• The polarity of a carbon-halogen bond leads to the carbon having a

partial positive charge

– In alkyl halides this polarity causes the carbon to become
activated to substitution reactions with nucleophiles

• Carbon-halogen bonds get less polar, longer and weaker in going

from fluorine to iodine
• Nucleophilic Substitution Reactions
• In this reaction a nucleophile is a species with an unshared electron
pair which reacts with an electron deficient carbon
• A leaving group is substituted by a nucleophile

• Examples of nucleophilic substitution

• Nucleophile
• The nucleophile reacts at the electron deficient carbon

• A nucleophile may be any molecule with an unshared electron pair

• Leaving Group
• A leaving group is a substituent that can leave as a relatively stable
entity
• It can leave as an anion or a neutral species
• A Mechanism for the SN2 Reaction

• A transition state is the high energy state of the reaction

– It is an unstable entity with a very brief existence (10-12 s)
• In the transition state of this reaction bonds are partially formed and
broken
– Both chloromethane and hydroxide are involved in the
transition state and this explains why the reaction is second
order
• The Stereochemistry of SN2 Reactions
• Backside attack of nucleophile results in an inversion of
configuration

• In cyclic systems a cis compound can react and become trans

product
• A Mechanism for the SN1 Reaction
• Step 1 is rate determining (slow) because it requires the formation of unstable ionic
products
• In step 1 water molecules help stabilize the ionic products
III. SN1 Mechanism
A. Kinetics
CH3 CH3
RLS: H3C C Br H3C C + Br
CH3 CH3

CH3 CH3 H
H3C C HOCH3 H3C C O
CH3 CH3 CH3

CH3 H CH3
-H+
H3C C O H3C C O CH3 + HBr
CH3 CH3 CH3
• Carbocations
• A carbocation has only 6 electrons, is sp2 hybridized and has an empty p
orbital

• The more highly substituted a carbocation is, the more stable it is

– The more stable a carbocation is, the easier it is to form
• Hyperconjugation stabilizes the carbocation by donation of electrons from an
adjacent carbon-hydrogen or carbon-carbon s bond into the empty p orbital
– More substitution provides more opportunity for hyperconjugation
• The Stereochemistry of SN1 Reactions
• When the leaving group leaves from a stereogenic center of an
optically active compound in an SN1 reaction, racemization will occur
– This is because an achiral carbocation intermediate is formed
• Racemization: transformation of an optically active compound to a
racemic mixture
III. SN1 Mechanism
A. Kinetics

Two-step mechanism:

R+

RBr + CH3OH

ROCH3 + HBr
III. SN1 Mechanism
C. Carbocation stability

R+ stability: 3º > 2º >> 1º > CH3+

R-X reactivity toward SN1: 3º > 2º >> 1º > CH3X

CH3+

1º R+
2º R+
3º R+
• Solvolysis
• A molecule of the solvent is the nucleophile in a substitution reaction
– If the solvent is water the reaction is a hydrolysis
III. SN1 Mechanism
C. Carbocation stability

Rearrangements possible:

EtOH CH3CH2O

Br
-H+

EtOH H
O
Et
III. SN1 Mechanism

Question. Which of the following compounds will react fastest by SN1? Which
by SN2?

A. Br
Br
Br

Br
B. Br
Br

Check Answer
III. SN1 Mechanism

Answer. Which of the following compounds will react fastest by SN1? Which
by SN2?

A. Br
Br
Br
fastest by SN2 - 1o fastest by SN1 - 2o

Br
B. Br
Br

fastest by SN2 - 1o fastest by SN1 - 3o

IV. SN1 vs SN2
A. Solvent effects
nonpolar: hexane, benzene
moderately polar: ether, acetone, ethyl acetate
polar protic: H2O, ROH, RCO2H
polar aprotic: DMSO DMF acetonitrile
O O
S C CH3 C N
CH3 CH3 H N(CH3)2

SN1 mechanism promoted by polar protic solvents

stabilize R+, X– relative to RX

in less polar solvents

R+X– in more polar solvents

RX
IV. SN1 vs SN2
A. Solvent effects

SN2 mechanism promoted by moderately polar & polar aprotic solvents

destabilize Nu–, make
them more nucleophilic

e.g., OH– in H2O: strong H-bonding to water makes OH– less reactive
OH– in DMSO: weaker solvation makes OH– more reactive (nucleophilic)

in DMSO
in H2O
RX + OH–

ROH + X–
• Factors Affecting the Rate of SN1 and SN2 Reactions
– The Effects of the Structure of the Substrate
– SN2 Reactions
• In SN2 reactions alkyl halides show the following general order of
reactivity

• Steric hinderance: the spatial arrangement of the atoms or groups at or

near a reacting site hinders or retards a reaction
– In tertiary and neopentyl halides, the reacting carbon is too
sterically hindered to react
IV. SN1 vs SN2 Rate = k1[RX] + k2[RX][Nu]
B. Summary

rate of SN1 increases (carbocation stability)

RX = CH3X 1º 2º 3º
rate of SN2 increases (steric hindrance)

react may go reacts

primarily by either primarily
by SN2 mechanism by SN1
(k1 ~ 0, k2 large) (k2 ~ 0, k1 large)

SN2 promoted good nucleophile (Rate = k2[RX][Nu])

-usually in polar aprotic solvent
SN1 occurs in absence of good nucleophile (Rate = k1[RX])
-usually in polar protic solvent (solvolysis)
IV. SN1 vs SN2
Question 8-4. What would be the predominant mechanism in each of the
following reactions? What would be the product?

KCN Br CH3OH
Br DMSO 

Br H2O Br
NaSCH3
 DMF

Check Answer
 IV. SN1 vs SN2
Answer 8-4. What would be the predominant mechanism in each of the
following reactions? What would be the product?

Br CH3OH OCH3
KCN
Br DMSO CN 
good nucleophile, 1o RX - SN2 poor nucleophile, 2o - SN1

Br H2O Br SCH3
OH NaSCH3
 DMF

poor nucleophile, 3o - SN1 good nucleophile, 2o - SN2