4.

Structural Effects on
Reactivity

4.1 Electronic Effects:

4.1.1 Inductive and field
effects
4.1.2 Resonance effect
4.2 Steric Effects
4.2.1 Steric hindrance
4.2.2 Strain
4.2.3 Stereo electronic
effect
4.3 Linear Free Energy
1

4.1 Electronic Effects

4.1.1 Inductive and field effect:
Inductive effect is a polarization through -bond; drop off
rapidly with number of -bonds.
Field effect is a polarization through space; drop off
rapidly with the distance.
In most cases, inductive and field effects operate together
and difficult to separate them. The following sytem is
designed to show only the field effects e.g.
H
H

Cl

Cl

Cl

Cl

COOH

pKa =

6.07

COOH

5.67

4.1.1 Inductive and field effects

(continued)
Electron donating group (+I): O -, COO-, CR3,
CHR2, CH2R, CH3, D
Electron withdrawing group (-I): NR 3+, SR2+,
NH3+, NO2, SO2R, CN, SO2Ar, CO2H, F, Cl, Br
, I, OAr, COOR, OR, COR, SH, SR, OH, CC
R, Ar, CH=CR2

4.1 Electronic Effects

4.1.2 Resonance effect (mesomeric effect) is caused by
electron delocalization of -bond; drop off gradually with
the number of -bonds.
Electron donating group (+M): O-, S-, NR2, NHR, NH2,
NHCOR, OR, OH, OCOR, SR, SH, Br, I, Cl, F, (R), Ar
Electron withdrawing group (-M): NO2, CN, COOH, COOR,
CONH2, CONHR, CONR2, CHO, COR, SO2R, SO2OR, NO,
Ar
Electronic effect on reactivity can be considered by
comparison of the effects on transition state and reactants
e.g.

OH

OH

Ar

C
O

NH2

OH-

Ar

Ar

NH2

O
Transition state

NH2

O
Intermediate

Electronic effect on reactivity

(continued)

OH

Ar

C
O

NH2

OH-

Ar

OH
Ar

NH2

O
Transition state

NH2

O
Intermediate

Electron withdrawing groups (-I and M) or Ar will

lower the free energy of T.S. These groups have mu
ch less effects on the free energy of reactants. The f
ree energy of activation is thus lowered with the elec
tron withdrawing groups.
5

4.2 Steric Effects

4.2.1 Steric hindrance (front strain, F-strain)
Relative rates of sovolysis of RBr with ethanol
R=

CH3CH3CH2 CH3CH2CH2 (CH3)2CHCH2 (CH3)3CCH2

Relative Rate: 17.6

0.28

0.030

4.2 x 10-6

4.2.2 Strain caused by steric repulsion

Relative rates of hydrolysis of RCl in 80% ethanol
R=

Me3C

Me2EtC MeEt2C Et3C

Me2(i-Pr)C Me(i-Pr)2C

Relative Rate: 1 1.7 2.6 3.0 0.9 13.6

------Hyper conjugation-------------Me
Me
(back strain)
R=
Relative Rate: 43.7

B-strain

0.35

I- strain
(internal strain)

4.2 Steric Effects

4.2.3 Stereo electronic effects
Conformational analysis
PhCONH

Cl - NH 3+

CH 3

OH

PhCONH

HCl PhCOO
H

Ph

OH

H
Ph

CH3

CH 3
Ph

H
Cl

t-Bu
H

Cl

t-Bu
H

H
H

t-BuOt-Bu

Cl
H

t-BuO- H
slow
7

t-Bu

4. 3 Linear free energy relationship

(LFER)
4.3.1 Hammett equation
For thermodynamic evaluation, log K/K0 = whereas
is the substituent constant and is the reaction constant
Hammett arbitrarily assigned = 1 for the ionization of
substituted benzoic acids to determine p and m .
O

log K/K0 = p
OH

X
O

log K/K0 = m
OH

+ H+

X
O-

X
O

+ H+
O-

= 0 for X = H
8

Hammett equation (continued)

When the resonance effect of an electron withdrawing
substituent can directly affect the reaction center the sub
stituent constants are correlated to - better than p. - is
determined from the ionization of p-substituted phenol.
X

OH

O- + H+

=1
When the resonance effect of an electron donating
substituent can directly affect the reaction center the sub
stituent constants are correlated to + better than p. + is
determined from the rate constants (log k/k0 = ) of the
following reaction in which is assigned as -1
CH3

C Cl
CH3

H2O 10%
X
acetone 90%

CH3
C+
CH3

CH3
X

C OH
CH3

The substituent constants ()

