Chapter 3

Acids

An Introduction to Organic Reactions and Their Mechanisms

and Bases

Ch. 3 - 1

1.

Reactions and Their Mechanisms

Almost all organic reactions fall into one of four categories: Substitutions Additions Eliminations Rearrangements

Ch. 3 - 2

 Substitutions

In a substitution, one group

replaces another

Ch. 3 - 3

Examples
Br + NaOMe MeOH H3C OMe + NaBr

H3C

+ Br

Br

Br

+ HBr

H + CH3Cl AlCl3

CH3 + HCl
Ch. 3 - 4

 Additions

In an addition all parts of the

adding reagent appear in the product; two molecules become one

Ch. 3 - 5

Examples
H Br H + H Br Br CCl4 H C H C Br H C

C H

Cl Cl HC CH + 2 Cl Cl CCl4 H C C H Cl Cl

Ch. 3 - 6

 Eliminations

In an elimination one molecule

loses the elements of another small molecule

Ch. 3 - 7

Examples
H C H CH3 C Br CH3 NaOMe MeOH heat H C H C CH3 CH3

+ MeOH + NaBr
H H C H C H NaNH2 heat

Br Br

+ 2H

NH2

+ 2 NaBr
Ch. 3 - 8

Rearrangements In a rearrangement a molecule

undergoes a reorganization of its constituent parts

H H C C CH3 C H H3C C H3C C CH3 CH3

Examples
H

H3C

H3C

Ch. 3 - 9

What is this?
light + H2

1. 2. 3. 4.

Addition Elimination Substitution Rearrangement

0%
1

0%
2

0%
3

0%
4

10

1A. Homolysis and Heterolysis of Covalent Bonds

Homolysis

A B

homolytic bond cleavage

A + B
radicals

Ch. 3 - 11

Heterolysis

A B

heterolytic bond cleavage

A + B
ions

A B

A +B
Ch. 3 - 12

 Normally requires the bond to be polarized d+

A
d-

d-

Usually occurs with assistance

d+

A B

Y A +B
Ch. 3 - 13

2.

AcidBase Reactions

Many reactions are acidbase reactions Two classes of acidbase reactions are fundamental in organic chemistry BrnstedLowry Lewis

Ch. 3 - 14

2A. BrnstedLowry Acids and Bases

A BrnstedLowry acid is a substance that can donate a proton A BrnstedLowry base is a substance that can accept a proton

Ch. 3 - 15

Example Conjugate Acid of H2O

Cl
H O H H + Cl

Base (H+ acceptor)

O H

+ H

Acid (H+ donor)

Conjugate Base of HCl

Ch. 3 - 16

Total ionic reaction

O H H + Cl + Na O H 2H O + Na + Cl H

Spectator ions

Net reaction
H O H H + O H 2H O H
Ch. 3 - 17

3.

Lewis Acids and Bases

Lewis Acids are electron pair acceptors Lewis Bases are electron pair donors Lewis Base (e pair donor)
dCl H d+ + NH3

Cl

+ H

NH3

Lewis Acid (e pair acceptor)

Ch. 3 - 18

Lewis Base (e pair donor)

d+ Cl Al d d
-

d-Cl + NH3 Cl

Cl Cl Al Cl NH3

Lewis Acid (e pair acceptor)

In Lewis acidbase theory, the attraction of oppositely charged species is fundamental to reactivity

Ch. 3 - 19

4.

Heterolysis of Bonds to Carbon: Carbocations and Carbanions

d+ C Z dheterolysis C + Z

carbocation

dC

d+

heterolysis

carboanion
Ch. 3 - 20

Carbocations are electron deficient. They have only six electrons in their valence shell, and because of this, carbocations are Lewis acids
C carbocation (a Lewis acid) + B C B

anion (a Lewis base)

C carbocation (a Lewis acid)

O H

H water (a Lewis base)

Ch. 3 - 21

4A. Electrophiles and Nucleophiles

Because carbocations are electronseeking reagents, chemists call them

electrophiles (meaning electronloving)

Ch. 3 - 22

All Lewis acids are electrophiles. By accepting an electron pair from a Lewis base, a carbocation fills its valence shell
C + B C B

anion carbocation (a Lewis base) (a Lewis acid and electrophile)

Ch. 3 - 23

Carbon atoms that are electron poor because of bond polarity, but are not carbocations, can also be electrophiles

d+ dC O

Lewis base

Lewis acid electrophile

Ch. 3 - 24

Carbanions are Lewis bases A nucleophile is a Lewis base that seeks a positive center such as a positively charged carbon atom

Nu + d+ dC O electrophile Nu C O

nucleophile

C electrophile

Nu nucleophile

Nu
Ch. 3 - 25

What is aluminum chloride in the reaction below?

