• SN2 Reaction bimolecular

• SN1 Reaction monomolecular

 SN1 & SN2 REACTION
Objective
✔ Be able to write the mechanisms for both the SN1 and SN2 reaction types
✔ Know the effect of the SN1 and SN2 reaction mechanisms on the
stereochemistry of reactions
✔ Recognize how the structure of the substrate affects the outcome of
nucleophilic reactions
✔ Understand the factors that affect the stability of carbocations .

•Understand how halide, oxygen, nitrogen, and carbon nucleophiles react

with various substrates
✔ Recognize the factors that make good nucleophiles and good leaving
groups
✔Know how a functional group adjacent to the site of a nucleophilic
substitution affects the course of reactions
✔ Know how the solvent affects the outcome of nucleophilic substitution
reactions
 ALKYL HALIDES

• a compound with a halogen atom

bonded to one of the sp3 hybrid
carbon atoms of an alkyl group
 R — C—X sp3-hybridized---
alkyl halide easily replaced by others
possible introducing a multiple bond

C C
sp2-hybridized---
X
their chemistry are quite
X different from alkyl halides

vinylic(or phenyl) halide

 FUNCTIONAL GROUP CHARACTERSITIC

+ - X= F,Cl,Br,I

C X
polarized

Size of X: ? F<Cl<Br<I
Electronegativity: ? F>Cl>Br>I

Bond Strength: ? R-F>R-Cl>R-Br>R-I

Bond Length: ? R-F<R-Cl<R-Br<R-I

Usage: important starting materials

 Nucleophilic substitution (SN1, SN2)
Elimination Reaction (E1, E2) of R-X

C X
+ -

• This reactions involve breaking the C-X bond.

 SN2 Reactions
REAKSI SUBSTITUSI NUKLEOFILIK
BIMOLEKULER
 SN2 Reactions

hydroxide ion methyl iodide

H SN2 H
-
HO - + H C I HO C H + I
nucleophile H H
Leaving
product
substrate group

• Substrate: the compound attacked by a reagent (nucleophile)

 SN2 Reactions Mechanism
– Nucleophile attacks the back side of the electrophilic
carbon, donating an e- pair to form a new bond

– Since carbon can only have 8 valence electrons,

the C-X bond
begins to break as the C-Nu bond begins to form
 SN2 Reactions Mechanism

• SN2 means: substitution, nucleophilic, bimolecular

– transition state of rate-determining step
involves collision of 2 molecules
• 2nd order overall rate law
– Rate = k[RX][Nu]

• Concerted reaction:
– a reaction that takes place in a single step with
bonds breaking and forming simultaneously
 Energy Diagram of SN2 Reactions

• transition state needs large Ea (due to 5-coordinate C atoms).

• no intermedites
• exothermic
 INVERSION OF CONFIGURATION
in SN2 Reactions
– The nucleophile attacks from the back side (the side
opposite the leaving group).
– Back-side attack turns the tetrahedron of the carbon
atom inside out.
Illustration of turning the umbrella inside out.
 SN2 Reactions
• Inversion of configuration:
– a process in which the groups bonded to a
chiral carbon are changed to the opposite
spatial configuration:
•R S or S R

• Walden inversion
 SN2 Reactions Mechanism
Example:
Predict the product formed by the SN2 reaction
between S-2-bromobutane
H and hydroxide ion.
H
DrawHOthe mechanism
C for
HO the
C reaction.
CH3 CH3
CH2CH3 CH2CH3

H H -
H
- C Br HO C Br HO C
OH CH3 CH3
CH2CH3 CH3 CH CH CH2CH3
2 3
H
+ Br -
HO C Br
 SN2 Reactions Application
• SN2 reactions can be used to convert alkyl halides to
other functional groups:
– RX + I - R-I
KNOW
– RX + OH - R-OH THESE!
– RX + R’O- R-OR’
– RX + NH3 R-NH3+ X-
• RX + xs NH3 R-NH2 Be able
– RX + CN- R-CN to apply
– RX + HS- R-SH these!
– RX + R’S- R-SR’
– RX + R’COO- R’CO2R
 (CH3)2CHCH S2CH
N2 Cl
2
Reactions
+ NH3 (xs)
Example:
What
CH3reagent
CH2CH2CHwould
Cl you
+ use to do the
NaCN
2
following reactions:

