Transcript x nu

Essential Organic Chemistry
Paula Yurkanis Bruice
Chapter 9
Substitution and Elimination
Reactions of Alkyl Halides
9.1 How Alkyl Halides React
Substitution Reactions
One group takes the place of another.
Y +
R
X
R
Y
takes the place of
Y
“displaces”
X
X
Y +
(Substitution)
X
Nucleophilic Substitution
NUCLEOPHILIC DISPLACEMENT
leaving
group
substrate
Nu:
-
+
nucleophile
R
X
R Nu +
product
The nucleophile “displaces” the leaving group.
This is a “substitution” reaction:
Nu substitutes for X (takes its place).
:X
-
Example 1
H3C
CH2 Br
+ NaI
acetone H3C
CH2 I
soluble
iodide displaces bromide at carbon
+ NaBr
insoluble
DISPLACEMENT REACTIONS
NUCLEOPHILIC SUBSTITUTION REACTIONS
(substitution at carbon)
can be compared to …
ACID–BASE REACTIONS
(substitution at hydrogen)
COMPARE THESE REACTIONS
DISPLACEMENT AT CARBON
-
Nu:
+
R
nucleophile
X
substrate
R Nu +
product
-
:X
leaving
group
DISPLACEMENT AT HYDROGEN
-
B:
base
+
H
acid
X
B H
conjugate
acid
+
-
:X
conjugate
base
THESE REACTIONS
FIND WIDE APPLICATION
SINCE WE CAN USE A WIDE
RANGE OF NUCLEOPHILES
NUCLEOPHILES
A WIDE SELECTION OF NUCLEOPHILES MAKES POSSIBLE THE SYNTHESIS
OF MANY TYPES OF ORGANIC COMPOUNDS:
R-Y + Nu
Nucleophile
-
- -
Cl ,Br ,I
-
OH
R'O-
C NO
R' C
O-
R' C C:-
SH
R-Nu + Y
Product
R
Class
alkyl halides
X
R OH
alcohols
R O R'
ethers
R C N
O
nitriles
esters
R' C
O R
R' C C R
R SH
alkynes
thiols
THE NUCLEOPHILE DOES NOT NEED TO BE CHARGED
HOWEVER, REACTIVE ATOMS BEAR A LONE PAIR
+
H O
H O R + Br -
+ R Br
H
H
O H
Under some circumstances
water will react.
H
-
H O R + H3 O + + Br
Nucleophile
Product
Class
alcohols
ethers
H O H
R
O
H
R' O H
R' O
R
NH3
R NH2
amines
R'
amines
R'
NH2
NH R
A Closer Look at Alkyl Halides
 Carbon and halogens have different electronegativity.
 Carbon-halogen bonds are polarized.
 Carbon is thought to be positive end of dipole.
 Nucleophiles can attack at positively charged carbon.
Br
Cl
H
H
H
H
H
l
H
H
H
H
A Closer Look at the Reactions
All substitution reactions follow a general scheme
RBr + NaOH
ROH + NaBr
Two reactions follow ...
From the outcome they look
Identical; however, a closer inspection
shows they are different!
TWO “LOOK-ALIKE” REACTIONS
RBr + NaOH
1)
ROH + NaBr
CH 3 Br + NaOH
80% ethanol
20% water
55oC
CH 3 OH + Br
-
Speed of reaction depends
on two concentrations
rate = k2[RBr][NaOH]
high conc. NaOH
2)
CH 3
CH 3
H 3C C Br + NaOH
80% ethanol
20% water 55oC
CH 3
H 3C C OH + Br
-
CH 3
(+ some alkene by E1, E2)
rate = k1[RBr]
low conc. NaOH
Speed of reaction independent
of nucleophile concentration
Two Different Substitution Reactions
We can distinguish two reactions based on
their kinetics.
First is SN2, depends on substrate AND
nucleophile concentration.
Second is SN1, depends only on substrate
concentration.
