NBS is commercially available. It can also be synthesized in the laboratory. To do so, sodium hydroxide and bromine are added to an ice-water solution of succinimide. The NBS product precipitates and can be collected by filtration. Crude NBS gives better yield in the Wohl-Ziegler reaction. In other cases, impure NBS may give unreliable results. It can be purified by recrystallization from 90–95 °C water.
Reactions
Addition to alkenes
NBS will react with alkenes 1 in aqueous solvents to give bromohydrins2. The preferred conditions are the portionwise addition of NBS to a solution of the alkene in 50% aqueous DMSO, DME, THF, or tert-butanol at 0 °C. Formation of a bromonium ion and immediate attack by water gives strongMarkovnikov addition and anti stereochemical selectivities. Side reactions include the formation of α-bromoketones and dibromo compounds. These can be minimized by the use of freshly recrystallized NBS. With the addition of nucleophiles, instead of water, various bifunctional alkanes can be synthesized.
Standard conditions for using NBS in allylic and/or benzylic bromination involves refluxing a solution of NBS in anhydrous CCl4 with a radical initiator—usually azobisisobutyronitrile or benzoyl peroxide, irradiation, or both to effect radical initiation. The allylic and benzylic radical intermediates formed during this reaction are more stable than other carbon radicals and the major products are allylic and benzylic bromides. This is also called the Wohl–Ziegler reaction. The carbon tetrachloride must be maintained anhydrous throughout the reaction, as the presence of water may likely hydrolyze the desired product. Barium carbonate is often added to maintain anhydrous and acid-free conditions. In the above reaction, while a mixture of isomeric allylic bromide products are possible, only one is created due to the greater stability of the 4-position radical over the methyl-centered radical.
Bromination of carbonyl derivatives
NBS can α-brominate carbonyl derivatives via either a radical pathway or via acid-catalysis. For example, hexanoyl chloride1 can be brominated in the alpha-position by NBS using acid catalysis. The reaction of enolates, enol ethers, or enol acetates with NBS is the preferred method of α-bromination as it is high-yielding with few side-products.
Electron-rich aromatic compounds, such as phenols, anilines, and various aromatic heterocycles, can be brominated using NBS. Using DMF as the solvent gives high levels of para-selectivity.
NBS electrophilically brominates the amine, which is followed by decarboxylation and release of an imine. Further hydrolysis will yield an aldehyde and ammonia.
Precautions
Although NBS is easier and safer to handle than bromine, precautions should be taken to avoid inhalation. NBS should be stored in a refrigerator. NBS will decompose over time giving off bromine. Pure NBS is white, but it is often found to be off-white or brown colored by bromine. In general, reactions involving NBS are exothermic. Therefore, extra precautions should be taken when used on a large scale.
