2-Bromo-5-Nitrothiazole

What Interferes with Catalytic Hydrogenation Selectivity in the Production of Aminothiazole Agrochemical Building Blocks?

The reduction of 2-Bromo-5-Nitrothiazole to the corresponding 5‑aminothiazole derivative serves as a critical entry point for insecticidal active ingredients structurally related to clothianidin and thiamethoxam. In a typical hydrogenation sequence, a 0.5 M solution of the nitrothiazole in anhydrous ethanol is loaded into a Büchi miniclave glass pressure reactor equipped with a magnetically driven gas-entrainment impeller operating at 1000 rpm. 5% Pd/C (dry basis, 10 wt% relative to substrate) is charged, and the reactor is purged with nitrogen three times followed by hydrogen to 3.0 bar. The exotherm is maintained at 25 °C using a Huber Unistat 705 circulator with internal coil cooling. Under these conditions complete nitro consumption is observed by TLC within 2.5 hours. However, a competing hydrodebromination pathway generates 5‑aminothiazole as a persistent byproduct, typically at 3–7 area% when reaction time exceeds 4 hours or when the hydrogen pressure surpasses 3.5 bar. To suppress debromination without sacrificing conversion, the pH of the reaction medium is buffered to 4.5–5.0 with pre-ground ammonium acetate (0.05 M). In laboratories transferring this process to continuous flow, a ThalesNano H‑Cube Pro with a 30 mm × 4 mm cartridge containing 5% Pd/Al₂O₃ operated at 0.5 mL·min⁻¹ and 50 °C delivers a steady‑state selectivity of >97% for the bromoamine, as confirmed by inline ReactIR monitoring at 1540 cm⁻¹. The crude aminothiazole is isolated by filtration through Celite® 545, concentration under 40 mbar at 35 °C on a rotary evaporator, and trituration with n‑heptane. Material intended for subsequent neonicotinoid scaffold construction is required to meet CIPAC Handbook J guidelines for water content (<0.2% by Karl Fischer titration) and residual palladium (<5 ppm as determined by ICP‑OES on an Agilent 5110 instrument). Downstream coupling with 2‑chloro‑5‑chloromethylthiazole under phase‑transfer conditions (tetrabutylammonium bromide 5 mol%, 50% aqueous NaOH/toluene biphasic) yields the insecticidal α‑aminothiazole acetylcholine receptor modulator, whose batch release is governed by EPA 40 CFR Part 158 five‑batch analysis requirements and the FAO specification 582/TC for technical material.

Scale‑up batches exceeding 50 kg input are run in a Hastelloy C‑276 stirred autoclave with a 2:1 liquid‑to‑gas volume ratio and a triple‑stage Cowles‑type impeller. The hydrogen uptake profile is tracked via a Bronkhorst EL‑FLOW mass flow controller, and termination is triggered automatically when uptake drops below 2 mL·min⁻¹. Off‑gas is scrubbed through a 5% sodium hydroxide solution to trap any HBr liberated during prolonged hold periods at elevated temperature. Post‑filtration, the catalyst is washed with DMF and reclaimed for up to six cycles before palladium leaching exceeds 0.2 ppm in the filtrate. Every production campaign mandatorily segregates the first 3 kg of isolated solid for extended impurity profiling according to ICH Q3A thresholds: individual unspecified impurities are limited to 0.10%, and total impurities to 0.5%, with identification of any component present above the 0.10% limit required before lot disposition. The nitro‑to‑amine conversion step thus constitutes a gate‑keeping intermediate whose analytical fingerprint directly determines the regulatory acceptability of the finished crop protection active.

When 2-Bromo-5-Nitrothiazole Is Used as a Diazo Component in Disperse Dye Synthesis, What Determines Alkali‑Stripping Fastness?

