Hofmann elimination

An ordinary amine cannot be eliminated directly — the amino group, even when protonated, is a poor leaving group. The Hofmann elimination is a clever workaround that turns an amine into an alkene. First you flood the amine with excess methyl iodide so that every lone pair on nitrogen picks up a methyl group, converting it into a quaternary ammonium salt (R-N+(CH3)3). Treat that salt with silver oxide and water to swap in hydroxide as the counterion, then heat. Now the trimethylamine group is a workable leaving group, hydroxide acts as the base, and an E2-type elimination ejects it to give the alkene.

What makes Hofmann elimination distinctive is its regiochemistry: it characteristically gives the less substituted, terminal alkene as the major product — the Hofmann product, the anti-Zaitsev outcome. Two factors conspire: the trimethylammonium leaving group is very bulky, and the hydroxide base must reach a beta proton past that bulk, so it preferentially removes the most accessible, least hindered hydrogen on a terminal carbon. The mechanism is E2 and so still requires an anti-periplanar beta hydrogen, but among the available ones, sterics select the least substituted.

Historically this 'exhaustive methylation' sequence was a structure-determination tool: chemists degraded an unknown amine (or alkaloid) and identified the alkene fragments to deduce the original skeleton. Today milder, more selective methods have largely replaced it for synthesis, but the Hofmann elimination remains the textbook archetype of how a special, bulky leaving group flips regioselectivity from Zaitsev to Hofmann — the clearest illustration that orientation is set by the transition state, not by a fixed rule.