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Ionic Reactions

Substitution Reactions and Transition State Theory

A great number of substitution reactions are known, and all involve


a competition between a pair of Lewis bases for a Lewis acid.
In substitution reactions both the nucleophile (Greek for nucleus
loving) and the leaving group are Lewis bases. Note that all
substitution reactions are at equilibrium and are reversible.
Although for a given reaction it may not be reversible in a practical
sense. For example in the reaction below HO¯ is a much stronger
nucleophile/base than I¯, which causes the equilibrium to be shifted
far to the right.

Sec. 8 - SN2/SN1 Forsey 1


Nucleophilic Substitution Reactions

Nu + R – X R – Nu + X
Alkyl halide Product Leaving Group
Nucleophile
(substrate) In this example a halide
heterolysis or carbon
halogen bond breaks

Nucleophile → Species with an unshared electron pair


Loves or seeks a positive center.

Leaving Group → A good leaving group must be able to leave as


a relatively stable weakly basic molecule or
ion; stable meaning non reactive.

Sec. 8 - SN2/SN1 Forsey 2


SN2 Reactions

CH3Cl + ¯OH CH3OH + Cl¯


Double [methyl chloride], keep [OH¯ ] constant → rate of reaction doubles
Double [OH¯ ], keep [methyl chloride] constant → rate of reaction doubles
Double both reactants and the rate increases four times.
Rate α [CH3Cl][OH¯ ] or rate = k[CH3Cl][OH¯ ] overall second order.

Conclusion → The reaction is bimolecular – two species are involved in the


rate determining step
SN 2
substitution nucleophilic bimolecular

H H
δ+ δ-
C L Nu C L
Nu
H H
H H

Inversion

Sec. 8 - SN2/SN1 Forsey 3


How are the electrons being transferred from one atom or
molecule to the other?
Does the nucleophile donate its Filled C-L
Nu C L σ bonding orbital
electrons to the C – L σ bond?

Net destabilizing interaction between two filled orbitals or weaker interaction

Electrons are transferred from the nonbonding electrons in a filled molecular orbital of
the nucleophile to the empty antibonding molecular orbital of the Lewis acid.

C L
Base Acid
donates Nu Empty orbital
accepts
electrons electrons
σ*
Filled
LUMO
HOMO

Nu C L What is the hybridization of the


transition sate. It trigonal planar.

Transition State
high energy  the carbon is surrounded by three
coplanar groups with 10e¯ around it

Sec. 8 - SN2/SN1 Forsey 4


Overview of SN2 Mechanism

Sec. 8 - SN2/SN1 Forsey 5


The transition state involves both the nucleophile and the Lewis
acid, which accounts for the bimolecular reaction

A transition state is the high


Transition Sate energy state of the reaction or
the rate determining step.
It is an unstable entity with a
Nu C L very brief existence (10-12 s)
In the transition state bonds
are partially formed and
broken. This called a
Free Energy

concerted reaction.

∆G‡
∆G‡ = Free energy of activation
∆G° = Free energy change

Nu C L
σ* ∆G°
Nu C L
Reactants

Products
Reaction Coordinate

Sec. 8 - SN2/SN1 Forsey 6


Transition State Theory: Free Energy Diagrams
Why does a reaction occur?
Remember from 1st year
∆G° = ∆H° - T∆S°
change in
total or disorder
change in
free energy
bonding energy
change
For a spontaneous energy to occur the Gibbs free energy (∆G°) must be negative. Thus
you can have different combinations of ∆H° and ∆S° values for a reaction to occur.
A process that gives off heat (∆H° is negative, exothermic) and becomes more
disordered (∆S° is positive) a spontaneous reaction will occur and ∆G° will be negative
for all temperatures
A process that has an increase in enthalpy (∆H° is positive, endothermic) and a
decrease increase in order (∆S° is negative) a reaction will be nonspontaneous at all
temperatures.
The questionable cases are those in which the entropy and enthalpy factors work in
opposition. In general the ∆H factor dominates al low temperature and the T∆S term at
high temperatures.

