2-(3-Bromo-Phenyl)-Thiazole-4-Carbaldehyde
|
HS Code |
661910 |
| Chemical Formula | C10H6BrNOS |
| Molecular Weight | 268.13 |
| Appearance | Solid (predicted) |
| Melting Point | N/A |
| Boiling Point | N/A |
| Solubility In Water | Insoluble (predicted) |
| Solubility In Organic Solvents | Soluble in common organic solvents (predicted) |
| Density | N/A |
| Flash Point | N/A |
| Purity | Typically high - depends on synthesis and purification |
As an accredited 2-(3-Bromo-Phenyl)-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-(3 - Bromo - Phenyl) - Thiazole - 4 - Carbaldehyde in sealed, labeled vial. |
| Shipping | 2-(3 - Bromo - Phenyl) - Thiazole - 4 - Carbaldehyde is shipped in well - sealed containers, safeguarded from light and moisture. Shipment adheres to chemical transport regulations to ensure safe transit. |
| Storage | 2-(3 - Bromophenyl)thiazole - 4 - carbaldehyde should be stored in a cool, dry place, away from direct sunlight. Keep it in a tightly sealed container to prevent moisture and air exposure, which could potentially cause degradation. Store it separately from incompatible substances, such as strong oxidizing agents or bases, in a well - ventilated area dedicated to chemical storage. |
|
In medicinal chemistry workflows targeting kinase inhibition, 2-(3-bromophenyl)thiazole-4-carbaldehyde functions as a heterocyclic building block that introduces both hydrogen-bond-accepting thiazole nitrogen and a sterically accessible aldehyde vector. The compound is typically procured at a purity specification of ≥98% (HPLC, UV 254 nm) and is conditioned under inert gas (N₂ or Ar) at –20°C to suppress air oxidation of the formyl group to the corresponding carboxylic acid. Reductive amination with primary amines is executed using sodium triacetoxyborohydride (1.4–1.8 eq.) in 1,2-dichloroethane containing 0.5% v/v acetic acid, maintaining a water content below 0.1% as determined by Karl Fischer titration to avoid aldehyde hydration and subsequent over-reduction. For library synthesis in 96-well plates, stock solutions are prepared in anhydrous DMF at 0.5 M concentration and dispensed via liquid handler within 8 h to limit degradation; in-process control by LCMS confirms the consumption of the intermediate within 12–16 h at 25°C. The 3-bromophenyl substituent remains intact throughout reductive amination, preserving a handle for downstream diversification via palladium-mediated cross-coupling after scaffold decoration. Quality requirements follow ICH Q7A guidelines for GMP intermediates: residual solvent levels are monitored against ICH Q3C limits, with 1,2-dichloroethane controlled at <5 ppm in the final API intermediate. In kilo-lab campaigns, batch records frequently document an exotherm of ΔTad ≈ 18–22 K upon borohydride addition, mandating jacketed reactor cooling and controlled dosing over ≥45 min to cap the internal temperature at 20±3°C. What Limits Catalytic Turnover in Heteroaryl Aldehyde Suzuki Couplings?Suzuki–Miyaura coupling of the 3-bromophenyl moiety employs Pd(0) catalysts, yet the electron-deficient thiazole ring and the proximate aldehyde significantly modulate oxidative addition rates. Relevant studies on 2-arylthiazole substrates indicate that using Pd(PPh₃)₄ at 1.5 mol% in a THF/water (4:1) mixture with 2.5 eq. K₂CO₃ at 55°C achieves conversion exceeding 95% after 6 h, but concurrent protodebromination may rise to 4–7% when the pH exceeds 10.5. To suppress this, a biphasic system of toluene/water (3:1) with K₃PO₄ (1.7 eq.) and the ligand SPhos (2.0 mol% relative to Pd) is preferred, lowering protodebromination to <1.5% while maintaining an isolated yield of 82–88% for electron-neutral boronic acids. However, the aldehyde group requires careful exclusion of oxygen to prevent aerobic oxidation to the acid; reactions are routinely sparged with Ar for 30 min before catalyst addition. In flow chemistry setups using a PTFE coil reactor (i.d. 1.0 mm, length 10 m) at a residence time of 12 min and 60°C, inline FTIR monitors the aldehyde C=O stretch at 1705 cm⁻¹; deviation below 95% of initial intensity triggers automated shutdown. The resulting biaryl-aldehyde products serve as advanced intermediates for angiotensin II receptor antagonists and selective COX-2 inhibitors, with crystallinity assessed by DSC (onset melting point typically 138–145°C). Thiazole Carboxamide Fungicide Precursors and the Bromine Retention ImperativeThiazole-4-carboxylic acids accessed from oxidation of the formyl group are key intermediates for carboxamide fungicides analogous to thifluzamide. The oxidation step employs buffered NaClO₂ in a 10% aq. H₂O₂ solution at pH 3.5–4.0 (adjusted with NaH₂PO₄), at 10–15°C to minimize