6-SN2(online).pptxConsider electron density distribution
Bond Polarity Allows the Bond to be Broken Easier
When X leaves and Y attacks (concerted or sequentially) determines the type of reaction
This process does not occur with alkanes (carbon-carbon bonds are difficult to break)
Type of Reactions that can Occur with Alkyl Halides
Substitutions: a halide ion is replaced by another atom or ion during the reaction
Therefore the halide ion has been substituted with another species
Eliminations: a halide ion leaves with another atom or ion -no other species is added to the structure
Therefore something has been eliminated
Nucleophilic vs. Electrophilic
Lewis introduced the terms nucleophile and electrophile to describe Lewis acids and bases
Nucleophile: a species that is attracted to the nucleus of another atom (therefore any species attracted to a positive charge)
Nucleo - nucleus Phile - attract
Electrophile: a species that is attracted to electrons (therefore attracted to a negative charge)
Electro - electron Phile - attract
Some Common Nucleophiles and Electrophiles Already Observed
HO CH3O
Amines with lone pair of electrons
Negatively charges ions Or species having a lone pair of electrons
Electrophiles
Carbon is a typical electrophilic site (electrophilic carbon)
When attached to a good leaving group
One Type of Substitution, SN2
Substitution – Nucleophilic – Bimolecular (2)
One substituent is substituted by another
Both the original starting material and the nucleophile (which becomes part of the product) are involved in the transition state for the rate determining step
Therefore this is a bimolecular reaction
Potential Energy Diagram for SN2
Species in a Given SN2 Reaction
nucleophile electrophile transition state products
Electron rich nucleophile reacts with electron poor electrophile
A SN2 reaction is dependent upon the characteristics of the nucleophile and substrate (electrophile)
Kinetics
A SN2 reaction is a second order reaction
First order in respect to both the nucleophile and the electrophile
Rate = k [CH3I][HO-]
Both methyl iodide and hydroxide are involved in the transition state so they both are involved in the rate equation
Factors Affecting Nucleophile Characteristics
1) Strength of nucleophile
A strong nucleophile has a high density of electrons available to form a new bond
H2O HO-
Strength of Nucleophile is also Determined by the Polarizability
During a SN2 reaction the nucleophile is forming a new bond with the electrophilic carbon
If the nucleophilic atom is more polarizable then the new bond can form at longer distances
Polarizability increases down the periodic table
Trends in Nucleophilicity
- A species with a negative charge is a stronger nucleophile than a similar species without a negative charge. In other words, a base is a stronger nucleophile than its conjugate acid
- Nucleophilicity decreases from left to right along a row in the periodic table. Follows same trend as electronegativity (the more electronegative atom has a higher affinity for
electrons and thus is less reactive towards forming a bond)
-Nucleophilicity increases down a column of the periodic table, following the increase in polarizability
2) Solvent Effects
Solvation impedes nucleophilicity
In solution, solvent molecules surround the nucleophile the solvent molecules impede the nucleophile from attacking the electrophilic carbon
smaller anions are more tightly solvated than larger anions in protic solvents
Any solvent with acidic hydrogens are protic solvents (usually involves O-H or N-H bonds)
Alcohols (methanol, ethanol, etc.) and amines are therefore protic solvents
To increase nucleophilicity of anions a solvent is necessary that does not impede the nucleophile (thus does not solvate the charged species)
Use polar/aprotic solvents (have dipole with no O-H or N-H bonds)
H3C C N H3C
acetonitrile acetone dimethylformamide (DMF)
Remember the Rate of a SN2 Reaction is Related to the Transition State Structure
The higher the energy of this structure, the higher the energy of activation
3) Sterics of Nucleophile
As the site of negative charge in the nucleophile becomes more sterically hindered the reaction becomes slower (higher energy of activation
ethoxide anion tert-butoxide anion
1) Leaving group ability
For a SN2 reaction to proceed not only is a strong nucleophile required but there must also be a good leaving group
Requirements: Electron withdrawing
(polarizes C-X bond to make carbon more electrophilic)
Needs to be stable after gaining two electrons (therefore not a strong base)
As polarizability increases, rate increases (stabilizes the transition state)
Leaving Group Stability
The stability of the leaving group is manifest in the energy diagram
-If it is unstable the energy of the products will be high therefore the reaction will become endothermic and
the equilibrium will favor the starting materials
-In the transition state the leaving group is only partially bonded therefore if the energy of the leaving group is high the energy of the transition state will also be high
and thus the rate will be slower
What makes a stable leaving group?
Good leaving groups are WEAK bases
Therefore the conjugate base of a strong acid can be a good leaving group
A leaving group obtains excess electron density after the reaction
Ability to handle the excess electron density determines the leaving group stability
Most Strong Nucleophiles are Poor Leaving Groups
Since strong nucleophiles have a high electron density at the reacting site this makes them poor leaving groups, which need to spread out the excess
electron density over the molecule
There are notable exceptions - Primarily the halides
I-, Br-, Cl- are good leaving groups and are also nucleophilic
Fluoride is the Exception
F- is a very poor leaving group - Should never have F- leave in a SN2 reaction
Due to poor polarizability of fluoride
Same reason why fluoride is a worse nucleophile than the other halogens, the leaving group needs to be polarizable to lower the energy of the transition state
2) Sterics of Substrate
As the number of substituents on the electrophilic carbon increases the rate decreases
Consider Approach of Nucleophile
Nucleophile must be able to react with electrophilic carbon in a SN2 reaction
Nucleophile must be able to react with “blue” electrophilic carbon for reaction to proceed
As the Length of a Substituent Chain Increases the Sterics Do Not Increase
As the Bulkiness, or Branching, of a Substituent Increases Though the Rate Drops Dramatically
Stereochemistry of SN2 Reaction
As the electrophilic carbon undergoes a hybridization change during the course of the reaction the substituents change in this view from pointing to the left in the starting material
to pointing to the right in the product
This is referred to as an “inversion of configuration” at the electrophilic carbon
Therefore the stereochemistry changes (three-dimensional arrangement in space)
Consequence of Inversion in a SN2 Reaction
A chiral carbon is still chiral but the chiralty is inverted (the R and S designation usually change