Sec. 8 - SN2/SN1 Forsey 7


Lets look at the reaction:

CH3–Cl + OH¯  CH3–OH + Cl ¯ at 60°C

∆H° = - 100 kJ mol-1


T = 333 K ∆G° = ∆H° - T∆S°
∆S° = 0.075 kJ mol-1 K-1 ∆G° = -100 kJ mol-1
Therefore a spontaneous reaction will occur
The reaction is said to be exergonic, ∆G° is negative
So what does this mean to the equilibrium

This is a very large Keq which means the reaction will go to completion
Remember the equilibrium always favors the species lower in energy or less reactive

Sec. 8 - SN2/SN1 Forsey 8


But don’t forget there is an energy barrier to
overcome before the reaction will occur

Energy Barrier that the


reactants must surmount
in order to reach the
lower energy level

Exergonic: The free energy level of the products is lower than that of the reactants

Sec. 8 - SN2/SN1 Forsey 9


Endergonic Reaction Positive
free-energy change

Energy Barrier (∆G‡) that


the reactants must
surmount is much larger
for a endergonic reaction
than for an exergonic
reaction

Sec. 8 - SN2/SN1 Forsey 10


Relationship between Temperature
and Rate of Reaction

For many reactions taking place at room temperature, a 10°C increase in temperature
will the cause the reaction rate to double.

The rate increases because more molecules have sufficient kinetic energy to
surmount the energy barrier (∆G‡).

T1 < T2

At T2 more molecules have sufficient


energy to surmount the energy barrier
or the free energy of activation (∆G‡).

Sec. 8 - SN2/SN1 Forsey 11


Nu So how does this all Relate to an SN2 Reaction

Nu

-
δ+ δ
Nu C L
Nu

An infinite number of possible pathways may lead from


reactants to products. The most probable pathway
requires the least amount of energy and the most likely
transition state lies at the top of the pathway that
requires the least amount of energy. A SN2 reaction has
a narrow pass through the energy valley which means
that the orientation of the reactants has to be very
specific before a reaction will occur.
Sec. 8 - SN2/SN1 Forsey 12
The only way for an SN2 reaction to occur is
through a back side attack

-
the only way in δ+ δ
Nu C L

- δ+
δ
Nu C L Nu C + L

Transition state
High energy Inversion
10 electrons around carbon What happens at a stereogenic carbon?

Sec. 8 - SN2/SN1 Forsey 13


Stereochemistry of SN2 Reactions

H3 C Br
CH3CH2S Na H3C
H acetone O H
H
solvent H
cis-1-bromo-3-cyclopentane H3C C CH3
What is the stereochemistry at the
stereogenic centers? lone pair of Transition State
electrons from
sulfur makes new
H3C Br σ bond

electrons from σ bond

+
+ Na Br
flip
-1-(ethylthio)-3-methylcyclopentane
H
SCH2CH3
H3C

Sec. 8 - SN2/SN1 Forsey 14


SN2 Reactions

1. Put charges and partial charges on atoms and molecules


2. Identify the electrophile (acid) and nucleophile (base)
3. Negative goes to positive. Show the flow of electrons with arrows
Arrows are your thought process

NaOH + CH3 Br

NH3 + CH3 Br CH3NH3 + Br

Sec. 8 - SN2/SN1 Forsey 15


SN2 Reactions

Na Br + CH3 OH

H2SO4
CH3OH Na Br

Sec. 8 - SN2/SN1 Forsey 16


SN2 Reactions

C6H13

C NaOH C
H C
Br
H3C
-(–)- 2-bromooctane
-(–)-2-octanol
transition state
[α] = - 9.90°
[α] = - 34.25°
enantiomeric purity = 100%
Start with enantiomeric purity = 100%

C
C

inversion of configuration

Sec. 8 - SN2/SN1 Forsey 17


SN1 Reactions

H2O
(CH3)3C-Cl + OH¯ (CH3)3C-OH + Cl¯
acetone

Double [tert-butyl chloride], keep [OH¯ ] constant → rate of reaction


doubles
Double [OH], keep [tert-butyl chloride] constant → rate stays the same
Rate [(CH3)3C-Cl] or rate = k[(CH3)3C-Cl] overall first order.

Conclusion → the reaction is unimolecular


SN1
substitution nucleophilic unimolecular

Sec. 8 - SN2/SN1 Forsey 18


SN1 Reactions
An SN1 occurs through a series or steps and forms intermediate species.
The rate of the reaction is determined by the slowest step.
The slow step is called the rate-limiting step or the rate determining step.

