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Reactions of Carbonyl Compounds

The most important compounds in organic chemistry are those containing the carbonyl (C=O) group. Many functional groups contain a C=O bond; aldehydes, ketones, carboxylic acids, esters, amides etc.

The carbon of a C=O bond is sp2 hybridised, as is the carbon of a C=C bond. The carbonyl group and the atoms attached to it lie in the same plane and the bond angles are around 120o. The carbon-oxygen bond length is typically ~120pm in aldehydes and ketones compared to ~140pm in alcohols and ethers. Oxygen is more electronegative than carbon and the C=O bond is polarised accordingly:

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As a consequence of this, a large number of reactions are based on the addition of a nucleophile to the carbon of the carbonyl group. A general mechanism for the addition step can be written as follows:

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The fate of this tetrahedral intermediate depends largely on the nature of the groups R and R'. If neither R nor R' is a good leaving group, the oxygen anion can be protonated by dilute acid to give the corresponding alcohol. If R or R' is a good leaving group, e.g. EtO-, a new carbonyl compound can be formed. An example to illustrate this is the addition of a Grignard reagent to an ester:

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However, there would be one problem if this approach were employed to prepare a sample of acetone. Can you see what it is?

The second main class of reactions encountered with carbonyl compounds involves the C=O group less directly. If there are hydrogens on the carbon adjacent (a) to the carbonyl group, they may be removed by a strong base to form an enolate ion:

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The proton is acidic because the carbonyl group can stabilise the negative charge. The pKa of an alpha proton in a ketone is ~20 and it can be removed by a strong base such as n-butyllithium, the pKa of an alpha proton in a 1,3-dicarbonyl compound is ~10 and it can be removed by a base such as ethoxide ion.

Once formed, the enolate ion can react with electrophiles in one of two ways; either at oxygen or at carbon. It is called an ambident nucleophile. In general, carbon electrophiles react at the carbon of the enolate. Some electrophiles react at oxygen and these include silicon (e.g. Me3SiCl).

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These a-alkylations are extremely important in synthetic chemistry and give access to a diverse range of functionalities and carbon frameworks. Most of the reactions follow the same basic pathway, i.e. formation of the enolate followed by reaction of the enolate with an electrophile, so it should not be too difficult to work out an unfamiliar example.

 

 

© University of Aberdeen 1998-2013  
Page author : Dr Mary Masson