Chemistry

What is an enolate?

The conjugate base of a carbonyl compound formed by removing the α-H; negative charge delocalized between the α-carbon and the oxygen.

Draw the resonance idea of an enolate.

C=C–O⁻ ↔ ⁻C–C=O (charge on carbon or oxygen).

Why does using hydroxide (pKa of H₂O 15.7) to form an enolate fail to give much enolate?

Ketone α-H pKa ≈ 20 > 15.7 so Keq < 1; equilibrium lies toward the ketone, giving only a small amount of enolate.

Why not use NH₂⁻ or other very strong bases?

They can be too nucleophilic and attack the carbonyl rather than just deprotonating.

What is LDA and why is it used?

Lithium diisopropylamide: very strong base (conj. acid pKa ≈ 35–36) that is bulky, so it deprotonates the α-H quantitatively without acting as a nucleophile.

Rule for predicting acid–base equilibrium direction.

Equilibrium favors the side with the weaker acid and weaker base (the acid with the higher pKa). Proton transfer goes from the stronger acid to the weaker acid.

How do you compute Keq from pKa values?

Keq = 10^(pKa of the acid formed − pKa of the acid reacting), i.e., 10^(pKa(product acid) − pKa(reactant acid)). Keq > 1 when the product acid is the weaker one.

Write the Henderson–Hasselbalch equation.

pH = pKa + log([A⁻]/[HA]).

When pH = pKa what is [A⁻]/[HA]?

1 (50% HA, 50% A⁻).

When pH is 2 units BELOW pKa, what is [A⁻]/[HA]?

0.01 (1/100): the protonated form dominates.

When pH is 2 units ABOVE pKa, what is [A⁻]/[HA]?

100: the deprotonated form dominates.

At the half-equivalence point of a titration, what is the pH?

pH = pKa (buffer region, 50% HA/50% A⁻).

In the histidine titration curve, what do the flat regions (A, C, E) represent?

Half-equivalence points where pH equals each ionizable group's pKa: A ≈ 1.8 (carboxylic acid), C ≈ 6 (imidazole N–H⁺), E ≈ 9.2 (ammonium).

Histidine has how many ionizable groups and which?

Three: α-COOH (lowest pKa), imidazole side chain (middle, ≈6), α-NH₃⁺ (highest, ≈9).

At A on the histidine titration, what is the ratio of carboxylic acid to carboxylate?

50% RCOOH (HA) and 50% RCOO⁻ (A⁻).

Why does the imidazole ring of histidine have a pKa near 6?

The protonated imidazolium delocalizes the positive charge over both N–H groups by resonance, giving it moderate acidity.

Which histidine group loses its proton first on adding base?

The most acidic: the carboxylic acid (pKa ≈ 1.8), then the imidazolium (≈6), then the ammonium (≈9.2).

Thermodynamics vs kinetics in one line.

Thermodynamics asks 'how far' (equilibrium, ΔG, K); kinetics asks 'how fast' (rates, k).

What is Gibbs free energy?

G = H − TS; ΔG predicts spontaneity (negative ΔG = favorable).

Relationship between ΔG° and Keq?

ΔG° = −RT ln Keq.

Components of ΔG?

ΔH (enthalpy; bond strengths, bond dissociation energies) and ΔS (entropy; disorder) at temperature T: ΔG = ΔH − TΔS.

What does a large negative ΔG imply for Keq?

Keq ≫ 1; equilibrium lies far toward products.

What does entropy measure?

Disorder (number of accessible states); more disorder = higher S.

Hydration of a carbonyl: what is the equilibrium?

R₂C=O + H₂O ⇌ R₂C(OH)₂ (gem-diol); the position depends on carbonyl electrophilicity (e.g., formaldehyde strongly favors hydrate; acetone strongly favors ketone).

What does bond dissociation energy tell you?

Bond strength: enthalpy required to homolytically break a bond; higher BDE = stronger bond.