o-Bromofluorobenzene-d₄
[CAS 50592-35-3]

Identification

• Classification: Chemical reagent >> Deuterated reagent
• Name: o-Bromofluorobenzene-d₄
• Synonyms: 1-bromo-2,3,4,5-tetradeuterio-6-fluorobenzene
• Molecular Formula: C₆BrD₄F
• Molecular Weight: 179.02
• CAS Registry Number: 50592-35-3
• SMILES: [2H]C1=C(C(=C(C(=C1[2H])F)Br)[2H])[2H]

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Boiling point: 151.5 °C 760 mmHg (Calc.)^*
• Flash point: 43.3 °C (Calc.)^*
• Index of refraction: 1.53 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H350
• Safety Statements: P280-P305+P351+P338

Discovery and Applications

o-Bromofluorobenzene-d4 is a deuterated halogenated aromatic compound derived from o-bromofluorobenzene, in which four hydrogen atoms on the benzene ring are replaced by deuterium atoms. It consists of a benzene ring bearing two adjacent substituents, bromine and fluorine, at the ortho positions, with isotopic labeling used to modify its spectroscopic properties without significantly altering its chemical framework.

Halogenated benzenes such as bromofluorobenzene are important intermediates in organic synthesis due to the complementary reactivity of bromine and fluorine substituents. Bromine is a relatively good leaving group in transition-metal-catalyzed cross-coupling reactions, while fluorine strongly influences the electronic properties of the aromatic ring through its high electronegativity and strong inductive effect. The ortho arrangement of these substituents introduces steric and electronic interactions that affect reactivity patterns in substitution and coupling reactions.

The presence of deuterium atoms in o-bromofluorobenzene-d4 does not significantly alter the molecule’s chemical reactivity in most contexts, because deuterium is chemically similar to hydrogen. However, the C–D bond is slightly stronger and vibrationally different from the C–H bond, which leads to measurable kinetic isotope effects. These effects are particularly important in mechanistic studies, where deuterated compounds are used to trace reaction pathways, determine rate-determining steps, or study hydrogen transfer processes.

Deuterated aromatic compounds are widely used in nuclear magnetic resonance (NMR) spectroscopy. In particular, deuteration reduces proton signal interference, improves spectral clarity, and allows for more precise analysis of complex mixtures or reaction mechanisms. o-Bromofluorobenzene-d4 is therefore useful as a labeled intermediate or internal standard in analytical and mechanistic chemistry.

From a structural standpoint, the benzene ring in o-bromofluorobenzene-d4 retains aromaticity, with delocalized π-electrons distributed over the ring system. The bromine atom exerts both inductive electron-withdrawing effects and weak resonance donation, while fluorine strongly withdraws electron density through induction. Together, these substituents significantly reduce electron density on the ring, making it less reactive toward electrophilic aromatic substitution but more suitable for nucleophilic aromatic substitution under appropriate conditions.

The isotope substitution with deuterium does not significantly affect the electronic distribution of the aromatic system, but it does influence vibrational modes and bond dissociation energies. This can lead to subtle differences in reaction kinetics, particularly in processes involving C–H (or C–D) bond cleavage.

In terms of physicochemical properties, o-bromofluorobenzene-d4 is a nonpolar to weakly polar aromatic compound with low water solubility. The presence of heavy halogens increases density and polarizability, while deuteration slightly increases mass without substantially changing polarity. As a result, the compound is typically handled in organic solvents and is stable under a wide range of standard laboratory conditions.

The synthetic preparation of deuterated aromatic compounds generally involves isotopic exchange reactions, catalytic deuteration, or construction of the aromatic ring from deuterated precursors. Halogenated benzene derivatives such as bromofluorobenzene are often selectively deuterated under catalytic conditions or through specialized synthetic routes using deuterium sources.

Overall, o-bromofluorobenzene-d4 is a deuterium-labeled ortho-substituted halobenzene characterized by a bromine atom, a fluorine atom, and four deuterium atoms on the aromatic ring. Its significance lies primarily in its use as a mechanistic probe and analytical standard in organic and physical chemistry, particularly in studies involving isotopic effects, reaction pathways, and spectroscopic analysis.