H O H C C C C O = C C H = H C O
H C O H3C aspirin CHEMISTRY 2000
Topic #3: Organic Chemistry Fall 2020 Dr. Susan Findlay See Exercises in Topic 12 Measuring Strength of Acids
When you hear the term “organic acid”, it usually refers to a carboxylic acid.
Carboxylic acids are readily deprotonated by strong bases:
.O. .O. -... H .. H C .. H + .O H C .. + O H C O .. H C O.- .. 3 .. 3 ... acid base conjugate base conjugate acid
This reaction is favoured in the forward direction because the products are lower in energy than the reactants. In particular, the conjugate base (acetate; ) is much more stable than the original base (hydroxide, ). − 𝐶𝐶𝐶𝐶3𝐶𝐶𝐶𝐶2 Therefore, acetate is a weaker base than hydroxide.− 𝑂𝑂𝑂𝑂 Therefore, acetic acid is a stronger acid than water. 2 Measuring Strength of Acids
An acid’s strength depends on the stability of its conjugate base: The conjugate base of (a strong acid; = 7) is (a very weak base) − 𝐻𝐻𝐻𝐻𝐻𝐻 𝑝𝑝𝑝𝑝𝑎𝑎 − 𝐶𝐶𝐶𝐶 The conjugate base of (a weak acid; = 14) is (a relatively strong base) − 𝐻𝐻2𝑂𝑂 𝑝𝑝𝑝𝑝𝑎𝑎 𝑂𝑂𝑂𝑂 The strength of an acid can therefore be said to be inversely related to the strength of its conjugate base (and vice versa).
Why is more stable than ? − − 𝐶𝐶𝐶𝐶3𝐶𝐶𝐶𝐶2 𝑂𝑂𝑂𝑂
3 Measuring Strength of Acids-
Consider the reaction below. Identify the acid, base, conjugate acid and conjugate base. Is this reaction product-favoured or reactant-favoured? The of is 5. The of is 14. 𝑝𝑝𝑝𝑝𝑎𝑎 𝐶𝐶𝐶𝐶3𝐶𝐶𝐶𝐶2𝐻𝐻 The 𝑎𝑎 of 2 is 0. 𝑝𝑝𝑝𝑝 𝐻𝐻 𝑂𝑂+ 𝑝𝑝𝑝𝑝𝑎𝑎 𝐻𝐻3𝑂𝑂 .O. .O. H .. H H ..+ H C .. H + O C .. + O H C O .. H C O.- 3 .. 3 ... H
4 Measuring Strength of Acids
The reaction on the previous page is equivalent to the acid dissociation equation for (as long as the solution is sufficiently dilute that 1): 𝐶𝐶𝐶𝐶3𝐶𝐶𝐶𝐶2𝐻𝐻 𝐻𝐻2𝑂𝑂 𝑋𝑋 ≈ - + CH3CO2H(aq) CH3CO2 (aq) + H (aq)
Its equilibrium constant is therefore the for :
𝐾𝐾𝑎𝑎 𝐶𝐶𝐶𝐶3𝐶𝐶𝐶𝐶2𝐻𝐻
Recall that we can relate the and for an acid via the following equation: 𝐾𝐾𝑎𝑎 𝑝𝑝𝐾𝐾𝑎𝑎
An acid is stronger if it has a large and a small . 5
𝑲𝑲𝒂𝒂 𝒑𝒑𝑲𝑲𝒂𝒂 Factors Affecting Strength of Acids
We can increase the strength of an acid by adding electron- withdrawing groups, further stabilizing its conjugate base.
To increase the acidity of acetic acid, replace one or more hydrogen atoms attached to carbon with halogens:
.O. .O. .O. .O. H C .. H H C .. H F C .. H F C .. H C O C O C O C O H .. H .. H .. F .. H F F F
pKa = 4.74 pKa = 2.66 pKa = 1.24 pKa = 0.23
This stabilization through σ bonds is called an inductive effect. Inductive effects are only meaningful when the electron withdrawing group is within a few bonds of the acidic hydrogen. 6 Factors Affecting Strength of Acids
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 values of ~15-18. (Inductive effects can lower these values to ~12) 𝑝𝑝𝑝𝑝𝑎𝑎 Phenols are typically more acidic than alcohols. Most have values of ~8-10. (The pK can go as low as 1 with the right groups a 𝑎𝑎 attached to the aromatic ring) 𝑝𝑝𝑝𝑝
Thiols (R-SH) are also typically more acidic than alcohols. Most have values of ~10-12. (Also subject to inductive effects)
Amines𝑝𝑝𝑝𝑝 are𝑎𝑎 not acidic in water, but can be deprotonated by some *very* strong bases in unreactive solvents like alkanes or ethers. Their values are typically ~35-40!
𝑝𝑝𝑝𝑝𝑎𝑎
7 Factors Affecting Strength of Acids
Sulfur and nitrogen are both less electronegative than oxygen. Why are thiols more acidic than alcohols, but amines less acidic?
8 Factors Affecting Strength of Acids
Phenol is “just an alcohol with a benzene ring”. Why is phenol more acidic than most non-aromatic alcohols?
9 Calculating pH of an Acidic Solution
A strong acid < 0 dissociates fully in water because it is a stronger acid than = 0 so reacts fully with to 𝑎𝑎 generate 𝑝𝑝𝑝𝑝and its +conjugate base. 3 𝑎𝑎 2 + 𝐻𝐻 𝑂𝑂 𝑝𝑝𝑝𝑝 𝐻𝐻 𝑂𝑂 𝐻𝐻3𝑂𝑂
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.)
10 Calculating pH of an Acidic Solution
Weak acids aren’t subject to solvent leveling, so we must perform equilibrium calculations (ICE table) if we want to calculate of a solution of weak acid.
𝑝𝑝𝑝𝑝 We can often simplify the math by making assumptions: If we have a relatively concentrated solution of a relatively weak acid, only a small percentage of the acid will dissociate so the equilibrium activity of will be very close to the initial activity. Assume this when . 𝐻𝐻𝐻𝐻 You have likely been taught to treat the initial concentration of 𝑎𝑎𝐻𝐻𝐻𝐻 ≫ 𝐾𝐾𝑎𝑎 in water as zero. It’s not. At 25 , it’s 10 . You can often + assume that the initial concentration of −will7 be negligible – but𝐻𝐻 not when working with very dilute℃ solutions+ or𝑀𝑀 very weak acids. You can assume that initial concentration𝐻𝐻 of is negligible when . + 𝐻𝐻 𝑎𝑎𝐻𝐻𝐻𝐻 � 𝐾𝐾𝑎𝑎 ≫ 𝐾𝐾𝑤𝑤 ALWAYS CHECK ASSUMPTIONS AFTER CALCULATING!!! Calculating pH of an Acidic Solution
Calculate the of a 0.32 solution of phenol = 9.95 at 25 . 𝑝𝑝𝑝𝑝 𝑀𝑀 𝑝𝑝𝑝𝑝𝑎𝑎 ℃
12 Calculating pH of an Acidic Solution
13 Calculating pH of an Acidic Solution
Calculate the of a 4.2 × 10 solution of CH3CO2H = 4.74 at 25 . −5 𝑝𝑝𝑝𝑝 𝑀𝑀 𝑝𝑝𝑝𝑝𝑎𝑎 ℃
14 Calculating pH of an Acidic Solution
15 Distribution Curves
We can also work backwards, using the equation to work out the percent dissociation of an acid at a given . 𝐾𝐾𝑎𝑎 𝑝𝑝𝑝𝑝 The tells us the activity (and therefore the concentration) of ( ) so, as long as we know the value for the acid, we’re 𝑝𝑝𝑝𝑝 set.+ 𝐻𝐻 𝑎𝑎𝑎𝑎 𝐾𝐾𝑎𝑎
= so = + − − 𝑎𝑎𝐻𝐻 ⋅ 𝑎𝑎𝐴𝐴 𝐾𝐾𝑎𝑎 𝑎𝑎𝐴𝐴 𝐾𝐾𝑎𝑎 + 𝑎𝑎𝐻𝐻𝐻𝐻 𝑎𝑎𝐻𝐻 𝑎𝑎𝐻𝐻𝐻𝐻
16 Distribution Curves
Calculate the percent dissociation of acetic acid = 4.74 at 4.00. 𝑝𝑝𝑝𝑝𝑎𝑎 𝑝𝑝𝑝𝑝
17 Distribution Curves
If we repeat this calculation at a large number of different values, we generate what is known as a distribution curve: 𝑝𝑝𝑝𝑝 - acetate (CH3CO2 )
acetic acid (CH3CO2H)
Note that the two curves cross at the of the acid! The of an acid is the at which it is exactly 50% dissociated. 18 𝑝𝑝𝑝𝑝𝑎𝑎 𝑝𝑝𝑝𝑝𝑎𝑎 𝑝𝑝𝑝𝑝 Distribution Curves
We can see why an acid will be 50% dissociated at its if we take the negative logarithm of both sides of the expression: 𝑝𝑝𝑝𝑝𝑎𝑎 log = log 𝐾𝐾𝑎𝑎 + − 𝐻𝐻 𝐴𝐴 𝑎𝑎 𝑎𝑎 ⋅ 𝑎𝑎 − 𝐾𝐾 − 𝐻𝐻𝐻𝐻 log = log 𝑎𝑎 log − + 𝑎𝑎𝐴𝐴 − 𝐾𝐾𝑎𝑎 − 𝑎𝑎𝐻𝐻 − 𝑎𝑎𝐻𝐻𝐻𝐻 = log − 𝑎𝑎𝐴𝐴 𝑝𝑝𝐾𝐾𝑎𝑎 𝑝𝑝𝑝𝑝 − 𝑎𝑎𝐻𝐻𝐻𝐻 + log = − 𝐴𝐴 𝑎𝑎 𝑎𝑎 𝑝𝑝𝐾𝐾 𝐻𝐻𝐻𝐻 𝑝𝑝𝑝𝑝 This is the Henderson𝑎𝑎 -Hasselbalch equation. We can see that if = 1 then log = 0 and = . As the acid’s 𝑎𝑎𝐴𝐴− 𝑎𝑎𝐴𝐴− percent𝑎𝑎 𝐻𝐻dissociation𝐻𝐻 rises,𝑎𝑎𝐻𝐻 so𝐻𝐻 does the and vice𝑎𝑎 versa. 𝑝𝑝𝑝𝑝 𝑝𝑝𝑝𝑝 19 𝑝𝑝𝑝𝑝 Distribution Curves for Polyprotic Acids
If an acid has multiple acidic protons whose values are different by several units, the distribution curve will look like 𝑎𝑎 several monoprotic distribution curves superimposed:𝑝𝑝𝑝𝑝
If the values are too close, the distribution curve will become more complex. 20 𝑝𝑝𝑝𝑝𝑎𝑎 Organic Bases (Amines)
When you hear the term “organic base”, it’s generally referring to an amine.
Amines are readily protonated by strong acids:
H .. + H ..+ H .. H N + O N + R R H R R O.. R H R
base acid conjugate acid conjugate base
The basicity of amines is due to the lone pair on the nitrogen atom which makes all amines (R = H, alkyl or combination) both Lewis bases and Brønsted bases.
21 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!
22 Measuring Strength of Bases
We can measure a base’s strength using either of two measures: We can refer to the (or ) of the conjugate acid. Since the strength of a base is inversely related to the strength of its 𝑎𝑎 𝑎𝑎 conjugate acid, we can𝐾𝐾 deduce𝑝𝑝𝑝𝑝 the strength of a base from the strength of its conjugate acid.
H H + + N N H H H C H H 3 H
pKa = 9.3 pKa = 10.6
Smaller for Conjugate Acid = 𝒂𝒂 Stronger𝒑𝒑𝒑𝒑 Conjugate Acid = Weaker Base
23 Measuring Strength of Bases
Alternatively, we can refer to the (or ) of the base itself. This is the equilibrium constant for reaction of the base with water: 𝐾𝐾𝑏𝑏 𝑝𝑝𝑝𝑝𝑏𝑏 H .. + N H .. H N -. .. R R + O R R + .O H R .. R ..
24 Measuring Strength of Bases
is inversely proportional to for the conjugate acid:
𝐾𝐾𝑏𝑏 𝐾𝐾𝑎𝑎 = or = 𝐾𝐾𝑤𝑤 𝐾𝐾𝑎𝑎 𝐾𝐾𝑎𝑎 ⋅ 𝐾𝐾𝑏𝑏 𝐾𝐾𝑤𝑤 𝐾𝐾𝑏𝑏 where = 10 at 25 . −14 𝐾𝐾𝑤𝑤 ℃ We can also say that + = . At 25 , = 14.
𝑝𝑝𝑝𝑝𝑎𝑎 𝑝𝑝𝑝𝑝𝑏𝑏 𝑝𝑝𝑝𝑝𝑤𝑤 ℃ 𝑝𝑝𝑝𝑝𝑤𝑤 .. .. N N H H H3C H H H H H + + N N H H pKb = 4.7 pKb = 3.4 H C H H 3 H
pKa = 9.3 pKa = 10.6
Larger = Smaller = Stronger Base
𝒃𝒃 𝒃𝒃 𝑲𝑲 𝒑𝒑𝒑𝒑 25 Calculating pH of a Basic Solution
The of aniline is 28. The of is 4. What are the and values for aniline? + 𝑝𝑝𝑝𝑝𝑎𝑎 𝐶𝐶6𝐻𝐻5𝑁𝑁𝑁𝑁2 𝑝𝑝𝑝𝑝𝑎𝑎 𝐶𝐶6𝐻𝐻5𝑁𝑁𝑁𝑁3 𝐾𝐾𝑏𝑏 𝑝𝑝𝐾𝐾𝑏𝑏
26 Calculating pH of a Basic Solution
We can calculate the of a solution of weak base by: Using the expression and nominal solution concentration to calculate then 𝑝𝑝𝑝𝑝 𝐾𝐾𝑏𝑏 Using the −expression ( = ) to calculate then 𝑎𝑎𝑂𝑂𝑂𝑂 Using to calculate pH. + − + 𝐾𝐾𝑤𝑤 𝐾𝐾𝑤𝑤 𝑎𝑎𝐻𝐻 � 𝑎𝑎𝑂𝑂𝐻𝐻 𝑎𝑎𝐻𝐻 + 25 = 10 Recall that,𝑎𝑎𝐻𝐻 at , . −14 ℃ 𝐾𝐾𝑤𝑤
27 Calculating pH of a Basic Solution
Calculate the of a 0.71 aqueous solution of aniline at 25 .
𝑝𝑝𝑝𝑝 𝑀𝑀 ℃
28 Calculating pH of a Basic Solution
29 Amino Acids: Acid and Base
Some textbooks present the structure of an amino acid as follows .O. H .. N C .. H H C O.. R H
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 7 solution). Instead, it exists as the zwitterion: . . 𝑝𝑝𝑝𝑝 ≈ H .O. H + N C ...- H C O... R H
30 Amino Acids: Acid and Base
Why is this? The for the proton is typically ~2 (slightly lower than the standard 3-5 range for carboxylic acids). 𝑝𝑝𝑝𝑝𝑎𝑎 −𝐶𝐶𝐶𝐶2𝐻𝐻 The for the conjugate acid of the amine group (i.e. for the proton) is typically ~9-10. 𝑎𝑎 𝑝𝑝𝑝𝑝+ Use− this𝑁𝑁𝑁𝑁 3data to sketch a distribution curve for the amino acid, labeling with the major species within each range.
𝑝𝑝𝑝𝑝
31