Nuclophilic Br- Reagents

Mechanism + Description

Typically S_N2 with displacement of another halogen (iodide) or other leaving group (sulphonate) etc. Also via reaction of Br with other electrophiles such as diazonium salts.

General comments

Normally simple bromide salts like Na/K/Li bromide are used, or tetraalkyl ammonium or phosphonium bromides like n-Bu₄NBr. Hydrogen bromide is typically used for deoxybromination, but can be used to add to unsaturated C-C bonds or ring-open epoxides etc.

Key references

J. Org. Chem., 2003, 68, 4281-4285 – Significantly Enhanced Reactivities of the Nucleophilic Substitution Reactions in Ionic Liquid

Synlett, 2012, 23, 2663-2666 – A Facile and Green Protocol for Nucleophilic Substitution Reactions of Sulfonate Esters by Recyclable Ionic Liquids [bmim][X]

“Sodium Bromide” In Paquette, L. A. Encyclopedia of Reagents for Organic Synthesis

Synthesis, 2007, 2534-2538 – Catalytic SandmeyerBromination

Relevant scale up example

None located.

Specific solvent issues with bromination

Many radical and electrophilc brominations have traditionally been carried out in chlorinated solvents – CCl₄, CHCl₃, C₂H₄Cl₂ and CH₂Cl₂. – if a chlorinated solvent is needed, CH₂Cl₂ should be used.

Radical brominations with Br₂ or NBS/DBDMH were traditionally carried out in CCl₄, C₆H₆, CHCl₃. A range of alternative solvents for radical bromination has been reported. Some alternatives to the above solvents are listed below.

Green Chemistry, 2003, 5, 470–474 – Carbon tetrachloride free benzylicbrominations of methyl aryl halides

Chlorobenzene, benzotrifluoride, n-hexane – less favoured
Cyclohexane, heptane, Dimethyl carbonate, MeCN, methyl acetate isopropyl acetate – favoured

Bromine, Br⁺ reagents and higher oxidation state Br compounds are oxidising reagents and can react violently with some organic solvents and  reagents, especially ethers if traces of peroxides are present. The use of DMSO in the presence of Br₂ or HBr should be treated with caution.

Org. Process Res. Dev. 1997, 1, 39-44 – Evaluation and Rapid Scale-Up of the Synthesis of the Pyrrolopyrimidines U-101033E and U-104067F Reaction of NBS with THF

Reaction between Br₂ and TBME

Unexpected reaction between NBS and NMP

DMSO – Technical information package

An explosion has been reported by an unexpected reaction of acetone with POCl3  POBr3 would probably show similar instability.

Org. Process Res. Dev. 2000, 4, 585−586 – Phosphorus Oxychloride and Acetone: An Incompatibility Investigation Using ARC