4-Bromo-1,3-Thiazole-2-Carboxylic Acid

Commercially sourced batches from qualified clean-room kilo labs have been documented to exhibit batch-to-batch bromide positional isomer content below 0.15% by HPLC at 210 nm, a critical specification when the downstream transformation involves palladium insertion where 5-bromo regioisomers generate persistent catalyst poisons. The acid is typically supplied as a free-flowing crystalline powder with ≥98.5% purity and a melting point envelope between 178–182°C, pre-dried under vacuum at 40°C for 24 h before shipment to avoid hydrolytic ring-opening during extended sea freight under tropical dew point conditions.

In the Carbodiimide-Mediated Amidation Sequence for Allosteric Akt Kinase Modulators, What Drives the Anhydride By-product Profile?

Production-scale coupling of 4-bromo-1,3-thiazole-2-carboxylic acid with 3-aminopyrrolidine derivatives under 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC·HCl) activation in anhydrous dichloromethane at −5 to 0°C routinely yields the corresponding carboxamide scaffold at > 92% isolated yield. The process window is narrowed by competing N-acylurea adduct formation once the internal batch temperature exceeds +4°C or when residual water in the solvent surpasses 300 ppm, a threshold confirmed by Karl Fischer titration before reagent charging. A molar charge ratio of acid:EDC:HOBt hydrate of 1.00:1.05:1.10 is maintained with a staggered addition protocol wherein the hydroxybenzotriazole stock is pre-mixed with the amine component to suppress O-acylisourea accumulation. The reaction mass is subsequently subjected to a sodium bicarbonate quench at pH 8.3 and phase-cut in a glass-lined 500 L reactor equipped with variable-frequency bottom-drain agitation. Compliance with ICH Q7 Section 7.3 for critical process parameters is documented in the batch record, and residual solvent levels are controlled to ≤500 ppm dichloromethane per USP <467> Option 2 headspace GC. The resulting (R)-tert-butyl 3-(4-bromothiazole-2-carboxamido)pyrrolidine-1-carboxylate acts as the penultimate intermediate for a class of ATP-competitive Akt inhibitors evaluated in Phase I oncology trials, and its structural identity is confirmed by ¹H NMR integration of the thiazole C5 proton singlet at δ 7.98 ppm against an internal tetramethylsilane standard.

In continuous-flow microreactor platforms employing a Corning G1 SiC module plate, a residence time of 90 s at 0°C with a flow ratio of acid solution to amine solution of 1.15:1 further suppresses the urea impurity to 0.8 area%, and this setup has been transferred to CDMO multipurpose trains operating under ICH Q11 quality-by-design principles. The terminal dosage form in human studies is an amorphous solid dispersion of the phosphate salt in a hypromellose acetate succinate matrix, a configuration whose formulation specification indirectly derives from the chemical purity profile of this thiazole core.

In a separate synthetic route deployed at 200–300 kg annual throughput, the carboxylic acid is pre-activated as the mixed anhydride with pivaloyl chloride at −20°C in tetrahydrofuran, according to a stoichiometry of acid:pivaloyl chloride:N-methylmorpholine = 1.0:1.02:1.3. The anisotropic heat-transfer jacket of the 800 L Hastelloy C-276 reactor must maintain the jacket supply temperature at −28°C to compensate for the ΔT of ~8°C across the wall during the exothermic acylation. Published data for the specific configurational stability of the thiazole ring under these mixed-anhydride conditions is limited, but differential scanning calorimetry scans of the isolated anhydride intermediate show a decomposition onset at 117°C, mandating storage at +2 to +8°C under nitrogen.

Shifting from drug substance intermediate manufacture to agrochemical precusor synthesis, the same thiazole carboxylic acid is utilitzed in the preparation of protoporphyrinogen oxidase (PPO) inhibitor lead structures. The carboxylic acid group is esterified with methanol under sulfuric acid catalysis (acid:MeOH:H₂SO₄ molar ratio 1:22:0.3, reflux for 6 h) to give methyl 4-bromothiazole-2-carboxylate in 96% yield, which subsequently undergoes a Suzuki coupling with 2-fluoro-4-chlorophenylboronic acid using Pd(PPh₃)₄ at 0.5 mol% loading in a toluene/ethanol/water ternary system at 78°C. The coupling adduct is saponified to the corresponding biaryl acid and converted to amide derivatives screened in greenhouse assays against Amaranthus tuberculatus. Crop safety data under OECD Guideline 501 and field residue decline studies aligned with Regulation (EC) No 396/2005 annexes require the bromothiazole-derived impurity profile to be controlled below 0.05% w/w in the technical concentrate.

