Grignard reagent

In ordinary organic chemistry carbon is usually the electron-poor partner, the one that gets attacked. A Grignard reagent flips that script: it is a piece of carbon turned into a powerful nucleophile, a carbon that attacks. It is one of the great workhorses for building carbon-carbon bonds, the very act at the heart of making bigger molecules from smaller ones.

A Grignard reagent has the formula R-Mg-X (an organic group R, a magnesium atom, and a halogen X). You make it by stirring an alkyl, vinyl, or aryl halide with magnesium metal in dry ether. The crucial trick is the carbon-magnesium bond: magnesium is far less electronegative than carbon, so the bond is strongly polarized toward carbon, leaving the carbon with a large partial negative charge. It behaves almost like a carbanion, R-minus, a carbon nucleophile. That nucleophilic carbon attacks the electron-poor carbon of a carbonyl group (C=O), forming a new C-C bond and giving an alcohol after a water work-up. With an aldehyde you build a secondary alcohol, with a ketone a tertiary one, with formaldehyde a primary one, and with CO2 you make a carboxylic acid.

Grignard reagents are how chemists assemble carbon skeletons at will, and they are central to synthesis. The catch is that the same nucleophilic carbon that makes them powerful also makes them ferociously basic: they react violently with any acidic proton, including the O-H of water or alcohols and the N-H of amines. So the reagent and all glassware must be scrupulously dry, and you cannot use a Grignard on a molecule that already carries an -OH, -NH, or -COOH group without protecting it first.