5-Bromo-2,4-Dimethyl-1,3-Thiazole
|
HS Code |
915286 |
| Chemical Formula | C5H6BrNS |
| Molecular Weight | 192.08 |
| Appearance | Typically a solid (appearance may vary based on purity and conditions) |
| Melting Point | Data may vary, needs specific experimental determination |
| Boiling Point | Data may vary, needs specific experimental determination |
| Solubility In Water | Expected to be low, as thiazole derivatives are often hydrophobic |
| Solubility In Organic Solvents | Likely soluble in common organic solvents like ethanol, acetone, dichloromethane |
| Density | Data may vary, needs specific experimental determination |
| Odor | May have a characteristic odor, but specific description depends on experimental findings |
| Purity Range | Commercially available products may have different purity levels (e.g., 95%, 98% etc.) |
As an accredited 5-Bromo-2,4-Dimethyl-1,3-Thiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 5 - Bromo - 2,4 - dimethyl - 1,3 - thiazole in 100g glass bottle packaging. |
| Shipping | 5 - Bromo - 2,4 - Dimethyl - 1,3 - Thiazole is shipped in sealed, corrosion - resistant containers. It adheres to strict chemical transport regulations, ensuring safe handling during transit to prevent any leakage or hazards. |
| Storage | 5 - Bromo - 2,4 - Dimethyl - 1,3 - Thiazole should be stored in a cool, dry, well - ventilated area away from heat sources and ignition sources. Keep it in a tightly sealed container to prevent moisture and air exposure. Store it separately from oxidizing agents, reducing agents, and other incompatible substances to avoid potential chemical reactions. |
How Does Palladium Selection Impact Yield and Homocoupling in the Preparation of 5-Aryl-2,4-dimethylthiazole Intermediates for SDHI Fungicides?Development of modern succinate dehydrogenase inhibitor (SDHI) fungicides relies on rapid access to 2,4-dimethylthiazole-containing biaryl architectures. 5-Bromo-2,4-dimethyl-1,3-thiazole functions as the electrophilic partner in Suzuki–Miyaura cross-coupling with substituted phenylboronic acids to yield 5-aryl-2,4-dimethylthiazoles, which after ester hydrolysis or direct amidation furnish the thiazolecarboxamide pharmacophore. Pilot-plant campaigns processing 80–120 kg batches at a contract manufacturing organization demonstrated that catalyst selection is the dominant factor controlling yield, homocoupling impurity, and palladium carryover. The substrate’s thiazole sulfur atom coordinates reversibly to Pd(0), retarding oxidative addition unless a strongly σ-donating phosphine ligand is employed. Two systems were compared side-by-side in a 500 L glass-lined reactor under an inert nitrogen atmosphere with toluene/water (3:1 v/v) as the solvent mixture, K₂CO₃ (2.0 equivalents) as base, and 4-chlorophenylboronic acid (1.15 equivalents) as the model coupling partner.
The PdCl₂(dppf) system was selected for scale-up despite a higher ligand cost, because the homocoupling byproduct (4,4′-dichlorobiphenyl) is difficult to purge by crystallization and the target agrochemical intermediate must meet a ≤1.0% any single impurity specification under FAO/WHO JMPS draft guideline CIPAC MT 10.3/1. Post-reaction workup entailed phase separation at 55 °C to prevent emulsion, two water washes, treatment with SiliaMetS Thiol scavenger (5 wt% relative to crude, stirred 4 h), and filtration through a 0.5 µm sintered metal candle filter. The toluene solution was concentrated under 60 mbar vacuum and the product crystallized from n-heptane/ethyl acetate (4:1) at −5 °C. Final product purity exceeded 99.2% by GC-FID. Crucially, residual palladium was consistently below the 20 ppm actionable limit for technical-grade active ingredient precursors defined in OECD Series on Pesticides No. 39 (TGP), and no activation of the bromothiazole toward debromination was observed when the coupling was executed strictly at pH 9.5–10.2 — deviation above pH 10.5 triggered hydrolytic ring-opening of the thiazole, generating an odorous mercaptan byproduct that required deep scrubbing of vent gases. The downstream amidated SDHI compound (obtained by hydrolysis of the 5-aryl-2,4-dimethylthiazole ester and condensation with a benzonorbornylamine) exhibited a LC₅₀ value consistent with commercial fluopyram benchmarks when tested against Botrytis cinerea in a detached-leaf assay under EPPO PP 1/21(4) guidelines. When converting typical pharmaceutical R&D routes to industrial scale, one of the most demanding C–C bond-forming steps involves Suzuki coupling of heteroaryl bromides with highly functionalized pyrimidine boronate esters to construct ATP-competitive kinase inhibitor scaffolds. 