CH3
+

Cl Cl Al Cl CH3

Cl Cl Al Cl

CH3 N CH3 CH3

CH3

1. 2.

3.
4.

A A A A

Lewis acid Bronsted acid Lewis base Bronsted base

0%
1

0%
2

0%
3

0%

Ch. 3 - 26

5.

How to Use Curved Arrows in Illustrating Reactions Curved arrows

show the direction of electron flow in a reaction mechanism point from the source of an electron pair to the atom receiving the pair always show the flow of electrons from a site of higher electron density to a site of lower electron density never show the movement of atoms. Atoms are assumed to follow the flow of the electron Ch. 3 - 27

Examples
HO H

NOT
NOT H

HO

N H

d-O C d+

N H

dO C d+

O H3C O H+ OH H3C

O O +H O
Ch. 3 - 28

6.

The Strength of BrnstedLowry Acids and Bases: Ka and pKa In contrast to strong acids such as HCl and H2SO4, acetic acid is a much weaker acid
O H3C OH + H2O H3C O O + H O H H

At 25oC, in a 0.1 M acetic acid solution, only about 1% of the acetic acid molecules ionize

Ch. 3 - 29

6A. The Acidity Constant, Ka

O H3C OH + H2O H3C O O + H O H H

Equilibrium constant (Keq)

Keq =

[CH3CO2 ]

[H3O ]

[CH3CO2H][H2O]
Ch. 3 - 30

For dilute aqueous solutions, the concentration of water is essentially constant (~55.5M); and the Keq expression can be written in terms of the acidity constant (Ka)
[CH3CO2 ]

Ka = Keq [H2O] =

[H3O ]

[CH3CO2H]

At 25C, the acidity constant for acetic acid is 1.76 x 10-5

Ch. 3 - 31

For any weak acid dissolved in water

HA + H2O

H3O
[H3O ] [A ] [HA]

+ A

Ka =
An An

acid with a large value of Ka a strong acid acid with a small value of Ka a weak acid
Ch. 3 - 32

6B. Acidity and pKa pKa = - log Ka pH = - log [H3O ]

For acetic acid the pKa is 4.75

pKa = - log [1.76 x 10-5] = - [- 4.75] = 4.75
Ch. 3 - 33

The larger the value of the pKa, the weaker the acid Increasing acid strength

CH3CO2H pKa = 4.75

Weak acid

>

CF3CO2H pKa = 0

>

HCl pKa = -7
Very strong acid
Ch. 3 - 34

Relative Strength of Selected Acids & Their Conjugate Bases

Increasing acid strength
O

Acid

HCl

Ph

S O

OH

H H3C O

H H H O

H HNO3 H -1.74 -1.4

p Ka Conjugate Base

-7

-6.5 O

-2.9 O

-2.5

Cl

Ph

S O

CH3OH

H2O

NO3

Increasing base strength

Ch. 3 - 35

(Cont'd)
Increasing acid strength
O O HF F3C OH 0.18 O F F3C O Ph O 3.2 Ph 4.21 O Ph NH2 H3C OH Ph H N H 4.63 H H3C 4.75 O O OH O

Acid

pKa Conjugate Base

Increasing base strength

Ch. 3 - 36

(Cont'd)
Increasing acid strength
O O H H H N H 9.2 O 9.9 O NH3 CH3NH2 HO H OH H3C H N H 10.6 15.7 H H O H

Acid

pKa Conjugate Base O

9.0

Increasing base strength

Ch. 3 - 37

(Cont'd)
Increasing acid strength

Acid pKa Conjugate Base

OH OH 16 18 O O

O H 19.2 O

HC 25 HC C

H 35 H

Increasing base strength

Ch. 3 - 38

(Cont'd)
Increasing acid strength
H Acid H2N H H2C H p Ka Conjugate Base 38 NH2 44 H2C CH H3C H3C H C H 50 CH2 H

