7-Hydroxy-4-(trifluoromethyl)coumarin
[CAS# 575-03-1]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyran compound
• Name: 7-Hydroxy-4-(trifluoromethyl)coumarin
• Synonyms: 4-(Trifluoromethyl)umbelliferone
• Molecular Formula: C₁₀H₅F₃O₃
• Molecular Weight: 230.14
• CAS Registry Number: 575-03-1
• EC Number: 624-706-9
• SMILES: C1=CC2=C(C=C1O)OC(=O)C=C2C(F)(F)F

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Melting point: 178 - 180 °C (Expl.)
• Boiling point: 311.4±42.0 °C 760 mmHg (Calc.)^*
• Flash point: 142.2±27.9 °C (Calc.)^*
• Index of refraction: 1.546 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Risk Statements: H300-H315-H319-H335-H336
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	2	H300
Specific target organ toxicity - single exposure	STOT SE	3	H335
Specific target organ toxicity - single exposure	STOT SE	3	H336

• Transport Information: UN 2811

Discovery and Applications

7-Hydroxy-4-(trifluoromethyl)coumarin is a fluorinated coumarin derivative with the molecular formula C₁₀H₅F₃O₃. It belongs to the class of 4-substituted coumarins, in which a trifluoromethyl group is attached at the 4-position and a hydroxy group at the 7-position. The compound was developed as part of efforts in the late 20th century to explore the chemical and photophysical properties of fluorinated coumarins. The presence of the trifluoromethyl group significantly increases the electron-withdrawing character at the 4-position, which affects the acidity of the 7-hydroxy group and modifies the overall reactivity and fluorescence properties of the molecule.

The primary application of 7-hydroxy-4-(trifluoromethyl)coumarin is in fluorescence-based chemical analysis. The compound exhibits strong fluorescence, which can be modulated by chemical interactions, pH, or complexation with metal ions. This makes it a valuable probe for detecting and quantifying various analytes in biochemical and environmental studies. Its stability, fluorescence efficiency, and spectral properties are enhanced by the trifluoromethyl group, which also contributes to increased photostability and reduced susceptibility to photobleaching.

In organic synthesis, 7-hydroxy-4-(trifluoromethyl)coumarin is used as a building block for the preparation of more complex fluorinated coumarin derivatives. The hydroxy group at the 7-position can participate in esterification, etherification, and condensation reactions, while the trifluoromethyl group can influence electronic properties, regioselectivity, and reactivity. This versatility allows chemists to design derivatives with tailored optical, chemical, or biological properties for research and industrial applications.

In pharmaceutical and medicinal chemistry, coumarin derivatives such as 7-hydroxy-4-(trifluoromethyl)coumarin have been investigated for their potential as enzyme inhibitors, anticoagulants, and therapeutic agents. The trifluoromethyl group can enhance bioavailability, metabolic stability, and lipophilicity of derivatives, while the hydroxy functionality allows for further chemical modification. Although the parent compound is mainly used as an intermediate or fluorescent probe, its derivatives have potential applications in drug development and biological studies.

In materials science, 7-hydroxy-4-(trifluoromethyl)coumarin has been used to produce fluorescent materials, dyes, and optical sensors. Incorporation of the trifluoromethyl group improves chemical and thermal stability, while the hydroxy group allows covalent attachment to polymer matrices or surfaces. These properties enable the design of functional materials for imaging, sensing, and photonic applications.

The discovery and continued use of 7-hydroxy-4-(trifluoromethyl)coumarin highlight its importance as a versatile fluorinated coumarin derivative. Its combination of strong fluorescence, chemical stability, and functionalizable hydroxy group make it a valuable tool in analytical chemistry, organic synthesis, pharmaceutical research, and materials science. The compound exemplifies how selective fluorination can enhance the properties and utility of coumarin-based molecules in both scientific and industrial contexts.

References

2019. BioTransformer: a comprehensive computational tool for small molecule metabolism prediction and metabolite identification. Journal of Cheminformatics, 11(1).
DOI: 10.1186/s13321-018-0324-5

1998. Determination of the CYP2B6 Component of 7-Ethoxy-4-Trifluoromethylcoumarin O-Deethylation Activity in Human Liver Microsomes. Methods in Molecular Biology, 107.
DOI: 10.1385/0-89603-519-0:117

1992. Synthesis of 4-trifluoromethyl-7-hydroxycoumarin derivatives. Structure of 3-cyano-4-trifluoromethyl-7-acetoxycoumarin. Bulletin of the Russian Academy of Sciences, Division of Chemical Science, 41(6).
DOI: 10.1007/bf00866588