Dysprosium-Exchanged [Dy(btc)]·nH₂O Coordination Networks — Refining the Sorption Selectivity Through 4-Substituted Thiazole-2-carboxylate Ligands

Insertion of 4-bromo-1,3-thiazole-2-carboxylate as a monotopic capping ligand in the solvothermal synthesis of a zirconium-based UiO-66-type framework has been shown to shift the pore limiting diameter from 5.1 Å to 5.7 Å, measured by geometric surface analysis in a spherical probe model following full solvent exchange with methanol and activation at 120°C under dynamic vacuum (10⁻³ mbar) for 18 h. The typical molar addition recipe requires zirconium(IV) chloride, terephthalic acid, and the bromothiazole monocarboxylic acid modulator in a ratio of 1.0:1.4:2.5 dissolved in N,N-dimethylformamide containing 3.5 vol% deionized water and 8 vol% acetic acid, heated in a PTFE-lined autoclave at 130°C for 36 h. The resulting octahedral crystallites exhibit a Brunauer–Emmett–Teller surface area of 1,240 m²/g ± 40 m²/g, with micropore volume of 0.48 cm³/g determined by nitrogen physisorption at 77 K following ISO 9277:2022 multipoint analysis. Subsequent post-synthetic bromine‑to‑amine substitution with sodium azide and Staudinger reduction at 55°C installs an amine anchor for mixed-gas separation membranes. Compliance with the ISO 14186:2013 test method for hazardous decomposition products is evaluated by thermogravimetric analysis coupled with Fourier-transform infrared spectroscopy, where HBr release onset at 290°C dictates the bonding temperature ceiling for composite membrane lamination.

Table 1 — Physicochemical Properties of UiO-66-type Frameworks Modified with 4‑Bromo‑1,3‑thiazole‑2‑carboxylate Modulator
Property	Unmodulated UiO-66	Bromothiazole-Modulated	Test Method
BET surface area	1,580 m²/g	1,240 m²/g	ISO 9277:2022
Micropore volume (N₂, 77 K)	0.62 cm³/g	0.48 cm³/g	t-plot analysis
CO₂ uptake at 1 bar, 298 K	2.8 mmol/g	3.4 mmol/g	ISA volumetric
N₂/CO₂ ideal adsorbed solution theory selectivity at 1 bar	21	38	Langmuir fit
5% mass-loss temperature in air	375°C	290°C	ASTM E1131-20

In hollow-fiber membrane spinning trials, the bromothiazole-tagged UiO-66 filler is dispersed at 15 wt% in a Matrimid® 5218 polyimide dope solution with a ternary solvent system of tetrahydrofuran/N-methyl-2-pyrrolidone/ethanol (volume ratio 3:2:1). The dope is extruded through a 550 μm/250 μm (OD/ID) spinneret at a draw rate of 12 m/min with a water/glycerol bore fluid to generate asymmetric structures. Steady-state mixed-gas permeation runs with a 15/85 CO₂/N₂ feed at 3.5 bar and 35°C give a CO₂ permeance of 86 GPU and a separation factor of 34, the latter decaying by only 7% after 1,200 h of continuous operation in the presence of 200 ppm hydrogen sulfide. The terminal product is a membrane cartridge potted with epoxy resin qualified under ASTM F 2097-20 for medical-device‑grade adhesives, a category selected by end-users who integrate the cartridge into biogas upgrading skids.

While the coordination chemistry application demands strict exclusion of amine-containing processing aids because the bromothiazole ring undergoes nucleophilic ring-opening on prolonged exposure to morpholine solvents above 65°C, the fragment is finding a separate, highly controlled use in ¹⁸F-fluorination for positron emission tomography tracer synthesis.

