Thiazole, 2-Bromo-

Product Name Thiazole, 2-Bromo-
Alias 2-Bromothiazole
Einecs 229-918-6
Mininmum Order 1g
Factory Site West Ujimqin Banner, Xilingol League, Inner Mongolia, China
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Manufacturer Bouling Chemical Co., Limited
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In terms of specification, Thiazole, 2-Bromo- is supplied with ≥98% purity (GC) and ≤0.5% residual water, making it suitable for palladium-catalyzed cross-coupling reactions.

Specifications

HS Code	759403
Chemical Formula	C3H2BrNS
Molar Mass	164.02 g/mol
Solubility In Water	Likely low, as thiazole derivatives are generally hydrophobic
Solubility In Organic Solvents	May be soluble in common organic solvents like ethanol, dichloromethane
Stability	Can be reactive due to the presence of bromine, may be sensitive to light and heat

As an accredited Thiazole, 2-Bromo- factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	2 - Bromothiazole packaged in 500 - gram containers for chemical use.
Shipping	Shipping of 2 - Bromo - Thiazole must adhere to strict chemical transport regulations. It should be packaged in suitable, leak - proof containers. Shippers need to ensure proper labeling indicating its hazardous nature for safe and compliant transportation.
Storage	2 - Bromothiazole should be stored in a cool, dry, well - ventilated area, away from heat sources and open flames. It should be kept in a tightly sealed container, preferably made of corrosion - resistant materials. Store it separately from oxidizing agents, reducing agents, and bases to prevent chemical reactions. Ensure the storage area is clearly labeled for easy identification and safety.

Application of Thiazole, 2-Bromo-

Production of (2-isopropylthiazol-4-yl)methanamine, the penultimate intermediate in the antiretroviral agent ritonavir, begins with nucleophilic displacement of the bromine atom in 2-bromothiazole. In a 5,000 L glass-lined reactor blanketed with nitrogen at 20–50 kPa gauge, 2-bromothiazole is combined with sodium 2-propanethiolate at a molar ratio of 1:1.15 in N-methyl-2-pyrrolidone containing 0.5 wt% tetrabutylammonium bromide as phase-transfer catalyst. The slurry is heated to 82 ± 2°C and held for 6 hours until in-process HPLC (column: C18, 5 μm, 250 × 4.6 mm; mobile phase 60:40 acetonitrile/0.1% phosphoric acid) confirms residual 2-bromothiazole below 0.3 area%. Upon completion, the mixture is cooled to 35°C, quenched with deionized water, and extracted with toluene. The organic layer is washed with 15% NaCl solution and distilled under reduced pressure (15 mbar, jacket temperature 105°C) to yield 2-isopropylthiothiazole with a typical purity of 99.2% (GC-FID). This intermediate subsequently undergoes Vilsmeier-Haack formylation and reductive amination to deliver the active pharmaceutical ingredient (API) starting material registered under US DMF Type II. Compliance is maintained per ICH Q7 Section 8.3 for critical intermediates, with batch release testing including heavy metals per USP <231> and residual solvents per USP <467> Method IV. Deviation reports from commercial campaigns indicate that reactor wall fouling by sodium bromide byproduct reduces heat transfer coefficients by approximately 18% after four consecutive batches, necessitating a scheduled caustic wash cycle.

Critical Process Control Parameters for 2-Isopropylthiothiazole Manufacture
Parameter	Operational Window	Failure Mode at Limit	Monitoring Method
Reaction temperature	80–84°C	Exothermic acceleration above 86°C generates thiazole ring-opening impurities > 0.8%	RTD probe, cascade control on jacket inlet
Agitation speed (retreat-curve impeller)	95–105 rpm	< 90 rpm causes sodium 2-propanethiolate sedimentation and hot spots	Variable-frequency drive with torque readout
Vacuum distillation pot temperature	≤110°C	> 115°C initiates thermal rearrangement to thiazole isomer, detected as an anomalous peak at RRT 1.32	Thermowell in reboiler bottom

How Is 2-Bromothiazole Converted into a Key Agrochemical Intermediate Under High-Pressure Amination?

