ORGANIC CHEMISTRY

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Chapter 9: ALKYL HALIDES

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 NOMENCLATURE OF ALKYL
HALIDES
Common names: alkylhalide (chloride, bromide…)

IUPAC names: halogeno + alkane (chloro, bromo…)

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Alkyl & halogen substituents are considered of
equal rank
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PREPARATION OF ALKYL HALIDES
Alkyl halides from alcohols

Only in acidic conditions

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Alkyl halides from alkenes

More stable

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 Alkyl halides from alkanes

Chlorination is much less selective

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REACTIONS OF ALKYL HALIDES
NUCLEOPHILIC SUBSTITUTION REACTIONS

SN1 vs SN2 – depending on alkyl structure,

nucleophile concentration & reactivity, and solvent
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 Stereochemistry of SN2 reactions

• The nucleophile attacks from the back side / the side

directly opposite the leaving group
• This attacks causes an inversion of configuration
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 Stereochemistry of SN1 reactions

•The nucleophile attacks from the back side & the front side at equal rates
• This results in the products being formed as a racemic mixture 10
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 BE CAREFUL!!!
Rearrangements in SN1

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 BE CAREFUL!!!
Rearrangements in SN1

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Factors affecting the rates of
SN1 & SN2

1. The structure of the substrate

2. The concentration & reactivity of

the nucleophile

3. The reaction solvent

4. The nature of the leaving group

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 Affects of substrate structure

Steric
hindrance
Steric effect in the SN2 reaction
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Affects of nucleophile concentration
& strength
1) Neither the concentration nor the
structure of the nucleophile affects the
rates of SN1 reactions since the
nucleophile does not participate in the
rate-determining step

2) The rates of SN2 reactions depend on

both the concentration and the structure
of the nucleophile
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 Nucleophilicity and basicity
The same attacking atom: a negative charge has stronger
basicity and better nucleophilicity than a neutral.

The attacking atoms are similar size: stronger basicity

means better nucleophilicity.

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 Nucleophilicity and basicity
The attacking atoms are very different in size: the smaller
has stronger basicity while the larger has greater
polarizability.

=> Nucleophilicity depends on the solvent.

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Nucleophilicity and basicity

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 Nucleophilicity and basicity

Nucleophilicity is affected by steric effect.

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Exercise

Compare nucleophilicity in an aqueous

solution of the following compounds:

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 Affects of solvents

Generally, polar aprotic solvents are good for SN2 reactions

while polar protic solvents are good for SN1 reactions
 Affects of leaving group
The best leaving groups are weak bases

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SN1 vs SN2

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 BE CAREFUL!!!
Benzyl/allyl halides vs. aryl/vinyl halides
Benzyl and allyl halides are REACTIVE
in both SN1 and SN2 reactions

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 BE CAREFUL!!!
Benzyl/allyl halides vs. aryl/vinyl halides
Benzyl and allyl halides are REACTIVE
in both SN1 and SN2 reactions

Resonance structures of allyl cation

could result in regioisomeric products. 28
 BE CAREFUL!!!
Benzyl/allyl halides vs. aryl/vinyl halides
Aryl and vinyl halides are UNREACTIVE
in both SN1 and SN2 reactions reactions

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Exercise
Which reaction in each of following pairs of nucleophilic
substitution reactions occurs more readily?
Exercise
Which reaction in each of following pairs of nucleophilic
substitution reactions occurs more readily?
Exercise
Draw products (ignore stereoisomerism) obtained
from nucleophilic substitution reactions of:
Exercise
Draw products (regarding stereoisomerism)
obtained from nucleophilic substitution reactions of:
 ELIMINATION REACTIONS

In an elimination reaction:
+ Groups / atoms are eliminated from a reactant
+ A double bond is formed between the 2 carbons
from which atoms are eliminated
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 BIMOLECULAR ELMINATION (E2)

Strong base

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Regioselectivity of E2 reactions

Zaitsev’s rule for an E2 reaction:

more substituted alkene
is normally obtained

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Keep in mind that the major product of an E2
reaction is always the more stable alkene
(not always the more substituted alkene)