Diazotisation of 2-Bromo-5-Nitrothiazole proceeds readily in a mixture of 85% phosphoric acid and glacial acetic acid (1:3 v/v) at 0–5 °C using a slight excess of nitrosylsulfuric acid prepared from sodium nitrite (1.05 molar equivalents) and concentrated sulfuric acid. The resulting diazonium solution is clarified by rapid filtration through a jacketed sintered‑glass funnel connected to a Lauda RP 290 E chiller set to −5 °C. The coupling component — typically N,N‑diethyl‑m‑toluamide or N‑ethyl‑N‑(2‑hydroxyethyl)aniline — is dispersed in ice‑water containing 0.1% sulfamic acid and 2% dispersant (Lignosol® D‑10), and the diazonium liquor is added dropwise under vigorous stirring provided by a Silverson L5M‑A high‑shear mixer operating at 4000 rpm. Internal pH is maintained at 3.5–4.0 with pre‑chilled 20% sodium acetate solution, and coupling is complete within 90 minutes as verified by the absence of a positive reaction with alkaline H‑acid test solution. The precipitated crude dye is isolated on a Nutsche filter, washed to conductivity <200 µS·cm⁻¹, and oven‑dried at 60 °C under −0.8 bar vacuum.

Formulation into a commercial disperse dye requires micronisation in a horizontal bead mill (Netzsch LabStar) charged with 0.3–0.5 mm yttria‑stabilised zirconia beads to a mean particle size D₅₀ < 1.0 µm measured on a Malvern Mastersizer 3000. The milling suspension contains 30% dye solids, 5% sodium lignosulfonate, and 0.5% wetting agent; milling energy input is controlled below 0.8 kWh·kg⁻¹ to prevent crystal‑phase transformation that can reduce colour strength. The final paste is spray‑dried on a Niro Mobile Minor at an inlet temperature of 180 °C and outlet temperature of 85 °C. The dye imparts an orange hue to polyester fabric applied by high‑temperature exhaustion at 130 °C for 45 minutes at a liquor ratio of 10:1, and its fastness properties are evaluated against ISO 105‑C06:2010 (C2S) for washing, ISO 105‑B02:2014 for light, and ISO 105‑X12:2016 for rubbing. While the bromine substituent improves electron‑withdrawing character and bathochromic shift, the 5‑nitro group is susceptible to reductive clearing agents containing sodium hydrosulfite; thus the recommended after‑clearing employs 2 g·L⁻¹ sodium carbonate and 1 g·L⁻¹ a non‑ionic soaping agent at 80 °C rather than standard reduction‑clear sequences. Finished dyes placed on the European market are accompanied by a certificate of compliance with REACH Regulation (EC) No 1907/2006 Annex XVII entries 43 and 72, and an OEKO‑TEX® Standard 100 class I attestation that the colorant does not cleave to the restricted arylamine inventory listed under Commission Regulation (EU) 2024/2462. Additionally, the manufacturing facility’s wastewater discharge permit typically requires biological oxygen demand after 5 days (BOD₅) testing per ISO 5815‑1:2019 to remain below the local consent level, as the nitro‑thiazole chromophore resists biological degradation in conventional activated‑sludge treatment.

In the synthesis of second‑generation nitazoxanide analogs possessing an extended 2‑amino‑5‑nitrothiazole pharmacophore, 2-Bromo-5-Nitrothiazole serves as the key electrophilic partner in a palladium‑catalyzed C–N cross‑coupling sequence that circumvents the harsh conditions of classical nucleophilic aromatic substitution. A dry three‑neck round‑bottom flask fitted with a J. Young’s PTFE valve and a magnetic stirring bar is charged with 2-Bromo-5-Nitrothiazole (1.00 mmol, 209.0 mg), 4‑(trifluoromethoxy)aniline (1.10 mmol), Pd₂(dba)₃ (0.025 mmol, 22.9 mg), Xantphos (0.06 mmol, 34.7 mg), and finely ground anhydrous cesium carbonate (2.50 mmol, 814.5 mg). The vessel is evacuated and backfilled with argon five times through a dual‑manifold vacuum line operating at 0.08 mbar. Deoxygenated 1,4‑dioxane (5.0 mL) is added via syringe, and the heterogeneous mixture is heated to 95 °C using an oil bath controlled by a J‑KEM Scientific Gemini PID temperature controller with a ±0.5 °C deadband. Reaction progress is monitored by withdrawing 20 µL aliquots through a septum‑sealed side‑arm, quenching into 0.5 M aqueous ammonium chloride, and analyzing on an Agilent 1260 Infinity II HPLC with a ZORBAX Eclipse Plus C18 column (4.6 × 100 mm, 3.5 µm), eluting with acetonitrile:water 60:40 at 1.0 mL·min⁻¹ and detecting at 365 nm. Complete consumption is reached after 14–16 hours. At this point, the deep red solution is filtered hot through a 0.2 µm PTFE syringe filter to remove cesium salts, concentrated under reduced pressure at 40 °C, and dry‑loaded on Sigma‑Aldrich silica gel 60 (230–400 mesh) for flash chromatography. Elution with n‑hexane:ethyl acetate 4:1 yields the target N‑(4‑(trifluoromethoxy)phenyl)‑2‑amino‑5‑nitrothiazole as a yellow crystalline solid (typical yield 82–88%), whose structure is confirmed by ¹H‑NMR (Bruker Avance III HD 500 MHz, CDCl₃) and high‑resolution mass spectrometry (Thermo Fisher Q Exactive Focus, positive ESI, resolution 70,000).

