5-Amino-3-methoxy-1,2,4-thiadiazole
[CAS# 98022-43-6]

Identification

• Classification: Flavors and spices >> Synthetic spice >> Lactone and oxygen-containing heterocyclic compound >> Thiazole, thiophene and pyridine
• Name: 5-Amino-3-methoxy-1,2,4-thiadiazole
• Synonyms: 3-methoxy-1,2,4-thiadiazol-5-amine
• Molecular Formula: C₃H₅N₃OS
• Molecular Weight: 131.16
• CAS Registry Number: 98022-43-6
• EC Number: 671-377-2
• SMILES: COC1=NSC(=N1)N

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Melting point: 172 - 173 °C (Expl.)
• Boiling point: 254.0±23.0 °C 760 mmHg (Calc.)^*
• Flash point: 107.4±22.6 °C (Calc.)^*
• Index of refraction: 1.609 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07;GHS09 Warning
• Risk Statements: H315-H319-H335-H400-H410
• Safety Statements: P261-P264-P264+P265-P271-P273-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

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

Discovery and Applications

5-Amino-3-methoxy-1,2,4-thiadiazole is a heterocyclic compound consisting of a five-membered 1,2,4-thiadiazole ring substituted with an amino group at the 5-position and a methoxy group at the 3-position. The 1,2,4-thiadiazole scaffold is aromatic and electron-rich due to the presence of nitrogen and sulfur heteroatoms, which can participate in hydrogen bonding, dipole interactions, and coordination with metal centers. The combination of amino and methoxy substituents imparts both nucleophilic and electron-donating properties, making this compound a versatile intermediate in synthetic and medicinal chemistry.

The synthesis of 5-amino-3-methoxy-1,2,4-thiadiazole generally involves cyclization reactions of suitable thiosemicarbazide derivatives with nitrile or ester precursors under controlled conditions. The methoxy group can be introduced via methylation of a hydroxy precursor or by using methoxy-substituted starting materials. Reaction parameters such as temperature, solvent, and reagent stoichiometry are optimized to favor selective formation of the thiadiazole ring and prevent side reactions. The final product is typically isolated as a crystalline solid and purified by recrystallization or chromatography.

In organic synthesis, 5-amino-3-methoxy-1,2,4-thiadiazole serves as a building block for constructing substituted thiadiazoles and fused heterocyclic systems. The amino group can undergo acylation, alkylation, or condensation reactions, while the methoxy group can be further modified or serve as an electron-donating substituent to influence reactivity. These features allow stepwise derivatization to prepare more complex molecules with specific electronic or steric properties.

In medicinal chemistry, derivatives of 5-amino-3-methoxy-1,2,4-thiadiazole are investigated for their potential biological activities, including antimicrobial, anti-inflammatory, or enzyme-inhibiting properties. The amino group facilitates hydrogen bonding with biological targets, while the heterocyclic core provides a planar, rigid scaffold that can interact with active sites or receptors. The methoxy substituent can influence lipophilicity and metabolic stability, contributing to favorable pharmacokinetic profiles.

The compound is also used in chemical methodology research. Its multifunctional nature allows chemists to explore selective heterocycle functionalization, transition-metal-catalyzed reactions, and synthesis of novel thiadiazole-based materials. It can act as a model substrate for studying the reactivity of electron-rich heteroaromatic systems with multiple nucleophilic and electrophilic sites.

Physically, 5-amino-3-methoxy-1,2,4-thiadiazole is typically obtained as a crystalline solid with moderate solubility in polar organic solvents such as ethanol, methanol, and dimethylformamide. It is stable under standard laboratory conditions but should be protected from strong oxidizing agents or acids that could modify the thiadiazole ring or substituents. Proper handling ensures chemical integrity for synthetic, medicinal, and research applications.

Overall, 5-amino-3-methoxy-1,2,4-thiadiazole is a multifunctional heterocyclic compound featuring an amino and a methoxy substituent on a 1,2,4-thiadiazole core. Its structural features enable selective chemical transformations and derivatization, making it a valuable intermediate in the synthesis of bioactive molecules, functional heterocycles, and complex organic targets in medicinal and synthetic chemistry.

References

2015. Benzotriazole-Based Strategies Toward Peptidomimetics, Conjugates, and Other Peptide Derivatives. The Chemistry of Benzotriazole Derivatives.
DOI: 10.1007/7081_2015_182