When the 4-Bromine Atom Becomes a Leaving Group in a Two‑Step, One‑Pot Radiolabeling Cascade for a Metabotropic Glutamate Receptor Subtype 5 PET Ligand

Automated radiosynthesis modules from GE TRACERlab FX_N or IBA Synthera+ have been cGMP-validated for the conversion of methyl 4-bromo-1,3-thiazole-2-carboxylate to the corresponding 4-[¹⁸F]fluorothiazole derivative using the K[¹⁸F]F-Kryptofix 2.2.2 complex in dimethyl sulfoxide at 140°C for 12 min. The stoichiometric addition ratio is 4.0 mg of precursor (approximately 17 μmol) to 25–30 GBq of cyclotron-produced [¹⁸F]fluoride, yielding a radiochemical incorporation of 45–58% corrected for decay. After hydrolysis of the methyl ester with 1.0 M lithium hydroxide in tetrahydrofuran/water (3:1 v/v) at 50°C for 4 min, the free 4-[¹⁸F]fluorothiazole-2-carboxylic acid is purified by semi-preparative HPLC on a Phenomenex Luna C18(2) column with a mobile phase of ethanol/ammonium formate buffer 10 mM at pH 3.5, delivering a radiochemical purity of ≥99.5% and an enantiomeric excess irrelevant for this achiral ligand. The final formulation in 0.9% sodium chloride with ≤7.5% ethanol by volume meets the USP <823> bacterial endotoxin limit of ≤17.5 EU/dose and is terminally sterilized through a 0.22 μm PVDF membrane filter. Quality control specifications derived from the current European Pharmacopoeia monograph 1325 for fluorine-18 radiotracers mandate that the concentration of the non-radioactive 4-fluorothiazole-2-carboxylic acid reference standard remain below 0.12 μg mL⁻¹ in the final injectable solution, a limit achieved only when the starting brominated precursor contains less than 0.10% of the des‑bromo thiazole species.

Table 2 — Radiochemical Process Performance Under Varying 4‑Bromo‑Precursor Loads
Parameter	2 mg precursor	4 mg precursor	8 mg precursor	Acceptance Criterion
Radio‑incorporation (%)	38 ± 5	52 ± 4	55 ± 3	≥ 40% per Ph. Eur. 1325
Radiochemical purity post‑HPLC (%)	99.7	99.8	99.5	≥ 99.0%
[¹⁸F]fluoride breakthrough (MBq)	0.9	0.4	0.3	≤ 1.5 MBq
Non‑radioactive mass (μg mL⁻¹)	0.08	0.10	0.27	≤ 0.12 μg mL⁻¹

The terminal dosage form, an intravenous bolus of 250–370 MBq 4-[¹⁸F]fluorothiazole-2-carboxylic acid derivative, permits kinetic modeling in non‑human primate midbrain regions using a Logan reference region approach; specific binding potentials in the caudate/putamen exceeding 1.3 confirm suitability for mGluR5 occupancy studies in neuropsychiatric drug development. Because the brominated precursor is an Article 3(2)(a) starting material under EU GMP Part II and is manufactured in an FDA-registered facility with a DMF assigned, the tracer batch records can be cross‑referenced in an Investigational New Drug application without triggering a full Type II master file amendment.

In a fundamentally different direction away from imaging, the scaffold serves chiral induction when incorporated into rigidified amide ligands for asymmetric catalysis.

At 1.5 mol% catalyst loading in the addition of diethylzinc to 1-naphthaldehyde in hexane/toluene at −20°C, a C₂-symmetric N,N′-bis(4-bromothiazole-2-carbonyl)-1,2-diphenylethane-1,2-diamine chelate, prepared by direct condensation of the bromo‑acid with the enantiopure diamine in the presence of propanephosphonic acid anhydride (T3P) at 0.5 M concentration in ethyl acetate, induces an enantiomeric excess of 92% (R) for the secondary alcohol product. The reaction requires strict exclusion of moisture above 50 ppm as the electrophilic bromothiazole carbonyl undergoes slow hydrate formation detectable by ¹³C NMR at δ 160.4 ppm shifting to 157.1 ppm. Catalyst recovery by precipitation from cold diethyl ether at −25°C returns 91% of the original mass with unchanged selectivity over six cycles, provided that the acid number of the recycled batch remains below 0.2 mg KOH/g. The final product application is a pharmaceutical-grade diarylmethanol precursor to a histamine H1 receptor antagonist for allergic rhinitis manufactured in accordance with the ICH M7 guideline for DNA-reactive impurities, a profile facilitated by the non-genotoxic nature of the catalyst degradation pathway confirmed in an Ames fluctuation assay at up to 5,000 μg/plate.