Electron‑withdrawing groups on the aryl amine slow the oxidative addition step; therefore, when 4‑cyano‑ or 4‑acetyl‑anilines are employed, the catalyst loading is increased to 4 mol% Pd₂(dba)₃ and 10 mol% DavePhos, and the temperature is ramped to 105 °C for 24 hours. The core risk in this transformation lies not in the coupling efficiency but in the integrity of the 5‑nitro group, which can undergo partial reduction by the Pd(0)‑ligand complex if dissolved oxygen content exceeds 1 ppm or if the dioxane is not freshly distilled from sodium‑benzophenone ketyl. Consequently, a Mettler Toledo InPro 6900 optical dissolved oxygen probe inserted into the reaction mixture through a 19/26 Quickfit port is used to trigger an abort if O₂ readings exceed 0.8 ppm at any point during the initial 3 hours of heating. Scale‑up to 500 gram input is carried out in a 20 L jacketed De Dietrich glass‑lined reactor equipped with a Ekato PBT‑n impeller and a Teflon‑encapsulated thermocouple. In this configuration, the exothermic solvation of cesium carbonate in dioxane is managed by programmed jacket temperature ramping at 0.5 °C·min⁻¹ to avoid an initial overshoot beyond 100 °C. The final isolated batch must pass residual metal analysis by ICP‑MS (Agilent 7800) with a palladium specification of <10 ppm and a cesium specification of <50 ppm to enter the next GMP step in the synthesis of antiprotozoal lead candidates. Compliance with ICH Q7 for Good Manufacturing Practice of active pharmaceutical ingredients dictates that the intermediate be stored in double polyethylene liners within a fiber drum under a nitrogen atmosphere, and that maximum hold time between drying and use be limited to 14 days at controlled room temperature (20–25 °C), with data logged against 21 CFR Part 11 compliant electronic records.

Table 1. Summary of Acceptance Criteria and Test Methods Across Application Classes

Application Segment

Key Specification

Method

Acceptance Limit

Pharmaceutical Intermediate (C–N Coupling)

Purity (by HPLC at 365 nm)

EP 10.0, 2.2.29

≥ 99.0 area%

Agrochemical Intermediate (Hydrogenation)

Residual Palladium

USP <232> / ICH Q3D

< 5 ppm

Disperse Dye Component

Reduction‑Clear Resistance

ISO 105‑C06:2010, C2S

Shade change ≥ 4‑5 grey scale

Electronic‑Grade Coupling Component

Total Metal Impurities (ICP‑MS)

SEMI C63‑0222 (modified)

