Organic Chemistry

Chapter 8
Substitution and Elimination
• If an sp3 C is bonded to electronegative
atom Substitution reactions and
Elimination reactions are possible

This chapter is all about substitution

 SN2 and SN1 Reactions
SN2 - Reaction – bonds break and form at the same time

p le
am
ex SN2

SN1 - CX bond breaks, forming a C+ then reacts with a nucleophile

+
C X

C+ + X -
SN 1

C+ + Nu: C Nu
 Nucleophilic Substitution Reactions

Either mechanism depends on the:

• structure of the alkyl halide
• reactivity of the nucleophile
• concentration of the nucleophile
• The solvent in which the Rx is carried out
• The leaving group
 SN2 Mechanism

• It’s a Substitution Reaction (S)

• It’s Nucleophilic (N)
• It’s rate is second order (2)
– Called bimolecular (rate is dependent on 2 reactants)
• (Substitution Nucleophilic Bimolecular)
CH3 Br + HO - CH 3OH + Br -
methyl bromide methyl alcohol

Rate = k [RX] [Nu:]

(Because rate is dependent of BOTH RX and Nu: it is 2 nd. order.)
 SN2 Mechanism
• SN2 Mechanism involves a “backside attack”
 SN2 Mechanism
The “backside attack” causes an Inversion of Configuration

Careful now….. Doesn’t mean R becomes S – new atoms are involved

 Steric Hindrance
• Groups that block the path from the
nucleophile to the electrophilic atom
produce steric hindrance
• This results in a rate differences or no
reaction at all
methyl halide ethyl halide isopropyl halide t-butyl halide
 Steric Hindrance
• Activation Energy is higher due to
steric hindrance…..
Substitution Reactions Depend
on a Good Leaving Group

• R-F alkyl fluorides

• R-Cl alkyl chlorides
• R-Br alkyl bromides
• R-I alkyl iodides
• Alkyl Halides make good “leaving groups”
– They are easily displaced by another atom
– They allow the Conversion of alkyl halides to other functional
groups
 SN2 Mechanism
• The Leaving Groups also affects rate
• RI reacts fastest, RF slowest
– Iodide is the best “leaving group”
– Fluoride is the worst “leaving group”

(…reacting with the same alkyl halide under the same conditions)
 Basicity
• The weaker the basicity of a group, the
better the leaving ability.
(Lewis base = e- pair donor)

– Leaving ability depends on basicity because a

weak base does not SHARE its e- as well as a
strong base.
– Weak bases are not strongly bonded to a
carbon
(weak bases are GOOD leaving groups)
 Nucleophiles – Strong/Weak
Good/Bad
Stronger base Weaker base
Better nucleophile poorer nucleophile

OH- > H 2O
CH3O- > CH3OH
-NH > NH3
2

CH3CH2NH- > CH3CH2NH2

(conjugate acids)
 Nucleophiles
• The strength of nucleophile depends
on reaction conditions.
• In the GAS phase (not usually used), direct
relationship between basicity and
nucleophilicity
 Solvent Effects
• In a solution phase reaction, the
solvent plays a large role in how the
reaction will occur
• Solvent effects can cause just the
opposite of what might be the expected
behavior of the nucleophile
• Solvents are categorized as either
protic or aprotic
 Protic Solvents
Protic solvents has a H bonded to a N or O
– It is a H bonder
– Examples: H2O, CH3OH, NH3, etc
– Solvent is attracted to the Nucleophile
and hinders its ability to attack the
electrophile
 Aprotic Solvents
• Use an aprotic solvent
• Solvates cations
• Does not H bond with anions (nucleophile free)
• Partial + charge is on inside of molecule
• Negative charge on surface of molecule (solvates
cation)
• Examples include:
– DMSO (dimethyl sulfoxide)
– DMF (dimethyl formamide)
– Acetone (CH3COCH3)
O O CH3 O
CH 3 S CH 3 HC N CH 3 CH3 C CH 3
dimethyl sulfoxide
N,N-dimethylformamide acetone
DMSO
DMF
 Nucleophiles
• In the organic solvent phase,
INVERSE relationship between basicity and
nucleophilicity with a protic solvent

Question…
 Nucleophiles
• Solvents can solvate the nucleophile
– Usually this is NOT good because the
nucleophile is “tied up” in the solvent and
LESS REACTIVE.

Ion-dipole interactions
 Nucleophiles
• Solvents can solvate the nucleophile

(Methanol is a polar protic solvent.)

SN2 Reactions
SN2 Reactions
SN2 Reactions
• SN2 reactions might be reversible
• Leaving group would become the nucleophile
• Compare basicity (nucleophile strength) to see which
is a better leaving group.
• The stronger base will displace the weaker
base
– If basicity is similar, the Rx will be reversible

CH -
CH33CH
CH22Br
Br ++ I I - CH
CH33CH
CH22 I I ++Br -
Br -
 SN2 Reactions
Compare basicity to see which is a better nucleophile.
 SN1 Reactions
• Reaction of t-butyl bromide with water should be
slow
– water is a poor nucleophile
– t-butyl bromide is sterically hindered
However
– Reaction is a million times faster than with CH3Br

CH3 CH 3
CH 3 CH3
CH3 C Br ++ HH2 OO CH 3 C OH ++ HBr
HBr
CH 3 C Br 2 CH3 C OH
CH3 CH 3
CH 3 CH3
t-butyl bromide t-butyl alcohol
t-butyl bromide t-butyl alcohol

(Maybe not an SN2 reaction!)

 SN1 Reactions
•
 SN1 Mechanism
• Rate determining step does not involve
nucleophile

Step 1

Step 2
SN1 Mechanism
 SN1 Reactivity
• Relative Reactivities in an SN1 Reaction

1o RX < 2o RX < 3o RX

Increasing Reactivity
 SN1 Stereochemistry
• Because a planer carbocation is formed,
nucleophilic attack is possible on both sides,
so both isomers are possible
 SN1 Stereochemistry

SN1 should yield racemic mixture but it doesn’t

This is due to the steric hindrance of the leaving group
 Stereochemistry
• As the leaving group goes (Marvin K) it
blocks the path of any incoming nucleophiles
SN1 vs SN2
Inversion of
configuration

racemization with
partial inversion
 What Makes SN1 Reactions
work the best
• Good Leaving Group
– The weaker the base, the less tightly it is held
(I- and Br- are weak bases)

• Carbocation
– How stable is the resulting carbocation?
• 3o > 2o > 1o > methyl

Increasing Stability
 What Doesn’t Matter In an
SN1 Reactions
• The Nucleophile
• It has NO EFFECT on rate of Rx!!!

• Solvolysis Reactions
• (the nucleophile is also the solvent)
Carbocation Rearrangements
Since a carbocation is the intermediate, you may see
rearrangements in an SN1 Rx

No rearrangements in an SN2 Rx
Carbocation Rearrangement
• Methyl Shift
 Benzylic, Allylic, Vinylic,
and Aryl Halides
• Benzylic and allylic halides can readily
undergo SN2 unless they are 3o
– (steric hindrance)
 Benzylic, Allylic, Vinylic,
and Aryl Halides
• Benzylic and allylic halides can also
undergo SN1 (they form stable carbocations)

• Even though 1o RX do not go SN1, 1o

benzylic and 1o allylic CAN react SN1!
 Vinylic,and Aryl Halides
• Vinylic halides and aryl halides
– do not undergo SN1 or SN2 reactions!
 e- repel incoming Nucleophile

Br
Br
SN1 vs SN2 Review
 SN1 vs SN2

Methyl, 1o RX… SN2 only

2o RX … SN1 and SN2
3o RX … SN1 only
Vinylic, aryl RX … neither SN1 nor SN2
1o, 2o benzylic, allylic RX … SN1 and SN2
3o benzylic, allylic RX … SN1 only
 Role of the Solvent
In an SN1, a carbocation and halide ion are formed

– Solvation provides the energy for X- being formed

– In SN1 the solvent “pulls apart” the alkyl halide
– SN1 cannot take place in a nonpolar solvent or in
the gas phase
– Increasing the polarity of the solvent will
INCREASE the rate of Rx if none of the
REACTANTS are charged.
– If reactants are charged it will DECREASE the rate.
 Role of the Solvent
• So….
• In an SN1 reaction, the reactant is RX. The
intermediate is charged and is STABILIZED by
a POLAR solvent

A POLAR solvent increases the

rate of reaction for an SN1
reaction.

