Ch. 3 - Acids and BasesWorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins

Most professors will give you their own list of pKa values to memorize. Most of the time, those values aren’t extremely useful (due to professors not giving much  thought to it).

Here is a list of the MINIMUM number of pKa values to memorize. By the time you get to your exam, you should at least know these values. 

Concept #1: The 12 pKa values you want to memorize (because they are important!). 

Clutch Student: “Johnny, my professor said I don’t have to memorize any pKa values for the exam”.

Me: It doesn’t matter. You’ll need to understand these values for the rest of Organic Chem I and II (even Orgo III in some schools). By not memorizing this easy list, you are doing yourself a huge disservice. Just believe me and go with the flow! 

Identify all of the relevant pKa values for the indicated protons. Rank them in order of increasing acidity.

Example #1: Identify all of the relevant pKa values for the indicated protons. Rank them in order of increasing acidity.

Pop quiz: If I were to ask you what the overall pKa for this molecule is, what pKa would you say? How do we figure that out?

The overall pKa of a molecule is equal to the pKa of the most acidic hydrogen. A chain is only as strong as its weakest link; if there is a proton that can easily dissociate, that will be the one that a base will choose to remove.

So the answer is approximately 10.

Practice: Rank the following organic compounds in the order of increasing pKa.

Error: In the video I actually made a mistake when I was ordering these values! Since the question is asking to order in terms of increasing pKa, just reverse the order that I gave you. Everything else is correct though!

Remember that the pKa of all these molecules is equal to the pKa of their most acidic hydrogen. 

Practice: Rank the following compounds in the order of increasing acidity.

