reductive amination

Reductive amination is the most practical, most-used way to make amines in the lab and in industry, and it is wonderfully intuitive once you see the picture: take an aldehyde or ketone, mix in an amine (or ammonia), and reduce. You are effectively gluing an amine onto a carbonyl carbon, converting C=O into C-N while controlling exactly how substituted the nitrogen ends up.

The mechanism is a two-act play. First, the amine's lone pair attacks the carbonyl carbon and, after losing water, forms an imine (R2C=N-R', a carbon-nitrogen double bond) — or an iminium ion if the conditions are acidic and the nitrogen is more substituted. Second, a hydride reducing agent delivers H- to that C=N, collapsing it to a single C-N bond and giving the amine. The clever part is choosing a mild, selective reductant — sodium cyanoborohydride (NaBH3CN) or sodium triacetoxyborohydride (NaBH(OAc)3) — that reduces the imine/iminium but leaves the starting carbonyl mostly untouched, so the equilibrium is funnelled toward product.

Why it wins over direct alkylation: it does not overalkylate. A primary amine plus an aldehyde gives a secondary amine and stops, because the new nitrogen is added as part of forming one C=N at a time, not by repeated SN2 on a halide. It is how chemists install -CH2R groups onto nitrogen cleanly, and it builds an enormous range of drug molecules. One honest limit: you can only add a group that corresponds to a carbonyl, so the new carbon attached to nitrogen always carries at least one hydrogen (you cannot make a quaternary carbon this way), and you cannot put an aryl group directly on nitrogen by this route.