Importance of Diazonium Salts in Synthetic Organic Chemistry

Diazonium salts occupy a uniquely important place in synthetic organic chemistry

because they let a chemist install, at a chosen position on a benzene ring, a

substituent that DIRECT electrophilic aromatic substitution chemistry could never place

there in the first place.

The core strategy, in three stages:

1. First install a strongly ring-directing group by ordinary electrophilic substitution -- most often $-\text{NO}_2$ by nitration, whose position (ortho/para or meta, depending on what else is already on the ring) is controlled by the normal rules of electrophilic aromatic substitution.
2. Reduce that nitro group to $-\text{NH}_2$ (Section 25.3), and diazotize the resulting aromatic primary amine (Section 25.14) to obtain the diazonium salt AT THE SAME RING POSITION the nitro group originally occupied.
3. Displace the diazonium group (Section 25.15) with whichever substituent is actually wanted at that position.

Why this matters -- the substituents this route reaches that direct substitution cannot:

• $-\text{F}$ cannot be introduced by direct electrophilic fluorination at all (elemental fluorine is far too reactive and unselective); the Balz-Schiemann route via a diazonium salt is the standard laboratory method.
• $-\text{I}$ is installed only inefficiently and non-selectively by direct electrophilic iodination (the reaction is reversible and needs an oxidising agent to proceed at all); via the diazonium salt plus $\text{KI}$, aryl iodides are obtained cleanly and in good yield.
• $-\text{CN}$ (a nitrile group directly on the ring) has no direct electrophilic aromatic substitution equivalent whatsoever -- there is no electrophilic '$\text{CN}^+$' reagent that reacts with benzene -- so the Sandmeyer route via $\text{CuCN}$ is essentially the ONLY practical way to place a nitrile directly on an aromatic ring.
• $-\text{OH}$ can, in principle, sometimes be introduced by other routes, but hydrolysing a diazonium salt is by far the cleanest, most general laboratory synthesis of a substituted phenol from the corresponding amine/nitro compound.

Worked example. To make fluorobenzene from benzene: nitrate benzene to nitrobenzene,

reduce ($\text{Sn}/\text{HCl}$) to aniline, diazotize aniline at $0$–$5^\circ\text{C}$ …