CHEM 2411 Chapter 06 Lecture Final Kirberger

Organic Chemistry,
8th Edition
L. G. Wade, Jr.
Chapter 6
Lecture
Alkyl Halides:
Nucleophilic Substitution and
Elimination
Rizalia Klausmeyer
Baylor University
Waco, TX
© 2013 Pearson Education, Inc.
Classes of Alkyl Halides
H H
• Alkyl halides: Halogen is H C C Br
directly bonded to sp3
H H
carbon. alkyl halide
• Vinyl halides: Halogen is H H
bonded to sp2 carbon of C C
H Cl
alkene.
vinyl halide
• Aryl halides: Halogen is I
bonded to sp2 carbon on
benzene ring.
aryl halide
2
© 2013 Pearson Education Inc.
Polarity and Reactivity
• Halogens more EN than C.

• Carbon—halogen bond is
polar, so carbon has partial
positive charge.
• Carbon can be attacked by a
nucleophile.
• Halogen can leave with the
electron pair.
3
IUPAC Nomenclature
• Name as haloalkane.
• Choose the longest carbon chain, even if the halogen is
not bonded to any of those carbons.
• Use lowest possible numbers for position.
1 2
Cl CH2CH2F
CH3CHCH2CH3 CH3CH2CH2CHCH2CH2CH3
1 2 3 4 1 2 3 4 5 6 7
2-chlorobutane 4-(2-fluoroethyl)heptane
4
Examples
CH3 Br
CH3CHCH2CH2CH2CHCH2CH2CH3
1 2 3 4 5 6 7 8 9
1 Br
6-bromo-2-methylnonane
H
F H
cis-1-bromo-3-fluorocyclohexane
5
More Examples
Cl
F Cl Br
Br
3-fluoro-2,4-dimethylpentane 3-bromo-5-chloro-4-ethylheptane
1-bromo-2-chloro-4-ethylcyclopentane
Cl I
Br
Cl Br
Br
5-chloro-4-(1-chloroethyl)-3-bromoheptane Cl 6-ethyl-3-iodo-5-isopropyl-4-propylnonane
2-bromo-4-(1-bromoethyl)-1-chlorocyclopentane
6
Systematic Common Names
• You may encounter common names where the

alkyl groups is a substituent on halide.
• Useful only for small alkyl groups.
CH3 CH3 CH3

CH3CHCH2 Br CH3CH2CH Br CH3C Br
CH3
isobutyl bromide sec-butyl bromide
tert-butyl bromide
7
Common Names of Halides
• CH2X2 is called methylene halide.

• CHX3 is a haloform.
• CX4 is carbon tetrahalide.
• Common halogenated solvents:

CH2Cl2 is methylene chloride.
CHCl3 is chloroform.
CCl4 is carbon tetrachloride.
8
Alkyl Halides Classification
• Methyl halides: Halide is attached to a methyl group.

• Primary alkyl halide: Carbon to which halogen is
bonded is attached to only one other carbon.
• Secondary alkyl halide: Carbon to which halogen is
bonded is attached to two other carbons.
• Tertiary alkyl halide: Carbon to which halogen is
bonded is attached to three other carbons.
9
Primary, Secondary, Tertiary Alkyl Halides
10
Types of Dihalides
• Geminal dihalide: Two halogen atoms are

bonded to the same carbon.
• Vicinal dihalide: Two halogen atoms are bonded
to adjacent carbons.
11
Uses of Alkyl Halides
• Industrial and household cleaners.

• Anesthetics:
– CHCl3 used originally as general anesthetic but it is
toxic and carcinogenic.
– CF3CHClBr is a mixed halide sold as Halothane.
• Freons are used as refrigerants and foaming agents.
– Freons can harm the ozone layer, so they have been
replaced by low-boiling hydrocarbons or carbon
dioxide.
• Pesticides such as DDT are extremely toxic to insects but
not as toxic to mammals.
– Haloalkanes can not be destroyed by bacteria, so they
accumulate in the soil to a level that can be toxic to
mammals, especially humans.
12
Dipole Moments
• Electronegativities of the halides:

F > Cl > Br > I
• Bond lengths increase as the size of the
halogen increases:
C—F < C—Cl < C—Br < C—I
• Bond dipoles:
C—Cl > C—F > C—Br > C—I
1.56 D 1.51 D 1.48 D 1.29 D
• Molecular dipoles depend on the
geometry of the molecule.
13
Dipole Moments and Molecular Geometry
Notice how the four symmetrically oriented polar bonds

of the carbon tetrahalides cancel to give a molecular
dipole moment of zero.
14
Interparticle Forces
δ-
1. Dipolar forces: Attraction between positive O
end of one polar molecule and negative end H H
of another (usually weak, ~0.5 -2.0 kcal)
δ+
2. Hydrogen Bonding: Attractive interaction of a δ-O
hydrogen atom with an electronegative atom H H
Hydrogen
(e.g. N, O, F) from another molecule or
bond δ+
chemical group.
– The H must be covalently bonded to δ- O
another electronegative atom.
– Stronger than dipolar and dispersion (12-
16 kcal) R δ+ R
3. London Dispersion Forces: Momentary Intermolecular
nonsymmetric electron distributions in dipolar
molecules (very weak) δ- O
R δ+ R
15
Boiling Points
• Greater intermolecular forces, higher b.p.