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In some E2 reactions, the less stable alkene is the
major product due to steric effects
Zaitsev’s product

Hofmann’s product
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 In E2 reactions of alkyl fluorides,
the less stable alkene is the major product
Zaitsev’s product

Hofmann’s product

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Reactivities of alkyl halides in an E2 reaction:

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 Stereochemistry of E2 reactions

highly favored in an E2 reaction

2 groups / atoms are removed from

opposite sides of C-C bond

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 Stereochemistry of E2 reactions
A reactant with one hydrogen on the b-carbon
One stereoisomer is formed and the configuration of the
product depends on the configuration of the reactant

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 Stereochemistry of E2 reactions
A reactant with two hydrogen on the b-carbon
Two stereoisomer are formed and the major product is the alkene
with the largest groups on opposite sides of the double bond

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UNIMOLECULAR ELMINATION (E1)

Weak base

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BE CAREFUL!!!
Rearrangements in E1

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Regioselectivity of E1 reactions: like E2,
the major product of an E1 reaction is the
more stable alkene

Reactivities of alkyl halides in an E1

reaction:
- Tertiary alkyl halides readily undergo E1
reactions while primary alkyl halides do
not undergo E1 reactions.
- Reactivity decreases when going from
R-I to R-F.
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 Stereochemistry of E1 reactions
The carbocation formed in the 1st step is planar,
so both syn & anti-elimination can occur
Two stereoisomer are formed and the major product is the alkene
with the largest groups on opposite sides of the double bond

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Exercise
Complete following reactions
(ignore stereoisomerism):
Exercise
Complete following reactions
(regarding stereoisomerism):
 SN vs E

High temperature favors elimination 50

Exercise
Complete following reactions
and determine their mechanisms:
Functional group interconversions
of 1o & 2o alkyl halides

Elimination reactions will occur for 3o alkyl halides

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Elimination reactions will occur for 3o alkyl halides

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Williamson ether synthesis

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Nucleophilic substitution

Elimination

Less hindered alkyl group is provided by the

alkyl halide and the more hindered alkyl group
comes from the alkoxide ion.
Intermolecular vs. intramolecular reactions

Intramolecular reactions are favored when:

- low concentration of reactant
- If the intramolecular reaction forms a five- or
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six-membered ring
Exercise
Determine the reactants used to
prepare following compounds:
GRIGNARD REAGENTS

Strong base

Strong nucleophile 58
REACTIONS OF GRIGNARD REAGENTS

Strong
base

Grignard reagents readily react with acidic

groups: -OH, -NH2, -NHR, -SH, -CCH, -COOH59
Reactions of Grignard reagents with
aldehydes & ketones

Only for the reaction of HCHO 60

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Numbers 1 & 2 are used to indicate that the acid is not added
until the reaction with the Grignard reagent is complete

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Reactions of Grignard reagents with
esters

Can NOT be isolated

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 Can be chiral

Alcohols from esters / acyl halides Can NOT be chiral 65

Reactions of Grignard reagents with
nitriles

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Reactions of Grignard reagents with
carbon dioxide

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Reactions of Grignard reagents with
epoxides

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Exercise
Complete following reactions:
Exercise
Complete following reactions:
 Exercise
Prepare the following compound by 4 ways from
benzene, acetylene, CH3OH, H2, Lindlar Pd, FeCl3,
Mg, dry ether, H2O, H2SO4, Br2, CH3COCl,
CH3CH2COCl, HgSO4, NaNH2 and HBr:
Exercise
Prepare following compounds from starting
materials (can use organic chemicals with no
more than 2 carbons and inorganic chemicals):
 Exercise
Prepare following compounds from benzene,
CH3CH2Br, CH3CH2COCl, (CH3)2CHCOCl, AlCl3,
FeBr3, Br2, NaCN, HCl, H2O, Zn, Hg, Mg, dry ether,
ethylene oxide, HBr, H2SO4, PBr3, pyridine,
NH2NH2, NaOH, CO2, HCHO and KMnO4: