Organic Chemistry For USTH Students Lecture 2: Electrophilic Addition To C C

Organic Chemistry
For USTH Students

Lecture 2: Electrophilic addition
to C=C
Dr. Doan Duy Tien
Contents
Electrophilic addition to C=C
+ General mechanism
+ Electrophilic Addition to CarbonCarbon Multiple Bonds
+ Addition of HX
+ Addition of HOH and addition of YX
+ Addition to allene and alkyne
+ Substitution at -carbon
+ Reactions via organoborane intermediates
Nucleophilic addition to C=C

+ Electron withdrawing group stabilze negative charge
+ Michael reaction with carbon nulceophiles
-1,2 addition favored for more reactive group without steric hindrance
-1,4 addition favored for strerically unhindered 4 position if 2 position is blocked
Structure and Bonding of C=C

Alkenes are also called olefins.
Alkenes contain a carboncarbon double bond.
Terminal alkenes have the double bond at the end of the carbon chain.
Internal alkenes have at least one carbon atom bonded to each end of the
double bond.
Cycloalkenes contain a double bond in a ring.
Structure and Bonding of C=C
Recall that the double bond consists of a bond and a bond. The
bond is stronger than the bond.
The carbon atom is sp2 hybridized to obtain trigonal planar geometry,
with bond angles of approximately 120.
2
sp
Hybridization
2p
There is one p orbital left over,

and it would be along the z axis.
3 sp2 orbitals
Orbital Picture of Ethylene

Hs
sp2
sp2
Hs
C
C
sp
2
Hs
px
sp2
sp2
H
C
sp2
C
H
Hs
Interesting Alkenes
Ethylene, an industrial starting material for many useful products
Interesting Alkenes
Addition Reactions
The characteristic reaction of alkenes is addition: the bond is broken
and two new bonds are formed.
No pi bond
Alkenes have exposed electrons, with the electron density of the bond
above and below the plane of the molecule.
Because alkenes are electron rich, simple alkenes do not react with
nucleophiles or bases, reagents that are themselves electron rich. Alkenes
react with electrophiles.
9
Addition Reactions
Because the carbon atoms of a double bond are both trigonal
planar, the elements of X and Y can be added to them from the
same side or from opposite sides.
10
Addition Reactions
Five addition reactions of cyclohexene
No pi bond
in products
11
Electrophilic Addition of
Hydrohalogenation(HX) to C=C
Two bonds are broken in this reaction: the weak bond of the
alkene and the HX bond, and two new bonds are formed: one
to H and one to X.
Recall that the HX bond is polarized, with a partial positive
charge on H. Because the electrophilic H end of HX is attracted
to the electron-rich double bond, these reactions are called
electrophilic additions.
12
Electrophilic Addition of Hydrohalogenation

(HX) to C=C
To draw the products of an addition reaction:
13

(HX) to C=C: The mechanism
The mechanism of electrophilic addition consists of two successive Lewis acidbase reactions. In step 1, the alkene is the Lewis base that donates an electron
pair to HBr, the Lewis acid, while in step 2, Br is the Lewis base that donates
an electron pair to the carbocation, the Lewis acid.
14

(HX) to C=C: Energy diagram
In the representative energy diagram below, each step has its own energy
barrier with a transition state energy maximum. Since step 1 has a higher
energy transition state, it is rate-determining. H for step 1 is positive
because more bonds are broken than formed, whereas H for step 2 is
negative because only bond making occurs.
Energy diagram for electrophilic addition:
CH3CH2=CH2 + HBr CH3CH2CH(Br)CH3
15

(HX) to C=C: Markovnikovs Rule
With an unsymmetrical alkene, HX can add to the double bond to give
two constitutional isomers, but only one is actually formed:
This is a specific example of a general trend called Markovnikovs rule.

Markovnikovs rule states that in the addition of HX to an unsymmetrical
alkene, the H atom adds to the less substituted carbon atom, that is, the
carbon that has the greater number of H atoms to begin with.
16

(HX) to C=C: Markovnikovs Rule
The basis of Markovnikovs rule is the formation of a carbocation in the
rate-determining step of the mechanism.
In the addition of HX to an unsymmetrical alkene, the H atom is added to
the less substituted carbon to form the more stable, more substituted
carbocation.
17

(HX) to C=C: Stereochemistry
Recall that trigonal planar atoms react with reagents from two
directions with equal probability.
Achiral starting materials yield achiral products.
Sometimes new stereogenic centers are formed from
hydrohalogenation:
A racemic mixture
18

The mechanism of hydrohalogenation illustrates why two enantiomers are
formed. Initial addition of H+ occurs from either side of the planar double
bond.
Both modes of addition generate the same achiral carbocation. Either
representation of this carbocation can be used to draw the second step of
the mechanism.
19

Nucleophilic attack of Cl on the trigonal planar carbocation also occurs
from two different directions, forming two products, A and B, having a
new stereogenic center.
A and B are enantiomers. Since attack from either direction occurs with
equal probability, a racemic mixture of A and B is formed.
20

Hydrohalogenation occurs with syn and anti addition of HX.
The terms cis and trans refer to the arrangement of groups in a particular
compound, usually an alkene or disubstituted cycloalkene.
The terms syn and anti describe stereochemistry of a process, for example,
how two groups are added to a double bond.
Addition of HX to 1,2-dimethylcyclohexene forms two new stereogenic
centers, resulting in the formation of four stereoisomers (2 pairs of
enantiomers).
21

Reaction of 1,2-dimethyl cyclohexene with HCl
22

(HX) to C=C: Summary
23
Electrophilic Addition of Water to C=C
24
Electrophilic Addition of Water to C=C
25
Electrophilic Addition of Alcohols to C=C

Alcohols add to alkenes, forming ethers by the same mechanism. For
example, addition of CH3OH to 2-methylpropene, forms tert-butyl methyl
ether (MTBE), a high octane fuel additive.
Note that there are three consequences to the formation of carbocation

intermediates:
1. Markovnikovs rule holds.
2. Addition of H and OH occurs in both syn and anti fashion.
3. Carbocation rearrangements can occur.
26
Electrophilic Addition of Halogen to C=C

Halogenation is the addition of X2 (X = Cl or Br) to an alkene to form a
vicinal dihalide.
27
Electrophilic Addition of Halogen to C=C
Carbocations are unstable because they

have only six electrons around carbon.
Halonium ions are unstable because of
ring strain.
28
Electrophilic Addition of Halogen to

C=C: Stereochemistry
Consider the chlorination of cyclopentene to afford both enantiomers of
trans-1,2-dichlorocyclopentane, with no cis products.
Initial addition of the electrophile Cl+ from (Cl2) occurs from either side
of the planar double bond to form a bridged chloronium ion.
29

In the second step, nucleophilic attack of Cl must occur from the backside.
Since the nucleophile attacks from below and the leaving group departs from
above, the two Cl atoms in the product are oriented trans to each other.
Backside attack occurs with equal probability at either carbon of the threemembered ring to yield a racemic mixture.
30

cis-2-Butene yields two enantiomers, whereas trans-2-butene yields a single
achiral meso compound.
Halogenation of cis- and trans-2-butene
31
Electrophilic Addition of Halogen in

Water to C=C: Halohydrin Formation:
Treatment of an alkene with a halogen X2 and H2O forms a halohydrin by

addition of the elements of X and OH to the double bond.
32

Even though X is formed in step [1] of the mechanism, its concentration is

small compared to H2O (often the solvent), so H2O and not X is the
nucleophile.
33

34
Electrophilic Addition to C=C:

Hydroboration - Oxidation
Hydroborationoxidation is a two-step reaction sequence that
converts an alkene into an alcohol.
35

With unsymmetrical alkenes, the boron atom bonds to the less substituted
carbon atom.
36

37
Biotransformation of C=C:
38
Biotransformation of C=C:
39
KEY CONCEPTS
40
KEY CONCEPTS
41
KEY CONCEPTS
42
Electrophilic Addition to CC
43
44
45
Problems
46
Problems
47
Problems
48
Organic Chemistry
For USTH Students
Lecture 3:
Electrophilic substitution in
Aromatic systems
Dr. Doan Duy Tien
49
Electrophilic substitution in Aromatic systems

Contents:
+ The General Mechanism
+ Halogenation
+ Nitration and Sulfonation
+ Nitration and Sulfonation
+ Substituted Benzenes: Inductive Effects, Resonance Effects
+ Electrophilic Aromatic Substitution of Substituted Benzenes
+ Application : Synthesis of the hallucinogenic effects of LSD
Interesting benzene rings
51
Structure of benzene
Aromaticity-Hckels Rule:
+ A molecule must be cyclic
+ A molecule must be planar
+ A molecule must be completely conjugated
+ A molecule must satisfy Hckels rule, and contain a particular number
of electrons. An aromatic compound must contain 4n + 2 electrons (n
= 0, 1, 2, and so forth).
52
Aromaticity-Hckels Rule ?
Drug for the treatment of type

2 diabetes; that increases the
bodys ability to lower blood
sugar levels,
Antimalarial drug
that reduces fever
53
Aromaticity-Hckels Rule ?
3
1
20
9
10
Mg
N
19
18
12
17
16
14
15
MeOOC
11
O phytyl
13
O
1
chlorophyll a
phytyl =
Molecule of life
Buckminsterfullerene, C60
54
Electrophilic Aromatic Substitution

Background:
The characteristic reaction of benzene is electrophilic aromatic
substitution: a hydrogen atom is replaced by an electrophile.
55

Background:
Benzene does not undergo addition reactions like
other unsaturated hydrocarbons, because addition
would yield a product that is not aromatic.
Substitution of a hydrogen keeps the aromatic ring
intact.
There are five common examples of electrophilic
aromatic substitution.
56

Mechanism:
57

Background:
The energy changes in electrophilic aromatic
substitution are shown below:
Figure 18.2 Energy diagram for electrophilic aromatic substitution:
PhH + E+ PhE + H+
58
Figure 18.1
Five examples
of electrophilic
aromatic
substitution
59

Nitration and Sulfonation:
Nitration and sulfonation introduce two different
functional groups into the aromatic ring.
Nitration is especially useful because the nitro group
can be reduced to an NH2 group.
60

Nitration and Sulfonation:
Generation of the electrophile in nitration requires
strong acid.
Generation of the electrophile in sulfonation requires

strong acid.
61

Friedel-Crafts Alkylation and Friedel-Crafts Acylation:
In Friedel-Crafts alkylation, treatment of benzene with
an alkyl halide and a Lewis acid (AlCl3) forms an alkyl
benzene.
62

In Friedel-Crafts acylation, a benzene ring is treated
with acid chloride (RCOCl) and AlCl3 to form a ketone.
Because the new group bonded to the benzene ring is
called an acyl group, the transfer of an acyl group from
one atom to another is an acylation.
63

Friedel-Crafts Alkylation:
64

65

Four additional facts about Friedel-Crafts alkylation
should be kept in mind:
[1] Vinyl halides and aryl halides are less reactive than
alkyl halides so do not react in Friedel-Crafts alkylation.
[2] Alkyl groups activate the benene ring toward further

EAS so polyalkylation can occur.
66

[3] Carbocation rearrangements can occur.
These results can be explained by carbocation

rearrangements.
67

68

Each carbocation can then go on to react with benzene
to form a product of electrophilic aromatic substitution.
For example:
Starting materials that contain both a benzene ring and

an electrophile are capable of intramolecular FriedelCrafts reactions.
69

Substituted Benzenes:
Considering the inductive effect, the NH2 group
withdraws electron density. The CH3 donates electron
density through hyperconjugation.
70