CH3CH2CH2Br + ? CH3CH2CH2OCH2CH3

CH3CH2I + ? CH3CH2C CH
 SN2 Reactions
Example:
Predict the product
(CH3)2CHCH 2
of the
CH2Cl following
+ NH 3
(xs) reactions:

CH3CH2CH2CH2Cl + NaCN

(CH3)2CHCH2CH2Cl + NH3 (xs)

CH3CH2CH2CH2Cl + NaCN
Problem
Write a stereochemical equation for this
nucleophilic substitution reaction:

(S)-2-bromohexane + CH3COO- →
 SN1 Reaction

REAKSI SUBSTITUSI NUKLEOFILIK

UNIMOLEKULER
• SN1 reaction – occurs in two distinct steps + one
undistinct step

• It happen when a tertiary alkyl halides in protic

solvents, by a mechanism that involves
✓ departure of the leaving group (step 1)
✓ prior to addition of the nucleophile (step 2)

• the ionization is the slowest step

 SN1 Reaction

t-butyl bromide with hydroxide ion

(CH3)3C—Br + OH - Acetone
(CH3)3C—OH + Br –
H2O

the reaction rate:

R=k[(CH3) 3CBr]
only t-butyl chloride is involved in the trasition state

the reaction be unimolecular SN1(substitution, nucleophilic, unimolecular)

 SN1 Reaction

t-butyl chloride with hydroxide ion

(CH3)3C—Cl + OH - Acetone
(CH3)3C—OH + Cl –
H2O

the reaction rate:

R=k[(CH3) 3CCl]
only t-butyl chloride is involved in the trasition state

the reaction be unimolecular SN1(substitution, nucleophilic, unimolecular)

 Mechanism for the SN1 reaction
(CH3)3C—Cl + OH- (CH3)3C—OH + Cl –

CH3 CH3
slow - + 3° carbocation
H3C C Cl
H2 O
Cl + H3 C C
CH3 (I) CH 3
Aided by polar solvent: heterolytic
cleavage of C-Cl bond (II) HO :
fast Lewis
H base
CH3
deprotonation CH3
+ H+ +
H3 O +H 3C C OH H 3C C OH Protonated
H2O as a lewis base (III) products
proton acceptor CH3 fast CH3 H
 ENERGI DIAGRAM for the SN1 reaction

(I) a slow step,rate-determining step(endothermal)

(II) protonated, (III) proton transfer to lewis base

(I) (II) (III)

Free
energy

(CH3)3C+/Cl
-
/2 H2O

(CH3)3COH/
(CH3)3Cl/H2O +
(CH3)3CO H2/ Cl-/H3+O
Cl-/H2O
 Rate-Limiting Step

• The overall rate of a reaction is controlled by the

rate of the slowest step
• The rate depends on the concentration of the
species and the rate constant of the step
• The highest energy transition state point on the
diagram is that for the rate determining step
(which is not always the highest barrier)
 Stereochemistry of SN1 Reaction

• The planar
intermediate
should lead to
loss of chirality
– A free
carbocation is
achiral

• Product should
be racemic
 C3 H7 C3 H7
Br - the carbocation
C Br C+ --a trigonal plane
slow ---achiral
H3 C C2 H5 H3 C C2 H5

C3 H7 ..
C3 H7
C3 H7
.. H H OH
**
C O+ C OH
C+ H
H3 C C2 H5 H3 C + H3O+
fast C2 H5
H3 C C2 H5
C3 H7 C3 H7
.. H ..
H OH
..
** H OH +O C HO C
** H C H3 C H3

attack from both front and C2 H5 C2 H5

back side with equal rates A mixture of two + H3O+
enantiomers
 SN1 in Reality
• Carbocation is biased to react on side opposite
leaving group
• Suggests reaction occurs with carbocation loosely
associated with leaving group during nucleophilic
addition
• Alternative that SN2 is also occurring is unlikely
 Effects of Ion Pair Formation
• If leaving group
remains associated,
then product has more
inversion than retention
• Product is only partially
racemic with more
inversion than retention
• Associated carbocation
and leaving group is an
ion pair
• How to predict which pathway
(SN1or SN2) following the
reaction of any alkyl halide with
any nucleophile under varing
condition ?
 SN1 versus SN2 Reactions

Whether an alkyl halide will undergo an SN1 or an SN2

reaction depends upon a number of factors.