Sec. 8 - SN2/SN1 Forsey 19


SN1 Mechanism

Overall reaction (CH3)3CCl + 2 H2O (CH3)3OH + H3O+ + Cl¯

Step 1 CH3 CH3


δ- CH3
δ+ H3C
+
C + Cl
H3C C Cl H3C C Cl
CH3
CH3 CH3
transition state 1st intermediate
What is the hybridization
or the carbon?

Sec. 8 - SN2/SN1 Forsey 20


Step 2 SN1 Mechanism
+
H +
CH3 H H OH2
+ O O
H3C C + Cl
H C
CH3 C H3C
H3C CH3 CH3
nucleophile H3C
1st intermediate H3C
(base)
2nd intermediate
electrophile Transition State
(acid)

Step 3
+

H +
H H
H H H O OH
O
O O H C
C H
C H3C
H3C CH3
CH3 H3C H3 C
H3 C base CH3
H3 C
+ H3O+ + Cl¯
acid
Sec. 8 - SN2/SN1 Forsey 21
Stability of Carbocations

What is the
hybridization of the
positively charged
carbon?

H
2p2 2p empty
H C sp3
H
potential energy

2sp2 H
2s2 sp3 C C sp2
H
H
1s2 1s2 H C sp3

C+ C+ H
H
Alkyl groups are electron donating. Hyperconjugation donates electron
density via a partial overlap the adjacent sigma bonds. Any time a charge is
dispersed or delocalized the system will be stabilized. The more interactions
of this kind that are possible, the more stable the ion. Thus tertiary cations
will be more stable than secondary and secondary cations are more stable
than primary cations
Sec. 8 - SN2/SN1 Forsey 22
Stability of Carbocations

No hyperconjugation
Will not form in a solution

Sec. 8 - SN2/SN1 Forsey 23


Stability of Carbocations

Remember: Hyperconjugation delocalizes the positive charge to adjacent σ


bonds but the charge does not resonate onto other atoms thus a carbocation that
is resonance stabilized would be more stable than a tertiary carbocation.
CH3
+ + more stable than H3C C +

CH3

+ +
+ +

(CH3)3C + CH3+

Sec. 8 - SN2/SN1 Forsey 24


SN1 Mechanism
What happens at a stereogenic carbon?

A
Br
H
C H2O +
O
H3C C
CH2CH2CH3 acetone H
H3CH2C
(R)-3-bromo-3-methylhexane B
B
optically active A use instead of last step
-H+
-H+
C
( )-3-methyl-3-hexanol
flip
( )-3-methyl-3-hexanol
C C

Sec. 8 - SN2/SN1 Forsey 25


Solvolysis Reactions
The solvent is the nucleophile
Solvent + Lysis: cleavage by the solvent

(CH3)3C-Br + H2O (CH3)3C-OH + HBr H2O  hydrolysis

(CH3)3C-Br + CH3CH2OH (CH3)3C-OCH2CH3 + HBr CH3CH2OH  ethanolysis


O
(CH3)3C-Cl + HCO2H (CH3)3C-OCH + HCl What is the nucleophile?

Sec. 8 - SN2/SN1 Forsey 26


Factors Affecting Rates of Substitution Reactions

Relative Rate → If a given alkyl halide and nucleophile reacts rapidly


by a SN2 and slowly by a SN1 mechanism then most of the molecules
will follow a SN2 pathway or visa versa. So how can you tell if a
reaction will follow a SN2 or a SN1 reaction?
Factors: 1) Structure of Substrate
2) The concentration and reactivity of nucleophile (SN2 only)
3) Effect of Solvent
4) Nature of Leaving Group
The effect of the substrate structure has on the rate reaction for SN2 reactions.
The reactions where conducted in a environment that promotes an SN2 reaction.
(we will talk about this more later)
Substituent Compound Relative Rate
Methyl CH3-X 30.0 Why do we
1° CH3CH2-X 1.0 have these
2° (CH3)2CH-X 0.025 results?

