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Introduction
Elimination reactions widely used for the generation of double
and triple bonds in compounds from a saturated precursor
molecule. The presence of a good leaving group is a
prerequisite in most elimination reactions. Traditional
classification of elimination reactions, in terms of the
molecularity of the reaction is employed. How the changes in
the nature of the substrate as well as reaction conditions
affect the mechanism of elimination are subsequently
discussed. The stereochemical requirements for elimination in
a given substrate and its consequence in the product
stereochemistry is emphasized.
ELIMINATION REACTIONS
Objective and Outline
- (^) beta-eliminations
- (^) E1 , E2 and E1cB mechanisms
- (^) Stereochemical considerations of these reactions
- (^) Examples of E1 , E2 and E1cB reactions
- (^) Alpha eliminations and generation of carbene
II. More details on β-eliminations
- (^) β -eliminations can be further subdivided into three categories
- depending upon the mechanistic pathway. The important aspect is to establish
the number of molecules taking part in the elimination step (molecularity of
the reaction)
- (^) The types of β -eliminations are
- (^) 1)E
- (^) 2)E
- (^) 3)E1cB
- (^) These are read as “Elimination bimolecular E2”, “Elimination unimolecular
E1”and “Elimination unimolecular conjugate base E1cB”
An illustration of a common elimination reaction is given below, The sequence of events involved are, (i)The attack of ethoxide on βhydrogen and its abstraction as a proton is the first event. This will leave two electrons of the C-H bond available for the formation of a new double bond between the carbon atoms. (ii)As the new double bond is created, the C-Br bond begins to break away (leaving group). This will result in the departure of the bromide ion. The events summarized above are the general steps, the extend of bond formation/breaking would depend on a number of factors described later.
Note: Often times, E2 elimination competes with SN2 reactions. This is due to the inherent propensity of the incoming nucleophile also to attack the carbon atom bearing the leaving group. Such situations will lead to substitution products. Examples of E2 elimination : Note that examples given here are non-traditional, selected from the list of recently available examples. Standard examples can be found in basic text books
Step 2 : Note: Even though a sp 3 C-H bond is not acidic in a general sense, the presence of a carbocationic center adjacent to it renders increased acidity such that even a weak base such as water can deprotate. Similar to the competition between E2 and SN 2 pathways, E1 mechanism competes with SN 1 . Formation of carbocation is a slower process, as compared to the reaction between a ‘reactive-carbocation’ and a base/solvent. Hence, carbocation formation is the rate determining step. Ideal conditions are for E1 mechanism are (a) highly substituted carbon atom for the carbocation center, such as a tert-carbon atom, (b) use of polar solvents (which can stabilize the resulting carbocation in addition to stabilizing a polar transition state involved in the heterolytic bond cleavage.
Examples for E1elimination: It can be readily noticed that the carbocation generated in the first step would be stabilized species due to effective delocalization promoted by the presence of two phenyl groups on the tert-carbon. III. E1cB Eliminations
- This is a two step base-induced β elimination.
- In this reaction base first abstracts the βhydrogen, giving rise to a carbanion or conjugate base of the substrate from which the leaving group departs subsequently to form the product.
- An interesting comparison can be done with the E1 pathway. The timing of departure of the groups is reversed as compared to that in E1 reaction. In E1cB, the deprotonation occurs ahead of leaving group departure
- Reaction usually follows second order kinetics but is designated as E1cB to indicate that the departure of the leaving group is from the initially formed conjugate base (i.e., carbanion).
IV.Variable transition state theory for elimination reaction Many βelimination reactions proceed via mechanisms, which are intermediate between the extremities such as E1cB and E1. This is called variable E2transition state theory. The timing of deprotonation and departure of the leaving group is the key to the following mechanistic continuum The other way to depict the variable transition state theory is to construct three dimensional potential energy diagram. Consider example of ethyl halide. The two intermediates involved in two extreme processes are;
When there are no suitable stabilizing groups, both primary carbocation and primary carbanion are highly unstable. If we construct a diagram in which progress of C-H bond breaking is one dimension, progress of C-X bond breaking is second dimension and energy of reactant system is third dimension, then following diagram is obtained. This is two dimensional representation which shows that E1 corresponds to complete C-X breakage before C-H bond breaking while E1cB corresponds to complete C-H breakage before C-X.
Important factors that influence the reaction mechanism E
- (^) electron donating ability of substituents
- (^) good leaving group
- (^) solvents of high polarity These factors will favor E1 pathway. Base is not important in the rate determining step but its presence is important. E Base participates in the rate-determining step
- (^) strength of base
- (^) nature of leaving group
- (^) nature of the solvent If strong base is used reaction will move towards E1cB like pathway whereas good leaving group with strongly ionizing solvent will cause it to move towards E1 pathway.
V. Orientation of double bond In a substrate where the double bond can be generated in different regions of the molecule, the obvious question is whether one can predict which one is likely to be the major product. Here comes the issue of ‘regio’‘selectivity’
Regioselectivity:
In many substrate, more than one kind of βhydrogens can be removed in an elimination reaction. Which of the βhydrogens is lost depends on various factors. Three rules generally govern regiochemistry. (1) Zaitsev’s Rule(Saytzev), (2) Hofmann Rule, (3) Bredt’s Rule Zaitsev`s rule : In an elimination reaction, the major product formed will be a more substituted alkene. This means that removal of the hydrogen form the more substituted β carbon atom should occur.
Hofmann rule: Although most compounds seem to follow Zaitsevs rule, some give product according to Hofmann rule i.e., less substituted alkene. Hofmann elimination is observed for compounds containing bulky leaving groups such as **_quaternary ammonium or sulfonium salts._** Bredtsrule: No double bond can be generated on a bridge head carbon of bicyclic compounds unless size of ring is sufficiently large. Note: The origin of why Bredt’s rule can be rationalized by considering the need for lateral overlap between two adjacent p-orbitals. Two p- orbitals can’t remain parallel due to the bridged bicyclic structure.
Other features of directionality of elimination reactions If compound already contains C=C or C=O functional groups, then the newly generated double bond tends to maintain conjugation with it. Many factors are responsible for regioselectivity. One of them is steric interaction. In E2 reaction when leaving group is bulky approach of base towards β-hydrogen is more likely to take place from less hindered side to produce less substituted alkene. Similarly, large base favors formation of Hofmann product. Acidity of terminal and internal βhydrogen is also important factor in determining the product ratios. Terminal hydrogens are more acidic, producing less substituted product, particularly in quaternary ammonium or sulfonium group containing compound. In case of E1 reaction, the rate controlling step is the formation of carbocation which is followed by product formation. Carbocation generated hence has choice to adopt more stable arrangement, before the removal of the proton. In most E1 reaction, the product predominantly will be in accordance with Zaitsevs rule i.e., thermodynamically more stable, highly substituted alkene. In general, Zaitsevs rule is directly applicable to molecules containing small leaving groups such as bromide.
