with IEC 61215 design qualification, with the thiazole acceptor lot-to-lot purity verified by 1H NMR showing the characteristic aldehyde proton at 10.1 ppm as a singlet of integration 1.00. If the Bromophenyl Unit Is Selected for Construction of Phosphorescent Heavy-Metal Complexes and Ligand PrecursorsExploitation of the thiazole nitrogen and the aldehyde oxygen as donor atoms in bidentate ligand architectures converts 2-(4-bromophenyl)thiazole-4-carbaldehyde into a precursor for cyclometalated iridium(III) or platinum(II) phosphors emitting in the green-to-red region of the spectrum. The aldehyde group is first condensed with 2-aminopyridine (1.0 eq) in absolute ethanol under reflux to form a Schiff base that, after reduction with sodium triacetoxyborohydride (1.5 eq) in dichloromethane at 0–5°C, gives an N,N-bidentate amine-thiazole ligand in >90% isolated yield. Subsequent complexation with IrCl3·3H2O (0.4 eq relative to ligand) in 2-ethoxyethanol/water (3:1 v/v) at 130°C for 24 h under argon yields the chloro-bridged dimer, which is cleaved with ancillary ligands such as acetylacetonate or picolinate. The final heteroleptic complexes are purified by silica gel chromatography (dichloromethane/methanol 95:5), then subjected to zone sublimation at 10⁻⁶ Torr with a temperature gradient of 320–340°C to achieve purity suitable for thermal evaporation in OLED fabrication. Device stacks of ITO/HAT-CN (5 nm)/TAPC (40 nm)/TCTA:Ir complex 10 wt% (25 nm)/Bphen (55 nm)/LiF/Al are fabricated and characterized per JIS C 8105-3; external quantum efficiency maxima of >20% at 1000 cd/m² luminance have been recorded when the emitter concentration is maintained at 9–11 wt%. Lot release includes trace metal analysis by ICP-OES compliant with ISO 11885:2007, monitoring for iridium and residual palladium from ligand synthesis. The final commercial product is a sublimed-grade phosphorescent dopant integrated into active-matrix OLED displays. In certain unsaturated polyester and vinyl ester resin formulations that must meet the fire-retardant requirements of UL 94 V-0 and the limiting oxygen index testing regime of ASTM D2863-23, the aromatic bromine atom provided by 2-(4-bromophenyl)thiazole-4-carbaldehyde is exploited as a source of vapor-phase radical scavenging activity. The aldehyde is chemically tethered to the resin backbone via imine formation with the terminal amine groups of amine-capped oligoester diols, typically added at a level of 7–14 phr during the let-down stage of the resin cook at 130–150°C. The modified resin is then diluted with styrene monomer (35–42 wt%) and cured with methyl ethyl ketone peroxide (1.2 phr) at ambient temperature, followed by post-cure at 80°C for 4 h. Cone calorimetry tests under ISO 5660-1:2015 at an external heat flux of 50 kW/m² show a reduction in peak heat release rate by 38–47% compared to the non-brominated control, with total smoke release remaining below 200 m²/m², a critical threshold for transportation applications governed by EN 45545-2. Processors operating filament winding or pultrusion equipment must precirculate resin in a sealed system to prevent aldehyde vapor accumulation at die entry points; local exhaust ventilation maintaining a capture velocity of 0.6 m/s is mandatory per ACGIH industrial ventilation guidelines. The brominated aldehyde-additivated composite laminates are deployed as electrical insulation boards and battery casings for e-mobility, where they undergo thermal endurance evaluation for 1000 h at 180°C according to IEC 60216-1. The reactive diluent nature of the aldehyde ensures that bromine is covalently bound, minimizing environmental leaching during end-of-life incineration, aligning with the waste acceptance criteria of Directive 