3-Trifluoromethylphenol
[CAS 98-17-9]

Identification

• Classification: Organic raw materials >> Alcohols, phenols, phenolic compounds and derivatives
• Name: 3-Trifluoromethylphenol
• Synonyms: m-Hydroxybenzotrifluoride; 3-Hydroxybenzotrifluoride; 3-(Trifluoromethyl)phenol; alpha,alpha,alpha-Trifluoro-m-cresol
• Molecular Formula: C₇H₅F₃O
• Molecular Weight: 162.11
• CAS Registry Number: 98-17-9
• EC Number: 202-645-5
• SMILES: C1=CC(=CC(=C1)O)C(F)(F)F

Properties

• Density: 1.3$+/-$0.1 g/cm³ Calc.^*, 1.333 g/mL (Expl.)
• Melting point: -2 - -1.8 $degree$C (Expl.)
• Boiling point: 178.0 $degree$C 760 mmHg (Calc.)^*, 178 - 179 $degree$C (Expl.)
• Flash point: 73.9 $degree$C (Calc.)^*, 73 $degree$C (Expl.)
• Index of refraction: 1.458 (Calc.)^*, 1.458 (Expl.)

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

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07 Danger
• Risk Statements: H301-H302-H312-H314-H315-H318-H319-H335-H412
• Safety Statements: P260-P261-P264-P264+P265-P270-P271-P273-P280-P301+P316-P301+P317-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P351+P338-P305+P354+P338-P316-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P363-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Acute toxicity	Acute Tox.	4	H312
Skin corrosion	Skin Corr.	1B	H314
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	3	H301
Eye irritation	Eye Irrit.	2	H319
Serious eye damage	Eye Dam.	1	H318
Skin corrosion	Skin Corr.	1	H314
Acute toxicity	Acute Tox.	4	H332
Skin corrosion	Skin Corr.	1C	H314
Flammable liquids	Flam. Liq.	4	H227

Discovery and Applications

3-Trifluoromethylphenol is an aromatic phenolic compound containing both a hydroxyl group and a trifluoromethyl substituent attached to a benzene ring. Its molecular formula is C₇H₅F₃O. The structure consists of a phenol core in which a trifluoromethyl group (–CF₃) is located at the 3-position (meta position) relative to the hydroxyl group.

The molecule combines two chemically significant functional groups: a phenolic hydroxyl group and a strongly electron-withdrawing trifluoromethyl substituent. The hydroxyl group imparts weak acidity, hydrogen-bonding capability, and nucleophilic behavior through the oxygen atom, while the –CF₃ group strongly affects the electronic properties of the aromatic ring.

The trifluoromethyl group is one of the most powerful electron-withdrawing substituents used in organic chemistry. Through its strong inductive effect, it decreases electron density in the aromatic ring and influences both reactivity and acidity. In 3-trifluoromethylphenol, this effect increases the acidity of the phenolic hydroxyl group compared with unsubstituted phenol, because the conjugate phenoxide ion is stabilized by the electron-withdrawing substituent.

The phenolic hydroxyl group can undergo typical phenol reactions, including esterification, etherification, oxidation, and deprotonation under basic conditions to form phenoxide salts. The aromatic ring may also participate in electrophilic substitution reactions, although the strongly deactivating –CF₃ group reduces overall ring reactivity compared with simple phenols.

The meta relationship between the hydroxyl and trifluoromethyl groups affects the directing effects during aromatic substitution. The hydroxyl group is an activating ortho/para director, whereas the trifluoromethyl group is a deactivating meta director. The combined influence of these substituents determines regioselectivity in synthetic transformations.

Fluorinated phenols such as 3-trifluoromethylphenol are important intermediates in medicinal chemistry, agrochemical synthesis, and specialty materials chemistry. The introduction of fluorine-containing groups often improves metabolic stability, lipophilicity, oxidative resistance, and biological activity in target molecules.

The trifluoromethyl substituent also increases hydrophobicity while maintaining a relatively compact steric profile. This balance of hydrophobic and electronic effects makes CF₃-substituted aromatic compounds especially valuable in pharmaceutical design.

Synthetically, 3-trifluoromethylphenol can be prepared through several routes, including hydroxylation of trifluoromethyl-substituted aromatic precursors, selective trifluoromethylation of phenol derivatives, or diazotization–hydrolysis sequences starting from corresponding amino compounds.

From a physicochemical perspective, the molecule exhibits moderate polarity due to the hydroxyl group, while the aromatic ring and trifluoromethyl group contribute hydrophobic character. The strong carbon–fluorine bonds confer high thermal and chemical stability.

The hydroxyl group allows intermolecular hydrogen bonding, which influences boiling point and solubility. However, the presence of the hydrophobic CF₃ group limits water solubility relative to simple phenol.

Spectroscopically, the compound displays characteristic aromatic and phenolic ultraviolet absorption features, while the fluorine atoms strongly influence nuclear magnetic resonance behavior due to fluorine coupling effects.

Historically, trifluoromethyl-substituted aromatic compounds gained major industrial importance with the expansion of organofluorine chemistry in pharmaceuticals and agrochemicals during the 20th century. Their unique combination of electronic and physicochemical properties made them valuable building blocks in modern synthetic chemistry.

Overall, 3-trifluoromethylphenol is a meta-substituted fluorinated phenol characterized by a hydroxyl group and a strongly electron-withdrawing trifluoromethyl substituent on an aromatic ring. Its altered acidity, enhanced chemical stability, and fluorinated aromatic character make it an important intermediate in organic, medicinal, and materials chemistry.

References

2025. Development of novel fluoro-substituted rivastigmine derivatives as selective AChE inhibitors for the treatment of AD. Medicinal Chemistry Research.
DOI: 10.1007/s00044-024-03250-y

2022. Functionalizing aromatic compounds with optical cycling centres. Nature Chemistry.
DOI: 10.1038/s41557-022-00998-x