Relative Strengths of Organic Acids and Bases

1. Relative Strengths of Organic Acids and Bases Background knowledge for today: Proton based definition of an acid is? Recall what does it mean for an acid or base to be “strong”? Recall that all acids and bases are in a constant equilibrium and the “one-sided-ness of that equilibrium in measured in what numeric terms?

2. New Vocabulary: Electrophilic/Electrophiles Nucleophilic/Nucleophiles (Req. free pair of e’s or pi bond) Which would be a B-L acid? Base?

3. HA + H2O ↔ A- + H3OorHA(aq) ↔ A-(aq)+ H+(aq)

4. Ka: Acid dissociation Constant p Ka Is the “negative logaritmic version” pKa = -log10Ka HA + H2O ↔ A- + H3OorHA(aq) ↔ A-(aq)+ H+(aq)High Ka = Strong acidLow Ka = Weak acidLow pKa (Strong Acid)High pKa (Weak Acid – Tends to reform)

5. THE ACIDITY OF ORGANIC ACIDS

6. Why are these acids acidic? In each case, the same bond gets broken - the bond between the hydrogen and oxygen in an -OH group. Writing the rest of the molecule as "X": “Organic Example”

7. So . . . if the same bond is being broken in each case, why do these three compounds have such widely different acid strengths?

8. The factors to consider Two of the factors which influence the ionization of an acid are: 1. the strength of the bond being broken, 2. the stability of the ions being formed. Factor #1: In these cases, you seem to be breaking the same oxygen-hydrogen bond each time, and so you might expect the strengths to be similar. However: The most important factor is the nature of the ions formed. You always get a hydroxonium ion - so that's constant - but the nature of the anion (the negative ion) varies markedly from case to case.

9. The Start: The “expected”: The Actual: Ethanoic acid / Acetic Acid This leads to a delocalized pi system over the whole of the -COO- group

10. Conclusion: The more you can spread charge around, the more stable an ion becomes. In this case, if you delocalize the negative charge over several atoms. This makes your anion unusually stable and so you are less likely to re-form the ethanoic acid. Meaning: It favors the formation of ions: it dissociates more: it produces more H ions: it becomes a strong acid

11. Phenol

12. In our last example: delocalization spreads charge over the whole of the COO- group. (Because oxygen is more electronegative than carbon) You can think of most of the charge being shared between the two oxygen. Phenol But here delocalization spreads this charge over the whole over only the oxygen. (Again because oxygen is more electronegative than carbon) This means: the charge is less distributed: less stable: reverts back to it’s original state more readily: produces less H+: And thus is a weaker acid

13. Now Try:EthanolCH3CH2OH

14. Ethanol This has nothing at all going for it. There is no way of delocalizing the negative charge. That intense negative charge will be highly attractive towards hydrogen ions, and so the ethanol will instantly re-form. Since ethanol is very poor at losing hydrogen ions, it is hardly acidic at all.

15. Variations in acid strengths Summary Thus Far: We now know the strength is largely a factor of the ion stability via the electron delocalization/distribution. Now: Certain attachments can either strengthen or weaken an acid. Two Categories: • Attachments that withdraw e’s from the O/COO by pulling towards themselves (NO2, Halogens) • Less charge gathered around O/COO • Makes the anion/conjegate base more stable • Favors formation of ions • Stronger acid results • Attachments that induce e’s towards the O/COO by pushing away from themselves. (Alkyl groups) • More charge gathered around O/COO • Makes the anion/conjegate base less stable • Favors formation of original reactant • Weaker acid results Deeper into the rabbit hole:

16. Variations in acid strengths In fact, the carboxylic acids have widely different acidities. One obvious difference is between methanoic acid, HCOOH, and the other simple carboxylic acids: pKa HCOOH 3.75 CH3COOH 4.76 CH3CH2COOH 4.87 CH3CH2CH2COOH 4.82 Consider:

17. Variations in acid strengths As the next table shows, the more chlorines you can attach the better: carboxylic acids: pKa CH3COOH 4.76 CH2ClCOOH 2.86 CHCl2COOH 1.29 CCl3COOH 0.65 Consider:

18. Variations in acid strengths Fluorine is even better (Why?), also note the increase over Cl is not as much as you might expect: carboxylic acids: pKa CH2FCOOH 2.66 CH2ClCOOH 2.86 CH2BrCOOH 2.90 CH2ICOOH 3.17 Consider:

19. Variations in acid strengths Finally, notice that the effect falls off quite quickly as the attached halogen gets further away from the -COO- end. Here is what happens if you move a chlorine atom along the chain in butanoic acid. carboxylic acids: pKa CH3CH2CH2COOH 4.82 CH3CH2CHClCOOH 2.84 CH3CHClCH2COOH 4.06 CH2ClCH2CH2COOH 4.52 Consider:

20. Other Push/Pull groups and how they can affect reactivity/acidity…Don’t forget to also consider a Benzene ring. Figure 19.8 How common substituents affect the reactivity of a benzene ring towards electrophiles and the acidity of substituted benzoic acids

21. Substituted Benzoic Acids Recall that substituents on a benzene ring either donate or withdraw electron density, depending on the balance of their inductive and resonance effects. These same effects also determine the acidity of substituted benzoic acids. [1] Electron-donor groups destabilize a conjugate base, making an acid less acidic—The conjugate base is destabilized because electron density is being donated to a negatively charged carboxylate anion.

22. [2] Electron-withdrawing groups stabilize a conjugate base, making an acid more acidic. The conjugate base is stabilized because electron density is removed from the negatively charged carboxylate anion.

23. Summary Figure 19.7 Summary: The relationship between acidity and conjugate base stability for acetic acid, phenol, and ethanol • Note that although resonance stabilization of the conjugate base is important in determining acidity, the absolute number of resonance structures alone is not what is important!

24. Would these factors also effect organic bases? All of the compounds we are concerned with are derived from ammonia and so we'll start by looking at the reason for its basic properties. • Just like with the acids, we’ll use the definition of a base as "a substance which combines with hydrogen ions (protons)". • Strength in a base will be how easily they take hydrogen ions from water molecules.

25. Ammonia as a weak base

26. As with acids… Two of the factors which influence the strength of a base are: the ease with which the lone pair picks up a hydrogen ion, the stability of the ions being formed. • The nitrogen is more negative in methylamine than in ammonia, and so it picks up a hydrogen ion more readily. • The ion formed from methylamine is more stable than the one formed from ammonia, and so is less likely to shed the hydrogen ion again.

28. Carboxylic Acids and the Acidity of the O—H Bond Structure and Bonding • Carboxylic acids are compounds containing a carboxy group (COOH). • The structure of carboxylic acids is often abbreviated as RCOOH or RCO2H, but keep in mind that the central carbon atom of the functional group is doubly bonded to one oxygen atom and singly bonded to another.

29. Structure and Bonding • The C—O single bond of a carboxylic acid is shorter than the C—O bond of an alcohol. • This can be explained by looking at the hybridization of the respective carbon atoms. • Because oxygen is more electronegative than either carbon or hydrogen, the C—O and O—H bonds are polar.

30. Physical Properties • Carboxylic acids exhibit dipole-dipole interactions because they have polar C—O and O—H bonds. • They also exhibit intermolecular hydrogen bonding. • Carboxylic acids often exist as dimers held together by two intermolecular hydrogen bonds. Figure 19.3 Two molecules of acetic acid (CH3COOH) held together by two hydrogen bonds

31. Reactions of Carboxylic Acids The most important reactive feature of a carboxylic acid is its polar O—H bond, which is readily cleaved with base.

32. The nonbonded electron pairs on oxygen create electron-rich sites that can be protonated by strong acids (H—A). • Protonation occurs at the carbonyl oxygen because the resulting conjugate acid is resonance stabilized (Possibility [1]). • The product of protonation at the OH group (Possibility [2]) cannot be resonance stabilized.

33. The polar C—O bonds make the carboxy carbon electrophilic. Thus, carboxylic acids react with nucleophiles. • Nucleophilic attack occurs at an sp2 hybridized carbon atom, so it results in the cleavage of the  bond as well.

34. Carboxylic Acids—Strong Organic BrØnsted-Lowry Acids • Carboxylic acids are strong organic acids, and as such, readily react with BrØnsted-Lowry bases to form carboxylate anions.

35. An acid can be deprotonated by a base that has a conjugate acid with a higher pKa. • Because the pKa values of many carboxylic acids are ~5, bases that have conjugate acids with pKa values higher than 5 are strong enough to deprotonate them.

37. Carboxylic acids are relatively strong acids because deprotonation forms a resonance-stabilized conjugate base—a carboxylate anion. • The acetate anion has two C—O bonds of equal length (1.27 Å) and intermediate between the length of a C—O single bond (1.36 Å) and C=O (1.21 Å).

38. Resonance stabilization accounts for why carboxylic acids are more acidic than other compounds with O—H bonds—namely alcohols and phenols. • To understand the relative acidity of ethanol, phenol and acetic acid, we must compare the stability of their conjugate bases and use the following rule: - Anything that stabilizes a conjugate base A:¯ makes the starting acid H—A more acidic.

39. Ethoxide, the conjugate base of ethanol, bears a negative charge on the O atom, but there are no additional factors to further stabilize the anion. Because ethoxide is less stable than acetate, ethanol is a weaker acid than acetic acid. • Phenoxide, the conjugate base of phenol, is more stable than ethoxide, but less stable than acetate because acetate has two electronegative O atoms upon which to delocalize the negative charge, whereas phenoxide has only one.

40. Figure 19.7 Summary: The relationship between acidity and conjugate base stability for acetic acid, phenol, and ethanol • Note that although resonance stabilization of the conjugate base is important in determining acidity, the absolute number of resonance structures alone is not what is important!

41. The Inductive Effect in Aliphatic Carboxylic Acids

43. Substituted Benzoic Acids Recall that substituents on a benzene ring either donate or withdraw electron density, depending on the balance of their inductive and resonance effects. These same effects also determine the acidity of substituted benzoic acids. [1] Electron-donor groups destabilize a conjugate base, making an acid less acidic—The conjugate base is destabilized because electron density is being donated to a negatively charged carboxylate anion.

44. [2] Electron-withdrawing groups stabilize a conjugate base, making an acid more acidic. The conjugate base is stabilized because electron density is removed from the negatively charged carboxylate anion.

45. Figure 19.8 How common substituents affect the reactivity of a benzene ring towards electrophiles and the acidity of substituted benzoic acids

46. Give the IUPAC name for each compound. a) 3,3’-dimethylhexanoic acid b) 4-chloropetanoic acid c) 2,4-diethylhexanoic acid

47. d) 4-isopropyl-6,8-dimethylnonanic acid

48. Draw the structure corresponding to the IUPAC name. a) 2-bromobutanoic acid b) 2,3-dimethylpentanoic acid c) 3,3’,4-trimethylheptanoic acid

49. d) 2-secbutyl-4,4’-diethylnonanoic acid e) 3,4-diethylcyclohexanecarboxylic acid

50. f) 1-isopropylcyclobutanecarboxylic acid