Ethyl 2-bromothiazole-4-carboxylate
[CAS# 100367-77-9]

Identification

• Classification: Flavors and spices >> Synthetic spice >> Lactone and oxygen-containing heterocyclic compound >> Thiazole, thiophene and pyridine
• Name: Ethyl 2-bromothiazole-4-carboxylate
• Synonyms: 2-Bromothiazole-4-carboxylic acid ethyl ester
• Molecular Formula: C₆H₆BrNO₂S
• Molecular Weight: 236.09
• CAS Registry Number: 100367-77-9
• EC Number: 640-217-3
• SMILES: CCOC(=O)C1=CSC(=N1)Br

Properties

• Density: 1.7±0.1 g/cm³, Calc.^*
• Melting Point: 67-71 °C (Expl.)
• Index of Refraction: 1.57, Calc.^*
• Boiling Point: 277.6±13.0 °C (760 mmHg), Calc.^*, 313.9-316.6 °C (Expl.)
• Flash Point: 121.7±19.8 °C, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H312-H315-H319-H332-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H312

Discovery and Applications

Ethyl 2-bromothiazole-4-carboxylate is a halogenated heterocyclic ester compound that contains a thiazole core substituted with a bromine atom at position 2 and an ethyl ester group at position 4. Thiazole rings, composed of a five-membered structure containing both sulfur and nitrogen atoms, are widely recognized in the field of heterocyclic chemistry. The synthesis and characterization of thiazole derivatives began in the late 19th century, and extensive developments throughout the 20th century led to the expansion of this class into numerous derivatives, including halogenated and ester-functionalized species such as ethyl 2-bromothiazole-4-carboxylate.

The synthesis of ethyl 2-bromothiazole-4-carboxylate can be achieved through established methods starting from thiazole-4-carboxylic acid derivatives, followed by bromination at the 2-position and esterification at the carboxylic acid group. The bromine atom at position 2 is particularly reactive and allows for further functionalization through nucleophilic substitution or cross-coupling reactions such as Suzuki, Stille, or Sonogashira couplings. This makes the compound an important intermediate in synthetic organic chemistry, enabling the construction of more complex molecules for potential use in pharmaceuticals, agrochemicals, and materials science.

Applications of ethyl 2-bromothiazole-4-carboxylate have been widely reported in the context of medicinal chemistry. The thiazole ring system is present in numerous bioactive molecules, and brominated thiazoles are frequently employed as core fragments in the synthesis of antimicrobial, antiviral, or anticancer agents. The carboxylate moiety further contributes to the versatility of this compound by allowing transformation into amides, acids, and alcohols under controlled reaction conditions. As a result, ethyl 2-bromothiazole-4-carboxylate is commonly used in the synthesis of pharmacologically active substances, where it serves as a scaffold for structure-activity relationship studies.

In addition to pharmaceutical applications, the compound finds relevance in the development of small molecules for use in agricultural chemistry. Thiazole derivatives have been incorporated into fungicides, herbicides, and insecticides, where they interact with specific biological targets in plants or pests. Ethyl 2-bromothiazole-4-carboxylate provides a functional platform for designing and modifying such bioactive structures.

The compound has also been explored in academic and industrial research as a component for designing heterocyclic libraries. In combinatorial synthesis, it offers a site for diversification via palladium-catalyzed coupling reactions. This approach is particularly valuable in drug discovery and chemical biology, where structural diversity is essential for high-throughput screening of molecular targets.

Owing to its structural simplicity, functional group compatibility, and chemical reactivity, ethyl 2-bromothiazole-4-carboxylate has become a reliable building block in synthetic schemes. It has been utilized to generate molecules containing extended conjugated systems, which are relevant in the design of organic electronic materials. While the compound is primarily employed as an intermediate rather than a final product, its value in synthetic strategies remains significant.

Commercial availability of ethyl 2-bromothiazole-4-carboxylate has supported its wide usage in research laboratories and industrial settings. Its synthesis follows reproducible and well-characterized procedures, and its storage and handling are relatively straightforward under standard laboratory conditions.

In summary, ethyl 2-bromothiazole-4-carboxylate is a structurally defined and synthetically useful compound that has been integrated into numerous applications in chemical synthesis. Its well-documented reactivity and role as an intermediate in the development of biologically and industrially relevant molecules reflect its enduring importance in the field of heterocyclic chemistry.

References

2-bromothiazole-4-carboxylate| 2022. Fragment-Sized Thiazoles in Fragment-Based Drug Discovery Campaigns: Friend or Foe? ACS Medicinal Chemistry Letters, 13(12).
DOI: 10.1021/acsmedchemlett.2c00429

2017. Synthesis of New 1,3-Thiazolecarbaldehydes. Russian Journal of General Chemistry, 87(12).
DOI: 10.1134/s1070363217120039

2017. Synthesis of Ring-Opened Analogues of Oxysterol-Binding Protein-Inhibiting Piperidinyl-thiazole Fungicides. Synlett, 28(14).
DOI: 10.1055/s-0036-1588473