Neopentyl (CH3)3CH2-X 0.0001


3° (CH3)3C-X ≈0

Sec. 8 - SN2/SN1 Forsey 27


Effect of Substrate on the Rates of SN2 Reactions
Steric Effects: A SN2 reaction requires the nucleophile to attack from the back of the carbon
bearing the leaving group to form and break the σ bonds. If there are bulky groups that interfere
or sterically hinder the attack by the nucleophile the rate of reaction will decrease.

Energy
barrier too
large
Free Energy

∆G‡ = for a
reaction
to occur

Sec. 8 - SN2/SN1 Forsey 28


Effect of Substrate on the Rates of SN2 Reactions

Energy
barrier too
large
Free Energy

∆G‡ = for a
reaction
to occur

Sec. 8 - SN2/SN1 Forsey 29


What about benzylic or allylic alkylhalides
(not in text book)
Substituent Compound Relative Rate
Methyl CH3-X 30.0
1° CH3CH2-X 1.0
2° (CH3)2CH-X 0.025
Allylic CH2 =CHCH2-X 40.0
Benzylic C6H5CH2-X 120.0

H L
H C
C C H
H

Nu

Hyperconjugation – adjacent π bond helps stabilize the transition


state by sharing some the negative charge

Sec. 8 - SN2/SN1 Forsey 30


Relative rates of reaction for SN2 reactions

Effect of Structure on the Rates of SN1 Reactions


The primary factor that determines the reactivity of organic substrates
in a SN1 reaction is the relative stability of the carbocation that is
formed (stability of the intermediate).

H
H C +

+ H
H
CH3 H3C C +
+ +
CH3
H3C C +
H
H3C C +
+
H
Free Energy

CH3 ∆G‡ =
+
+

Sec. 8 - SN2/SN1 Forsey 31


Why does the leaving group leave in a SN1 reaction?

Free Energy

∆G‡ ∆G°

Reaction coordinate
CH3 The formation of the ions in the 1st step in a SN1
+
reaction is both endergonic and endothermic and
C Cl
the transition state for this process should show a
H3C CH3 strong resemblance to the product of that step.
Thus when you think about what stabilizes the
intermediate the same processes (delocalization of
bond breaking
carbocation) will help stabilize the transition state
the carbocation must be
and will help the reaction proceed.
somewhat stable or the bond
will not break.

Sec. 8 - SN2/SN1 Forsey 32


The Hammond-Leffler Postulate

Generally the transition state looks most like the species it is closest to in energy

The transition state for an endergonic


reaction looks very much like the products.
Any bonds that are forming are more than
SN2 SN1 half formed, and any bonds that are
1st step breaking are more than half broken

The transition state for an exergonic reaction


looks very much like starting the materials. If a
bond is forming in the reaction, that bond is
less than half formed and if a bond is
breaking, it is less than half broken in the
transitions state

Sec. 8 - SN2/SN1 Forsey 33


So what does this mean?
In a endergonic process, like a SN1 reaction, the free energy of the transition state is closely
related to the intermediate that is formed. Thus there is parallelism between the formation
of the intermediate and the transition state energy and it can be assumed that the more
stable the intermediate, the faster it will form. This associates a thermodynamic property to
a kinetic rate and for most reactions this statement is true. Thus a tertiary carbocation will
form at a faster rate than a secondary.
For a exergonic process the transition state is closely related to the reactants. If the carbon
center is statically unhindered and the attacking species is a strong nucleophile the
reaction will occur readily. H H

∆G‡ = δ−
H H δ+ C Br

Free Energy
δ− δ+
Nu C Br
H

H A methyl carbocation is
very unstable and
H3C H3C destabilizes the transition
state – increases ∆G‡
δ− δ+
Reaction coordinate
Nu C Br
H3C CH

Free Energy
3
H3C
δ−
The steric interaction between the δ+ C Br
nucleophile and the Lewis acid Reaction coordinate
generates more strain in the
transition state – increases ∆GSec.

8 - SN2/SN1 H3Forsey
C 34
Relative Reactivity
Relatively
stable Highly unstable carbocation
carbocation
Efficiency of No SN1 No SN1
SN1
CH3 H H H

H3C C L H3C C L H C L H C L

CH3 CH3 CH3 H

3° 2° 1° methyl
No SN2 Efficiency of
SN2
Steric Little steric interaction
interaction

Will t-butylbromide ((CH3)3CBr) undergo a SN2 reaction?


