Acidity and Basicity Notes

Inductive Effects on Acidity

• Introduction: Inductive effects influence the acidity of carboxylic acid derivatives by stabilizing the conjugate base.
• Equilibrium: Consider the equilibrium between a carboxylic acid and water:
  $RCOOH + H<em>2O \rightleftharpoons RCOO^- + H</em>3O^+$
• Acidity Trend: The acidity increases with the number of electron-withdrawing chlorine atoms due to the inductive stabilization of the conjugate base.
• pKa Values: Observe the trend in pKa values for acetic acid derivatives:
  • $CH<em>3CO</em>2H$: pKa = 4.72
  • $ClCH<em>2CO</em>2H$: pKa = 2.86
  • $Cl<em>2CHCO</em>2H$: pKa = 1.29
  • $Cl<em>3CCO</em>2H$: pKa = 0.65
• Delocalization: Delocalization of the negative charge in the conjugate base enhances its stability.
• Electron-Withdrawing Groups: Electron-withdrawing groups like $CCl_3$ stabilize the conjugate base, increasing acidity.

Hybridization and Acidity

• Hybridization Effects: Hybridization affects pKa values because s orbitals are closer to the nucleus and stabilize electrons more effectively than p orbitals.
• s Character: Higher s character in an orbital leads to more tightly held electrons.
• Hybridization Examples:
  • sp: 50% s character
  • sp2: 33% s character
  • sp3: 25% s character
• Acidity Prediction: Anions in sp orbitals are the most stable, suggesting alkynes should be the most acidic.
• pKa Rationalization: Use hybridization to explain the pKa values of ethane, ethene, and ethyne.

Delocalization Effects on Acidity

• Delocalization Impact: Delocalization has a significant impact on pKa values.
• Example: Compare the acidities of cyclohexanol (pKa = 16) and phenol (pKa = 10).
• Phenol Acidity: Phenol is more acidic than a typical alcohol due to the delocalization of the negative charge in its conjugate base (phenoxide ion).
• Substitution Effects: Consider the effects of substituents on the phenol ring:
  • $NO_2$: pKa = 7.1 (inductively and mesomerically electron-withdrawing)
  • $Cl$: pKa = 9.2 (inductively electron-withdrawing)
  • $H$: pKa = 9.9
  • $OH$: increasing acidity

Basicity

• Definition: Basicity is the ability of a species to accept a proton.
• Measuring Base Strength: For anions, stronger acids have weaker conjugate bases.
• Neutral Bases: For neutral bases like $NH<em>3$, the pKa of its conjugate acid ($NH</em>4^+$) is used to measure base strength (pKaH = 9.24).
• Formic Acid Example: Formic acid (pKa = 3.7) is a stronger acid than the conjugate acid of acetylide; therefore, the formate anion is a weaker base than the acetylide anion.

Factors Affecting Base Strength

• Accessibility of Electrons: The more accessible the electrons of a base, the stronger the base.
  • Negatively charged bases are stronger than neutral ones.
  • Bases with localized charge are stronger than those with delocalized charge.
• Stabilization of Positive Charge: The ability to stabilize the positive charge through delocalization or solvation enhances basicity.

Trends in Neutral Nitrogen Bases (Amines)

• Prediction: Substituents that increase electron density on N enhance basicity.
• Alkyl Substitution: Alkyl groups are inductively electron-donating, which should increase electron density on N.
• General Reaction: Illustrative reaction of an amine acting as a base:
  $NR<em>3 + H</em>2O \rightleftharpoons NR_3H^+ + OH^-$

Results of Alkyl Substitution on Amine Basicity

• Observation 1: All amines have pKaH > 9.24, making them stronger bases than $NH_3$.
• Observation 2: Primary amines ($R-NH_2$) have similar pKaH values.
• Observation 3: Secondary amines ($R_2NH$) are slightly more basic.
• Observation 4: Tertiary amines ($R_3N$) are less basic than primary amines.
• Competing Factors: These trends are due to:
  • Increasing substitution enhancing electron density.
  • Stabilization through solvation in water.
• pKaH Values for Amines:
  *Methyl:
  *primary: 10.6
  *secondary: 10.8
  *tertiary: 9.8
  *Ethyl:
  *primary: 10.7
  *secondary: 11
  *tertiary: 10.8
  *n-Pr:
  *primary: 10.7
  *secondary: 11
  *tertiary: 10.3
  *n-Bu:
  *primary: 10.7
  *secondary: 11.3
  *tertiary: 9.9

Solvation and Inductive Effects on Amine Basicity

• Increasing Substitution: Increases electron density on N, making the lone pair more available. Alkyl groups stabilize the positive charge via electron donation.
  • Solvation: Hydrogen bonding to water stabilizes the charge. More hydrogen bonding leads to greater stabilization, which decreases with increasing alkyl substituents.
• Depiction of Solvation: Visual representation of hydrogen bonding between amines and water molecules.
  • Electron-Withdrawing Groups: Electron-withdrawing groups decrease the availability of the lone pair, reducing base strength.
  • Hybridization: Higher s character means the lone pair is held tighter, reducing basicity (sp < sp2 < sp3).
  • Example: Methylamine pKaH = 10.8

Conjugation and Delocalization Effects

• Compare the pKaH of cyclohexylamine (10.7) and aniline (4.6); aniline is much weaker base
• The lone pair of aniline is partially conjugated/delocalized with the benzene ring(makes lone pair less available to act as a base).
• This stability from delocalization is lost upon protonation.
• Amides protonate on O
• Delocalization makes an amide N sp2 hybridized with lone pair in a p orbital
• this delocalization ties up the lone pair making it less available to act as a base - pKaH = 0
• Protonation on N is disfavored - Protonation occurs on O to give a positive charge that can be delocalized

Amidines and Guanidines as Strong Bases

• Reason: Stabilization of the conjugate acid through resonance.
  • Amidine: Two equivalent resonance forms upon protonation, delocalizing the positive charge over both N atoms (pKaH ~ 12).
    • Guanidine: Three equivalent resonance forms, delocalizing the positive charge over all three N atoms equally (pKaH ~ 13.6).
• Resonance Structures: Visual representations of the resonance forms in amidines and guanidines.

Key pKa Values to Know

• Functional Group-Specific Values: Important pKa values categorized by functional group.