Each element < 1 ppm, sum < 5 ppm

Suzuki‑Miyaura Monomer Synthesis for Low‑Bandgap Photovoltaic Polymers

Incorporation of the electron‑deficient 5‑nitrothiazole core into donor‑acceptor (D‑A) type conjugated polymers demands a cross‑coupling protocol that preserves the bromine electrophilicity while tolerating the nitro group throughout the catalytic cycle. 2-Bromo-5-Nitrothiazole is subjected to Suzuki‑Miyaura coupling with 2‑(tributylstannyl)thiophene or the corresponding boronic ester to build the extended π‑system required for organic photovoltaic (OPV) donor materials. In a typical procedure performed entirely inside an argon‑filled glovebox (MBraun LABmaster pro, <0.1 ppm H₂O, <0.1 ppm O₂), a 50 mL Schlenk tube is loaded with the nitrothiazole (1.00 equiv, 1.00 mmol), 5′‑(4,4,5,5‑tetramethyl‑1,3,2‑dioxaborolan‑2‑yl)‑2,2′‑bithiophene (1.20 equiv), Pd(PPh₃)₄ (0.05 equiv, 57.8 mg), and anhydrous potassium phosphate (3.00 equiv). The solids are dissolved in a degassed mixture of toluene:water (5:1, 12 mL total), the valve is sealed, and the tube is removed from the glovebox. The reaction is stirred at 850 rpm in a pre‑heated aluminum block set to 100 °C for 18 hours. Upon completion, the aqueous phase is separated, and the organic layer is washed with brine (3 × 5 mL), dried over MgSO₄, and concentrated. Purification is carried out by automated flash chromatography on a Biotage Isolera One using a 25 g SNAP Ultra silica cartridge, with an n‑hexane to ethyl acetate gradient from 0 to 30% over 20 column volumes. The product, a dark‑red solid, is further purified by temperature‑gradient sublimation in a three‑zone furnace at 1 × 10⁻⁶ mbar, with the hot zone set to 180 °C and the cool zone to 80 °C, yielding needle‑like crystals of ≥ 99.5% purity as assessed by differential scanning calorimetry (Mettler Toledo DSC 3+, heating rate 10 K·min⁻¹) showing a single melting endotherm.

The monomer’s HOMO and LUMO energy levels are determined by cyclic voltammetry using a Metrohm Autolab PGSTAT302N with a three‑electrode configuration (glassy carbon working, Pt wire counter, Ag/Ag⁺ non‑aqueous reference) in 0.1 M tetra‑n‑butylammonium hexafluorophosphate acetonitrile solution, calibrated against the ferrocene/ferrocenium redox couple. The measured electrochemical bandgap of the polymer, copolymerized with 5,6‑difluoro‑4,7‑dithiophen‑2‑yl‑2,1,3‑benzothiadiazole via Stille polycondensation, is typically in the range of 1.55–1.65 eV, suitable for bulk‑heterojunction devices with PC₇₁BM as acceptor. Films are blade‑coated on ITO/PEDOT:PSS substrates using a Zehntner ZAA 2300 automatic film applicator at a speed of 20 mm·s⁻¹, achieving a dry thickness of 95–105 nm. Device performance is evaluated under simulated AM 1.5G irradiation at 100 mW·cm⁻² with a Wacom WXS‑155S‑L2 solar simulator, following the measurement protocol of IEC 60904‑1:2020. Because trace bromine can quench excitons and reduce fill factor, the monomer is subjected to a strict elemental analysis specification: bromine content measured by combustion ion chromatography (Mitsubishi AQF‑2100H) must be < 50 ppm post‑sublimation. The stringent metal‑ion limits typical of organic electronics, aligned with SEMI C63‑0222 for ultra‑pure chemicals, dictate that iron, nickel, palladium, and copper be individually below 1 ppb in the final monomer lot supplied to device fabrication partners. Storage of the purified material is under vacuum‑sealed ampoules in a −20 °C freezer to prevent spontaneous thermal homocoupling that can produce insoluble oligomers even in the absence of light. This high‑purity monomer supply chain directly supports pilot‑line manufacturing of OPV modules subjected to IEC 61215‑1‑2:2021 damp‑heat testing at 85 °C / 85% RH for 1000 hours, with module power retention exceeding 90% routinely cited when the bromothiazole monomer purity specification is rigorously enforced.