Will n-butylbromide undergo a SN1 reaction?

Sec. 8 - SN2/SN1 Forsey 35


Rearrangements of Carbocations

CH3
Why does this
CH3
+ methanide + happen?
H3C C C CH3 H3C C C CH3
migration H
2° 3° H
H
CH3 H CH3 H
H C C
H
+ H
C C
CH3 CH3 H3C
+
methanide +
H3C H
H3C C CH2 H3 C C CH2 Lewis
Lewis
1° migration 3° acid
CH3 CH3 base

H
H H H
H H
+
hydride + C CH3
CH3CH2 CH CH2 CH3CH2 CH CH2 H2C +
migration 2° H C C

H2C H

Sec. 8 - SN2/SN1 Forsey 36


What is the product of the following SN1 reaction?

CH3 Br
CH3OH
H3C C C CH3
weak base
CH3 H poor nucleophile

Sec. 8 - SN2/SN1 Forsey 37


What is the mechanism for the following reaction?
OH

conc. H2SO4
OH O

Sec. 8 - SN2/SN1 Forsey 38


How about vinyl and aryl compounds?
allylic and benzylic very reactive in both SN1 and SN2

Br sp3
Br Br
+
+ Br
sp3
Nu
allylic SN1
SN2
resonance benzylic
hyperconjugation
stabilized

vinyl and aryl compounds are very nonreactive in both SN1 and SN2
sp2 +
Br
+ Br Br
Br sp2
vinyl
+

SN1 Br aryl
empty p orbital is at sp2 short strong bond
90° w.r.t. π bond and will Under most conditions a
not resonate nucleophile will not displace
The cation will not the leaving group in a SN2 reaction
form under most conditions
Sec. 8 - SN2/SN1 Forsey 39
Other Factors

What effect does the concentration and strength of the nucleophile have on the
rate of reaction?

For an SN2 reaction increasing the concentration of the nucleophile increases


the rate of reaction (2nd order).

For an SN1 reaction increasing the concentration of the nucleophile while


keeping the temperature and ionic strength constant, the rate of the reaction
will not increase (1st order)
Nucleophilicity
What makes a good nucleophile?

CH3O + CH3I CH3OCH3 + I very fast Why?

CH3OCH3 + I very slow


CH3OH + CH3I
H

Sec. 8 - SN2/SN1 Forsey 40


Trends in Nucleophilicity
Trend → A negatively charged nucleophile is always a stronger
nucleophile than its conjugate acid.

¯ NH2 > NH3 , ¯ SH > SH2 , ¯ OH > H2O , ¯ OR > HOR

Trend → In a group of nucleophiles in which the nucleophilic atom is


the same, nucleophilicity parallels basicities.

RO¯ > HO¯ >> RCOO¯ > ROH > H2O

Trend → Nucleophilicity decreases from left to right in the periodic


table, following the increasing in electronegativity from left to right. The
more electronegative elements have more tightly held nonbinding
electrons that are less reactive to forming new bonds.

HO¯ > F ¯ NH3 > H2O R3P > R3S

Sec. 8 - SN2/SN1 Forsey 41


Trends in Nucleophilicity

Trend → Nucleophilicity increases down the periodic tab following the increase
in size and polarizability (in solvents that can hydrogen bond).
I ¯ > Br¯ > Cl ¯ > F ¯ HSe¯ > HS ¯ > HO ¯ R3P > R3S

Steric Effects (Hindered nucleophile) → The presence of bulky groups on the


nucleophile will slow down the rate of reaction of a SN2 reaction.

t-butoxide is a stronger
H3 C
base CH3CH2O Strong base
Strong base H3C O than ethoxide but
poor nucleophile because it is hindered ethoxide good nucleophile
H3C
t-butoxide is a weaker
t-butoxide nucleophile

