NUCLEOPHILIC SUBSTITUTION

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NUCLEOPHILIC SUBSTITUTION
THE GENERAL REACTION AND TERMINOLOGY
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SUBSTITUTION REACTIONS
One group takes the place of another.


Y takes the place of X ( Substitution )
Y displaces X
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NUCLEOPHILIC SUBSTITUTION
NUCLEOPHILIC DISPLACEMENT
leaving group
substrate
product
nucleophile
The nucleophile displaces the leaving group.
This is a substitution reaction
Nu substitutes for X (takes its place).
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IMPORTANT
This is a reaction at sp3 (tetrahedral) carbon
atoms.
sp3
sp2
sp
yes
no
Compounds that have sp2 or sp carbons
generally do not give nucleophilic substitution
reactions.
.. of course there are a few special cases that
do react, but we wont discuss them in
this chapter.
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EXAMPLES
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EXAMPLE 1

(s)
soluble
insoluble
iodide displaces bromide at carbon

NaI is soluble in acetone, NaCl and NaBr are not
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E1 competes
EXAMPLE 2
more about this later
solvolysis of t-butyl chloride in water
water displaces chloride at carbon

The extra proton is taken by a second water
molecule.
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DISPLACEMENT REACTIONS
NUCLEOPHILIC SUBSTITUTION REACTIONS
( substitution at carbon )
can be compared to ..
ACID-BASE REACTIONS
( substitution at hydrogen )
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COMPARE THESE SUBSTITUTIONS
DISPLACEMENT AT CARBON
nucleophile
substrate
product
leaving group
DISPLACEMENT AT HYDROGEN
base
acid
conjugate acid
conjugate base
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THESE REACTIONS HAVE A WIDE RANGE OF SUBSTRATES
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COMMON SUBSTRATES
( Leaving group varies )
see Table 10-3
alkyl halides
alcohols
alcohols require acid and then H2O leaves
tosylates
ABBREVIATION
alkyl p-toluenesulfonate
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THERE IS ALSO A WIDE RANGE OF
NUCLEOPHILES
A WIDE VARIETY OF COMPOUNDS CAN BE MADE
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NUCLEOPHILES
see Table 10-4
A WIDE SELECTION OF NUCLEOPHILES MAKES POSSIBLE
THE SYNTHESIS OF MANY TYPES OF ORGANIC COMPOUNDS
R-Y Nu R-Nu Y
Nucleophile
Product
Class
alkyl halides
R
X
alcohols
R
O
H


ethers
R
O
R
nitriles
C
N
R
O
esters
R
'
C
O
R
alkynes
R
'
C
C
R
thiols
S
H
R
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THE NUCLEOPHILE DOES NOT HAVE TO BE CHARGED

-
O
H
O
H
R

R
B
r

B
r
H
H
O
H
Under some circumstances water will react.
H
-

O
H
R


B
r
H
O
3
Nucleophile
Product
Class
alcohols
O
R
H
ethers


O
R
R
amines
R
N
H
2
amines
R
'
N
H
R
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LOOK-ALIKE REACTIONS
RBr NaOH ROH NaBr
Two reactions follow....
Both appear to be identical and follow the
general pattern shown above.
However, they are different !
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TWO LOOK-ALIKE REACTIONS
RBr NaOH ROH NaBr
1)
55oC
high conc. NaOH
2)
55oC
( some alkene by E1,E2 )
low conc. NaOH
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Notice that substrate in reaction 1 has no
b-hydrogens .. why not?
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REACTION 1 THE SN2 REACTION
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55oC
rate k2 RBr NaOH
k2 0.022 liter/mole-sec
-
bimolecular concerted
SN2
substitution
nucleophilic
bimolecular
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Concerted (one step) reaction
Concerted (one step) reaction
SN2
E
N
E
Ea
R
G
Y
starting
D
H
material
product
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REACTION 2 THE SN1 REACTION
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55oC
rate k1 RBr
k1 0.010 liter/mole-sec
unimolecular two steps
slow
SN1
fast
substitution
also
nucleophilic
alkene (via E1)
unimolecular
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TWO STEP REACTION
carbocation
SN1
intermediate
TS
1
TS
E
2
N
E
Ea
2
R
G
Ea
1
Y
starting
step 1
step 2
D
H
material
product
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TWO STEP REACTION
SN1
E
N
E
R
G
Ea
Y
1
Ea
2
DH
step 1
step 2
product