– Dipole-dipole attractions not significantly different for
different halides.
– London forces greater for larger atoms.
• Greater mass, higher b.p.
• Spherical shape decreases b.p.
(CH3)3CBr CH3(CH2)3Br
73 C 102 C
16
Densities
• Alkyl fluorides and alkyl chlorides (those

with just one chlorine atom) are less dense than water
(1.00 g/mL).
• Alkyl chlorides with two or more chlorine atoms are
denser than water.
• All alkyl bromides and alkyl iodides are denser than
water.
17
Preparation of Alkyl Halides
• Free radical halogenation (Chapter 4)

– Chlorination produces a mixtures of products.
This reaction is not a good lab synthesis, except
in alkanes where all hydrogens are equivalent.
– Bromination is highly selective.
• Free radical allylic halogenation
– Halogen is placed on a carbon directly attached
to the double bond (allylic).
18
Halogenation of Alkanes
• Chlorination is not selective.

• Bromination is highly selective:
3º carbons > 2º carbons > 1º carbons
19
Allylic Bromination
• Allylic radicals are resonance stabilized.

• Bromination occurs with good yield at the allylic
position (sp3 C next to C C).
20
Reaction Mechanism
• The mechanism involves an allylic radical

stabilized by resonance.
• Both allylic radicals can react with bromine.
21
N-Bromosuccinimide
• N-Bromosuccinimide (NBS) is an allylic

brominating agent.
• Keeps the concentration of Br2 low.
22
Example of Allylic Halogenation with NBS
File Name: AAAKWEA0
23
Reactions of Alkyl Halides
24
The SN2 Reaction
• The halogen atom on the alkyl halide is replaced with the

nucleophile (HO-).
• Since the halogen is more electronegative than carbon,
the C—I bond breaks heterolytically and the iodide ion
leaves.
25
SN2 Mechanism
• Bimolecular nucleophilic substitution (SN2).

• Concerted reaction: New bond forming and old bond
breaking at same time.
• Reaction is second order overall.
• Rate = kr[alkyl halide][nucleophile].
26
SN2 Energy Diagram
• The SN2 reaction is a one-step reaction.

• Transition state is highest in energy.
27
Uses for SN2 Reactions
28
SN2: Nucleophilic Strength
• Stronger nucleophiles react faster.

• Strong bases are strong nucleophiles, but not all
strong nucleophiles are basic.
29
Basicity Versus Nucleophilicity
• Basicity is defined by the equilibrium constant for

abstracting a proton.
• Nucleophilicity is defined by the rate of attack on
the electrophilic carbon atom
30
Steric hindrance (bulkiness)
hinders nucleophilicity
more than it hinders basicity.
31
Trends in Nucleophilicity
• A negatively charged nucleophile is stronger than its

neutral counterpart:
• Nucleophilicity decreases from left to right:
• Increases down periodic table, as size and

polarizability increase:
32
Polarizability Effect
Bigger atoms have a soft shell that can start to overlap the carbon
atom from a farther distance.
33
Solvent Effects: Protic Solvents
• Polar protic solvents have acidic hydrogens (O—H or N—

H) that can solvate the nucleophile, reducing their
nucleophilicity.
• Nucleophilicity in protic solvents increases as the size of
the atom increases.
34
Solvent Effects: Aprotic Solvents
• Polar aprotic solvents do not have acidic protons and

therefore cannot hydrogen bond.
• Some aprotic solvents are acetonitrile, DMF, acetone, and
DMSO.
• SN2 reactions proceed faster in aprotic solvents.
35
Crown Ethers
• Crown ethers solvate

the cation, so the
nucleophilic strength
of the anion increases.
• Fluoride becomes a
good nucleophile.
36
Leaving Group Ability
The best leaving groups are:

• Electron-withdrawing, to polarize the carbon atom.
• Stable (not a strong base) once they have left.
• Polarizable, to stabilize the transition state.
37
Do not write SN2 reactions that show
hydroxide ions, alkoxide ions, or other
strong bases serving as leaving groups.
38
Structure of Substrate on SN2 Reactions
• Relative rates for SN2:
CH3X > 1° > 2° >> 3°
• Tertiary halides do not react via the SN2

mechanism, due to steric hindrance.
39
Effect of Substituents on the Rates of SN2 Reactions
40
Steric Effects of the Substrate on SN2 Reactions
• Nucleophile approaches from the back side.