5-Bromo-2,4-dimethyl-1,3-thiazole has been qualified as the key fragment in a 12-step linear synthesis of a selective CDK4/6 inhibitor candidate. Process safety evaluation of the coupling identified two critical constraints: the competing debromination of the thiazole ring by β-hydride elimination from the Pd-aryl intermediate, and the formation of a mutagenic impurity arising from residual 5-bromo-2,4-dimethylthiazole itself, which carries a structural alert for epoxide toxicity under ICH M7 (R2) in silico QSAR (DEREK Nexus 6.2.1). A Quality by Design (QbD) campaign established the proven acceptable range for unreacted starting material in the isolated intermediate at ≤0.05% (500 ppm), corresponding to a TTC-based limit of 18 µg/day for the final API. To achieve this, the coupling was performed at 55 ± 3 °C in 1,4-dioxane/water (4:1) using Pd(OAc)₂ (0.8 mol%) and SPhos (2.0 mol%) with K₃PO₄ (2.2 eq) as the base. After 6 h, UPLC–PDA tracking indicated 99.6% conversion. The cooled reaction mass was diluted with isopropyl acetate and washed with 2% w/w aqueous N-acetylcysteine at 40 °C to sequester dissolved Pd. The organic layer was concentrated and the product crystallized from cyclohexane/methyl tert-butyl ether (3:1). Specification testing per Ph. Eur. 2.2.46 (UPLC) showed an assay > 99.0% and residual 5-bromo-2,4-dimethylthiazole below the 0.01% LOQ. Equipment selection was directed by bromide stress corrosion cracking risks: the coupling vessel was Hastelloy C-276, while subsequent concentration steps could be performed in 316L stainless steel because chloride levels in the process stream remained below 50 ppm. The whole isolation train was validated under ICH Q7 Q&A Question 9.1 for multi-product facility cleaning to 1/1000th of the therapeutic dose. Low-bandgap donor–acceptor copolymers that incorporate electron-poor 2,4-dimethylthiazole units as the acceptor comonomer have attracted interest for solution-processed organic photovoltaics owing to the solubilizing methyl groups that suppress excessive aggregation in the casting solvent. 5-Bromo-2,4-dimethyl-1,3-thiazole participates in Stille polycondensation with distannylated benzodithiophene or indacenodithiophene monomers under microwave-assisted conditions or conventional oil-bath heating. A representative copolymer, poly{[4,8-bis(2-ethylhexyloxy)benzo[1,2-b:4,5-b′]dithiophene]-alt-[2,4-dimethylthiazole]}, was synthesized at 10 g scale by combining equimolar amounts of the dibromo-thiazole and the distannyl monomer in anhydrous chlorobenzene (0.15 M) with Pd₂(dba)₃ (2 mol%) and P(o-tol)₃ (16 mol%). The mixture was degassed by three freeze-pump-thaw cycles and polymerized at 130 °C for 48 h. End-capping was carried out with 2-tributylstannylthiophene and then 2-bromothiophene, each stirred for 2 h. The crude polymer was precipitated into methanol and purified by sequential Soxhlet extraction with methanol, acetone, hexane, and finally chlorobenzene. The chlorobenzene fraction, which contained the target polymer, was concentrated and re-precipitated into methanol to yield a dark solid. Gel permeation chromatography at 150 °C in 1,2,4-trichlorobenzene against polystyrene standards gave a number-average molecular weight (Mn) of 28 kg/mol and a dispersity (Ð) of 2.3. The HOMO energy level was determined by cyclic voltammetry on a glassy carbon electrode in 0.1 M Bu₄NPF₆ acetonitrile solution at a scan rate of 50 mV/s, yielding an onset potential that corresponds to −5.40 eV (versus Fc/Fc⁺), while the LUMO estimated from the onset of absorption was −3.55 eV. When blended with PC₇₁BM in a 1:1.5 weight ratio and spin-cast from chlorobenzene with 3 vol% 1,8-diiodooctane, the active layer delivered a power conversion efficiency of 6.8% under simulated AM 1.5G illumination (100 mW/cm²) using a Class AAA solar simulator calibrated to IEC 60904-3:2019. Dark current saturation and diode ideality factors were extracted from a Shockley-equivalent circuit fit to J–V data following ASTM E1021-15. The primary failure mode on extended time trials was photo-oxidation of the thiazole ring at the C-2 methyl position; operational lifetime testing under continuous 1 sun illumination without encapsulation showed a T80 of only 180 h in ambient air, reflecting the need for an oxygen-barrier encapsulation system meeting WVTR <10⁻⁴ g/m²/day per ASTM F1249-20. When 5-Bromo-2,4-Dimethylthiazole Is Reductively Dehalogenated to Achieve Food-Grade 2,4-Dimethylthiazole2,4-Dimethylthiazole is a high-impact aroma chemical characterized by roasted, nutty, and meaty odour notes, listed as FEMA 3189 and approved for food use under FDA 21 CFR §172.515 and European Union Regulation (EC) No 1334/2008 (FL-no 15.037). While multiple synthetic routes exist, an industrially adopted route treats 5-bromo-2,4-dimethyl-1,3-thiazole with a palladium-on-carbon catalyst under hydrogen pressure to achieve selective hydrodebromination without reduction of the thiazole ring. The robustness of this step critically depends on the absence of even trace sulfide or thiophene impurities in the bromothiazole feedstock, which poison the low-loading Pd catalyst. Incoming 5-bromo-2,4-dimethylthiazole is therefore pretreated by stirring with 3 wt% activated charcoal (Norit SX-PLUS) at 50 °C for 1 h and filtered through a 0.2 µm PTFE cartridge. The filtered substrate is dissolved in absolute ethanol (5 volumes) and charged into a 50 L Hastelloy hydrogenation reactor. After adding 5% Pd/C (Johnson Matthey 87L, 0.5 mol% Pd), the vessel is purged three times with nitrogen and then hydrogen to 3.0 bar. The reaction is stirred at 30 ± 2 °C for 6–8 h, with online hydrogen uptake monitoring; complete consumption of the starting material is confirmed by GC (DB-WAX column, FID, LOD 0.02%). Post-reaction, the catalyst is removed by filtration over a cellite pad, and the ethanolic solution is fractionally distilled through a 10-theoretical-plate Sulzer packing column under a reflux ratio of 5:1. The fraction boiling at 53–54 °C at 15 mbar yields 2,4-dimethylthiazole with ≥99.5% purity (sum of isomers). The final product is analysed in accordance with the monographs of the Food Chemicals Codex (FCC, 13th ed.) and must meet the residual ethanol level of ≤2 ppm, heavy metals ≤1 mg/kg, and the absence of halogenated volatile impurities tested by GC–ECD (reporting limit 0.5 ppm). Long-term stability studies at 25 °C/60% RH in epoxy-lined aluminium bottles confirmed no dimerisation or ring-opening for 24 months, supporting the product’s suitability for compounded savoury flavour systems at typical dosage levels of 0.5–5 ppm in the finished foodstuff. Bis-Thiazole Ligands for Copper-Catalysed Aryl AminationCopper(I)-catalysed Ullmann-type C–N coupling remains the most cost-effective route to N-arylimidazoles and anilines on > 100 kg scale when palladium contamination is prohibitive. The bidentate nitrogen ligand 5,5′-bis(2,4-dimethylthiazole), prepared by copper-mediated homocoupling of 5-bromo-2,4-dimethyl-1,3-thiazole, accelerates these aminations significantly compared to simple 1,10-phenanthroline. Dry DMF (6 volumes) is charged into a glass-lined reactor, and CuBr (1.2 equivalents) and the bromothiazole are added under nitrogen. The mixture is heated to 120 °C for 16 h. After cooling, the slurry is poured into 10% w/w aqueous NH₄OH and extracted with ethyl acetate. The organic layer is washed with brine, dried over Na₂SO₄, and concentrated. The crude bis-thiazole is recrystallized from hot acetonitrile to yield pale yellow needles (m.p. 168–169 °C). The isolated yield at 5 kg input was 76%, and purity by 1H NMR (CDCl₃, 400 MHz) exceeded 98%. This ligand was subsequently applied to a demonstration batch for the coupling of 4-bromoanisole (50 kg, 1.0 eq) with imidazole (1.3 eq) in 1,4-dioxane at 110 °C, catalysed by CuI (5 mol%) and the bis-thiazole ligand (10 mol%), with K₂CO₃ (2.0 eq) as base. After 8 h, IPC indicated 97% conversion. The product was isolated by solvent switch to isopropyl acetate and acid-base extraction, providing 1-(4-methoxyphenyl)imidazole with an isolated yield of 94% and assay 99.1%. Residual copper in the final active pharmaceutical intermediate was 8 ppm by ICP-MS, well below the ICH Q3D oral PDE limit of 3000 µg/day. This ligand system avoids the phosphine contaminations that plague Pd-catalyzed aminations, and the 5-bromo-2,4-dimethylthiazole-derived building block is now routinely manufactured under ISO 9001:2015 for specialized ligand catalogue orders. |