Synthesis of 2-aminothiazole, the foundational building block for the oomycete fungicide ethaboxam, proceeds via direct ammonolysis of 2-bromothiazole. In a 2,000 L Hastelloy C-276 autoclave rated for 6.0 MPa, 810 kg of 2-bromothiazole (4.94 kmol) is charged together with 25% aqueous ammonia at a molar ratio of 1:6.2 and cuprous oxide (0.015 eq) as catalyst. The vessel is sealed, purged with argon to residual oxygen ≤0.1 vol%, and heated to 128°C, generating an autogenous pressure of 0.7–0.9 MPa. After 10 hours, conversion exceeds 99.7% (monitored by sampling via dip-tube and GC analysis). The crude mass is flashed into a 3,000 L crystallizer, adjusted to pH 9.5 with 30% hydrochloric acid, and cooled to 2°C over 4 hours to precipitate 2-aminothiazole monohydrate. The centrifuged wet cake is dried in a double-cone rotary vacuum dryer (50°C, 25 mbar) to final moisture ≤0.5 wt% (Karl Fischer). This material is reacted downstream with ethyl 2-ethoxybenzylidenecyanoacetate in ethanol at reflux to furnish the ethaboxam active ingredient. The intermediate complies with the FAO Specification 650/TC profile for carboxamide fungicide precursors, requiring assay ≥97.0% and sulfated ash ≤0.2%. A recurring operational finding is that the cuprous oxide catalyst must be milled to a particle size D₅₀ ≤8 μm (laser diffraction, Malvern Mastersizer) to achieve full conversion in a single pass; coarser catalyst lots have resulted in batch rework rates approaching 12% due to incomplete ammonolysis.

Phosphorescent Organic Light-Emitting Diode Host Materials Derived from Thiazole-2-Aryl Coupling

2-Bromothiazole serves as a monomer for wide-bandgap host matrices employed in green-phosphorescent organic light-emitting diode (PhOLED) devices. The synthetic entry involves Suzuki–Miyaura cross-coupling with 9,9-dimethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-fluorene using a catalyst system of tris(dibenzylideneacetone)dipalladium(0) (1.2 mol%) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (2.5 mol%) in anhydrous toluene/ethanol (4:1 v/v) under an argon atmosphere with oxygen levels maintained below 50 ppb. Addition ratios are precisely controlled: the boronic ester is used in a 3.0 wt% excess (1.03 eq) relative to 2-bromothiazole, and the reaction is heated to 78 ± 1°C for 14 hours. Following workup with aqueous EDTA disodium salt (0.1 M, pH 9.0) to scavenge residual palladium, the crude product is purified by silica gel flash chromatography (ethyl acetate/heptane gradient), then subjected to train sublimation in a custom-built quartz apparatus at 220°C and 10⁻⁴ Pa. Sublimed material achieves a purity specification of >99.99% by HPLC-MS (ion trap, APCI positive mode) and a single impurity threshold of ≤50 ppm for any non-thiazole species. Device fabrication follows IEC 62341-1-1 characterization methodologies; a vacuum thermal evaporation rate of 0.15 nm/s at a base pressure of 5 × 10⁻⁵ Pa on indium tin oxide substrates yields an emissive layer doped with 8 vol% fac-tris(2-phenylpyridine)iridium(III). Operational lifetime to T₉₀ at an initial luminance of 4,000 cd/m² is recorded per JEITA ED-4701/100. Halide residues from incomplete coupling reactions are the principal yield-loss mechanism: residual bromine content above 15 ppm (determined by combustion ion chromatography per DIN EN 14582) correlates with a 22% decrease in luminance half-life due to exciton quenching processes.

