Elimination reactions

Chapter 5: Structure and Preparation of Alkenes. Elimination Reactions

In order to view some of the structures for this section, you will need the web "plug-in", "CHIME". If you do not have it already installed, you should be able to download it for free from the linked Website. CHIME is a browser that allows you to visualize and manipulate molecules as 3D structures.  Check here if you don't know how to use Chime.

1,2-elimination

Elimination reactions are important as a method for the preparation of alkenes.
The term "elimination" describes the fact that a small molecule is lost during the process.
A 1,2-elimination indicates that the atoms that are lost come from adjacent C atoms.
The two most important methods are:

There are three fundamental events in these elimination reactions:
  1. removal of a proton
  2. formation of the CC p bond
  3. breaking of the bond to the leaving group
Depending on the relative timing of these events, different mechanisms are possible: In many cases the elimination reaction may proceed to alkenes that are constitutional isomers with one formed in excess of the other. This is described as regioselectivity.

Zaitsev's rule, based on the dehydration of alcohols, describes the preference for eliminations to give the highly substituted (more stable) alkene, which may also be described as the Zaitsev product. The rule is not always obeyed, some reactions give the anti-Zaitsev product.

Similarly, eliminations often favor the more stable trans-product over the cis-product (stereoselectivity)
Carbocations

Stability:
The general stability order of simple alkyl carbocations is: (most stable) 3o > 2o > 1o > methyl (least stable)

[carbocation stability order]

This is because alkyl groups are weakly electron donating due to hyperconjugation and inductive effects. Resonance effects can further stabilize carbocations when present.

Structure:
 
A simple representation of a carbocation
Alkyl carbocations are sp2 hybridized, planar systems at the cationic C center. 
The p-orbital that is not utilized in the hybrids is empty and is often shown bearing the positive charge since it represents the orbital available to accept electrons.
Computer model of CH3+

Reactivity:

electrostatic potential of CH3+ (side view) As they have an incomplete octet, carbocations are excellent electrophiles and react readily with nucleophiles (substitution).
Alternatively, loss of H+ can generate a p bond (elimination).

The electrostatic potential diagrams clearly show the cationic center in blue, this is where the nucleophile will attack.
 

electrostatic potential of CH3+ (top view)

Rearrangements:
Carbocations are prone to rearrangement via 1,2-hyride or 1,2-alkyl shifts provided it generates a more stable carbocation. For example:
 

3,3-dimethyl-2-butanol dehydrates to give mainly 2,3-dimethyl-2-butene
Notice that the "predicted" product is only formed in 3% yield, and that products with a different skeleton dominate. 
The reaction proceeds via protonation to give the better leaving group which departs to give the 2o carbocation shown.  A methyl group rapidly migrates taking its bonding electrons along, giving a new skeleton and a more stable 3o carbocation which can then lose H+ to give the more stable alkene as the major product. 
1,2-alkyl shift
2o carbocation to 3o carbocation

This is an example of a 1,2-alkyl shift.  The numbers indicate that the alkyl group moves to an adjacent position.
Similar migrations of H atoms, 1,2-hydride shifts are also known.

Reactions involving carbocations:
1. Substitutions via the SN1
2. Eliminations via the E1
3. Additions to alkenes and alkynes (HX, H3O+)


E1 mechanism

E1 indicates a elimination, unimolecular reaction, where rate = k [R-LG].
This implies that the rate determining step of the mechanism depends on the decomposition of a single molecular species.

Overall, this pathway is a multi-step process with the following two critical steps:
 

loss of the leaving group creates the carbocation intermediate loss of the leaving group, LG, to generate a carbocation intermediate, then 
base removes a beta proton, forming the C=C loss of a proton, H+, from the carbocation to form the p-bond

Lets look at how the various components of the reaction influence the reaction pathway:

R-
Reactivity order :   (CH3)3C-  >  (CH3)2CH-   >  CH3CH2-  >  CH3-

In an E1 reaction, the rate determining step is the loss of the leaving group to form the intermediate carbocation. The more stable the carbocation is, the easier it is to form, and the faster the E1 reaction will be.  Some students fall into the trap of thinking that the system with the less stable carbocation will react fastest, but they are forgetting that it is the generation of the carbocation that is rate determining. Since carbocation intermediates are formed during an E1,  there is always the possibility of rearrangements (e.g. 1,2-hydride or 1,2-alkyl shifts) to generate a more stable carbocation. This is usually indicated by a change in the position of the alkene or a change in the carbon skeleton of the product when compared to the starting material.
 