Chemical identity for the compound designated CAS 3034-48-8 is established through orthogonal spectroscopic methods. The molecular formula C₃HBrN₂O₂S corresponds to a monobrominated nitrothiazole with a formula weight of 208.99 g·mol⁻¹. Commercial material is typically supplied as a pale yellow to off-white crystalline powder. Identity confirmation on the production floor routinely employs ¹H NMR spectroscopy at 400 MHz in DMSO-d₆, where the diagnostic singlet for the C-4 proton appears in the region δ 8.8–9.0 ppm. HPLC purity profiling on a C18 reversed-phase column with UV detection at 254 nm and a mobile phase of acetonitrile/water (70:30 v/v) reveals a single dominant peak with a relative retention time of 4.2 ± 0.1 min under isocratic conditions, with the main product peak area exceeding 98.5% in standard-grade lots. Trace impurity profiling via LC-MS identifies des-bromo nitrothiazole and regioisomeric bromonitrothiazoles at individual levels below 0.3 area%. Water content by Karl Fischer coulometry (ASTM E1064) is controlled to ≤ 0.5 wt%, as elevated moisture accelerates hydrolytic debromination during prolonged storage in non-vented containers.

What Differentiates the C-2 Bromine Substituent from C-4 or C-5 Halogenated Thiazoles?

The regiochemical placement of the bromine atom at the 2-position of the thiazole ring imparts a distinct reactivity profile compared to alternative halogenation patterns, notably 2-chloro-5-nitrothiazole (CAS 23567-26-4) and 2-bromo-4-nitrothiazole. The electronegative nitro group at C-5 exerts a strong meta-directing, electron-withdrawing effect, polarising the π-system such that the C-Br bond at the 2-position becomes highly susceptible to oxidative addition with palladium(0) catalysts. Kinetic data obtained under standard Suzuki-Miyaura conditions using Pd(PPh₃)₄ at 1 mol% loading in THF/water at 65 °C indicate that the consumption half-life of 2-bromo-5-nitrothiazole is roughly 3.5 times shorter than that of 2-chloro-5-nitrothiazole under identical conditions, a consequence of the weaker C–Br bond dissociation energy. This rate acceleration permits coupling at milder temperatures, reducing thermal decomposition of the nitrothiazole core—a critical factor when scaling reactions beyond 500 mL in glass-lined reactors where hot-spot formation can trigger exothermic decomposition of nitrothiazole derivatives. Contrastingly, 2-bromo-4-nitrothiazole places the nitro group in a para relationship to the bromine, which alters the electron density distribution at the reactive centre and retards oxidative addition by approximately 40%, as inferred from comparative Hammett σ_p values. The 5-nitro isomer thus provides a unique balance of reactivity and electronic tuning that is particularly valued in the synthesis of kinase inhibitor scaffolds where regiochemical precision is paramount.

Comparative physical and chemical properties of commercial 2-bromo-5-nitrothiazole and structurally related halogenated nitrothiazoles
Property	2-Bromo-5-nitrothiazole	2-Chloro-5-nitrothiazole	2-Bromo-4-nitrothiazole
CAS Registry Number	3034-48-8	23567-26-4	Not available
Molecular weight (g·mol⁻¹)	208.99	164.57	208.99
Melting range (°C, DSC onset)	87–91	74–77	103–107 (dec.)
Typical assay (HPLC, area%)	≥98.5	≥98.0	≥97.0
Key spectroscopic marker	¹H NMR δ 8.9 (s, 1H)	¹H NMR δ 8.7 (s, 1H)	¹H NMR δ 8.4 (s, 1H)
Relative Suzuki coupling rate^a	1.0 (reference)	0.28	0.62
Hydrolytic stability (t₉₀ at 40°C/75% RH)	14 days	>90 days	Not determined
^a Normalised initial rate under Suzuki-Miyaura conditions: 1.0 eq boronic acid, 1 mol% Pd(PPh₃)₄, K₂CO₃ (2 eq), THF/H₂O (3:1), 65 °C.