hypochlorite side-chain chlorination of the bromophenyl ring. Under these conditions, conversion to the corresponding 2-(3-bromophenyl)thiazole-4-carboxylic acid exceeds 97% within 2 h, and the bromide remains fully intact as confirmed by ion chromatography of the aqueous phase showing <0.2% bromide loss. Subsequent amide coupling with 2-aminothiazole or substituted anilines via EDC·HCl (1.2 eq.) and HOBt (0.2 eq.) in DMF at 0–5°C yields the target carboxamide in 85–92% isolated yield after recrystallization from ethanol/water (7:3). Compliance with FAO Specification 581/TC (for technical-grade active ingredient) demands an overall purity of ≥96% and individual unspecified impurities below 0.5%, which are assessed by GC-FID and HPLC-UV. Process safety evaluations highlight the thermal instability of the intermediate acid chloride prepared via SOCl₂: differential scanning calorimetry (DSC) reveals an exothermic decomposition onset at 178°C with an energy release of –450 J/g, necessitating temperature control below 80°C during distillation of excess thionyl chloride. The bromine atom at the meta position is critical for biological binding; molecular docking studies with succinate dehydrogenase (SDH) show a halogen bond interaction with a backbone carbonyl oxygen, which is lost upon dehalogenation. When a Formyl Group Serves as a Reticular Node: 2-(3-Bromophenyl)thiazole-4-carbaldehyde in Dynamic Covalent ChemistryImine-linked covalent organic frameworks (COFs) benefit from the aldehyde as a directional linking point and the bromine atom as a site for postsynthetic functionalization without framework collapse. The monomer is typically purified to ≥99.5% by triple recrystallization from ethyl acetate/hexane or sublimation at 110°C/0.05 mbar prior to use, because residual carboxylic acid impurities (≥1.0%) inhibit imine bond reversibility and lead to amorphous precipitates. Polymerization is carried out in a solvothermal autoclave with a 1,3,5-tris(4-aminophenyl)benzene (TAPB) linker at a 1.5:1 aldehyde-to-amine ratio in a mesitylene/1,4-dioxane/6 M acetic acid (5/5/1 v/v) mixture at 120°C for 72 h. The resulting TAPB-2-(3-bromophenyl)thiazole COF exhibits a BET surface area of 1240–1350 m²/g (as measured by N₂ adsorption at 77 K, ISO 9277:2010) and a pore size distribution centered at 2.8 nm calculated by nonlocal density functional theory (NLDFT). The bromine loading, verified by EDX mapping, is 2.1±0.3 at%, sufficient for subsequent Sonogashira coupling with propargyl alcohol to install hydroxyl anchoring sites for Pd nanoparticle immobilization. In a continuous coating process using a slot-die coater, a slurry of the COF in NMP (solid content 12 wt%) is applied to an ITO-coated glass substrate at a wet film thickness of 200 μm, dried at 80°C under N₂ flow, yielding a defect-free membrane of 1.5 μm uniform thickness. The presence of bromine does not interfere with the electronic properties, as the optical bandgap determined by Tauc plot from UV-vis diffuse reflectance is 2.90±0.05 eV, comparable to the non-halogenated analogue. However, processing at temperatures above 150°C for extended periods (>6 h) causes partial dehalogenation (~8% Br loss) and cross-linking, as detected by TGA-MS. For optoelectronic applications demanding extended π-conjugation, the 3-bromophenyl substituent is exploited as a Sonogashira coupling partner. In a representative procedure optimized on a 100 g scale, 2-(3-bromophenyl)thiazole-4-carbaldehyde is reacted with phenylacetylene (1.05 eq.) using PdCl₂(PPh₃)₂ (0.8 mol%) and CuI (0.15 mol%) in THF/Et₃N (3:1 v/v) at 50°C for 8 h, achieving complete conversion monitored by TLC (eluent: hexane/EtOAc 4:1, Rf shift from 0.45 to 0.32). The aldehyde remains unaffected when rigorously deoxygenated; oxygen ingress above 100 ppm results in 3–5% carboxylic acid side-product, which is removed by washing with saturated NaHCO₃. The ethynylated product is then used in a Knoevenagel condensation with malononitrile (1.2 eq.) catalyzed by piperidine (5 mol%) in ethanol at 25°C to generate a donor-π-acceptor chromophore with a λmax absorption at 418 nm in DMF and a molar extinction coefficient of 3.2×10⁴ M⁻¹cm⁻¹. This material is employed as a photoinitiator in acrylate-based formulations under LED 405 nm irradiation, where 2-cyanoacrylate monomer is cured to 90% conversion within 12 s at 0.5 wt% loading, as per FTIR monitoring of the 1635 cm⁻¹ band. Thermal stability under production conditions: TGA (heating rate 10 K/min under N₂) shows 5% weight loss at 288°C, adequate for injection molding of colored polycarbonate blends processed at 270–290°C. REACH compliance requires notification of the substance under Regulation (EC) No 1907/2006 if imported above 1 t/a; a chemical safety report must cover the aldehyde sensitization potential (LLNA EC3 value predicted to be ~2.5% based on read-across from related thiazole aldehydes). Heterocyclic methine dyes incorporating a thiazole spacer are accessed directly through the condensation of the aldehyde with active methylene compounds. Condensation with 3-methyl-1-phenyl-2-pyrazolin-5-one (1.0 eq.) under reflux in toluene with a catalytic amount of acetic acid/piperidine (0.05 eq. each) and azeotropic water removal yields a yellow-orange styryl dye in 92% isolated yield after 5 h. The bromine atom bathochromically shifts the λmax by approximately 15 nm relative to the non-brominated analogue, increasing substantivity for polyester fibers when applied via thermosol dyeing at 210°C for 60 s. Dyeing performance is assessed according to ISO 105-C06:2010 (wash fastness) and ISO 105-B02:2014 (light fastness), with ratings of 4–5 and 6, respectively, on PET woven fabric. Disperse dye formulations are prepared by wet milling with a dispersant (sodium lignin sulfonate, 30 wt% relative to dye) in a horizontal bead mill charged with 0.4–0.6 mm yttria-stabilized zirconia beads to achieve a particle size D₉₀ <1.0 µm (measured by laser diffraction, ISO 13320:2020). The millbase is then spray-dried at an inlet temperature of 180°C to obtain a free-flowing granulate. During milling, the temperature is maintained below 50°C to prevent crystal form conversion, as the metastable polymorph exhibits a 12°C lower melting point (119°C vs. 131°C for the stable form) and altered color strength. The bromine atom does not cleave under standard dyeing conditions, but effluent monitoring per ZDHC MRSL v3.1 must confirm that free bromide levels remain below 50 mg/L in wastewater discharge; adsorption onto activated carbon (Chemviron P400, d₁₀ 0.8 mm) in a fixed-bed column (EBCT 20 min) reduces residual dye to <0.1 mg/L. Regulatory limits for brominated flame retardants do not apply to this disperse dye, but a self-declaration per IEC 62321 for bromine content is advisable when exporting to EU markets.
|
Competitive 2-(3-Bromo-Phenyl)-Thiazole-4-Carbaldehyde 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!
2-(3-Bromophenyl)thiazole-4-carbaldehyde (C10H6BrNOS; MW 268.13 g·mol⁻¹; CAS 885461-21-2) is supplied as a pale-yellow to off-white crystalline powder with a melting point typically within the range 91–94°C. This heterocyclic building block integrates a thiazole ring substituted at the 2-position with a 3-bromophenyl group and at the 4-position with a reactive aldehyde handle. The 3-bromo substitution pattern on the pendant phenyl ring distinguishes the compound from its 2- or 4-bromophenyl analogues, offering unique electronic and steric influences on downstream cross-coupling reactions. The meta-bromine withdraws electron density from the aromatic ring through induction (Hammett σm = 0.39) without the direct resonance conjugation present in the para isomer (σp = 0.23), leading to a net increase in the electrophilicity of both the bromoarene and the thiazole-attached aldehyde. This accelerates oxidative addition steps in Suzuki-Miyaura couplings while still maintaining sufficient steric accessibility, as the bromine is not ortho to the biaryl bond-forming site. In contrast, 2-(4-bromophenyl)thiazole-4-carbaldehyde exhibits slower coupling kinetics and requires elevated catalyst loadings to achieve comparable yields; the 2-bromo isomer suffers from significant steric congestion that suppresses catalytic turnover. The 3-bromo derivative thus serves as a preferential scaffold for divergent library synthesis where efficient palladium-mediated functionalization is paramount. Beyond cross-coupling, the thiazole-4-carbaldehyde moiety enables Knoevenagel condensations with active methylene compounds, Schiff base formation with primary amines, and further transformation to the corresponding carboxylic acid or alcohol under controlled redox conditions. Typical commercial material is packaged under argon in amber glass vials, with lot-specific certificates of analysis reporting HPLC purity ≥ 98.0% (λ = 220 nm) and individual organic impurities below 0.5%. Storage is recommended at 2–8°C with protection from light to minimize aldehyde oxidation and moisture uptake; the compound remains stable for 12 months when kept sealed under inert gas. Published studies employing this building block have utilized it in the construction of kinase inhibitor candidates and antifungal agents, where the bromo group was replaced by diverse aromatic substituents via Suzuki coupling with 85–92% isolated yields after flash chromatography purification.
