5-Bromothiophene-2-carboxylic acid
[CAS# 7311-63-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Thiophene compound
• Name: 5-Bromothiophene-2-carboxylic acid
• Synonyms: 5-Bromo-2-thiophenecarboxylic acid
• Molecular Formula: C₅H₃BrO₂S
• Molecular Weight: 207.04
• CAS Registry Number: 7311-63-9
• EC Number: 615-911-4
• SMILES: C1=C(SC(=C1)Br)C(=O)O

Properties

• Density: 1.9±0.1 g/cm³, Calc.^*
• Melting point: 140-142 ºC (Expl.)
• Index of Refraction: 1.650, Calc.^*
• Boiling Point: 318.9±27.0 ºC (760 mmHg), Calc.^*
• Flash Point: 146.7±23.7 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

Discovory and Applicatios

5-Bromothiophene-2-carboxylic acid is a halogenated thiophene derivative, consisting of a thiophene ring with a bromine atom at the 5-position and a carboxyl group (-COOH) at the 2-position. Thiophene, a five-membered aromatic ring containing sulfur, is a widely studied structure due to its stability and versatile reactivity. The bromine substitution in 5-bromothiophene-2-carboxylic acid enhances its reactivity, making it a valuable intermediate in organic synthesis, medicinal chemistry, and material science.

The discovery of 5-bromothiophene-2-carboxylic acid is tied to the growing interest in thiophene derivatives, which are known for their electronic properties and stability. The bromine atom in the compound plays a crucial role in increasing the reactivity of the thiophene ring, allowing it to undergo various substitution reactions. The synthesis of 5-bromothiophene-2-carboxylic acid typically involves the bromination of thiophene-2-carboxylic acid using bromine or brominating agents such as N-Bromosuccinimide (NBS). This reaction introduces the bromine atom selectively at the 5-position, resulting in the desired product.

One of the major applications of 5-bromothiophene-2-carboxylic acid is in organic synthesis. The bromine atom makes it an excellent precursor for further transformations, particularly substitution reactions with nucleophiles. These reactions allow the introduction of various functional groups into the thiophene ring, leading to the synthesis of more complex organic molecules. This reactivity is particularly useful in the preparation of biologically active compounds, agrochemicals, and pharmaceuticals. Moreover, the carboxyl group (-COOH) in 5-bromothiophene-2-carboxylic acid can be involved in esterification and amidation reactions, making it a versatile intermediate for the formation of various derivatives.

In medicinal chemistry, 5-bromothiophene-2-carboxylic acid has shown promise as a building block for the synthesis of biologically active compounds. Thiophene derivatives are known for their diverse pharmacological activities, including antimicrobial, anticancer, and anti-inflammatory effects. The bromine substitution enhances the compound’s interaction with biological targets, potentially improving its potency and selectivity. Researchers have explored 5-bromothiophene-2-carboxylic acid derivatives in drug development, particularly for cancer and infection treatment. The carboxyl group also facilitates conjugation with other pharmacologically active molecules, enhancing their solubility, stability, and bioavailability.

In material science, 5-bromothiophene-2-carboxylic acid is used in the development of organic semiconductors. Thiophene-based compounds are core elements of organic light-emitting diodes (OLEDs), organic photovoltaics (OPVs), and organic field-effect transistors (OFETs). The bromine atom enhances the electronic properties of the thiophene ring, making 5-bromothiophene-2-carboxylic acid a valuable building block for the synthesis of organic semiconducting materials. These materials are used in flexible, low-cost electronic devices, offering potential for applications in renewable energy and electronics.

Additionally, 5-bromothiophene-2-carboxylic acid has potential in catalytic applications. The bromine atom interacts with metals, forming complexes that can be used in catalytic reactions such as cross-coupling and polymerization. These complexes could offer new pathways for efficient chemical transformations, broadening the applications of this compound in synthetic chemistry.

In agrochemicals, 5-bromothiophene-2-carboxylic acid is a useful precursor for the synthesis of herbicides, fungicides, and insecticides. Thiophene derivatives are known to exhibit biological activity against pests and plants, and the bromine atom enhances the stability and efficacy of these compounds. Thus, 5-bromothiophene-2-carboxylic acid contributes to crop protection and pest management in agriculture.

In conclusion, 5-bromothiophene-2-carboxylic acid is a versatile compound with a wide range of applications. Its reactivity, especially at the brominated position, makes it an important intermediate in organic synthesis and a valuable building block for pharmaceuticals, agrochemicals, and electronic materials. As research progresses, its applications in drug development, material science, and catalysis are expected to expand, highlighting the compound’s significance in various industrial sectors.

References

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DOI: 10.1007/s00044-019-02400-x

2018. Structural basis for potent inhibition of d-amino acid oxidase by thiophene carboxylic acids. European Journal of Medicinal Chemistry, 159.
DOI: 10.1016/j.ejmech.2018.09.040

2011. Propylphosphonic Anhydride (T3P®)-Mediated One-Pot Rearrangement of Carboxylic Acids to Carbamates. Synthesis, 2011(8).
DOI: 10.1055/s-0030-1259964