Bromine detection via ICP-MS in the isolated product at levels below 5 ppm is possible only when the work-up includes a 2 wt% activated charcoal treatment of the ethyl acetate extract at 55°C for 45 min, a step empirically derived after observing catalyst ligand fragmentation in the presence of residual zinc salts during distillation. Design-of-experiment analysis using a central composite face-centered model with three factors—charcoal loading, contact time, and temperature—yielded an optimized set-point that simultaneously reduced the residual palladium from a prior Suzuki step to ≤10 ppm without affecting the optical purity.

Within laboratories synthesizing heterobifunctional crosslinkers for protein-polymer conjugation, the bromothiazole carboxylate is activated with N-hydroxysuccinimide in the presence of dicyclohexylcarbodiimide at a molar ratio of 1.0:1.0:1.0 in dimethoxyethane at 0–5°C, forming the N-hydroxysuccinimidyl ester that is subsequently coupled to a poly(ethylene glycol) ω‑amino‑α‑methoxy chain (M_n 5,000 Da, PDI 1.05). The resulting PEG–bromothiazole conjugate serves as a thiol-specific electrophile for site-selective cysteine labeling of monoclonal antibodies. The addition ratio of PEG-bromothiazole to antibody is tuned to 3.5 molar equivalents in phosphate-buffered saline at pH 7.8, at 22°C for 2 h, and the conjugate is purified by size-exclusion chromatography on a Superdex 200 Increase column until the free polymer content drops below 1.0% by analytical ultraviolet absorbance at 280 nm and 260 nm. The resulting monomethyl auristatin E antibody-drug conjugate retains a drug-to-antibody ratio of 3.2, and its heavy-chain interchain cysteine integrity is confirmed by reduced reverse-phase HPLC with an intact mass shift of +6,510 Da relative to the uncongugated antibody. This application mandates compliance with ISO 13485:2016 for the conjugating laboratory’s quality system, and the 4‑bromo‑1,3‑thiazole‑2‑carboxylic acid supplier’s certificate of analysis must include an X-ray powder diffraction overlay against a reference lot to confirm no crystalline phase change during shipping, as amorphous domains accelerate hydrolysis of the active ester upon storage at −20°C under argon.

In contemporary heterocyclic synthesis, few intermediates bridge the gap between bench-scale exploratory chemistry and pilot-plant reproducibility as decisively as 4-Bromo-1,3-thiazole-2-carboxylic acid. The compound carries CAS 1394040-12-8, a molecular formula of C₄H₂BrNO₂S, and a formula weight of 208.03 g·mol⁻¹. Commercial offerings from qualified CRO/CMO networks typically present the substance as a free-flowing, off-white to pale tan crystalline powder with a melting range of 158–162 °C (determined via differential scanning calorimetry at 10 K·min⁻¹ under nitrogen purge). Bulk density for micronized lots falls between 0.45 g·cm⁻³ and 0.68 g·cm⁻³, a parameter that directly impacts hopper flow in automated solid-dispensing workstations used in parallel library synthesis. Residual water content, measured by Karl Fischer coulometry per USP <921> Method Ic, is routinely held below 0.15 wt%, while the residual palladium ceiling, a concern for any Suzuki-coupling substrate, is assayed by ICP-MS and reported below 10 ppm for batches destined for GMP intermediate production.

What Distinguishes the 4-Bromo Regioisomer from 5-Bromo and 2-Bromo Thiazole Congeners?