(However, this is true only if the reactant is uncharged.)

*
 Role of the Solvent In SN2
• In an SN2 reaction, one of the reactants is the
nucleophile (usually charged).
• The POLAR solvent will usually stabilize the
nucleophile.

A POLAR solvent decreases the

rate of reaction for an SN2
reaction.

(However, this is true only if the nucleophile is charged.)

 Polar Aprotic Solvents
• Polar Aprotic Solvents include:
– DMF N,N-dimethylformamide
– DMSO dimethylsulfoxide
– HMPA hexamethylphosphoramide
– THF Tetrahydrofuran
– And even… acetone
 Polar Aprotic Solvents
Polar Aprotic Solvents
– do not H bond
– solvate cations well
– do NOT solvate anions (nucleophiles) well
– good solvents for SN2 reactions
 Polar Aprotic Solvents

• DMSO
• DMF
• Acetone
• HMPA
 Nucleophile Review
Effectiveness Nucleophile
Br - , I -
HO- , CH 3 O- , RO -
strong
CN - , N 3 -
CH3 S - , RS -
CH3 CO2 - , RCO 2
-

moderate CH3 SH, RSH, R 2 S

NH3 , RNH 2 , R 2 NH, R 3 N
H2 O
weak CH3 OH, ROH
CH3 CO2 H, RCO 2 H
SN1/SN2 Problems -1
• Predict the type of mechanism for this
reaction, and the stereochemistry of each
product

CH3 CHCH2 CH3 + CH3 OH/H 2 O

Cl
(R)-enantiomer
CH3 CHCH2 CH3 + CH3 CHCH2 CH3 + HCl
OH OCH3
SN1/SN2 Problems -1
• Predict the type of mechanism for this
reaction, and the stereochemistry of each
product

CH3 CHCH2 CH3 + CH3 OH/H 2 O

Cl
(R)-enantiomer
CH3 CHCH2 CH3 + CH3 CHCH2 CH3 + HCl
OH OCH3
SN1/SN2 Problems -2
• Predict the mechanism of this reaction

CH3
+ -
DMSO
CH3 CHCH2 Br + Na CN

CH3

CH3 CHCH2 CN + Na + Br -
SN1/SN2 Problems -2
• Predict the mechanism of this reaction

CH3
+ -
DMSO
CH3 CHCH2 Br + Na CN

CH3

CH3 CHCH2 CN + Na + Br -
 SN1/SN2 Problems -3
• Predict the mechanism. If the starting
material has the R configuration, predict
the configuration of product

Br
CH3 CHCH2 CH3 + CH3 S - Na +
acetone

SCH 3
CH3 CHCH2 CH3 + Na + Br -
 SN1/SN2 Problems -3
• Predict the mechanism. If the starting
material has the R configuration, predict
the configuration of product

Br
CH3 CHCH2 CH3 + CH3 S - Na +
acetone

SCH 3
CH3 CHCH2 CH3 + Na + Br -
SN1/SN2 Problems -4
• Predict the mechanism

O
Br + CH 3 COH
acetic acid
O

OCCH 3 + HBr
SN1/SN2 Problems -4
• Predict the mechanism

O
Br + CH 3 COH
acetic acid
O

OCCH 3 + HBr
 SN1/SN2 Problems -5
• Predict the mechanism

CH3 (CH 2 ) 5 CH2 Br + (CH 3 ) 3 P toluene

+
CH3 (CH 2 ) 5 CH2 -P(CH 3)3 Br -
 SN1/SN2 Problems -5
• Predict the mechanism

CH3 (CH 2 ) 5 CH2 Br + (CH 3 ) 3 P toluene

+
CH3 (CH 2 ) 5 CH2 -P(CH 3)3 Br -
END