4-Bromofluorobenzene: Applications and Safety Profile

General Description

4-Bromofluorobenzene is also known as 1-bromo-4-fluorobenzene or p-bromofluorobenzene. It is one of the bromofluorobenzenes and the others are o-bromofluorobenzene and m-bromofluorobenzene. 4-Bromofluorobenzene is a mixed aryl halide (aryl fluoride and aryl bromide) with the formula C6H4BrF, a colourless liquid of low acute toxicity. It is a derivative of benzene, with a bromine atom bonded para to a fluorine atom. It has been used as a precursor to some pharmaceuticals, as an agrochemical intermediate, and in organic synthesis.

The photodissociation of 1-Bromo-3-fluorobenzene

For bromofluorobenzene (BrFPh), Narasimham et al. measured the infrared absorption spectrum and the Raman spectrum of p-BrFPh. Varsanyi et al. investigated the ultraviolet absorption spectra of o-, m-, and p-BrFPh. However, the REMPI spectra of bromofluorobenzene isomers at the S1 state have not been measured.

The vibrations of o-, m- and p-bromofluorobenzene (BrFPh) in the first electronically excited state are studied by (1 + 1) resonance-enhanced two-photon ionization spectroscopy by Zhang et al. The observed vibrational bands were assigned based on a comparison with the results from theoretical calculations. The band origins of the S1 S0 electronic transitions of o-, m- and p-BrFPh, which were influenced by positive resonance effect and negative inductive effect, are found to be 36986.68 cm1 , 36961.48 cm1 and 36223.20 cm1, respectively. Meanwhile, the potential barrier height (the energy of the crossing points between the bound S1 state and a repulsive state relative to the S1 minimum) of p-BrFPh is determined to be lower than 2815 cm1 (0.3490 eV) by the REMPI spectra of bromine atom and p-BrFPh molecule.

Quantum chemical calculations with relativistic effects were performed on the photodissociation of o-, m-, and p-bromofluorobenzene (o-, m-, and p-BrFPh) at 266 nm by Liu et al. The method of multistate second-order multiconfigurational perturbation theory in conjunction with spin-orbit interaction through complete active space state interaction was employed to calculate the potential energy curves for the ground and low-lying excited states of o-, m-, and p-BrFPh along their photodissociation reaction coordinates. The dissociation mechanisms with products of Br(2P3/2) and Br*( 2P1/2) states were clarified with the computed potential energy curves and the surface crossings. The current calculations augmented previous theoretical investigations by including relativistic effects and resolved some differences of experimental assignment regarding the dissociation channels of o-, m-, and p-BrFPh.

Toxicity

1-Bromo-4-fluorobenzene belongs to the class of compounds known as aryl halides. 1-Bromo-4-fluorobenzene is used as an intermediate in agrochemical production, in organic reactions, such as the preparation of Grignard reagents, and the production of various therapeutic drugs. It is also used as an internal standard in gas chromatography-mass spectrometry for the analytical determination of volatile organic compounds (VOCs) in various media.

One acute oral lethality study was located. Groups of 10 male Sprague-Dawley (S-D) rats were administered a single dose of 1,000, 2,000, 3,000, or 5,000 mg/kg of 1-bromo-4-fluorobenzene (∼98% purity) in corn oil via gavage and sacrificed after a 14-day observation period. The median lethal dose (LD50) was 2,700 mg/kg. At nonlethal doses (specific levels not reported), tremors, limpness, and weight loss (3−19%) were observed 1−2 days after dosing. At lethal doses, death occurred within 3 days of dosing, preceded by tremors, absence of righting and/or grasping reflex, limpness, ataxia, lung noise, clear ocular discharge, and body-weight loss (8−21%). No other endpoints (e.g., gross or histological pathology) were examined. NTP (2005) reported additional rat LD50 values of 2,248 and 3,788 mg/kg, citing an abstract from the TOXCENTER database; a source and/or confirmation of these values was not located.

Reference

[1] Chen Qin . “The REMPI spectra of o-, m- and p-bromofluorobenzene and the photodissociation of p-bromofluorobenzene.” Journal of Molecular Spectroscopy 273 (2012): Pages 37-43.

[2] Wen-Zuo Li, Ya-Jun Liu, Shu-Feng Chen. “Relativistic multireference calculation of photodissociation of o-, m-, and p-bromofluorobenzene.” Journal of Chemical Physics 134 11 (2011): 114303.

[3] Provisional Peer-Reviewed Toxicity Values for 1-Bromo-4-fluorobenzene (CASRN 460-00-4) https://hhpprtv.ornl.gov/issue_papers/Bromo4fluorobenzene1.pdf