Uses
3,5-Dibromobenzonitrile is a chemical compound that can be found at high concentrations in the brain of patients with neurodegenerative diseases. 3,5-Dibromobenzonitrile has been shown to bind to metabotropic glutamate receptor 5 (mGluR5) and activate it; it also binds to glutamate receptors. The uptake of 3,5-dibromobenzonitrile by the body is dependent on its molecular orbital type and the functional groups present. Brain tissue samples from patients with neurodegenerative diseases have shown an increase in the amount of 3,5-dibromobenzonitrile binding to mGluR5. This increased binding may be due to a change in the molecular orbitals or functional groups on mGluR5, as well as an increase in expression of this receptor in diseased brains.
Synthesis
General procedure for the synthesis of 3,5-dibromobenzonitrile from 1,3,5-tribromobenzene: iPrMgCl (2M in THF, 4.1 mL) and THF (5 mL) were added to a flask containing dry LiCl (0.35 g, 8.24 mmol) at 15 °C. After stirring for 15 min, a solution of 3-bromobenzonitrile (1.46 g, 8.03 mmol) in THF (1 mL) was slowly added to the reaction mixture and stirring was continued for 15 min. Subsequently, DMF (1.3 mL, 12 mmol) was slowly added at 0 °C and the mixture was stirred for 2 hours. After completion of the reaction, aqueous NH3 (7 mL, 28-30%) and I2 (4.06 g, 16 mmol) were added to the mixture and stirred for 2 h at room temperature. The reaction mixture was poured into saturated aqueous Na2SO3 solution and extracted with CHCl3 (3 x 30 mL). The organic layers were combined, dried with Na2SO4 and filtered. After removing the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 9:1, v/v) to afford pure 3,5-dibromobenzonitrile (0.73 g) in 71% yield. Most of the nitrile compounds involved in this study were commercially available and were identified by comparison with authentic samples.
References
[1] Tetrahedron, 2013, vol. 69, # 5, p. 1462 - 1469