Some of the more common factors include

the natures of the carbon skeleton,

the nature of the nucleophile,
the leaving group,
and the solvent,
 Nature of the carbon skeleton

Primary alkyl halides, which exhibit no steric hindrance of the rear

lobe of the bonding orbital and have little inductive stability of their
cations generally undergo SN2 mechanisms.

Only those molecules that form extremely stable cations undergo

SN1 mechanisms.
Normally, only tertiary alkyl halides that yield tertiary carbonications
which is stabilized by inductive effect (or other compound which is resonance-stabilized
carbocations) undergo SN1 mechanisms rather than SN2 mechanisms.

In addition, the tertiary alkyl halides molecules exhibit steric hindrance

of the rear lobe of the bonding orbital, which inhibits SN2
mechanisms from occurring.
 Factors affecting SN1and SN2

1. The structure of the substrate

2. The concentration and reactivity of the
nucleophile
3. The nature of the leaving group
4. The effect of the solvent
THE EFFECT OF THE STRUCTURE OF THE SUBSTRATE

(1) Electronic effects

Methyl > primary > secondary >>tertiary (unreactive)

(the general order of reactivity in SN2 reactions for simple
alkyl haildes)
CH3

H3C C CH 2 X
(2) Steric effects
e.g., a neopentyl halide: CH3

Unreactive for SN2

High Steric Hindrance
steric effect:
an effect for space-filling properties

steric hindrance:
the spatial arrangement of the groups near the
reacting site hinders(retards) a reaction

Large groups can often hinder the formation

 Effect of Substrate structure On SN2
– The back side of the electrophilic carbon
becomes increasingly hindered as the number or
size of its substituents increases
Order of Reactivity in SN2
• The more alkyl groups connected to the
reacting carbon, the slower the reaction
 Characteristics SN2 Reactions

• The relative rate of reactivity of simple alkyl halides in

SN2 reactions is:
methyl > 1o > 2o >>>3o

• 3o alkyl halides do not react at all via an SN2

mechanism.
 Key factor determining SN1 reaction

The relative stability of the formed carbocation

Most cases, tertiary halides (beside allylic and benzylic halides) react by
an SN1 mechanism, sometimes, secondary halides do, too.

R C+
R
 Effect of structure on SN1

• Tertiary halida is the most reactive because its

form stable carbocation
 Allylic and benzylic Carbocation
• Delokalisasi muatan kation menambah stabilitas.
• allyl primer lebih stabil daripada alkyl primer

•benzyl primer lebih stabil dari pada allyl

 Halida Alilik dan Benzilik
• Produk antara Allylic dan benzylic distabilkan
oleh delokalisasi muatan

• allylic and benzylic primer lebih reaktif pada

mekanisme reaksi SN2 dan SN1
EFFECT OF Nucleophiles STRENGTH

SN1
• Rate is not affected by identity and
concentration of the nucleophile

SN2

Rate is directly proportional to

the concentration of nucleophile

55
 RELATIVE STRENGTHS OF NUCLEOPHILES:

depends on:
charge, basicity, solvent, polarizability and substituents
1. A negatively charged nucleophile is always a more
reactive nucleophile than it s conjuagte acid: e.g., HO- is
better than H2O, RO- is better than ROH

