Acids & Bases/ Organic Chemistry

1. Chapter 3 Structure and Bonding Acids and Bases Acids & Bases/ Organic Chemistry Dr. Ron Rusay Fall 2012

2. Models of Acids and Bases • Arrhenius: Acids produce H+ & bases produce OH ion in aqueous solutions . • Brønsted-Lowry: Acids are H+ donors & bases are proton acceptors. • HCl + H2O  Cl + H3O+ acid base

3. Comprehensive Tutorial Acid & Base Principles in Organic Chemistry Highly recommended viewing http://chemconnections.org/organic/Movies%20Organic/acidsbases.mov

4. Acid-Base EquilibriumConjugate Acid/Base Pairs HA(aq) + H2O(l)  H3O+(aq) + A(aq) conj conj acid base acid base • conjugate acid: formed when the proton is transferred to the base. • conjugate base: everything that remains of the acid molecule after a proton is lost. http://chemconnections.org/organic/Movies%20Org%20Flash/ConjugateAcidBaseActivity.swf

5. QUESTION: 3.1 Aniline, C6H5NH2, was isolated in the 1800s and began immediate use in the dye industry. What is the formula of the conjugate acid of this base? A. C6H5NH2+ B. C6H5NH3+ C. C6H5NH– C6H5NH+ C6H5NH2

6. Weak Acids • Weak acids are only partially ionized in solution. • or • Ka is the acid dissociation constant.

7. Organic Acids & Bases • Organic acids are weak acids, eg. Acetic acid. • However, there can be substantial differences in their relative strengths. What could you use to compare relative acidities? • Organic bases are weak bases and relate to ammonia. • However, there can be substantial differences in their relative strengths. What could you use to compare relative basicity?

8. Conjugates Ka x Kb = ? What do pKa and pKb refer to? pKa + pKb = ? Remember: pH + pOH = pKw

10. Strengths of Bases from pKa Values Values for pKb are not commonly found in the reference literature. Therefore, a comparison of relative basicity is made by using the pKa values of the corresponding conjugate acids.

11. Which is the stronger acid? Which is the stronger base?

12. QUESTION: 3.2 Use information on the table above to determine which of the following bases would have the weakest conjugate acid: OC6H5–; C2H3O2–; OCl–; NH3 A. OC6H5– B. C2H3O2– C. OCl– D. NH3

13. QUESTION: 3.3 Use information on the table above to determine the order of increasing base strength for the following bases: OC6H5–; C2H3O2–; ClO2–; NH3 A. OC6H5– < NH3 <C2H3O2– < ClO2– B. C2H3O2– < ClO2– < NH3 < OC6H5– C. ClO2– < C2H3O2– < NH3 < OC6H5– D. NH3 < OC6H5– < C2H3O2– < ClO2–

14. Acid and Base Equilibria The equilibrium favors the weaker of the acid vs. its conjugate acid or base vs. its conjugate. Weak wins! http://chemconnections.org/organic/Movies%20Org%20Flash/acid-base-eq.swf

15. QUESTION: 3.4 Consider the following equilibria. Identify the weaker of the two: acid vs. its conjugate acid in each reaction. Which reactions favor formation of product? 1. 2. All do: 1-6 1, 4, 5 2, 3, 6 1, 5 None do. 3. 4. 5. 6. Worksheet 5: Acids & Bases http://chemconnections.org/organic/chem226/226assign-12.html#Worksheets

16. Organic Acids & Bases • Organic molecules in context can be considered as behavingrelatively as weak acids or weak bases. • Formal Charge is important in considering which. • Knowing the Formal Charge allows a prediction. • (+) positive atoms behave acid-like, (-) negative atoms behave base-like. • This can be used in predicting how molecules will react--- or don’t react, and the products of reactions.

17. Formal Charge / Acids & BasesElectrophiles / Nucleophiles / Reactivity Worksheet 1 http://chemconnections.org/organic/chem226/226assign-12.html#Worksheets

18. Structure and Acid-Base Properties Important factors that effect acidity in binary compounds, egHCl (having only two elements): • Bond Length (shorter = stronger bonds; lower acidity) • Bond Strength (longer = weaker bonds; higher acidity: more dissociation, more protons [hydronium ions] in solution) • Bond Polarity (smaller e.n. differences favor higher acidities)

19. Electronegativity, Charge Density, Bond Polarity and Acid-Base Properties • Explain which is the stronger acid: HBr or HF.

20. HBris a stronger acid than HF. The greater the e.n. difference, the more polar the bond, the shorter and stronger the bond, and since it is harder to dissociate (break), the weaker the acid.

21. Strength of Oxyacids(Three atoms: ternary vs. binary) Induction or a ”Push-Pull” electronic effect influences the proton, which weakens the oxygen-hydrogen bond. Chlorine (higher e.n.) pulls electrons more than Iodine (lower e.n.)

22. QUESTION: 3.5 • Rank 1.0M solutions of HBrO,HIO and HClO in order of increasing acidity. HBrO , Ka = 2.1 x 10-8 HIO , Ka = 2.3 x 10-11 HClO , Ka = 3.0 x 10-8 A) HBrO <HIO < HClO B) HIO <HBrO < HClO C) HClO <HBrO < HIO D) HIO <HClO < HBrO

23. Question: 3.6True (A) / False (B) • HBrO4 is a weaker acid than HBrO2. • HClO2 , Ka = 1.2 x 10-2 • HBrO , Ka = 2.06 x 10-8 • HIO , Ka = 2.3 x 10-11 • HClO , Ka = 3.0 x 10-8

24. QUESTION: 3.7 • Rank 1.0M solutions of HBrO,HIO and HClOin order of increasing pH HBrO , Ka = 2.1 x 10-8 HIO , Ka = 2.3 x 10-11 HClO , Ka = 3.0 x 10-8 A) HBrO <HIO < HClO B) HIO <HBrO < HClO C) HClO <HBrO < HIO D) HIO <HClO < HBrO

25. QUESTION: 3.8 • Use the concept of induction “push-pull”. Rank the following organic acids in order of decreasing acidity from most acidic to least. 1) Br-CH2COOH 2) I-CH2COOH 3) CH3COOH • A) 2 > 1 > 3 B) 3 > 2 > 1 • C) 2 > 3 > 1 D) 1 > 2 > 3

26. QUESTION: 3.9 • Rank the following acids in order of decreasing acidity. • ClCH2COOH B) Cl2CHCOOH C) Cl3CCOOH D) CH3COOH • A > B > C > D 3) C > B > A > D • D > C > B > A 4) B > C > A > D

27. Question: 3.10True (A) / False (B) Trichloroacetic acid, Cl3CCOOH, is more acidic than trifluoroacetic acid, F3CCOOH.

28. Comparing Acid-Base Strengths • Consider four possible factors (ARIO)* that affect the stabilization of a formal charge. The more effectively a conjugate base can stabilize its formal negative charge the weaker it is as a base. Conceptually, consider that it is done by spreading the negative charge, lowering electron density, and/or by reducing orbital size, which increases electron proximity and attraction to the positive nucleus. These factors make for a weaker base compared to a molecule that cannot affect the charge distribution as well. The corollary is that its parent acid is a stronger acid. ARIO: • The type of Atom that has the formal charge. (A more electronegative atom is better at stabilizing negative charge.) • Resonance (Delocalizing the negative charge makes for a weaker base.) • Induction (“Push-Pull” electronic effects.) • The type of Orbital where the charge resides: *Professor David Klein, U. of Chicago

29. Approximate pKa Values of Functional Groups Professor William Blatchley, Keene State College

30. Induction Substituent Effects: “Electron Donating”:Positive effect on pKa, (Weaker Acid) eg. (butyric vs. acetic acid)“Electron Withdrawing”: Negative effect on pKa, (Stronger Acid) eg. chlorine X-CH2COOH pKa acetic acid (X = H-) 4.75 butyric acid (X = CH3CH2-) 4.85 chloroacetic acid (X = Cl-) 2.87 4-chlorobutyric acid (X = ClCH2CH2-) 4.52 3-chlorobutyric acid (X = CH3CH2Cl-) 4.05 2-chlorobutyric acid (CH3CH2CHCl-COOH) 2.88 alkyl groups are weakly electron donating chlorines are electron withdrawing (Note: the proximity of chlorine has an important effect)

31. Question: 3.11 Using ARIO principles, predict which of the protons in the following structure of acetylsalicylic acid is the most acidic.

32. An Organic Base in ContextErythroxylon spp. • It is a very valuable plant. The leaves are chewed by indigenous tribes in the Andes to boost their energy. • It has been used as a psycho-therapeutic, an opthalmic anesthetic and was purportedly used in a popular beverage many years ago that is at the heart of a $20 billion corporation. • However, both its base and conjugate acid are currently controlled substances under U.S. Federal Regulations: Title 21 secs. 329.1 & 1308.12 (1987). • Can you name the beverage and the base?

33. The beverage reportedly produced using the extract of leaves of Erythroxylon coca: The compound: cocaine, is an organic base:Merck Index, #2450, 11th ed.: Caution: May be habit forming….

34. Acid -Base Chemistry(Physical Properties) • m.p. 98 oC • b.p. (very volatile > 90 oC) Solubility: • Water: 1.67 x 10-3g/mL • CHCl3: 1.43 g/mL • Ether: 0.29 g/mL What structural feature makes cocaine a base? What simple compound can you relate it to?

35. “Regular” Cocaine Conjugate Acidof Cocaine(Physical Properties) • m.p. >195 oC Solubility: • Water: 2.5 g/mL • CHCl3: 0.08 g/mL • Ether: insoluble What accounts for the differences in solubilities of the base and conjugate acid?

36. Comparison(Physical Properties) • m.p. 98 oC • b.p. (very volatile > 90 oC) Solubility: • Water: 1.67 x 10-3g/mL • CHCl3: 1.43 g/mL • Ether: 0.29 g/mL • m.p. >195 oC Solubility: • Water: 2.5 g/mL • CHCl3: 0.08 g/mL • Ether: insoluble Crack Cocaine: (Base) Regular Cocaine (Conjugate Acid) http://en.wikipedia.org/wiki/Cocaine

37. Curved Arrows inOrganic Reactions • When bonds break and form, electrons move, and we can show their electron movements with curved arrows. • Consider the following generic acid/base reaction. • Each double-headed, curved arrow above shows the movement of two electrons. (A single headed arrow represents a single electron, as in Free Radical Reactions.) • Viewing all of the curved arrows represents the reaction MECHANISM, which accounts for where the electrons came from, how they moved, and where they wound up.

38. Acid -Base Reactions

39. Acid Base Reactions

40. QUESTION: 3.12 Aniline, C6H5NH2, was isolated in the 1800s and began immediate use in the dye industry. What is the formula of the species present in a solution of aniline that is at a pH = 2? A. C6H5NH2+ B. C6H5NH3+ C. C6H5NH– C6H5NH+ C6H5NH2

41. Which form is favored? Acid or Conjugate Base? Solution effects: The pH of the surroundings (i.e. independent of the acid-conjugate base pH contribution) controls which form is favored, acid or conjugate base, and relates to the following equation. • If the pH of the surroundings is < than a compound’s pKa, the compound will exist primarily in its acidic form. • If thepHof the surroundings is > than a compound’s pKa, the compound will exist primarily in its basic form. • NOTE: Remember that a buffer solution (surroundings) maintains a nearly constantpH within certain parameters.

42. A weak acid RCO2H,pKa = 5.2 50% acid 50% base 1% acid 99% base 90% acid 10% base 10% acid 90% base 99% acid 1% base

43. QUESTION: 3.13 Aspirin has a pKa of 3.5. In the stomach,pH ~ 2, what form of aspirin is favored?

44. QUESTIONS from Worksheet: The pKa of a general anesthetic, sodium pentothal, is 7.4.  If a patient is given sodium pentothal orally instead of iv, will it put the patient to sleep? What information is needed to answer this fundamental anesthesiology (“gas passer”) question? A drug has a pKa of 7.8 and is a known teratogen.  If given iv to a pregnant woman whose blood pH is within normal levels, will this drug cross the placenta and affect the baby? What information is needed to answer this anesthesiology (“gas passer”) question?

45. Lewis Acids and Bases • Lewis Acid: electron pair acceptor • Lewis Base: electron pair donor • Example:

47. Question: 3.14 Select the chemical equation that depicts the correct movement of electrons in the reaction of ammonia with hydrogen chloride. A) B) C) D)

50. Acid-Base ReactionsShowing a reaction with arrows Worksheet 5: Acids & Bases http://chemconnections.org/organic/chem226/226assign-12.html#Worksheets