9.2 The Mechanism of An SN2 Reaction
CH 3 Br + NaOH
80% ethanol
20% water
55oC
CH 3 OH + Br
-
rate = k2[RBr][NaOH]
H O
CH3
Br
80% ethanol
20% water
Rate dependence of the reaction
is interpreted in a way that
we expect a bimolecular reaction
with a concerted mechanism
CH3 OH + Br
SN2
-
substitution
nucleophilic
bimolecular
SN2 Reaction
Rate dependence is 2nd order
Two molecules have to come together to
form new bonds
Bimolecular reaction
Mechanism
ENERGY PROFILE
E
N
E
R
G
Y
-
HO
Br
Br-
Mechanism
ENERGY PROFILE
E
N
E
R
G
Y
-
HO
HO-
Br
Br-
Mechanism
ENERGY PROFILE
E
N
E
R
G
Y
-
HO
HO-
Br
Br-
Mechanism
ENERGY PROFILE
E
N
E
R
G
Y
-
HO
HO-
Br
Br-
Mechanism
ENERGY PROFILE
E
N
E
R
G
Y
-
HO
HO
Br
Br-
Mechanism
ENERGY PROFILE
E
N
E
R
G
Y
-
HO
HO
-Br
Br
Br-
Mechanism
ENERGY PROFILE
E
N
E
R
G
Y
-
HO
HO
Br-
Br-
Stereochemistry
Old bond is broken simultaneously with the
new bond formed.
Well-defined outcome
Stereochemistry is inverted
Factors Affecting SN2
Steric effects
Approaching the polarized carbon gets more and more difficult.
Energy Profile of SN2
SN2
9.3 Factors that Affect SN2 Reactions
Leaving Group
• I– > Br– > Cl– > F–
• The lower the basicity, the better the leaving
group.
Nucleophile
• HO– > H2O; CH3O– > CH3OH
• The better the base, the better the nucleophile
• NH2– > HO– > F–
9.4 The Mechanism of An SN1 Reaction
SN1
CH 3
H 3C C Br + NaOH
CH 3
80% ethanol
20% water 55oC
CH 3
H 3C C OH + Br
CH 3
rate = k1[RBr]
Rate depends only on substrate concentration.
Two independent steps that differ significantly in speed.
Unimolecular
SN1
substitution
nucleophilic
unimolecular
SN1
CH3
CH3
H3C C Br + NaOH
80% ethanol
20% water
CH3
H3C C OH + BrCH3
slow
O H
CH3
H3C C +
fast
+ Br-
CH3
Assuming the formation of a carbocation intermediate
as the rate-determining step, explains speed of reaction
SN1
Reaction profile
CH3
Br-
Br
CH3
CH3
-
OH
SN1
Reaction profile
CH3
Br-
Br
CH3
CH3
Bond gets longer
-
OH
SN1
Reaction profile
CH3
Br-
Br
CH3
CH3
Bond gets longer
and longer
Rehybridization sp3  sp2
-
OH
SN1
Reaction profile
CH3
Br
-
CH3
CH3
Bond gets longer
and longer
Rehybridization sp3  sp2
-
OH
SN1
Reaction profile
CH3
Br
-
CH3
CH3
Bond gets longer
and longer
Rehybridization sp3  sp2
sp2-Hybridized intermediate formed
-
OH
SN1
Reaction profile
CH3
Br
-
CH3
-
OH
CH3
Bond gets longer
and longer
Rehybridization sp3  sp2
sp2-Hybridized intermediate formed
Nucleophile approaches
Rehybridization sp3  sp2 takes place
-
OH
SN1
Reaction profile
CH3
Br
-
CH3
CH3
OH
Bond gets longer
and longer
Rehybridization sp3  sp2
sp2-Hybridized intermediate formed
Nucleophile approaches
Rehybridization sp3  sp2 takes place
-
OH
SN1
Reaction profile
CH3
Br
-
OH
CH3
CH3
Bond gets longer
and longer
Rehybridization sp3  sp2
sp2-Hybridized intermediate formed
Nucleophile approaches
Rehybridization sp3  sp2 takes place
Bond forms
-
OH
SN1
Reaction profile
CH3
Br
-
CH3
OH
CH3
Bond gets longer
and longer
Rehybridization sp3  sp2
sp2-Hybridized intermediate formed
Nucleophile approaches
Rehybridization sp3  sp2 takes place
Bond forms
-
OH
Energy Profile of SN1
transition state
E
N
E
R
G
Y
carbocation
intermediate
1
SN1
transition state
2
activation energy2
activation energy1
starting
material
step 1
step 2
REACTION COORDINATE
2
DH
product
SN1
Rate dependence is 1st order
Rate depends only on formation of cation
Unimolecular reaction
The intermediate requires rehybridization
sp3sp2
Stereochemistry
First, old bond is broken. In a second step,
we form new bond.
