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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.

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:

• Dehydration (-H₂O) of alcohols, and
• Dehydrohalogenation (-HX) of alkyl halides.

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:

• Loss of the LG to form a carbocation,  removal of H⁺ and formation of C=C bond : E1 reaction
• Simultaneous H⁺ removal, C=C bond formation and loss of the LG : E2 reaction
• Removal of H⁺ to form a carbanion, loss of the LG and formation of C=C bond (E1cb reaction)

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) 3^o > 2^o > 1^o > methyl (least stable)

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

Structure:
 

Reactivity:

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

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 S_N1
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:
 

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:

• good leaving groups
• stable carbocations
• weak bases.

A typical example is the acid catalyzed dehydration of 2^o or 3^o alcohols.
 
 

Carbocations

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

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

Structure:
 

Reactivity:

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

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 S_N1
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:

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 180^o or antiperiplanar. This conformation postitions the s bonds that are broken in the correct alignment to become the p bond. More details ?

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:

• high concentration of a strong base
• poorer leaving groups
• R-LG that would not lead to stable carbocations  (when the E1 mechanism will occur).

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 180^o 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.
 
 

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

 

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:
 

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):

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)

Similarly, eliminations often favor the more stable trans-product over the cis-product.

Help with chime files

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.

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:

• Dehydration (-H₂O) of alcohols, and
• Dehydrohalogenation (-HX) of alkyl halides.

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:

• Loss of the LG to form a carbocation,  removal of H⁺ and formation of C=C bond : E1 reaction
• Simultaneous H⁺ removal, C=C bond formation and loss of the LG : E2 reaction
• Removal of H⁺ to form a carbanion, loss of the LG and formation of C=C bond (E1cb reaction)

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) 3^o > 2^o > 1^o > methyl (least stable)

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

Structure:
 

Reactivity:

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

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 S_N1
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:
 

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:

• good leaving groups
• stable carbocations
• weak bases.

A typical example is the acid catalyzed dehydration of 2^o or 3^o alcohols.
 
 

Carbocations

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

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

Structure:
 

Reactivity:

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

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 S_N1
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:

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 180^o or antiperiplanar. This conformation postitions the s bonds that are broken in the correct alignment to become the p bond. More details ?

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:

• high concentration of a strong base
• poorer leaving groups
• R-LG that would not lead to stable carbocations  (when the E1 mechanism will occur).

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 180^o 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.
 
 

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

 

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:
 

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):

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)

Similarly, eliminations often favor the more stable trans-product over the cis-product.

Help with chime files

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