Chem 31:

SN1 and SN2 Reactions

Alkyl Halides and their Reactions with Nucleophiles
Nucleophiles and Leaving Groups
Bimolecular vs. Unimolecular Substitution
General Mechanism

What components are needed to perform a substitution?

A. Nucleophile
B. Electrophile with leaving group
• Usually alkyl halides
Alkyl Halides that undergo Substitution
Methyl Primary (1o) Secondary (2o) Tertiary (3o)

Methyl chloride n-Butyl chloride sec-Butyl chloride tert-Butyl chloride

Allyl chloride

Benzyl chloride

Good substrates Bad substrates

Common Alkyl Halides

4
The SN2 Mechanism

• Kinetics: Rate = k[Nuc][Substrate]

• Reaction is concerted.
• Inversion of configuration occurs (Walden Inversion)

(R)-2-chlorobutane
The SN2 Mechanism
• RDS is the approach of the nucleophile to the alkyl halide.
• SN2 is sensitive to sterics
The SN1 Mechanism

• Kinetics: Rate = k[Substrate]

• Reaction is multi-step, the first of which is the loss of a leaving group.
• Racemization occurs, but with slight excess of inverted product.

(R)-2-chlorobutane
The SN1 Mechanism

• The RDS involves the formation of the carbocation.

• The stability of the carbocation determines reactivity to SN1
Drawing SN2 and SN1 Products

Draw the products of the following substitution reactions.

SN2

SN1
Factors that Affect Substitution Reactions

1.Type of substrate (alkyl halide)

2.Nucleophilicity
3.Leaving group capability
4.Solvent
Nucleophilicity

Nucleophilicity – property of a molecule that determines how fast it

reacts with electrophiles.
Basicity – degree to which it can abstract H+ from an acid.
Factors affecting Nucleophilicity

1. Basicity
 Basicity  Nucleophilicity
Factors affecting Nucleophilicity

2. Polarizability
 Polarizability (Size)  Nucleophilicity
Factors affecting Nucleophilicity

3. Steric Hindrance
 Sterics  Nucleophilicity
Factors affecting Nucleophilicity

4. Solvent/Solvation of Nucleophile
Protic solvents decrease nucleophilicity.

Nucleophilicity in protic solvents

F– Cl– Br– I–
Solvation

Which is more nucleophilic: KCN in water or KCN in acetonitrile?

Ashenhurst, J. (2011, Feb. 1). The Most Annoying Exceptions in Org 1 (Part 1). Retrieved May 3, 2018 from
www.masterorganicchemistry.com
Factors affecting Nucleophilicity

Aprotic solvents decrease nucleophilicity.

Stronger bases are more nucleophilic.

Nucleophilicity in aprotic solvents

F– Cl– Br– I–
Basicity

Which is more nucleophilic: OH– or SH– in aprotic solvent?

Some Common Solvents
The Leaving Group
• The leaving group must be stable when it leaves the substrate.
• LG’s are usually conjugate bases of weak acids.
The Leaving Group
Better LG = FASTER SUBSTITUTIONS
Predicting whether SN2 or SN1 will Occur

SN 2
• Needs STRONG nucleophiles
• Me >1o, benzylic, allylic
>2o>>3o
• Favored in aprotic solvent
SN 1
• Can work with WEAK
nucleophiles
• 3o, benzylic allylic > 2o >>
1o > Me
• Favored in protic solvent
Predicting whether SN2 or SN1 will Occur
Choice of Solvent
Choice of Solvent
Choice of Solvent

Reagents/Intermediates in Protic Solvent Reagents/Intermediates in Aprotic Solvent

Determine whether the following
reactions will under unimolecular
or bimolecular substitution.
Determine the reagents needed to perform the
following transformations.
Some Substitution Reactions

Substitutions on Alkyl Halides

Some Substitution Reactions

• Solvolysis
• Synthesis of Alkynes from Acetylene
• Substitutions on Alcohols
• Lucas Test
• Williamson Ether Synthesis
• Epoxide Ring Opening (Base vs. Acid Catalyzed)
• Intramolecular Reactions/Cyclization
Biological SN2 Reactions
• S-adenosylmethionine (SAM) – a coenzyme that is involved in
methyltransferase reactions in biological systems
Biological SN2 Reactions

• Conversion of noradrenaline to adrenaline

Biological SN2 Reactions
• Alkylating agents as carcinogens

O2

Cytochrome P450
Molecular Orbital Theory and SN2

• Why a backside attack?

Nuc : LG
Introduction to Elimination Reactions

• Often, substitution reactions are problematic because of

competing elimination reactions.