We have a carbocation intermediate.
This requires rehybridization sp3  sp2
Stereochemical information is lost.
Racemate formed.
Br
OH
HO+
OH
9.5 Factors that Affect SN1 Reactions
Cation stability
• 3o alkyl halide > 2o alkyl halide > 1o alkyl
halide.
Leaving group
• The weaker the bond, the easier to break.
• RI > RBr > RCl > RF
Nucleophile
• NO EFFECT.
9.6 Comparing SN2 and SN1 Reactions
9.7 Elimination Reactions of Alkyl Halides
In an elimination reaction the starting material
loses the elements of a small molecule such as
HCl or HBr during the course of the reaction
to form the product.
C C
H X
-HX
Example
Alkyl halide + strong base and heat  LOSS OF HCl
H3CH2CH2CH2C Cl
H3CH2CH2CHCH3
Cl
NaOH
D
NaOH
D
H3CH2CCH CH2
H3CCH CH2CH3
Elimination
In this case the nucleophile reacts as a base;
we observe elimination reactions.
A hydrogen is removed from a carbon atom.
The halogen is removed from the adjacent
carbon.
Note that the elimination reaction is the
reverse of an addition reaction.
E2 Reaction
THE REACTION IS A
b-ELIMINATION
The b-hydrogen
is attached to the
b-carbon.
H
C C
b-carbon
Cl
a-carbon
The functional
group is attached
to the a-carbon.
Since the b-hydrogen is lost this reaction is
called a b-elimination.
Mechanism of E2
THE BASE TAKES THE b-HYDROGEN
B:
B
H
H
C C
:Cl
.. :
C C
..
: Cl
.. :
Bond formation (p bond) and breaking bonds
(C-H and C-X s bond) take place simultaneously
Regioselectivity
WHAT HAPPENS IF THERE IS MORE
THAN ONE b-HYDROGEN?
b
b’
H
H
C C C
Br
a
Regioselectivity
b
b’
Major product - b-H
H3C CH CH CH3
H H H H
2-butene
H C C C C H
H H Br H
2-bromobutane
Major product is the one
with lowest energy
H3C CH2 CH
CH2
1-butene
Minor product – b’-H
Regioselectivity
In some cases we have more than two b-hydrogens
b
b’
1-methylcyclohexene
Major product
- b-H
CH3
Cl
Minor product
– b’-H
NaOCH3
CH3OH/ D
methylenecyclohexane
b``
b’’ = b
1-methylcyclohexene
E1
ALKYL HALIDES + WEAK BASE
(SOLVOLYSIS)
The removal of a b-hydrogen becomes difficult without
a strong base and a different mechanism (ionization)
begins to take place …
… if the substrate is capable.
The E1 Elimination Reaction (two steps)
weak
base
H
C C
X
slow
step one
B:
carbocation
H
C C
+
:X
3 o > 2o > 1o
step
two
unimolecular
fast
rate = k[RX]
C C
Works best in a
polar solvent.
+
IONS
FORMED
also favored
if a resonancestabilized
carbocation
is formed
ENERGY PROFILE
two-step reaction
E
N
E
R
G
Y
E1
carbocation
intermediate
TS1
TS2
Ea2
Ea1
starting
material
step 1
slow
step 2
DH
product
Regioselectivity
H3C
CH3
CH3 H3C
E1 H3C
CH3
+
H3C
Cl
CH3
major
CH2
minor
Major products in E1 eliminations are the alkenes that
are thermodynamically most stable.
9.9 Competition Between SN2/E2 and SN1/E1
Consider “concentration” and “reactivity”
SN2/E2 are favored by a high concentration of
a good nucleophile/strong base.
SN1/E1 are favored by a poor nucleophile/
weak base.
10.10 Competition Between Substitution and
Elimination