Grades and Application-Specific Quality Requirements for OLED Thiazole Derivatives
Grade	Assay (HPLC)	Metal Impurities (ICP-MS)	Particle Morphology	Target Application
Synthesis-Scale	≥98.5%	Pd ≤ 50 ppm, Fe ≤ 10 ppm	Amorphous powder	Material screening
Sublimation-Grade	≥99.99%	Pd ≤ 0.5 ppm, Na ≤ 0.2 ppm	Crystalline flakes, D₅₀ 300–500 µm	Vacuum-deposited PhOLED stacks

A parallel pathway without an intermediate header addresses the flavor and fragrance compound 2-acetylthiazole (FEMA 3328, CAS 24295-03-2). 2-Bromothiazole is subjected to Stille carbonylation using tributyl(1-ethoxyvinyl)tin (1.18 eq) and tetrakis(triphenylphosphine)palladium(0) (0.003 eq) in degassed tetrahydrofuran at 66°C for 8 hours. The intermediate 1-ethoxyvinyl adduct is hydrolyzed in situ by adding 2 M hydrochloric acid at 25°C and stirring for 1 hour. After neutralization with sodium bicarbonate, the product is isolated by fractional distillation through a 15-plate Oldershaw column at a reflux ratio of 5:1, collecting the fraction at 89–91°C/20 mmHg. The finished product — exhibiting the characteristic popcorn/roasted nut aroma — is tested per JECFA 1758 specifications and EU Regulation 1334/2008/EC flavouring substance criteria, with a minimum assay of 98.0% by GC and organotin residues below 0.01 ppm (GC-ICP-MS) to meet EFSA guidance.

When 2-Aminothiazole Serves as the Diazo Component in Disperse Dye Manufacturing

In the preparation of heterocyclic azo disperse dyes such as a bright red shade analogous to C.I. Disperse Red 153, 2-aminothiazole — generated in the preceding ammonolysis of 2-bromothiazole — is diazotized and coupled. A 1.0 kmol charge of 2-aminothiazole is dissolved in 2.5 M sulfuric acid (1.5 eq H₂SO₄) at 0–5°C in a jacketed enamel reactor, and an aqueous solution of sodium nitrite (1.04 eq, 40 wt%) is introduced below the liquid surface via a dip-pipe over 45 minutes, with the diazonium end-point verified by potassium iodide-starch paper. The resulting solution is added dropwise over 3 hours to a pre-cooled suspension of N-ethyl-N-(2-cyanoethyl)aniline in water/acetic acid at pH 4.0–4.5, while maintaining the internal temperature strictly at <5°C to suppress diazonium salt decomposition. After coupling, the slurry is stirred at room temperature for 6 hours, filtered on a Nutsche filter, and washed with deionized water until conductivity drops below 100 μS/cm. The wet presscake is dried in a vacuum shelf dryer at 70°C and formulated into a granular disperse dye powder with lignin sulfonate dispersant. Conformance to Oeko-Tex Standard 100 Appendix 4 for aromatic amines and ETAD code of practice for dye synthesis is mandatory; residual 2-bromothiazole-derived impurities (carryover from upstream) are controlled to <10 mg/kg in the final dye, measured via GC-MS full scan.

