Overview
This lecture covers strategies for estimating pKa values and introduces the key principles (the "cardinal rule") for predicting acid strength when pKa tables are limited. The focus is on understanding how charge, atom identity, resonance, and inductive effects influence acidity.
Using pKa Tables and Estimations
- pKa tables provide values for common acids and bases, but do not include every possible molecule.
- To estimate an unknown pKa, find a similar compound in the table with the same functional group and similar structure.
- This approach gives an approximate value, but may fail for molecules with unusual substituents or highly electronegative atoms.
Limitations of pKa Tables
- Substituents like fluorine or chlorine can drastically change acidity, making simple comparisons with similar molecules inaccurate.
- Guiding principles are needed when tables don't help or produce incorrect estimations.
The Cardinal Rule: Principles for Predicting Acidity
- C: Charge—Acidity increases if the acidic hydrogen is attached to a positively charged atom.
- A: Atom—As you move right across a period, the acidity increases due to higher electronegativity stabilizing the conjugate base.
- R & D: Resonance & Delocalization—Resonance in the conjugate base stabilizes negative charge, increasing acidity.
- IN: Inductive Effects—Electronegative atoms near the acidic site pull electron density, stabilizing the conjugate base and increasing acidity.
Charge and Acidity
- A proton on a positively charged atom (e.g., NH4+) is more acidic than on a neutral atom (e.g., NH3).
- Charged species are higher in energy and more willing to lose a proton.
Atom Electronegativity and Effective Electronegativity
- Among similar acids, the one whose conjugate base is on a more electronegative atom is more acidic.
- In hydrocarbons, SP hybridized carbons are more electronegative (due to s-character) than SP2 or SP3, stabilizing negative charge better.
Comparing Acids Within a Group
- As you go down a group, atom size increases, making the conjugate base more stable by spreading out charge (size effect trumps electronegativity).
- Example: HCl (pKa ~ -7) is a stronger acid than HF (pKa ~ 3.2) due to the larger, more stable chloride anion.
Resonance and Delocalization
- Resonance allows charge to be delocalized in the conjugate base (as in carboxylates), increasing stability and acidity.
- Non-resonance-stabilized bases (like alkoxides) are less stable, making their acids weaker.
Inductive Effects
- Electronegative atoms near the acidic site stabilize negative charge by pulling electron density, increasing acidity.
- If the acidic site has a positive charge, inductive effects can destabilize the acid by further lowering electron density.
Applying Multiple Principles
- In complex molecules, all principles (charge, atom, resonance, induction) may need to be applied together to compare acidities.
Key Terms & Definitions
- pKa — A measure of acid strength; lower pKa means stronger acid.
- Conjugate base — The species formed after an acid donates a proton.
- Electronegativity — The tendency of an atom to attract electrons.
- Resonance — Delocalization of electrons across multiple atoms, stabilizing a molecule.
- Inductive effect — Electron withdrawal through sigma bonds by electronegative atoms.
Action Items / Next Steps
- Practice predicting relative acidities using the cardinal rule principles.
- Prepare to analyze molecules using multiple guiding principles at once for the next class.