Resonance effects are only observed with substituents
containing lone pairs or bonds.
An electron-donating resonance effect is observed

whenever an atom Z having a lone pair of electrons is
directly bonded to a benzene ring.
71

An electron-withdrawing resonance effect is observed
in substituted benzenes having the general structure
C6H5-Y=Z, where Z is more electronegative than Y.
Seven resonance structures can be drawn for
benzaldehyde (C6H5CHO). Because three of them place
a positive charge on a carbon atom of the benzene ring,
the CHO group withdraws electrons from the benzene
ring by a resonance effect.
72

The inductive and resonance effects in compounds

having the general structure C6H5-Y=Z (with Z more
electronegative than Y) are both electron withdrawing.
73

These compounds represent examples of the general
structural features in electron-donating and electron
withdrawing substituents.
74

EAS and Substituted Benzenes:
First, consider tolueneToluene reacts faster than
benzene in all substitution reactions.
The electron-donating CH3 group activates the
benzene ring to electrophilic attack.
Ortho and para products predominate.

The CH3 group is called an ortho, para director.
75

Now consider nitrobenzeneIt reacts more slowly
than benzene in all substitution reactions.
The electron-withdrawing NO2 group deactivates the
benzene ring to electrophilic attack.
The meta product predominates.

The NO2 group is called a meta director.
76

All substituents can be divided into three general types:
77

78

To understand how substituents activate or deactivate
the ring, we must consider the first step in
electrophilic aromatic substitution.
The first step involves addition of the electrophile (E+)
to form a resonance stabilized carbocation.
The Hammond postulate makes it possible to predict

the relative rate of the reaction by looking at the
stability of the carbocation intermediate.
79

80

Orientation Effects in Substituted Benzenes:
There are two general types of ortho, para directors
and one general type of meta director.
All ortho, para directors are R groups or have a
nonbonded electron pair on the atom bonded to the
benzene ring.
All meta directors have a full or partial positive charge

on the atom bonded to the benzene ring.
81

Orientation Effects in Substituted Benzenes:
Figure 18.7 The reactivity and
directing effects of common
substituted benzenes
82

Limitations in Electrophilic Aromatic Substitutions:
Benzene rings activated by the strong electrondonating groups, OH, NH2, and their derivatives (OR,
NHR, and NR2), undergo polyhalogenation when
treated with X2 and FeX3.
83

Limitations in Electrophilic Aromatic Substitutions:
A benzene ring deactivated by strong electronwithdrawing groups (i.e., any of the meta directors)
is not electron rich enough to undergo Friedel-Crafts
reactions.
Friedel-Crafts reactions also do not occur with NH2

groups because the complex that forms between the
NH2 group and the AlCl3 catalyst deactivates the ring
towards Friedel-Crafts reactions.
84

Disubstituted Benzenes:
1. When the directing effects of two groups reinforce,
the new substituent is located on the position
directed by both groups.
85

2. If the directing effects of two groups oppose each
other, the more powerful activator controls the
reaction.
86

3. No substitution occurs between two meta
substituents because of crowding.
87

Planning Synthesis of Benzene Derivatives:
In a disubstituted benzene, the directing effects indicate
which substituent must be added to the ring first.
Let us consider the consequences of bromination first

followed by nitration, and nitration first, followed by
bromination.
88

Pathway I, in which bromination precedes nitration,
yields the desired product. Pathway II yields the
undesired meta isomer.
89

Halogenation of Alkyl Benzenes:
90

Halogenation of Alkyl Benzenes:
Note that alkyl benzenes undergo two different
reactions depending on the reaction conditions:
With Br2 and FeBr3 (ionic conditions), electrophilic

aromatic substitution occurs, resulting in replacement
of H by Br on the aromatic ring to form o and p isomers.
With Br2 and light or heat (radical conditions),
substitution of H by Br occurs at the benzylic carbon91of
the alkyl group.

