NUCLEOPHILIC SUBSTITUTION
THE GENERAL REACTION AND TERMINOLOGY
SUBSTITUTION REACTIONS
One group takes the place of another.
Y +
Y +
Y Y
takes the place of displaces
( Substitution )
NUCLEOPHILIC SUBSTITUTION
NUCLEOPHILIC DISPLACEMENT substrate leaving group
Nu: - +
nucleophile
R Nu +
product
:X-
The nucleophile displaces the leaving group.
This is a substitution reaction : Nu substitutes for X (takes its place).
IMPORTANT:
This is a reaction at sp3 (tetrahedral) carbon atoms.
sp3 sp2 sp
C C X X C C X
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.
EXAMPLES
EXAMPLE 1
NaI + CH3 Br
acetone
CH3 I
+ NaBr (s)
soluble
insoluble
iodide displaces bromide at carbon
* NaI is soluble in acetone, NaCl and NaBr are not
EXAMPLE 2
CH3 H3C C Cl + 2 H2O CH3
CH3 H3C C OH + H3O + + ClCH3
COMPARE THESE SUBSTITUTIONS
DISPLACEMENT AT CARBON
Nu: - +
nucleophile
R Nu +
product
:Xleaving group
substrate
DISPLACEMENT AT HYDROGEN
B:
:X
base
acid
conjugate conjugate acid base
THESE REACTIONS HAVE A WIDE RANGE OF SUBSTRATES
COMMON SUBSTRATES
( Leaving group varies )
alcohols
+ R OH R O H H
alcohols require acid and then H2O leaves see Table 10-3
alkyl halides
R Cl R Br R I
tosylates
O R O S O CH3
ABBREVIATION
R O
Ts
alkyl p-toluenesulfonate
THERE IS ALSO A WIDE RANGE OF NUCLEOPHILES
A WIDE VARIETY OF COMPOUNDS CAN BE MADE
NUCLEOPHILES
R-Y + Nu R-Nu + Y
see Table 10-4
A WIDE SELECTION OF NUCLEOPHILES MAKES POSSIBLE THE SYNTHESIS OF MANY TYPES OF ORGANIC COMPOUNDS:
Nucleophile
Cl ,Br ,I
OH
-
Product
R X
Class
alkyl halides
- -
R OH R O R R C N O
R' C O R
alcohols ethers
nitriles
RO
C N -
O R' C O-
esters
alkynes thiols
R' C C:SH
-
R' C C R R SH
THE NUCLEOPHILE DOES NOT HAVE TO BE CHARGED
H O H + R Br H O R + Br H O H H H O R + H3O + + B r
-
Under some circumstances water will react.
Nucleophile
H O H R O H
Product
R O H
R R O
Class alcohols ethers amines amines
NH3
R' NH2
R NH2
R' NH R
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 !
TWO LOOK-ALIKE REACTIONS
RBr + NaOH ROH + NaBr
80% ethanol 20% water 55oC
1)
CH3 Br + NaOH
CH3 OH + Br
rate = k2 [RBr] [NaOH] 2)
high conc. NaOH
CH3 H3C C Br + NaOH CH3
rate = k1 [RBr]
80% ethanol 20% water 55oC
CH3
Br H3C C OH +
( + some alkene by E1,E2 )
CH3
low conc. NaOH
Notice that substrate in reaction 1 has no b-hydrogens .. why not?
REACTION 1 THE SN2 REACTION
CH3 Br + NaOH
80% ethanol 20% water 55oC
CH3 OH + Br
rate = k2 [RBr] [NaOH]
k2 = 0.022 liter/mole-sec
H O
CH 3 Br
80% ethanol 20% water
CH3 OH + Br
bimolecular concerted
SN2
substitution nucleophilic bimolecular
Concerted (one step) reaction
transition state TS
E N E R G Y
SN2
Ea
starting material
DH product
REACTION 2 THE SN1 REACTION
CH3 H3C C Br + NaOH CH3
80% ethanol 20% water 55oC
CH3
H3C C OH + Br
rate = k1 [RBr]
CH3
k1 = 0.010 liter/mole-sec
CH3 H3C C Br + NaOH CH3
80% ethanol 20% water
CH3 H3C C OH + Br CH3
-
unimolecular two steps
slow
O H CH3 H 3C C + CH3 + Br
-
fast
also
SN1
substitution nucleophilic unimolecular
alkene (via E1)
TWO STEP REACTION
TS1 carbocation intermediate TS2 Ea2 Ea1
SN1
E N E R G Y
starting material
step 1
step 2
DH product
TWO STEP REACTION
carbocation intermediate TS2
E N E R G Y starting material
TS1
SN1
Ea1
Ea2 DH
step 1
step 2
product
