Chapter 9

ALKYL HALIDES
1
NOMENCLATURE
IUPAC name: alkyl group + halide
2
NOMENCLATURE
3
HOW ALKYL HALIDES REACT
Nucleophilic substitution (SN)
Example
4
Bimolecular nucleophilic substitution (SN2)
5
Biomolecular nucleophilic substitution (SN2)
6
Effect of nucleophile
7
Effect of nucleophile
8
Trends in nucleophilicity
A negative charge is a stronger nucleophile than a neutral.
From left to right in the periodic table: nucleophilicity decreases
Down the periodic table: nucleophilicity increases
9
Trends in nucleophilicity
Comparison of fluoride and iodide ions
10
Steric effect on nucleophilicity
11
Effect of alkyl halides
Reactivity: CH3 > primary > secondary, no reaction

for tertiary alkyl halides. 12
Effect of solvent
Polar, protic solvents (water, alcohols)

are not good for SN2. 13
Effect of solvent
Polar, aprotic solvents such as DMF, DMSO,

acetone, acetonitrile are great choices for SN2. 14
Effect of leaving group
Good leaving groups should be weak bases
15
Opposite-side substitution -> inversion of configuration at

the asymmetric carbon
16
inversion of
configuration
inversion of
configuration
no
inversion!
17
Unimolecular nucleophilic substitution (SN1)
18
Stability of carbocation
would dictate how
easy/difficult the reaction is
19
Stability of carbocations
20
Stability of carbocations
✓ The more substituted carbocation is, the more stable it is.
✓ Allylic and benzylic carbocations are extremely favorable.
21
Effect of solvent
Protic solvents such as water and alcohols are

effective, because solvated ions are stabilized
(by forming hydrogen bonds with solvents).
22
Rearrangement of carbocations
23
Rearrangement of carbocations
24
formation of racemic mixture
25
trigonal planar geometry
Comparison of SN1 and SN2
The most important factor is alkyl halide. 26

Notes in nucleophilic substitution
For benzyl/allyl halides
Benzyl and allyl halides are ACTIVE in both SN1 and SN2
reactions.
27
Resonance structures of the allyl cation could result in

regioisomeric products.
28
For phenyl/vinyl halides
Phenyl and vinyl halides are INERT in either SN1 or SN2

reactions.
29
For phenyl/vinyl halides
very unstable
carbocations 30
Elimination
31
Bimolecular elimination (E2)
Correct
mechanism
highly unfavored!
Incorrect
mechanism
32
Regioselectivity in E2
Following the Zaitsev rule: the more substituted alkene is the

major product.
33
Regioselectivity in E2
Exception 1: the major is the one with conjugated system.
Exception 2: bulky base takes the least hindered proton.
34
Stereoselectivity in E2
E2 is an anti-elimination: H and halogen groups leave from
opposite sites of the reference plane.
35
using sawhorse
projection
the dihedral angle

between C–H and
C–X is 180° 36
only 1H at Ca
37
38
Unimolecular elimination (E1)
Formation of carbocation → rearrangement?

39
Unimolecular elimination (E1)
Critically thinking
of rearrangement!
40
Williamson ether synthesis
Example
41
Williamson ether synthesis
Because the mechanism of the ether synthesis is SN2,
tertiary alkyl halides are INERT.
42
Organometallic compounds
Alkyl halides react with metal to form organometallics that switch
the electronic properties, from electrophilic to nucleophilic.
43
Grignard reagent
Examples
Solvents for synthesis

of Grignard reagents 44
Grignard reagent
Grignard reagents are very strong bases!!!
Grignard reagents are not tolerant in the presence of

compounds with acidic protons such as carboxylic acids,
alcohols, phenols, water, terminal alkynes.
45
Reactions of Grignard reagent
With CO2
H2O is also OK
46
With CO2
Examples
47
With aldehydes/ketones
Grignard reagent reacts with HCHO to afford primary alcohols.
48
Grignard reagent
reacts with aldehydes
not HCHO to afford
secondary alcohols.
Example
49
Grignard reagent
reacts with ketones to
afford tertiary
alcohols.
Example
50
With epoxides
S N2
51
With epoxides
Grignard reagent attacks the less hindered carbon of the
unsymmetrical epoxide.
52
Synthesis of alkyl halides
Free-radical halogenation of alkanes
Chlorination is
not selective if
there are more
than one active
C–H bond.
53
Free-radical halogenation of alkanes
Halogenation is selective to the C–H bond adjacent

to the benzene ring/conjugated system.
54
Reactions of alcohols with hydrogen halides
The reactions only occur in the presence of acid.
55
Mechanism
Formation of carbocation → rearrangement? 56

57

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Chapter 9

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ALKYL HALIDES

IUPAC name: alkyl group + halide

From left to right in the periodic table: nucleophilicity decreases

Down the periodic table: nucleophilicity increases

Steric effect on nucleophilicity

Reactivity: CH3 > primary > secondary, no reaction

Polar, protic solvents (water, alcohols)

Polar, aprotic solvents such as DMF, DMSO,

Good leaving groups should be weak bases

Opposite-side substitution -> inversion of configuration at

Protic solvents such as water and alcohols are

formation of racemic mixture

The most important factor is alkyl halide. 26

Resonance structures of the allyl cation could result in

Phenyl and vinyl halides are INERT in either SN1 or SN2

Following the Zaitsev rule: the more substituted alkene is the

Exception 1: the major is the one with conjugated system.

Exception 2: bulky base takes the least hindered proton.

the dihedral angle

Formation of carbocation → rearrangement?

Solvents for synthesis

Grignard reagents are not tolerant in the presence of

Halogenation is selective to the C–H bond adjacent

The reactions only occur in the presence of acid.

Formation of carbocation → rearrangement? 56

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