Chemical Identity and Physical Properties

1-Chloro-2-(trifluoromethoxy)benzene (CAS 2106-51-6, Aladdin SKU C130119) is an ortho-substituted benzene derivative carrying a chlorine atom at the 1-position and a trifluoromethoxy group (–OCF3) at the 2-position. Its molecular formula is C₇H₄ClF₃O with a molecular weight of approximately 196.55 g/mol.

The compound presents as a colorless to pale yellow liquid under ambient conditions. The –OCF3 group is a strongly electron-withdrawing substituent that significantly reduces electron density on the aromatic ring, activating the ring toward nucleophilic aromatic substitution at positions bearing leaving groups and modulating lipophilicity in drug-candidate molecules. The presence of three fluorine atoms confers high metabolic stability and improved membrane permeability to molecules incorporating this motif.

Key physicochemical parameters (verify against current certificate of analysis): density approximately 1.45 g/mL, boiling point in the range of 145–150 °C (literature estimate; confirm with supplier CoA), and low water solubility consistent with its lipophilic character (logP estimated >3).

Synthetic Applications and Research Uses

1-Chloro-2-(trifluoromethoxy)benzene serves as a key electrophilic building block in a variety of transition-metal-catalyzed cross-coupling reactions. The aryl chloride bond is amenable to palladium-catalyzed Suzuki–Miyaura, Negishi, Heck, and Buchwald–Hartwig coupling reactions under appropriate catalyst/ligand systems, enabling efficient construction of complex biaryl and aryl–heteroaryl scaffolds bearing the –OCF3 motif.

In medicinal chemistry, the trifluoromethoxy group is valued for its ability to increase lipophilicity, enhance metabolic stability against cytochrome P450-mediated oxidation, and improve oral bioavailability of drug candidates. The ortho-chloro/trifluoromethoxy combination creates a sterically and electronically differentiated aromatic platform useful for structure–activity relationship (SAR) studies.

The compound also finds utility in agrochemical synthesis and in the preparation of specialty materials where fluorinated arenes are incorporated to tune electronic and thermal properties. Researchers have employed structurally related trifluoromethoxy arenes as ligand precursors and in the synthesis of liquid-crystal materials.

Safe Handling, Storage, and Disposal

Hazard overview: As a halogenated aromatic compound, 1-Chloro-2-(trifluoromethoxy)benzene should be treated as a potential irritant to skin, eyes, and the respiratory tract. Always consult the current Safety Data Sheet (SDS) supplied with the product before use. Specific GHS classifications and H/P statements should be verified in the product SDS (flag for review).

Personal protective equipment (PPE): Wear chemical-resistant gloves (nitrile or neoprene recommended), safety goggles or face shield, and a laboratory coat. Work in a fume hood or with adequate local exhaust ventilation to prevent inhalation of vapors.

Storage: Store in a tightly sealed container in a cool (below 25 °C), dry, well-ventilated area away from direct light, heat sources, and incompatible materials (strong oxidizers, strong bases). Keep container upright to prevent leakage.

Spill management: Contain spills immediately using inert absorbent material (vermiculite, dry sand). Avoid washing to drain. Collect and transfer to a labeled waste container for disposal in accordance with local regulations governing halogenated organic waste.

Disposal: Dispose of as halogenated organic solvent waste through a licensed hazardous waste contractor in compliance with applicable federal, state, and local regulations.

Quality, Purity, and Specification Guidance

When ordering 1-Chloro-2-(trifluoromethoxy)benzene (C130119) from Aladdin Scientific, researchers should request and review the Certificate of Analysis (CoA) for each lot received. The CoA documents purity (typically assessed by GC), water content, and appearance, providing a traceable quality record essential for reproducible experimental outcomes.

For sensitive catalytic reactions such as palladium cross-coupling, high purity grades (≥97% or ≥98% GC) are recommended to minimize catalyst poisoning by trace impurities. Confirm the exact purity specification available for the current lot with your Aladdin Scientific account manager or on the product detail page.

NMR characterization: the ¹H NMR spectrum in CDCl₃ is expected to display aromatic proton signals in the 7.1–7.6 ppm region consistent with a 1,2-disubstituted benzene pattern. ¹⁹F NMR should show the –OCF3 resonance near –57 to –58 ppm (verify against literature). Confirm identity by comparison with reference spectra or supplier-provided spectral data.