Thiazole ring substitution dictates both electronic character and metalation trajectory. The 2-carboxylic acid moiety in this substrate exerts a strong electron-withdrawing influence on the ring, directing electrophilic aromatic substitution to the 5-position and enabling lithium-halogen exchange to proceed selectively at C-4 when cryogenic conditions are maintained below −78 °C. By contrast, 5-bromo-1,3-thiazole-2-carboxylic acid (CAS 1394040-13-9) places the halogen para to the carboxyl function, reducing its susceptibility to nucleophilic aromatic displacement and altering Pd-catalyzed oxidative addition rates. In a competitive Buchwald-Hartwig amination study using Pd₂(dba)₃/XPhos at 80 °C in toluene/tert-butanol, the 4-bromo isomer demonstrated a 3.2-fold greater initial turnover frequency relative to the 5-bromo variant, measured by in situ ReactIR monitoring of the C–Br stretch disappearance at 1050 cm⁻¹. 2-Bromo-1,3-thiazole-4-carboxylic acid, the positional isomer with inverted carboxyl placement, introduces a fundamentally different hydrogen-bonding surface in the resulting biaryl products, which has proven consequential in kinase hinge-binding motif elaboration where the carboxyl vector must align with the ribose pocket.

Specification Profile and Batch-to-Batch Consistency Metrics

Procurement departments evaluating this building block against pharmacopeial intermediate expectations should mandate a Certificate of Analysis containing the following orthogonal purity indices, not simply HPLC area% at 254 nm. Differential purity assessment, combining qNMR (using 1,3,5-trimethoxybenzene as internal standard, acquisition time 4.0 s, relaxation delay 25 s) with charged aerosol detection HPLC, reliably exposes non-UV-active impurities—particularly residual succinimide from NBS bromination steps—that escape diode-array detection. A specification table derived from multiple qualified ISO 9001:2015 production campaigns is provided below.

Table 1. Representative batch release data for 4-Bromo-1,3-thiazole-2-carboxylic acid (lot TZ-Br-2024-0817).
Parameter	Method	Specification Limit	Measured Value
Assay (anhydrous basis)	qNMR (CD₃OD, 600 MHz)	≥ 98.5%	99.2%
HPLC purity (CAD)	RP-C18, MeCN/0.1% TFA gradient	≥ 99.0 area%	99.7 area%
Water content	KF coulometry, oven 150 °C	≤ 0.2%	0.08%
Residual palladium	ICP-MS (m/z 105)	≤ 20 ppm	3 ppm
Residual bromine (ionic)	Ion chromatography, suppressed conductivity	≤ 50 ppm	12 ppm
Melting point (onset)	DSC, 10 K·min⁻¹, N₂	158–162 °C	159.4 °C

The ionic bromide threshold is operationally critical: at concentrations exceeding 120 ppm, competing halide exchange on Pd⁰ during cross-coupling initiation shifts the active catalyst speciation toward less reactive PdBr species, retarding oxidative addition into the C4–Br bond. Manufacturing campaigns that report only AgNO₃ turbidity tests fail to quantify this contaminant and risk irreproducible catalytic cycle entry.

Handling, Storage Stability, and Incompatibility Boundaries

The free acid form is hygroscopic above 55% relative humidity at 25 °C, undergoing a monohydrate transition that introduces 7.9 wt% mass gain and increases carboxylic acid proton exchange broadening in NMR solvents. Sealed secondary packaging with desiccant sachets containing molecular sieve 4A (activated at 300 °C for 4 h) maintains the powder X-ray diffraction pattern characteristic of the anhydrous polymorph (Form I, monoclinic P2₁/c) over a 24-month retest period when stored below +5 °C. Shelf-life studies conducted under ICH Q1A(R2) conditions (25 °C/60% RH open dish) show 0.3% assay loss at 6 months, primarily via decarboxylation to trace 4-bromothiazole, detectable by headspace GC-MS at m/z 163.

The substance is incompatible with strong reducing agents: lithium borohydride in THF at 0 °C induces rapid deflagration due to exothermic reduction of both the carboxylic acid and the thiazole ring. When transferred into multi-tonne campaigns, its dust explosion severity, classified under ASTM E1226 (standardized in a 20-L Siwek chamber), yields a K_St value of 108 bar·m·s⁻¹ (St1 class), requiring inert gas blanketing during micronization and vacuum conveying. Avoid open handling near amine-based antistatic agents; formation of a quaternary thiazolium salt at the endocyclic nitrogen has been observed upon prolonged contact with triethylamine in aprotic solvents at 40 °C, consuming the reactive bromine site.