Additional Problems
Asteltoxin, isolated from the cultures of Aspergillus stellatus, exhibits a potent inhibitory effect on the activity of E. coli BF1-ATPase. During S. L. Schreiber’s synthesis of asteltoxin, compound 1 was treated with a strong base to form anion 2 (J. Am. Chem. Soc. 1984, 106, 4186–4188): (b) Determine whether each of the following bases would be suitable for deprotonating compound 1 and explain your decision in each case: (i) NaOH, (ii) NaNH2, or (iii) CH3CO2Na.
The structure of montelukast, an antiasthma drug, is shown here.  (b) Use Table 1.8 to identify the most acidic and most basic sites in the molecule. (Although you won't find an exact matchin structure, make a prediction based on analogy with similar groups in simpler molecules.)
(a) One acid has a pKa of 2, the other has a pKa of 8. What is the ratio of their Ka's?
Rank the following in order of decreasing acidity. Although none of these specific structures appear in Table 1.8, you can use analogous structures in the table to guide your reasoning.
Rank the following in order of decreasing basicity. As in the preceding problem, Table 1.8 should prove helpful. 
Considering only the most acidic proton in each molecule ( bold), rank in order of increasing acidity. (1 = least acidic, highest pka; 5 = most acidic, lowest pka)
Glutamic acid, being a constituent of protein, is present in every food that contains protein, but it can only be tasted when it is present in an unbound form. Glutamic acid is often used as a food additive and flavor enhancer when it is sold as its salt monosodium glutamate (MSG). The structure of glutamic acid is given below. Determine the site of deprotonation and convert the structure to the sodium salt. The answer's carbon skeleton is provided to give you a head start on the answer, just fill it in the rest of the way. Label acid, base, conjugate acid, and conjugate base. 
Complete the following two structures by adding appropriate numbers of lone pair electrons, H atoms, and formal charges to the atoms in the boxes. You must adjust your answers to indicate the predominant species at each indicated pH value. (You do not have to add anything such as H atoms to atoms not drawn in the boxes.) This problem is testing your understanding of the relationship of protonation state to pH to pKa values for certain functional groups we have discussed. Next, in the space provided, write the overall charge on each structure at the indicated pH. For your reference, here are the relevant pKa values:
Rank the acidity of the labeled protons in the following molecule from the most acidic to least acidic:   a. Hb > Ha > Hc b. Ha > Hb > Hc c. Hc > Hb > Ha d. Hc > Ha > Hb e. Hb > Ha > Hc
Hydrogen atom(s) from which position(s) is/are most easily abstracted when the following organic compound is treated with BuLi?   a. 1 b. 7 c. 3, 4 d. 1, 6, 7, 8 e. 1, 3, 4, 7
Which proton in this compound would be most acidic? A) A B) B C) C D) D
Which of the indicated protons in this compound would have the smallest pKa value? a) A b) B c) C d) D
Circle the weakest base.
Which one has the lowest pKa? a) HO b) H2O c) H3O+
Order the following in increasing order of acidity. Hl, Acetic Acid, Ethanol, and Octane. 
Order the following molecules by increasing pKa values: CH2 = CH2 (1), HOEt (2), H2SO4 (3), CH3CH2CH2CH2CO2H (4). ___ < ___ < ___ < ___   NH3 (1), CH4 (2), OH2 (3), HF (4). ___ < ___ < ___ < ___
Which is the order from the most acidic to least acidic? (A) III > IV > II > I (B) II > UV > I > III (C) II > III > IV > I  (D) IV > II > III > I 
Compound A has a pKa of 7 and compound B has a pKa of 10. Compound A is how many times more acidic than compound B? (a) 3 (b) 3000 (c) 1000
Consider the acidity/basicity of each group on the main molecule. 
​​Circle the least acidic proton in the following compound and explain your answer.  
Consider the acidity/basicity of each group on the main molecule. A) Determine the site of protonation/deprotonation in the reactant and use electron arrows to react the structures with the acid or base provided to produce the correct corresponding salt. The answer’s skeleton is provided to give you a head start on the answer. B) Label acid, base, conjugate acid and conjugate base for each reaction. 
Identify the strongest Bronsted acid:  
Rank the acidity of the labeled protons in the following molecule from lowest to highest acidity.   
Circle the most acidic proton in each of the following molecules.
In each case, identify the more stable anion. Explain why it is more stable.
In each group of compounds below, select the most  acidic compound:
In each group of compounds below, select the most acidic compound:
For each pair of compounds below, identify the more acidic compound:
For each pair of compounds below, identify the more acidic compound:
For each pair of compounds below, identify the more acidic compound:
For each pair of compounds below, identify the more acidic compound:
For each pair of compounds below, identify the more acidic compound:
Which statement regarding the two amino acids (phenylalanine & tryptophan) below is true? A) tryptophan is a stronger acid than phenylalanine as it has a larger pKa B) tryptophan is a weaker acid than phenylalanine as it has a larger pKa C) phenylalanine is a stronger acid than tryptophan as it has a smaller pKa D) phenylalanine is a weaker acid than tryptophan as it has a smaller pKa E) B) and C) are both true 
Rank the following anions in terms of increasing basicity:
For each compound below, identify the most acidic proton in the compound: 
For each compound below, identify the most acidic proton in the compound: 
For each compound below, identify the most acidic proton in the compound: 
For each compound below, identify the most acidic proton in the compound: 
Fill in the appropriate pKa values below. Remember that certain factors will affect these general pKa values.
Acid HA has pKa = 20; acid HB has pKa = 10. (a) Which is the stronger acid?
For each compound below, identify the most acidic proton in the compound:
For each compound below, identify the most acidic proton in the compound:
(a) Arrange the following compounds in order of decreasing acidity and explain your answer: CH3CH2NH2, CH3CH2OH, and CH3CH2CH3.
Arrange the following compounds in order of decreasing acidity: (a) CH3CH=CH2, CH3CH2CH3, CH3C≡CH
Arrange the following compounds in order of decreasing acidity:  
Arrange the following in order of increasing basicity: (a) CH3NH2, CH3NH3+, CH3NH-  
Arrange the following in order of increasing basicity: (b) CH3O-, CH3NH-, CH3CH2-
Arrange the following in order of increasing basicity: (c) CH3CH=CH-, CH3CH2CH2-, CH3≡C-
Consider the following compound with molecular formula  C 4H8O: (a) Draw a constitutional isomer that you expect will be  approximately one trillion (10 12) times more acidic than the compound above.
Consider the following compound with molecular formula  C 4H8O: (b) Draw a constitutional isomer that you expect will be less acidic than the compound above.
There are only four constitutional isomers with molecular formula  C4H9NO2 that contain a nitro group (–NO2). Three of these isomers have similar pKa values, while the fourth isomer has a much higher pKa value. Draw all four isomers and identify which one has the higher pKa. Explain your choice.
First, complete and balance each of the equations below. Then, choosing among ethanol, hexane, and liquid ammonia, state which (there may be more than one) might be suitable solvents for each of these reactions. Disregard the practical limitations that come from consideration of “like dissolves like” and base your answers only on relative acidities. (a) CH3(CH2)8OD + CH3(CH2)8Li →
Rank the following from least to most acidic.
First, complete and balance each of the equations below. Then, choosing among ethanol, hexane, and liquid ammonia, state which (there may be more than one) might be suitable solvents for each of these reactions. Disregard the practical limitations that come from consideration of “like dissolves like” and base your answers only on relative acidities. (b) NaNH2 + CH3C≡CH → (The conjugate acid of this amine, aniline, has a pKa of 4.63.)  
BONUS: Using pK a values given, what is the major product of the following reaction of the acetylide base with guanine (HCCH/HCC-, pK a = 24)?
Below is the structure of rilpivirine, a promising new anti-HIV  drug that combats resistant strains of HIV. Its ability to side-step resistance will be discussed in the upcoming chapter. (b) Identify which of these two protons is more acidic. Explain your choice.
Asteltoxin, isolated from the cultures of Aspergillus stellatus, exhibits a potent inhibitory effect on the activity of E. coli BF1-ATPase. During S. L. Schreiber’s synthesis of asteltoxin, compound 1 was treated with a strong base to form anion 2 (J. Am. Chem. Soc. 1984, 106, 4186–4188):(a) Identify the most acidic proton in  1 and justify your choice using any necessary drawings.
I. Supply the pKa values for each of the following:a) etheneb) propynec) methaned) e)II. Will the reaction below proceed efficiently as written?
Which of the following would represent the strongest acid?a. pKa = 10.5b. Ka = 2.5 x 10 ­-5c. Ka = 2.5 x 10 -6d. pKa = 4.90
(b) Arrange the conjugate bases of the acids given in part
Predict the pKa for the following molecules:
Rank the indicated protons in decreasing order of acidity.(A) II>I>III(B) I>III>II(C) II>III>I(D) I>II>III(E) III>II>I
Draw the structure of the predominant form of CH3CH2NH3+ (PKa = 11.0) at pH a 14.