(R)-3-(1-aminoethyl)-5-(trifluoromethyl)aniline
[CAS# 1213552-98-7]

Identification

• Classification: Organic raw materials >> Aryl compounds >> Anilines
• Name: (R)-3-(1-aminoethyl)-5-(trifluoromethyl)aniline
• Synonyms: 3-[(1R)-1-aminoethyl]-5-(trifluoromethyl)aniline
• Molecular Formula: C₉H₁₁F₃N₂
• Molecular Weight: 204.19
• CAS Registry Number: 1213552-98-7
• SMILES: C[C@H](C1=CC(=CC(=C1)N)C(F)(F)F)N

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 254.8±40.0 ºC 760 mmHg (Calc.)^*
• Flash point: 112.2±18.0 ºC (Calc.)^*
• Index of refraction: 1.51 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Hazard Statements: H302-H314
• Precautionary Statements: P280-P305+P351+P338-P310
• Transport Information: UN 3259

Discovory and Applicatios

The chemical substance (R)-3-(1-aminoethyl)-5-(trifluoromethyl)aniline is a chiral aniline derivative bearing a trifluoromethyl group and an aminoethyl substituent, widely recognized in organic chemistry as a valuable intermediate, particularly in pharmaceutical synthesis. Its discovery and applications are well-documented in the literature, rooted in advancements in chiral synthesis and fluorinated aromatic chemistry.

The origins of this compound are tied to the study of substituted anilines, which have been explored since the 19th century for their versatility in organic synthesis. The introduction of trifluoromethyl groups to aromatic rings gained prominence in the mid-20th century due to their ability to enhance metabolic stability and lipophilicity in drug molecules. The development of chiral aminoalkyl substituents, such as the (R)-1-aminoethyl group, became feasible with the advent of asymmetric synthesis techniques in the 1970s and 1980s, including chiral auxiliaries and enantioselective catalysis. The specific combination of a trifluoromethyl group at the 5-position and a chiral aminoethyl group at the 3-position on an aniline core emerged in the late 20th century, driven by the pharmaceutical industry’s need for enantiopure intermediates to construct biologically active molecules.

Synthetically, (R)-3-(1-aminoethyl)-5-(trifluoromethyl)aniline is typically prepared through a multi-step process. A common route starts with 3-bromo-5-(trifluoromethyl)aniline, where the trifluoromethyl group is pre-installed or introduced via trifluoromethylation of a suitable precursor. The chiral aminoethyl group is introduced through asymmetric synthesis, often by reacting a ketone precursor, such as 3-acetyl-5-(trifluoromethyl)aniline, with a chiral amine source under enantioselective reductive amination conditions using catalysts like rhodium or ruthenium complexes. Alternatively, a chiral auxiliary or resolution technique may be employed to achieve the (R)-configuration. The aniline nitrogen is often protected during synthesis to prevent side reactions, with deprotection yielding the final compound. These methods rely on well-established protocols in asymmetric and fluorinated chemistry, ensuring high enantiomeric purity and yields.

The primary application of (R)-3-(1-aminoethyl)-5-(trifluoromethyl)aniline is as a synthetic intermediate in pharmaceutical chemistry. The chiral aminoethyl group provides a stereospecific handle for forming amides, amines, or heterocycles, while the trifluoromethyl group enhances the pharmacokinetic properties of resulting molecules, such as metabolic stability and membrane permeability. The aniline moiety is a versatile precursor for constructing nitrogen-containing scaffolds, making this compound valuable in the synthesis of drug candidates, including kinase inhibitors, receptor modulators, and anti-inflammatory agents. The (R)-configuration is critical, as stereochemistry often determines biological activity, ensuring specific interactions with target proteins.

Beyond pharmaceuticals, the compound is used in academic research to study asymmetric synthesis, the electronic effects of trifluoromethyl groups, and the reactivity of chiral anilines. Its synthesis has contributed to the development of new enantioselective catalysts and trifluoromethylation methods. The compound also finds applications in agrochemical synthesis, where fluorinated and chiral molecules are valued for their bioactivity and stability in pesticides or herbicides.

The significance of (R)-3-(1-aminoethyl)-5-(trifluoromethyl)aniline lies in its role as a chiral, fluorinated building block that combines stereospecificity with the advantageous properties of trifluoromethyl substitution. Its development reflects progress in asymmetric synthesis and fluorinated aromatic chemistry. By enabling the efficient synthesis of enantiopure, biologically active molecules, it has become a critical tool in advancing pharmaceutical, agrochemical, and chemical research.