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Page 1: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

Alkyl Halides

Why are alkyl halides reactive?

Consider electron density distribution

Page 2: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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)

Page 3: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 4: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

**Therefore nucleophiles are often negatively charged species and electrophiles are positively charged species

Page 5: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

Some Common Nucleophiles and Electrophiles Already Observed

HO CH3O

Cl Br I

H3N

Nucleophiles

Hydroxides or alkoxides

halides

Amines with lone pair of electrons

Negatively charges ions Or species having a lone pair of electrons

Electrophiles

H3C Br

!+ !-

Positive or partially positive sites

Carbon is a typical electrophilic site (electrophilic carbon)

When attached to a good leaving group

Page 6: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 7: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

Potential Energy Diagram for SN2

Page 8: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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)

Page 9: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 10: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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-

Electron density plots

Page 11: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

Ea Lowers with Stronger Nucleophile

Page 12: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 13: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 14: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 15: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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 NH3C

O

CH3H

O

NCH3

CH3

acetonitrile acetone dimethylformamide (DMF)

Page 16: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 17: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 18: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

Substrate (Electrophile) Factors for SN2 Reactivity

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)

Page 19: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 20: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 21: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 22: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 23: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

2) Sterics of Substrate

As the number of substituents on the electrophilic carbon increases the rate decreases

Page 24: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

Page 25: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

As the Length of a Substituent Chain Increases the Sterics Do Not Increase

Page 26: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

As the Bulkiness, or Branching, of a Substituent Increases Though the Rate Drops Dramatically

Page 27: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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)

Page 28: Alkyl Halides Why are alkyl halides reactive? Consider ...utdallas.edu/~biewerm/6-SN2.pdf · Why are alkyl halides reactive?! Consider electron density distribution! ... In solution,

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

but this depends on the priority of the new substituents)


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