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Structure / Reactivity

Relationships
Basic Premise of Organic Chemistry - The
nature of the chemical reaction an organic
molecule undergoes is dependent upon the
functional groups present in the molecule.
Corollary - Structural features in the
molecule at sites that are not directly
involved in a particular chemical
transformation can affect both the kinetics
and the equilibrium of the chemical
reaction.
Structure / Reactivity
Relationships
Organic chemists generally
classify the manner in which
substituents modify chemical
reactivity into three categories:
Inductive and Field effects (Polar effects)
Resonance effects (Conjugative effects)
Steric effects
Polar Effects

Acid
pK
a
Acid
pK
a
Acid
pK
a
CH
3
COOH
4. 80 CH
3
COOH 4. 80 CH
3
COOH 4. 80
FCH
2
COOH
2. 66
ClCH
2
COOH 2. 86
Cl
2
CHCOOH 1. 30
Cl
3
CCOOH
0. 65
Cl(CH
2
)
2
COOH 4. 00
HOCH
2
COOH
3. 83
(CH
3
)
3
NCH
2
COOH
+
1. 83
NCCH
2
COOH 2. 43
H
3
N(CH
2
)
4
COOH
+
HOOCCH
2
COOH
2. 83
4. 27
-
O
2
CCH
2
COOH
5. 69
CH
3
CH
2
COOH 4. 88
-
O
2
C(CH
2
)
4
COOH
5. 41
(CH
3
)
3
CCOOH
5. 05
HCOOH
3. 77
Summary of Common Substituents grouped according to their Inductive effect

-I (electron withdrawing) +I (elec tron donating)
NH
3
+
,
NR
3
+
NO
2
C N
C
O
OH
,
C
O
NH
2
C
O
OR
, C
O
X
C
O
H, C
O
R
OH , OR
SH
,
SR
C C, C C
F
Cl
Br
I
CH
3
CH
2
R
CHR
2
CR
3
C
O
O
Examples of Resonance Effects

Case I: COOH
K
a
= 6. 3x10
-5
COOH HO
K
a
= 2. 9x10
-5
Case II: OH
O
2
N
K
a
met a
para
OH O
2
N
K
a <
Case III: K
b
for C
6
H
5
CH
2
NH
2

>>
K
b
for C
6
H
5
NH
2
Case IV:
K
b
for R C
O
NH
2 <
K
b
for R NH
2
K for R C
O
OH
>
a
K for R OH
a
Case V:
H
3
C
COOH
K
a
met a
para
H
3
C COOH
K
a
>
Summary of Common Substituents grouped according to Resonance and Inductive effects


NO
2
C N
C
O
OH
,
C
O
NH
2
C
O
OR
, C
O
X
C
O
H
, C
O
R
F Cl Br I CH
3
CH
2
R
CHR
2
CR
3
, ,
,
OH , OR
SH
,
CF
3
SR
-R, -I
NH
2
NHR NR
2
, ,
O C
O
R
,
NH C
O
R
+R, -I +R, +I
O
-
, S
-
Examples of Steric Inhibition
of Resonance

Case I: O
2
N NH
2
is less basic than O
2
N NH
2
Br
Br
despite the
presence of more electron withdrawing (base weakening) groups in the
latter c ompound.
Case II: O
2
N Br
+ R
2
NH O
2
N NR
2
+ HBr
O
2
N Br
H
3
C
H
3
C
+ R
2
NH O
2
N NR
2
H
3
C
H
3
C
+ HBr
Special Substituent effect -
Hydrogen bonding
Case I:
N
N
O
OCH
2
C
6
H
5
C
6
H
5
CH
2
N
N
OCH
2
C
6
H
5
C
6
H
5
CH
2
O
N
N
O
C
6
H
5
CH
2
OH
N
N
C
6
H
5
CH
2
O
OH
Case II: C
H
3
C CH
3
O
C
H
3
C
OH
CH
2
K
eq
C
CH
3
O
C
O
H
3
C
K
eq
C C
O
H
3
C
OH
CH
2
'
K
eq
'
K
eq >>
Case III: H
C C
H
COOH HOOC
maleic acid
H
C C
HOOC
COOH
H
fumaric acid
Maleic acid has an unusually large first acid ionization constant
and an unusually small second acid ionization constant relative to
fumaric acid.