Cleavage and Uses of Ethers

Ethers are, deliberately, among the least reactive classes of organic compound in routine use --

which is exactly why they make such good solvents -- but their carbon-oxygen bonds are not

completely inert, and can be broken under sufficiently forcing conditions.

Cleavage by hydrogen halides. Heating an ether with excess concentrated hydroiodic acid (HI is

used because iodide is both a strong nucleophile and the conjugate base of a strong acid; HBr reacts

similarly but more slowly, and HCl barely cleaves ethers at all under comparable conditions) breaks

the $\text{C--O}$ bond. The first equivalent of HI protonates the ether oxygen, and iodide then

attacks one of the two carbons, cleaving that $\text{C--O}$ bond to give an alcohol and an alkyl

iodide:

If HI is present in excess (as it typically is, since the reaction is normally run with excess

HI to drive it to completion), the alcohol product formed in this first step does not survive:

under the same hot, strongly acidic, iodide-rich conditions it reacts exactly as any alcohol would

with HI, converting on to the corresponding alkyl iodide as well, so the overall, fully-driven

reaction with excess reagent consumes two equivalents of HI per ether and gives two molecules of

alkyl iodide plus water:

Which bond breaks, and by which mechanism. For a simple dialkyl ether with primary or

secondary alkyl groups, cleavage proceeds by an $S_N2$ mechanism, with iodide attacking the less

sterically hindered of the two carbons; if one of the alkyl groups is tertiary (or benzylic/

allylic), cleavage instead proceeds by an $S_N1$ mechanism through the more stable carbocation at

that carbon, and iodide ends up on that more substituted carbon instead. For an alkyl aryl ether such as anisole, however, the outcome is governed by a stronger, structural rule rather than

by relative rates: the aryl-oxygen bond never breaks, regardless of reaction conditions,

because that bond has substantial partial double-bond character (from the same resonance

delocalisation of the oxygen lone pair into the ring discussed for phenol's acidity and directing

effect) and because the alternative -- forming a highly unstable, non-resonance-stabilised aryl

cation -- is far too costly energetically to compete. Cleaving anisole with excess HI therefore

always gives phenol (from the aryl-oxygen side, left intact as $-\text{OH}$ once the alkyl

group departs) plus the corresponding alkyl iodide (from the alkyl-oxygen side, which does

break), never iodobenzene, no matter how forcing the conditions.

Uses of ethers. Diethyl ether was, historically, the first widely used general anaesthetic in

surgery, prized for reliably inducing unconsciousness, but it has been almost entirely superseded in

modern medicine by safer, faster-acting agents, chiefly because diethyl ether is highly flammable …