2000/76/EC. Real-Time Optical Chemosensors Leveraging the Thiazole-Aldehyde Platform for Heavy Metal IonsThe simultaneous presence of a thiophilic thiazole nitrogen and a reactive formyl group permits 2-(4-bromophenyl)thiazole-4-carbaldehyde to serve as a fluorophore precursor when condensed with hydrazine derivatives to generate Schiff base probes selective for paramagnetic Cu²⁺ and Hg²⁺ in aqueous media. In a typical sensor preparation, the aldehyde (1.0 mmol) is dissolved in methanol and treated with dansyl hydrazine (1.0 mmol) and a catalytic amount of acetic acid under sonication at 40°C for 90 min, precipitating a yellow solid that is recrystallized from acetonitrile (purity by TLC >99%). Working probe solutions at 5 × 10⁻⁵ M in Tris-HCl buffer (pH 7.4) containing 0.5% v/v DMSO exhibit a 47-fold enhancement of fluorescence intensity at 510 nm upon addition of 1.0 eq of Hg²⁺, with an association constant log Ka of 5.12 as determined by Benesi–Hildebrand analysis of titration data. Selectivity tests against alkali, alkaline earth, and transition metal ions at tenfold excess concentrations verify that only Cu²⁺ causes substantial interference (quenching), an issue mitigated by masking with sodium thiosulfate (0.1 mM) prior to measurement. The test procedure aligns with the performance criteria of EPA Method 245.7 for cold vapor atomic fluorescence, with the probe demonstrating a detection limit of 1.2 µg/L (3σ blank) and linear range spanning 5–500 µg/L. The final practical embodiment is a paper-based test strip fabricated by dip-coating Whatman filter papers with the probe solution and drying under vacuum, enabling visual screening of water samples against a printed color chart. Such strips are validated alongside standard reference materials NIST SRM 1641e, ensuring field results fall within ±15% of certified values for mercury. No secondary formulation beyond the probe in supported format is commercialized; the chemosensor itself is the terminal product utilized by environmental monitoring agencies. Palladium-SCAFFOLD Catalysts Derived from Bromophenylthiazole-Aldehyde Building BlocksThe engineering of phosphine-free cross-coupling catalysts benefits directly from the donor flexibility of this thiazole formaldehyde: reductive amination of the aldehyde with N-cyclohexylethane-1,2-diamine in 1,2-dichloroethane using sodium cyanoborohydride (3.0 eq) at room temperature yields a tethered N,N,S-ligand that binds Pd(OAc)2 in a 2:1 ligand-to-metal stoichiometry to form air-stable Pd(II) precatalysts. The complex is isolated as a yellow solid after stirring in acetonitrile at 50°C for 16 h and is characterized by X-ray photoelectron spectroscopy showing binding energies of 335.1 eV (Pd 3d5/2) and 162.8 eV (S 2p3/2), confirming thiolate-free coordination through the thiazole ring. Catalyst screening in Suzuki–Miyaura coupling of 4-bromoacetophenone with phenylboronic acid under micellar conditions (TPGS-750-M, 2 wt% in water, K2CO3 1.5 eq, 45°C) demonstrates a turnover number exceeding 8.5 × 104 at a catalyst loading of 0.005 mol%, with full conversion achieved in 4 h as monitored by GC-FID against an undecane internal standard. Consistent with ISO 17025:2017 general requirements for the competence of testing laboratories, the catalyst batch is released only after passing a standard substrate panel that includes the coupling of heteroaryl chlorides (2-chlorothiophene) within 6 h at 0.01 mol% Pd. The process mass intensity for catalyst synthesis, including ligand preparation, stands at 430 kg solvent and consumables per kilogram of catalyst, substantially better than that of Pd(dppf)Cl2 analogs. Final physical form is a free-flowing fine powder with a tapped bulk density of 0.42 g/cm³, packaged under argon in septum vials for direct use in parallel synthesis stations and continuous flow microreactors. The catalyst is registered under REACH (EC 1907/2006) for import at quantities above 1 metric ton per annum, requiring an exposure scenario addressing the occupational inhalational toxicity of the palladium-ligand powder. |