Group p

m p+

m+

p-

Group p
m p+ m + pO- -0.81 -0.47 -4.27 -1.15 - N=NPh 0.34 0.28 0.17 COOH 0.44 0.35 0.42 0.32 0.73
NMe2 -0.63 -0.10 -1.7- COOR 0.44 0.35 0.48 0.37 0.68
NH2-0.57 -0.09 -1.3-0.16
COMe 0.47 0.36 0.87
OH -0.38
0.13 -0.92 - CF3
0.53 0.46 0.57
OMe -0.28
0.10 -0.78
0.05 NH3+
0.60 0.86 CN
0.70 0.62 0.66 0.56 1.00
CMe3 -0.15 -0.09 -0.26 -0.06 SO2Me 0.73 0.64 NO2
0.81 0.71 0.79 0.73 1.27
Me -0.14 -0.06 -0.31 -0.10 - NMe3+ 0.82 0.88 0.41 0.36 N2+
1.93 1.65 1.88 3
H 0
0 0 0 0
Ph 0.05
0.05 -0.18
0 Electron withdrawing groups
COO0.11
0.02 -0.41 -0.10
have positive .
Electron donating groups
F
0.15
0.34 -0.07
0.35 have negative
.
10
Cl 0.24
0.37
0.11
0.40 -

Hammett equation (continued)

can be categorized into three groups using inductive (I)
and resonance (mesomeric, M) effects
(- I): Me, Et, Me3C
(+M,+I): Ac, CN, NO2, CF3, Me3N+
(-M, +I): AcNH, AcO, NH2, Br, Cl, F, OH, MeO, EtO, Ph
Hammett Equation is an LFER
G0 = -RT ln K0
Gx = -RT ln Kx
G0 - Gx = RT ln K0/Kx = 2.3 RT
Gx = G0 - 2.3 RT
G0 and 2.3 RT are constant at a specific temperature. If
changing of the substituent on the substrate does not change t
11
he reaction mechanism is also constant and G
x has linear re

4.4 Mechanistic implication

of LFER
If a plot of log k/k against an appropriate set of give a
0

linear line, the LFER is valid and the slope of the plot is (th
e reaction constant).
The linear line obtained from the plot indicates that the
reaction mechanism and the coordination of the transition st
ates do not change upon the variation of the substituent.
The values can be used to give information about the
structures of the transition states
A positive indicates that the reaction center in the
transition state becomes more negative comparing to the sta
rting material.
A negative indicates that the reaction center in the
transition state becomes more positive comparing to the star
ting material.
12

4.4 Mechanistic implication

of
LFER
The size of suggests how well the charge on the reaction

center in the transition state can be transferred to the substit

uent.
Exercise: Propose a reasonable mechanism for saponification
of methylbenzoate ( = +2.38) and specify the rate determining
step of the reaction.
Exercise: Match the following values i.e. +2.45, +0.75, -2.39
and -7.29 to the following reactions.
(a) nitration of substituted benzene
(b) ionization of substituted benzenethiols
(c) ionization of substituted benzenephosphonic acids
(d) reaction of substituted N,N-dimethylanilines and methyl
iodide
Exercise: What is the isokinetic temperature? 13

4.4 Mechanistic implication

ofan appropriate
LFER set of is sometime not
A plot of log k/k against
0

linear.
The curved line obtained from the plot indicates that the
coordination of the transition states are shifted upon the variatio
n of the substituent.
The reflected line obtained from the plot usually indicates that
change of the rate determining step upon the variation of the su
bstituent.
Exercise: Propose a reasonable mechanism for the following
reaction and specify the rate determining step that agrees with the
values
O
O
ArCH

O + H2NNHCNH2

ArCH NNHCNH2

= 3.5 for electron donating groups

= -0.25 for electron withdrawing groups14

Answer to the exercise

O
C OCH3

OHrds.

OC OCH3
OH

-CH3O-

O
C OH

CH3O- CH3OH

(a) Nitration of substituted benzene 7.29

(b) ionization of substituted benzenethiols +2.45
(c) ionization of substituted benzenephosphonic
acids +0.75
(d) reaction of substituted N,N-dimethylanilines
with methyl iodide 2.39

15

O
C O-

Answer to the exercise

O
ArCH

O + H2NNHCNH2

O-

ArCHNHNHCNH2

OH

ArCHNHNHCNH2
H+
OH2+

ArCHNHNHCNH2
O
ArC

NNHCNH2

-H+

O
ArC

NNHCNH2
H

16