Hydrates & cyanohydrins — Carbonyl Chemistry

Acetals get a section of their own because they are useful as protecting groups. But the same nucleophilic addition runs with two simpler nucleophiles — water and cyanide — and those two cases are where you can actually watch the equilibrium respond to structure.

Hydrates: addition of water

Water adds to a carbonyl to give a gem-diol, two OH groups on one carbon, usually called a hydrate. The reaction is reversible and for most carbonyls it lies far to the left:

Carbonyl	Percent hydrate at equilibrium
Acetone	0.1%
Acetaldehyde	~50%
Formaldehyde	~99.9%
Chloral, CCl₃CHO	~100%, and the hydrate is isolable

That spread is three orders of magnitude in percent hydrate — and closer to six if you compare equilibrium constants, since the percentages at the ends of the table are both pinned near their limits. Either way it has exactly the two causes you would predict.

Sterics. Addition turns a flat sp² carbon into a crowded sp³ one, so substituents that were 120° apart are squeezed to 109°. Two methyls resist that; two hydrogens do not.
Electronics. Alkyl groups donate electron density into the carbonyl and stabilize it, making the starting material more comfortable. Electron-withdrawing groups do the opposite, which is why chloral — three chlorines pulling — is fully hydrated.

A third cause shows up once a ring is attached. Benzaldehyde hydrates far less than acetaldehyde, even though both are aldehydes carrying one substituent, because the C=O is conjugated with the ring and addition destroys that conjugation. It is the same principle as the other two: anything that makes the starting material comfortable holds the equilibrium back.

This is the reactivity order of the whole chapter, made measurable. Aldehyde > ketone toward every nucleophile, for these two reasons together, and the hydration equilibrium is simply the easiest place to see the size of the effect.

Why the hydrate matters even when it is the minor species

The reactivity order of the chapter, with numbers on it. Aldehyde beats ketone toward every nucleophile, and hydration is where you can see how large the gap actually is — three orders of magnitude between acetone and formaldehyde, from nothing more than removing two methyl groups.The two causes usually agree, which is what makes the trend so reliable — and the interesting cases are the ones where they do not. Hexafluoroacetone is more crowded than acetone and essentially completely hydrated, because six fluorines outweigh the crowding. Cyclopropanone is fully hydrated for the opposite reason again: the ring already strains the sp² carbon, so addition relieves strain instead of creating it, and the steric argument runs backwards.

The next chapter will put two chromium reagents side by side and ask why they stop in different places. Jones oxidation takes a primary alcohol all the way to a carboxylic acid; PCC stops at the aldehyde. The difference is water, and the reason is this section. In aqueous conditions the aldehyde hydrates, the hydrate is an alcohol again, and the oxidant attacks it a second time. Under anhydrous conditions no hydrate forms, so the second oxidation has nothing to grip and the sequence halts at the aldehyde.

So a species that is nobody's idea of the main component controls the outcome, because it is the only form that can react further. That is a general lesson worth keeping, and it gets more striking the smaller the equilibrium amount is: glucose holds well under a tenth of a percent of its open-chain form and still reduces silver quantitatively. An equilibrium does not have to favor an intermediate for that intermediate to decide the product.

Cyanohydrins: addition of cyanide

Cyanide adds to give a cyanohydrin — an OH and a CN on the same carbon. Unlike hydration, this one is synthetically useful, because it makes a new carbon–carbon bond.

R₂C=O + HCN → R₂C(OH)CN

Cyanide is a decent nucleophile and a weak enough base not to cause trouble, and the addition is run near pH 8–10: enough cyanide present as CN⁻ to attack, enough HCN present to protonate the alkoxide.

What makes it worth doing is what the nitrile can become:

Hydrolysis → an α-hydroxy carboxylic acid.
Reduction with LiAlH₄ → a β-amino alcohol.
Dehydration → an α,β-unsaturated nitrile.

Retrosynthetically, a cyanohydrin is a one-carbon extension that arrives with a functional group already on it. Set it beside the other three — formaldehyde plus a Grignard gives a primary alcohol, CO₂ plus a Grignard gives an acid, a nitrile plus a Grignard gives a ketone — and the choice is again about what you want at the end rather than about the carbon count.

Bisulfite adducts, and a use for a bad reaction

Sodium bisulfite, NaHSO₃, adds to aldehydes and unhindered ketones to give a salt that is soluble in water and insoluble in organic solvents. That reversal of solubility is the useful part: shake a mixture with aqueous bisulfite and the carbonyl compound moves into the water layer while everything else stays behind. The addition is reversible with acid or base, so the compound is released again afterward, which makes the sequence a purification. Where the adduct crystallizes out instead, it can simply be filtered.

It also discriminates. Aldehydes and methyl ketones form the adduct readily; hindered ketones do not — which makes it a way to separate them, and another instance of the same sterics that set the hydration equilibrium.

What carries forward

Water, cyanide and bisulfite all do the same thing: add reversibly to a carbonyl. How far each goes is decided by sterics and electronics, in the same direction every time, which is why the hydration percentages are worth knowing as a ruler rather than as facts. And one of the three makes a C–C bond, which is why cyanohydrins appear in syntheses and hydrates do not.