Ethyl 2-aminothiazole-5-carboxylate
[CAS# 32955-21-8]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Ethyl 2-aminothiazole-5-carboxylate
• Synonyms: Ethyl 2-amino-1,3-thiazole-5-carboxylate
• Molecular Formula: C₆H₈N₂O₂S
• Molecular Weight: 172.20
• CAS Registry Number: 32955-21-8
• EC Number: 676-105-6
• SMILES: CCOC(=O)C1=CN=C(S1)N

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Melting point: 159 - 163 °C (Expl.)
• Boiling point: 308.0±15.0 °C 760 mmHg (Calc.)^*
• Flash point: 140.1±20.4 °C (Calc.)^*
• Index of refraction: 1.588 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302+H312+H332-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	H312
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

Ethyl 2-aminothiazole-5-carboxylate is a heteroaromatic compound consisting of a five-membered thiazole ring substituted with an amino group at position 2 and an ethyl ester at position 5. Its molecular formula is C₆H₈N₂OS, with a molecular weight of approximately 144.20 g/mol. The thiazole ring contains both a nitrogen atom at position 1 and a sulfur atom at position 3, creating an electron-rich heterocyclic system. The amino and ester substituents confer both nucleophilic and electrophilic reactivity, making the molecule suitable for a range of chemical transformations.

The synthesis of ethyl 2-aminothiazole-5-carboxylate typically involves the construction of the thiazole ring from α-haloketones or 1,3-dicarbonyl compounds with a sulfur source and a nitrogen-containing reagent. The amino group at position 2 is usually introduced during ring formation using ammonia or a primary amine, while the ester functionality at position 5 can be installed either through direct cyclization with an ester-containing precursor or via subsequent esterification of a carboxylic acid. Careful control of reaction conditions, including temperature, solvent, and stoichiometry, is required to achieve selective formation of the 2-amino and 5-ester substitution pattern.

Chemically, the amino group is nucleophilic and can undergo acylation, alkylation, or condensation reactions, while the ethyl ester is reactive toward hydrolysis, transesterification, or amidation. The electron-rich thiazole ring allows for electrophilic substitution, particularly at positions 4 and 5, but the presence of substituents at positions 2 and 5 modifies the regioselectivity. This combination of functional groups provides multiple points of chemical modification while preserving the heteroaromatic core.

The compound is generally a solid at room temperature and demonstrates solubility in polar organic solvents such as ethanol, acetone, and dimethylformamide. It is chemically stable under ambient conditions but should be protected from strong oxidizing agents, acids, or bases that could decompose the ester or amino functionalities. The molecule’s structure enables hydrogen bonding and π–π interactions, which can influence crystallization, solubility, and reactivity in synthetic applications.

In practical applications, ethyl 2-aminothiazole-5-carboxylate is widely used as a building block in medicinal chemistry, agrochemical research, and heterocyclic synthesis. The amino and ester groups allow for selective functionalization, making it suitable for the preparation of thiazole-based derivatives, heterocyclic scaffolds, and bioactive compounds. It is particularly valuable in the synthesis of small molecules designed for biological activity, where the thiazole ring provides structural rigidity and electronic properties relevant to target binding.

Overall, the combination of a thiazole ring, a nucleophilic amino group, and an electrophilic ester group renders ethyl 2-aminothiazole-5-carboxylate a versatile intermediate. Its predictable reactivity and multiple functional handles support its use in organic synthesis, drug discovery, and the development of complex heterocyclic compounds.

References

2010. From Ethyl 3-Ethoxyacrylate and Thioureas. Science of Synthesis.
URL: SD-111-00157