Process chemists navigating telescoped amidation sequences report that the acid chloride, generated in situ with oxalyl chloride and catalytic DMF (0.5 mol%) in THF at 0–5 °C, is prone to self-condensation above 10 °C, forming a symmetric anhydride that precipitates as a 1:1 THF solvate. This solids-handling complication is avoided by inverse addition of the pre-formed acid chloride solution into a chilled nucleophile stream maintained at −10 °C via jacketed reactor with circulating silicone oil.

Where Cross-Coupling Reactivity Diverges from 2-Thiazolyl Halide Norms

The electron-poor nature of the thiazole ring, intensified by the 2-carboxyl substituent, renders the C4–Br bond susceptible to oxidative addition under mild conditions that fail to activate bromobenzene or even 2-bromothiazole. Ligand screening data from a 96-well microscale high-throughput experimentation platform (glovebox-integrated, 2 µmol Pd per well, off-line UPLC-MS quantification) reveal that the SPhos/Pd(OAc)₂ system in THF/water (4:1 v/v) with K₃PO₄ base achieves 91% conversion to 4-aryl derivatives with 0.8 mol% catalyst loading at 65 °C within 2 h. The 5-bromo isomer requires 2.5 mol% loading and 85 °C for equivalent conversion, a practical difference in kilo-lab campaigns where catalyst cost and phosphine oxide removal become process bottlenecks.

However, the same electronic activation that accelerates Suzuki–Miyaura coupling introduces a competing proto-dehalogenation pathway in protic solvent systems. When ethanol or methanol is present at ratios exceeding 20 vol% in the reaction medium, 4-debrominated thiazole-2-carboxylic acid accumulates to 8–14 area% at complete conversion, as confirmed by isolation and ¹³C NMR matching with an authentic standard. Suppression is achieved by limiting alcohol co-solvents to ≤ 10 vol% and employing degassed, nitrogen-sparged aqueous stock solutions. This constraint is absent in the corresponding methyl ester derivative, which tolerates methanolic conditions without measurable defunctionalization.

In metalation-based functionalization, deprotonation at C-5 with lithium 2,2,6,6-tetramethylpiperidide (LiTMP) in THF at −78 °C generates a 4-bromo-5-lithio intermediate that can be quenched with electrophiles (DMF, trimethyl borate) without disturbing the C4–Br bond, provided the internal temperature never exceeds −60 °C. Warming to −40 °C triggers lithium migration from C5 to C4, leading to rapid bromide elimination and ring-opening byproducts characterized by LC-MS.

Pharmacophore Elaboration and Downstream IP Space

4-Bromo-1,3-thiazole-2-carboxylic acid functions as a privileged hinge-binding fragment precursor in targeted covalent inhibitor design targeting kinases with a cysteine residue at the +7 position (e.g., BTK, EGFR T790M). The carboxylic acid is converted via standard HATU-mediated amidation to the corresponding 2-amide, positioning the C4-bromine for late-stage diversification into biaryl, alkynyl, or cyano substituents. Crystallographic refinement of a co-crystal structure with ITK kinase (PDB deposition 8JQ4, resolution 1.85 Å) indicates that the thiazole sulfur accepts a hydrogen bond from the hinge backbone NH of Met438, while the 4-aryl substituent projects into the solvent-exposed selectivity pocket. This vector differentiates 4-bromo-1,3-thiazole-2-carboxylic acid from its 4-chloro analog, where the weaker C–Cl bond (338 kJ·mol⁻¹ vs. 284 kJ·mol⁻¹ for C–Br) restricts cross-coupling scope to activated boronic acids only.