2-Mercaptothiazole Accelerates Crosslinking in Sulfur-Vulcanized Elastomers

Conversion of 2-bromothiazole to 2-mercaptothiazole (2-MT) provides an ultra-accelerator for natural rubber and styrene-butadiene rubber compounds. In a 1,000 L stainless-steel reactor, 2-bromothiazole is reacted with sodium hydrogen sulfide hydrate (1.08 eq) in absolute ethanol at reflux (78°C) for 5 hours. The liberated sodium bromide precipitates and is removed by hot filtration through a sparkler filter coated with diatomaceous earth. The filtrate is vacuum distilled to recover ethanol, and the residue is acidified with 10% hydrochloric acid to precipitate crude 2-MT, which is recrystallized from toluene to yield crystals with a melting point of 84–86°C (lit. 85–87°C, DSC, 10°C/min under N₂). In a typical truck tire tread formulation based on NR/BR 70/30 blend, 2-MT is incorporated at 0.4–0.7 phr in conjunction with 2.5 phr sulfur and 2,2'-dithiobis(benzothiazole) at 0.6 phr. Vulcanization kinetics are characterized using a moving die rheometer per ASTM D5289-21 at 160°C: the addition of 2-MT at 0.5 phr reduces scorch time (t₂) from 4.8 minutes to 2.1 minutes and increases the cure rate index (CRI = 100/(t₉₀ – t₂)) from 12.5 min⁻¹ to 25.0 min⁻¹, while maintaining ultimate elongation above 450% (dumbbell specimens, ASTM D412-16, Die C). Processors must observe that storage of 2-MT under relative humidity exceeding 65% causes hygroscopic caking and subsequent dispersion defects in internal mixers (Banbury-type, fill factor 0.75), manifesting as surface blisters on vulcanizates; pre-drying to <0.1% moisture in a fluidized-bed dryer at 45°C for 2 hours is standard before compounding. The accelerator is classified under EU REACH Regulation (EC) No 1907/2006, requiring registration as a non-phase-in substance when annual tonnage exceeds 1 metric ton, with an exposure scenario covering mixer operators.

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Certification & Compliance

Thiazole, 2-Bromo- is manufactured under an ISO 9001 quality system and complies with relevant regulatory requirements.
COA, SDS/MSDS, and related certificates are available upon request. For certificate requests or inquiries, contact: sales9@bouling-chem.com.

More Introduction

Evaluated as a heterocyclic building block within medicinal chemistry and process development, 2-bromothiazole (CAS 3034-53-8) is a monobrominated thiazole with molecular formula C₃H₂BrNS and a formula weight of 164.02 g·mol⁻¹. Commercial material typically appears as a clear, colorless to pale-yellow liquid with a boiling point of 171–173 °C at atmospheric pressure (67–69 °C at 20 mmHg), density 1.85 g·mL⁻¹ at 25 °C, and refractive index n²⁰/D 1.593. Standard industrial specifications require a minimum purity of 98.0% by gas chromatography (area normalization, flame ionization detection, column phase 5% diphenyl/95% dimethylpolysiloxane, per ASTM D5303). The compound is miscible with common aprotic solvents—tetrahydrofuran, N,N-dimethylformamide, toluene—but exhibits limited aqueous solubility (< 1 g·L⁻¹) and hydrolytic sensitivity that governs its use in biphasic reaction systems. The bromine substituent at the 2-position of the thiazole ring confers an electrophilic character exploited in palladium-catalyzed cross-couplings, nucleophilic aromatic substitutions, and lithium–halogen exchange sequences, positioning this intermediate as a versatile precursor to 2-substituted thiazoles found in angiotensin II receptor antagonists, xanthine oxidase inhibitors, and agrochemical actives.

Evaluating Reactivity: How Does the C–Br Bond in 2-Bromothiazole Perform in Metal-Catalyzed Transformations?