2. In a group of nucleophiles having the same nucleophilic

atom, nucleophilicities parallel basicities(the order of
basicity)
 RELATIVE STRENGTHS OF NUCLEOPHILES:

depends on:
charge, basicity,, polarizability, substituents, and solvent
• A negatively charged nucleophile is always a more
reactive nucleophile than it s conjuagte acid:
• HO- is better than H2O,
• RO- is better than ROH
• CH3O- is berter than CH3OH
• CH3CH2O- is better not (CH3)3CO-
experiments: COMPARISON OF CHARGE
-
1. CH3Cl + OH : CH3OH + Cl – Fast
2. CH Cl + H O
3 2 CH OH + Cl –
: 3 2 Very slow
nucleophilicities:
basicity: OH- > H2O

3. CH3Cl+H2N - : CH3NH2 + Cl – Very fast

4. CH3Cl+H3N : +
CH NH + Cl –
3 3 Slow
nucleophilicities:
H2N - > H3N
basicity:
 •Nucleophilicity decrease to the right in an row of the periodic table:
•COMPARISON BASICITY OF N and O

1. CH3CH2Br + H3N: CH3 CH2NH3 + + Br –Fast

2. CH3CH2Br + H2O: CH3CH2OH2 + + Br – Slow

nucleophilicities: H3N > H2O

3. CH3CH2Br + H2N – CH3 CH2NH3 + Br – Fast
4. CH3CH2Br + HO – CH3CH2OH + Br – Slow

nucleophilicities: H N – > HO –
2
– – –
NH2 > HO > NH3 > F > H2O
 Reactivity of Nucleophile

• Anions is more nucleofilic than neutral

• Stronger nucleophilic with increasing atomic size.
• Depend on solvent
Neutral or negatively charged Lewis base
 Sterically hindered nucleophiles
are poor ones

-
CH3 I + CH3 O - CH3O CH 3 + I

very easy
CH3 CH3
- -
CH3 I + CH3 C O CH3 C CH3 + I
CH3 CH3

very difficult
 Nature of the leaving group
In general, good leaving groups are those capable of forming stable ions
or molecules upon displacement from the original molecule.

Conversely, poor leaving groups form ions of poor to moderate stability.

Strong bases, such as OH−, NH2−, and RO−, make poor leaving groups.

Water, which is less basic than a hydroxide ion, is a better leaving group.

Poor bases usually make good leaving groups.

A poor base is an ion or group in which the electrons are tightly bound
to the molecule due to high electronegativity or resonance.
 Effect of Leaving Group on SN2
• A good leaving group reduces the barrier to a reaction
• Stable anions that are weak bases are usually excellent
leaving groups and can delocalize charge
 good leaving groups

Some good leaving groups are the sulfate ion and the p-
toluenesulfonate (tosylate ion).

The following list ranks atoms and molecules in order of their stability as
leaving groups, from most to least stable.
Very weak base make a good
Leaving Group

66
 Poor Leaving Groups
• If a group is very basic or very small, it is
prevents reaction
 Effect of Leaving Group on SN1

• In acid, OH of an alcohol is protonated and leaving group

is H2O, which is still less reactive than halide
Poor leaving group

Good leaving group

Problem
Rank in order of SN2 reactivity
CH3Br, CH3OTs, (CH3)3Cl, (CH3)2CHCl
• how the solvent affects the
outcome of nucleophilic
substitution reactions
 Effect of of the solvent

Polar protic solvents (solvent of high dielectric constants ) such as water

favor SN1 reactions, Because during reaction, the solvent able
to produce both a cation and an anion which are capable of
stabilizing the carbocation formed.

Because SN2 reactions occur via a concerted mechanism (a

mechanism which takes place in one step, with bonds breaking and forming at the same time)
and no ions form polar protic solvents would have little effect
upon carbocation but influence the reactivity of the nucleophile
Solvents with low dielectric constants tend not to stabilize
nucleophile and thus favor SN2 reactions.
PROTIC SOLVENT On SN2 REACTION

Polar Protic Solvents

Has partially positive hydrogen
Which can solvate (clustered around or
surround) the nucleophiles and make it less
reactive.