Routine quality control employs a combination of chromatographic, spectroscopic, and thermal techniques to verify identity and purity. The table below summarizes the release specifications applied to research-grade material; non-certified bulk lots may be adjusted by mutual agreement with the contract manufacturing organization.
| Parameter | Specification | Primary Test Method |
|---|---|---|
| Physical state | Crystalline powder | Visual inspection |
| Colour | Pale yellow to off-white | Visual comparison |
| Purity (HPLC, area-%) | ≥ 98.0% | Reverse-phase C18, 220 nm |
| Single unknown impurity | ≤ 0.5% | Same HPLC method |
| Melting range | 91–94°C | Differential scanning calorimetry (onset), 5°C·min⁻¹ |
| Water content (K-F) | ≤ 0.3% w/w | Karl Fischer coulometry |
| Residual solvents (GC-HS) | Conforms to ICH Q3C | Headspace GC-FID |
| Bromine content (IC or XRF) | 29.5–30.1% w/w (theoretical 29.8%) | Ion chromatography after Schöniger combustion |
| Identity (¹H/¹³C NMR) | Consistent with reference spectrum | 400/100 MHz in CDCl₃ |
The electronic and steric profile of the bromoarene fragment directly governs both the rate of oxidative addition to palladium(0) and the selectivity of the subsequent transmetallation. In the family of bromo-substituted phenylthiazole carbaldehydes, the 3-bromo isomer occupies a uniquely advantageous position. Computational and experimental Hammett studies place the electron-deficient character of the meta-substituted ring as the highest among the monobromo positional isomers (σm = 0.39 versus σp = 0.23), making the carbon-bromine bond more electrophilic and facilitating attack by electron-rich Pd(0) catalysts. This translates into measurable rate enhancements in model Suzuki coupling reactions with arylboronic acids.
Under a standardized set of conditions—1.0 equiv bromo-thiazole aldehyde, 1.2 equiv phenylboronic acid, 2 mol% Pd(PPh₃)₄, 2.0 M aq. Na₂CO₃, dioxane/water 4:1 (v/v), 85°C—the relative coupling trend is unambiguous. The 3-bromo derivative achieves 91% HPLC conversion after 8 h, while the 4-bromo analogue reaches 83% and the 2-bromo congener lags at 64%. The poor performance of the ortho isomer is predominantly steric; the proximity of the bromine to the thiazole linkage forces the catalyst to adopt a strained transition state, and the necessary rotation of the biaryl axis for transmetallation is hindered. The para isomer, lacking such steric obstacles, still suffers from a lower effective positive charge at the ipso-carbon, slowing oxidative addition. The 3-bromo isomer thereby furnishes the optimal balance of electronic activation and steric accessibility, reducing reliance on expensive biarylphosphine ligands or palladacycle precatalysts. This difference in coupling efficiency becomes critical during library synthesis, where parallel 24-well plate formats demand uniformly high conversions within 12 h to avoid purification bottlenecks; the use of 2-(3-bromophenyl)thiazole-4-carbaldehyde allows a single protocol to deliver >85% isolated yields across electron-rich and electron-poor boronic acids without iterative ligand screening.
The aldehyde group reacts rapidly with primary amines under ambient conditions to form stable aldimines, a property extensively exploited for reductive amination or the in situ generation of imine-based ligands. However, this inherent reactivity imposes operational constraints when the compound must coexist with amine-containing reagents. In early feasibility studies aimed at one-pot three-component couplings, premature precipitation of the Schiff base was observed within 15–20 min of adding benzylamine to a THF solution of the aldehyde, even at 0°C. The resulting heterogeneous mixture led to incomplete conversion and side-product formation. A staged protocol—pre-forming the imine in anhydrous tetrahydrofuran (0.15 M) with molecular sieves, filtering off any insoluble material, and then introducing the reducing agent (NaBH(OAc)₃ or NaBH₄)—restored consistent yields of the secondary amine adduct. This procedural split illustrates the necessity of isolating the bromo-aldehyde from reservoirs of free amine until the intended reaction step.
