Transcript Dr. Amit Basak

Lecture 5
Ionic reactions
Q. What is called chemical reactions?
Ans. In a chemical reaction, pre-existing bonds are broken and new bonds
are formed.
Q. What are ionic reactions?
Ans. If bond breaking and bond making take place in a heterolytic fashion
the reaction is called ionic reaction.
On the other hand, if bond breaking and bond making take place in a
homolytic fashion, the reaction is called a free radical reaction.
R
X
R
X
heterolytic cleavage
homolytic cleavage R
R +
+
X
X
Ionic Reactions :
1) Nucleophilic substitution :
+
Y
R
X
R
+
Y
X
R = aliphatic as well as aromatic
2) Eletrophilic substitution :
R
H
R1
+
R
X
+
X
H
R = aromatic
3) Nucleophilic addition :
X
+
R1
X
R2
Y
H
R1
XH
R2
Y
Y
R2
X = O , NH
4) Eletrophilic addition :
Y
+
Y
X
5) Rearrangements :
R1
X
R1
_X
2
R
R1
Y
R2
R3
X
R2
3
R
R3
X
R1
R2
Y
R3
Nucleophilic Substitution at a saturated carbon :
Y
+
C
X
C
Y
X
+
Two types of discrete mechanism :
SN1
SN2
Substitution
Nucleophilic
Bimolecular
Substitution
Nucleophilic
unimolecular
SN1 :
R
X
slow
R
X
+
fast Y
Rate = K[RX]
R
Y
SN2 mechanism :
Y
+
R X
Y
R
+
X
Rate = K[R__X ] [Y]
2nd order kinetics
Q. Are all SN2 reactions follow 2nd order kinetics?
Ans. If Y- is in large excess as compared to R-X, ( eg. If solvent is
the nucleophile) then
K [Y ]
Pseudo – first order reaction
~K
1
Rate = K1[R_X]
Effect of structure and solvent :
Which mechanism will be operative will depend on structure and solvent
polarity.
T.S. for SN2
_
_
C
Y
X
Y
_

C
X

Y
C
_
Inversion of configuration (Walden inversion)
R1
R1
C
Y
H
X
Y
C
H
R2
R2
Why backside attack?
Y
C
X
To ensure maximum overlapping
leading to stability of T.S.
Important Point to Remember :
Inversion of configuration does not mean R going to S or vice versa.
It means that bond formation takes place opposite to that of bond
breaking….…..which leads to the inversion.
it is like inversion of umbrella in a storm.
Problem :
nucleophile
leaving group
C6H13
C
Me
H
I
I*
C6H13
I*
C
_
( )
Me
H
(+)
Rate of racemization = 2 * rate of inversion or incorporations
For SN1 :
R1
R2
R1
C
R1
R2
R2
Nu
X
R3
R1
C
Nu
+ Nu
R3
R3
R2
C
R3
Racemization is expected
Extent of inversion = extent of retention
However, due to ion pair formation, more inversion then retention.
Ion pair mechanism :
R1
R2
R1
C
X
R3
X
R3
More inversion then retention.
Problem :
Rate of solvolysis in EtOH :
Br
Explain?
R2
1
Br
10-6
Br
10-14
Lecture - 6
Factors Affecting the Rates of SN1 and SN2 reactions :
1) The structure of the substrate
2) Concentration and Reactivity of Nucleophile (for bimolecular
reactions only)
3) The effect of solvent.
4) The nature of leaving group
Effect of substrate structure :
For SN2
methyl > primary > secondary >> tertiary (unreactive)
R
Substituent
Methyl
1o
2
o
3o
Neopentyl
X
Y
RY + X
Compound
H3C
H3CH2C
(H3C)2HC
(H3C)3C
(H3C)3CH2C
Relative Rate
30
X
1
X
X
0.02
0
X
X
0.00001
Solvent effect
For SN1 :
Greater the ionizing ability of the solvent, faster will be the reaction.
Dielectric constant reflects the ionizing ability.
H3C
H3C
H2C
water
H3C
C
Br
MeOH
H3C
H3C
C
+
OH
H3C
C
OMe
+
Br
H3C
H3C
Rate of increase of [ Br- ] increases with increase in proportion of water.
Dielectric constant
H2O
80
MeO H
33
Q. What will be the effect of solvent polarity on the following SN1 reaction?
_
X
R1
NR3
R1
X
+
NR3
Effect of Nucleophile :
rapid
CH3O
+
H3C
I
CH3OCH 3
+
I
CH3OCH 3
+
HI
very
CH3OH
Nucleophilicity of
+
H3C
CH3O
I
slow
>
CH3OH
1) A negatively charged nucleophile is always stronger than its conjugate acid.
> is the same,
> nucleophilic atom
2) In a group of nucleophiles in which
OH
NH2
OH2
NH3
nucleophilities parallel basicities.
>
>
>
>
3) In polar protic solvents, in a particular group, nucleophilicity increases
OR
RCO2
OH
OH2
ROH
as we go down the group.
>
I
Br
>
Cl
>
F
4) In polar aprotic solvents, reverse trend follows :
F
>
Cl
>
Br
>
I
Hammond’s postulate :
In a particular step, the T.S. resembles the entity (substrate,
product or intermediate) that is closer in energy.
In SN1,
carbocation ( R+) is the intermediate.
T.S. should resemble more of the carbocation.
T.S. stability will be reflected in the stability of the carbocation.
Reason :
Steric effect
R1
R1
Y
-
X
90o
Y
R2
R3
X
R2
-
Product
R3
Steric hindrance offered by R1/ R2/ R3 to the approach of Nucleophile.
If R1 or R2 or R3 is bulky, this steric hindrance will slow down the reaction.
For SN1 :
R
X
slow
+
R
Y
fast
X
R
Y
Stability of carbocation determines the rate.
SN2
SN1
Inversion of configuaration
ideally Racemization
Retention of configuaration :
SNi ( substitution nucleophilic internal)
Me
Me
SO C 2l
OH
Ph
Cl
Ph
H
+
SO2
+
H
SN 2
Rate = K [ROH] [ SOCl2]
However, it can’t be a simple SN2.
SNi
O
1)
R
SOCl2
fast
OH
R
O
S
Cl
+ HCl
O
2)
O
Slow
R
O
S
Cl
- SO2
R
R
S
Cl
Retention
O
ion pair
Problem :
Me
Me
OH
Ph
H
SO C 2l
Py
Cl
Cl
Ph
H
Inversion
HC l
Neighbouring Group Participation :
“Retention” “Anchimeric asssitance”
O
HO2C
1) OH
HO
C
Me
Br
C
2) H
Me
H
OH
H
In presence of OH , carboxylate will be produced.
O
Inversion
O
C
Me
Double Inversion = Retention
O
Inversion
Me
Br
O
C
OH
H
H
O2C
HO2C
H
OH
Me
OH
Me
H
H
Qn.
Hydrolysis of EtS–CH2CH2 – Cl is 10 4 times faster than that of
EtO–CH2CH2–Cl. Explain?
Biological Nucleophilic Substitution :
CH3
H3C
N
Choline (important in transmission of nerve
pulses)
CH2CH2OH
CH3
HO
HO
Adrenaline (Bronchodilator causes blood
pressure elevations)
CHCH2NHCH3
OH
HO 2C
SCH3
ATP (Adenosine triphosphate)
+
O
O
O
P
P
P
O
O
H2N
O
Methionine
H2C
O
OH
Adeni ne
O
HO HO
CH3
HO 2C
CH3
S
CH2
H2N
O
Adeni ne
H C
3
N
CH3
CH2CH2OH
H3C
good methylating agent
N
CH2CH2OH
CH3
choline
OH OH
CH2CH2Cl
H3C
N
H2
C
H3C
CH2CH2Cl
N
CH2
DNA
CH2CH2Cl
N - mustard
DNA
(anticancer agent)
H2
C
H3C
N
Cytotoxic
H2C
DNA
CH2
ClH2C
rupture of DNA