5-Bromo-1,2-oxazole
[CAS# 1133930-99-0]

Identification

• Classification: Organic raw materials >> Heterocyclic compound
• Name: 5-Bromo-1,2-oxazole
• Synonyms: 5-Bromoisoxazole
• Molecular Formula: C₃H₂BrNO
• Molecular Weight: 147.96
• CAS Registry Number: 1133930-99-0
• SMILES: C1=C(ON=C1)Br

Properties

• Density: 1.8±0.1 g/cm³ Calc.^*
• Boiling point: 182.7±13.0 ºC 760 mmHg (Calc.)^*
• Flash point: 64.3±19.8 ºC (Calc.)^*
• Index of refraction: 1.508 (Calc.)^*

Discovory and Applicatios

5-Bromo-1,2-oxazole is a halogenated heterocyclic compound comprising a five-membered aromatic ring with adjacent nitrogen and oxygen atoms at positions 1 and 2, and a bromine atom substituted at position 5. Its molecular formula is C₃H₂BrNO. The compound belongs to the oxazole family, which is notable for its presence in a variety of biologically active molecules. The addition of a bromine atom at the 5-position of the oxazole ring enhances its chemical reactivity, making it a valuable synthetic intermediate in organic chemistry.

The oxazole ring system was first identified in the 19th century, and since then, numerous derivatives have been developed for applications in medicinal and synthetic chemistry. The halogenation of oxazoles, including bromination at the 5-position, was explored during the development of modern electrophilic substitution techniques. This regioselective halogenation was refined to provide access to halogenated heterocycles that could be used in a variety of transformations, particularly in cross-coupling chemistry.

5-Bromo-1,2-oxazole serves as an essential precursor in the synthesis of complex molecules. Due to the reactivity of the carbon–bromine bond, this compound undergoes palladium-catalyzed coupling reactions such as Suzuki–Miyaura, Stille, and Heck reactions. These reactions are frequently employed in constructing new carbon–carbon bonds, making the compound a useful intermediate for generating structurally diverse oxazole derivatives.

In medicinal chemistry, oxazole derivatives are known for their diverse biological properties, including antimicrobial, antiviral, anti-inflammatory, and anticancer activity. The 5-bromo derivative is commonly used in structure–activity relationship studies, where it provides a point of diversification via substitution or coupling at the 5-position. This allows researchers to generate analogs and evaluate their biological performance systematically. Its small size and reactivity make it suitable for incorporation into larger bioactive frameworks.

In agrochemical research, compounds derived from 5-bromo-1,2-oxazole have been explored as potential crop protection agents. Its use as a synthetic building block extends into materials science as well. Some derivatives have been evaluated in the development of functional polymers or advanced materials due to the oxazole ring's electronic characteristics and stability. The ring's aromaticity and heteroatom content impart desirable thermal and optical properties in various polymeric applications.

The synthesis of 5-bromo-1,2-oxazole generally involves electrophilic bromination of oxazole under controlled conditions. Reagents such as N-bromosuccinimide are commonly used, and solvent and temperature conditions are optimized to achieve regioselectivity. Alternatively, it may be prepared by cyclization reactions followed by bromination, depending on the available starting materials. The reaction conditions must be managed carefully to avoid overbromination or degradation of the ring system.

From a safety standpoint, 5-bromo-1,2-oxazole is handled with typical laboratory precautions applicable to halogenated heterocycles. It should be stored in a dry, cool environment, away from direct light and incompatible substances. Protective equipment, including gloves, safety goggles, and fume hoods, is recommended during handling and reaction procedures. Due to its brominated nature, appropriate waste disposal measures should be followed in compliance with environmental regulations.

5-Bromo-1,2-oxazole continues to be an important compound in synthetic organic chemistry. Its bromine substituent allows for diverse chemical modifications, enabling the construction of new molecular architectures with potential use in pharmaceuticals, agrochemicals, and material science. Its discovery and development reflect the broader advancement of heterocyclic chemistry, particularly the strategic use of halogen atoms to enable precise molecular design.

References

2020. Synthesis and application of haloisoxazoles. Chemistry of Heterocyclic Compounds, 56(12).
DOI: 10.1007/s10593-020-02845-8