Bigger Nucleophiles is less solvated, therefore more

reactive in polar protic solvent (water)

74
 Polar Aprotic on SN2

Polar aprotic solvents let the the nuclephile unsolvated (naked)

because the positif center of the solvent is sterically hindered.
Nucleophiles become more reactive and favor SN2

Trends of nucleophility is inverted to that is observed in polar protic solvent

 NUCLEOPHILITY IN DIFFERENT SOLVENTS :

Nucleophilicity (in methanol solution)

CH3CO2 (-) < Cl(-) < Br(-) < N3(-) < CH3O(-) < CN(-) < I(-) < SCN(-) < CH3S(-)

Nucleophilicity in DMSO solution:

I(-) < SCN(-) < Br(-) < Cl(-) ~ N3(-) < CH3CO2 (-) < CN(-) ~ CH3S(-) < CH3O(-)
 The Effect Solvent on SN2
• POLAR PROTIC slow SN2 reactions
• Because it can produce partially positive charge of hydrogen (-OH or –NH)
which capable of associating with nucleophile
(Energy is required to break interactions between reactant and solvent)

• POLAR APROTIC permit faster reaction

• It can nor produce partially positive charge of hydrogen, thus only weaker
interactions with the nucleophile.
 Pengaruh POLAR PROTIC pada reaksi SN1

• It does not make the nucleofphile more active, but

stabilized carbocation-like transition state, lower DG‡,
thus favor SN1 reaction
• Water-ethanol are the common solvent.

continue….
 Solvent Is Critical in SN1
• Stabilizing carbocation also stabilizes
associated transition state and controls
rate

Solvation of a carbocation by
water stabilizes carbocation
 SOLVATION OF CATION

Carbocation is stabilized by solvation

SN1 reaction is favored
80
 Polar Solvents Promote SN1
• Solvent polarity is measured as dielectric polarization (P)
– Nonpolar solvents have low P, Polar SOLVENT have high P values

Polar, protic and unreactive Lewis base solvents

facilitate formation of carbocation
 Effects of Solvent on Energies
• Polar solvent stabilizes transition state and
intermediate more than reactant and product
 Summary SN1 versus SN2
Untuk kedua jenis reaksi, alkyl iodides bereaksi lebih cepat
karena gugus pergi lebih superior.

Factor SN1 SN2

continue….
83
 Overall Summary

Factor SN1 SN2

 -MeOH
1. CH3 CH2 CH2 OSO2CH3 + Cl CH3 CH2 CH2 Cl
slow
- MeOH
2. CH3 CH2 CH2 OSO2CH3 + Br CH3 CH2 CH2 Br
faster
MeOH
-
3. CH3 CH2 CH2 OSO2CH3 + I CH3 CH2 CH2 I
fastest
 Question A :

- ?
Br + CH3I CH3Br+I-

-
?
I + CH3 Br CH3I+ Br -
 Answer to Question A :
actone or DMF
Cl-+ CH3I CH3Cl+I-
in aprotic solvents: - -
nucleophilicity: Br>I
- -
leaving group: I > Br
methanol or water
I- + CH3 Cl CH3I+ Cl -

in protic solvents: - -
nucleophilicity: I > Cl
- -
leaving group: Cl > I
F: SN1and SN2 reactions:
aspects SN1 favors: ---forming stable carbocations
by use of weak nucleophiles
by use of highly ionizing solvents
aspects SN2 favors:
by use of relatively unhindered alkyl halide
by use of a strong (or a concentrated) nucleophile
by use of a polar aprotic solvent
the order of reactivity SN2 :
methyl > R-CH2-X > (R)2CH-X
tertiary halides do not react by an SN2 mechanism
Organic Synthesis: Functional Group Transformations
Using SN2 Reactions

continue….