Oxidation and Reduction of Substituted Benzenes:
Arenes containing at least one benzylic CH bond are
oxidized with KMnO4 to benzoic acid.
Substrates with more than one alkyl group are

oxidized to dicarboxylic acids. Compounds without
a benzylic hydrogen
are inert to oxidation.
92

We now know two different ways to introduce an alkyl
group on a benzene ring:
1. A one-step method using Friedel-Crafts alkylation.
2. A two-step method using Friedel-Crafts acylation to
form a ketone, followed by reduction.
Figure 18.8 Two
methods to prepare
an alkyl benzene
93

Although the two-step method is longer, it must be
used to synthesize certain alkyl benzenes that
cannot be prepared by the one-step Friedel-Crafts
alkylation because of possible rearrangements.
94

A nitro group (NO2) that has been introduced on a
benzene ring by nitration with strong acid can
readily be reduced to an amino group (NH2) under a
variety of conditions.
95
+ Application : Synthesis of the hallucinogenic effects of LSD

Application: Swimming pool test kit for
chlorine
NH2
CH3
o-toluidine
NH2
Cl2 (aq.)
Cl
CH3
Cl
bright yellow!
97

Naproxen production: Albemarle Company
Heck Coupling: Nobel prize 2010:
Anti-inflammatory drug
KEY CONCEPTS
99
KEY CONCEPTS
100
KEY CONCEPTS
101
KEY CONCEPTS
102
Problems
103
Problems
104
Problems
105
Problems
106
Reaction of Carbocation
Key intermediate for biosynthesis
107

Organic Chemistry For USTH Students Lecture 2: Electrophilic Addition To C C

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Organic Chemistry For USTH Students Lecture 2: Electrophilic Addition To C C

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Organic Chemistry

For USTH Students

Dr. Doan Duy Tien

Nucleophilic addition to C=C

Structure and Bonding of C=C

Cycloalkenes contain a double bond in a ring.

Structure and Bonding of C=C

There is one p orbital left over,

Orbital Picture of Ethylene

Electrophilic Addition of Hydrohalogenation

Electrophilic Addition of Hydrohalogenation

Electrophilic Addition of Hydrohalogenation

Electrophilic Addition of Hydrohalogenation

This is a specific example of a general trend called Markovnikovs rule.

Electrophilic Addition of Hydrohalogenation

Electrophilic Addition of Hydrohalogenation

Electrophilic Addition of Hydrohalogenation

Electrophilic Addition of Hydrohalogenation

Electrophilic Addition of Hydrohalogenation

Electrophilic Addition of Hydrohalogenation

Reaction of 1,2-dimethyl cyclohexene with HCl

Electrophilic Addition of Hydrohalogenation

Electrophilic Addition of Water to C=C

Electrophilic Addition of Water to C=C

Electrophilic Addition of Alcohols to C=C

Note that there are three consequences to the formation of carbocation

Electrophilic Addition of Halogen to C=C

Electrophilic Addition of Halogen to C=C

Carbocations are unstable because they

Electrophilic Addition of Halogen to

Electrophilic Addition of Halogen to

Electrophilic Addition of Halogen to

Halogenation of cis- and trans-2-butene

Electrophilic Addition of Halogen in

Treatment of an alkene with a halogen X2 and H2O forms a halohydrin by

Electrophilic Addition of Halogen in

Even though X is formed in step [1] of the mechanism, its concentration is

Electrophilic Addition of Halogen in

Electrophilic Addition to C=C:

Electrophilic Addition to C=C:

Electrophilic Addition to C=C:

Dr. Doan Duy Tien

Electrophilic substitution in Aromatic systems

Interesting benzene rings

Drug for the treatment of type

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

Generation of the electrophile in sulfonation requires

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

[2] Alkyl groups activate the benene ring toward further

Electrophilic Aromatic Substitution

These results can be explained by carbocation

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution

Starting materials that contain both a benzene ring and