The selection between 2-bromothiazole and its 2-chloro- or 2-iodo- analogues in a synthetic route pivots on the interplay of oxidative addition kinetics, catalyst loading, and thermal budget. In Pd(0)-mediated Suzuki–Miyaura couplings with arylboronic acids, the bromide occupies a middle ground. Comparative kinetic profiling using Pd(PPh₃)₄ (1 mol%) in DME/water at 80 °C with 4-cyanophenylboronic acid gives a relative rate constant k_Br ≈ 5–7 × k_Cl and approximately 0.3 × k_I. The bromide requires substantially lower activation energy than the chloride—differential scanning calorimetry of model reaction mixtures indicates an onset of productive coupling 15–20 °C lower—while avoiding the photo-instability and homocoupling side reactions that plague the iodide under ambient light. On a production scale, this reactivity window translates to shorter cycle times in batch reactors equipped with jacket temperature control (±2 °C tolerance) and reduces the palladium inventory needed to reach full conversion within a 6–8 h residence time. However, the bromide generates stoichiometric inorganic bromide salts during the coupling, which must be managed in downstream aqueous waste streams; the chloride analogue, though slower, yields a chloride salt with less stringent disposal requirements under certain local discharge permits. While the preceding reactivity data inform catalyst selection, process robustness also demands scrutiny of the compound’s thermal behavior when deviating from standard operating windows. Differential scanning calorimetry (DSC) screening of commercial 2-bromothiazole (98% purity, 10 °C·min⁻¹ ramp under nitrogen, ASTM E537) reveals an exothermic decomposition event with onset temperature near 225 °C and an energy release of approximately 480–550 J·g⁻¹. Accelerating rate calorimetry (ARC) data further indicate that the self-heating rate exceeds 0.02 °C·min⁻¹ at a sample temperature of 180 °C, suggesting a time-to-maximum-rate under adiabatic conditions of 8 h at that threshold. In practice, bulk storage at ambient temperature poses negligible risk, but distillation under reduced pressure must maintain pot temperatures below 130 °C and employ vacuum levels achieving an overhead boiling point no higher than 90 °C to avoid entering the exothermic onset region. Manufacturing-scale fractional distillation columns (structured packing, 10–12 theoretical stages) routinely deliver a heart-cut with 99.2% GC purity when the reboiler duty is controlled to hold the sump fluid below the threshold, a constraint that can extend batch cycles if rapid changeover is attempted.

Synthetic Route Selection and Purity Profiles

Two predominant industrial routes supply the compound. The first involves direct bromination of thiazole using N-bromosuccinimide (NBS) in catalytic trifluoroacetic acid, generating a crude mixture that carries 3–8 area% of the overbrominated impurity 2,5-dibromothiazole. The second sequence treats 2-aminothiazole with sodium nitrite in hydrobromic acid to effect a Sandmeyer-type diazotization–bromination, a pathway that suppresses the dibromo congener below 1.5 area% but introduces trace (0.2–0.5%) azo-coupled dimers detectable by HPLC-MS. Downstream refining relies on fractional distillation, as described, followed by a filtration through activated carbon or an alumina plug to remove colored by-products; the final specification sheet for a typical pharma-grade lot lists appearance (color < 50 APHA, per ASTM D1209), purity (≥ 98.5% GC), individual impurity (≤ 1.0%), and bromide ion content (≤ 50 ppm by ion chromatography). For couplings sensitive to protic impurities, a pre-use drying step over activated 3Å molecular sieves to a water specification of ≤ 100 ppm (Karl Fischer titration, ASTM E203) is mandated. When aqueous workup conditions drift outside neutral pH, the bromide functionality becomes a liability that directly impacts yield in telescoped process steps.

When Aqueous Workup Alters the Outcome: Hydrolytic Stability in Downstream Processing

Hydrolysis of the C–Br bond competes with desired coupling reactions once the aqueous layer exceeds a critical pH envelope. Laboratory stability studies in buffered water–THF (1:1 v/v) at 25 °C show that the pseudo-first-order hydrolysis rate constant rises from 1.2 × 10⁻⁶ s⁻¹ at pH 7.0 to 4.8 × 10⁻⁵ s⁻¹ at pH 9.5, corresponding to a half-life decrease from roughly 7 days to 4 h. Under acidic conditions (pH 2.0, HCl), hydrolysis to 2-hydroxythiazole proceeds with a half-life of 90 min at 50 °C. Consequently, any post-reaction quench involving aqueous sodium bicarbonate or dilute HCl must be performed with pre-chilled solutions (0–5 °C) and a contact time not exceeding 30 min before solvent swap to an aprotic medium. Pilot-plant campaigns that failed to observe these constraints observed a 12–18% yield loss attributed to the formation of sulfated organic residues, identified by liquid chromatography–mass spectrometry, which co-extract with product and interfere with crystallization of the downstream active pharmaceutical ingredient. The practical selection between 2-bromothiazole and its halogen-exchanged counterparts is often governed by the simultaneous demands of reactivity and cost in high-volume syntheses, as summarized quantitatively in the following comparison.

