3. Acids and Bases

Rank the following compounds from easiest to hardest at removing a proton from its methyl substituent:

Explain the relative acidities.

Glycine has pK_a values of 2.3 and 9.6. Do you expect the pK_a values of glycylglycine to be higher or lower than these values?

Fosamax (shown on the previous page) has six acidic groups. The active form of the drug, which has lost two of its acidic protons, is shown in the box. 

(Notice that the phosphorus atom in Fosamax and the sulfur atom in [Problem 36] can be surrounded by more than eight electrons because P and S are below the second row of the periodic table.)

a. Why are the OH groups bonded to phosphorus the strongest acids of the six groups?

b. Which of the remaining four groups is the weakest acid?

Protonated cyclohexylamine has a Ka = 1 * 10-11. Using the same sequence of steps as in Problem 94, determine which is a stronger base: cyclohexylamine

or aniline.

e. Which has a greater Ka: cyclohexylammmonium ion or anilinium ion?

f. Which is a stronger acid: cyclohexylamine or aniline?

The pK_a values of a few ortho-, meta-, and para-substituted benzoic acids are shown below:

The relative pK_a values depend on the substituent. For chloro-substituted benzoic acids, the ortho isomer is the most acidic and the para isomer is the least acidic; for nitro-substituted benzoic acids, the ortho isomer is the most acidic and the meta isomer is the least acidic; and for amino-substituted benzoic acids, the meta isomer is the most acidic and the ortho isomer is the least acidic. Explain these relative acidities.

c. NH₂: meta > para > ortho

Explain why, when the guanidino group of arginine is protonated, the double-bonded nitrogen is the nitrogen that accepts the proton.

Which compound is the strongest base?

Consider the following compounds that vary from nearly nonacidic to strongly acidic. Draw the conjugate bases of these compounds, and explain why the acidity increases so dramatically with substitution by nitro groups.

Choose the more acidic member of each pair of isomers, and show why the acid you chose is more acidic.

(d)

(e)

Choose the more acidic member of each pair of isomers, and show why the acid you chose is more acidic.

(f)

(g)

The pK_a of ascorbic acid (vitamin C, page 55) is 4.17, showing that it is slightly more acidic than acetic acid (CH₃COOH, pK_a 4.74).

a. Show the four different conjugate bases that would be formed by deprotonation of the four different OH groups in ascorbic acid.

b. Compare the stabilities of these four conjugate bases, and predict which OH group of ascorbic acid is the most acidic.

Choose the more basic member of each pair of isomers, and show why the base you chose is more basic.

c.

d.

Choose the more basic member of each pair of isomers, and show why the base you chose is more basic.

e.

The following compounds can all react as bases.

b. Rank the conjugate acids in the order you would predict, from most stable to least stable.