Questions: Aldehydes and Ketones: Structure and Reactivity

Question 1

Why does a nucleophile attack the carbonyl carbon rather than the carbonyl oxygen, even though the oxygen bears the partial negative charge (δ−) in the ground state?

• A. The oxygen lone pairs are too tightly held to react
• B. The carbonyl carbon carries the partial positive charge (δ+) and is the electrophilic site that attracts nucleophiles
• C. The C=O pi bond blocks access to the oxygen
• D. Nucleophiles attack both carbon and oxygen with equal probability

Answer: (B)

The C=O bond is polarized so that carbon is δ+ and oxygen is δ−. Nucleophiles are electron-rich species attracted to electron-poor sites — so they attack the δ+ carbon. The δ− oxygen actually repels nucleophiles. Attack at carbon leads to a productive tetrahedral intermediate; attack at oxygen would require breaking a much stronger bond and leads nowhere useful. The misconception that negative charge marks the site of nucleophilic attack is one of the most common errors in carbonyl chemistry.

Question 2

Aldehydes are generally more reactive than ketones toward nucleophilic addition.

• T. True
• F. False

Answer: True

Both steric and electronic factors favor aldehydes. Electronically, ketones have two alkyl groups flanking the carbonyl; these groups donate electron density through hyperconjugation and induction, reducing the partial positive charge on carbon and making it less electrophilic. Sterically, two alkyl groups block nucleophile approach more than the one alkyl group (plus H) in an aldehyde. Formaldehyde (two H atoms, no alkyl groups) is the most reactive common carbonyl compound.

Question 3

What makes the alpha C–H bond of a ketone (pKa ≈ 20) far more acidic than a typical alkane C–H bond (pKa ≈ 50)?

Model answer: When the alpha proton is removed, the resulting carbanion is stabilized by resonance with the adjacent carbonyl group — the negative charge delocalizes from the alpha carbon onto the electronegative oxygen, forming the enolate ion. Resonance stabilization of the conjugate base always increases acidity (lowers pKa). A typical alkane C–H loses a proton to form an unstabilized carbanion with no resonance, which is why those bonds are far less acidic.

Enolate formation underlies much of synthetic organic chemistry — aldol condensation, Claisen condensation, and alkylation reactions all depend on generating the alpha carbanion. The roughly 30-unit pKa difference between an alpha C–H and a typical C–H is entirely due to resonance stabilization of the enolate. Whenever you see a C–H bond adjacent to an electron-withdrawing group, expect enhanced acidity.