• It must overlap the back lobe of the C—X sp3 orbital.
41
Stereochemistry of SN2
SN2 reactions will result in an inversion of

configuration also called a Walden inversion.
42
Back-Side Attack in the SN2 Reaction
43
(R) and (S) are just names. Don’t
rely on names to determine the
stereochemistry of a reaction.
44
The SN1 Reaction
• The SN1 reaction is a unimolecular

nucleophilic substitution.
• It has a carbocation intermediate.
• Rate = kr[alkyl halide].
• Racemization occurs.
45
SN1 Mechanism
Step 1: Formation of the carbocation.
Step 2: Attack of the nucleophile.
• If the nucleophile is an uncharged molecule like water or an alcohol, the positively

charged product must lose a proton to give the final uncharged product.
46
SN1 Mechanism: Step 1
Formation of carbocation (rate-determining step)
47
• The nucleophile attacks the carbocation,

forming the product.
48
• If the nucleophile was neutral, a third step

(deprotonation) will be needed.
49
SN1 Energy Diagram
• Forming the
carbocation is an
endothermic step.
• Step 2 is fast with a
low activation energy.
50
Rates of SN1 Reactions
• Order of reactivity follows stability of

carbocations (opposite to SN2).
– 3° > 2° > 1° >> CH3X
– More stable carbocation requires less energy
to form.
• A better leaving group will increase the rate
of the reaction.

51
Solvation Effect
• Polar protic solvent is best because it can solvate

both ions strongly through hydrogen bonding.
52
Structure of the Carbocation
• Carbocations are sp2 hybridized and trigonal planar. The

lobes of the empty p orbital are on both sides of the
trigonal plane.
• Nucleophilic attack can occur from either side, producing
mixtures of retention and inversion of configuration if the
carbon is chiral.
53
Carbocation Stability
Carbocations are stabilized by inductive effect and by

hyperconjugation.
54
Stereochemistry of SN1
The SN1 reaction produces mixtures of enantiomers. There

is usually more inversion than retention of configuration.
55
Rearrangements
• Carbocations can rearrange to form a more stable

carbocation.
• Move the smallest group on the adjacent carbon:
– Hydride shift: H- on adjacent carbon moves.
– Methyl shift: CH3- on adjacent carbon moves.
56
Hydride and Methyl Shifts
• Since a primary carbocation cannot form, the methyl group on the

adjacent carbon will move (along with both bonding electrons) to the
primary carbon, displacing the bromide and forming a tertiary
carbocation.
• The smallest groups on the adjacent carbon will move: If there is a
hydrogen, it will give a hydride shift.
57
SN1 or SN2 Mechanism?
SN2 SN1
CH3X > 1º > 2º 3º > 2º
Strong nucleophile Weak nucleophile (may
also be used as solvent)
Polar aprotic solvent Polar protic solvent
Rate = k[alkyl halide][Nuc] Rate = k[alkyl halide]
Inversion at chiral carbon Racemization
No rearrangements Rearranged products
58
Elimination Reactions
• Elimination reactions produce double bonds.

• Also called dehydrohalogenation (-HX).
59
The E1 Reaction
• Unimolecular elimination.
• Two groups lost: a hydrogen and the halide.
• Nucleophile acts as base.
• The E1 and SN1 reactions have the same
conditions so a mixture of products will be
obtained.
60
E1 Mechanism
Step 1: Ionization to form a carbocation.
Step 2: Solvent abstracts a proton to form an alkene.
61
A Closer Look
62
E1 Energy Diagram
The E1 and the SN1 reactions have the same first step:
Carbocation formation is the rate-determining step for both
mechanisms.
63
Double Bond Substitution Patterns
tetrasubstituted trisubstituted disubstituted monosubstituted
• The more substituted double bond is more stable.

• In elimination reactions, the major product of the reaction
is the more substituted double bond: Zaitsev’s rule.
64
Zaitsev’s Rule
• If more than one elimination product is possible,

the most-substituted alkene is the major product
(most stable).
major product
(trisubstituted)
65
E1 Competes with the SN1
• Substitution results from nucleophilic attack on the

carbocation.
• Ethanol serves as a base in the elimination and as a
nucleophile in the substitution.
66
A Carbocation Can…
• React with its own leaving group to return

to the reactant.
• React with a nucleophile to form a
substitution product (SN1).
• Lose a proton to form an elimination
product (E1).
• Rearrange to give a more stable
carbocation, then react further.
67
The E2 Reaction
• Elimination, bimolecular.
• Requires a strong base.
• This is a concerted reaction: The proton is
abstracted, the double bond forms, and the
leaving group leaves, all in one step.
68
The E2 Mechanism
• Order of reactivity for alkyl halides:

3° > 2 ° > 1°
• Mixture may form, but Zaitsev product
predominates.
69
E2 Stereochemistry
• The halide and the proton to be abstracted must

be anti-coplanar ( = 180º) to each other for the
elimination to occur.
• The orbitals of the hydrogen atom and the halide
must be aligned so they can begin to form a pi
bond in the transition state.
• The anti-coplanar arrangement minimizes any
steric hindrance between the base and the
leaving group.
70
E2 Stereochemistry
71
E1 or E2 Mechanism?
• Tertiary > secondary • Tertiary > secondary

• Base strength unimportant • Strong base required
(usually weak)
• Good ionizing solvent • Solvent polarity not
important.
• Rate = k[alkyl halide] • Rate = k[alkylhalide][base]
• Zaitsev product • Zaitsev product
• No required geometry • Coplanar leaving groups
(usually anti)
• Rearranged products • No rearrangements
72
Substitution or Elimination?
• Strength of the nucleophile determines order:

Strong nucleophiles or bases promote
bimolecular reactions.
• Primary halides usually undergo SN2.
• Tertiary halides are a mixture of SN1, E1, or E2.
They cannot undergo SN2.
• High temperature favors elimination.
• Bulky bases favor elimination.
73
Secondary Alkyl Halides
• Secondary alkyl halides are more challenging:

– Strong nucleophiles will promote SN2/E2.
– Weak nucleophiles promote SN1/E1.
• Strong nucleophiles with limited basicity favor SN2.
Bromide and iodide are good examples of these.
74
Solved Problem 1
Predict the mechanisms and products of the following reaction.
Solution
75
Solved Problem 2
Predict the mechanisms and products of the following reaction.
Solution
76

CHEM 2411 Chapter 06 Lecture Final Kirberger

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CHEM 2411 Chapter 06 Lecture Final Kirberger

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Organic Chemistry,

• Halogens more EN than C.

• You may encounter common names where the

CH3 CH3 CH3

• CH2X2 is called methylene halide.

• Common halogenated solvents:

• Methyl halides: Halide is attached to a methyl group.

• Geminal dihalide: Two halogen atoms are

• Industrial and household cleaners.

• Electronegativities of the halides:

Notice how the four symmetrically oriented polar bonds

• Greater intermolecular forces, higher b.p.

• Alkyl fluorides and alkyl chlorides (those

• Free radical halogenation (Chapter 4)

• Chlorination is not selective.

• Allylic radicals are resonance stabilized.

• The mechanism involves an allylic radical

• N-Bromosuccinimide (NBS) is an allylic

File Name: AAAKWEA0

• The halogen atom on the alkyl halide is replaced with the

• Bimolecular nucleophilic substitution (SN2).

• The SN2 reaction is a one-step reaction.

• Stronger nucleophiles react faster.

• Basicity is defined by the equilibrium constant for

• A negatively charged nucleophile is stronger than its

• Nucleophilicity decreases from left to right:

• Increases down periodic table, as size and

• Polar protic solvents have acidic hydrogens (O—H or N—

• Polar aprotic solvents do not have acidic protons and

• Crown ethers solvate

The best leaving groups are:

• Relative rates for SN2:

CH3X > 1° > 2° >> 3°

• Tertiary halides do not react via the SN2

• Nucleophile approaches from the back side.

SN2 reactions will result in an inversion of

• The SN1 reaction is a unimolecular

Step 1: Formation of the carbocation.

Step 2: Attack of the nucleophile.

• If the nucleophile is an uncharged molecule like water or an alcohol, the positively

Formation of carbocation (rate-determining step)

• The nucleophile attacks the carbocation,

• If the nucleophile was neutral, a third step

• Order of reactivity follows stability of

© 2013 Pearson Education Inc.

• Polar protic solvent is best because it can solvate

• Carbocations are sp2 hybridized and trigonal planar. The

Carbocations are stabilized by inductive effect and by

The SN1 reaction produces mixtures of enantiomers. There

• Carbocations can rearrange to form a more stable

• Since a primary carbocation cannot form, the methyl group on the

• Elimination reactions produce double bonds.

Step 1: Ionization to form a carbocation.

Step 2: Solvent abstracts a proton to form an alkene.

tetrasubstituted trisubstituted disubstituted monosubstituted

• The more substituted double bond is more stable.

• If more than one elimination product is possible,

• Substitution results from nucleophilic attack on the

• React with its own leaving group to return

• Order of reactivity for alkyl halides:

• The halide and the proton to be abstracted must

• Tertiary > secondary • Tertiary > secondary

• Strength of the nucleophile determines order: