1. CHEMISTRY 2000 Topic #4: Organic Chemistry Spring 2010 Dr. Susan Lait == aspirin

2. 2 Organic Acids (Carboxylic Acids) When you hear the term “organic acid”, it’s generally referring to a carboxylic acid. Carboxylic acids are readily deprotonated by bases such as NaOH e.g. The reason that this reaction is favoured in the forward direction is that the products are more stable than the reactants. In particular, the conjugate base (acetate; CH 3 CO 2 - ) is much more stable than the original base (hydroxide, OH - ). This makes hydroxide a stronger base than acetate. It also makes acetic acid (pK a =4.7) a stronger acid than water (pK a =14). acidconjugate acidconjugate basebase

3. 3 Organic Acids (Carboxylic Acids) The strength of an acid is dependent on the stability of its conjugate base: The conjugate base of HCl (a strong acid; pK a =-7) is Cl - (a stable anion and very weak base) The conjugate base of H 2 O (a weak acid; pK a =14) is OH - (less stable than Cl - and a relatively strong base) The strength of an acid can also be said to be inversely related to the strength of its conjugate base (and vice versa). Why is CH 3 CO 2 - more stable than OH - ?

4. 4 Organic Acids (Carboxylic Acids) Is the reaction below product-favoured or reactant-favoured? Since this reaction is equivalent to the acid dissociation equation (as long as the solution is sufficiently dilute that the X H2O  1) its equilibrium constant is the K a for CH 3 CO 2 H: Recall that we can relate the K a and pK a for an acid via the following equation: An acid is stronger if it has a large K a and a small pK a.

5. 5 Organic Acids (Carboxylic Acids) We can increase the strength of an acid by adding electron- withdrawing groups, further stabilizing its conjugate base. e.g.To increase the acidity of acetic acid, replace one or more hydrogen atoms of the methyl group with halogens: This stabilization through  bonds is called an inductive effect. Inductive effects are strongest when close to the acidic hydrogen. (CF 3 CH 2 CH 2 CH 2 CO 2 H is not significantly more acidic than CH 3 CH 2 CH 2 CH 2 CO 2 H) We saw inductive effects in CHEM 1000 when we looked at the strength of the oxoacids (e.g. HClO 2 vs. HClO 3 vs. HClO 4 )

6. 6 Organic Acids (Others) Carboxylic acids are among the most acidic organic molecules; however, a number of other functional groups contain acidic hydrogen atoms: Alcohols are typically about as acidic as water. Most have pK a values of ~15-18. (Inductive effects can lower these values to ~12) Phenols are typically more acidic than alcohols. Most have pK a values of ~8-10. (The pK a can go as low as 1 with the right groups attached to the aromatic ring) Thiols (R-SH) are also typically more acidic than alcohols. Most have pK a values of ~10-12. (Also subject to inductive effects) Amines are not acidic in water, but can be deprotonated by some *very* strong bases in unreactive solvents like alkanes or ethers. Their pK a values are typically ~35-40! Sulfur and nitrogen are both less electronegative than oxygen. Why are thiols more acidic than alcohols, but amines less acidic?

7. 7 Organic Acids (Others) Phenol is “just an alcohol with a benzene ring”. Why is phenol more acidic than most non-aromatic alcohols?

8. 8 Calculating pH of an Acidic Solution We know that a strong acid (pK a < 0) dissociates fully in water because it is a stronger acid than H 3 O + (pK a = 0) so reacts fully with H 2 O to generate H 3 O + and its conjugate base. This effect is known as solvent leveling: No acid stronger than the conjugate acid of the solvent can exist in any solution. No base stronger than the conjugate base of the solvent can exist in any solution. (Hydroxide isn’t the strongest base – not by a long shot! It’s just the strongest base that can exist in water.) Weak acids aren’t subject to solvent leveling, so we must consider what percentage of acid molecules have dissociated. If we have a relatively concentrated solution of a relatively weak acid, it is likely that the percent dissociation of the acid is small and that the actual concentration of acid is relatively close to the nominal concentration (i.e. concentration listed on the bottle or in the question). As a solution becomes more dilute, this assumption becomes less fair. ALWAYS CHECK YOUR ASSUMPTIONS AFTER CALCULATING!!!

9. 9 Calculating pH of an Acidic Solution Consider a 0.32 M solution of phenol (pK a =9.95) at 25.00  C.

10. 10 Calculating pH of an Acidic Solution Consider a 4.2  10 -5 M solution of CH 3 CO 2 H (pK a =4.74) at 25.00  C.

11. 11 Distribution Curves We can also work backwards, using the K a equation to work out the percent dissociation of an acid at a given pH. The pH tells us the activity (and therefore the concentration) of H + (aq) so, as long as we know the K a value for the acid, we’re set. Calculate the percent dissociation of acetic acid (pK a =4.74) at pH 4.00. so

12. 12 Distribution Curves If we repeat this calculation at a large number of different pH values, we generate what is known as a distribution curve: acetic acid (CH 3 CO 2 H) acetate (CH 3 CO 2 - ) Note that the two curves cross at the pK a of the acid! The pK a of an acid is the pH at which it is exactly 50% dissociated.

13. 13 Distribution Curves It is easy to see why an acid will be 50% dissociated at its pK a if we take the negative logarithm of the K a equation on page 11: This is the Henderson-Hasselbach equation. We can see that if a A- /a HA = 1 then log(a A- /a HA ) = 0 and pH = pK a. As the acid’s percent dissociation rises, so does the pH and vice versa.

14. 14 Distribution Curves for Polyprotic Acids If an acid has multiple acidic protons whose pK a values are different by several units, the distribution curve will look like several monoprotic distribution curves superimposed: If the pK a values are too close, the distribution curve will become more complex.

15. 15 Organic Bases (Amines) When you hear the term “organic base”, it’s generally referring to an amine. Amines are readily protonated by acids: e.g. The basicity of amines is due to the lone pair on the nitrogen atom which makes all amines (R = H, alkyl or combination) Lewis bases. baseconjugate baseconjugate acidacid

16. 16 Organic Bases (Amines) We have seen one other functional group containing nitrogen. Why is an amine considered a good base, but an amide is not? The nitrogen atom of an amide is so weakly basic that the oxygen of the carbonyl group will be protonated over it!

17. 17 Quantifying Basicity We can measure a base’s strength using either of two measures: We can refer to the K a (or pK a ) of the conjugate acid. Since the strength of a base is inversely related to the strength of its conjugate acid, we can deduce the strength of a base from the strength of its conjugate acid. Smaller pK a = Stronger Conjugate Acid = Weaker Base

18. 18 Quantifying Basicity Alternatively, we can refer to the K b (or pK b ) of the base itself. This is the equilibrium constant for reaction of the base with water: K b is inversely proportional to K a for the conjugate acid: or where K w = 10 -14 under standard conditions. Larger K b = Smaller pK b = Stronger Base

19. 19 Calculating pH of a Basic Solution We can calculate the pH of a solution of weak base by: Using the K b expression and nominal solution concentration to calculate a OH- then Using the K w expression (K w = a H+ · a OH- ) to calculate a H+ then Using a H+ to calculate pH. Recall that, at 25  C, K w = 10 -14. The pK a of aniline (C 6 H 5 NH 2 ) is 28 and the pK a of C 6 H 5 NH 3 + is 4. What are the K b and pK b values for aniline?

20. 20 Calculating pH of a Basic Solution Calculate the pH of a 0.71 M aqueous solution of aniline at 25  C.

21. 21 Amino Acids: Acid and Base Some textbooks present the structure of an amino acid as follows in order to show that the name comes from having an amine group and a carboxylic acid group. This is not how an amino acid actually exists in biological systems (or other pH ~7 solution). Instead, it exists as the zwitterion:

22. 22 Amino Acids: Acid and Base Why is this? The pK a for the –CO 2 H proton is typically ~2 (slightly lower than the standard 3-5 range for carboxylic acids). The pK a for the conjugate acid of the amine group (i.e. for the –NH 3 + proton) is typically ~9-10. Use this data to sketch a distribution curve for the amino acid, labeling with the major species within each pH range.

23. 23 Beyond Water: Implications of Acid-Base Chemistry It’s easy to forget that not all chemistry is done in aqueous solution, but the pK a scale doesn’t just go from 0 to 14! Often times, the solvent for a reaction is chosen based (at least in part) on acid-base considerations… Consider the following reaction: What would happen if we tried to perform it in aqueous solution?

24. 24 Beyond Water: Implications of Acid-Base Chemistry Solvent leveling can be useful, though. Sodium methoxide (NaOCH 3 ) can be prepared via a couple of different methods, both of which use methanol as the solvent: We saw in CHEM 1000 that adding Na (s) to H 2 O gives NaOH and H 2(g) Similarly, adding Na (s) to CH 3 OH gives NaOCH 3 and H 2(g) : Adding a very strong base (e.g. a source of H - such as NaH) to CH 3 OH will also produce NaOCH 3 along with the conjugate acid of the base: