(CHP - 225)

Chapter 11

Reactions of Alkyl Halides:

Nucleophilic Substitutions
and Eliminations

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Nucleophilic substitution and base-induced elimination are two of the most
widely occurring and versatile reaction types in organic chemistry

 Alkyl halides possess a substantial dipole moment

 Slight positive charge (δ+) on carbon atoms
 Slight negative charge (δ-) on halogens
 Carbon atom in C─X bond is considered to behave as an electrophile in
polar reactions

11.1 The Discovery of Nucleophilic Substitution Reactions

In 1896, Walden showed pure enantiomeric (+)- and (–)- malic acids can be
interconverted through a series of simple substitution reactions.

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Following the work of Walden, further investigations were undertaken during the
1920s and 1930s to clarify the mechanism of nucleophilic substitution reactions
and to find out how inversions of configuration occur.

The inversion of stereochemical configuration must therefore take place in step 2,

the nucleophilic substitution of tosylate ion by acetate ion.

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11.2 The SN2 Reaction
short for substitution, nucleophilic, bimolecular reaction.

 SN2 Reactions are second order reactions.

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 Factors Effecting SN2 Reactions

1. The Substrate
Steric Effects in the SN2 Reaction

 The more the alkyl groups connected to the reacting carbon, the slower the
reaction

• Vinylic halides (R2C = CRX) and aryl halides are not shown on
this reactivity list because they are unreactive toward SN2
displacement. This lack of reactivity is due to steric factors:

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2. The Attacking Nucleophile

• Nucleophilicity roughly parallels basicity

• Nucleophilicity usually increases going down a column of the
periodic table.
• Negatively charged nucleophiles are usually more reactive than
neutral ones.

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3. Leaving Group
Leaving group (leaving nucleophile) that provide optimal stability to
the negative charge in the transition state are considered the best.

● Weak bases are good leaving groups, and strong bases are poor
leaving groups

–
● Since OH is a poor leaving group, SN2 reaction with an alcohol
requires conversion to an alkyl chloride, an alkyl bromide or
tosylate using thionyl chloride (SOCl2), phosphorus tribromide
(PBr3) or para-toluenesulfonyl chloride.

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 ● Generally, ethers do not undergo SN2 reactions. Epoxides are an
exception as they are more reactive due to angle strain than
ethers

4. The Solvent

Polar aprotic solvents, which are polar but don’t have an -OH or -NH
group, are the best.

• Protic solvents, such as methanol and ethanol, slow down S N2

reactions by solvation of the reactant nucleophile. The solvent
molecules hydrogen-bond to the nucleophile and form a cage
around it, thereby lowering its energy and reactivity.

• Polar aprotic solvents increase the rate of S N2 reaction by

increasing the ground energy of the nucleophile. High polarity
gives it the ability to dissolve a number of salts, but they tend to
solvate metal cations instead of nucleophilic anions.

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DMF dimethylformamide (CH3)2NCHO,
DMSO dimethyl sulfoxide (CH3)2SO
HMPA hexamethylphosphoramide (CH3)2N]3PO
MeCN Acetonitrile (CH3CN),

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11.4 The SN1 Reaction
short for substitution, nucleophilic, unimolecular
reaction.
 Tertiary alkyl halides react rapidly in protic solvents like water which also
act as a neutral nucleophile.

Reaction rate = Rate of disappearance of alkyl halide

= k  [RX]

SN1 reactions are first-order reactions and takes place in two steps.

 In first step alkyl halide dissociates spontaneously in the slow, rate

limiting step to generate a carbocation intermediate.
 In the second step, the carbocation intermediate reacts with water as a
nucleophile in a fast step to yield protonated alcohol as product.
 The rate equation does not contain the concentration of the
nucleophile

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 Characteristics of carbocations:
 Planar
 sp2-hybridized
 Achiral

 A symmetric intermediate carbocation reacts with a nucleophile equally

from either sides to produce a racemic, 50:50 enantiomer mixture
 In some cases, SN1 reactions with enantiomerically pure substrates result in
racemization with an excess of 0–20%

 Saul Winstein proposed that the presence of the two ions by

dissociation of the substrate shields the carbocation at one side from
reacting with the departing ion

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 Factors Effecting SN1 Reactions
1. The Substrate

Stability of the carbocation intermediate determines the rate of the S N1

reaction

i. More substituted carbocation is more stable

ii. More resonance forms of a carbocation leads to more stability

 Allyl Carbocation

 Benzyl Carbocation

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 iii. Primary allylic and benzylic substrates react well in both S N2 and
SN1 reactions as they are about 50 kJ/mol weaker than the
corresponding saturated bonds and are therefore more easily broken.

2. The Attacking Nucleophile

The added nucleophile is not associated with the rate-limiting method of the
SN1 reaction and hence has no influence on the reaction rate

3. Leaving Group
Like SN2 reaction in SN1 reaction, the best leaving groups are those that are
most stable (that is, those that are the conjugate bases of strong acids).

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4. The Solvent Polar protic solvents are best for SN1 reaction as they

i. stabilize the carbocation by solvation.

ii. decreases the transition-state energy leading to carbocation

intermediate hence increases the rate of SN1 reaction

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11.7 Elimination Reactions

A nucleophile/Lewis base reacts with an alkyl halide resulting in a

substitution or an elimination

Zaitsev’s Rule

In the elimination of HX from an alkyl halide, the more highly

substituted alkene product predominates

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E2 reaction (Elimination, bimolecular) (1 step reaction)

 Simultaneous cleavage of C–H bond and C–X bond produces the alkene
without intermediates

E2 reactions show second-order kinetics

Rate Law: rate = k [RX] [Base]

Factors Favoring E2
• Leaving group should be of medium characteristics
i. Good leaving group favors E1 reaction
ii. Bad leaving group like -OH needs to be protonated and reaction
becomes dehydration
- -
• Strong Base base should have strong basic characteristics e.g. OH or RO
and very weak nucleophilic characteristics
• Bulky substrate so that base could not reach positively charged C of C – X bond
to avoid SN2.
• Alcohol as solvent to make base more bulky so that it could not reach
positively charged C of C – X bond to avoid SN2.

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 Syn periplanar geometry: H and X are on the same side of the molecule
Anti periplanar geometry: H and X are on opposite sides of the molecule

Anti periplanar geometry is preferred over syn periplanar geometry in

E2 reactions. It is because like SN2 in an E2 reaction, an electron pair from a
neighboring C – H bond pushes out the leaving group on the opposite side of
the molecule.

The anti periplanar requirement for E2 reactions overrides Zaitsev’s rule and can
be met in cyclohexanes only if the hydrogen and the leaving group are trans
diaxial. If either the leaving group or the hydrogen is equatorial, E2 elimination
can’t occur.

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E1 Reaction (Elimination, unimolecular) (2 step reaction)

i. C–X bond breakage to produces a carbocation (R+) intermediate

ii. C–H bond breakage to abstract H+

E1 reactions show first-

order kinetics

Rate Law: rate = k [RX]

Factors Favoring E1 • Good leaving group (so C–X bond breakage

takes place in first step)
• Weak base (to let it be a subsequent step)

● Normally both E1 and SN1 reactions occur together

● There is no geometric requirement on the E1 reaction because the

halide and the hydrogen are lost in separate steps.

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E1cB Reactions (Elimination, unimolecular, conjugate base) (2 step reaction)

i. C–H bond breakage yielding a carbanion (R-) intermediate

ii. C–X bond breakage yielding the alkene

In contrast to the E1 reaction, which involves a carbocation

intermediate, the E1cB reaction takes place through a carbanion
intermediate.

Factors Favoring E1cB

• Bad leaving group e.g. -OH (so C–H bond breakage takes
place in first step)
• The substrate is usually an alcohol rather than an alkyl
halide, and the H atom removed is usually adjacent to a

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 carbonyl group

The poor leaving group disfavors the alternative E1 and E2 possibilities, and the carbonyl group
makes the adjacent hydrogen unusually acidic by resonance stabilization of the anion
intermediate. We’ll look at this acidifying effect of a carbonyl group in Section 22-5.

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