91
Organic Synthesis: Functional Group Transformations

Stereochemistry can be controlled in SN2 reactions

continue….
Problem 11.7

Benzene, ether, chloroform are not protic

or very polar. How would they affect SN2
reactions?
 Elimination Reaction of RX
two substituents are lost from adjacent carbons,
forming a new p bond

H H
CH3CH3
-
H H CH3CH3
CH O
H H
C C
C CCH CH33
3
C C
C C
H H CH3CH3
H H
Br Br

• Example : Dehydrohalogenation:
– an elimination reaction in which H+ and X- are lost,
forming an alkene
 Dehydrohalogenation

a strong base, favor elimination

100
ELIMINATION VS SUBSTITUTION

Alkoxide is a strong base

101
ALKOXIDE FROM ALKOHOL

102
 Zaitsev’s RULE (1875)

• Elimination of HX from alkyl halide, produce the most

substituted alkene as the dominant product
 Mechanisms of Elimination Reactions

• E2:
Concerted (one step) transfer of a proton to
a base and departure of leaving group

• E1:
X- leaves first to generate a carbocation
– a base abstracts a proton from the
carbocation
 The E2 Reaction Mechanism

• A proton is transferred to base Product alkene forms

• as leaving group begins to stereospecifically
depart

Transition state
combines leaving of X
and transfer of H
Reaksi E2 (cont)
 E2 Stereochemistry

• the developing  orbital in the

transition state requires periplanar
geometry, anti arrangement

Allows
orbital
overlap
 Geometry of Elimination – E2
• Antiperiplanar allows orbital overlap and
minimizes steric interactions
 Predicting Product
• E2 is stereospecific
• Meso-1,2-dibromo-1,2-diphenylethane with base gives cis 1,2-diphenyl
• RR or SS 1,2-dibromo-1,2-diphenylethane gives trans 1,2-diphenyl
 E2 Reaction Kinetics
• One step – rate law has base and alkyl
halide
• Transition state bears no resemblance to
reactant or product
• Rate = k[R-X][B]
• Reaction goes faster with stronger base,
better leaving group
 Kinetic Isotope Effect
• Substitute deuterium for hydrogen at  position
• Effect on rate is kinetic isotope effect (kH/kD = deuterium isotope effect)
• Rate is reduced in E2 reaction
– Heavier isotope bond is slower to break
– Shows C-H bond is broken in or before rate-limiting step
Practice problem
E2 rxn of (1S,2S)-1,2-dibromo-1,2-diphenylethane
 Elimination From Cyclohexanes
• Abstracted proton and leaving group should
align trans-diaxial to be anti periplanar (app) in
approaching transition state (see Figures 11-19
and 11-20)
• Equatorial groups are not in proper alignment
 E1 REACTION MECHANISM
Carbocation formation
E1 REACTION (cont)
SN2 vs E2
 (SN2 versus E2)

In this case, which reaction path will be dominant ?

Substate: Backside attact is

Primary not hindered

Strong nucleophile

SN2 >E2
 SN2 vs E2

In this case, which reaction path will be dominant ?

Substrate : Nucleophile attact is

secondary sterically hindered
Temperature is medium high

Nucleophile :
Strong base

SN2 < E2
 SN2 vs E2
In this case, which reaction path will be dominant ?

Potassium tert-butoxide
(bulky base),

Sterically hindered
Difficult to get close positive
center of carbon for substitution
to occur
SN2 < E2
 E1 vs SN1
Both involve the formation of carbocation

In this case, which reaction path will be dominant ?

Low
Substrate →Tersier
temperature
SN2 < SN1 or E1

SN1 > E1
 SN1 vs E1
In this case, which reaction path will be dominant ?
SN2 < SN1 or E1

Substrate: Temperature is higher

tertiery

<

SN1 < E1


 SN1, SN2, E1, E2 : Dapatkah dibuat batas yang jelas?

Untuk suatu kasus, bagaimana memprediksi apa yg akan terjadi? Apakah

terjadi Eliminasi atau Substitusi? Reaksinya bimolekuler atau unimolekuler?
Sayangnya tidak ada jawab yang rigid tegas, akan tetapi memungkinkan
memahami beberapa kecenderungan dan membuat generalisasi.