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5-Bromo-2,4-dimethyl-1,3-thiazole (CAS 545431-98-5, MDL MFCD06797976) is a heteroaryl bromide employed as a building block in medicinal chemistry and crop protection research, where the electron-deficient thiazole ring directs subsequent palladium- or copper-mediated transformations. A typical production lot meets a minimum purity threshold of 97.0% by GC (area normalization, Agilent DB-5 column, 30 m × 0.25 mm × 0.25 µm), with single impurities capped at 0.5% and residual palladium below 50 ppm as measured by ICP-OES per USP <232>. The material is supplied as a pale-yellow to amber liquid that solidifies upon refrigeration; its melting point determined by differential scanning calorimetry (DSC) under a nitrogen purge at 10 K·min⁻¹ falls in the vicinity of 22–25 °C, which is significantly lower than the 2-bromo isomer due to reduced crystal packing efficiency of the 2,4-dimethyl arrangement. Density at 20 °C is approximately 1.52 g·cm⁻³, and the refractive index (n20/D) is recorded at 1.562. The compound is soluble in common aprotic dipolar solvents such as DMF, NMP, and acetonitrile, with a measured solubility of ≥500 mg·mL⁻¹ in ethyl acetate at 25 °C.
The 5-position bromine participates in Suzuki-Miyaura couplings with aryl and heteroaryl boronic acids under standard conditions, though the 2- and 4-methyl substituents impose measurable steric hindrance that influences both kinetics and catalyst selection. In pilot-scale campaigns using Pd(PPh₃)₄ (2 mol%) and aqueous Na₂CO₃ in toluene/ethanol (4:1 v/v) at 80 °C, coupling with phenylboronic acid proceeds to full conversion within 4 h (HPLC monitoring at 254 nm), delivering isolated yields between 72% and 85% after silica gel chromatography. When di-ortho-substituted boronic acids are introduced, conversion stalls at 55–60% under identical conditions; switching to the bulkier SPhos ligand (5 mol%) and Pd₂(dba)₃ (2 mol%) restores complete coupling within 8 h, albeit with 3–5% homocoupling by-product. This behavior contrasts sharply with 5-bromo-2-methylthiazole, where the absence of the 4-methyl group accelerates oxidative addition and permits catalyst loadings as low as 0.5 mol%. The methyl at C4 effectively shields the bromine from the palladium center in the transition state, elevating the activation energy by an estimated 8–12 kJ·mol⁻¹ relative to the 4-unsubstituted analogue according to DFT studies available in the open literature. Therefore, process chemists selecting this intermediate for library synthesis routinely pre-screen catalyst-ligand combinations via high-throughput experimentation (HTE) on a 10 µmol scale before scaling to the multi-gram range.
Negishi couplings employing organozinc reagents generated from alkyl iodides and Rieke zinc require rigorous exclusion of moisture (≤10 ppm H₂O in THF) to avoid proto-dehalogenation; a pre-drying step over activated 3 Å molecular sieves and a nitrogen-purged glovebox environment is standard practice. In a manufacturing context, batch-to-batch variability in the zinc activation step has been traced to trace peroxide levels in aged THF, quantifiable via iodometric titration (ASTM E475-16). Sonogashira coupling with trimethylsilylacetylene progresses smoothly with CuI (5 mol%) and PdCl₂(PPh₃)₂ (2 mol%) in triethylamine at 50 °C, yielding the 5-alkynyl derivative with ≥90% GC purity after aqueous work-up. Importantly, the 2,4-dimethyl substitution pattern suppresses unwanted Glaser-type homocoupling of the alkyne component, an advantage over less sterically demanding 2-unsubstituted thiazoles where oxidative dimerization frequently consumes 15–25% of the terminal acetylene.
Liquid-phase handling of 5-bromo-2,4-dimethyl-1,3-thiazole on automated synthesis platforms requires careful calibration of dispensing parameters due to its density and moderate viscosity. When aspirated through a 1 mm PTFE transfer line under 0.5 bar positive argon pressure, a 5.0 mL aliquot displays a gravimetric repeatability of ±0.03 g (n=20), which is acceptable for library production but inadequate for kilo-scale manufacturing; at scales above 500 g, direct addition through a mass flow meter with a Coriolis sensor is substituted to meet a target dosing accuracy of ±0.1%. Maintenance logs from contract manufacturing organizations note that prolonged storage of the neat liquid in stainless-steel containers at ambient temperature accelerates pitting corrosion on 316L surfaces if the storage atmosphere is not rigorously dry; a specification of ≤5 ppm aqueous content is enforced, with periodic inspection per NACE TM0169.
Regioselective deprotonation of the thiazole ring offers a complementary route to elaborate the heterocycle. Treatment with lithium diisopropylamide (LDA, 1.2 equiv) in anhydrous THF at −78 °C abstracts the C2-methyl proton adjacent to the ring nitrogen; the resulting stabilized lithiated species quenches with halogen electrophiles to install a second halogen at the exocyclic methyl position. For example, addition of hexachloroethane yields the chloromethyl derivative in 70–78% isolated yield. Crucially, competing lithium-halogen exchange at the C5 bromine is kinetically suppressed at this temperature, as evidenced by the absence of debrominated product in quenched reaction aliquots analyzed by GC-MS. This selectivity profile is reversed in 4-bromo-2,5-dimethylthiazole, where the bromine atom’s adjacency to the ring sulfur enhances its electrophilicity and leads to predominant metal-halogen exchange within 10 min at −78 °C. Thus, the 5-bromo-2,4-dimethyl isomer is uniquely suited for sequential functionalization campaigns in which the bromine is reserved for a late-stage cross-coupling step after the methyl group has been derivatized.
Scale-up of the lithiation step in a 100 L glass-lined reactor with a jacket temperature of −75 °C requires controlled addition of LDA solution over 90–120 min to keep the internal temperature below −65 °C; failure to maintain this window results in a 10–15% increase in the debrominated impurity that is difficult to remove by fractional distillation. Post-quench, the reaction mass is neutralized with acetic acid in toluene and washed with brine, after which the organic layer is dried over Na₂SO₄ and concentrated under reduced pressure (≤50 mbar, bath ≤40 °C). The crude oil is then purified by short-path distillation, collecting the fraction boiling at 92–95 °C at 0.5 mbar.
Material cut from the first 10% of the distillate invariably contains higher levels of a ring-opened thioamide by-product arising from trace water ingress during the lithiation; this cut is discarded or recycled by hydrolysis to the parent thiazole. Operators on the line reference an internal process control protocol aligned with the principles of ISO 9001:2015 Clause 8.5.2 to document these fractionation decisions. The purified product is stored under argon in amber glass bottles at 2–8 °C, where stability data compiled over 36 months indicate ≤0.2% decomposition per year when headspace moisture is excluded. Exposure to ambient air (relative humidity >60%) without desiccant cap leads to gradual darkening and a 2–3% purity drop within 48 h, attributed to oxidative hydrolysis of the thiazole ring. Thus, handling protocols mandate a purged, airtight transfer system during dispensing.
| Property | 5-Bromo-2,4-dimethyl-1,3-thiazole | 2-Bromo-4-methylthiazole | 5-Bromo-2-methylthiazole |
|---|---|---|---|
| CAS | 545431-98-5 | 63806-92-2 | 63806-96-6 |
| Melting range (°C) | 22–25 | 41–44 | 31–34 |
| Boiling point (°C/mbar) | 105–108 / 12 | 75–78 / 15 | 82–85 / 10 |
| Purity specification (GC, area%) | ≥97.0 | ≥98.0 | ≥97.5 |
| Residual Pd (ppm) | ≤50 | ≤30 | ≤40 |
| Relative cross-coupling rate1 | 1.0 | 3.2 | 2.5 |
1Relative Suzuki coupling rate with 4-methoxyphenylboronic acid, Pd(PPh₃)₄ 1 mol%, K₂CO₃, THF/H₂O, 65 °C. Rate constant kobs normalized to 5-bromo-2,4-dimethyl-1,3-thiazole = 1.0.
