Hofmann Elimination
The Hofmann elimination is the preparation of alkenes from the treatment of quaternary ammonium salts with silver oxide, water, and heat.
General features: The Hofmann elimination is a β-elimination. Thus, the β-hydrogen is abstracted by the base (hydroxide ion) from the β-carbon atom. It is also an anti elimination (the leaving group has to be antiperiplanar). Besides, some side reactions occur when the base acts as a nucleophile, delivering then alcohol byproducts.
Hofmann Elimination
Reaction Mechanism
1. Formation of the ammonium iodide salt. 2. Substitution of the iodide ion with the hydroxide ion by the reaction between iodide and silver oxide and the successive deprotonation of water by the silver oxide ion. 3. Elimination reaction facilitated by heat. The elimination follows the Hofmann Rule: basically, the less substituted alkene is obtained.
Example
Experimental Procedure
To a solution of the amine (0.95 mmol, 1 eq) in dry THF (20 mL) was added potassium carbonate (2 eq) and iodomethane (58 eq). After stirring for 20 h at room temperature, the mixture was concentrated in vacuo to give the crude salt, which was used in the next step without purification.
A solution of DMSO (11 eq) in dry DCM (4 mL) was added to a solution of oxalyl dichloride (5 eq) in dry DCM (20 mL) at -78 ºC. After stirring for 30 min, the quaternary ammonium salt in dry DCM (6 mL) was added to the solution at -78 ºC. The solution was stirred for 2.5 h at -78 ºC, then triethylamine (27 eq) was added and the reaction mixture was allowed to warm to room temperature. After stirring for 40 min, the mixture was diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The combined organic layer was washed with saturated aqueous sodium chloride, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to afford the desired alkene (81% yield).
Learn More Named Reactions
[instagram-feed feed=2]