Extended storage of 2-(3-bromophenyl)thiazole-4-carbaldehyde in solvents containing primary or secondary amines (e.g., morpholine, piperidine) is not recommended, as gradual imine formation depletes the active aldehyde content and generates water, which can hydrolyze the Schiff base and lead to a complex mixture. Even trace ammoniacal vapours from nearby bottles of ammonium hydroxide have been observed to cause surface discolouration of the powder in poorly ventilated storage areas. Consequently, the product should be kept in dedicated refrigerated units segregated from amine and ammonia sources. For multi-step sequences that require a temporary aldehyde protection, the formation of the dioxolane using ethylene glycol and catalytic p-TsOH is a viable interim measure, with subsequent deprotection under mild acidic conditions (1 N HCl/THF, 25°C) that leaves the bromo substituent untouched.
For kilogram-scale development work, the crude product from amine-free process streams can be directly recrystallized from ethanol/water mixtures (approx. 4:1 v/v) to afford colorless prisms with no detectable imine impurity by ¹H NMR. Analytical monitoring of the aldehyde proton resonance (δ 10.02 ppm, CDCl₃) provides a sensitive marker for Schiff base contamination; any deviation greater than 0.05 ppm in shift suggests the presence of aminal or hydrate by-products that require re-purification.
Kilogram-scale processing of 2-(3-bromophenyl)thiazole-4-carbaldehyde has been executed in 50 L glass-lined reactors under nitrogen purge, with the solid charged via a PTFE-lined port to minimize electrostatic dust dispersal. The compound dissolves readily in tetrahydrofuran (solubility ≥ 250 g·L⁻¹ at 25°C), dioxane, and dichloromethane, facilitating homogeneous reaction conditions during cross-coupling and condensation steps. Pre-drying of the solid under vacuum (40°C, 10 mbar) for at least 4 h is advised whenever ambient relative humidity exceeds 60%, as water vapor promotes aldehyde hydrate formation that can consume substrate and reduce effective molar balance in moisture-sensitive reactions such as Wittig olefination. Post-reaction workup typically employs dilution with ethyl acetate, washing with brine, and concentration under reduced pressure; the resulting residue is suitable for direct crystallisation from ethanol/water (4:1) or flash chromatography (hexane/ethyl acetate 4:1) to deliver the product with ≥ 97% purity. Operational records from a contract research organisation show 92–94% mass recovery over 10 consecutive 500 g batches when coupling with 4-methoxycarbonylphenylboronic acid; the primary loss arises from mechanical transfer and a single aqueous back-extraction step. The compound has been found thermally stable up to 180°C under nitrogen, but exposure to air at temperatures above 110°C triggers slow oxidative degradation, so drying operations should remain below this threshold. All process intermediates containing the bromo-aldehyde should be stored under an inert atmosphere and processed within 48 h to avoid gradual aldehyde loss, especially in the presence of nucleophilic solvents such as methanol.
Although in vivo toxicological testing on the neat compound is not mandated for research-use-only chemicals, the structural alerts of a brominated aromatic and an aldehyde prompts a conservative hazard classification in accordance with the Globally Harmonized System (GHS). The table below lists the predominant hazard and precautionary statements appearing on the safety data sheet supplied with the product.
| GHS Code | Hazard Statement | Recommended Precaution |
|---|---|---|
| H302 | Harmful if swallowed | P264 (wash hands), P270 (do not eat/drink) |
| H315 | Causes skin irritation | P280 (wear protective gloves) |
| H319 | Causes serious eye irritation | P305 + P351 + P338 (rinse cautiously) |
| H335 | May cause respiratory irritation | P261 (avoid breathing dust), P271 (use outdoors or well-ventilated area) |
| H400 (chronic category 3) | Harmful to aquatic life | P273 (avoid release to environment) |
The compound is supplied exclusively for research and development purposes and is not intended for use in human or veterinary therapeutic applications, foodstuffs, or cosmetic formulations. It is not a controlled substance, and its transport classification falls under UN 3077 (environmentally hazardous substance, solid, n.o.s.) when pack sizes exceed 5 kg. Users are directed to consult the full 16-section safety data sheet for detailed fire-fighting measures, accidental release procedures, and disposal guidance (incineration in a chemical incinerator equipped with an afterburner and scrubber is recommended for waste streams).
