2-Methyl-3-trifluoromethylaniline
[CAS# 54396-44-0]

Identification

• Classification: Organic raw materials >> Organometallic salt
• Name: 2-Methyl-3-trifluoromethylaniline
• Synonyms: 3-Amino-2-methylbenzotrifluoride
• Molecular Formula: C₈H₈F₃N
• Molecular Weight: 175.15
• CAS Registry Number: 54396-44-0
• EC Number: 259-145-5
• SMILES: CC1=C(C=CC=C1N)C(F)(F)F

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 38 - 42 °C (Expl.)
• Boiling point: 203.0±40.0 °C 760 mmHg (Calc.)^*, 227.6 - 230.5 °C (Expl.)
• Flash point: 83.8±20.1 °C (Calc.)^*, 96 °C (Expl.)
• Index of refraction: 1.481 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07 Danger
• Risk Statements: H302-H312-H314-H315-H318-H319-H330-H332-H335
• Safety Statements: P260-P261-P264-P264+P265-P270-P271-P280-P284-P301+P317-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P351+P338-P305+P354+P338-P316-P317-P319-P320-P321-P330-P332+P317-P337+P317-P362+P364-P363-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	2	H330
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H301
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

2-Methyl-3-trifluoromethylaniline is an aromatic amine compound characterized by a benzene ring substituted with a methyl group at the 2-position, a trifluoromethyl group (-CF₃) at the 3-position, and an amino group (-NH₂) attached directly to the ring. The molecular formula for this compound is C₈H₈F₃N, reflecting its composition of carbon, hydrogen, fluorine, and nitrogen atoms.

The presence of the amino group classifies the molecule as an aniline derivative, which is a fundamental class of compounds widely used in chemical synthesis and industrial applications. The amino group is a nucleophilic site and can participate in various reactions such as acylation, sulfonation, diazotization, and coupling reactions to form azo dyes or other functional derivatives.

The methyl substituent at the 2-position is an electron-donating group through hyperconjugation and inductive effects. Its proximity to the amino group influences the electronic environment of the aromatic ring, potentially affecting the reactivity and orientation of electrophilic substitution reactions.

The trifluoromethyl group at the 3-position is a strongly electron-withdrawing substituent due to the high electronegativity of fluorine atoms. This group impacts the compound’s lipophilicity, metabolic stability, and acidity/basicity of the amino group. The -CF₃ group is also known to enhance chemical and thermal stability, which is valuable in pharmaceutical and agrochemical design.

Synthetically, 2-methyl-3-trifluoromethylaniline can be prepared by selective substitution reactions on suitably substituted aromatic precursors or by reduction of corresponding nitro derivatives. The introduction of the trifluoromethyl group typically involves trifluoromethylation reactions using reagents such as trifluoromethyl iodide or copper-mediated trifluoromethylation.

In practical applications, derivatives of trifluoromethylanilines are utilized in the pharmaceutical industry as intermediates in the synthesis of active pharmaceutical ingredients (APIs), due to their ability to modify the biological activity and pharmacokinetic properties of drugs. Their unique electronic characteristics also make them valuable in materials science, for example in the development of specialty polymers and agrochemicals.

Physicochemically, 2-methyl-3-trifluoromethylaniline is generally a liquid or low-melting solid, soluble in organic solvents such as ethanol, dichloromethane, and acetone. Analytical techniques including nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and mass spectrometry are commonly used for its characterization, confirming the substitution pattern and purity.

In summary, 2-methyl-3-trifluoromethylaniline is a functionalized aromatic amine with both electron-donating and electron-withdrawing groups on the benzene ring. Its chemical properties and synthetic versatility make it a valuable compound in pharmaceutical synthesis, materials science, and industrial chemistry.

References

2017. An improved solvent-free synthesis of flunixin and 2-(arylamino) nicotinic acid derivatives using boric acid as catalyst. Chemistry Central Journal, 11(1).
DOI: 10.1186/s13065-017-0355-4

2017. One-pot green synthesis and cytotoxicity of new α-aminophosphonates. Research on Chemical Intermediates, 44(1).
DOI: 10.1007/s11164-017-3060-y

2018. Ruthenium-Catalyzed Ortho C(sp2)-H Amidation of Benzaldehydes with Organic Azides. Synlett, 29(7).
DOI: 10.1055/s-0036-1591765