The 2,4-dimethyl substitution pattern also influences the compound’s behavior as a ligand precursor. Attempts to convert the bromide into a phosphine ligand via lithium-bromine exchange followed by treatment with chlorodiphenylphosphine succeed with 60–65% yield, but the resulting 5-diphenylphosphino-2,4-dimethylthiazole displays a markedly lower donating capacity (Tolman electronic parameter χ ≈ 15.2) compared to the 2-phosphino isomer due to the electron-withdrawing effect of the adjacent sulfur. This weakens its binding to palladium(II) in catalytic cycles, making it less suitable for demanding reductive elimination steps. In practice, it finds utility as a labile ligand in copper-catalyzed click chemistry, where dissociation is beneficial.
When 5-bromo-2,4-dimethyl-1,3-thiazole is employed as the electrophilic component in a Buchwald-Hartwig amination, the anticipated C–N bond formation competes with direct ring-opening at elevated temperatures. Screening data from a 24-well parallel pressure reactor (each well 6 mL working volume) identified a narrow thermal window: with BrettPhos Pd G3 precatalyst (1.5 mol%) and sodium tert-butoxide in dioxane, full conversion to the 5-aminothiazole requires 105 °C over 16 h, while excursions beyond 110 °C generate a colored polar impurity consistent with thiazole ring fragmentation (confirmed by LC-MS, [M+H]+ = 162.1). Maintaining internal temperature within ±3 °C of the setpoint is therefore critical; this is achieved with a jacketed reactor equipped with a PID controller tuned for a 2.5-second derivative time to dampen exothermic peaks during catalyst injection. Published data for this specific configuration is limited to proprietary process development reports, but the general thermal lability of 5-halothiazoles above 120 °C is corroborated by differential scanning calorimetry studies (ΔHdecomp ≈ −450 J·g⁻¹), placing it in the same risk category as other electron-deficient heteroaryl halides. On the isolation side, the aqueous solubility of the product 5-amino-2,4-dimethylthiazole is pH-dependent; achieving an effective extraction into methyl tert-butyl ether demands adjustment of the aqueous phase to pH 5.0 with dilute acetic acid. At pH 7.0, loss to the aqueous layer exceeds 8% per extraction cycle. A post-reaction work-up protocol standardized against USP <1664> guidelines for residual solvents verifies that the MTBE level in the isolated solid is below 500 ppm after drying under vacuum at 45 °C for 12 h.
In agrochemical discovery programs, this thiazole bromide has been utilized to prepare 2,4-dimethyl-5-arylthiazole fungicide candidates. Field trial formulations containing the active ingredient synthesized from this intermediate must comply with CIPAC MT 184 for suspension concentrate stability. Differences in the 2,4-disubstitution pattern alter the leaf-penetration kinetics relative to 4-methyl-only derivatives; a measured octanol-water partition coefficient (log P) of 2.75 for the resulting 5-phenyl derivative increases wax solubility sufficiently to reduce the foliar wash-off rate by 30% under simulated rainfall (mm/h intensity per ASTM E1700). Such data informs the selection of this specific isomer over other bromothiazoles in early-stage structure-activity-relationship campaigns.
| Standard / Regulation | Applicable Aspect | Compliance Parameter |
|---|---|---|
| REACH (EC) No 1907/2006 | Registration, volume tracking | Tonnes per annum threshold 1–10 t/a |
| FDA 21 CFR 175.105 | Indirect food additive (adhesives) | Residual level ≤5 ppb in food simulant |
| ASTM D7359-18 | Halogen determination via oxidative pyrohydrolytic combustion | Total bromine content 41.2–42.5% w/w (theor. 41.82%) |
| ISO 14597:1997 | Chlorine/bromine ratio check by XRF | Cl impurity ≤200 ppm |
Process safety evaluations must account for the exothermic decomposition of neat 5-bromo-2,4-dimethyl-1,3-thiazole when heated above 200 °C in an adiabatic calorimeter (Phi-factor 1.1). The onset temperature for a detectable self-heat rate of 0.02 °C·min⁻¹ is observed at 165 °C in an ARC (accelerating rate calorimeter) test. Consequently, all distillations are limited to bath temperatures ≤130 °C and vacuum levels no higher than 0.5 mbar. Operators wear positive-pressure respirators when handling drums in unventilated zones, as the compound’s odor threshold is estimated below 1 ppm and acute inhalation toxicity data (OECD 403) indicates an LC₅₀ (rat, 4 h) of 0.8 mg·L⁻¹, classifying it as acutely toxic under GHS Category 3.
