Roldan M.

de Guia
Department of Biochemistry
Faculty of Pharmacy
University of
Santo Tomas
 Structural Effects
π elect ro n d elo ca li za ti on
(R eso na nce )
.. ..
.. NH2
CH2 CH Cl :
.. O
.. C ..
NH2

..
Cl : :O:
..
CH3 C
..
O
.. H
 Structural Effects
π electron delocalization (Resonance)
 Structural Effects
π electron delocalization (Resonance)
 Structural Effects
π electron delocalization (Resonance)

:O:
H
:O: C H

.. .. -
:O :O: ..
NH2
N+
 Structural Effects
Hype rcon juga ti on
H
H C CH CH2
H

+
H H H
..- + ..- ..-
H C CH CH2 H C CH CH2 H C CH CH2
H H +
H
 Structural Effects
Hyperconjugation

Dienes

CH2 CH CH CH2 cumulative

conjugated

isolated
 Structural Effects
Hyperconjugation
H H H
+ +
H C H H C H H C H

- ..

..
-
 Structural Effects
Hyperconjugation

H O H
+ -
O
H C C H C C
H H H H

O
O
 Structural Effects
+
CH3 CH3
+
CH2 + CH3
CH2 +
C
H3C CH3

H
- -
:CH3 O2N C:
H

H
. CH C.
3

H
 Structural Effects
Induc ti ve Ef fe ct
Ele ctr on at tr act ing i nd uct ive
eff with
ect excess positive charges
+ + +
R N R NH3 NO2
R
those with electronegative atoms
F
NH2 OH OCH3 Cl
Br
groups exhibiting orbital electronegativity

C N N N

those with easily polarizable valence electrons

-
I
 Structural Effects
Induc ti ve Ef fe ct
Ele ctr on at tr act ing i nd uct ive
eff ect δ+ δ−
H3C Cl

δ+ δ++ δ− δ−
δ+
CH3 CH2 Cl CH3 CH2 O
H δ+

CH3
+
H3C N CH3

--
 Structural Effects
Induc ti ve Ef fe ct
Ele ctr on re pel lin g i nd uct ive ef fect
alkyl groups
CH3

negative groups
- - -
COO S O

O -
H3C S H3C
H3C C --
CH C N
O
H3C
O O O
R C C O R S O
O O O
 Structural Effects
St eric Ef fec t
 Structural Effects
Hydroge n B ond ing δ+
F H δ+ F H

δ+
O H δ+ O H

δ+
N H δ+ N H

H O
H
O H
F OH
OH
R H O H O
O
H R C C R
O H
H O H
O H O
R C O

O H
 Acids and Bases

Brønsted–Lowry Acids and Bases

 An acid is a proton donor
 A base is a proton acceptor

HBr + H2O Br + H3O

acid base

NH3 + H2O NH4 + OH

base acid

Note that water can act as an acid or a base

 Acids and Bases

Brønsted–Lowry Acids and Bases

HBr + H2O Br + H3O

O O
HBr + Br + H
H H H
H
acid base conjugate conjugate
base acid

Every acid–base reaction involving proton transfer

has two conjugate acid–base pairs.
 Acids and Bases

Lewis Acids and Bases

 A Lewis acid is an electron pair acceptor.
(think empty orbital)

 A Lewis base is an electron pair donor.

(think filled orbital)

The result of a Lewis acid–base reaction is often

called an adduct.
 Acids and Bases

Lewis Acids and Bases

O
H + O H H
H H H
Lewis acid Lewis base Adduct
Electron Electron New covalent
deficient rich bond
 Acids and Bases

Lewis Acids and Bases

Examples of Lewis Acids:

Fe3+ AlCl3 H3O+
Examples of Lewis Bases:
−
NH3 H2O Cl
Acids and Bases
 Acids and Bases
 pH = – log[H3O+]

HA + H2O A + H3O

A H3O
Ka =
HA

pKa = – log (Ka)

 Acids and Bases
Acid Strength
HA + H2O H3O+ + A-

- WEAK ACID
A Has a strong conj. base
E (∴higher energy)
N
E - STRONG ACID
R
A Has a weak conj. base
ionization
G easier (∴lower energy)
Y HA
Acids and Bases
 Acids and Bases

Acid Strength
 Factors that influence stability of the
conjugate base include:
• Resonance
• Electronegativity
• Atomic Size
• Hybridization
• Inductive Effects
 Acids and Bases
Resonance Effects
increasing quality
of resonance pKa Values

R OH 18 R CH3 45 R NH2 28

CH3 30
OH 10 NH2 25
O
CH3O C CH3 25
O O O
R C OH 5 R C CH3 R C NH2 15
20

O O
R C CH2 C R 9
 Acids and Bases
 The Acetate Ion
O O

CH3 C OH -H+ CH3 C O

Base
acetic acid

O
CH3 C O

acetate ion

Resonance Stabilized
Equivalent structures (charges on oxygens)
 Acids and Bases
 The Phenolate Ion
O O O O O

-
More resonance structures, but not more stable than acetate
Nonequivalent structures (note charges on carbon and oxygen)
 Acids and Bases

increasing
Electronegativity
electronegativity pKa Values
O
CH4 >45 RCH3 45
R C CH3 20

NH3 34 RNH2 35
O
H2O 16 ROH 18 R C NH2 15

HF 3.5 O
R C OH 5
 Acids and Bases

increasing
Electronegativity
size pKa Values
O
HF 3.5 F– 1.36 Å H2O 16
R C OH
HCl –7 1.81 Å H2S 7
Cl– O
4 R C SH
H2Se
HBr –9 Br – 1.95 Å
3 S
H2Te
I– R C SH
HI –10 2.16 Å
 Acids and Bases
Inductive Effects
Electron-withdrawing Groups Electron-donating Groups

δ− δ+ δ+ δ−
Cl C CH3 C

F, Cl, Br, O, N R, CH3, B, Si

electronegative elements alkyl groups and elements
pull electron density less electronegative than carbon
away from carbon push electron density toward carbon
 Acids and Bases
Inductive Effects
Chlorine helps to stabilize δ− δ+O
– CO2– by withdrawing Cl C
electrons
O
This effect diminishes with distance—it extends for about 3 bonds

O
δ − δ + δ−δ+ δ− δ+
Cl C C C
O
 Acids and Bases

increasing Inductive Effects increasing

electronegativity substitution
pKa Values

I CH2COOH 3.13 CH3 COOH 4.75

Br CH2COOH 2.87 Cl CH2 COOH 2.81

Cl
Cl CH2COOH 2.81 1.29
Cl CH COOH
Cl
F CH2COOH 2.66 Cl C COOH 0.65
Cl
 Electrophiles
 e- pair acceptor
 electron poor R R.
 may possess formal positive charge R C+
 incomplete octets R X.
 greatly reduced e- density
 those that can yield e- poor species
: CH2 NO2+

+
CO2 R C+
X2 in protic solvent X AlCl3 O
H2O
O SO3 δ+ δ−
C OH + CH3 AlCl4 BF3
R O SO3H
H+ FeBr3
 Nucleophiles
 e- pair donor
 excess negative charges
OH-
 fractional negative charges CN-
 may have a lone pair e- RO-

R NH2-
O X-
R C: - C
R -
O N3-
R
O-