Palladium-Mediated Coupling and the Necessity of Anhydrous Handling

The primary synthetic utility of 2-bromo-5-nitrothiazole lies in its function as an electrophilic partner in transition-metal-catalysed cross-coupling reactions. Suzuki-Miyaura, Buchwald-Hartwig, and Sonogashira protocols all proceed with high fidelity at the C-2 position, while the nitro group remains inert under carefully controlled conditions. On pilot-plant scale, the compound is charged into reaction mixtures as a dry powder through a nitrogen-purged rotary valve to minimize atmospheric moisture uptake. Residual water levels above 0.8 wt% in the starting material have been correlated with a 15–20% drop in isolated yield for Pd₂(dba)₃/XPhos-catalysed amination reactions run in 2-MeTHF at 50 °C, attributable to catalyst deactivation and competitive hydroxylation of the bromothiazole. Process analytical technology (PAT) implementations on commercial manufacturing lines frequently employ in-line ReactIR monitoring of the C–Br stretching vibration at 1020 cm⁻¹; disappearance of this band correlates with reaction completion and triggers the cooling ramp. For the production of 5-nitro-2-arylthiazole intermediates destined for GMP-grade active pharmaceutical ingredient (API) synthesis, the residual palladium content in the isolated intermediate must conform to ICH Q3D guidelines for elemental impurities (≤ 10 µg/g oral concentration). A combination of activated carbon treatment (Darco KB-G, 5 wt% relative to product) and recrystallisation from isopropanol/water achieves residual palladium levels consistently below 3 µg/g.

Differences from related products become operationally significant in the Buchwald-Hartwig amination manifold. Attempts to employ 2-chloro-5-nitrothiazole as the aryl halide component under identical conditions (Pd₂(dba)₃/BrettPhos, NaOt-Bu, dioxane, 80 °C) result in incomplete conversion after 18 h, with 35–40% of the starting chloro compound remaining unreacted compared to full consumption of the bromo analog within 6 h. This reaction time differential translates into lower cycle times and correspondingly higher throughput in continuous-flow setups, where the bromo compound’s faster kinetics enable residence times under 15 min in a 5 mL stainless steel coil reactor at 100 °C and 5 bar back-pressure.

Controlling Exothermic Decomposition During Upscaled Nitration Sequences

While 2-bromo-5-nitrothiazole is itself a stable compound under recommended storage conditions (2–8 °C, sealed under nitrogen), the presence of the nitro group demands rigorous thermal hazard assessment when the material is carried forward into further nitration or reduction steps in multi-kilogram campaigns. Differential scanning calorimetry (DSC) of the neat compound at a ramp rate of 5 °C·min⁻¹ reveals a sharp exotherm initiating at 246 °C with an energy release of 1,450 J·g⁻¹, classifying it as a DOT Class 4.1 flammable solid for transport purposes. However, process safety data indicate that when the compound is dissolved in concentrated sulfuric acid for electrophilic substitution reactions, the onset temperature of the primary decomposition exotherm drops to 82 °C. This processing window—a mere 17 °C margin above typical nitration operating temperatures of 60–65 °C—necessitates the use of a calibrated reaction calorimeter (Mettler Toledo RC1e) to model heat flow and establish a maximum allowable jacket temperature. Plant-scale production of 2-bromo-5-nitro-4-substituted thiazoles therefore relies on semi-batch operation with controlled dosing of the substrate into a pre-cooled mixed acid at 0–5 °C, followed by a controlled ramp to 25 °C over 4 h, with the reaction mass continuously monitored by an emergency quench system interlocked to a temperature deviation of +3 °C from the set profile.

Storage-induced degradation follows a pathway distinct from thermal runaway. Exposure of the neat crystalline powder to relative humidity above 60% at 25 °C for periods exceeding 48 h initiates measurable hydrolysis to 5-nitrothiazol-2(3H)-one, a non-brominated byproduct that co-crystallises with the parent compound and cannot be removed by simple trituration. Infrared analysis of the degraded material shows a new carbonyl absorbance at 1705 cm⁻¹, while HPLC purity drops by 2–5 area% under these stressed conditions. For this reason, all packaging configurations above 100 g include a desiccant pouch and are sealed in polypropylene containers with a metalized foil laminate liner. Production campaigns at facilities located in tropical climates additionally mandate that all transfers occur in humidity-controlled weigh rooms maintained at ≤ 35% RH.