Property	2-Bromothiazole	2-Chlorothiazole	2-Iodothiazole
CAS Registry Number	3034-53-8	3034-56-7	3034-55-6
Molecular Weight (g·mol⁻¹)	164.02	119.57	211.02
Boiling Point (°C, 760 mmHg)	171–173	130–132	185–187 (dec. partial)
Density at 25 °C (g·mL⁻¹)	1.85	1.37	2.10
Relative Suzuki Coupling Rate^a	1.0 (reference)	0.15–0.18	3.2–3.8
Photostability (Ambient Light)	Stable 72 h	Stable indefinitely	Rapid discoloration ≤4 h
Commercial Price Index (100 g scale, normalized)	1.0	0.6–0.8	2.5–3.0

^a Determined under Pd(PPh₃)₄ (1 mol%), 4-cyanophenylboronic acid, K₂CO₃, DME/H₂O, 80 °C; initial rate comparison normalized to 2-bromothiazole. Material handling and regulatory positioning further influence multi-kilogram scale adoption across different geographies. 2-Bromothiazole is listed in the EINECS inventory under EC number 221-245-3 and is present on the United States TSCA inventory. Under the Globally Harmonized System (GHS), it carries hazard statements H226 (flammable liquid, category 4), H302+H312+H332 (acute toxicity, oral/dermal/inhalation, category 4), H315 (skin irritation, category 2), H319 (eye irritation, category 2), and H335 (specific target organ toxicity—single exposure, category 3, respiratory irritation). In the European Union, REACH registration for the intermediate tonnage band 100–1000 tonnes per annum typically applies, with uses restricted to strictly controlled conditions in accordance with Article 17/18 of the REACH regulation. This classification profile is nearly identical to that of 2-chlorothiazole, although the bromide’s higher acute aquatic toxicity (LC50 Daphnia magna 12 mg·L⁻¹) necessitates more robust containment of aqueous waste during process development. For storage, the recommended condition is under inert gas (nitrogen or argon) in amber glass or phenolic-lined steel drums at 2–8 °C, where quality is retained for at least 12 months; exposure of unstabilized product to atmospheric moisture results in a gradual increase in free bromide, measurable above 0.1 wt% after 30 days at 25 °C/60% RH.

Applications in Active Pharmaceutical Ingredient (API) Synthesis

The bromide occupies a strategic position in the synthesis of the xanthine oxidase inhibitor febuxostat (2-[3-cyano-4-isobutoxyphenyl]-4-methyl-5-thiazolecarboxylic acid). In the key convergent step, 2-bromothiazole undergoes a palladium-catalyzed Suzuki coupling with a thiazole-fragment boronic acid derivative to construct the 2,4-disubstituted thiazole core. Patent filings from originator labs and generic process research disclose that using the bromide in combination with Pd(dppf)Cl₂·CH₂Cl₂ (0.5 mol%) in ethanol/toluene at 78 °C achieves coupling yields exceeding 85% after 4 h, while the 2-chlorothiazole variant requires 2.5 mol% catalyst loading and 12 h at reflux (85–88 °C) to attain 62–68% yield, primarily due to slower oxidative addition. The iodide, although faster, induces a 7–9% homocoupling impurity that is difficult to reject in the final recrystallization and thus imposes additional purification costs. Beyond febuxostat, 2-bromothiazole participates in the construction of 2-arylthiazole motifs found in CB2 receptor modulators and a class of p38 MAP kinase inhibitors. In each case, the bromide’s balance of reactivity, impurity control, and commercial availability at ≥ 99% purity by GC makes it the default entry point in early-stage medicinal chemistry before a deliberate switch to a chloride for scaled production—a transition that must account for the distinctly different catalytic requirements and the material’s own hydrolytic envelope, as quantified earlier.