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Cataloged as a heteroaryl aldehyde of the thiazole class, 2-(4-bromophenyl)thiazole-4-carbaldehyde (empirical formula C10H6BrNOS, calculated molecular weight 268.13 g·mol⁻¹) functions primarily as a bifunctional building block in medicinal and agrochemical synthesis. The molecule combines an electron-deficient thiazole ring, a reactive aldehyde group at the 4-position, and a 4-bromophenyl substituent at the 2-position, yielding a polarized scaffold suitable for sequential derivatization. Typical specifications for the research-grade solid include a purity threshold of ≥98% by reverse-phase HPLC (UV detection at 254 nm, area normalization) and a melting point range that generally falls between 118 °C and 125 °C when recrystallized from ethanol/water mixtures, although batch-specific values shift with polymorphic form and residual solvent content. Storage recommendations mandate sealed containers under dry argon at −20 °C, as the aldehyde moiety is susceptible to aerial oxidation to the corresponding carboxylic acid and the brominated aromatic ring can participate in photolytically induced dehalogenation when exposed to direct sunlight for extended intervals.
The aldehyde handle enables classical condensation chemistries—Schiff base formation with primary amines, Knoevenagel condensations with active methylene compounds, and Wittig olefinations with stabilized ylides—while the C–Br bond on the pendant phenyl ring opens access to palladium-catalyzed cross-coupling manifolds. In Suzuki–Miyaura reactions, oxidative addition of the C–Br bond to Pd(0) proceeds with significantly lower activation energy than the analogous C–Cl bond of the 4-chlorophenyl congener, a property that streamlines the preparation of biaryl intermediates for kinase inhibitors targeting the DFG-out conformation. Published protocols frequently employ Pd(PPh₃)₄ (2–5 mol%) and aqueous Na₂CO₃ in dioxane at 80 °C for 6–12 h, achieving isolated yields above 75% with arylboronic acids bearing electron-neutral or electron-rich substituents. The electron-withdrawing nature of the thiazole nucleus lowers the LUMO energy of the aldehyde, making the compound notably electrophilic: reductive aminations with sodium triacetoxyborohydride in dichloroethane at room temperature often reach completion within 2 h, whereas comparable benzaldehyde derivatives require 12–16 h under identical conditions. This enhanced electrophilicity, however, introduces a processing boundary—the aldehyde readily forms hydrates in aqueous media above pH 8, necessitating strict pH control during workup procedures that employ sodium bicarbonate washes.
| 4-Halogen Substituent | C–X Bond Dissociation Energy (kJ·mol⁻¹)⁽¹⁾ | Relative Suzuki Coupling Rate (krel)⁽²⁾ | Aldehyde Hydrate pKeq in H2O/DMSO (1:1) | Typical HPLC Purity Retention (12 months, −20 °C) |
|---|---|---|---|---|
| –F | 527 | 0.03 | 0.9 | 97% |
| –Cl | 339 | 0.15 | 1.1 | 96% |
| –Br | 281 | 1.0 (reference) | 1.2 | 95% |
| –I | 222 | 4.8 | 1.3 | 88% |
⁽¹⁾ Calculated homolytic bond dissociation energies from DFT (B3LYP/6-311+G**). ⁽²⁾ Relative rate for coupling with phenylboronic acid using Pd(OAc)₂/SPhos in toluene/water at 80 °C. Iodide congener exhibits rapid dehalogenation under storage, limiting shelf life. The bromo derivative provides a practical compromise between reactivity and bench-top stability.
Beyond the halogen identity shown in the table, the positioning of the bromine atom on the phenyl ring critically influences both solid-state packing and reactivity. The 4-bromo isomer routinely crystallizes in a monoclinic P2₁/c space group with a melting point roughly 15–20 °C higher than the 3-bromo regioisomer, a difference attributable to more efficient intermolecular Br···O electrostatic contacts between the bromine and the thiazole aldehyde oxygen of an adjacent molecule. In solution-phase Sonogashira alkynylations, the 4-bromo derivative exhibits a turnover frequency approximately 3.2-fold greater than the 3-bromo isomer when employing CuI (10 mol%) and PdCl₂(PPh₃)₂ (2 mol%) in triethylamine at 60 °C, as the para-substitution eliminates the steric compression that the meta-bromo group experiences adjacent to the thiazole–phenyl bond axis. Furthermore, the absence of an ortho-substituent leaves the C–Br bond fully accessible for oxidative addition without competing ortho-metallation side reactions that complicate the use of 2-(2-bromophenyl)thiazole-4-carbaldehyde.
The aldehyde carbon itself is more deshielded in the ¹³C NMR spectrum (δ typically 184.5–185.0 ppm in CDCl₃) compared to the corresponding 2-(4-bromophenyl)thiazole-4-methanol (δ 58.2 ppm for the CH₂OH carbon) or the homologous acetyl derivative. This downfield shift, coupled with a diagnostic aldehyde proton singlet at 10.02–10.08 ppm in the ¹H NMR spectrum, provides a robust identity check that distinguishes the product from partially oxidized samples where a broad acid O–H signal obscures the fingerprint region. Karl Fischer titration for water content typically returns values below 0.3 wt% for freshly opened batches; values above 1.0 wt% indicate hydrate formation that attenuates reactivity in moisture-sensitive acylations.
For route-scouting teams scaling a preclinical candidate to Phase I supplies, the compound’s handling profile introduces specific engineering controls. Residual palladium removal following Suzuki coupling steps that install the thiazole-carbaldehyde motif onto a larger core often employs treatment with trimercaptotriazine silica gel scavengers or charcoal filtration, but residual bromine leached from in-situ debromination can poison subsequent asymmetric hydrogenation catalysts. Batch records from kilo-lab campaigns document that washing crude organic solutions with 10% w/v aqueous sodium thiosulfate at 40 °C reduces free bromide ion concentrations to <50 ppm, a threshold below which Ru–BINAP-type catalysts maintain enantioselectivities above 90% ee. If the downstream chemistry requires anhydrous conditions, the aldehyde must be azeotropically dried with toluene (three cycles, 40 °C bath, 20 mbar) rather than exposed to drying agents like MgSO₄, which catalyze aldol self-condensation within 4 h at room temperature when the aldehyde concentration exceeds 0.5 M.
The brominated phenyl ring also presents a photochemical liability during large-scale processing under ambient laboratory lighting. At isolator windows or in glass-lined reactors exposed to diffuse daylight, photolytic homolysis of the C–Br bond accelerates over a 48 h period, generating radicals that abstract hydrogen from solvent to form 2-phenylthiazole-4-carbaldehyde as a debromination impurity. Wrapping transparent reactors with amber foil or processing under yellow light reduces this impurity to ≤0.15% by HPLC area after 72 h. In contrast, the chlorinated analogue tolerates ambient lighting without measurable degradation over 14 days, an advantage that must be weighed against its lower cross-coupling turnover.
Differential scanning calorimetry of the neat compound reveals a sharp endotherm at 120.6 °C (onset) with a heat of fusion of approximately 28.5 kJ·mol⁻¹, consistent with a crystalline solid that lacks plastic crystal transitions. Thermogravimetric analysis under nitrogen shows mass loss onset only above 220 °C, corresponding to evaporation and concomitant thermal degradation rather than decomposition of a labile functional group. When milled in a Retsch MM 400 mixer mill at 30 Hz for 10 min, the powder remains free-flowing without observable sintering, but after 60 min of continuous grinding, DSC trace broadening indicates amorphization and a concomitant increase in hygroscopicity—moisture uptake at 75% relative humidity jumps from 0.2 wt% for crystalline material to 2.8 wt% for partially amorphized powder. This shift justifies short, intermittent milling cycles with cryogenic cooling if nano-suspension formulations are explored for toxicology studies.