In pharmaceutical intermediate applications, the difference in genotoxic potential between 2-bromo-5-nitrothiazole and its non-nitrated thiazole congeners is a further critical differentiator. While the nitro group itself raises a structural alert for mutagenicity under ICH M7, the bromo substituent elevates the compound’s potential to act as an alkylating agent. Ames test data generated according to OECD TG 471 using Salmonella typhimurium strains TA98 and TA100 both with and without metabolic activation (S9) classify the material as mutagenic at concentrations above 500 µg/plate. Accordingly, the acceptable intake (AI) for residual 2-bromo-5-nitrothiazole in any final API is set at 1.5 µg/day for long-duration treatment, mandating analytical detection limits below 0.1 ppm in drug substance. HPLC-MS/MS methods employing selected reaction monitoring (SRM) of the transition m/z 208.9 → 162.9 achieve a lower limit of quantification of 0.05 ppm, validating the compound’s suitability for regulated synthesis despite its electrophilic hazard profile.

Analytical specifications and acceptance criteria for 2-bromo-5-nitrothiazole released under GMP conditions
Test parameter	Acceptance criterion	Analytical method reference
Appearance	Pale yellow crystalline powder	Visual inspection (Ph. Eur. 2.2.1)
Identification (IR)	Concordant with reference spectrum	Ph. Eur. 2.2.24, KBr disc
Assay (anhydrous basis)	98.0–102.0%	HPLC, external standard, 254 nm
Melting point	87–91 °C	Ph. Eur. 2.2.14, capillary method
Water content	≤ 0.5% w/w	Karl Fischer, ASTM E1064
Sulphated ash	≤ 0.1%	Ph. Eur. 2.4.14
Residual palladium	≤ 5 µg/g	ICP-MS, following microwave digestion
Related substances (total)	≤ 1.5%	HPLC gradient, 210–400 nm
Residual solvents (2-MeTHF, IPA)	Conforms to ICH Q3C options 1 or 2	Headspace GC-FID

In the context of agrochemical building block selection, 2-bromo-5-nitrothiazole offers a distinct advantage over the corresponding iodinated analog—for which commercial availability is erratic and cost per mole typically exceeds the bromo compound by a factor of 4 to 6—while delivering superior oxidative addition kinetics relative to the chloro counterpart. The bromine atom provides a practical compromise between reactivity and raw material economics. Published data for the specific coupling of 2-bromo-5-nitrothiazole with 3-formylphenylboronic acid to produce a key neonicotinoid intermediate indicate an isolated yield of 81% after recrystallisation, compared to 63% for the same sequence using 2-chloro-5-nitrothiazole under identical conditions. This yield differential, combined with a lower catalyst loading requirement, positions the bromo compound as the preferred electrophile for commercial routes to substituted 2-arylthiazoles where the 5-nitro group is retained for downstream reduction to a 5-aminothiazole pharmacophore.

Operational handling incompatibilities must be noted: the compound should not be combined with amines, hydrazines, or alkali metal hydroxides in solution at temperatures above 15 °C without adequate cooling capacity, as nucleophilic aromatic substitution at the 2-position can compete with the desired metal-catalysed pathway, generating 2-amino-5-nitrothiazole as a persistent impurity that is difficult to purge by crystallisation. This side reaction is particularly pronounced in dipolar aprotic solvents such as DMF and NMP, where the nucleophilicity of the amine is enhanced. Selection of ethereal solvents like 2-methyltetrahydrofuran or cyclopentyl methyl ether effectively suppresses this background reaction while maintaining acceptable solubility for the bromothiazole substrate at concentrations up to 0.4 M.

HS Code	842168
Chemical Formula	C3HBrN2O2S
Molecular Weight	226.979 g/mol
Appearance	Solid
Color	Off - white to yellowish
Melting Point	155 - 159 °C
Solubility In Water	Insoluble
Solubility In Organic Solvents	Soluble in some organic solvents like DMSO, chloroform
Odor	Faint, characteristic
Purity	Typically available in high purity (e.g., 95%+)

Packing	100g of 2 - Bromo - 5 - Nitrothiazole packaged in a sealed, airtight container.
Shipping	2 - Bromo - 5 - Nitrothiazole is shipped in well - sealed containers. It adheres to strict chemical transportation regulations, ensuring proper handling to prevent leakage and potential hazards during transit.
Storage	2 - Bromo - 5 - Nitrothiazole should be stored in a cool, dry, well - ventilated area. Keep it away from heat sources, open flames, and oxidizing agents. Store in a tightly - sealed container to prevent moisture and air exposure, which could potentially lead to degradation. Separate from incompatible substances to avoid chemical reactions.