The key to understanding the chemistry of aldehydes and ketones is to understand the electronic structure and properties of the carbonyl group.
The C=O double bond is very polarized because oxygen is much more electronegative than carbon. So, it is able to pull the π electrons of the C=O double bond toward itself and away from carbon. Remember, the degree of steric hindrance determines relative rates of reaction: unhindered methyl electrophiles react fastest, and more hindered secondary carbon electrophiles react slowest, assuming all other reaction conditions are identical. Bulky groups on either side of C=O block access to the electrophilic carbon, resulting in a decrease in reactivity.
This bond polarization renders the carbon atom electrophilic and accounts for two kinds of reactions of aldehydes and ketones. First, these molecules of acidic protons α (i.e. next to) the carbonyl group. An α-proton is acidic because the electrons left behind upon deprotonation can delocalize into the π system of the carbonyl. Second, the electrophilic carbon of the carbonyl group makes aldehydes and ketones susceptible to nucleophilic attack.
Due to the reactive nature of the carbonyl (C=O) group in aldehydes and ketones, substituents may be added to groups containing aldehydes and ketones to reduce the carbonyl reactivity; aldehydes and ketones with attached carbon chains may have resonance from the carbonyl group as well.
Synthesis of anti-tumor drug Combretastatin and its derivatives
MCAT Official Prep (AAMC)
• Bulky groups like cyclic rings may be used adjacent to the carbonyl group in aldehydes and ketones to reduce the reactivity of the C=O.
• The alpha carbon can be stabilized via resonance from the C=O.
• Bulky groups on either side of C=O block access to the electrophilic carbon, resulting in a decrease in reactivity.
• An α-proton is acidic because the electrons left behind upon deprotonation can delocalize into the π system of the carbonyl.
• The electrophilic carbon of the carbonyl group makes aldehydes and ketones susceptible to nucleophilic attack.
Steric hindrance: The prevention or retardation of inter- or intramolecular interactions as a result of the spatial structure of a molecule.
Electronegative: A measure of the tendency of an atom to attract a bonding pair of electrons.
Carbanion: A carbon atom with a negative charge.
Deprotonation: The removal (transfer) of a proton (H+) from a Brønsted–Lowry acid in an acid-base reaction.
Nucleophilic attack: A fundamental class of reactions in which a leaving group is replaced by an electron-rich compound.
Carbonyl group: A functional group composed of a carbon atom double-bonded to an oxygen atom (C=O).