CHEM 232

Acid-base chemistry
Reference: David R. Klein, Organic Chemistry As A Second Language, 2004, Ch. 3.

The first reactions we will cover in this course are acid-base reactions. The two most important aspects of acid-base chemistry are: 1. determining the relative strengths of acids and bases 2. predicting the direction of equilibrium To determine relative strengths, you must know the structures of your reagents and analyze those structures based on a few simple qualities. To predict equilibrium, you simply need to know the relative strengths of the acids involved the reaction. Relative strengths of acids To determine the relative strengths of two acids, you must look at the stability of the conjugate base. Four factors must be taken into account, shown here in order of their importance: 1. Identity of the charged atom When comparing atoms across a row of the periodic table, the important factor is electronegativity. A more electronegative atom can better handle a negative charge, and so the conjugate base with the negative charge on that atom is more stable. e.g.
OH

is more acidic than

O

because

is more stable than

When comparing atoms down a column of the periodic table, the important factor is the size of the ion. A larger atom has the negative charge spread over a greater volume and so is more stable. e.g.
SH

is more acidic than

S

OH

because

is more stable than

2. Resonance If a conjugate base can be stabilized with resonance it is more stable than one that cannot be so stabilized.
OH

e.g.

is more acidic than

OH

because its conjugate base can be stabilized by resonance:

O O

3. Induction The presence of electronegative atoms close to a negative charge can stabilize that charge through the phenomenon of induction. This is a through-bond redistribution of electron density that can have a stabilizing effect on a molecule with a negative charge.
Cl Cl Cl OH
H H H OH

e.g.

is more acidic than

because the negative charge of the conjugate base can be partially redistributed to the electronegative chlorine atoms. 4. Orbitals A negative charge on a sp-hybridized carbon is lower in energy because the electron density is held closer to the nucleus than electrons in sp2 or sp3 orbitals. Therefore a negatively-charged alkyne is more stable than an alkene or alkane. ORDER OF ACIDITY:
H H H

>
H

>
H

PRACTICE PROBLEMS Decide which of the following compounds is more acidic and state the reason for your answer.
OH

1.

or

OH

2.
NH2 OH

or

3.

or

Using these rules you will be able to predict the relative acidities of any pair of acids, except for one. The one exception to these rules is that alkynes are more acidic than amines. For this reason NH2- is often used for deprotonating alkynes.
NaNH2

pKa is a quantitative measurement of the acidity of a compound. You do not need to memorize exact pKa values for particular compounds, but you should know pKa ranges for certain classes of compounds such as those shown in the table below. Functional group Carboxylic acids Alcohols Alkynes Amines Alkenes Alkanes Approximate pKa 4-6 15-17 25 35-40 45 50

Predicting the position of acid-base equilibria The equilibrium position of an acid-base reaction can be easily predicted once the relative acidities of the acids involved are determined. The equilibrium will always favor formation of the weakest acid and the weakest base. When shown a reaction and asked to predict the position of the equilibrium (which is the same thing as asking which of the reagents is present in greater quantity), three steps should be taken: 1. Decide which of the reagents are acting as acids and which as bases. Use the Brnsted-Lowry or Lewis definitions to identify the acid and base on each side of the reaction. The base will have a lone pair or double bond that will react with a proton or other site of electron deficiency on the acid. 2. Determine the relative acidities of the two acids in the reaction. Use the rules outlined above to determine which acid is stronger. The strongest acid will be on the same side of the reaction as the strongest base, and the weakest acid on the same side as the weakest base. 3. Indicate that the equilibrium lies towards formation of the weakest acid. The reaction will favor formation of the weakest acid and weakest base. These will be present in greater quantity because they have less potential energy than the strongest acid and base. PRACTICE PROBLEMS Predict the position of equilibrium for the following reactions.
OH O

NH2

NH

OH

NH2

NH

NH

NH2