Chapter 11

Displacement Reactions
On Saturated Carbons:
SN1 & SN2 Substitution
Reactions

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 Learning Goals
• Be able to draw the two mechanisms of substitution reactions, explain their kinetics
& the steps.
• Know the factors that can affect these two substitution mechanisms.
• Be able to explain the order of reactivity of the various alkyl halides for SN2 & SN1
rxns.
• Be able to explain how the solvent can affect SN1 & SN2 reactions.
• Be able to explain how the nucleophile can affect both substitution reactions.
• Be able to explain how the leaving group can affect both substitution reactions.
• Be able to show the differences between SN1 & SN2 reactions using chiral
substrates.
• Be able to write an order of reactivity for a series of nucleophiles in protic & aprotic
solvents.
• Be able to work out which of a pair of reactions would take place more quickly
• Be able to work out whether a reaction will take place by the SN1 or SN2 routes,
using the reaction conditions & solvents given.
• Recognize when a carbocation rearrangement will occur and predict the products
formed in the SN1 reaction. 2
 Displacement Reactions of
Alkyl Halides
Displacement reaction: one component of a molecule
is replaced by another

Nucleophilic substitution reaction: a displacement

reaction in which a nucleophile displaces another group

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 Reaction Rates of SN2 Displacements

SN2 stands for substitution nucleophilic bimolecular.

It involves a bimolecular rate-determining step.

SN2 proceeds in a single step in a concerted reaction.

All bond-making and bond-breaking steps occur simultaneously.
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 Mechanisms for SN2 Displacements

Mechanism for SN2 displacement reactions can vary depending on

whether the nucleophile is negatively charged or neutral.

Negative nucleophile:

Neutral nucleophile:

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 Stereochemistry of SN2 reactions
The SN2 reaction inverts the configuration of the a-carbon.

• The nucleophile approaches the a-carbon from the opposite side of the
leaving group by in-line fashion.
• This is sometimes called a “backside attack.”
• Frontside approach is sterically impeded by the presence of the
departing leaving group.
• Backside approach allows for optimal overlap of the interacting orbitals.

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 Nucleophilicity in SN2 Displacement Reactions

The ability of the nucleophile to donate electrons is the most

significant determinant of SN2 rate.

Effect of negative charge: Negatively charged bases have

more available electrons compared to their conjugate acids.
- better electron donors

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 Effect of Electronegativity

Atoms with higher electronegativity are less nucleophilic because

they are less able to share their valence electrons to make a bond.

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 Effect of atomic size
• Large atoms hold their valence electrons less tightly.
• Electron clouds can more easily be distorted by nearby
charges (more polarizable).
• Electrons can be attracted to nearby positive charges to make
bonds (increases nucleophilicity).

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Effect of Electron Delocalization
Delocalization in nucleophiles usually impairs their reactivity.

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Steric Congestion near the Nucleophilic Atom
Reactivity of nucleophile is impaired by steric congestion
near the nucleophilic atom.

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 Structure of the Electrophile in SN2 Displacement
Reactions

Halogens as leaving groups

• The same factors that make a weak base also make a good
leaving group.

• Halogens are a very common leaving group for

displacement reactions because the halides are all weak
bases.

halogen leaving
group ability

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 Ways to Convert OH Groups into
Good Leaving Groups
OH− is a poor leaving group (strong base).It can be converted to a good leaving
group using two main approaches:
Method 1: Acid catalysis

General principle of catalysis:

• a base accelerates reactions by activating the nucleophile
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• an acid accelerates reactions by activating the electrophile
Method 2: Sulfonate esters
A strong electron-withdrawing group is attached to oxygen,
which significantly reduces its basicity. Sulfonate anions are
excellent leaving groups.

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Electrophile Substitution Patterns Near the a-Carbon
The number of substituents on the a-carbon influences the
mechanism of the displacement reaction.

Tertiary alkyl substrates proceed via SN1 mechanism (to be

discussed next).
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 Reaction Rate of SN1 Mechanism
SN1 stands for substitution nucleophilic unimolecular.
Involves a unimolecular rate-determining step.

SN1 reactions involve several steps.

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 Carbocations Stabilized by Charge Delocalization
• Substrates that form stabilized cations tend to undergo SN1
reactions.

They may form more than one product.

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Nucleophilic reactions of oxonium ions

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 Carbocation Rearrangements
Presence of a carbocation can complicate SN1 displacements because it provides
an opportunity for competing reactions
to occur. Rearrangements are common.

Carbocations are more stable when they have more substituents. Rearrangements
occur when it is possible to form a more stable carbocation.

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 Allylic and Benzylic Cations

Allylic and benzylic cations can form from rearrangements

due to their particularly high stability.

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Alkyl Group Migrations and Carbocation Stability

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 Effect of the Leaving Group
In general, good leaving groups such as the sulfonate groups
(OTs, OMs, OTf ) accelerate SN1 reactions.

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 Stereochemistry of SN1 reactions
Recall: Carbocations are sp2 hybridized and flat.
Nucleophiles are free to approach either side of these ions.

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 SN1 and SN2 as a Reactivity Continuum
Although we identify SN1 and SN2 as distinct mechanisms,
many nucleophilic displacements have characteristics of both.
Evidence for reactivity continuum:
1. Many SN2 substrates are sensitive to inductive effects.

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 SN1 and SN2 as a Reactivity Continuum

2. SN1 reactions that produce completely racemic products

from enantiomerically pure starting materials are rare.

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 Different Solvent Effects
In general:
• Protic solvents (H2O, alcohols, amines)
➢ stabilize carbocations very well
➢ very polar and capable of extensive hydrogen bonding
➢ effective at solvating small anions, which decreases
nucleophilicity
➢ favour SN1 reactions

• Polar aprotic solvents

➢ enhance nucleophilicity
➢ favour SN2 reactions

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 Polar Protic Solvents and SN1
Reactions

Protic solvents accelerate SN1 reactions by

• hydrogen bonding to the leaving group, assisting its departure
• stabilization of the carbocation by donation of a pair of
electrons

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 Polar Aprotic Solvents

Polar aprotic solvents do not have a hydrogen bond donating

group.
They cannot solvate anions, which increases nucleophilicity.

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 Predicting SN1
and SN2 Reaction Mechanisms

To predict mechanism of nucleophilic displacement,

three characteristics of the reaction must be examined:
1. structure of the electrophile
2. strength of the nucleophile
3. solvent

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1. Structure of the Electrophile
This is the most important feature in distinguishing SN1 and
SN2.

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2. Strength of the Nucleophile
• Both the SN1 and SN2 pathways are possible in reactions
involving secondary electrophiles and those that can form
stabilized carbocations.
• In these cases, mechanism is determined by nucleophile
strength.

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3. Solvent used

In general, protic solvents strongly favour SN1 reactions, and

aprotic solvents favour SN2 reactions:
• polar protic solvents (H2O, alcohols, amines) stabilize
carbocations (favours SN1)
• aprotic solvents increase nucleophilicity (favours SN2)

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 Practical Considerations for Planning
Displacement Reactions
From a synthesis perspective, SN2 reactions are favoured over SN1 due to the
following:
• lack of carbocation intermediate (less prone to rearrangements and competing
reactions)
• better control of stereochemistry
If SN1 must be used, optimal conditions will be those that strongly favour SN1 (protic
solvent, good nucleophile).

A typical
retrosynthesis for a
displacement
reaction:

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 Special Nucleophiles and Electrophiles Used in
Displacement Reactions
Using hydroxide to generate secondary alcohols is challenging due to its strong
basicity. Often leads to competing elimination product:

Alternative approach: Acetate is less basic, and avoids elimination product.

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 Using Alkoxides to Make Ethers

Williamson ether synthesis:

• SN2 reaction between an alkoxide and an alkyl halide to form
an ether

Typical reaction:

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Typical retrosynthesis for Williamson ether synthesis:

Forward reactions:

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 Using Epoxide Electrophiles in Synthesis
Epoxides have a large amount of ring strain and are easily opened.
Ring opening is regioselective:

Basic conditions:

Acidic conditions:

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Ring opening follows typical SN2 stereochemistry:

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 Role of Nucleophiles in Carbon-Carbon Bond Formation

Acetylides and cyanides:

• These are strong nucleophiles that are able to undergo
controlled SN2 displacements.
• They are useful in forming carbon-carbon bonds.

Nitrile product can be reduced to amine:

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Acetylides are generated by deprotonating acetylenes:

Alkyne can subsequently be reduced by hydrogenation:

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 Primary Amines
• Amines are excellent nucleophiles for SN2 reactions.
• However, adding electron-donating alkyl groups
increases nucleophilicity.
• Controlling substitution reactions is a challenge as the
product is more nucleophilic than the initial reactant:

• To avoid over-alkylation, masked amines are often

used.
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 Gabriel Synthesis

This uses a nucleophilic phthalimide salt to form a product that

can be converted to a primary amine.

Conversion to amine:

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 Azides

Azides can be used to form amines:

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 Key Concepts
• Nucleophilic substitution reactions: SN1 and SN2. nucleophile substitutes for a halogen in
alkyl halide
• SN2: bimolecular, one-step mechanism, two molecules in transition state of RDS, rate depends
on concentration of alkyl halide and nucleophile, inversion of configuration for asymmetric
reactants; favored by high concentration of strong nucleophile in aprotic polar solvent
• SN1: unimolecular, two step mechanism, one molecule in transition state of RDS, rate depends
on concentration of alkyl halide, carbocation rearrangements can occur, racemization for
asymmetric reactants, in most cases solvent is nucleophile (solvolysis); favored by poor
nucleophile in protic polar solvent
• Protic solvent: hydrogen bond donors (water, alcohols, acetic acid)
• Aprotic solvent: NOT hydrogen bond donors (DMF, DMSO, acetonitrile, HMPA, acetone, THF,
DCM, benzene, hexanes, ethyl acetate)
• Rate of reactions affected by leaving group ability: the weaker the base, the better the leaving
group
• Methyl halides and primary alkyl halides: only SN2 reaction
• Tertiary alkyl halides: SN1 reaction
• Vinylic and aryl halides: neither SN2 or SN1
• Secondary alkyl, benzylic and allylic halides: both SN1 and SN2
• If reactants in the RDS are charged: increasing solvent polarity = decrease rate of
reaction
• If reactants in the RDS are neutral: increasing solvent polarity = increase rate of reaction
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Summary: Patterns in Nucleophilic Displacements on
Saturated Carbons

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