-LG
The only event in the rate determining step of the E1 is breaking the C-LG bond. Therefore, there is a very strong dependence on the nature of the leaving group, the better the leaving group, the faster the E1 reaction will be.  In the acid catlaysed  reactions of alcohols, the -OH is protonated first to give an oxonium ion, providing the much better leaving group, a water molecule (see scheme below).

B
Since the base is not involved in the rate determining step, the nature of the base is unimportant in an E1 reaction. However, the more reactive the base, the more likely an E2 reaction becomes.

Selectivity
E1 reactions usually favor the more stable alkene as the major product : more highly substituted and trans- > cis-
 

This E1 mechanistic pathway is most common with:

A typical example is the acid catalyzed dehydration of 2o or 3o alcohols.
 
 
E1 MECHANISM FOR ALCOHOLS
Step 1:
An acid/base reaction. Protonation of the alcoholic oxygen to make a better leaving group. This step is very fast and reversible.  The lone pairs on the oxygen make it a Lewis base.
E1 mechanism for ROH
Step 2:
Cleavage of the C-O bond allows the loss of the good leaving group, a neutral water molecule, to give a carbocation intermediate. This is the rate determining step (bond breaking is endothermic)
Step 3:
An acid/base reaction. Deprotonation by a base (a water molecule) from a C atom adjacent to the carbocation center leads to the creation of the C=C
E1 MECHANISM FOR ALKYL HALIDES
Step 1:
Cleavage of the polarized C-X bond allows the loss of the good leaving group, a halide ion, to give a carbocation intermediate. This is the rate determining step (bond breaking is endothermic)
E1 mechanism for RX
Step 2:
An acid/base reaction. Deprotonation by a base (here an alkoxide ion) from a C atom adjacent to the carbocation center leads to the creation of the C=C 


Carbocations

Stability:
The general stability order of simple alkyl carbocations is: (most stable) 3o > 2o > 1o > methyl (least stable)

[carbocation stability order]

This is because alkyl groups are weakly electron donating due to hyperconjugation and inductive effects. Resonance effects can further stabilize carbocations when present.

Structure:
 
A simple representation of a carbocation
Alkyl carbocations are sp2 hybridized, planar systems at the cationic C center. 
The p-orbital that is not utilized in the hybrids is empty and is often shown bearing the positive charge since it represents the orbital available to accept electrons.
Computer model of CH3+

Reactivity:

electrostatic potential of CH3+ (side view) As they have an incomplete octet, carbocations are excellent electrophiles and react readily with nucleophiles (substitution).
Alternatively, loss of H+ can generate a p bond (elimination).

The electrostatic potential diagrams clearly show the cationic center in blue, this is where the nucleophile will attack.
 

electrostatic potential of CH3+ (top view)

Rearrangements:
Carbocations are prone to rearrangement via 1,2-hyride or 1,2-alkyl shifts provided it generates a more stable carbocation. For example:
 

3,3-dimethyl-2-butanol dehydrates to give mainly 2,3-dimethyl-2-butene
Notice that the "predicted" product is only formed in 3% yield, and that products with a different skeleton dominate. 
The reaction proceeds via protonation to give the better leaving group which departs to give the 2o carbocation shown.  A methyl group rapidly migrates taking its bonding electrons along, giving a new skeleton and a more stable 3o carbocation which can then lose H+ to give the more stable alkene as the major product. 
1,2-alkyl shift
2o carbocation to 3o carbocation

This is an example of a 1,2-alkyl shift.  The numbers indicate that the alkyl group moves to an adjacent position.
Similar migrations of H atoms, 1,2-hydride shifts are also known.

Reactions involving carbocations:
1. Substitutions via the SN1
2. Eliminations via the E1
3. Additions to alkenes and alkynes (HX, H3O+)



E2 mechanism

E2 indicates an elimination, bimolecular reaction, where rate = k [B][R-LG].
This implies that the rate determining step involves an interaction between these two species, the base and the organic substrate.

This pathway is a concerted process with the following characteristics:

concerted H+ removal and loss of leaving group
Simultaneous removal of the proton, H+, by the base, loss of the leaving group, LG, and formation of the p- bond
Let's look at how the various components of the reaction influence the reaction pathway:

Effects of R-
In an E2 reaction, the reaction transforms 2 sp3 C atoms into sp2 C atoms. This moves the substituents further apart decreasing any steric interactions. So more highly substituted systems undergo E2 eliminations more rapidly. This is the same reactivity trend as seen in E1 reactions.

-LG
The C-LG bond is broken during the rate determining step, so the rate does depend on the nature of the leaving group. However, if a leaving group is too good, then an E1 reaction may result.

B
Since the base is involved in the rate determining step, the nature of the base is very important in an E2 reaction. More reactive bases will favor an E2 reaction.

Stereochemistry
E2 reactions occur most rapidly when the H-C bond and C-LG bonds involved are co-planar, most often at 180o or antiperiplanar. This conformation postitions the s bonds that are broken in the correct alignment to become the p bond. More details ?

antiperiplanar arrangement in E2 reaction
Selectivity
The outcome of E2 reactions is controlled by the stereochemical requirements described above. Where there is a choice, the more stable alkene will be the major product.

The E2 pathway is most common with:

A typical example is the dehydrohalogenation of alkyl halides using KOtBu / tBuOH.


E2 Stereochemistry

E2 reactions occur most rapidly when the H-C bond and C-LG bonds involved are co-planar, most often at 180o with respect to each other. This is described as an antiperiplanar conformation. This conformation positions the s bonds that are being broken in the correct alignment to become the p bond.
 
 

antiperiplanar arrangement in E2 reaction
anti orbital alignment in the E2 reaction The staggered, antiperiplanar alignment is preferred because it aligns the two s bonds that become the p bond. Newman projection of antiperiplanar alignment in the E2 reaction

Show antiperiplanar alignment
Reset colours

Synperiplanar arrangments where the angle between the H-C bond and C-LG is 0o are also known, usually in systems that are either inflexible rings or intramolecular eliminations.
 

syn orbital alignment in the E2 reaction The eclipsed, synperiplanar alignment also aligns the two s bonds that become the p bond, but is less favorable than the antiperiplanar arrangement. Newman projection of synperiplanar alignment in the E2 reaction

 

These alignments are examples of a stereoelectronic effect because they involve the specific spatial postioning of the bonds (electrons) in order for the process to occur.

Implications:
 

elimination of 4-bromo-t-butylcyclohexane The cis- isomer undergoes elimination over 500 times faster than the trans- isomer. 

In the cyclic system, in order for the preferred antiperiplanar arrangement favored by E2 reactions, the C-H and C-LG bonds both need to be axial.

Recall that in chapter 3 that we learned that the t-butyl group has a strong preference for the equatorial position on cyclohexanes and acts as a "lock". In the trans isomer, this means that the -Br is also equatorial and is therefore anti to C-C bonds, not C-H. Since the cyclohexane is locked it cannot ring flip into the geometry required for the E2 and elimination is slow.
In contrast, in the cis isomer, the -Br is axial and is anti to 2 C-H bonds and the E2 occurs rapidly. Use the CHIME images below to show the antiperiplanar bonds if you need to.

 

Show antiperiplanar bonds 
Reset colours 


Selectivity

In many cases elimination reactions may proceed to alkenes that are isomeric but with one formed in excess of the other.

 Regioselectivity (products are constitutional isomers):

dehydration of 2-methylcychexanol gives mainly tri-substituted alkene
dehydrohalogenation of 2-bromo-2-methylbutane gives mainly tri-substituted alkene

Zaitsev's rule, based on experiment observations of the dehydration of alcohols, expresses the preference for eliminations to give the highly substituted (more stable) alkene, which may also be described as the Zaitsev product.
The rule is not always obeyed, some reactions give the anti-Zaitsev product which is sometimes described as the Hoffman product. (Hoffman studied the elimination of ammonium salts)
Care is needed with E2 eliminations of cyclic systems since the antiperiplanar alignment of the C-H and C-LG bonds can dictate that the anti-Zaitsev products dominate.

Stereoselectivity (products are stereoisomers)

dehydration of 3-pentanol gives mainly trans-2-pentene
dehydrohalogenation of 2-bromopentane gives mainly trans-2-pentene
Similarly, eliminations often favor the more stable trans-product over the cis-product.

Help with chime files