Weinreb amide
/ WINE-reb /
Chemists often want exactly one addition to an acyl group — to make a ketone from an acid derivative, or an aldehyde, and then stop, with no over-reaction. Ordinary esters and amides frustrate that wish: hydride or an organometallic tends to add twice and overshoot. The Weinreb amide is the clever fix, a specially designed amide that adds once and then refuses to react again until you want it to.
A Weinreb amide is an N-methoxy-N-methyl amide, R-CO-N(OCH3)(CH3). The trick is the methoxy oxygen. When a Grignard reagent, an organolithium, or a hydride adds to the carbonyl, the resulting tetrahedral alkoxide does not collapse to expel the nitrogen and re-form a reactive carbonyl. Instead, the nearby oxygen and nitrogen chelate the metal, forming a stable five-membered metal-containing ring that locks the intermediate in its tetrahedral form. Because the carbonyl is not regenerated during the reaction, a second equivalent cannot add. Only on aqueous workup does the chelate break down, releasing the carbonyl product — a single, clean ketone (or aldehyde, if hydride was used).
This controlled, stop-at-one behavior makes the Weinreb amide a favorite for synthesis. React it with a Grignard or organolithium to get a ketone in one clean step (no tertiary-alcohol over-addition); react it with LiAlH4 or DIBAL-H to get an aldehyde without sliding down to the alcohol. It is a textbook example of how a thoughtfully chosen functional group can tame a reaction that would otherwise run too far.
A Weinreb amide R-CO-N(OCH3)CH3 + CH3MgBr gives the methyl ketone R-CO-CH3 in one clean addition. The chelated tetrahedral intermediate blocks a second addition, so no tertiary alcohol forms.
A Weinreb amide gives a ketone from an organometallic without over-addition.
The whole point is what an ordinary ester cannot do: with an ester, a Grignard adds twice and gives a tertiary alcohol, not a ketone. The Weinreb amide's chelated intermediate is what stops at the single-addition stage.