Ringkasan reaksi substitusi dan eliminasi

Halida SN1 SN2 E1 E2

RCH2X Sangat terbantu Terjadi jika
Tak ada Tak ada digunakan basa
kuat

R2CHX Dpt terjadi dgn Terjadi bersaingan Dpt terjadi dgn Terbantu jika
halida alilik dan dengan E2 halida alilik dan digunakan basa
benzilik benzilik kuat

R3CX Terbantu dalam Terjadi bersaingan Terbantu jika

pelarut hidroksilik Tak ada dengan SN1 digunakan basa

SN1 dan E1 biasanya terjadi pada kondisi solvolysis

SN1 and E1 usually occur only under solvolysis conditions.
 Alkil Halida Primer

CH3CH2CH2CH2Br Na+ -CN CH3CH2CH2CH2CN

THF-HMPA
1- Bromobutana Pentananitril (90%)
SN2
APROTIC RS-, I-,CN-, NH3, Br-
Anion →NAKED nukleofil kuat

CH3CH2CH2CH2Br CH3CH2CH2=CH2
(CH3)3CO-K+
1- Bromobutana 1-Bromobutena (85%)
E2
tert-butoksida
basa kuat, sterically hindered
 Secondary Alkyl halide SN2, E2 ? SN1, E1
SN1, E1 Aprotik,basa lemah → SN2
SN2, E2
protik Aprotik,basa kuath → E2
Nu/Basa lemah SN2, E2 >> SN1, E1
aprotik
Alilik, benzilik
SN2> E2
Alkil halida sekunder

SN2< E2
basa kuat
CH3CH2O-, OH-, NH2-
 Suhu tinggi E1>SN1
Nu Lemah→SN1, E1 Basa Kuat →E2 HALIDA TERTIER

SN2 sulit SN2 E2

Halida tertier

SN1 E1

Solvolysis
 SN2 E2

SN1 E1

Solvolysis
 QUIZ
By considering the substrate, nucleophile, leaving group,
solvent, give the explanation why should the below reaction take
place to follow nucleofilic substitution reaction (SN2 or SN1) or
Elimination reaction (E2 or E1) mechanism. Write in 3D style, the
structure of the reactant, transition state, intermediate, and product
with theirs R/S orientation and the electron movement, and the
energy diagram.

1. Reaction of (S)-2-iodohexane with CH3CH2S– in solvent

dimethylsulfoxide (CH3)2SO.
2. Reaction of 1-bromo-1-methylpropyl benzene with H2O.
3. Reaction of (CH3)2CHCHBrCH2CH3 with potassium hydroxide.
4. Reaction of (1R,2R)-1,2-dibromo-1,2-diphenylethane with KOH
5. Predict the mayor product of reaction when (CH3)2CHBr is
reacted with etanol and basic catalyst KOH. Give the
mechanism reaction.
NUCLEOPHILIC SUBSTITUTIONS
Of ALCOHOLS

H
C C O H
H
NUCLEOPHILIC SUBSTITUTION REACTIONS
(SN1)
Acid-catalyzed

• Reaction with HX
OH NaBr, H2SO4 Br
heat
150 oC

• This reaction can happen because the

protonation of the OH group to make a better
leaving group.
 MECHANISM of Acid-catalyzed SN1

• Step 1: protonation of the alcohol:

H

OH + OH
Br-
+ HBr

• Step 2: loss of water to form carbocation:

H
+ OH
+ H2O
+
• Step 3: attack of the nucleophile:

Br
+ -
Br
+
Potential Energy Diagram for SN1 Reaction
OTHER METHOD FOR MODIFYING OH
INTO GOOD LG
ELIMINATION (E1) Acid-catalyzed dehydrations
E1 WITH CARBOCATION REARRANGEMENT
 OTHER REACTION OF ALCOHOLS

H
C C O H
H
• Acid/base reactions
• Oxidation reactions (to yield ketones,
aldehydes and carboxylic acids)
 ACID/BASE REACTIONS of
amphiprotic Alcohols

• Act as acid in presence of strong base:

- +
2 CH 3CH2OH + 2 Na 2 CH 3CH2O Na + H2

CH3CH2OH + NaH CH3CH2O- Na+ + H2

alkoxide
• Act as base in presence of strong acid:
+
CH3CH2OH + H2SO4 CH3CH2OH + HSO4-
H
oxonium ion