2-Bromo-5-Nitrothiazole: Properties, Synthesis & Applications

2-Bromo-5-nitrothiazole is a halogenated, electron-deficient thiazole heterocycle widely employed as a versatile synthetic building block in medicinal chemistry, agrochemical research, and the preparation of biologically active compounds.

CAS Number

3034-48-8

Molecular Formula

C₃HBrN₂O₂S

Molecular Weight

209.02 g/mol

Appearance

Pale yellow to yellow crystalline solid

Key Functional Groups

C-2 bromine (electrophilic substitution site), C-5 nitro group (electron-withdrawing activator)

Primary Use

Synthetic intermediate for cross-coupling reactions and nucleophilic aromatic substitution

SKU

B124453

Chemical Structure and Properties

2-Bromo-5-nitrothiazole belongs to the thiazole family of 1,3-heterocycles containing both sulfur and nitrogen atoms in a five-membered aromatic ring. The compound features a bromine substituent at the 2-position and a nitro group at the 5-position, creating a highly electron-deficient aromatic system.

The nitro group at C-5 exerts a strong electron-withdrawing inductive and mesomeric effect, significantly lowering the electron density across the ring. This electronic activation makes the C-2 carbon bearing the bromine atom particularly susceptible to both oxidative addition in transition-metal-catalyzed cross-coupling reactions and nucleophilic aromatic substitution (SNAr) by suitable nucleophiles.

The compound is typically a pale yellow to yellow crystalline solid at room temperature. Due to the presence of the nitro group and the heavy bromine atom, it exhibits moderate thermal stability and should be stored in a cool, dry environment away from strong reducing agents and bases.

Synthesis and Key Reactions

2-Bromo-5-nitrothiazole is commonly accessed via bromination of 5-nitrothiazole or through nitration of 2-bromothiazole under controlled conditions. The two-step approach—starting from commercially available thiazole, performing directed nitration, and then electrophilic or radical bromination at C-2—is also reported in the literature, though specific reaction conditions should be verified against primary sources.

Palladium-catalyzed cross-coupling: The C–Br bond at the 2-position participates readily in Suzuki–Miyaura (with arylboronic acids), Negishi, and Buchwald–Hartwig amination reactions. The electron-poor character of the ring facilitates oxidative addition to Pd(0) species, often allowing milder reaction conditions compared to electron-neutral aryl bromides.

Nucleophilic aromatic substitution (SNAr): The combined electron-withdrawing power of the ring nitrogen, the C-5 nitro group, and the thiazole sulfur activates the C-2 position toward displacement of bromide by O-, N-, and S-nucleophiles, providing direct access to 2-amino-, 2-alkoxy-, and 2-thioether-5-nitrothiazole derivatives.

Nitro group reduction: Controlled reduction of the nitro group (e.g., using iron/acetic acid, zinc/ammonium chloride, or catalytic hydrogenation) affords the corresponding 2-bromo-5-aminothiazole, a further building block for diazotization, acylation, and sulfonamide formation.

Applications in Medicinal and Agricultural Chemistry

The thiazole scaffold is a privileged heterocyclic motif present in numerous pharmacologically active molecules, including antibiotics (e.g., thiazole-containing natural products), antifungal agents, and kinase inhibitors. 2-Bromo-5-nitrothiazole serves as a key precursor enabling rapid diversification of this scaffold through the reactions described above.

Drug discovery: Researchers employ 2-Bromo-5-nitrothiazole to introduce the 5-nitrothiazole pharmacophore or, after nitro reduction, the 5-aminothiazole pharmacophore into candidate drug molecules. Nitroaromatic and nitroheterocyclic compounds have demonstrated activity against anaerobic bacteria and parasitic organisms; the specific biological activity of derivatives prepared from this building block should be assessed experimentally.

Agrochemical research: Nitrothiazole derivatives have been investigated as fungicidal and bactericidal agents in crop protection. 2-Bromo-5-nitrothiazole provides a convenient entry point for synthesizing novel analogues for structure–activity relationship (SAR) studies.