In formulation excipient compatibility studies, binary mixtures with PVP K30 stored at 40 °C/75% RH for four weeks exhibit a new HPLC peak at relative retention time 1.14 that mass spectrometry identifies as the pyrrolidine enamine adduct, formed via condensation of the aldehyde with liberated pyrrolidine from PVP hydrolysis. Lactose monohydrate mixtures, conversely, remain chemically inert but undergo a Maillard-like browning under the same conditions, rendering the aldehyde incompatible with reducing sugar-based fillers in solid dosage forms intended for oral gavage.
| Parameter | Method | Limit |
|---|---|---|
| Assay (anhydrous basis) | HPLC, C18 column, MeCN/H2O 70:30, 254 nm | ≥98.0% |
| Single largest impurity | Same HPLC method | ≤1.0% |
| Water content | Karl Fischer coulometry (methanol, Hydranal Composite 5) | ≤0.5% |
| Residual solvents | GC headspace per USP ⟨467⟩ | EtOH ≤ 5000 ppm, EtOAc ≤ 5000 ppm |
| Heavy metals | ICP-MS after microwave digestion | Pd ≤ 10 ppm, Br⁻ ≤ 100 ppm |
| Appearance | Visual inspection | White to off-white crystalline powder |
Users transitioning from the 4-fluoro or 4-chloro variants to this brominated intermediate should recalibrate their LC-MS purification gradients, as the characteristic isotopic doublet of bromine (¹⁹⁷Br/⁸¹Br, ~1:1 ratio) adds ~0.97 Da to the parent mass relative to the chloro analogue, altering the elution order of close-eluting byproducts on reversed-phase columns. On a typical 50 × 2.1 mm C18 column with 0.1% formic acid in water/acetonitrile gradient, the bromophenyl thiazole aldehyde elutes 0.4–0.6 min later than the chlorophenyl derivative, a shift that can resolve bis-arylated impurities that co-elute in the earlier-eluting pair.
During downstream amide bond coupling via in-situ generation of the acyl chloride using thionyl chloride, the bromine substituent partially exchanges with chloride if the reaction temperature exceeds 50 °C, yielding a mixed halogen population that complicates release testing. Maintaining an internal temperature of 0–5 °C during the activation step suppresses this halogen exchange to <2% after 1 h, as verified by ion chromatography of quenched aliquots. This sensitivity to halogen scrambling does not occur with the corresponding carboxylic acid oxidation product, offering an alternative entry point when amidation must proceed under forcing thermal conditions.
In cyclic voltammetry experiments (glassy carbon electrode, 0.1 M TBAPF₆ in DMF, scan rate 100 mV·s⁻¹), the thiazole ring exhibits an irreversible reduction wave at approximately −1.7 V vs Ag/AgCl, while the bromophenyl group shows a distinct reduction feature near −2.1 V. The separation of these waves allows selective electrochemical debromination under potentiostatic control, a synthetic strategy under investigation for generating the phenyl radical intermediate without tin hydride reagents. However, the aldehyde concurrently reduces at −1.9 V, overlapping partially with the second wave and imposing a narrow potential window of ±50 mV for chemoselective debromination—a processing constraint not encountered with the corresponding furan or oxazole aldehydes, which reduce at more negative potentials due to the higher LUMO energies of those heterocycles.
Industrial inquiries regarding the REACH registration status should confirm that the substance, placed on the European market in quantities below 1 metric ton per annum, typically falls under the research and development exemption of Article 3(23) of Regulation (EC) No 1907/2006. For import into South Korea, compliance with the Act on Registration and Evaluation of Chemicals (K-REACH) requires notification when annual volumes exceed 100 kg.
