19.2 Preparing Aldehydes and Ketones

Synthesis of Aldehydes and Ketones

Synthesis methods for aldehydes

Oxidation of primary alcohols is the most common route to aldehydes. The key challenge: you need to stop the oxidation at the aldehyde stage and prevent it from going all the way to a carboxylic acid.

• Pyridinium chlorochromate (PCC) and pyridinium dichromate (PDC) are mild, selective oxidizing agents that convert primary alcohols to aldehydes without over-oxidation. Both are Cr(VI)-based reagents, but they operate under anhydrous conditions, which is what keeps the reaction from pushing past the aldehyde.
• The mechanism proceeds through a chromate ester intermediate: the alcohol attacks the chromium center, forming a chromate ester, which then undergoes an E2-like elimination to produce the carbonyl and reduced chromium species.

Partial reduction of esters offers another way to make aldehydes.

• Diisobutylaluminum hydride (DIBAL-H) at low temperature ($-78°C$) reduces an ester to an aldehyde by delivering just one equivalent of hydride.
• Why does it stop at the aldehyde? At $-78°C$, the tetrahedral alkoxide intermediate is stable enough that it doesn't collapse and accept a second hydride. The bulky isobutyl groups on DIBAL-H also slow further reduction. Upon aqueous workup, the intermediate breaks down to release the aldehyde.
• If you warm the reaction or use excess DIBAL-H, you'll get the primary alcohol instead, so temperature control is critical.

Preparation approaches for ketones

Oxidation of secondary alcohols reliably gives ketones. Because ketones can't be oxidized further under normal conditions (there's no H on the carbonyl carbon to lose), you don't need to worry about over-oxidation the way you do with aldehydes.

• You can use stronger oxidizing agents here: chromic acid ($H_2CrO_4$, prepared from $Na_2Cr_2O_7$ and $H_2SO_4$), as well as PCC or PDC.
• The mechanism is the same chromate ester pathway described above for primary alcohols.

Ozonolysis of alkenes cleaves $C=C$ double bonds to form carbonyl compounds.

1. Bubble $O_3$ through a solution of the alkene in an inert solvent (typically $CH_2Cl_2$) at low temperature.
2. Ozone undergoes a [2+3] cycloaddition with the alkene, forming an unstable molozonide.
3. The molozonide rearranges to a more stable ozonide.
4. Treat the ozonide with a mild reducing agent such as dimethyl sulfide (DMS) or zinc dust to cleave it into carbonyl products.

What you get depends on the substitution of the original alkene:

• A symmetrical tetrasubstituted or disubstituted alkene gives a single ketone product (two equivalents).
• An unsymmetrical alkene gives a mixture of a ketone and an aldehyde (or two different aldehydes/ketones, depending on substitution).

Aldehydes vs. ketones in synthesis

Understanding when each method applies helps you choose the right synthetic route.

Similarities

• Both can be made by oxidizing alcohols through the same chromate ester mechanism (primary alcohols → aldehydes; secondary alcohols → ketones).

Differences

Functional Group Interconversion and Reaction Mechanisms

Oxidation and reduction are the core transformations linking alcohols and carbonyl compounds. In oxidation-state terms:

• Alcohol → aldehyde or ketone is a two-electron oxidation (loss of two H atoms, one from O–H and one from C–H).
• Aldehyde or ketone → alcohol is a two-electron reduction (gain of two H atoms, as with $NaBH_4$ or $LiAlH_4$).

The mechanisms across these reactions share common features:

• Formation of reactive intermediates (chromate esters, tetrahedral alkoxide intermediates, ozonides)
• Electron transfer between substrate and reagent
• Bond reorganization steps such as elimination or rearrangement that release the final product

Recognizing these patterns makes it easier to predict products and write mechanisms for new reactions you haven't seen before.