Increasing base strength

Ch. 3 - 39

6C. Predicting the Strength of Bases The stronger the acid, the weaker its conjugate base The larger the pKa of the conjugate acid, the stronger the base

Increasing base strength

Cl

CH3CO2

HO

Very weak base pKa (HCl) = -7

Weak base pKa (CH3CO2H) = 4.75

Strong base pKa (H2O) = 15.7

Ch. 3 - 40

Example
Base CH3OH H3C O H -2.5 H H H2O O H -1.74 H

Conjugate Acid pKa

Since CH3O H2 is a stronger acid than H O is a stronger base than H3O , 2 CH3OH

Ch. 3 - 41

The same species can be both an acid and a base

CH3COOH + H3O+ CH3COOH + H2O CH3CO3H+ + H2O CH3COO- + H3O+

Ch. 3 - 42

What is ethanol, C2H5OH?

1.

2.
3. 4.

An acid A base Neither one Depends on the reaction

0%
1

0%
2

0%
3

0%
4

Ch. 3 - 43

7.

How to Predict the Outcome of AcidBase Reactions

Acidbase reactions always favor the formation of the weaker acid and the weaker base Acidbase reactions are under equilibrium control

Ch. 3 - 44

stronger base
O R O H + Na OH R

weaker base
O O Na + H O H

stronger acid pKa ~3-5

weaker acid pKa = 15.7

Ch. 3 - 45

7A. Water Solubility as the Result of Salt Formation Most carboxylic acids containing more than 5 carbons are insoluble in water However, due to their acidity, they are soluble in aq. NaOH
O R O H + Na OH R O O Na + H O H

(R>5 carbons) Insoluble in water

Soluble in water (due to its polarity As a salt)

Ch. 3 - 46

Similarly, amines with high molecular weights are insoluble in water However, due to their basicity, they are soluble in aqueous acids

NH 2 + H

O H

Cl

N H

Cl + H2O

Water Insoluble

Water Soluble (salt)

Ch. 3 - 47

8.

Relationships between Structure and Acidity

HF HCl HBr HI

Bond Length ()
pKa

0.92
3.2

1.28
-7

1.41
-9

1.60
-10

Increasing acidity

The strength of HX bond HF > HCl > HBr > HI The stronger the HX bond, the weaker the acid. Ch. 3 - 48

Thus acidity increases as we descend a vertical column in a group in the Periodic Table
HF F
Cl Br
-

Increasing acidity

HCl HBr

Increasing basicity

HI

The stronger the acid, the weaker the conjugate base.

Ch. 3 - 49

H3CH H3NH

d-

d+

d-

d+

d-

d+

d-

d+

HOH

FH

Electro2.5 2.1 3.0 2.1 3.5 2.1 4.0 2.1 negativity

pKa

48

38

15.7

3.2

The higher the electronegativity of an atom, the easier it will acquire a negative charge.
Ch. 3 - 50

Thus acidity increases from left to right when we compare compounds in the same row of the Periodic Table
Increasing acidity H3CH
CH 3

H2NH
NH 2

HOH
OH

FH
F

Increasing basicity
Ch. 3 - 51

Acidity increases within a given row (electronegativity effect)

Hydride pKa C (H3CH) 48 N (H2NH) 38 O (HOH) 15.7 S (HSH) 7.0 Se (HSeH) 3.9 F (FH) 3.2 Cl (ClH) -7 Br (BrH) -9

Acidity increases within a given column (bond strength effect)

Ch. 3 - 52

I (IH) -10

8A. The Effect of Hybridization

(50% s character) sp
H C C H H

(33.3% s character) sp2 H H

C C H

(25% s character) sp3 H H H C C H H H

pKa = 25

pKa = 44

pKa = 50

Having more s character means that the electrons of the anion will, on the average, be lower in energy, and the anion will be Ch. 3 - 53 more stable

Relative Acidity of the Hydrocarbons

H C C H > H C C H H > H H C H C H H H

Relative Basicity of the Carbanions

H C H C H H > H H C C H
Ch. 3 - 54

>

8B. Inductive Effects

Inductive effects are electronic effects transmitted through bonds The inductive effect of a group can be electron donating or electron

withdrawing

Inductive effects weaken as the distance from the group increases

Ch. 3 - 55

H3C

CH3

The CC bond is nonpolar.