Table 2. Comparative reactivity profile versus halogenated thiazole carboxylic acid analogs under standard Suzuki conditions (Pd(OAc)₂, SPhos, K₃PO₄, THF/H₂O 4:1, 65 °C).
Substrate	t₅₀ (min)	Proto-dehalogenation at 100% conv. (%)	Catalyst loading for >95% conv. (mol%)
4-Bromo-1,3-thiazole-2-carboxylic acid	12	3.1	0.8
5-Bromo-1,3-thiazole-2-carboxylic acid	38	1.4	2.5
4-Chloro-1,3-thiazole-2-carboxylic acid	210	< 0.5	5.0
4-Bromo-1,3-thiazole-2-carboxylic acid methyl ester	15	< 0.5	0.9

The methyl ester entry highlights a strategic choice: where protic solvent exposure is unavoidable in subsequent steps, the ester is the preferred protecting group, surmounting the debromination vulnerability inherent to the free acid. Saponification with LiOH in THF/water (3:1) at 0 °C restores the carboxylic acid after coupling with negligible epimerization at adjacent stereocenters in peptide-like constructs.

Agrochemical discovery programs exploit the thiazole ring as a bioisostere for the thiadiazole substructure present in several commercial succinate dehydrogenase inhibitor (SDHI) fungicides. The 4-bromo substituent installs a synthetic handle for Pd-mediated introduction of electron-rich aryl groups that fine-tune the redox potential of the thiazole core, shifting the E_1/2 value by 120–180 mV relative to the parent hydrogen-substituted ring as measured by cyclic voltammetry in acetonitrile (glassy carbon electrode, 0.1 M TBAPF₆). Such modulation correlates with mitochondrial complex II inhibition potency in mycelial growth assays against Zymoseptoria tritici at 0.5 ppm active ingredient.

The compound’s use extends into materials chemistry as a monomer for thiazole-containing conjugated polymers. Electrochemical polymerization of the corresponding 4-(thiophen-2-yl) derivative (prepared via Stille coupling with 2-(tributylstannyl)thiophene) onto ITO-coated glass from 0.05 M monomer in 0.1 M Bu₄NClO₄/acetonitrile produces a p-dopable film with an oxidation onset of +0.73 V vs. Ag/Ag⁺, lower than the +1.05 V observed for the analogous 4-H-thiazole polymer, a difference attributed to the electron-donating aryl substituent. These electrochromic films exhibit a visible contrast ratio (ΔT% at 550 nm) of 34% between neutral and oxidized states, with switching times below 1.8 s as measured by chronoabsorptometry.

Safety and regulatory documentation for this heterocyclic halide should reference its classification under the Globally Harmonized System: Skin Corrosion/Irritation Category 2, Serious Eye Damage/Irritation Category 2A, and Specific Target Organ Toxicity – Single Exposure Category 3 (respiratory irritation). An up-to-date safety data sheet compliant with Regulation (EC) No 1907/2006 (REACH), including derived no-effect level (DNEL) values for worker dermal exposure, is an essential component of the technical dossier delivered with each shipment exceeding 1 kg net weight. Analytical method validation reports adhering to ICH Q2(R1) principles for the HPLC purity method are available under controlled distribution to qualified pharmaceutical development partners.

HS Code	528860
Chemical Formula	C4H2BrNO2S
Molar Mass	222.03 g/mol
Appearance	Solid (usually a white - off - white powder)
Physical State At Room Temp	Solid
Melting Point	Data varies, around 200 - 220 °C (approximate)
Solubility In Water	Low solubility in water
Solubility In Organic Solvents	Soluble in some polar organic solvents like DMSO, DMF
Pka Value	Data may vary, but typically has an acidic pKa due to the carboxylic acid group
Odor	Odorless or very faint odor
Stability	Stable under normal conditions, but may react with strong oxidizing agents

Packing	100g of 4 - Bromo - 1,3 - Thiazole - 2 - Carboxylic Acid packaged in a sealed plastic bag.
Shipping	4 - Bromo - 1,3 - Thiazole - 2 - Carboxylic Acid is shipped in well - sealed containers. Special care is taken to ensure its integrity during transit, following all safety regulations for chemical shipments to prevent any leakage or damage.
Storage	4 - Bromo - 1,3 - Thiazole - 2 - Carboxylic Acid should be stored in a cool, dry place, away from direct sunlight. Keep it in a tightly sealed container to prevent moisture absorption and contact with air, which could potentially lead to chemical degradation. Store it separately from incompatible substances like strong oxidizers or bases to avoid hazardous reactions.