Nucleophiles don’t have to be highly polarized or negatively charged to react with aldehydes and ketones: neutral ones will as well. How do we know? This ¹³C NMR spectrum was obtained by dissolving formaldehyde, H₂C=O, in water. You will remember from Chapter 3 that the carbon atoms of carbonyl groups give ¹³C signals typically in the region of 150–200 ppm. So where is formaldehyde’s carbonyl peak? Instead, we have a signal at 83 ppm—where we would expect tetrahedral carbon atoms singly bonded to oxygen to appear.

What has happened is that water has added to the carbonyl group to give a compound known as a hydrate or 1,1-diol.

This reaction, like the addition of cyanide we discussed at the beginning of the chapter, is an equilibrium, and is quite general for aldehydes and ketones. But, as with the cyanohydrins, the position of the equilibrium depends on the structure of the carbonyl compound. Generally, the same steric factors (p. 129) mean that simple aldehydes are hydrated to some extent while simple ketones are not. However, special factors can shift the equilibrium towards the hydrated form even for ketones, particularly if the carbonyl compound is reactive or unstable. Formaldehyde is an extremely reactive aldehyde as it has no substituents to hinder attack—it is so reactive that it is rather prone to polymerization. And it is quite happy to move from sp² to sp³ hybridization because there is very little increased steric hindrance between the two hydrogen atoms as the bond angle changes from 120° to 109° (p. 129). This is why our aqueous solution of formaldehyde contains essentially no CH₂O—it is completely hydrated. A mechanism for the hydration reaction is shown below. Notice how a proton has to be transferred from one oxygen atom to the other, mediated by water molecules.

Formaldehyde reacts with water so readily because its substituents are very small: a steric effect. Electronic effects can also favour reaction with nucleophiles—electronegative atoms such as halogens attached to the carbon atoms next to the carbonyl group can increase the extent of hydration by the inductive effect according to the number of halogens substituents and their electron-withdrawing power. They increase the polarization of the carbonyl group, which already has a positively polarized carbonyl carbon, and make it even more prone to attack by water. Trichloroacetaldehyde (chloral, Cl₃CHO) is hydrated completely in water, and the product ‘chloral hydrate’ can be isolated as crystals and is an anaesthetic. You can see this quite clearly in the two IR spectra below. The first one is a spectrum of chloral hydrate from a bottle—notice there is no strong absorption between 1700 and 1800 cm⁻¹ (where we would expect C=O to appear) and instead we have the tell-tale broad O–H peak at 3400 cm⁻¹. Heating drives off the water, and the second IR spectrum is of the resulting dry chloral: the C=O peak has reappeared at 1770 cm⁻¹ and the O–H peak has gone.

●Steric and electronic effects

• Steric effects are concerned with the size and shape of groups within molecules.

 • Electronic effects result from the way that electronegativity differences between atoms affect the way electrons are distributed in molecules. They can be divided into inductive effects, which are the consequence of the way that electronegativity differences lead to polarization of σ bonds, and conjugation (sometimes called mesomeric effects) which affects the distribution of electrons in π bonds and is discussed in the next chapter. Steric and electronic effects are two of the main factors dominating the reactivity of nucleophiles and electrophiles.

The chart shows the extent of hydration (in water) of a small selection of carbonyl com pounds: hexafluoroacetone is probably the most hydrated carbonyl compound possible! The larger the equilibrium constant, the more the equilibrium is to the right.

Cyclopropanones—three-membered ring ketones—are also hydrated to a significant extent, but for a different reason. You saw earlier how acyclic ketones suffer increased steric hindrance when the bond angle changes from 120° to 109° on moving from sp2 to sp3 hybridization. Cyclopropanones (and other small-ring ketones) conversely prefer the small bond angle because their substituents are already confined within a ring. Look at it this way: a three-membered ring is really very strained, with bond angles forced to be 60°. For the sp² hybridized ketone this means bending the bonds 60° away from their ‘natural’ 120°. But for the sp3 hybridized hydrate the bonds have to be distorted by only 49° (= 109° – 60°). So addition to the C=O group allows some of the strain inherent in the small ring to be released— hydration is favored, and indeed cyclopropenone and cyclobutanone are very reactive electrophiles.

●The same structural features that favour or disfavour hydrate formation are important in determining the reactivity of carbonyl compounds with other nucleophiles, whether the reactions are reversible or not. Steric hindrance and more alkyl substituents make carbonyl compounds less reactive towards any nucleophile; electron-withdrawing groups and small rings make them more reactive.