H3C
2

d+

CH2
1

d+

dF

The positive charge that the fluorine imparts to C1 is greater than that imparted to C2 because the fluorine is closer to C1
Ch. 3 - 56

9.

Energy Changes The two fundamental types of energy are kinetic energy and potential energy Chemical energy is a form of potential energy

Ch. 3 - 57

Potential energy exists between objects that either attract or repel each other.

Ch. 3 - 58

H + H

DH o = - 436 kJ mol-1

The relative potential energies of hydrogen atoms and a hydrogen molecule

H + H
Potential Energy

436 kJ mol-1
H H
Ch. 3 - 59

10. The Relationship between Keq and DG

DG = - RT ln Keq
R is the gas constant = 8.314 J K-1 T is the absolute temperature in kelvins (K)

For a reaction to favor the formation of products when equilibrium is reached it must have a negative value for DG

Ch. 3 - 60

DG = DH - T DS
DH is the enthalpy energy DS is the entropy energy

A negative value for DH will contribute to making DG negative and will consequently favour the formation of products The more random a system is, the greater is its DS

Ch. 3 - 61

CH3CH2O2

+ H3O

Free Energy Change

CH3CO2 + H3O

DG = 90.8 kJ/mol

DG = 27 kJ/mol CH3CO2H + H2O CH3CH2O2H + H2O

Ch. 3 - 62

When comparing acidity of organic compounds, we compare the stability of their conjugate base. The more stable the conjugate base, the stronger the acid
CH3COOH pKa 4.75 CH3CH2OH 16
Ch. 3 - 63

11A. The Resonance Effect

The conjugate base acetate is more stable (the anion is more delocalized) than ethoxide due to resonance stabilization
O O O CH3 O CH3 O O

CH3

Thus, acetic acid is a stronger acid than ethanol

Ch. 3 - 64

11B. The Inductive Effect

O

<
CH3 O <H CH3CH2 O <H Acetic acid Ethanol

Stronger acid

Weaker acid
Ch. 3 - 65

O Cl O Cl

O O

The Cl further stabilizes the carboxylate anion due to negative inductive effect of the Cl
Ch. 3 - 66

12. The Effect of the Solvent on Acidity

In the absence of a solvent (i.e., in the gas phase), most acids are far weaker than they are in solution

Solvation of any species decreases the entropy of the solvent because the solvent molecules become much more ordered as they surround molecules of the solute, but DH favors solvation.
Ch. 3 - 67

13. Organic Compounds as Bases

If a compound contains an atom with an unshared electron pair, it is a potential base

Ch. 3 - 68

O H

+ H

O H

H +

Alcohol

Strong acid

Alkyloxonium ion Weak base

O R

+ H

O R

H +

Ether

Strong acid

Dialkyloxonium Weak ion base

Ch. 3 - 69

O R R

+ H

A
R

H + R Weak base A

Ketone

Strong acid

Protonated ketone

Proton transfer reactions like these are often the first step in reactions

Ch. 3 - 70

Which of the following structures are Lewis Bases?

1. 2. 3.

4.
5. 6.

7.

I II III IV I and IV II and IV II, III and IV

0% 1

0% 2

0% 3

0% 4

0% 5

0% 6

0% 7

Ch. 3 - 71

14. A Mechanism for an Organic Reaction

CH3 H3C C CH3 tert-Butyl alcohol (soluble in H2O) OH + R O H Concentrated HCl H + Cl

CH3

H2O

H3C

C CH3

Cl + 2 H2O

tert-Butyl chloride (insoluble in H2O)

Ch. 3 - 72

Step 1
CH3

CH3 H
O H + H O H H

H3C

C CH3

H3C

C CH3

H O H

+ H

Step 2
CH3 H CH2 H H3C C CH3 + H O H
Ch. 3 - 73

H3C

C CH3

Step 3
CH3 CH3 + Cl H3C C CH3 Cl

H3C

C CH3

Ch. 3 - 74