When bulky groups interfere with a reaction because of their size we call this
steric hindrance. Steric hindrance has little effect on basicity because basicity
usually involves attack on an unhindered proton. Thus by choosing a less
hindered or hindered base you can make the attacking species act like a
nucleophile and perform a SN2 reaction or react as a Bronsted-Lowry base and
abstract a proton. We will talk more about this later
Sec. 8 - SN2/SN1 Forsey 42
Nucleophilicity increases down the periodic tab following the increase in size
and polarizability (in solvents that can hydrogen bond). Why?
All strong bases are good nucleophiles but not all weak bases are poor
nucleophiles. Why is iodide such a strong nucleophile compared to fluoride
even though it is a very weak base?
Polarizability
Iodine’s electrons are far away from the nucleus, are loosely held and are polarizable.
Its electrons can move freely towards a positive charge and can engage in partial
bonding as it attacks the electrophilic carbon atom. Remember from Hammond-
Leffler Postulate that for a exergonic reaction the transition state resembles the
reactants and bond formation and breaking is less than half formed.

H H H H

Free Energy
δ−
“hard” non δ+
C Br C Br
polarizable valence
shell H little bonding H
F
Reaction coordinate

H H

Free Energy
“soft” H H δ−
δ+
polarizable C Br C Br
valence shell
H H Reaction coordinate
more bonding
I Transition State
∆G‡ =
Sec. 8 - SN2/SN1 Forsey 43
Remember bonding occurs between the highest occupied molecular orbital of
the nucleophile and the lowest unoccupied molecular orbital of the Lewis acid.
The table below shows some nucleophiles segregated into categories. It is not
possible to do much better than this as nucleophilicity is a property that
depends on the reaction partner. A good nucleophile with respect to carbon
may or may not be a good nucleophile with respect to displacement on some
other atom. Energy matching is important in the reaction. If we change the
reaction partner and thus the energy of the orbitals involved, we will change
the stabilization involved as well

Excellent Relative Good Nucleophile Relative Fair Nucleophile Relative


Nucleophile Rate Rate Rate
NC¯ Cyanide 126,000 HO¯ Hydroxide 16,000 Cl¯ Chloride 1,000
HS¯ Thiolate 126,000 Br¯ Bromide 10,000 CH3COO¯ Acetate 630
I¯ Iodide 80,000 N3¯ Azide 8,000 F¯ Fluoride 80
NH3 Ammonia 8,000 CH3OH Methanol 1

NO2 Nitrite 5,000 H2O Water 1

Sec. 8 - SN2/SN1 Forsey 44


Solvent Effects
Protic Solvents → solvents whose molecules have hydrogen atoms bonded to
electronegative atoms such as R-OH, R-NH2, H2O, RCOOH. These solvents can
extensively hydrogen bond with the solute, or reagents
Aprotic Solvents → solvents whose molecules do not have hydrogen atoms bonded
to electronegative atoms such as chloroform, hexane, acetone, and benzene. These
solvents can not extensively hydrogen bond with the solute, or reagents
Solvent Effects on SN2 Reactions: Polar Protic and Aprotic Solvents

Polar Protic
Small “hard” ions form stronger hydrogen bonds
than larger polarizable “soft” ions. Thus for an
strong H ion like F¯ is hindered and must shed or displace
bonding the solvent as the ion is attacking the
electrophilic carbon

H
H
H O

H
O

H O

O
H
H
H O
H
O

O
H
H

H H
H H
H

H
H

H
O O
O

H O
H

H
H H

H
O
O H

H H
H C Br H
O

H
H

H
H O O
H

O
O
H H H O H
H

H
H O H
H

O
O
O H
H
O

H
Sec. 8 - SN2/SN1 Forsey 45
H
H
H

H
H

H
Polar Protic Solvents

Polar solvents have a hydrogen atom attached to strongly electronegative atoms


They solvate nucleophiles and make them less reactive

Larger nucleophilic atoms are less solvated and therefore more reactive in
polar protic solvents

Larger nucleophiles are also more polarizable and can donate more electron density
Relative nucleophilicity in polar solvents:

Sec. 8 - SN2/SN1 Forsey 46


Polar Aprotic Solvents
Polar aprotic solvents do not have a hydrogen attached to an electronegative atom

They solvate cations well but


leave anions unsolvated because
positive centers in the solvent
are sterically hindered
Polar aprotic solvents lead to
generation of “naked” and very
reactive nucleophiles.
Trends for nucleophilicity are the
same as for basicity

They are excellent solvents for SN2 reactions

Sec. 8 - SN2/SN1 Forsey 47


Polar Aprotic Solvents

Would the following SN2 reaction react faster in DMF or ethanol?

CH3CH2CH2Br + NaC≡N  CH3CH2CH2C≡N + NaBr Aprotic solvent  DMF

Polar aprotic solvents not only make the anion less stable or more reactive, polar
aprotic solvents help stabilize the slightly polar transition state of an SN2 reaction.
O δ- O δ-
C δ+ δ+
H3 C δ+ CH3 Diethylether
Acetone
Remember: Like Dissolves Like

Polar Protic Solvents


For most SN1 reactions ions are formed in the first step. A polar solvent that
stabilizes the ions generated by ionization will favor the ionization process. Also if
the transition state is stabilized by the solvent the reaction is more likely to occur
because the activation energy is decreased. Thus polar protic solvents will greatly
increase the rate of ionization or the rate of reaction

Sec. 8 - SN2/SN1 Forsey 48


Polar Protic Solvents
+

Cl Cl δ +
H 3C
C C CH 3 Cl
δ+ H 3C
H 3C H 3C
CH 3 CH 3
H 3C H 3C

∆G‡2 Less polar solvent (slower)


+
R
Remember from Hammond-Leffler Postulate that for a
endergonic reaction the transition state resembles the
+ products and bond formation and breaking is more than
R half formed. Thus the polar transition state in a
Free Energy

∆G‡1 SN1reaction is stabilized by a polar solvent as well as the


intermediate that is formed.

∆G‡2 > ∆G‡1

more polar solvent (slower)


Reaction coordinate
Sec. 8 - SN2/SN1 Forsey 49
Effect of Leaving Group
The best leaving groups are those that are stable ions or molecules after they depart, i.e. weak
bases. The stability of the anions (L ¯ ) is related to the ease of dissociation of its conjugate
acid, H-L and thus the pka of H-L.

Low pka values (strong acids) good leaving groups, L ¯ → weak base

High pka values (weak acids) poor leaving groups. L ¯→ strong base
Acid pka Leaving Name
Group

HI -10 I¯ Iodide Good


Leaving
HBr -9 Br¯ Bromide
Groups
HCl -7 Cl¯ Chloride
HOSO2R -6.5 ¯ OSO2R Sulfonate
H3O + -1.7 H2O Water
HF 3.2 F¯ Fluoride Poor
Leaving
H2S 7 SH¯ Thiolate
groups
HCN 9.2 CN¯ Cyanide
H2O 15.7 OH¯ Hydroxide
HOR 16 to 18 OR¯ Alkoxide

Sec. 8 - SN2/SN1 Forsey 50


Summary SN1 vs. SN2

Stereochemistry

SN2

SN1

Sec. 8 - SN2/SN1 Forsey 51


What are the products of the following reactions ?

acetone
Br + NaC≡N

Br
+ CH3OH

Cl + CH3OH

Br
NH2
+

a lot missing
Sec. 8 - SN2/SN1 Forsey 52
What are the products of the following reactions ?

OH
Na SCH3 +

Br
NaH + CH3CH2C≡C-H
hexane

O
O
O S CH3 acetic acid
+
O O

a lot missing
Sec. 8 - SN2/SN1 Forsey 53
What are the products of the following reactions ?
O
ClCH2CH2CH2COOH + Na OH
Cl CH2CH2CH2C O Na + H2O
acid-base reaction 4 3 2 1
very fast 1°
Intramolecular ring formation reactions are more favorable than
SN2 intermolecular reactions (between two different molecules) because
the nucleophile is held in close proximity to the electrophile by the
carbon chain at all times. Thus attaining the proper orientation
required for the SN2 reaction is much more probable than for a
a lactone intermolecular reaction. For example:
is 5000 O
CH3CH2O + CH3CH2Cl  CH3CH2OCH2CH3 + Cl times
slower Cl O + Cl
intermolecular than
Intramolecular

+ CH3CH2OH

Br

Sec. 8 - SN2/SN1 Forsey 54


a lot missing
Organic Synthesis: Functional Group Transformations Using 
SN2 Reactions

Sec. 8 - SN2/SN1 Forsey 55