(R)-1-(3-Nitro-5-(trifluoromethyl)phenyl)ethan-1-amine hydrochloride
[CAS# 2230840-47-6]

Identification

• Classification: Chemical reagent >> Organic reagent >> Amine salt (ammonium salt)
• Name: (R)-1-(3-Nitro-5-(trifluoromethyl)phenyl)ethan-1-amine hydrochloride
• Synonyms: (1R)-1-[3-nitro-5-(trifluoromethyl)phenyl]ethanamine;hydrochloride
• Molecular Formula: C₉H₁₀ClF₃N₂O₂
• Molecular Weight: 270.64
• CAS Registry Number: 2230840-47-6
• SMILES: C[C@H](C1=CC(=CC(=C1)[N+](=O)[O-])C(F)(F)F)N.Cl

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319
• Precautionary Statements: P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Discovory and Applicatios

The chemical substance (R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethan-1-amine hydrochloride is a chiral amine hydrochloride salt featuring nitro and trifluoromethyl substituents on a phenyl ring, widely utilized as a synthetic intermediate in pharmaceutical chemistry. Its discovery and applications are well-documented in the literature, rooted in advancements in chiral amine synthesis and fluorinated aromatic chemistry.

The origins of this compound are tied to the study of substituted aromatic amines, which have been explored since the 19th century for their versatility in organic synthesis. The trifluoromethyl group, recognized in the mid-20th century for enhancing metabolic stability and lipophilicity in drug molecules, became a key substituent in medicinal chemistry. Nitro groups, valued for their electron-withdrawing properties and potential for reduction to amines, have been similarly employed. The development of chiral amines, such as the (R)-1-aminoethyl group, gained momentum in the 1970s and 1980s with the advent of asymmetric synthesis techniques, including enantioselective catalysis and chiral auxiliaries. The specific combination of nitro and trifluoromethyl groups at the 3- and 5-positions, respectively, with a chiral amine at the benzylic position, emerged in the late 20th century to meet the pharmaceutical industry’s demand for enantiopure intermediates. The hydrochloride salt form enhances solubility and stability, facilitating handling in synthetic processes.

Synthetically, (R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethan-1-amine hydrochloride is typically prepared through a multi-step process. A common route starts with 3-nitro-5-(trifluoromethyl)acetophenone, where the nitro and trifluoromethyl groups are pre-installed or introduced via nitration and trifluoromethylation of a suitable precursor. The chiral amine is formed through enantioselective reductive amination of the ketone using a chiral catalyst, such as a rhodium or ruthenium complex, with an ammonia source, or by employing a chiral auxiliary to control stereochemistry. The resulting amine is then converted to its hydrochloride salt by treatment with hydrochloric acid to improve crystallinity and stability. These steps leverage well-established protocols in asymmetric synthesis and fluorinated chemistry, ensuring high enantiomeric purity and yields.

The primary application of (R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethan-1-amine hydrochloride is as a synthetic intermediate in pharmaceutical chemistry. The chiral amine serves as a stereospecific handle for forming amides, amines, or heterocycles, while the trifluoromethyl group enhances metabolic stability and lipophilicity, and the nitro group provides a site for reduction to an aniline, enabling further functionalization. This compound is used in the synthesis of drug candidates, such as kinase inhibitors, receptor antagonists, and anti-inflammatory agents, where the (R)-configuration ensures specific interactions with biological targets. The nitro group’s versatility allows for the construction of diverse scaffolds, making it valuable in medicinal chemistry.

In academic research, the compound is employed to study asymmetric synthesis, the electronic effects of nitro and trifluoromethyl substituents, and the reactivity of chiral amines. Its synthesis has contributed to the development of enantioselective catalysts and trifluoromethylation methods. The compound also finds use in agrochemical synthesis, where fluorinated and chiral molecules are valued for their bioactivity in pesticides or herbicides.

The significance of (R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethan-1-amine hydrochloride lies in its role as a chiral, multifunctional intermediate that combines stereospecificity with the advantageous properties of nitro and trifluoromethyl groups. Its development reflects progress in asymmetric synthesis, fluorinated chemistry, and salt formation techniques. By enabling the efficient synthesis of enantiopure, biologically active molecules, it has become a critical tool in advancing pharmaceutical, agrochemical, and chemical research.