Materials science: Electron-deficient heteroarenes including nitrothiazoles are of interest as acceptor units in push–pull chromophores and organic semiconductors, though this remains a less explored area for this specific compound.

Handling, Safety, and Storage

As with all nitroaromatic and organobromine compounds, appropriate laboratory safety practices must be observed when handling 2-Bromo-5-nitrothiazole. Researchers should consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific before use.

Personal protective equipment (PPE): Chemical-resistant gloves, safety goggles, and a laboratory coat are recommended. Work should be performed in a well-ventilated fume hood to avoid inhalation of dust or vapors.

Storage: Store in a tightly sealed container in a cool (2–8 °C or as specified on the product label), dry location, away from incompatible materials including strong reducing agents, oxidizers, and strong bases. Protect from prolonged exposure to light.

Disposal: Dispose of waste material in accordance with local, national, and institutional regulations governing halogenated and nitro-containing organic waste.

Note: The specific hazard classification and GHS pictograms should be verified against the current SDS (SKU B124453) available from Aladdin Scientific.

Why Choose Aladdin Scientific's B124453

Aladdin Scientific offers 2-Bromo-5-nitrothiazole (SKU B124453) as a high-purity research reagent suitable for synthetic chemistry applications. Each lot is quality-controlled to meet defined purity specifications, supporting reproducible research outcomes.

Researchers and procurement teams benefit from competitive pricing, flexible pack sizes, and reliable stock availability. Full documentation including the Certificate of Analysis (CoA) and Safety Data Sheet (SDS) is available upon request or via the Aladdin Scientific online portal.

For inquiries about bulk quantities, custom specifications, or technical support regarding the use of B124453 in your research workflow, please contact Aladdin Scientific's technical team directly.

Frequently asked questions

What reactions can 2-Bromo-5-nitrothiazole undergo at the C-2 position?

The C-2 bromine is an excellent handle for palladium-catalyzed cross-coupling reactions (Suzuki–Miyaura, Negishi, Buchwald–Hartwig amination) and nucleophilic aromatic substitution (SNAr) with O-, N-, and S-nucleophiles. The electron-withdrawing nitro group at C-5 activates this position toward both reaction types.

How should 2-Bromo-5-nitrothiazole (B124453) be stored to maintain stability?

Store the compound in a tightly sealed container in a cool, dry location (typically 2–8 °C or as specified on the product label), away from strong reducing agents, oxidizers, strong bases, and prolonged light exposure. Always consult the current SDS for the most accurate and up-to-date storage guidance.

Can the nitro group of 2-Bromo-5-nitrothiazole be selectively reduced without affecting the C–Br bond?

Selective nitro reduction while retaining the aryl bromide is achievable under carefully controlled conditions, such as using iron powder in acetic acid or zinc/ammonium chloride systems at low temperatures. However, catalytic hydrogenation conditions may risk hydrodehalogenation; specific conditions should be optimized experimentally and verified in the literature.

What is the molecular weight of 2-Bromo-5-nitrothiazole?

The molecular weight of 2-Bromo-5-nitrothiazole (C₃HBrN₂O₂S) is approximately 209.02 g/mol.

Is 2-Bromo-5-nitrothiazole suitable for use as a pharmacophore building block in drug discovery?

Yes. The compound provides access to the 5-nitrothiazole pharmacophore directly or to the 5-aminothiazole pharmacophore after reduction. Both motifs appear in biologically active molecules investigated for antibacterial, antiparasitic, and other therapeutic applications. Biological activity of specific derivatives must be confirmed experimentally.

References

1. Pozharskii, A. F.; Soldatenkov, A. T.; Katritzky, A. R. Heterocycles in Life and Society. Wiley, 2011. (General reference on thiazole pharmacology and synthetic utility.)
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed. Oxford University Press, 2012. (General mechanistic reference for SNAr and cross-coupling reactions.)
3. Aladdin Scientific. Product Certificate of Analysis and Safety Data Sheet for 2-Bromo-5-nitrothiazole, SKU B124453. (Available from supplier upon request.)

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.