The carbonyl group has unique structural and reactivity properties by virture of the polarization of (mainly) the pi system toward the more electronegative oxygen. This imparts electrophilic character to the carbon and nucleophilic character to the oxygen.
A number of methods for the preparation of ketones and aldehydes have been introduced in previous chapters. They include:
- Oxidation of alcohols with Cr+6. PCC must be used with primary alcohols in order that the oxidation does not proceed to the carboxylic acid;
- Hydration of either a symmetrical or a terminal alkyne (other alkynes result in mixtures of ketones).
- Ozonolysis of an alkene.
- Friedel-Crafts acylation of an aromatic compound.
There are typically two pathways for addition to carbonyl groups:
- Activation of the carbonyl group by addition of either a proton or a Lewis acid to the oxygen;
- preparation of a reagent with high nucleophilicity.
Carbonyl groups undergo rapid and reversible reaction with water under both acidic and basic conditions. Except for the special case of formaldehyde (and some special ketones and aldehydes bearing electron withdrawing groups), the equilibrium favors the carbonyl compound.
The typical reactions of carbonyl compounds involve addition to the carbonyl carbon with loss of the pi bond. The conversion of ketones and aldehydes to ketals and acetals "hides" this reactivity as in these derivatives the pi bond is no longer present. Because formation of ketals and acetals is reversible, these derivatives can be used to protect the carbonyl group from reaction.
Various nitgrogen compounds react with ketones (and aldehydes) to form derivatives in which the oxygen has been replaced by nitrogen..
Nitrogen Compound Derivative
Primmary amines imines
Secondary amines enamines
The reactions appears not to be acid catalyzed. Charge separation in intermediates can be avoided by using a proton relay mechanism in which a small molecules such as water simultaneously gains and looses a proton.
Reaction of a hydrazone with NaOH at 200 C results in complete removal of the oxygen with the conversion of the carbonyl group into a methylene (CH2) group. The same conversion can be effected by conversion of the ketone to a thioketal followed by reaction with Raney nickle (R-Ni). Not a very useful reaction has the reaction conditions are harsh (meaning that other functional group can be reduced as well).
Reaction of alkyl halides (best are primary) with triphenyl phosphine followed by deprotonation with a strong base such as butyl lithium forms a phosphorane. These react with aldehydes and ketones to form alkenes with lose of triphenylphosphine oxide. When a phosphorane derived from a primary alkyl halide is reacted with an aldehyde, the cis alkene is formed almost exclusively.
Reaction of a carboxylic acid peracid (RCO3H) with a ketone results in the insertion of an oxygen between the carbonyl carbon and one of the two alpha carbons. When the ketone is unsymmetrical, insertion occurs at the more substituted alpha carbon.